Nearly half of the world’s population is at risk of malaria. In areas with high malaria transmission, young children and pregnant women are particularly vulnerable to malaria infection and death. Since 2000, expanded access to WHO-recommended malaria prevention tools and strategies – including effective vector control and the use of preventive chemotherapies – has had a major impact in reducing the global burden of this disease.
4.1. Vector control
Background
The Guidelines commence by providing general recommendations on malaria vector control, followed by more specific recommendations on individual interventions and good practice statements on their deployment. The interventions are divided into categories of those recommended for large-scale deployment and those recommended as supplementary. Interventions that are recommended for large-scale deployment are those that have demonstrated public health value, i.e., have proven protective efficacy to reduce or prevent infection and/or disease in humans at the community level, and - in the case of insecticide treated nets (ITNs) - at the individual level, and that are broadly applicable for populations at risk of malaria in most epidemiological and ecological settings. Supplementary interventions are those with conditional recommendations that may be applicable for specific populations, situations or settings. These include personal protection measures that have a primary use-pattern of protecting individual users, although they may have some as yet unproven impact when deployed at the community level.
Vectors, their behaviour and distribution
Malaria is transmitted through the bites of infective female Anopheles mosquitoes. There are more than 400 different species of Anopheles mosquitoes, of which around 40 are malaria vectors of major importance. Anopheles mosquitoes lay their eggs in water. The eggs hatch to produce larvae, which undergo several moults before emerging from the pupal stage as adult mosquitoes. Different species of Anopheles mosquito have their own preferred aquatic habitats; for example, some prefer small, shallow collections of fresh water such as puddles and animal hoof prints, whereas others prefer large, open water bodies including lakes, swamps and rice fields.
Immediately after emerging from the pupal stage, mosquitoes rest on the water surface until their wings have fully expanded and hardened. After taking an initial meal of plant nectar, female mosquitoes seek a blood meal, as they require protein to develop their eggs. In the majority of species of Anopheles, the females feed on warm-blooded animals, usually mammals. Different mosquito species demonstrate preferences for feeding on animals (zoophily) or on humans (anthropophily); however, these preferences are not absolute, and females may take a blood meal from a non-preferred host when these are present in the area. Blood-feeding can take place inside human habitations (endophagy) or outdoors (exophagy), depending on the mosquito species. Several factors have been implicated in the attraction of female mosquitoes to a host, including exhaled carbon dioxide, lactic acid, host odours, warmth and moisture. Different host individuals may be more or less attractive to mosquitoes than other individuals of the same species.
Female Anopheles mosquitoes feed predominantly at night, although some species may bite during the day in heavily shaded conditions, and some exhibit a peak in biting activity in the early evening or early morning. The interplay between the peak biting time of the Anopheles vector and the activity and sleeping patterns of the human host has important consequences for malaria transmission and the choice of appropriate vector control interventions.
After blood-feeding, female mosquitoes rest in order to digest the blood meal and mature their eggs. Female mosquitoes may rest indoors (endophily) or outdoors (exophily), and this depends on innate species preferences as well as the availability of suitable resting sites in the local environment. The mosquitoes’ choice of post-feeding resting site also has major implications for the selection of control interventions.
It is important to note that while an individual species of Anopheles will characteristically exhibit certain biting and resting behaviours, these are not absolute; subpopulations and individuals may exhibit different behaviours depending on a combination of intrinsic genetic factors, availability of preferred hosts and availability of suitable resting sites. Environmental and climatic factors, including rainfall, moonlight, wind speed, etc., as well as the deployment of vector control interventions can all influence biting and resting behaviours. For example, the highly efficient African malaria vector Anopheles gambiae s.s. is generally considered to be human-biting, indoor-biting and indoor-resting, but it can also exhibit more zoophilic and exophagic tendencies. Anopheles arabiensis is a species that generally exhibits an outdoor biting and resting habit, but may exhibit indoor biting and resting tendencies, depending on the availability of alternative hosts.
Accurate species identification is crucial for all studies and surveillance activities on field populations of vectors. Many of the vectors belong to species complexes and require advanced molecular analyses for species identification, necessitating appropriate laboratory resources. Without accurate species identification, the data collected on behaviour, distribution and infection rates will have limited use for decision-making by control programmes.
Background and rationale for vector control
The role of arthropods in the transmission of diseases to humans was first elucidated in the late 19th and early 20th centuries. Since effective vaccines or drugs were not always available for the prevention or treatment of these diseases, control of transmission often had to rely principally on control of the vector. Early control activities included the screening of houses, the use of mosquito nets, the drainage or filling of swamps and other water bodies used by insects for breeding, and the application of oil or Paris green to breeding places. Following the discovery of the insecticidal properties of dichlorodiphenyltrichloroethane (DDT) in the 1940s and subsequent discovery of other insecticides, the focus of malaria vector control shifted to the deployment of insecticides to target both the larval and adult stages of mosquito vectors.
Nowadays, it is well established that effective vector control programmes can make a major contribution to advancing human and economic development. Aside from direct health benefits, reductions in vector-borne diseases enable greater productivity and growth, reduce household poverty, increase equity and women’s empowerment, and strengthen health systems (12). Despite the clear evidence in broad support of vector control efforts, the major vector-borne diseases combined still account for around 17% of the estimated global burden of communicable diseases, claiming more than 700 000 lives every year (13). Recognizing the great potential to enhance efforts in this area, WHO led the development of the Global vector control response 2017–2030 (13), which is outlined in the subsequent section.
The control of malaria, unlike that of most other vector-borne diseases, saw a major increase in financial resources from 2000 to about 2010, leading to a significant reduction in the global burden. However, since 2010, total malaria funding has largely stagnated. Moreover, the funding gap between the amount invested and the resources needed has continued to widen significantly in recent years, largely as a result of population growth and the need to switch to more expensive tools. This gap increased from US$ 1.3 billion in 2017 to US$ 2.3 billion in 2018, and to US$ 2.6 billion in 2019 (3).
Between 2000 and 2015, the infection prevalence of Plasmodium falciparum in endemic Africa was halved and the incidence of clinical disease fell by 40% (14). Malaria control interventions averted an estimated 663 million (credible interval (CI) 542–753 million) clinical cases in Africa, with ITNs making the largest contribution (68% of cases averted). Indoor residual spraying (IRS) contributed an estimated 13% (11–16%), with a larger proportional contribution where intervention coverage was high (14).
Global vector control response 2017–2030
The vision of WHO and the broader infectious diseases community is a world free of human suffering from vector-borne diseases. In 2017, the World Health Assembly welcomed the Global vector control response 2017–2030 (13) (GVCR) and adopted a resolution to promote an integrated approach to the control of vector-borne diseases. The approach builds on the concept of integrated vector management (IVM), but with renewed focus on improved human capacity, strengthening infrastructure and systems, improved surveillance, and better coordination and integrated action across sectors and diseases.
The ultimate aim of the GVCR is to reduce the burden and threat of vector-borne diseases through effective, locally adapted, sustainable vector control in full alignment with Sustainable Development Goal 3.3: to end epidemics of malaria by 2030. The 2030 targets are: to reduce mortality due to vector-borne diseases globally by at least 75% (relative to 2016); to reduce case incidence due to vector-borne diseases globally by at least 60% (relative to 2016); and to prevent epidemics of vector-borne diseases in all countries. Detailed national and regional priority activities and associated interim targets for 2017–2022 have also been defined.
Priority activities set out in the GVCR fall within four pillars that are underpinned by two foundational elements:
Pillars of action:
Strengthen inter- and intra-sectoral action and collaboration.
Engage and mobilize communities.
Enhance vector surveillance, monitoring and evaluation of interventions.
Scale up and integrate tools and approaches.
Foundations:
Effective and sustainable vector control is achievable only with sufficient human resources, an enabling infrastructure and a functional health system. National programmes should lead a vector control needs assessment across the relevant sectors (15) to help appraise current capacity, define the requisite capacity to conduct proposed activities, identify opportunities for improved efficiency in vector control delivery, and guide resource mobilization to implement the national strategic plan.
In some settings, vector control interventions have the potential to reduce transmission and disease burden of more than one disease. Examples include the deployment of ITNs against malaria and lymphatic filariasis (in settings where Anopheles mosquitoes are the principal vector), against malaria and leishmaniasis in India, and larval control for malaria and dengue vectors in cities with particular vector habitats. With the recently documented invasion of Anopheles stephensi in the Horn of Africa, the integrated surveillance and control of this vector alongside Aedes provides a clear opportunity for GVCR implementation. More approaches effective against Aedes spp. mosquitoes generally have the potential to impact dengue, chikungunya, Zika virus disease and possibly yellow fever where their vectors and distributions overlap.
Prevention, mitigation and management of insecticide resistance
Widespread and increasing insecticide resistance poses a threat to effective malaria vector control. Failure to mitigate and manage insecticide resistance is likely to result in an increased burden of disease, potentially reversing some of the substantial gains made in controlling malaria over the last decade.
WHO maintains a global insecticide resistance database and an online mapping tool that consolidate information on the status of the insecticide susceptibility of Anopheles mosquitoes in malaria-endemic countries (16). The latest data revealed that almost 90% of the malaria-endemic countries reporting insecticide resistance have detected resistance of their vectors to at least one insecticide class. Globally, resistance to pyrethroids is widespread, having been detected in at least one malaria vector in 70% of the sites for which data were available. Resistance to organochlorines was reported in 63% of the sites. Resistance to carbamates and organophosphates was less prevalent, detected in 32% and 35% of the sites that reported monitoring data, respectively (3).
To date, there is no evidence of operational failure of vector control programmes as a direct result of increasing frequency of pyrethroid resistance (17)(18). Based on past experience, however, it is likely that operational failure will eventually occur if effective insecticide resistance management (IRM) strategies are not designed and implemented. Ideally, such strategies should be implemented early to prevent spread and increase in the intensity of resistance. The overarching concepts of such resistance management strategies were outlined in the Global plan for insecticide resistance management in malaria vectors (GPIRM) in 2012 (19).
Guidance on monitoring of insecticide resistance, interpretation of test results interpretations and implications for decision-making are given in the WHO Test procedures for monitoring insecticide resistance in malaria vector mosquitoes (20) and in the Framework for a national plan for monitoring and the management of insecticide resistance in malaria vectors (21). When deciding whether adjustments to the national malaria strategic plan are required in a given area, at least the following must be considered for that locality:
current and past transmission levels;
current and past interventions deployed, including the coverage, usage and duration of efficacy;
the insecticide resistance profile of the main vector species (including resistance intensity and resistance mechanisms); and
other entomological information including vector species distribution, abundance, and other bionomic data.
The susceptibility of mosquitoes to insecticides and determination of the species-specific presence, intensity and mechanisms of resistance in vector populations can be used to guide the selection of the most appropriate insecticidal products to deploy. Generally, if mosquitoes are found to be resistant to an insecticide, insecticides with a different mode of action should be deployed. However, there are reports of mosquitoes having differential susceptibility to insecticides within the same class, and questions have been raised about the level of cross-resistance between pyrethroid products (19). The Global Fund recently commissioned a review of the interpretation of insecticide resistance assays when selecting insecticidal products (22). The review aimed to answer the question: in areas where pyrethroid resistance exists, but mosquitoes of the same population differ in their susceptibility to different pyrethroids, should programmes consider selecting one pyrethroid over another in order to manage insecticide resistance? Based on a review of evidence from molecular, laboratory and field data, the authors concluded that differences between adult mosquito mortalities in pyrethroid insecticide resistance assays are not indicative of a true or operationally relevant difference in the potential performance of pyrethroids currently in common use (deltamethrin, permethrin, α-cypermethrin and λ-cyhalothrin). Consequently, switching between pyrethroid insecticides (to improve intervention efficacy) should not be used as a means of managing insecticide resistance. This finding supports WHO’s past and present position. Given that pyrethroid resistance in mosquitoes is widespread, WHO encourages the development and continued evaluation of nets treated with alternative insecticides (23).
Key technical principles for addressing insecticide resistance are as follows:
Insecticides should be deployed with care and deliberation in order to reduce unnecessary selection pressure and maximize impact on disease. National malaria programmes should consider whether they are using insecticides judiciously, carefully and with discrimination, and if there is a clear epidemiological benefit.
Vector control programmes should avoid using a single class of insecticide everywhere and over consecutive years. Whenever possible, vector control programmes should diversify from pyrethroids to preserve their effectiveness. Although pyrethroids will continue to be used for ITNs in the near term, they should not generally be deployed for IRS in areas with pyrethroid ITNs, whether alone or combined with insecticides from a different class.
IRM principles and methods should be incorporated into all vector control programmes, not as an option, but as a core component of programme design.
National malaria programmes should engage with the agricultural sector to coordinate insecticide use, with the aim of avoiding use of the same classes of insecticide for both crop protection and public health within the same geographical area.
Routine monitoring of insecticide resistance is essential to inform the selection and deployment of insecticides.
The additional costs of deploying new vector control tools as part of a comprehensive IRM response should be balanced against the potential long-term public health impact. Where feasible formal economic evaluation is encouraged to investigate the likely incremental costs and effectiveness of potential IRM approaches, relative to feasible alternatives, for a given context.
Approaches
Historically, the most common way insecticides have been deployed to control malaria vectors has been through “sequential use”. In essence, this is when a single insecticide class is used continuously or repeatedly until resistance has rendered it less effective or ineffective, after which a switch is made to an insecticide with a different mode of action to which there is no (or less) resistance. In theory, this may allow for an eventual switch back to the original insecticide class if resistance decreases to the point that it is no longer detectable by means of bioassays.
The agricultural industry has had some success in managing resistance by using different insecticides over space and time. Similar approaches have been proposed with the aim of preventing or delaying the spread and increase of resistance by removing selection pressure or by killing resistant mosquitoes. However, there is no empirical evidence of the success of these strategies for malaria vector control, which is likely to depend on mosquito genetics, behaviour and population dynamics, and the chemical nature of the insecticides and their formulation. These strategies include mixtures of insecticides, mosaic spraying, rotations of insecticides and deployment of multiple interventions in combination.
Mixtures are co-formulations that combine two or more insecticides with different modes of action. Mixtures are widely used as drug treatments in co-formulated combination therapy. Effective deployment of a mixture requires the presence of resistance to all insecticides in the mixture to be rare, so that any individual mosquito that survives exposure to one insecticide is highly likely to be killed by the other insecticide or insecticides. Ideally, all insecticides in a mixture should have a similar residual life and remain bioavailable over time; in practice, this is difficult to achieve, particularly for vector control products that are meant to last for a number of years, such as long-lasting insecticide-treated nets (LLINs). An ITN product containing a pyrethroid and a pyrrole insecticide and another containing a pyrethroid and a juvenile hormone mimic have been developed and prequalified by WHO (
24). WHO will require data on the epidemiological impact of these products to enable assessment of their public health value and to develop a WHO recommendation. A mixture of a pyrethroid and a neonicotinoid insecticide for IRS was recently prequalified by WHO.
Rotations involve switching between insecticides with different modes of action at pre-set time intervals, irrespective of resistance frequencies. The theory is that resistance frequencies will decline (or at least not increase) during the period of non-deployment of insecticides with a specific mode of action.
Mosaics involve the deployment of insecticides with different modes of action in neighbouring geographical areas. The optimal spatial scale (size of areas) for mosaics has yet to be determined, and rotations are generally considered to be more practical and feasible.
Combinations expose the vector population to two classes of insecticides with differing modes of action through the co-deployment of different interventions in the same place. For instance, pyrethroid-only LLINs combined with a non pyrethroid IRS (where both are at high coverage) is a potential approach to IRM, although there is little evidence to indicate that such a combination of interventions would lead to additional epidemiological impact relative to one intervention deployed at high coverage (see recommendation under
section 4.1.2).
For vector control, there is still little evidence and no consensus on the best IRM approach or approaches to apply in a given situation. A 2013 review of experimental and modelling studies on insecticide, pesticide and drug resistance concluded that mixtures generally lead to the slowest evolution of resistance (25). However, more recently, an exploration of overlaps between agriculture and public health found that – owing to caveats and case specificity – there is only weak evidence of one IRM approach being better than another, and that the standard practice of using insecticides until resistance emerges before switching to an alternative (i.e., sequential use) may be equally effective under certain circumstances. More research is needed to compare resistance management approaches in the field (26) and to improve understanding of the biological mechanisms that are likely to favour different approaches in different situations (27)(28).
Evidence-based planning
Given the heavy reliance on insecticidal interventions – primarily ITNs and IRS – insecticide resistance of local vectors is a key consideration in vector control planning and implementation. Ideally, IRM practices should be implemented as part of routine operations, rather than waiting for resistance to spread or increase and for control failure to be suspected or confirmed. A pragmatic approach must be taken that seeks to select appropriate vector control interventions based on the insecticide resistance profile of the major malaria vectors in the target area. To outline how resistance will be monitored and managed, national malaria programmes should develop and implement national plans in accordance with the WHO Framework for a national plan for monitoring and management of insecticide resistance in malaria vectors (21). Detailed information on insecticide resistance monitoring methods and on how to use the data to inform the selection of appropriate interventions will be provided in the revised WHO Test procedures of monitoring insecticide resistance in malaria vectors anticipated to be published in 2021.
IRM plans should be revisited regularly to consider new information, and to integrate new interventions once they have been supported by WHO recommendations and prequalified. Further information on insecticide resistance monitoring and, more broadly, on entomological surveillance is included in the WHO reference manual on malaria surveillance, monitoring and evaluation, which outlines priority data across different transmission settings (29).
Vector control across different malaria transmission settings
Understanding the degree of risk of malaria transmission in a given geographic area provides the foundation for the design of cost-effective intervention programmes to decrease malaria burden, eliminate transmission and prevent re-establishment of malaria. The risk of malaria transmission is the product of receptivity, importation risk and infectivity of imported parasites, and is referred to as the malariogenic potential. The receptivity of an ecosystem to malaria transmission is determined by the presence of competent vectors, a suitable climate and a susceptible human population. Importation risk, sometimes referred to as vulnerability, refers to the probability of influx of infected individuals and/or infective anopheline mosquitoes. Infectivity depends on the ability of a given Plasmodium strain to establish an infection in an Anopheles mosquito species and undergo development until the mosquito has sporozoites in its salivary glands.
National malaria programmes should undertake stratification by malariogenic potential in order to: differentiate receptive from non-receptive areas; identify receptive areas in which malaria transmission has already been curtailed by current interventions; distinguish between areas with widespread transmission and those in which transmission occurs only in discrete foci; and determine geographical variations and population characteristics that are associated with importation risk (7).
