Background
Malaria continues to cause unacceptably high levels of disease and death, as documented in successive editions of the World malaria report (3). According to the latest report, there were an estimated 241 million cases and 627 000 deaths globally in 2020. Malaria is preventable and treatable, and the global priority is to reduce the burden of disease and death while retaining the long-term vision of malaria eradication. Here, we present the WHO Guidelines for malaria developed by the WHO Global Malaria Programme (GMP) as a comprehensive and inclusive resource for advice on malaria.
The Global technical strategy for malaria 2016–2030 (4) (GTS) provides an overarching framework to guide malaria control and elimination efforts. Adopted by the World Health Assembly in May 2015 and update adopted in May 2020, the Strategy defines goals, milestones and targets on the path to a world free of malaria (). The goals focus attention on the need to both reduce morbidity and mortality, and to progressively eliminate malaria from countries that had malaria transmission in 2015. The GTS presents a framework through which the goals can be achieved ().
Goals, milestones and targets for the Global technical strategy for malaria 2016–2030.
The GTS (4) states that it is essential for malaria programmes to ‘ensure access to malaria prevention, diagnosis and treatment as part of universal health coverage’ ( - Pillar 1). Universal health coverage (UHC) means that all individuals and communities receive the health services they need without suffering financial hardship. It includes the full spectrum of essential, quality health services, from health promotion to prevention, treatment, rehabilitation and palliative care. For malaria, WHO has recommended a range of interventions namely, vector control, chemoprevention, diagnostic testing and treatment to reduce transmission and prevent morbidity and mortality. A UHC approach means ensuring that individuals and communities are covered by the appropriate mix of these interventions, based on local context, to control and ultimately eliminate malaria.
Global technical strategy for malaria 2016 - 2030: framework, pillars and supporting elements.
The principal objective of national malaria programmes (NMPs) is to combine a selection of these interventions into packages that are tailored to achieve sustainable and equitable impact in a given setting. To decide upon the appropriate intervention package and allocation of resources that will achieve this objective and contribute to UHC, programmes should use a process that combines the analysis of impact and value for money with extensive stakeholder engagement and discussion. The process should be informed by past and current malaria transmission intensity and incidence data; contextual vulnerability related to the human host, parasites, vectors, and past and present intervention coverage; acceptability; and equality of access and use (including analysis of financial barriers and how to address them). When the objective is elimination, a similar process is undertaken although the types of interventions and value for money analysis will be different than in high-burden settings.
Following progressive reductions in malaria burden between 2000 and 2015, progress stalled. By 2017, the world was off track to achieve the malaria morbidity and mortality reduction targets. In response, a revitalization effort called “High burden to high impact (HBHI)” was launched in 2018 (5). This approach focuses attention on how to get back on track: garnering political will to reduce the toll of malaria; using strategic information to drive impact; developing better guidance, policies and strategies; and improving coordination of support for national malaria responses. Although the impetus for articulating these key activities was the need to get back on track to achieve the GTS morbidity and mortality targets, these activities apply equally well to all malaria-endemic countries and to ensure continued progress towards the GTS elimination goals.
Objectives
These consolidated WHO Guidelines for malaria aim to provide the latest evidence-based recommendations in one reference to support countries in their efforts to reduce and ultimately eliminate malaria. The objectives of the Guidelines are:
to provide evidence-based and context-sensitive recommendations on the appropriate choice(s) for malaria prevention (vector control and chemotherapies) and case management (diagnosis and treatment) across all transmission settings;
to support the development by WHO Member States of evidence-based national malaria policies for prevention and case management across all transmission settings;
to encourage the use of local data to inform subnational stratification to maximize the impact of available resources; and
to inform the research agenda to enable updates to the Guidelines by identifying gaps in evidence that constrain the development of guidance or weaken current recommendations.
Evidence base
These Guidelines are based on the synthesis of the available evidence on the health effects of interventions, and the grading of the certainty of that evidence using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. The synthesized and graded evidence on the health effects of interventions, as well as any evidence on contextual factors, is used to develop an evidence-to-decision (EtD) framework for each recommendation (6). The judgement of the different factors in the EtD framework (including the certainty of evidence) facilitates the determination of the strength and direction of each recommendation.
Expert input is important for the interpretation of the evidence, and the development of guidance may rely on expert opinion, particularly in areas where the evidence is currently weak, scarce or absent. For example, the vector control recommendations presented in the Guidelines are based on a consideration of the evidence gained from randomized controlled trials (RCTs) and other types of trials and studies, as well as the technical knowledge and experience of the GDG and External Review Group involved in the standard guideline development process. Details of how evidence is considered are presented in Section 8: Methods. Details of contributors for specific recommendations are presented in Section 10: Contributors and interests.