Specific packages of interventions may be designed for implementation in the various strata identified. These may include:
enhancement and optimization of vector control;
further strengthening of timely detection, high-quality diagnosis (confirmation), and management and tracking of cases;
strategies to accelerate clearance of parasites or vectors in order to reduce transmission rapidly when possible;
information, detection and response systems to identify, investigate and clear remaining malaria foci.
Access to effective vector control interventions will need to be maintained in the majority of countries and locations where malaria control has been effective. This includes settings with ongoing malaria transmission, as well as those in which transmission has been interrupted but in which some level of receptivity and vulnerability remains. Malaria elimination is defined as the interruption of local transmission (reduction to zero incidence of indigenous cases) of a specified malaria parasite species in a defined geographical area as a result of deliberate intervention activities. Following elimination, continued measures to prevent re-establishment of transmission are usually required (29). Interventions are no longer required once eradication has been achieved. Malaria eradication is defined as the permanent reduction to zero of the worldwide incidence of infection caused by all human malaria parasite species as a result of deliberate activities.
A comprehensive review of historical evidence and mathematical simulation modelling undertaken for WHO in 2015 indicated that the scale-back of malaria vector control was associated with a high probability of malaria resurgence, including for most scenarios in areas where malaria transmission was very low or had been interrupted. Both the historical review and the simulation modelling clearly indicated that the risk of resurgence was significantly greater at higher entomological inoculation rates (EIRs) and case importation rates, and lower coverage of active case detection and case management (30).
Once transmission has been reduced to very low levels approaching eliminations, ensuring access to vector control for at-risk populations remains a priority, even though the size and specific identity of the at-risk populations may change as malaria transmission is reduced.
As malaria incidence falls and elimination is approached, increasing heterogeneity in transmission will result in foci with ongoing transmission in which vector control should be enhanced. Such foci may be due to particularly intense vectorial capacity, lapsed prevention and treatment services, changes in vectors or parasites that make the current strategies less effective, or reintroduction of malaria parasites by the movement of infected people or, more rarely, infected mosquitoes. Guidance on entomological surveillance across the continuum from control to elimination is provided elsewhere (29).
Once elimination has been achieved, vector control may need to be continued by targeting defined at-risk populations to prevent reintroduction or resumption of local transmission.
It is acknowledged that malaria transmission can persist following the implementation of a widely effective malaria programme. The sources and risks of residual transmission may vary by location, time and the existing components of the current malaria programme. This variation is potentially due to a combination of both mosquito and human behaviours, such as when people live in or visit forest areas or do not sleep in protected houses, or when local mosquito vector species bite and/or rest outdoors and thereby avoid contact with IRS or ITNs.
Supplementary interventions may be used in addition to ITNs or IRS in specific settings and circumstances. Recommendations on larviciding with chemical or biological insecticides are outlined in a subsequent chapter. Implementation of supplementary interventions should be in accordance with the principles outlined in the Global vector control response 2017–2030 (13).
Once elimination has been achieved, vector control coverage should be maintained in receptive areas where there is a substantial risk for reintroduction.
There is a critical need for all countries with ongoing malaria transmission, and in particular those approaching elimination, to build and maintain strong capacity in disease and entomological surveillance and health systems. The capacity to detect and respond to possible resurgences with appropriate vector control relies on having the necessary entomological information (i.e., susceptibility status of vectors to insecticides, as well as their biting and resting preferences). Such capacity is also required for the detailed assessment of malariogenic potential, which is a pre-condition for determining whether vector control can be scaled back (or focalized).
Summary of recommendations
Vector control is a vital component of malaria prevention, control and elimination strategies. Development of WHO recommendations for vector control interventions relies on evidence from well-designed and well-conducted trials and studies with epidemiological endpoints that demonstrate the public health value of the intervention (31). The consolidated Guidelines incorporate: i) recommendations based on systematic reviews of the available evidence on the effectiveness of vector control interventions; and ii) existing WHO recommendations developed previously. Evidence profiles reporting impact on malaria outcomes, as published in the systematic reviews are provided for each intervention. Evaluation and reviews of additional vector control interventions are ongoing, and recommendations based on this evidence will be added to the Guidelines. In cases where readers observe inconsistencies with earlier WHO publications, the Guidelines should be considered to supersede prior guidance.
The Guidelines cover interventions that are recommended for large-scale deployment and those that are recommended as supplementary interventions. Malaria vector control interventions recommended for large-scale deployment are applicable for all populations at risk of malaria in most epidemiological and ecological settings, namely: i) deployment of ITNs that are prequalified by WHO, which in many settings continue to be long-lasting insecticidal nets (LLINs); and ii) IRS with a product prequalified by WHO. Once optimal coverage with one of these interventions has been achieved, supplementary interventions may be considered for deployment depending on the specifics of the settings.
4.1.1. Interventions recommended for large-scale deployment
Interventions that are recommended for large-scale deployment in terms of malaria vector control are those that have proven protective efficacy to reduce or prevent infection and/or disease in humans and are broadly applicable for populations at risk of malaria in most epidemiological and ecological settings.
Vector control interventions applicable for all populations at risk of malaria in most epidemiological and ecological settings are: i) deployment of ITNs that are prequalified by WHO, and ii) IRS with a product prequalified by WHO. The exception to this is DDT, which has not been prequalified. This insecticide may be used for IRS if no equally effective and efficient alternative is available, and if it is used in line with the Stockholm Convention on Persistent Organic Pollutants (32). Between 2000 and 2015, 78% of the clinical malaria cases averted was attributed to insecticidal vector control, namely through the widespread scale-up of ITNs and IRS (14).
Programmatic targets against malaria, as detailed within national strategic plans, should be used to guide the decision-making process to assemble context-appropriate intervention packages. Decision-making around the intervention mix to deploy and the coverage level of each intervention needs to consider available local data to guide the stratification of interventions, the available funding, the relative cost-effectiveness of available intervention options, the resources required to provide access within the broader context of UHC, the feasibility of deploying the intervention(s) at the desired coverage level, and the country’s strategic goal. The resulting optimal coverage of the components of an intervention package for a given geographical area will also depend on other site-specific factors such as past and present transmission intensity, past and present intervention coverage, acceptability, and equity of access/use.
For malaria vector control interventions recommended for large-scale deployment namely, ITNs and IRS, optimal coverage refers to providing populations at risk of malaria with access to ITNs coupled with health promotion to maximize use, and ensuring timely replacement; or providing these populations with regular application of IRS. Either intervention should be deployed at a level that provides the best value for money while reflecting programmatic realities. In practice, this often means quantifying of commodities to provide full access by the population at risk while realizing that this will not result in 100% coverage or 100% access due to various system inefficiencies. Being cognizant of such constraints, decision-making should then consider other alternatives as part of the intervention package, ranging from chemoprevention to supplementary vector control, instead of pursuing the idealistic goal of providing full population coverage.
Insecticide-treated nets
WHO recommends ITNs – which in many settings are pyrethroid-only LLINs – for use in protecting populations at risk of malaria, including in areas where malaria has been eliminated but the risk of reintroduction remains. An ITN repels, disables and/or kills mosquitoes that come into contact with the insecticide on the netting material in addition to providing a physical barrier, thereby protecting the individual user. In addition, some studies have indicated that ITNs produce a “community effect”, which means that when enough ITNs are being used in a community, the survival of the mosquito population as a whole is affected; this effect increases the protection against malaria for ITN users and extends protection to members of the community who do not sleep under an ITN (33)(34)(35)(36)(37). However, such a community effect has not been observed in all settings (38)(39)(40). WHO GMP commissioned a review to examine the evidence for a community effect and to investigate the biological mechanisms by which ITNs provide both personal- and community-level protection against malaria. The review also investigated what factors may determine the presence of a community effect and moderate its intensity (Paintain & Lines, unpublished findings).
The review concluded that a community effect does occur in the majority of settings, and that its extent is driven by a number of contextual factors. These factors include vector behaviour (particularly the extent of anthropophily, i.e., the propensity to feed on people, and endophagy, i.e., the tendency of mosquitoes to blood-feed indoors); the relative availability of human and non-human hosts in the locality; the level of ITN coverage and use in a community; the insecticide used (its residual insecticidal activity and repellency); and the resistance of the local malaria vectors, both physiological and behavioural, to the insecticide on the net.
The ITN coverage threshold for when the community effect becomes apparent depends on a large number of contextual factors. Regardless of the context-dependent starting threshold, the extent of the community-level protection increases as ITN coverage and net use in a given community increases. Because ITNs kill insecticide-susceptible mosquitoes that come into contact with the insecticide on the netting material, more mosquitoes will be killed as ITN coverage increases. This killing effect reduces both mosquito population density and mosquito longevity, resulting in fewer malaria vectors overall and a lower infectivity rate as fewer mosquitoes will survive the time it takes for the malaria parasite to develop in the mosquito. Consequently, the reduced density, age and proportion of the local mosquito population that is infective offer an additional level of protection to the community as a whole beyond the individual protection provided by ITNs.
Large-scale field trials (37)(41) and transmission models (42)(43) originally suggested that community coverage (i.e., the proportion of human population using an ITN with effective insecticide treatments each night) of ≥ 50% is expected to result in some level of community-wide protection. The WHO-commissioned review indicated that this area-wide protection may start to occur at lower coverage levels (Paintain & Lines, unpublished findings). The review modelled the short-term effect of increasing ITN coverage on the EIR (infectious bites per person per year) in an area with high malaria transmission and an insecticide susceptible, anthropophilic vector, assuming fixed human infectiousness. In the coverage range of 15% to 85%, an additional 20% increase in coverage of the human population at risk was shown to result in a reduction in malaria transmission intensity of approximately 50% (these findings are taken from the report submitted to WHO; findings may be revised if indicated by peer review). Additional ITN coverage is always beneficial in terms of providing more protection to individuals – both users and non-users of ITNs – and, conversely, any reduction in coverage may result in increased malaria transmission. However, there may be diminishing marginal returns to increasing coverage at higher levels. In terms of absolute cases of malaria averted, a reduction in malaria transmission when increasing ITN coverage from 80% to 100% may not generate the same impact as a 20% increase in coverage at lower levels of coverage; the marginal costs required to increase coverage at high levels (>80%) will also increase due to growing system inefficiencies. At the country level, these diminishing returns must be balanced against potential investments in other cost-effective malaria prevention and control activities by means of a well-informed prioritization process.
Three main ITN classes are recognized by WHO as given below. These classes are formally established once public health value by a first-in-class product has been demonstrated:
ITNs designed to kill host-seeking insecticide-susceptible mosquito populations that have demonstrated public health value compared to untreated nets and whose entomological effects consist of killing and reducing the blood-feeding of insecticide-susceptible mosquito vectors. This intervention class covers pyrethroid-only nets prequalified by WHO and conventionally treated nets that rely on periodic retreatment with a WHO prequalified self-treatment kit. Public health value has been demonstrated for products within this class and WHO recommends use of pyrethroid-only nets prequalified by WHO for large scale deployment.
ITNs designed to kill host-seeking insecticide-resistant mosquitoes and for which a first-in-class product demonstrates public health value compared to the epidemiological impact of pyrethroid-only nets. This class includes nets that are treated with a pyrethroid insecticide and a synergist such as piperonyl butoxide (PBO) and is thought to also include nets treated with insecticides other than pyrethroid-based formulations. Public health value has been demonstrated for this class and WHO has issued a recommendation for the use of pyrethroid-PBO nets. Public health value has not been demonstrated for a first-in-class net treated with non-pyrethroid formulations and no recommendation is in place for such nets.
ITNs designed to sterilize and/or reduce the fecundity of host-seeking insecticide-resistant mosquitoes for which a first-in-class product demonstrates public health value compared to the epidemiological impact of pyrethroid-only nets. Public health value of products in this class has yet to be demonstrated. This class is thought to includes nets treated with pyrethroid + pyriproxyfen (an insect growth regulator). This class will be created once the public health value of a first-in-class ITN product containing an insect growth regulator has been demonstrated. No recommendation is in place for such nets.
ITNs are most effective where the principal malaria vector(s) mosquitoes bite predominantly at night after people have retired under their nets. ITNs can be used both indoors and outdoors, wherever they can be suitably hung (although hanging nets in direct sunlight should be avoided, as sunlight can affect insecticidal activity).
Indoor residual spraying
IRS is the application of a residual insecticide to potential malaria vector resting surfaces, such as internal walls, eaves and ceilings of houses or structures (including domestic animal shelters), where such vectors might come into contact with the insecticide. IRS with a product that has been prequalified by WHO PQ is recommended for large-scale deployment in most malaria-endemic locations. DDT, which has not been prequalified, may be used for IRS if no equally effective and efficient alternative is available, and if it is used in line with the Stockholm Convention on Persistent Organic Pollutants.
IRS is most effective where the vector population is susceptible to the insecticide(s) being applied, the majority of mosquitoes feed and rest indoors and where most structures are suitable for spraying.
Strong recommendation for, High certainty evidence
Pyrethroid-only nets (2019)
WHO recommends pyrethroid-only long-lasting insecticidal nets (LLINs) that have been prequalified by WHO for deployment for the prevention and control of malaria in children and adults living in areas with ongoing malaria transmission.
WHO recommends ITNs that have been prequalified by WHO for use in protecting populations at risk of malaria, including in areas where malaria has been eliminated or transmission interrupted but the risk of reintroduction remains.
ITNs are most effective where the principal malaria vector(s) bite predominantly at night after people have retired under their nets. ITNs can be used both indoors and outdoors, wherever they can be suitably hung (though hanging nets in direct sunlight should be avoided, as sunlight can affect insecticidal activity).
Practical Info
The current WHO policy recommendation for ITNs applies only to those mosquito nets that have been prequalified by WHO and that contain only an insecticide of the pyrethroid class (categorized as ‘pyrethroid-only LLINs’) (24). For ITNs that currently do not have a policy recommendation, including nets treated with another class of insecticide either alone or in addition to a pyrethroid insecticide, WHO will determine the data requirements for assessing their public health value based on technical advice from the Vector Control Advisory Group (VCAG).
Evidence To Decision
Benefits and harms
ITNs significantly reduce all-cause child mortality, malaria mortality, incidence of P. falciparum malaria and prevalence of P. falciparum, and incidence of severe malaria disease compared to no nets.
No undesirable effects were identified in systematic review. However, ITNs may play an as yet undetermined role in insecticide resistance development in Anopheles vectors; some users complain that they are too hot to sleep under; brand new nets recently removed from packaging may cause slight, transitory irritation to skin, eyes, nose, etc.
Certainty of the Evidence 
The systematic review determined that there is HIGH certainty evidence that ITNs generate significant desirable effects in terms of reducing malaria deaths, clinical disease and infections compared to no nets and when compared to untreated nets.
Preference and values
Resources and other considerations
The table below, compiled by the Guidelines Development Group, lists resources that should be considered for the deployment of ITNs. Note that this table does not include resource needs for product selection or assessment of impact of the intervention.
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| Line Item (Resource) | Resource Description |
|---|
|
Staff
|
Competent, trained, supervised and adequately remunerated enumerators Transport logisticians and drivers Stock managers Distribution team staff (including those trained in behaviour-change communication [BCC]) Teachers/health facility staff, where appropriate, trained for distribution channel Entomologists for quality control (QC) assessments Environmental assessment support staff
|
|
Training
|
Training in enumeration, distribution, logistics management, BCC, monitoring and evaluation (M&E) and quality assurance assessments.
|
|
Transport
|
Shipping of ITNs may require large trucks for transport of containerized nets from port of entry to centralized warehouses and onward to the district or other level. Vehicles to provide transport of ITNs and potentially distributors to the community (last mile) to enumerate persons/households, provide BCC and distribute ITNs. Vehicle maintenance costs Fuel
|
|
Supplies
|
ITNs Inventory management forms Recipient lists, distribution forms, including recipient sign-off sheets, daily distribution reports, inventory status reports, recipient status reports, and BCC materials (e.g. flip charts, posters, banners, staff clothing) M&E data collection forms ITN quality/durability assessment materials – e.g., cone bioassay material
|
|
Equipment
|
|
|
Infrastructure
|
Appropriate national and regional storage Adequate lower level storage for ITNs at the district/school/health facility Office space for management
|
|
Communication
|
Communication with other ministries and sectors e.g. environment, transport Communication with the general public, e.g., through the education sector and advertising on local media to encourage uptake and appropriate use and care of ITNs Communication with the community/local leaders
|
|
Governance/programme management
|
|
Other considerations:
Optimal coverage should be achieved and maintained in endemic settings
Improved post-distribution monitoring of nets is needed: durability, usage, coverage
Justification
The systematic review (44) followed the original 2003 analysis, which included insecticide-treated curtains and ITNs together and included two studies solely evaluating insecticide-treated curtains and one study evaluating both ITNs and insecticide-treated curtains. There was no obvious heterogeneity that would lead to a subgroup analysis to examine whether the effects were different, and the results from studies evaluating insecticide-treated curtains were consistent with the results of those evaluating ITNs. The GDG drew on the analysis to make recommendations related to ITNs only.
The systematic review (44) produced high-certainty evidence that, compared to no nets, ITNs are effective at reducing the rate of all-cause child mortality, the rate of uncomplicated episodes of P. falciparum, the incidence rate of severe malaria episodes, and the prevalence of P. falciparum. ITNs may also reduce the prevalence of P. vivax, but here the evidence of an effect is less certain.
Compared to untreated nets, there is high certainty evidence that ITNs reduce the rate of uncomplicated episodes of P. falciparum and reduce the prevalence of P. falciparum. There is moderate certainty evidence that ITNs also reduce all-cause child mortality compared to untreated nets. The effects on the incidence of uncomplicated P. vivax episodes and P. vivax prevalence are less clear.
The systematic review did not identify any undesirable effects of pyrethroid ITNs.
Research needs:
Determine the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection), as well as potential harms and/or unintended consequences of new types of nets and insecticides in areas where resistance to pyrethroids is high.
Determine the comparative effectiveness and durability of different net types.
Determine the effectiveness of nets in situations of residual/outdoor transmission.
Determine the impact of ITNs in transmission ‘hotspots’ and elimination settings.
Conditional recommendation, Moderate certainty evidence
Pyrethroid-PBO nets (2019)
WHO conditionally recommends pyrethroid-PBO nets prequalified by WHO for deployment instead of pyrethroid-only ITNs for the prevention and control of malaria in children and adults living in areas with ongoing malaria transmission where the principal malaria vector(s) exhibit pyrethroid resistance that is: a) confirmed, b) of intermediate level, and c) conferred (at least in part) by a monooxygenase-based resistance mechanism, as determined by standard procedures.
Practical Info
Mosquito nets that include both a pyrethroid insecticide and the synergist PBO have become available. PBO acts by inhibiting certain metabolic enzymes (e.g., mixed-function oxidases) within the mosquito that detoxify or sequester insecticides before they can have a toxic effect on the mosquito. Therefore, compared to a pyrethroid-only net, a pyrethroid-PBO net should, in theory, have an increased killing effect on malaria vectors that express such resistance mechanisms. However, the entomological and epidemiological impact of pyrethroid-PBO nets may vary depending on the bioavailability and retention of PBO in the net, and on the design of the net (i.e. whether only some or all of the panels are treated with PBO). At present, it is unknown how these differences in the design/composition of pyrethroid-PBO nets affect their relative efficacy. A non-inferiority design for experimental hut studies with entomological endpoints is being explored by WHO as a means to provide clarity in this respect.
Evidence To Decision
Benefits and harms
Prevalence of malaria may be decreased with pyrethroid-PBO nets compared to standard pyrethroid-only LLINs in areas of high insecticide resistance.
No undesirable effects were identified in systematic review. However, like pyrethroid- only ITNs, pyrethroid-PBO nets may play an as yet undetermined role in insecticide resistance development in Anopheles vectors; some users complain that they are too hot to sleep under; brand new nets recently removed from packaging may cause slight, transitory irritation to skin, eyes, nose, etc.
Certainty of the Evidence 
The systematic review determined that the evidence for the effect of pyrethroid-PBO nets on malaria infection prevalence in an area with highly pyrethroid-resistant mosquitoes was MODERATE.
Preference and values
Resources and other considerations
Similar resources are needed for the deployment of pyrethroid-PBO nets as those listed for pyrethroid-only ITNs. (See provided under ‘Resources and other considerations’ for pyrethroid-only ITNs.)
Other considerations:
Determination of insecticide resistance status in primary vectors and mechanisms of resistance is required.
Improved post-distribution monitoring of nets is needed: durability, usage, coverage.
Justification
Pyrethroid-PBO nets combine pyrethroids and a synergist. The synergist inhibits certain metabolic enzymes within the mosquito that would otherwise provide a protective effect against the insecticide. Therefore, compared to a pyrethroid-only net, a pyrethroid-PBO net should have an increased killing effect on malaria vectors that express such resistance mechanisms.
The systematic review (45) identified one cluster RCT in the United Republic of Tanzania with epidemiological data (46). The study indicated that a pyrethroid-PBO net product had additional public health value compared to a pyrethroid-only LLIN product in an area where the principal malaria vector(s) had confirmed pyrethroid resistance (results from CDC bottle bioassays indicated that <30% of mosquitoes were killed following exposure to pyrethroids). Resistance was conferred (at least in part) by monooxygenase-based resistance mechanisms, as determined by standard procedures. Mathematical modelling work, drawing on mosquito mortality data obtained from WHO test kit assays, CDC bottle bioassays and experimental hut trials, indicated that the added benefit of pyrethroid-PBO nets compared to pyrethroid-only LLINs is expected to be greatest where pyrethroid resistance is at “intermediate levels”, which was defined as a range of 10% to 80% mosquito mortality after exposure to a pyrethroid insecticide in WHO test kits or CDC bottle bioassays (47).
Based on the above evidence, WHO concluded and recommended the following in 2017:
Based on the epidemiological findings and the need to deploy products that are effective against pyrethroid-resistant mosquitoes, pyrethroid-PBO nets were given a conditional endorsement as a new WHO class of vector control products.
National malaria control programmes and their partners should consider the deployment of pyrethroid-PBO nets in areas where the principal malaria vector(s) have pyrethroid resistance that is: a) confirmed, b) of an intermediate level (as defined above by the mathematical modelling studies), and c) conferred (at least in part) by a monooxygenase-based resistance mechanism, as determined by standard procedures. Deployment of pyrethroid-PBO nets must only be considered in situations where coverage with effective vector control (primarily ITNs or IRS) will not be reduced. The primary goal must be to ensure continued access and use of ITNs at levels that ensure optimal coverage for all people at risk of malaria as part of an intervention package.
Pyrethroid-PBO nets should not be considered a tool that can alone effectively manage insecticide resistance in malaria vectors. It is an urgent task to develop and evaluate ITNs treated with non-pyrethroid insecticides and other innovative vector control interventions for deployment across all settings, in order to provide alternatives for use in a comprehensive IRM strategy.
The conditional recommendation will be reviewed and potentially revised once the 2018 systematic review (45) has been updated to include data from a second trial on pyrethroid-PBO nets which was completed in Uganda in 2020.
Research needs:
Good practice statement
Achieving and maintaining optimal coverage with ITNs for malaria prevention and control (2019)
To achieve and maintain optimal ITN coverage, WHO recommends that countries apply mass free net distribution through campaigns, combined with other locally appropriate delivery mechanisms such as continuous distribution using antenatal care (ANC) clinics and the Expanded Programme on Immunization (EPI).
Recipients of ITNs should be advised (through appropriate communication strategies) to continue using their nets beyond the three-year expected lifespan of the net, irrespective of the condition and age of the net, until a replacement net is available.
Practical Info
To achieve and maintain optimal ITN coverage, countries should apply a combination of mass free net distribution through campaigns and continuous distribution through multiple channels, in particular through ANC clinics and the EPI. Mass campaigns are the only proven cost-effective way to rapidly achieve high and equitable coverage. Complementary continuous distribution channels are also required because coverage gaps can start to appear almost immediately post-campaign due to net deterioration, loss of nets, and population growth.
Mass campaigns should distribute one ITN for every two persons at risk of malaria. However, for procurement purposes, the calculation to determine the number of ITNs required needs to be adjusted at the population level, since many households have an odd number of members. Therefore, a ratio of one ITN for every 1.8 persons in the target population should be used to estimate ITN requirements, unless data to inform a different quantification ratio are available. In places where the most recent population census is more than five years old, countries can consider including a buffer (e.g. adding 10% after the 1.8 ratio has been applied) or using data from previous ITN campaigns to justify an alternative buffer amount. Campaigns should also normally be repeated every three years, unless available empirical evidence justifies the use of a longer or shorter interval between campaigns. In addition to these data-driven decisions, a shorter distribution interval may be justified during humanitarian emergencies, as the resulting increase in population movement may leave populations uncovered by vector control and potentially increasing their risk of infection as well as the risk of epidemics.
Continuous distribution through ANC and EPI channels should remain functional before, during and after mass distribution campaigns. In determining the optimal mix of ITN delivery mechanisms to ensure optimal coverage and maximized efficiency, consideration should be given to the required number of nets, the cost per net distributed and coverage over time. For example, during mass distribution campaign years, other delivery schemes may need to be altered to avoid-over supply of ITNs.
‘Top-up’ campaigns (i.e., ITN distributions that take into account existing nets in households and provide each household only with the additional number of nets needed to bring it up to the target number) are not recommended. Substantial field experience has shown that accurate quantification for such campaigns is generally not feasible and the cost of accounting for existing nets outweighs the benefits.
There should be a single national ITN plan and policy that includes both continuous and campaign distribution strategies. This should be developed and implemented under the leadership of the national malaria control programme, based on an analysis of local opportunities and constraints, and identification of a combination of distribution channels with which to achieve optimal coverage and minimize gaps. This unified plan should include a comprehensive net quantification and gap analysis for all public sector ITN distribution channels. As much as possible, the plan should include major ITN contributions by the private sector.
Therefore, in addition to mass campaigns, the distribution strategy could include:
ANC, EPI and other child health clinics: These should be considered high-priority continuous ITN distribution channels in countries where these services are used by a large proportion of the population at risk of malaria, as occurs in much of sub-Saharan Africa.
Schools, faith- and community-based networks, and agricultural and food-security support schemes: These can also be explored as channels for ITN distribution in countries where such approaches are feasible and equitable. Investigating the potential use of these distribution channels in complex emergencies is particularly important.
Occupation-related distribution channels: In some settings, particularly in Asia, the risk of malaria may be strongly associated with specific occupations (e.g., plantation and farm workers and their families, miners, soldiers and forest workers). In these settings, opportunities for distribution through channels such as private sector employers, workplace programmes and farmers’ organizations may be explored.
Private or commercial sector channels: These can be important channels for supplementing free ITN distribution through public sector channels. Access to ITNs can also be expanded by facilitating the exchange of vouchers or coupons provided through public sector channels for a free or subsidized ITN at participating retail outlets. ITN products distributed through the private sector should be regulated by the national registrar of pesticides in order to ensure that product quality is in line with WHO recommendations.
The procurement of ITNs with attributes that are more costly (e.g., nets of conical shape) is not recommended for countries in sub-Saharan Africa, unless nationally representative data clearly show that the use of ITNs with particular attributes increases significantly among populations at risk of malaria. To build an evidence base to support the purchase of more costly nets, investigation into the preferences and into whether meeting preferences translates into increased use of ITNs may also be warranted, particularly in situations where standard nets are unlikely to suit the lifestyle of specific population groups at risk of malaria, such as may be the case for nomadic populations.
The lifespans of ITNs can vary widely among individual nets used within a single household or community, as well as among nets used in different settings. This makes it difficult to plan the rate or frequency at which replacement nets need to be procured and delivered. All malaria programmes that have undertaken medium- to large-scale ITN distributions should conduct ITN durability monitoring in line with available guidance to inform appropriate replacement intervals. Where there is evidence that ITNs are not being adequately cared for or used, programmes should design and implement BCC activities aimed at improving these behaviours.
In countries where untreated nets are widely available, national malaria control programmes should promote access to ITNs. Strategies for treating untreated nets can also be considered, for example, by supporting access to insecticide treatment kits.
As national malaria control programmes implement different mixes of distribution methods in different geographic areas, there will be a need to accurately track ITN coverage at subnational levels. Subnational responses should be triggered if coverage falls below programmatic targets. Tracking should differentiate among the contributions of various delivery channels to overall ITN coverage.
Countries should generate data on defined standard indicators of coverage and access rates in order to ascertain whether optimal coverage has been achieved and maintained. The data should also inform changes in implementation in order to improve performance and progress towards the achievement of programmatic targets. Currently, the three basic survey indicators are: i) the proportion of households with at least one ITN; ii) the proportion of the population with access to an ITN within their household; and iii) the proportion of the population reporting having slept under an ITN the previous night (by age [<5 years; 5–14 years; 15+ years], gender and access to ITN).
Justification
In December 2017, WHO published updated recommendations on Achieving and maintaining universal coverage with LLINs for malaria control (48). These recommendations were developed and revised based on expert opinion through broad consultation, including multiple rounds of reviews by the Malaria Policy Advisory Group (MPAG). Under the section on ‘practical information’, these recommendations have been summarized and slightly revised to clarify that these recommendations are not specific to LLINs, but apply to ITNs in general.
Good practice statement
Management of old ITNs (2019)
WHO recommends that old ITNs should only be collected where there is assurance that: i) communities are not left without nets, i.e., new ITNs are distributed to replace old ones; and ii) there is a suitable and sustainable plan in place for safe disposal of the collected material.
If ITNs and their packaging (bags and baling materials) are collected, the best option for disposal is high-temperature incineration. They should not be burned in the open air. In the absence of appropriate facilities, they should be buried away from water sources and preferably in non-permeable soil.
WHO recommends that recipients of ITNs be advised (through appropriate communication strategies) not to dispose of their nets in any water body, as the residual insecticide on the net can be toxic to aquatic organisms (especially fish).
Practical Info
It is important to determine whether the environmental benefits outweigh the costs when identifying the best disposal option for old ITNs and their packaging. For malaria programmes in most endemic countries, there are limited options for dealing with ITN collection. Recycling is not currently a practical option in most malaria-endemic countries (with some exceptions for countries with a well-developed plastics industry). High-temperature incineration is likely to be logistically difficult and expensive in most settings. In practice, when malaria programmes have retained or collected packaging material in the process of distributing ITNs, it has mostly been burned in the open air. This method of disposal may lead to the release of dioxins, which are harmful to human health.
If such plastic material (with packaging an issue at the point of distribution and old ITNs an intermittent issue at household level when the net is no longer in use) is left in the community, it is likely to be re-used in a variety of ways.
While the insecticide exposure entailed by this kind of re-use has yet to be fully studied, the expected negative health and environmental impacts of leaving the waste in the community are considered to be less than amassing it in one location and/or burning it in the open air.
Since the material from nets represents only a small proportion of total plastic consumption, it will often be more efficient for old ITNs to be dealt with as part of larger and more general solid-waste programmes. National environment management authorities have an obligation to consider and plan for what happens to old ITNs and packing materials in the environment in collaboration with other relevant partners.
Justification
Currently, ITNs and the vast majority of their packaging (bags and baling materials) are made of non-biodegradable plastics (49). The large-scale deployment of ITNs has given rise to questions as to the most appropriate and cost-effective way to deal with the resulting plastic waste, particularly given that most endemic countries do not currently have the resources to manage ITN collection and waste disposal programmes.
A pilot study was conducted to examine patterns of ITN usage and disposal in three African countries (Kenya, Madagascar and United Republic of Tanzania). Findings of this pilot study, along with other background information were used to generate recommendations through the WHO Vector Control Technical Working Group (VCTEG) and MPAG on best practices with respect to managing waste.
The following are the main findings from the pilot study and other background material:
ITNs entering domestic use in Africa each year contribute approximately 100 000 tonnes of plastic and represent a per capita rate of plastic consumption of 200 grams per year. This is substantial in absolute terms; however, it constitutes only approximately 1% to 5% of the total plastic consumption in Africa and thus is small compared to other sources of plastic and other forms of plastic consumption.
The plastic from ITNs is treated with a small amount of pyrethroid insecticide (less than 1% per unit mass for most products), and plastic packaging is therefore considered a pesticide product/container.
Old ITNs and other nets may be used for a variety of alternative purposes, usually due to the perceived ineffectiveness of the net, loss of net physical integrity or presence of another net.
ITNs that no longer serve a purpose are generally disposed of at the community level along with other household waste by discarding them in the environment, burning them in the open, or placing them into pits.
ITN collection was not implemented on a large scale or sustained in any of the pilot study countries. It may be feasible to recycle ITNs, but it is not practical or cost-effective at this point, as there would need to be specialized adaptation and upgrading of recycling facilities before insecticide-contaminated materials could be included in this process.
Two important and potentially hazardous practices are: i) routinely removing ITNs from bags at the point of distribution and burning discarded bags and old ITNs, which can produce highly toxic fumes including dioxins, and ii) discarding old ITNs and their packaging in water, as they may contain high concentrations of residual insecticides that are toxic to aquatic organisms, particularly fish.
Insecticide-treated plastics can be incinerated safely in high-temperature furnaces, but suitable facilities are lacking in most countries. Burial away from water sources and preferably in non-permeable soil is an appropriate method to dispose of net bags and old ITNs in the absence of a suitable high-temperature incinerator.
In most countries, ministries of environment (national environment management authorities) are responsible for setting up and enforcing laws/regulations to manage plastic waste broadly. Although some countries have established procedures for dealing with pesticide-contaminated plastics, it is unrealistic to expect national malaria control and elimination programmes to single-handedly address the problem of managing waste from ITNs. Environmental regulations; leadership and guidance from national environmental authorities; and oversight from international agencies, such as the United Nations Environment Programme, are all necessary.
Strong recommendation for, Low certainty evidence
Indoor residual spraying (2019)
WHO recommends IRS using a product prequalified by WHO for the prevention and control of malaria in children and adults living in areas with ongoing malaria transmission
DDT, which has not been prequalified, may be used for IRS if no equally effective and efficient alternative is available, and if it is used in line with the Stockholm Convention on Persistent Organic Pollutants.
IRS is considered an appropriate intervention where:
the majority of the vector population feeds and rests indoors;
the vectors are susceptible to the insecticide that is being deployed;
people mainly sleep indoors at night;
the malaria transmission pattern is such that the population can be protected by one or two rounds of IRS per year;
the majority of structures are suitable for spraying; and
structures are not scattered over a wide area, resulting in high transportation and other logistical costs.
Practical Info
Insecticide formulations currently used for IRS (24) fall into five major insecticide classes with three modes of action, based on their primary target site in the vector. These are listed below, where applicable with examples of the active ingredients contained in IRS products that have been prequalified by WHO:
Sodium channel modulators
Pyrethroids: alphacypermethrin, deltamethrin, lambda-cyhalothrin, etofenprox, bifenthrin
Organochlorines: No prequalified product available
Acetylcholinesterase inhibitors
Organophosphates: malathion, fenitrothion, pirimiphos-methyl
Carbamates: bendiocarb, propoxur
Nicotinic acetylcholine receptor competitive modulators
IRS products using four of these insecticide classes have been prequalified by WHO; as of August 2020, there were no organochlorine IRS formulations prequalified (24), but DDT continues to be used in a few countries. The prequalified products have been assessed for their safety, quality and entomological efficacy, which includes evaluation of their mortality effect on mosquitoes when applied to a range of interior surfaces of dwellings found in malaria-endemic areas. Residual efficacy needs to continue for at least three months after the application of the insecticide to the substrate, usually cement, mud or wood (51). Insecticides are available in various formulations to increase their longevity on different surfaces.
IRS is considered an appropriate intervention where:
the majority of the vector population feeds and rests indoors;
the vectors are susceptible to the insecticide that is being deployed;
people mainly sleep indoors at night;
the malaria transmission pattern is such that the population can be protected by one or two rounds of IRS per year;
the majority of structures are suitable for spraying; and
structures are not scattered over a wide area, resulting in high transportation and other logistical costs.
Indoor residual spraying: an operational manual for IRS for malaria transmission, control and elimination
IRS is a vector control intervention that can rapidly reduce malaria transmission. It involves the application of a residual insecticide to internal walls and ceilings of housing structures where malaria vectors may come into contact with the insecticide. This operational manual (52) aims to assist malaria programme managers, entomologists and public health officers in designing, implementing and sustaining high-quality IRS programmes.
Evidence To Decision
Benefits and harms
IRS significantly reduces all-cause child mortality, malaria mortality, P. falciparum incidence and prevalence, and incidence of severe disease compared to no IRS.
No undesirable effects were identified in systematic review. However, IRS may play an as yet undetermined role in insecticide resistance development in Anopheles vectors; IRS requires householders to grant permission for spray teams to enter the house; IRS requires householders to remove personal items from houses prior to spraying (e.g., foodstuffs); some insecticide formulations leave unsightly residue on sprayed surfaces.
Certainty of the Evidence 
The certainty of the evidence identified in the systematic review is graded LOW. The Guidelines Development Group considers that despite the LOW certainty of the evidence included in the systematic review, a strong recommendation for the intervention is warranted based on the fact that there is a considerable body of evidence stretching back several decades pertaining to implementation trials and programmatic data. The Guidelines Development Group considers that this body of evidence, when viewed as a whole, provides strong evidence of the effectiveness of IRS as a malaria prevention and control intervention. ITNs are considered to be an equally effective alternative intervention.