Target audience
The primary audience for these guidelines is policy-makers in ministries of health and the managers of NMPs in endemic countries. The Guidelines may also be of interest to health care practitioners, environmental health service professionals, procurement agencies, the private sector, and civil society groups. The Guidelines are also intended for use by international development partners, donors and funding agencies in order to support decision-making on allocation of resources for interventions and procurement of appropriate malaria control products. In addition, the Guidelines are intended to guide researchers, research funders and those interested in the outcomes of research to address the evidence gaps that are constraining the development of guidance or weakening current recommendations.
Etiology
Malaria is a life-threatening disease caused by the infection of red blood cells with protozoan parasites of the genus Plasmodium that are transmitted to people through the bites of infected female Anopheles mosquitoes. Four species of Plasmodium (P. falciparum, P. vivax, P. malariae and P. ovale) most commonly infect humans. P. falciparum and P. vivax are the most prevalent species and P. falciparum is the most dangerous. A fifth species, P. knowlesi (a species of Plasmodium that primarily infects non-human primates) is increasingly being reported in humans inhabiting forested regions of some countries of South-East Asia and the Western Pacific regions, and in particular on the island of Borneo.
Malaria transmission, acquisition of immunity, and clinical manifestations of disease
The intensity of transmission depends on factors related to the parasite, the vector, the human host and the environment. Transmission tends to be more intense in places where the mosquito lifespan is longer and where the females prefer to bite humans rather than other animals. The survival and longevity of female mosquitoes is of critical importance in malaria transmission, as the malaria parasite generally requires a period of 7–10 days to develop inside the mosquito into a form that is infective to humans. Female mosquito longevity is dependent on intrinsic, genetic factors, as well as on environmental factors including temperature and humidity. The strong human-biting habit of the African vector species is one of the reasons why approximately 90% of the world’s malaria cases occur in Africa.
Transmission intensity is usually assessed as the incidence of cases or the prevalence of infection. Most countries have information on the annual parasite incidence (number of new parasitologically confirmed malaria cases per 1000 population per year) from routine surveillance and/or on the parasite prevalence from surveys, often conducted during or just after periods of peak transmission (7).
The following categories of transmission intensity are indicative and meant to provide an adaptable framework in which each country can conduct a stratification exercise to classify geographical units according to local malaria transmission.
Areas of high transmission are characterized by an annual parasite incidence of about 450 or more cases per 1000 population and a P. falciparum prevalence rate of ≥35%.
Moderate transmission areas have an annual parasite incidence of 250–450 cases per 1000 population and a prevalence of P. falciparum/P. vivax malaria of 10–35%.
Areas of low transmission have an annual parasite incidence of 100–250 cases per 1000 population and a prevalence of
P. falciparum/P. vivax of 1–10%. It should be noted that the incidence of cases or infections is a more useful measure in geographical units in which the prevalence is low, given the difficulty of measuring prevalence accurately at low levels (
8).
Very low transmission areas have an annual parasite incidence of < 100 cases per 1000 population and a prevalence of P. falciparum/P. vivax malaria that is > 0 but < 1%.
The relation between parasite incidence, parasite prevalence and the number of cases presenting to health facilities per week can be estimated using models (9). Differences in transmission from one area to another may be due to geographical characteristics, such as altitude, temperature, humidity, rainfall patterns, proximity to water bodies, land use, vector species and distribution, socio-demographic characteristics, access to antimalarial treatment, and coverage with vector control. In most endemic areas, seasonal patterns of transmission are observed, with high transmission during part of the year. Both the intensity and timing of transmission are important considerations in designing elimination strategies.
The manifestation of clinical disease depends strongly on the background level of acquired protective immunity, which is a consequence of the pattern and intensity of malaria transmission in the area of residence. In areas of moderate to high transmission, partial immunity to clinical disease and a reduced risk of developing severe malaria are acquired in early childhood. The pattern of acquired immunity is similar across the Sahel subregion, where malaria transmission is intense only during the three- or four-month rainy season and low at other times. In both these situations, clinical disease is confined mainly to young children, who may develop high parasite densities that can progress rapidly to severe malaria. By contrast, in these settings, adolescents and adults are partially immune and suffer clinical disease much less frequently, although they are often infected with low blood-parasite densities. Immunity is modified in pregnancy and gradually lost, at least partially, when individuals move out of the endemic areas for prolonged periods (e.g., a year or more).