Preference and values
Resources and other considerations
The table below compiled by the GDG lists resources that should be considered for the deployment of IRS. Note that this table does not include resource needs for product selection or assessment of impact of the intervention.
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| Line Item (Resource) | Resource Description |
|---|
|
Staff
|
Competent, trained, supervised and adequately remunerated enumerators Transport logisticians, drivers Stock managers Spray personnel Entomologists for quality check assessments (QC) Environmental assessment support staff
|
|
Training
|
Training in enumeration, logistics management, spray technique, environmental safety, personal protective equipment (PPE) use and maintenance, spray pump operation and maintenance, insecticide mixing and clean-up, entomological quality assessments, BCC and M&E
|
|
Transport
|
Movement of insecticide requires environmentally compliant vehicles and ground transport plans. Spray team movement typically requires significant numbers of small vehicles capable of movement across challenging roads/terrain. Individual spray personnel may in some cases also require bicycles Transportation of pesticide-contaminated spray pumps and clothing to clean-up sites typically using spray team transportation Insecticide-contaminated residues and packaging must be transported from remote clean-up sites under an environmentally compliant transport plan often using small trucks Vehicles to provide transport for staff that provide BCC and entomological staff and associated supplies for QC wall cone bioassays Vehicle maintenance costs Fuel
|
|
Supplies
|
PPE Spray pump repair parts Insecticide and packaging (including return/clean packaging) Soap/bathing materials Inventory management forms Documentation paperwork/forms or electronic devices Entomological supplies for wall cone bioassays and maintenance of adult mosquitoes M&E data collection forms
|
|
Equipment
|
Computer and communication equipment Spray pumps appropriate for the specific insecticide Collection tanks/wash buckets and cleaning supplies (varies with insecticide)
|
|
Infrastructure
|
Appropriate national and regional/provincial storage Temporary insecticide storage depots at the local level Office space for management Clean-up sites (soak pits/evaporation pools) Training facilities with spray practice capacity Insectary to maintain mosquitoes exposed in QC wall cone bioassays
|
|
Communication
|
Communication with other ministries and sectors, e.g., environment, transport Communication with the general public, e.g., through the education sector and advertising on local media to encourage uptake Communication with the community/local leaders
|
|
Governance/programme management
|
|
Other considerations include:
Decisions on selection of insecticide to be used will depend on the resistance profile of the local vector population.
Optimal coverage should be maintained in endemic settings.
The primary vector(s) should be endophilic.
Implementation of the intervention should take place prior to the onset of the peak transmission season.
It is important to monitor the residual activity of the insecticide(s).
Justification
When carried out correctly, IRS has historically been shown to be a powerful intervention to reduce adult mosquito vector density and longevity and, therefore, to reduce malaria transmission. However, despite its long tradition and the large body of associated operational experience, few RCTs have been conducted on IRS and so the availability of data suitable for use in a meta-analysis is limited (50). The GDG determined that the data from these randomized trials, as well as the large body of evidence generated from other studies, warranted the continued recommendation of IRS for malaria prevention and control. An updated systematic review of data on IRS interventions from recent studies, RCTs and other designs is needed to further underpin this recommendation or modify it as appropriate.
Research needs:
Further evidence is needed of the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences of IRS.
Determine the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) as well as harms and/or unintended consequences of IRS in urbanized areas with changing housing designs.
Determine the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences of IRS using new insecticides in areas where mosquitoes are resistant to currently deployed insecticides.
Determine the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) of IRS in areas with different mosquito behaviours (such as in areas with outdoor transmission).
Given the relatively high cost of implementing IRS, especially in the context of growing insecticide resistance, and when delivering IRS in more remote areas, there is a need to investigate new approaches to delivering IRS to increase the cost-effectiveness of this intervention.
Good practice statement
Access to ITNs or IRS at optimal coverage levels (2019)
WHO recommends ensuring access to effective vector control using ITNs or IRS at optimal coverage levels for all populations at risk of malaria in most epidemiological and ecological settings.
Evidence To Decision
Benefits and harms
In areas of intense malaria transmission, those receiving IRS had lower incidence of malaria compared to those who received ITNs. However, there may be little or no difference between IRS and ITNs in terms of parasite prevalence. In areas of unstable malaria, ITNs were associated with lower malaria incidence and parasite prevalence.
No undesirable effects were identified in the systematic review. However, as stated under the evidence-to-decision table for ITNs, ITNs may play an as yet undetermined role in insecticide resistance development in Anopheles vectors; some users complain that they are too hot to sleep under; and brand-new nets recently removed from packaging may cause slight, transitory irritation to skin, eyes, nose, etc. Similarly, IRS may play an as yet undetermined role in insecticide resistance development in Anopheles vectors; it requires householders to grant permission for spray teams to enter the house; householders are required to remove personal items from houses prior to spraying (e.g., foodstuffs); and some insecticide formulations leave unsightly residue on sprayed surfaces.
Certainty of the Evidence
The certainty of the evidence subjected to systematic review is graded LOW or VERY LOW. The Guidelines Development Group considers that despite the LOW certainty of the evidence included in the systematic review, a strong recommendation for either intervention is warranted based on the fact that there is a considerable body of evidence stretching back several decades pertaining to implementation trials and programmatic data of IRS. The GDG considers this body of evidence, when viewed as a whole, provides strong evidence of the effectiveness of IRS as a malaria prevention and control intervention and that ITNs are considered to be an equally effective alternative intervention.
Preference and values
Resources and other considerations
Similar resources and other considerations apply as to those for IRS and ITNs
Justification
In terms of the relative effectiveness of IRS compared to ITNs, the systematic review published in 2010 (50) reported was only low certainty evidence available for areas of intense transmission and for areas with unstable transmission. It was therefore not possible to arrive at a definitive conclusion on their comparative effectiveness. WHO therefore currently views these two interventions as being of equal effectiveness, and there is no general recommendation to guide the selection of one over the other. Preferences of national malaria programmes, beneficiaries or donors are usually based on operational factors, such as perceived or actual implementation challenges (see Section 4.1.6.2) and the requirement for insecticide resistance prevention, mitigation and management (see Section 4.1). Financial considerations such as cost and cost-effectiveness are also major drivers of decision-making, and selection of malaria vector control interventions should thus be embedded in a prioritization process that considers the cost and effectiveness of all available malaria interventions and aims at achieving maximum impact with the available resources. Evaluations of the relative cost and cost-effectiveness of ITNs and IRS are ongoing to inform revision of the Guidelines.
4.1.2. Combining ITNs and IRS
Conditional recommendation against, Moderate certainty evidence
Prioritize optimal coverage with either ITNs or IRS over combination (2019)
WHO recommends against combining ITNs and IRS and that priority be given to delivering either ITNs or IRS at optimal coverage and to a high standard, rather than introducing the second intervention as a means to compensate for deficiencies in the implementation of the first intervention.
In settings where optimal ITN coverage, as specified in the strategic plan, has been achieved and where ITNs remain effective, additionally implementing IRS may have limited utility in reducing malaria morbidity and mortality. Given the resource constraints across malaria-endemic countries, it is recommended that effort be focused on good-quality implementation of either ITNs or IRS, rather than deploying both in the same area. However, the combination of these interventions may be considered for resistance prevention, mitigation or management should sufficient resources be available.
Practical Info
Given the resource constraints across malaria-endemic countries, the deployment of a second vector control intervention on top of optimal coverage with an existing one should only be considered as part of a broader prioritization analysis aimed at achieving maximum impact with the available resources. In many settings, a switch from ITNs to IRS or vice versa, rather than their combination, is likely to be the only financially feasible option.
Evidence To Decision
Benefits and harms
No benefit of adding IRS to areas where pyrethroid-only ITNs are being used was identified in systematic review.
In areas of confirmed pyrethroid resistance, IRS with a non-pyrethroid insecticide may increase effectiveness against malaria.
No undesirable effects were identified in systematic review. However, the cost of combining two interventions will significantly increase commodity and operational costs.
Certainty of the Evidence
The evidence identified in the systematic reviews showing no benefit of adding IRS in situations where ITNs are already being used is graded as MODERATE.
Preference and values
Resources and other considerations
The degree of pyrethroid resistance and its impact on the effectiveness of pyrethroid-only ITNs should be considered.
Status of vector resistance to the proposed IRS active ingredient needs to be known.
In resource-constrained situations, it is unlikely to be financially feasible to deploy both ITNs and IRS.
It is important to monitor:
vector population densities, EIRs and behaviour
insecticide resistance status and investigations of cross-resistance
quality control of the IRS and ITNs
coverage (access and use) of ITNs
coverage of IRS.
Justification
The systematic review published in 2019 (53) on the deployment of IRS in combination with ITNs (specifically pyrethroid-only LLINs) provided evidence that, in settings where there is optimal coverage with ITNs and where these remain effective, IRS may have limited utility in reducing malaria morbidity and mortality. WHO guidance was developed accordingly to emphasize the need for good-quality implementation of either ITNs or IRS, rather than deploying both in the same area (54). However, the combination of these interventions may be considered for resistance prevention, mitigation or management should sufficient resources be available
Insecticide resistance threatens the effectiveness of insecticidal interventions and hence is a key consideration in determining which vector control interventions to select to ensure impact of is maximized. One approach to the prevention, mitigation and management of vector insecticide resistance is the co-deployment (or combination) of interventions with different insecticides (see Section 4.1 on ‘Prevention, mitigation and management of insecticide resistance’). Therefore, WHO guidance developed based on systematic review (53) differentiated between the effect of combined interventions on malaria morbidity and mortality versus the utility of this approach in a resistance management strategy (54).
A summary of the conclusions (with slight updates for clarity) used to develop the above recommendations is as follows:
In settings with high ITN coverage where ITNs remain effective, IRS may have limited utility in reducing malaria morbidity and mortality. However, IRS may be implemented as part of an IRM strategy in areas where there are ITNs (
19).
Malaria control and elimination programmes should prioritize the delivery of ITNs or IRS at optimal coverage and to a high standard, rather than introducing the second intervention as a means to compensate for deficiencies in the implementation of the first intervention.
If ITNs and IRS are to be deployed together in the same geographical location, IRS should be conducted with a non-pyrethroid insecticide.
Evidence is needed to determine the effectiveness of combining IRS and ITNs in malaria transmission foci, including in low transmission settings. Evidence is also needed from different eco-epidemiological settings outside of Africa.
All programmes in any transmission setting that decide to prioritize the combined deployment of ITNs and IRS over other potential use of their financial resources should include a rigorous programme of M&E (e.g., a stepped wedge introduction of the combination) in order to confirm whether the additional inputs are having the desired impact. Countries that are already using both interventions should similarly undertake an evaluation of the effectiveness of the combination versus either ITNs or IRS alone.
The approach of combining interventions for resistance management was developed largely based on experience with agricultural pest management, and the evidence base from public health remains weak.
These findings and conclusions were substantiated by a systematic review of the evidence published in 2019 (53). The review is currently being updated with evidence from further trials that have been conducted since. Once published, the evidence will be reviewed by WHO.
Research needs:
Further evidence is needed on the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences of combining non-pyrethroid IRS with ITNs vs ITNs only in areas with insecticide resistant mosquito populations.
Determine whether there are comparative benefits (incidence of malaria [infection or clinical] and/or prevalence of malaria infection), as well as potential harms and/or unintended consequences of combining non-pyrethroid IRS with ITNs vs IRS only in areas with insecticide-resistant mosquito populations.
Determine the acceptability of combining IRS and ITNs among householders and communities.
Evaluate new tools for monitoring the quality of IRS and ITN interventions.
Good practice statement
No scale-back in areas with ongoing local malaria transmission (2019)
In areas with ongoing local malaria transmission (irrespective of both the pre-intervention and current level of transmission), WHO recommends that vector control interventions should not be scaled back. Ensuring access to effective malaria vector control at optimal levels for all inhabitants of such areas should be pursued and maintained.
Practical Info
Access to effective vector control interventions will need to be maintained in the majority of countries and locations where malaria control has been effective. This includes settings with ongoing malaria transmission, as well as those in which transmission has been interrupted but in which some level of receptivity and importation risk remains. Malaria elimination is defined as the interruption of local transmission (reduction to zero incidence of indigenous cases) of a specified malaria parasite species in a defined geographical area as a result of deliberate intervention activities. Following elimination, continued measures to prevent re-establishment of transmission are usually required (29). Interventions are no longer required once eradication has been achieved. Malaria eradication is defined as the permanent reduction to zero of the worldwide incidence of infection caused by all human malaria parasite species as a result of deliberate activities.
There is a critical need for all countries with ongoing malaria transmission, and in particular those approaching elimination, to build and maintain strong capacity in disease and entomological surveillance and health systems. The capacity to detect and respond to possible resurgences with appropriate vector control relies on having the necessary entomological information (i.e., susceptibility status of vectors to insecticides, as well as their biting and resting preferences). Such capacity is also required for the detailed assessment of malariogenic potential, which is a pre-condition for determining whether vector control can be scaled back (or focalized).
If areas where transmission has been interrupted are identified, the decision to scale-back vector control should be based on a detailed analysis that includes assessment of the receptivity and importation risk of the area, as well as an assessment of the active disease surveillance system, and capacity for case management and vector control response.
Justification
A comprehensive review of historical evidence and mathematical simulation modelling undertaken for WHO in 2015 indicated that the scale-back of malaria vector control was associated with a high probability of malaria resurgence, including for most scenarios in areas where malaria transmission was very low or had been interrupted (30). Both the historical review and the simulation modelling clearly indicated that the risk of resurgence was significantly greater at higher EIRs and case importation rates, and lower coverage of active case detection and case management.
Once transmission has been reduced to very low levels approaching elimination, ensuring optimal access to vector control for at-risk populations remains a priority, even though the size and demographics of the at-risk populations may change as malaria transmission is reduced.
As malaria incidence falls and elimination is approached, increasing heterogeneity in transmission will result in foci with ongoing transmission in which vector control may need to be optimized and enhanced. Such foci may be the result of particularly high vectorial capacity, lapsed prevention and treatment services, changes in parasites that make the current strategies less effective, or reintroduction of malaria parasites by the movement of infected people or infected mosquitoes. Monitoring the coverage, quality and impact of vector control interventions is essential to maintain the effectiveness of control. Guidance on entomological surveillance across the continuum from control to elimination is provided elsewhere (29).
Once elimination has been achieved, vector control may need to be continued by targeting defined at-risk populations to prevent reintroduction or re-establishment of local transmission.
It is acknowledged that malaria transmission can persist following the implementation of a widely effective malaria programme. The sources and risks of residual transmission may vary by location, time and the existing components of the current malaria programme. This variation is potentially due to a combination of both mosquito and human behaviours, such as when people live in or visit forest areas or do not sleep in protected houses, or when local mosquito vector species bite and/or rest outdoors and thereby avoid contact with IRS or ITNs/LLINs.
Once elimination has been achieved, optimal vector control coverage should be maintained in receptive areas where there is a substantial risk for reintroduction.
4.1.3. Supplementary interventions
Larval source management (LSM)
LSM in the context of malaria control is the management of water bodies that are potential larval habitats for mosquitoes. Such management of water bodies is conducted to prevent the development of the immature stages (eggs, larvae and pupae) and hence the production of adult mosquitoes, with the overall aim of preventing or controlling transmission of malaria. There are four types of LSM:
habitat modification: a permanent alteration to the environment, e.g. land reclamation, filling of water bodies;
habitat manipulation: a recurrent activity, e.g. flushing of streams, drain clearance;
larviciding: the regular application of biological or chemical insecticides to water bodies; and
biological control: the introduction of natural predators into water bodies.
Topical repellents, insecticide-treated clothing and spatial/airborne repellents
Topical repellents, insecticide-treated clothing and spatial/airborne repellents have all been proposed as potential methods for preventing malaria in areas where the mosquito vectors bite or rest outdoors, or bite in the early evening or early morning when people are not within housing structures. These methods have also been proposed for specific population groups, such as those who live or work away from permanent housing structures (e.g., migrants, refugees, internally displaced persons, military personnel) or those who work outdoors at night. In these situations, the effectiveness of ITNs or IRS may be reduced. Repellents have also been proposed for use in high-risk groups, such as pregnant mothers. Despite the potential to provide individual protection against bites from malaria vectors, the deployment of the above personal protection methods in large-scale public health campaigns has been limited, at least partially due to the scarcity of evidence of their public health value. Daily compliance and appropriate use of repellents seem to be major obstacles to achieving such potential impact (56). Individuals’ use of the intervention to achieve personal protection faces the same obstacles.
Space spraying
Space spraying refers to the release of fast-acting insecticides into the air as smoke or as fine droplets as a method to reduce the numbers of adult mosquitoes in dwellings and also outdoors. Application methods include thermal fogging; cold aerosol distribution by handheld or backpack sprayers, ground vehicles or aerial means; and repetitious spraying by two or more sprays in quick succession. Space spraying is most often deployed in response to epidemics or outbreaks of mosquito-borne disease, such as dengue.
Housing modifications
In the context of malaria control, housing modifications are defined as any structural changes, pre- or post-construction, of a house that prevents the entry of mosquitoes and/or decreases exposure of inhabitants to vectors with the aim of preventing or reducing the transmission of malaria. Housing modifications may encompass a wide range of interventions – from those made at the outset in the structural design of the house and the choice of materials used, to modifications made to existing homes, such as the screening or closure of gaps. In 2018, the WHO Department of Public Health, Environmental and Social Determinants of Health published the WHO Housing and health guidelines (56). This document brings together the most recent evidence to provide practical recommendations for reducing the health burden due to unsafe and substandard housing. The review concluded that improved housing conditions have the potential to save lives, prevent disease, increase quality of life, reduce poverty, and help mitigate climate change. It was, however, noted that further evidence was needed on the impact of improved housing in preventing vector-borne diseases.
Available evidence indicates that poor-quality housing and neglected peri-domestic environments are risk factors for the transmission of a number of vector-borne diseases such as malaria, arboviral diseases (e.g. dengue, yellow fever, chikungunya and Zika virus disease), Chagas disease and leishmaniasis (57). Together with metal roofs, ceilings, and finished interior walls, the closing of open eaves, screening doors and windows with fly screens or mosquito netting, and filling holes and cracks in walls and roofs may reduce the mosquitoes’ entry points into houses and potentially reduce transmission of malaria and other vector-borne diseases. A recent review indicated that housing quality is an important risk factor for malaria infection across the spectrum of malaria endemicity in sub-Saharan Africa (58).
Structural housing interventions that may reduce exposure of inhabitants to mosquitoes fall largely into two categories:
Primary house construction:
house designs, such as elevating houses (e.g., using stilts) and using fewer or smaller windows;
construction materials, such as cement or brick walls, corrugated iron roofing, door designs with fewer openings, and closure of eaves that minimize entry holes for mosquitoes.