In areas of low and very low transmission, as found in much of Asia, Latin America and other malaria-endemic areas, the transmission fluctuates widely by season, year, and over relatively small distances. P. vivax is an important cause of malaria in these regions. This generally low transmission delays acquisition of immunity, so that adults and children alike suffer from acute clinical malaria, with a significant risk for progression to severe malaria if left untreated. Epidemics may occur in these low or very low transmission areas when the inoculation rate increases rapidly because of a sudden increase in vectorial capacity. Epidemics may result in a very high incidence across all age groups, which can overwhelm health services.
In moderate and high transmission areas with sustained high coverage of vector control and access to treatment, reduced exposure to malaria infection may change the population structure of acquired immunity to reflect that found in low or very low transmission areas, resulting in a corresponding change in the clinical epidemiology of malaria and an increasing risk of epidemics if control measures are not sustained.
Recommendations and supporting implementation guidance
Evidence-informed recommendations are a critical component to support the development of national malaria strategic plans; they are intended to communicate “what to do”. A second critical element is the strategic use of local data. This informs an understanding of the contextual diversity within each malaria-endemic country. Local data provide an understanding of the different types of settings – or strata – within each country. This is an essential prerequisite to identify the optimal mix of interventions and the best means to deliver them in the different subnational strata.
GMP is working with countries to strengthen the generation and use of local information for stratification, the definition of optimal mixes of interventions, and the rational, safe and ethical prioritization of resources to maximize impact. Local data are also essential to understand the impact of the strategies deployed, providing opportunities to further refine sub-national strategies and inform global knowledge.
WHO also develops implementation guidance such as operational and field manuals to support the “how” aspect of delivering the recommended tools and strategies. Operational manuals and other guidance hold practical information for increasing the target population’s access to interventions. These documents are referenced and linked to these Guidelines. GMP is working to align this implementation guidance with the recommendations in the WHO Guidelines for malaria. However, where there are inconsistencies, the Guidelines should be the default resource for national decisions. Countries may use the implementation guidance to define ways in which a recommendation can be implemented effectively – for example, intermittent preventive treatment for malaria in pregnancy could be implemented through antenatal care and/or community distribution. The intention of the guidance is to enable delivery, not to prescribe exactly how it should be done.
Strategic information to tailor programmatic response and selection of interventions
As malaria control improves, malaria transmission and risk become increasingly heterogeneous, both between and within countries. Thus, a “one-size-fits all” approach to programme decisions on intervention selection becomes inefficient. The situation requires stratification of the country at subnational levels according to past, present and future malaria risk, the structure and function of the health system, and other contextual factors. Stratification provides a rational basis to identify context-specific packages of interventions to target specific populations in the different subnational strata. Local data are essential to complete stratification and to inform the selection of the optimal mixes of interventions to maximize impact. Given that resource constraints usually limit the implementation of all desirable interventions in all areas of malaria risk, a prioritization exercise must also be conducted to ensure that resource allocation also optimizes intervention mixes and resultant impact. Guidance on these activities is available in Section 7: Surveillance.
The choice of interventions in each stratum should be informed by WHO’s recommendations. However, given the complexities of malaria, with heterogeneity of risk and the unique contexts that every programme has to consider, global guidance is not intended and should not be used to provide prescriptive guidance on what should be done in every situation. These Guidelines signal a paradigm shift towards a problem-solving approach using local data to identify recommendations that are relevant at a country level and based on local context, defining stratum-specific packages of interventions that optimize impact and are prioritized for resource allocation. This shift moves away from overly prescriptive recommendations and will clearly distinguish evidence-informed recommendations from contextual considerations. The contextual considerations at national and subnational levels will inform how recommendations should be applied and strategies that may increase access for the target population.
Accurate stratification of malaria transmission intensity is essential for effective targeting of interventions. As countries progress towards elimination, finer scale mapping is required, and stratification should be more specific, ideally at the level of localities or health facility catchment areas (10)(11). As transmission intensity is progressively reduced, stratification needs to include vulnerability and receptivity to malaria, i.e., the risk for importation of malaria cases and the inherent potential of the vector-human ecosystem to transmit malaria.
Conclusion
These Guidelines therefore provide a framework within which NMPs and their implementing partners may adopt and adapt the recommendations for use. Good quality surveillance data can also feed into this process by providing the granular local information needed to inform and evaluate national programme decisions (see Section 7: Surveillance). Where the boundaries of current knowledge are pushed, it is particularly important to ensure adequate attention to monitoring and evaluation. The information generated can then feed into updated guidance.