Modifications to existing house designs:
non-insecticidal interventions which include screening and covering of potential entry points, filling eaves with mud, sand, rubble or cement, installing ceilings and conducting wall maintenance to fill in any cracks;
insecticidal interventions which include insecticidal screening of mosquito entry points, particularly eaves, and the installation of lethal house lures.
Housing modifications are likely to be most effective against mosquitoes that display endophilic and/or endophagic behaviours (i.e., indoor resting and feeding, respectively).
Conditional recommendation, Low certainty evidence
Larviciding (2019)
WHO conditionally recommends the regular application of biological or chemical insecticides to water bodies (larviciding) for the prevention and control of malaria in children and adults living in areas with ongoing malaria transmission as a supplementary intervention in areas where optimal coverage with ITNs or IRS has been achieved, where aquatic habitats are few, fixed and findable, and where its application is both feasible and cost-effective.
Since larviciding only reduces vector density, it does not have the same potential for health impact as ITNs and IRS – both of which reduce vector longevity and provide protection from biting vectors. As a result, larviciding should never be seen as a substitute for ITNs or IRS in areas with significant malaria risk but represents a potential supplementary strategy for malaria control. Larviciding will generally be most effective in areas where larval habitats are few, fixed and findable, and likely less feasible in areas where the aquatic habitats are abundant, scattered and variable.
The following settings are potentially the most suitable for larviciding as a supplementary measure implemented alongside ITNs or IRS:
urban areas: where breeding sites are relatively few, fixed and findable in relation to houses (which are targeted for ITNs or IRS);
arid regions: where larval habitats may be few and fixed throughout much of the year.
Practical Info
Larviciding is most likely to be cost-effective in urban areas where the appropriate conditions are more likely to be present. Larviciding is not generally recommended in rural settings, unless there are particular circumstances limiting the larval habitats and specific evidence confirming that such measures can reduce malaria incidence in the local setting.
WHO’s 2013 Operational manual on larval source management (60) concluded that ITNs and IRS remain the backbone of malaria vector control, but LSM represents an additional (supplementary) strategy for malaria control in Africa. Larviciding will generally be most effective in areas where larval habitats are few, fixed and findable, and likely less feasible in areas where the aquatic habitats are abundant, scattered and variable. Determination of whether or not specific habitats are suitable for larviciding should be based on assessment by an entomologist. The WHO operational manual focuses on sub-Saharan Africa, but the principles espoused are likely to hold for other geographic regions that fit the same criteria. The following settings are potentially the most suitable for larviciding as a supplementary measure implemented alongside ITNs or IRS:
urban areas: where breeding sites are relatively few, fixed and findable in relation to houses (which are targeted for ITNs or IRS);
arid regions: where larval habitats may be few and fixed throughout much of the year.
Evidence To Decision
Benefits and harms
Larviciding for non-extensive larval habitats less than 1 km2 may have an effect in reducing malaria incidence and parasite prevalence compared to no larviciding. However, it is not known if there is an effect in large-scale aquatic habitats.
No undesirable effects were identified in systematic review. However, larviciding may affect non-target fauna; communities may not accept its application to sources of drinking water or water used for other domestic purposes.
Certainty of the Evidence
For larval habitats less than 1 km2, the systematic review assessed that the evidence that larviciding reduces malaria incidence is MODERATE. The certainty of evidence that larviciding in small-scale habitats reduces parasite prevalence is graded as LOW. In larger habitats, the evidence for impact on incidence or prevalence is graded as VERY LOW.
Preference and values
Resources and other considerations
The table below compiled by the Guidelines Development Group lists resources that should be considered for implementing larviciding. Note that, this table does not include resource needs for product selection or assessment of impact of the intervention.
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| Line Item (Resource) | Resource Description |
|---|
|
Staff
|
Competent, trained, supervised and adequately remunerated larvicide operators and skilled entomological technicians, divided into separate teams for surveillance and application of larvicide Transport logisticians and drivers Stock managers Mapping technicians and assistants Environmental assessment support staff
|
|
Training
|
Anopheles larval habitat identification and classification Larvicide application and safety Entomological sampling and identification of Anopheles mosquitoes - larvae, pupae and adults Training for awareness campaigns and to encourage acceptability
|
|
Transport
|
Appropriate vehicles to provide transport of larvicide, equipment, entomological sampling materials and workers to the community Vehicle maintenance costs Fuel
|
|
Supplies
|
|
|
Equipment
|
Larvicide application equipment Larvae, pupae and adult monitoring equipment Mosquito identification equipment, e.g. microscopes Computer/communication equipment
|
|
Infrastructure
|
Appropriate storage facilities for larvicide and equipment Office space for management Insectary for collected larvae and to rear/maintain mosquitoes
|
|
Communication
|
Communication with other ministries and sectors e.g., environment, transport, ministry of works/other infrastructure sectors and city/local councils Communication with the general public e.g. through the education sector and media for awareness of campaigns and to encourage acceptability Communication with the community/local leaders
|
|
Governance/programme management
|
Supervision of mapping and application Supervision of standard monitoring of larval, pupal and adult populations to assess entomological impact Environmental impact assessment supervision
|
Other considerations include:
Justification
Larviciding is deployed for malaria control in several countries, including Somalia and Sudan. However, the systematic review on larviciding conducted in 2019 (59) assessed that the certainty of evidence of impact on malaria incidence or parasite prevalence was moderate or low in non-extensive habitats. Since larviciding only reduces vector density, it does not have the same potential for health impact as ITNs and IRS – both of which reduce vector longevity (a key determinant of transmission intensity) and provide protection from biting vectors. As a result, larviciding should never be seen as a substitute for ITNs or IRS in areas with significant malaria risk.
Larval habitat modification and/or larval habitat manipulation (2021)
No recommendation can be made because the evidence on the effectiveness of a specific larval habitat modification and/or larval habitat manipulation intervention for the prevention and control of malaria was deemed to be insufficient.
Practical Info
Although the available evidence which met the inclusion criteria for the systematic review was considered insufficient to develop specific recommendations, national programmes may decide to use environmental management (habitat modification and/or manipulation) to avoid the creation, and reduce the availability of, larval habitats, where deemed appropriate, based on expert guidance and local knowledge. If such strategies are employed, the selection of the specific intervention(s) should be highly contextual, i.e., it should take into account the specific environment the type of intervention(s) that are relevant to that environment, the resources needed and their availability, the feasibility of the intervention(s), their acceptability by local stakeholders and how they might impact equity. The selection should also take into account previous experience either gained locally or from other areas of similar ecological and epidemiological characteristics where such intervention(s) have been implemented. Additionally, the selection of the comparator should consider other interventions that are known to be cost-effective, for example, larviciding. Where the decision is taken to invest resources into larval habitat modification and/or larval habitat manipulation, the intervention(s) should be designed and conducted with the explicit aim of generating data to demonstrate effective malaria control and preferably, supported with environmental and entomological data as secondary end-points.
When assessing the impact of environmental management against malaria, it is important that the testing of the intervention(s) being investigated is/are specifically conducted for the purpose of preventing or controlling malaria by reducing the availability and productivity of larval habitats. For example, dams are generally constructed for water management, irrigation or power production purposes, not for malaria control. In fact, in some cases, their construction may result in increased larval production due to the creation of standing water bodies. The controlled release of water from the impoundment of a dam, however, is considered an example of habitat manipulation, a recurrent activity which potentially controls mosquito larvae by increasing the flow rate of downstream water with the aim of preventing mosquito development and so controlling malaria transmission. This is one example of the multitude of interventions that fall under the broad category of habitat modification and/or manipulation. To be able to generate evidence on the efficacy of larval habitat modification and/or manipulation in preventing malaria, and to facilitate the interpretation of the evidence once generated, it is important to well define the interventions that are being evaluated and, importantly, compare how the water conditions of larval habitats at the intervention and control sites are affected. For example, if the intervention aimed to increase the water flow of downstream areas, the evaluation should include an assessment of whether this was achieved, as well as to what extent this impacted the development of the immature and adult stages of the mosquito and, ultimately, whether there was an epidemiological impact on against malaria in the intervention arms compared to control areas. This information will then support the evolution of WHO guidance in this area and, ultimately, guide the choice and implementation of efficacious interventions.
Evidence To Decision
Benefits and harms
The systematic review identified two studies that provided low or very low certainty evidence that the controlled release of water from flood gates of dams or spillways (overflow channels) across streams to flush downstream areas with water may reduce malaria incidence and parasite prevalence. Both studies were conducted in very specific settings.
No undesirable effects were identified in the systematic review.
Certainty of the Evidence
The certainty of evidence that release of water using flood gates in dams or spillways on streams reduces malaria incidence or parasite prevalence is graded as LOW or VERY LOW.
Preference and values
No research was identified to determine preference and values
Resources and other considerations
No research was identified that assessed cost effectiveness or resource needs.
Justification
The systematic review to inform WHO recommendations in this area identified only two controlled before-and-after studies meeting the inclusion criteria with epidemiological outcomes that investigated the impact of larval habitat manipulation/modification alone. Two other identified studies combined habitat manipulation with larviciding and so the effect of the two could not be separated. The two eligible studies investigated the impact of larval habitat manipulation against malaria (Martello, E., Yogeswaran, G. & Leonardi-Bee, J. unpublished findings). One study was conducted in an urban area of the Philippines in 1960 and the other in a forested area of India in 2008 where annual IRS was also conducted. The studies provided low or very low certainty evidence that the controlled release of water from flood gates of dams to discharge excess water or using spillways (overflow channels) across streams to automatically flush downstream areas with water (continually or intermittently) reduced clinical malaria incidence or parasite prevalence. The evidence was downgraded due to the lack of appropriate randomization or poor statistical reporting. The studies examined very specific interventions, each studied in a single site, which limited their generalizability. The systematic review reported a number of other studies with only entomological outcomes investigating a wide range of highly heterogeneous interventions falling under the broad term of larval habitat manipulation and/or modification, some of which may only be appropriate in specific ecologies. Given the broad range of interventions and settings in which larval habitat manipulation and/or modification may be applied, the potential impact, feasibility, acceptability and resource needs for each intervention is likely to be highly variable.
Although it is acknowledged that there is a wealth of historical research on environmental management of malaria, unfortunately this literature was insufficiently robust to be included in this systematic review. Therefore, there remains a continued need to robustly demonstrate the epidemiological impact environmental management (habitat modification and/or manipulation) through measurement of malaria incidence or prevalence through further well-designed intervention studies.
Research needs:
The GDG encourages funding of high-quality research on the impact of habitat manipulation and/or modification on malaria transmission to inform the development of specific WHO recommendations in this area. A number of evidence gaps and associated requirements were identified:
Determine the impact (incidence of clinical malaria and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences of the different interventions.
Epidemiological evidence is required on the efficacy against malaria of the same intervention implemented in different settings (where vector species may differ).
Detailed descriptions of the interventions deployed, as well as larval habitat types and vector species targeted. The impact of the intervention on the water conditions of the larval habitats should be assessed, i.e. properties of the habitat that the intervention aims to modify such as water flow, volume, sunlight penetration, salinity or other physical conditions.
Evidence on contextual factors, (i.e., acceptability, feasibility, resource use, cost-effectiveness, equity, values and preferences) related to larval habitat modification and/or manipulation is needed.
Larvivorous fish (2019)
No recommendation can be made because no evidence on the effectiveness of larvivorous fish for the prevention and control of malaria was identified.
Evidence To Decision
Benefits and harms
No desirable effects were identified in the systematic review. However, fish can serve as an additional source of nutrition.
No undesirable effects were identified in the systematic review.
The GDG recognizes that there are specific settings in which the intervention is currently implemented, and in these specific settings programme staff consider it to be effective.
Certainty of the Evidence
The systematic review did not identify any eligible studies demonstrating the effect of larvivorous fish on malaria transmission or disease outcomes.
Preference and values
Resources and other considerations
There is evidence that this intervention would require mosquito aquatic habitats to be large, permanent and few.
Local capacity for breeding fish, maintaining fish and monitoring aquatic habitats would be needed.
The characteristics of settings in which this intervention might be applicable would be needed.
Justification
The systematic review conducted in 2017 on use of larvivorous fish (61) did not identify any studies demonstrating impact on malaria and so there is insufficient evidence to support a recommendation. The GDG recognizes that there are specific settings in which the intervention is currently implemented, and in these specific settings programme staff consider it to be effective. In some of the settings where larvivorous fish are being deployed, programmatic evidence exists; however, this was not determined appropriate for inclusion in the systematic review due to unsuitable study design or other concerns. The GDG acknowledges that there may be data at country/programme level that it is not aware of.
Research needs:
Conditional recommendation against, Low certainty evidence
Topical repellents (2019)
WHO conditionally recommends against the deployment of topical repellents for the prevention and control of malaria at the community level in areas with ongoing malaria transmission.
Further work is required to investigate the potential public health value of topical repellents to separate out potential effects at the individual and/or community level. Analysis conducted to date indicates that no significant impact on malaria can be achieved when the intervention is deployed at community-level due to the high level of individual compliance needed.
Evidence To Decision
Benefits and harms
No desirable effects were identified in systematic review. Based on expert opinion and in line with current WHO recommendations, topical repellents may still be useful in providing personal protection against malaria.
No undesirable effects were identified in the systematic review.
Certainty of the Evidence
The systematic review assessed that the evidence of a benefit from the deployment of topical repellents as a malaria prevention tool in a public health setting is of LOW certainty.
Preference and values
Resources and other considerations
Adherence to daily compliance remains a major limitation
Justification
The evidence from the RCTs included in the systematic review conducted in 2018 (62) provided low certainty evidence of a possible effect of topical repellents on malaria parasitaemia (P. falciparum and P. vivax). The evidence is insufficiently robust to determine whether topical repellents have an effect on clinical malaria.
Research needs:
Conditional recommendation against, Low certainty evidence
Insecticide-treated clothing (2019)
WHO conditionally recommends against deployment of insecticide-treated clothing for the prevention and control of malaria at the community level in areas with ongoing malaria transmission; however, insecticide-treated clothing may be beneficial as an intervention to provide personal protection against malaria in specific population groups.
In the absence of insecticide-treated nets, there is some evidence that insecticide-treated clothing may reduce the risk of malaria infection in specific populations such as refugees and military; it is presently unclear if the results are applicable to the general population.
Evidence To Decision
Benefits and harms
There is some evidence of the use of insecticide -treated clothing on clinical P. falciparum and P. vivax malaria in refugee camps or other disaster settings in the absence of ITNs
No evidence was available on epidemiological effects in the general at-risk population.
No undesirable effects were identified in the systematic review.
Certainty of the Evidence
The systematic review assessed that the evidence of a benefit from the use of insecticide-treated clothing in specific populations as a malaria prevention tool is of LOW certainty.
Preference and values
Resources and other considerations
Such clothing may be beneficial as a tool to provide personal protection against malaria in specific population groups (refugees, military).
Justification
The systematic review carried out in 2018 (62) provided low certainty evidence that insecticide-treated clothing may have protective efficacy against P. falciparum and P. vivax cases, at least in certain specific populations (refugees, military personnel and others engaged in occupations that place them at high risk) and where ITNs were not in use. There was no evidence available on epidemiological effects in the general at-risk population.
Research needs:
Determine the impact (incidence of malaria (infection or clinical) and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences of insecticide-treated clothing in the general population.
Identification of approaches to enhance acceptability/desirability and increase uptake and adherence is needed.
Development of formulations that improve the durability of insecticidal efficacy is needed.
Spatial/Airborne repellents (2019)
No recommendation can be made because the evidence on the effectiveness of spatial/airborne repellents for the prevention and control of malaria was deemed to be insufficient.
Evidence To Decision
Benefits and harms
No desirable effects were identified in systematic review. The meta-analysis showed that spatial repellents had no impact on Plasmodium species’ parasitaemia.
No undesirable effects were identified in the systematic review.
Certainty of the Evidence
The systematic review assessed that the evidence that spatial/airborne repellents has an impact on malaria is of VERY LOW certainty.
Preference and values
Justification
The systematic review published in 2018 (62) concluded that there is very low certainty evidence that spatial or airborne repellents may have a protective efficacy against malaria parasitaemia. Therefore, no recommendation on the use of spatial/airborne repellents in the prevention and control of malaria can be made until more studies assessing malaria epidemiological outcomes have been conducted.
Research needs:
Determine the impact (incidence of malaria (infection or clinical) and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences of spatial/airborne repellents.
Development of spatial repellent insecticide formulations that provide a long-lasting effect is required.
Conditional recommendation against, Very low certainty evidence
Space spraying (2019)
WHO conditionally recommends against using space spraying for the prevention and control of malaria in children and adults living in areas with ongoing malaria transmission; IRS or ITNs should be prioritized instead.
Evidence To Decision
Benefits and harms
No desirable effects were identified by systematic review. Anticipated desirable effects of space spraying are likely to be small, as insecticide formulations used are short-lived. Anopheles mosquitoes are generally considered to be less susceptible to space spraying than Culex or Aedes.
No undesirable effects were identified by systematic review.
Certainty of the Evidence 
The systematic review identified only observational studies reporting number of malaria cases per month. These are graded as VERY LOW certainty evidence.
Preference and values
Resources and other considerations
Justification
Only observational studies were identified by the systematic review and the certainty of the evidence was graded as very low (63). The lack of data from RCTs, other trial designs or quasi-experimental studies has therefore hampered a comprehensive assessment of this intervention and the review concluded that it is unknown whether space spraying causes a reduction in incidence of malaria. Anticipated desirable effects of space spraying are likely to be small, as insecticide formulations used are short-lived. Anopheles mosquitoes are generally considered to be less susceptible to space spraying than Culex or Aedes. Space spraying is frequently applied when cases are at their peak, which is followed by a decline in cases, whether or not control measures are applied. Nevertheless, space spraying is often deployed in response to outbreaks of mosquito-borne disease. Due to the high visibility of this intervention, the decision to use this approach is usually made to demonstrate that the authorities are taking action in response to the outbreak. This practice should be strongly discouraged given the limited evidence of the intervention’s effectiveness, the high cost and the potential for wastage of resources. The GDG therefore felt it necessary to develop a clear recommendation against space spraying for malaria control.
Research needs:
Conditional recommendation, Low certainty evidence
House screening (2021)
WHO conditionally recommends the use of untreated screening of residential houses for the prevention and control of malaria in children and adults living in areas with ongoing malaria transmission.
This recommendation addresses the use of untreated screening of windows, ceilings, doors and/or eave spaces, and does not cover other ways of blocking entry points in houses.
Practical Info
If house screening is being considered as a means to prevent malaria, it is important to identify who the end-user will be and how the intervention will be implemented, i.e. whether this would be a tool that the program promotes for individuals or communities to implement at their own cost, or if screening of houses is undertaken as a programmatic initiative. Depending on the approach, the resources needed, feasibility, up-take and impact on equity may vary and would need to be considered.
Screening of houses may be done post-construction or could be a standard feature for new homes. Intersectoral collaboration, for example between health, housing and environmental sectors, is crucial in the implementation of house screening. It is also important to consider what standards and criteria, if any, need to be set for screening materials and designs as they are for buildings.
Screening of residential houses should be part of an integrated vector management (IVM) approach as promoted under the Global Vector Control Response (13) and deployment of interventions recommended for large-scale deployment (such as ITN or IRS) should be maintained.
In settings where national or local government authorities are not able to provide screening of residential houses as a public health strategy (e.g., due to feasibility/ resource challenges), they should promote its use amongst affected communities.
If house screening is deployed or adopted by communities to prevent malaria, post-distribution monitoring of the intervention is needed to assess material durability, usage, and coverage. This information should guide how regularly screens require replacement or repair and provide information on the sustainability of the intervention.
Evidence To Decision
Benefits and harms
The systematic review (64) concluded that screening may reduce clinical malaria and parasite prevalence of infection, and probably reduces anaemia and entomological inoculation rates.
The systematic review noted the following unintended consequences of the intervention:
Pooled analysis of the two trials showed that individuals living in fully screened houses (covered eaves, windows and doors) were around 16% less likely to sleep under a bed net (RR 0.84 95% CI 0.65 to 1.09; 2 trials, 203 participants).
In one study from the Gambia, individuals living in houses with screened ceilings were around 31% less likely to sleep under a bed net (RR 0.69 95% CI 0.50 to 0.95; 1 trial; 135 participants).
None of the other pre-specified outcomes (all-cause mortality; other disease incidence; adverse effects; unintended effects other than bed net usage) were reported in the included studies.
The GDG noted some other potential undesirable effects, that were judged to be small :
Inhabitants of screened houses may not use other effective interventions such as ITNs
Screening may reduce airflow and result in increased indoor temperatures and reduced ventilation. As a result, occupants may open doors and windows
Reduced airflow and ventilation may result in increased respiratory problems and infections, and increased indoor air pollution
Certainty of the Evidence
The systematic review assessed that the evidence of an impact of house screening on clinical malaria incidence, malaria parasite prevalence and EIR is of LOW certainty. The certainty of evidence for reductions in anaemia was graded as MODERATE.
Preference and values
No research was identified regarding preferences and values.
Resources and other considerations
Resources needed for the screening of houses may depend on whether the intervention is deployed by the programme or implemented by the community. The table below compiled by the GDG lists resources that should be considered. Note that this table does not include resource needs for product selection or assessment of impact of the intervention.
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| Line Item (Resource) | Resource Description |
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Staff
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Competent, trained, supervised and adequately remunerated skilled carpenters/construction workers/community members Behavioural change communication (BCC) staff Transport logisticians and drivers Demonstrators/teachers Monitoring and evaluation (M & E) staff
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Training
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Transport
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Supplies
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Adequate construction material for screening (including but not limited to wood/screen, fasteners). BCC materials (e.g. flip charts, posters, banners, staff clothing) M & E data collection forms
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Equipment
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Infrastructure
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Communication
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Communication with other ministries and sectors e.g. environment, transport, housing, city/local councils and large infrastructure projects, as well as coordination with local building regulators Communication with the community/local leaders Communication with the general public e.g. through the education sector and media for awareness and to encourage uptake
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Governance/ programme management
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Equity
National programs considering the adoption of screening of residential houses as a public health strategy should assess how the implementation of a screening program would affect health equity in the community. Depending on how the intervention is deployed, the effect on equity may vary. For example, if individuals are encouraged to screen houses themselves, equity may be reduced. If the intervention is deployed at the programme level, it may be increased. The impact on equity may also depend on house structure and conditions, as some features may not allow for screening.
Acceptability
The studies included in the systematic review used in-depth interviews and focus group discussions to assess community acceptance of the interventions. In both studies, participants reported that the intervention reduced the number of indoor mosquitoes and house flies. Most participants in both trials chose to have screening after the duration of the trial. Additionally, participants in the study from The Gambia reported a reduction in entry of other animals, such as bats, cockroaches, earwigs, geckos, mice, rats, snakes, and toads. In both trials, participants expressed concern that screening would be damaged by domestic animals and children, or that it would become dirty. In the Ethiopian study, some participants reported that they made further efforts to reduce mosquito entry after screening installation, such as filling in wall openings with mud.
Feasibility
National programs considering the adoption of screening of residential houses as a public health strategy should assess:
Whether the structure and condition of residential houses in respective communities allow for the installation of screening and are accessible.
Whether adequate resources are available, particularly if houses require screening to be made bespoke and if there is a need to renovate some houses to allow screening
The level of community buy-in (acceptability and/or willingness to implement the intervention)
The feasibility of implementation if it is on a large scale, including the impact on resource use and potential changes in cost-effectiveness of the program, but also taking into account values, preferences and cultural norms of the main stakeholders.
How the intervention will be delivered and maintained
Justification
The systematic review to inform WHO guidance in this area identified only two eligible published studies assessing epidemiological outcomes (64). Both studies investigated the impact of house screening (screening of windows, ceilings, doors and/or eaves) with untreated materials against malaria.
The evidence for the assessed outcomes was rated as low to moderate certainty due to risk of bias and imprecision. In the trials included in the systematic review, research teams deployed screening at the community level and as a result, currently there is no evidence as to the benefits and harms of individuals or communities deploying screens themselves. The review identified several studies that were yet to be published on the efficacy of insecticide-treated screening, eave tubes or other forms of housing interventions but the data were not yet available for inclusion in the review. The panel concluded that untreated screening of residential houses may prevent malaria and reduce malaria transmission. The panel judged that policy makers considering house screening should assess the feasibility, acceptability, impact on equity and resources needed for screening houses in their contexts.
Research needs:
WHO encourages funding of high-quality research on the impact of interventions under the broad category of ‘housing modifications’ to further inform the development of specific WHO recommendations. Four trial results awaiting publication are likely to enrich the current evidence-base on housing modifications for preventing malaria and controlling malaria transmission, and publication of these studies is strongly encouraged.
A number of specific evidence gaps and associated requirements were identified:
Further evidence is required on the impact (incidence of malaria (infection or clinical) and/or prevalence of malaria infection) and potential harms/unintended consequences of house screening, as well as other house modification interventions deployed singly or in combination.
Epidemiological evidence is required on the efficacy against malaria of the same intervention implemented in different settings (where vector species may differ).
Evidence on contextual factors (i.e., acceptability, feasibility, resource use, cost-effectiveness, equity, values and preferences) related to house screening, as well as other house modification interventions is needed.
Resources needed, costs and cost-effectiveness, for various deployment options (at the programme-, community-, individual-level) of house screening need to be identified.
Deployment mechanisms and community buy-in for house screening as well as other house modification interventions.
4.1.4. Other considerations for vector control
4.1.4.1. Special situations
Residual transmission
WHO acknowledges that even full implementation of ITNs or IRS will not be sufficient to completely halt malaria parasite transmission across all settings (65). Some residual malaria parasite transmission will occur, even with optimal access to and usage of ITNs or in areas with high IRS coverage. Residual transmission occurs as a result of a combination of human and vector behaviours, for example, when people reside in or visit forest areas or do not sleep in protected houses, or when local mosquito vector species exhibit one or more behaviours that allow them to avoid ITNs or IRS, such as biting outside early in the evening before people have retired indoors and/or resting outdoors.
There is an urgent need for greatly improved knowledge of the bionomics of the different sibling species within malaria vector species complexes, and new interventions and strategies in order to effectively address residual transmission. While this knowledge is being gained and interventions are being developed, national malaria control programmes must prioritize the effective implementation of current interventions to reduce transmission to the lowest level possible. At the same time, they should collaborate with academic or research institutions to generate local evidence on the magnitude of the problem of residual transmission of malaria, including information on human and vector behaviours, and the effectiveness of existing and novel interventions.
Residual transmission is difficult to measure, as is the specific impact of supplementary tools on this component of ongoing transmission. Standardized methods for quantifying and characterizing this component of transmission are required in order to evaluate the effectiveness of single or combined interventions in addressing this biological challenge to malaria prevention and control and elimination.
Epidemics and humanitarian emergencies
In the acute phase of a humanitarian emergency, the first priorities for malaria control are prompt and effective diagnosis and treatment. Vector control also has the potential to play an important role in reducing transmission. However, the evidence base on the effectiveness of vector control interventions deployed in these settings is weak (66).
During the acute phase, decisions on vector control and prevention will depend on:
Malaria infection risk;
Behaviour of the human population (e.g. mobility, where they are sleeping or being exposed to vector mosquitoes);
Behaviour of the local vector population (e.g. indoor resting, indoor biting, early evening or night biting);
The type of shelter available (e.g. ad-hoc refuse materials, plastic sheeting, tents, more permanent housing).
Effective case management can be supplemented with distribution of ITNs, first targeting population groups most susceptible to developing severe malaria, but with the ultimate goal of achieving and maintaining optimal coverage. IRS can also be applied in well-organized settings, such as transit camps, but is generally unsuitable where dwellings are scattered widely, of a temporary nature (less than three months) or constructed with surfaces that are unsuitable for spraying. IRS is best suited for protecting larger populations in more compact settings, where shelters are more permanent and solid.
Some vector control interventions and personal protection measures have been specifically designed for deployment in acute emergency situations. Plastic sheeting is sometimes provided in the early stages of humanitarian emergencies to enable affected communities to construct temporary shelters. In these new settlements, where shelter is very basic, use of insecticide-treated plastic sheeting (ITPS) to construct shelters may be a practical, acceptable and feasible approach. Laminated polyethylene tarpaulins that are impregnated with a pyrethroid during manufacture are suitable for constructing such shelters. As with IRS, ITPS is only effective against indoor resting mosquitoes, but the degree to which it impacts transmission has yet to be confirmed. Moreover, pyrethroid-treated plastic sheeting should not be deployed in areas where the local malaria vectors are resistant to pyrethroids.
Another intervention with potential for deployment in emergency situations is the long-lasting insecticide impregnated blanket or topsheet. Blankets or lightweight topsheets are often included in emergency relief kits. One advantage of blankets and topsheets is that they can be used anywhere people sleep (e.g. indoors, outdoors, any type of shelter). However, as with ITPS, the evidence base regarding the effectiveness of this approach is currently limited. Data from community RCTs of long-lasting pyrethroid-treated wash-resistant blankets and topsheets would be required to determine public health value and develop specific policy recommendations for such interventions.
In the post-acute phase, optimal coverage with ITNs or IRS may be feasible. Deployment of insecticide-treated plastic sheeting for shelter construction may be more practical in situations where ITN use or the application of IRS is not possible, although currently there is no WHO policy recommendation for this intervention.
Migrant populations and populations engaged in high-risk activities
As noted above, topical repellents and insecticide-treated clothing may be practical interventions for providing personal protection to specific populations at risk of malaria due to occupational exposure, e.g. military personnel, night-shift workers, forestry workers. However, the available evidence does not support the large-scale deployment of such interventions for reducing or preventing infection and/or disease in humans when assessed at the population level and few studies have reported disease outcomes at the individual level. Data demonstrating epidemiological impact would be required to determine their public health value for these populations.
4.1.4.2. Implementation challenges
Vector control plays a vital role in reducing the transmission and burden of vector-borne disease, complementing the public health gains achieved through disease management. Unfortunately, at present, the potential benefits of vector control are far from being fully realized. WHO identifies the following reasons for this shortfall (67):
The skills to implement vector control programmes remain scarce, particularly in the resource-poor countries in most need of effective vector-borne disease control. In some cases, this has led to control measures being implemented that are unsuitable, poorly targeted or deployed at insufficient coverage. In turn, this has led to suboptimal resource use and sometimes avoidable insecticide contamination of the environment;
Insecticide application in agriculture and poor management of insecticides in public health programmes have contributed to resistance in disease vectors; and
Development programmes, including irrigated agriculture, hydroelectric dam construction, road building, forest clearance, housing development and industrial expansion, all influence vector-borne diseases, yet opportunities for intersectoral collaboration and for adoption of strategies other than those based on insecticides are seldom realized.
Acceptability, participation and ethical considerations
Acceptability and end-user suitability of the vector control interventions included in the Guidelines were considered when developing the Evidence-to-Decision Frameworks, as part of the GRADE process.
ITNs are generally acceptable to most communities. In many malaria-endemic countries, untreated nets were in use for many years prior to the introduction of ITNs and, even where there is not a long history of their use, they have become familiar tools for preventing mosquito bites. Individuals often appreciate the extra privacy afforded by a net, as well as its effectiveness in controlling other nuisance insects. In very hot climates, ITNs may be less acceptable, as they are perceived to reduce air flow, making it too hot to allow for a comfortable sleep. In areas where mosquito densities are low or where malaria transmission is low, individuals and communities may perceive less benefit in using nets.
Community acceptance of IRS is critical to the programme’s success, particularly as it involves disruption to the household, requiring householders to remove certain articles and allow spray teams to enter all rooms of the house. Repeated, frequent spraying of houses over extended periods can lead to refusal by householders. Reduced acceptance has been an impediment to effective IRS implementation in various parts of the world (68).
Larviciding for malaria vector control is currently not deployed at the scale of ITNs or IRS, and many communities are therefore unfamiliar with it. Larviciding is likely to be more acceptable in communities that have a good understanding of the lifecycle of mosquitoes and the link with the transmission of malaria or other diseases. Community members may have concerns about larvicides being applied to drinking water or other domestic water sources. A well-designed community sensitization programme is required to ensure that communities fully understand the intervention and that any concerns about health and safety aspects are addressed.
Community participation in the implementation of vector control interventions is often in the form of “instruction” and “information”, with decisions about the need for interventions being made at international and national levels. Taking into account communities’ views on the recommended interventions may promote acceptance and adherence to the intervention. Increased levels of participation (e.g. consultation, inclusion and shared decision-making) should ideally be included in the future development of improved and new vector control interventions, from inception through to the planning and implementation stages.
WHO acknowledges that appropriate policy-making often requires explicit consideration of ethical matters in addition to scientific evidence. However, the ethical issues relevant to vector-borne disease control and research have not previously received the analysis necessary to further improve public health programmes. Moreover, WHO Member States lack specific guidance in this area. The Seventieth World Health Assembly (69) requested the Director-General “to continue to develop and disseminate normative guidance, policy advice and implementation guidance that provides support to Member States to reduce the burden and threat of vector-borne diseases, including to strengthen human-resource capacity and capability for effective, locally adapted, sustainable and ethically sensitive vector control; to review and provide technical guidance on the ethical aspects and issues associated with the implementation of new vector control approaches in order to develop mitigating strategies and solutions; and to undertake a review of the ethical aspects and related issues associated with vector control implementation that include social determinants of health, in order to develop mitigating strategies and solutions to tackle health inequities.” As a first step towards developing appropriate guidelines within the next two years, a scoping meeting was convened by WHO to identify the ethical issues associated with vector-borne diseases (70). Further work has been undertaken to develop guidance. Once available, it will be reflected in the Guidelines.
Unique ethical issues associated with vector control that were identified at the February 2017 scoping meeting include the ethics of coercive or mandated vector control, the deployment of insecticides (and growing vector resistance to insecticides), and research on and/or deployment of new vector control technologies. Genetically modified mosquitoes are one such innovation that presents potential challenges, including how to prevent their spread beyond the intended geographical target areas and limit potential effects on the local fauna. WHO has established a robust evaluation process for new vector control interventions (31) in order to ensure that these are fully and properly assessed prior to any WHO recommendation for their deployment.
Equity, gender and human rights
The aim of all of the work of WHO is to improve population health and decrease health inequities. Sustained improvements to physical, mental and social well-being require actions in which careful attention is paid to equity, human rights principles, gender and other social determinants of health. A heightened focus on equity, human rights, gender and social determinants is expressed in the WHO Thirteenth General Programme of Work.
In pursuit of this outcome, WHO is committed to providing guidance on the integration of sustainable approaches that advance health equity, promote and protect human rights, are gender-responsive and address social determinants into WHO programmes and institutional mechanisms; promoting disaggregated data analysis and health inequality monitoring; and providing guidance on the integration of sustainable approaches that advance health equity, promote and protect human rights, are gender-responsive and address social determinants into WHO’s support at country level (71).
WHO advocates for optimal coverage with recommended vector control interventions. As such, malaria vector control is expected to be implemented without discrimination on the basis of age, sex, ethnicity, religion or other characteristics. In some cases, special effort is required to reach populations that are geographically isolated or adopt a nomadic lifestyle.
In contrast to the situation observed with HIV and TB, malaria has not been associated with systematic discrimination against individuals or groups assumed to be at a high risk of infection. However, malaria disproportionately affects the most vulnerable populations, including the rural poor, pregnant women, children, migrants, refugees, prisoners and indigenous populations. For these populations, social inequality and political marginalization may impede access to health services, and there may be additional barriers created by language, culture, poor sanitation, lack of access to health information, lack of informed consent in testing and treatment, and inability to pay user fees for medical services. National malaria control programmes are increasingly encouraged to identify vulnerable groups and situations of inequitable access to services and to design approaches, strategies and specific activities to remove human rights and gender-related inequities.
Resource implications and prioritization
In this edition of the Guidelines, resource implications and the cost-effectiveness of vector control interventions were largely addressed by drawing on expert opinion within the GDG due to limited data to inform discussions. Although it is recognized that resource considerations should ideally be based on evidence, there was insufficient clarity on how to collate and present such data to the GDG and how to reflect this within the Guidelines at the time of writing. For future revisions of the Guidelines, it is envisaged that this area will be expanded upon for both new and existing recommendations.
The most recent systematic review of the cost and cost-effectiveness of vector control interventions was published in 2011, drawing on studies published between 1990 and 2010 (72). The body of evidence collated was based on the use of ITNs/LLINs and IRS in a few sites in sub-Saharan Africa. The authors found large variations in the costs of intervention delivery, which reflected not only the different contexts but also the various types of costing methodologies employed; these studies were rarely undertaken alongside clinical and epidemiological evaluations. The review reported that, while ITNs/LLINs and IRS were consistently found to be cost-effective across studies, evidence to determine their comparative cost-effectiveness was insufficient. WHO GMP is working with partners to update the evidence review on the cost and cost-effectiveness evidence of the vector control interventions as part of an ongoing broader systematic review on the cost and cost-effectiveness of malaria control interventions and this review will be drawn upon in future GDG discussions. WHO GMP is also working with partners to ensure that the internal database on the cost and cost-effectiveness evidence of malaria control interventions is maintained, to support future GDG deliberations. It is also planned that systematic reviews commissioned in future will include a search of the literature on both the cost and cost-effectiveness of interventions under consideration. This information will be collated in advance of the GDG meetings to be considered as part of the evidence to decision framework alongside other evidence for an intervention, such as its epidemiological impact, acceptability, feasibility, and impact on equity. Furthermore, it is envisaged that the gaps in the economic evidence for the previously approved recommendations will be gradually closed by means of systematic searches of the literature for studies adding to the evidence in this area.
Given that resource considerations are highly context-specific and that the guideline content will not be sufficient to inform resource prioritization at (sub-)national levels, GMP is conducting further work to support country-level decision-making as part of the High burden to high impact initiative, and will expand on this work with a particular focus on informing deployment of an increasing number of interventions across different settings.
Human resources and entomological capacity
The Global vector control response 2017–2030 (13) notes that effective and sustainable vector control is achievable only with sufficient human resources, an enabling infrastructure and a functional health system. A vector control needs assessment (15) will help to appraise current capacity, define what is needed to conduct proposed activities, identify opportunities for improved efficiencies in vector control, and guide resource mobilization.
Formulating an inventory of existing human, infrastructural (functioning insectary and entomological laboratory for species identification and resistance testing, vehicles, spray equipment, etc.), institutional and financial resources available, and making an appraisal of existing organizational structures for vector control are essential first steps. The inventory should cover all resources available at national and subnational levels, including districts. A broader appraisal of relevant resources available outside of the vector-borne disease programme, including in municipal governments, non-health ministries, research institutions and implementing partners, should be conducted. An evaluation of career structures within national and subnational programmes is also important. A comprehensive plan for developing the necessary human, infrastructural and institutional capacity within programmes should be formulated. The plan should identify any additional resources and associated costs involved in achieving the desired objectives and set out clear terms of reference for the different staffing positions required.
Capacity-building priorities for established staff should be defined through a comprehensive training needs assessment led by the ministry of health and aligned with available WHO guidance (73).
4.1.4.3. Monitoring and evaluation of vector control
Monitoring involves routine data collection and reporting to determine progress made in the implementation of a programme or strategy. Evaluation involves rigorous assessment and attribution of impacts to a programme or strategy. The combination of monitoring and evaluation facilitates understanding of the cause-and-effect relationship between implementation and impact and is used to guide planning and implementation, to assess effectiveness, to identify areas for improvement, and to account for resources used.
Monitoring and evaluation of vector control interventions is covered in detail in the WHO reference manual on malaria surveillance, monitoring and evaluation (29). In addition, a brief synopsis of quality assurance is provided below.
Quality assurance of vector control interventions
Quality assurance is the implementation of systematic and well-planned activities to prevent substandard services or products.
Lower than expected effectiveness may be due to a variety of factors related to implementation. These can include incorrect application of the intervention, inadequate procurement planning, poor quality of deployed products and failure to achieve optimal coverage. Quality assurance efforts should be continuous, systematic and independent. Continuous monitoring and supervision are required to ensure that staff are adequately trained and follow technical guidelines for pesticide application and personal safety. Vector control programmes must include a quality assurance programme designed to monitor the effectiveness of the control activities. A quality assurance programme should monitor applicator performance and control outcomes.
The WHO Model Quality Assurance System for Procurement Agencies (74) details the quality assurance steps and processes involved in procuring pharmaceutical products and diagnostics, but the principles are equally applicable to vector control products.
For vector control products, the key elements of quality assurance are:
Sourcing only products prequalified by WHO for deployment against malaria vectors;
Requesting the supplier/manufacturer to provide a Certificate of Analysis for each batch of the product actually being supplied;
Pre-shipment inspection and sampling according to WHO guidance and/or International Organization for Standardization (ISO) standards, performed by an independent sampling agent;
Pre-shipment testing conducted by an independent quality control laboratory (WHO prequalified, or ISO 17025 or Good Laboratory Practice accredited) to determine that the product conforms to approved specifications according to the WHO/CIPAC test methods;
Testing on receipt in country (post-shipment quality control testing) should only be conducted if specific risks related to transport have been identified or specific concerns over potential product performance justify this additional expense;
Tender conditions should include provisions for free-of-cost replacement of shipments that fail quality control checks and disposal of failed lots;
Post-marketing surveillance may be required, depending on the product and context, to monitor performance over time in order to ensure that products continue to conform to their specifications and/or recommended performance as set by WHO. For ITNs, this may require testing both physical durability and insecticidal efficacy. For IRS products, bioefficacy on sprayed surfaces of a different nature (e.g. mud, brick), as applicable, should be periodically tested according to WHO procedures when an insecticide is first introduced into a country. Subsequent measurement of insecticide decay on sprayed surfaces should be done only if necessary, as it will incur additional expense. Countries can make post-marketing surveillance a priority in cases where there are no country-specific data on certain ITNs or IRS products, or where anecdotal data on poor performance of certain products may exist. Agreement on the need and scope of the proposed activities should be reached by all in-country stakeholders, including the national regulatory authority. All evaluations should follow WHO guidance.
Quality assurance of the field application of vector control interventions should form an integral part of the national programme’s strategy and should include:
High-quality training for all staff engaged in field implementation of vector control interventions;
Regular supervision, monitoring and follow-up of field operations;
Periodic testing of the quality of IRS operations through WHO cone bioassay of sprayed surfaces;
Periodic testing of the insecticide concentration on ITNs using WHO cone bioassay and/or chemical analysis.
The WHO cone bioassay (preferably using fully susceptible anophelines obtained from insectaries) is currently the only tool available for assessing the bioefficacy of ITNs and the quality of the application of IRS insecticides to walls and other internal surfaces. Colorimetric assays are under development that aim to rapidly quantify the amount of insecticide on a sprayed surface in the field without the need for a bioassay on live mosquitoes. These colorimetric assays, when available, should enable programmes to increase the speed and ease of quality assurance testing of IRS applications.
4.1.5. Research needs
WHO’s guideline development process for new vector control interventions relies on evidence from at least two well-designed and well-conducted studies with epidemiological endpoints to demonstrate the public health value of the intervention. If the initial two studies generate contradictory or inconsistent results or suffer from design limitations that preclude comprehensive assessment of an intervention’s potential public health value, further trials with epidemiological endpoints may be required. As such, WHO encourages the use of appropriate study designs, including the generation of baseline data and appropriate follow-up times that consider the characteristics of the intervention and its intended deployment, expected durability/residual efficacy and replacement intervals, and the epidemiology (e.g., pathogen transmission intensity) of the selected study site. WHO encourages studies to be conducted for durations that maximize the likelihood that the study objectives and targeted statistical power will be robustly achieved so as to strengthen the evidence used to inform deliberations by a GDG regarding a potential WHO recommendation. Detailed descriptions of the setting, interventions deployed, and vector species targeted are required. Investigators are encouraged to share their study design and methodology with WHO prior to commencing the study in order to enable the VCAG to validate whether the data generated are likely to provide quality evidence to inform the development of a WHO recommendation. High research standards should be employed in conducting, analysing and reporting studies, ensuring that studies are adequately powered, and appropriate randomization methods and statistical analyses are used. WHO requires studies to be conducted in compliance with international ethical standards and good clinical and laboratory practices. Further information on evaluation standard for vector control interventions can be found in Norms, standards and processes underpinning WHO vector control policy development (31).
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| Intervention | Research needs |
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| Pyrethroid-only ITNs | Determine the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences* of new types of nets and insecticides in areas where resistance to pyrethroids is high. |
| Determine the comparative effectiveness and durability of different net types. |
| Determine the effectiveness of nets in situations of residual/outdoor transmission. |
| Determine the impact of ITNs in transmission ‘hotspots’ and elimination settings. |
| Pyrethroid-PBO nets | Further evidence is needed on the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences on pyrethroid-PBO nets. |
| Indoor residual spraying (IRS) | Further evidence is needed on the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences of IRS. |
| Determine the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) as well as harms and/or unintended consequences of IRS in urbanized areas with changing housing designs. |
| Determine the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences of IRS using new insecticides in areas where mosquitoes are resistant to currently deployed insecticides. |
| Determine the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) of IRS in areas with different mosquito behaviours (such as in areas with outdoor transmission). |
| Given the relatively high cost of implementing IRS, especially in the context of growing insecticide resistance, and when delivering IRS in remote areas, there is a need to investigate new approaches to the implementation of IRS to increase cost-effectiveness. |
| Combining IRS and ITNs | Further evidence is needed on the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences of combining non-pyrethroid IRS with ITNs vs ITNs only in areas with insecticide resistant mosquito populations. |
| Determine whether there are comparative benefits (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences of combining non-pyrethroid IRS with ITNs vs IRS only in areas with insecticide resistant mosquito populations. |
| Determine the acceptability of combining IRS and ITNs among householders and communities. |
| Evaluation of new tools for monitoring the quality of IRS and ITN interventions is needed. |
| Larviciding | Further evidence is needed on the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences of larviciding. |
| Evaluation of new technologies for identifying aquatic habitats is needed. |
| Larval habitat manipulation/modification | Determine the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences of the different interventions. Epidemiological evidence is required on the efficacy against malaria of the same intervention implemented in different settings (where vector species may differ). |
| Detailed descriptions of the interventions deployed, as well as larval habitat types and vector species targeted are needed. The impact of the intervention on the water conditions of the larval habitats should be assessed, i.e. properties of the habitat that the intervention aims to modify such as water flow, volume, sunlight penetration, salinity or other physical conditions. |
| Evidence is needed on contextual factors, (i.e., acceptability, feasibility, resource use, cost-effectiveness, equity, values and preferences) related to larval habitat modification and/or manipulation. |
| Larvivorous fish | Determine the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences of the use of larvivorous fish. |
| Topical repellents | Determine the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences of topical repellents for individuals in specific settings and target populations. |
| Insecticide-treated clothing | Determine the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences of insecticide-treated clothing in the general population. |
| Identify approaches to enhance acceptability/desirability and increase uptake and adherence. |
| Develop formulations that improve the durability of insecticidal efficacy. |
| Spatial/airborne repellents | Determine the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences of spatial/airborne repellents. |
| Develop spatial repellent insecticide formulations that provide a long-lasting effect. |
| Repellents in general | Generate epidemiological and/or entomological evidence of whether repellents cause diversion of malaria mosquitoes from a treated area to a neighbouring untreated area. |
| Space spraying | Determine the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences of space spraying, particularly in emergency situations. |
| House modifications | Further evidence is needed on the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) as well as potential harms/unintended consequences of house screening, and other housing modification interventions deployed singly or in combination. |
| Epidemiological evidence is required on the efficacy against malaria of the same intervention implemented in different settings (where vector species may differ). |
| Evidence is needed on contextual factors (i.e., acceptability, feasibility, resource use, cost-effectiveness, equity, values and preferences) related to house screening, and other housing modification interventions. |
| Determine the resources needs, costs and cost-effectiveness, for various deployment options (at the programme-, community-, individual-level) for house screening. |
| Develop deployment mechanisms and community buy-in for house screening and other housing modification interventions. |
| Insecticide resistance management | Determine the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) of different strategies for insecticide resistance management such as using rotations of insecticides, mosaics, etc. |
| Determine the impact of insecticide resistance on key outcomes (malaria mortality, clinical disease and prevalence of infection). |
- *
Harms/unintended consequences may include undesirable effects on individuals, the community, mosquito bionomics and the environment.
Other research needs and evidence gaps required to further update guidance were identified as follows:
evidence on the linkage or correlation between the epidemiological and entomological endpoints used to demonstrate impact;
evidence on contextual factors (i.e., structural challenges and opportunities, acceptability, feasibility, resource use, cost-effectiveness, equity, values and preferences in various settings) related to different vector control interventions;
evidence to support the resources listed and other considerations for resource use provided under each recommended intervention in order to aid guidance on prioritization of interventions (wherever possible, following examples provided in other WHO guidance and guidelines); and
evidence of the benefits (incidence of clinical malaria and/or or prevalence of malaria infection) as well as harms/unintended consequences of deployment of interventions in special situations. For example, a) interventions designed to control outdoor transmission of malaria, and b) protecting specific populations with high occupational exposure to malaria.
4.3. Vaccine
The use of vaccines for the prevention of malaria
Immunization is a success story for global health and development, saving millions of lives every year. Between 2010 and 2018, 23 million deaths were averted with the measles vaccine alone. The number of infants vaccinated annually – more than 116 million, or 86% of all infants born – has reached the highest level ever reported. More than 20 life-threatening diseases can now be prevented through immunization. Since 2010, 116 countries have introduced vaccines that they did not previously use, including those against major killers such as pneumococcal pneumonia, diarrhoea, cervical cancer, typhoid, cholera and meningitis (87).
A vaccine has the potential to increase the proportion of children with access to one or more approaches to malaria prevention tools (e.g. ITNs). Introduction of the RTS,S/AS01 vaccine in the Malaria Vaccine Implementation Programme extended the reach of malaria prevention tools; across the three pilot countries more than two thirds of children who reportedly did not sleep under an ITN received at least the first dose of RTS,S/AS01. Overall, vaccine introduction increased to over 90% the proportion of children in each of the three countries with access to one or more malaria prevention tool (ITN or RTS,S/AS01). Vaccine uptake was equitable by sex and socioeconomic status and had no negative effects on the uptake of other childhood vaccinations, ITN use, or health-seeking behaviour for febrile illness (88).
Malaria vaccine pipeline
The RTS,S/AS01 vaccine is the first and currently the only malaria vaccine to be recommended for use by WHO. RTS,S/AS01 is the result of decades of public–private scientific partnership, with origins dating back to 1983. Although there are a handful of P. falciparum malaria vaccine candidates in the clinical stages of evaluation, RTS,S/AS01 is the first vaccine to have completed Phase 3 evaluations (89) and the first to be provided to children through routine immunization services as part of phased pilot introductions. In 2015, RTS,S/AS01 received a positive scientific opinion from the European Medicines Agency (90) and in 2019, it received national regulatory authorization for use in the pilot areas of Ghana, Kenya and Malawi for the Malaria Vaccine Implementation Programme. A separate trial of RTS,S/AS01 took advantage of the vaccine’s high initial efficacy by administering a primary series of three doses at monthly intervals and subsequent annual single doses just prior to the intense, 4–5 month-long high transmission season. The vaccine was non-inferior to seasonal malaria chemoprevention (SMC); the combination of the vaccine and SMC was significantly better than either SMC alone or RTS,S/AS01 alone (91).
Two vaccine candidates are approaching late-stage clinical evaluation: the R21/MatrixM vaccine candidate targeting PfCSP protein (92) and the attenuated whole sporozoite vaccine PfSPZ (93). Additional candidates targeting other malaria life-cycle stages include the Rh5 blood-stage vaccine candidate (94) and Pfs25 and Pfs230 vaccine candidates targeting sexual-stage antigens to prevent human-to-mosquito transmission (NCT02942277). New technologies, such as DNA-and mRNA-based vaccines (95), the ongoing development of adjuvants (96), and delivery platforms such as virus-like particles (VLPs; the delivery platform used for RTS,S/AS01) and vesicle-based technologies are being explored for use in malaria vaccines. WHO has developed guidelines on the quality, safety, and efficacy of the recombinant malaria vaccines targeting preerythrocytic and blood stages of P. falciparum (97) and a set of preferred product characteristics (PPCs). The PPCs include attributes ranging from safety and efficacy to route of administration, product stability and storage, in order to help support the ongoing development of new malaria vaccines. These PPCs (98) are currently being updated to reflect recent advances in malaria vaccine research and development.
National programmes for immunization and malaria
The RTS,S/AS01 malaria vaccine should be provided as part of a comprehensive malaria control strategy. All malaria control interventions provide partial protection and the highest impact is achieved when multiple interventions are used concomitantly. Appropriate mixes of interventions should be identified for different subnational strata. These are defined by national malaria programmes (NMPs) on the basis of the local malaria epidemiology (e.g. transmission intensity, age pattern of severe disease, vector species, insecticide resistance patterns) and contextual factors (e.g. structure and function of the formal health system).
Where applicable, the malaria vaccine should be integrated into relevant immunization guidelines and malaria control strategies, including national strategic plans to define the package of interventions needed to optimize malaria control and elimination in a country. WHO is developing operational guidance on principles for the subnational tailoring of malaria interventions.
Country considerations and planning for malaria vaccine introduction should rely on data-driven decision-making in which NMP and Expanded Programme on Immunization (EPI) staff consider parasite prevalence, disease burden, existing malaria interventions, vaccine delivery, the logistics, strength and support of the immunization programme, and the availability of funding support, among other factors. Decision making on whether to adopt and implement the malaria vaccine should be in close collaboration between the NMP and the EPI and other relevant ministry of health departments. In pilot countries, the NMP actively participated in the vaccine introduction and implementation activities in order to ensure that malaria control perspectives were incorporated and to maximize opportunities for integration. Malaria vaccine technical working groups were established with joint participation from the EPI and NMP to provide technical guidance on decision-making and a forum for alignment. The EPI leads the logistics of vaccine roll-out and delivery to relevant health facilities. The EPI manages the planning and activities required for vaccine introduction and programme implementation, such as vaccine and supplies procurement; advocacy; communications and social mobilization; training and supervision of health personnel; logistics and cold chain for vaccine storage; service delivery; and monitoring and evaluation. Both fixed sites for vaccination at health care facilities and opportunities for mobile vaccination delivery or outreach services should be considered. To increase uptake, periodic mass vaccination campaigns or periodic intensified routine immunization activities can be deployed. Monitoring of coverage levels occurs through routine health facility data; the malaria vaccine can be integrated into the District Health Information Software 2 (DHIS2) platform alongside NMP and EPI indicators.
Please refer to the WHO malaria vaccine position paper for more information on the malaria vaccine (99).
Please refer to WHO Immunization, Vaccines and Biologicals for more resources and published guidance, including the forthcoming “Guide for introducing a malaria vaccine."
Strong recommendation for, High certainty evidence
The RTS,S/AS01 malaria vaccine should be used for the prevention of P. falciparum malaria in children living in regions with moderate to high transmission as defined by WHO.
The RTS,S/AS01 malaria vaccine should be provided in a four-dose schedule in children from 5 months of age.
Countries may consider providing the RTS,S/AS01 vaccine seasonally, with a five-dose strategy, in areas with highly seasonal malaria or with perennial malaria transmission with seasonal peaks.
Countries that choose to introduce the vaccine in a five-dose seasonal strategy are encouraged to document their experiences, including adverse events following immunization.
RTS,S/AS01 malaria vaccine should be provided as part of a comprehensive malaria control strategy.
Practical Info
Vaccine characteristics, content, dosage, administration and storage
RTS,S/AS01 is a pre-erythrocytic recombinant protein vaccine, based on the RTS,S recombinant antigen. It comprises the hybrid polypeptide RTS, in which regions of the P. falciparum circumsporozoite protein known to induce humoral (R region) and cellular (T region) immune responses are covalently bound to the hepatitis B virus surface antigen (S). The vaccine is currently produced as a two-dose RTS,S powder to be reconstituted with a two-dose AS01 adjuvant system suspension. After reconstitution, the total volume is 1ml (two doses of 0.5 ml). No preservative is included in either the RTS,S formulation or the AS01 adjuvant system. The vials should therefore be discarded at the end of the vaccination session, or within six hours after opening, whichever comes first. The reconstituted 0.5ml vaccine should be administered by injection into the deltoid muscle in children aged 5 months or older. The shelf life of the RTS,S/AS01 vaccine is three years. A vaccine vial monitor is on the AS01 vial (90).
Schedule
WHO recommends that the first dose of vaccine be administered from 5 months of age. There should be a minimum interval of four weeks between doses. The vaccine should be administered in a three-dose primary schedule, with a fourth dose provided 12–18 months after the third dose to prolong the duration of protection. However, there can be flexibility in the schedule to optimize delivery, for example, to align the fourth dose with other vaccines given in the second year of life. Children who begin their vaccination series should complete the four-dose schedule (99).
Optional schedule for settings with highly seasonal malaria or perennial malaria with seasonal peaks
Countries may consider providing the RTS,S/AS01 vaccine seasonally, with a five-dose strategy in areas with highly seasonal malaria or with perennial malaria transmission with seasonal peaks. This strategy seeks to maximize vaccine impact by ensuring that the period of highest vaccine efficacy (just after vaccination) coincides with the period of highest malaria transmission. The primary series of three doses should be provided at monthly intervals, with additional doses provided annually prior to the peak transmission season. Countries that choose seasonal deployment of the RTS,S/AS01 vaccine are strongly encouraged to document their experiences, including the vaccine’s effectiveness, feasibility and occurrence of any adverse events following immunization—as additional input for future updates to the guidance. WHO also encourages international and national funders to support relevant learning opportunities (99).
Co-administration
RTS,S/AS01 given in conjunction with routine childhood vaccines has been evaluated in several trials (105)(106). Non-inferiority criteria were met for all vaccines given with RTS,S/AS01, in comparison with the same vaccines given without RTS,S/AS01. RTS,S/AS01 can be given concomitantly with any of the following monovalent or combination vaccines: diphtheria, tetanus, whole cell pertussis, acellular pertussis, hepatitis B, Haemophilus influenzae type b, oral poliovirus, measles, rubella, yellow fever, rotavirus and pneumococcal conjugate vaccines (90). No co-administration studies have been conducted with RTS,S/AS01 and meningococcus A, typhoid conjugate, cholera, Japanese encephalitis, Tick-borne encephalitis, rabies, mumps, influenza or varicella vaccines (99).
Identifying areas for vaccine introduction
Decisions about where to introduce the malaria vaccine should be made in the context of national planning of mixes of malaria interventions and strategies and considering the need for subnational tailoring of packages of interventions. Subnational tailoring considers variations in malaria epidemiology, health system structure and function, and broader contextual considerations.
Current WHO guidance defines moderate or high transmission settings as those with an annual incidence greater than about 250 cases per 1000 population or a prevalence of P. falciparum infection in children aged 2—10 years (PfPR2-10) of approximately 10% or more. These are indicative values and should not be used as strict thresholds.
Vaccine safety
The RTS,S/AS01 vaccine is safe and well tolerated. There is a small risk of febrile seizures within seven days (mainly within 2—3 days) of vaccination. As with any vaccine introduction, proper planning and training of staff to conduct appropriate pharmacovigilance should take place beforehand.
The only contraindication to use of RTS,S/AS01 vaccine is severe hypersensitivity to any of the vaccine components (90).
Vaccination of special populations
Malnourished or HIV-positive infants may be vaccinated with the RTS,S/AS01 vaccine using a standard schedule. These children may be at particular risk from malaria infection and the vaccine has been shown to be safe in these groups.
The vaccine should be provided to infants and young children aged 5—17 months of age who relocate to an area of moderate to high transmission, including during emergency situations.
The vaccine has been developed for use in young children living in malaria-endemic settings, and has not undergone full clinical testing in adults, nor is it recommended for adults. The vaccine is not indicated for travellers, who should use chemoprophylaxis and vector control methods to prevent malaria when traveling to endemic settings.
Surveillance
As for all new vaccines, the effectiveness and safety of the RTS,S/AS01 vaccine should be monitored post-introduction. Countries that choose to introduce the vaccine in a five-dose seasonal strategy are encouraged to document their experience, including adverse events following immunization.
Research priorities
The WHO-coordinated Malaria Vaccine Implementation Programme will continue through 2023, with continued monitoring of data on safety, impact, coverage achieved and the added benefit of the fourth dose. In areas with highly seasonal malaria or with perennial malaria transmission with seasonal peaks, operational research is needed specifically related to the seasonal delivery of vaccine doses, including annual preseason dosing after a primary series given through the routine health clinics. Further evaluation will be required to determine how best to deliver the combination of SMC and seasonal malaria vaccination in areas. Data should be collected on safety, immunogenicity, and effectiveness of annual doses beyond the fifth dose.
Considerations for immunization and health systems
The additional visits needed for RTS,S/AS01 are opportunities to provide other integrated and preventive health services. Efforts should be made to take advantage of these visits to catch up on missed vaccinations, administer Vitamin A, carry out deworming and other preventive interventions, and remind parents of the importance of continuing to use an ITN every night and seeking prompt diagnosis and treatment for fever.
A framework for allocation of limited supply
Supplies of the RTS,S/AS01 vaccine are expected to be limited in the short to medium term, and demand is expected to be high. WHO is working with partners to develop a framework to guide the allocation of the initial limited doses of malaria vaccine, using a transparent process that incorporates input from key parties, with appropriate representation and consultation. This framework will include dimensions of market dynamics, learning from experience, scientific evidence for high impact, implementation considerations and social values, including fairness and equity.
Evidence To Decision
Benefits and harms
The RTS,S/AS01 vaccine, provided in a four-dose schedule, has been demonstrated in clinical trials and the pilot implementation studies to have meaningful impact, with a substantial reduction in hospitalization for life-threatening severe malaria, which is considered to be a surrogate indicator for the impact on mortality.
There were significant reductions in clinical malaria (51%); and severe malaria (45%), demonstrated after 12 months’ follow-up of the first three doses in the Phase 3 trial (
89).
There were significant reductions in clinical malaria (39%); severe malaria (29%); severe malaria anaemia (61%); malaria-related hospitalization (37%); and the need for blood transfusions (30%), demonstrated over 46 months’ follow-up after the first three doses in the Phase 3 trial in children who received a fourth dose 18 months after the third dose (
89).
There were 1774 clinical malaria cases averted per 1000 children vaccinated with four RTS,S/AS01 doses over 46 months’ follow-up in the Phase 3 trial (
89).
There were significant reductions in clinical malaria (24%) demonstrated after 7 years’ follow-up after vaccination among a subset of children in the Phase 3 trial living in areas of moderate to high transmission; they did not have an excess risk of clinical or severe malaria (
100).
There were significant reductions in hospitalization with severe malaria (29%) and hospitalization with malarial parasitemia or antigenemia (21%), demonstrated among children who were age-eligible for three doses of vaccine delivered through routine systems by the ministries of health in parts of Ghana, Kenya, and Malawi (
101).
Median estimates ranged from 200 to 700 deaths averted per 100 000 children vaccinated with a 4-dose schedule in areas of moderate to high transmission (
102).
There were substantially greater reductions in uncomplicated malaria (63%), hospital admissions with severe malaria (70%), and death from malaria (73%) among children who received the combination of RTS,S/AS01 seasonal vaccination and SMC when compared to SMC alone. Seasonal vaccination with RTS,S/AS01 before the peak transmission season was non-inferior to SMC in preventing clinical malaria (
91).
The RTS,S/AS01 vaccine is safe and well tolerated (99).
There is a small risk of febrile seizures within seven days (mainly within 2–3 days) of vaccination (
90).
As with any vaccine introduction, proper planning and training of staff to conduct appropriate pharmacovigilance should take place beforehand (
99).
As for all new vaccines, the effectiveness and safety of the RTS,S/AS01 vaccine should be monitored post-introduction (
99).
More information can be found in the Full evidence report on the RTS,S/AS01 malaria vaccine background paper (88) sections 5.3.2 and 6.1 (MVIP safety, methods and results); sections 5.3.3 and 6.2 (MVIP impact, methods and results); sections 7.2 (Phase 3 results); section 8 (Additional data since Phase 3 completion); section 9 (Modelled public health impact and cost-effectiveness estimates).
Further details on “Benefits and harms” are also included in the SAGE/MPAG Evidence-to-Recommendations framework (Annex 9 page 13-16; PDF page 308-311) (88).
Certainty of the Evidence
The overall rating of the evidence on RTS,S/AS01 malaria vaccine is considered to be HIGH. The certainty of evidence ranged from very low to high.
Critical outcomes related to effectiveness of RTS,S/AS01 were mostly rated HIGH in the large-scale Phase 3 clinical trial and MODERATE (due to large confidence intervals [CIs]) in the pilot implementation study.
Overall the certainty of evidence for the safety outcomes was rated MODERATE. Three safety signals, thought to be chance findings, were identified in the Phase 3 trial; these rare, unexplained events were graded with LOW and VERY LOW certainty of evidence:
An excess of meningitis and cerebral malaria (in the context of overall reduction in severe malaria).
An excess of deaths among girls who had received RTS,S/AS01 (shown in a post hoc analysis compared to boys).
The Malaria Vaccine Pilot Evaluations were designed to answer the outstanding questions related to safety. Evidence on the safety outcomes of meningitis, cerebral malaria, and gender-specific mortality is now graded MODERATE certainty reflecting the wide CIs related to relatively rare events. Multiple WHO advisory committees reviewed the data from the pilot implementation study and concluded that there was no evidence that the Phase 3 safety signals were causally related to RTS,S/AS01. Additionally these safety signals were not seen in the Phase 2 trials (103) or subsequent Phase 3 trials (100)(91).
More information can be found in the Full evidence report on the RTS,S/AS01 malaria vaccine background paper’s (88) Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Evidence summary table by the Cochrane Response (Annex 9a page 2-10; PDF page 297-305) and the SAGE/MPAG Evidence-to-Recommendations framework (Annex 9b page 17; PDF page 312).
Preference and values 
Malaria remains a primary cause of childhood illness and mortality in much of sub-Saharan Africa.
Preferences and values of the target population have been assessed in several ways:
Qualitative interviews with caregivers and health providers revealed the perceived value of the vaccine in reducing the severity and frequency of malaria. Positive attitudes and trust among caregivers increased substantially over time, driven mainly by their perception of the vaccine’s health benefits in their own children and the broader community.
Malaria vaccine coverage from cross-sectional household surveys and from routine facility-based administrative data indicated that the vaccine was acceptable to the target population with relatively rapid scale–up for a new vaccine with a unique schedule and dropout between doses comparable to other vaccines (see “
Feasibility” section).
Coverage of other interventions from household survey and routine administrative data in areas where the vaccine has been introduced indicated that the vaccine had no negative effects on the uptake of other childhood vaccinations, on ITN use, or health–seeking behaviour for febrile illness.
Note: Midline surveys and the second round of the qualitative study were conducted between the provision of the third dose and the provision of the fourth dose and thus did not capture data on the uptake/coverage/acceptability of the fourth dose.
More information can be found in the Full evidence report on the RTS,S/AS01 malaria vaccine background paper (88) sections 5.3.4.2 and 6.3.1 (routine data, methods and results); sections 5.3.4.3 and 6.3.2 (household survey methods and results), and sections 5.3.4.5 and 6.3.4 (qualitative health utilization study methods and results).
Further details on “Values and Preferences" are also included in the SAGE/MPAG Evidence-to-Recommendations framework (Annex 9 page 18 or PDF page 313).
Resources and other considerations
The resources required are likely to be comparable to other new vaccine introductions.
Mathematical models examined the addition of the vaccine to existing malaria control interventions and treatment (102).
At an assumed vaccine price of US$5 per dose and PfPR2-10 of 10-65%, the models predicted a median ICER compared with no vaccine of $25 (95%CI 16–222) per clinical case averted and $87 (95%CI 48–224) per DALY averted for the four-dose schedule.
Public health impact and cost-effectiveness tended to be greater at higher levels of transmission.
Overall, the model estimated that ICERs were only marginally lower for the seasonal vaccination strategies (i.e. more cost-effective) despite the higher number of overall doses delivered.
Caution is required in the comparison of cost-effectiveness estimates for different interventions evaluated with different methods, outcome measures, time intervals and context (e.g. with different concurrent health interventions and standards of care). Nevertheless, the predictions of RTS,S/AS01 cost per DALY averted are broadly positive and comparable with other new vaccines, based on mathematical models, and other malaria interventions.
is based on the evidence reviewed by the RTS,S/AS01 SAGE/MPAG Working Group on the incremental cost estimates of introducing and delivering the RTS,S/AS01 malaria vaccine within routine immunization programmes in subnational areas of the malaria vaccine pilot countries: Ghana, Kenya and Malawi. The line items account for the activities conducted in the first 1–2 years of vaccine implementation (through December 2020).
More information on the evidence can be found in the Full evidence review on the RTS,S/AS01 malaria vaccine background paper (88) sections 5.3.4.6 and 6.3.5 (cost of introduction and delivery study methods and results) and section 9 (Modelled public health impact and cost-effectiveness). Further details on “Resource use” and “Cost-effectiveness” are also included in the SAGE/MPAG Evidence-to-recommendations framework (Annex 9 page 19-20; PDF page 314-315).
Line items from RTS,S/AS01 cost of delivery and vaccine introduction study.
Equity
Vaccine uptake was equitable by sex and socioeconomic status.
Vaccine uptake had no negative effect on the uptake of other childhood vaccinations, ITN use or health-seeking behaviour for febrile illness.
Introduction of RTS,S/AS01 extended the reach of malaria prevention tools; across the three pilot countries, more than two thirds of the children who reportedly did not sleep under an ITN received at least their first dose of the malaria vaccine.
Overall, vaccine introduction increased to over 90% the proportion of children in each of the three pilot countries with access to one or more malaria prevention tools (ITN or RTS,S/AS01).
More information on the evidence can be found in the Full evidence report on the RTS,S/AS01 malaria vaccine background paper (88) section 10 (Equity considerations). Further details on “Equity” are also included in the SAGE/MPAG Evidence-to-Recommendations framework (Annex 9 page 21; PDF page 316).
Acceptability
RTS,S/AS01 malaria vaccine considered acceptable to the following groups:
Target population (including eligible children and their caregivers): This is based on administrative data and household surveys that indicate good uptake and coverage, and modest drop-out rates. Continued increases in uptake suggest that the additional visits needed to receive the vaccine are acceptable to the target populations. Qualitative data indicate high acceptance and desirability of the vaccine.
Key stakeholders (including ministries of health and immunization programme managers): This is based on post-introduction evaluations, the good uptake and coverage of the malaria vaccine, and qualitative study interviews with health providers. Chief concerns from health providers were around the operational challenges faced in introducing and delivering RTS,S/AS01 (i.e. increased workload, training, eligibility).
Household surveys found no impact on the use of ITNs in intervention areas following the introduction of RTS,S/AS01, indicating that both interventions are acceptable and the vaccine has not displaced ITN use. Overall health-seeking behaviour for febrile illness was also similar between the implementing and comparison groups as well as between the baseline and midline surveys.
More information on the evidence can be found in the Full evidence report on the RTS,S/AS01 malaria vaccine background paper (88) sections 5.3.4.2 and 6.3.1 (routine data, methods and results); sections 5.3.4.3 and 6.3.2 (household survey methods and results), sections 5.3.4.4 and 6.3.3 (post-introduction evaluation methods and results) and sections 5.3.4.5 and 6.3.4 (qualitative health utilization study methods and results). Further details on “Acceptability” are also included in the SAGE/MPAG Evidence-to-Recommendations framework (Annex 9 page 22; PDF page 317).
Feasibility
Vaccine introduction is feasible with good and equitable coverage of RTS,S/AS01 seen through routine immunization systems even in the context of the COVID-19 pandemic.
Administrative data from the start of pilot programme vaccinations in 2019 and April 2021 (24 months in Ghana and Malawi, and 18 months in Kenya) showed that:
More information on the evidence can be found in the Full evidence report on the RTS,S/AS01 malaria vaccine background paper (88) sections 5.3.4.2 and 6.3.1 (routine data, methods and results). Further details on “Feasibility” are also included in the SAGE/MPAG Evidence-to-Recommendations framework (Annex 9 page 23; PDF page 318).
Justification
A Framework for WHO recommendation on RTS,S/AS01 malaria vaccine (104), endorsed by SAGE and MPAG in 2019, provided guidance on how data from the MVIP should inform WHO recommendations, with the aim of ensuring that a recommendation could be made as soon as the risk–benefit of the vaccine was established with the necessary level of confidence, such that the vaccine would not be unnecessarily withheld from countries in need if it was found to be safe and beneficial.
The Framework stated that a WHO recommendation could be made if and when concerns regarding the safety signals were satisfactorily resolved, and evidence on severe malaria or mortality was assessed as consistent with a beneficial impact of the vaccine.
The Framework clarified that a recommendation should not be predicated on attaining high coverage, including high coverage with the fourth vaccine dose, based on: (1) data from the Phase 3 long-term follow up study showing that children living in areas of perennial moderate to high malaria transmission benefit from three or four doses of the vaccine; and (2) experience that it usually takes time for new vaccines to attain high coverage, particularly when administered in the second year of life.
The RTS,S/AS01 vaccine is considered safe and well tolerated. There is a small risk of febrile seizures within seven days (mainly within 2–3 days) of vaccination. As with any vaccine introduction, proper planning and training of staff to conduct appropriate pharmacovigilance should take place beforehand.
RTS,S/AS01 has a demonstrated ability to quickly achieve high coverage and high impact when delivered through routine immunization systems, with a 30% reduction in severe malaria observed after the vaccine was introduced in areas where ITNs are widely used and there is good access to diagnosis and treatment. Modelling shows that the vaccine is cost–effective in areas of moderate to high malaria transmission.
RTS,S/AS01 increases access to malaria prevention with no negative effect on the uptake other childhood vaccinations, ITN use, or health–seeking behaviour for febrile illness.
