Annex 7Research priorities
1. Admission and discharge criteria for children who are 6–59 months old with severe acute malnutrition
Priority issues
To refine cut-off values of mid-upper arm circumference to identify severe acute malnutrition in children who are 6–11 months, 12–23 months and 24–59 months of age, through assessment of treatment outcomes.
To test strategies to improve active community screening and routine health-facility screening, and investigate barriers to service access and uptake, to enhance treatment coverage.
Other issues (no specific order)
To evaluate the validity of mid-upper-arm circumference values versus weight-for-height Z-score as discharge criteria for end of treatment (in relation to response to treatment, relapse and mortality) and determine the appropriate cut-off values.
To assess the sensitivity and specificity of mid-upper-arm circumference measurements at the lower and higher age ranges of children who are 6–59 months of age, controlled for stunting and the presence of oedema.
To establish mid-upper-arm circumference thresholds to identify severe acute malnutrition in infants who are less than 6 months of age and children who are 5 years of age and older.
To assess the response to treatment according to initial anthropometric criteria and clinical and biochemical characteristics.
To assess the correlation of anthropometric indicators with risk of death and response to treatment of severe acute malnutrition in infants who are less than 6 months of age and children who are 5 years of age and older, especially in the context of high and low HIV prevalence.
2. Where to manage children with severe acute malnutrition who have oedema
3. Use of antibiotics in the management of children with severe acute malnutrition in outpatient care
Priority issues
What is the clinical effect and cost effectiveness of giving oral antibiotics to children and infants with severe acute malnutrition who do not require inpatient management in:
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settings with predominantly wasting (e.g. West Africa, South Asia); and
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non-HIV settings (randomized controlled trial with mortality as main outcome)?
What is the effect of giving broad-spectrum antibiotics to infants and children with severe acute malnutrition without complications, who do not require inpatient management, on:
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the prevalence of population-based antimicrobial resistance;
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therapeutic efficacy.
Other issues (no specific order)
What clinical algorithms or point-of-care technologies can identify the presence of significant bacterial infections in infants and children with uncomplicated severe acute malnutrition?
What is the positive and negative predictive value of the appetite test for identifying children with severe acute malnutrition and clinically important infection?
What are the most effective antibiotics for managing children with complicated severe acute malnutrition who are admitted for inpatient care:
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stratified by HIV status, complications, type of severe acute malnutrition (oedematous versus wasting) and age;
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taking account of in vivo and in vitro resistance versus effectiveness?
What are the most effective antibiotics for managing children with complicated severe acute malnutrition who are admitted for inpatient care:
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stratified by HIV status, complications, type of severe acute malnutrition (oedematous versus wasting) and age;
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taking account of in vivo and in vitro resistance versus effectiveness?
4. Vitamin A supplementation in the treatment of children with severe acute malnutrition
Priority issues
What is the efficacy of daily low-dose vitamin A supplementation compared to single high-dose vitamin A in the treatment of children with severe acute malnutrition either with bilateral pitting oedema or presenting with severe diarrhoea or shigellosis?
What is the most effective way to improve and sustain the vitamin A status of children with severe acute malnutrition after discharge from treatment?
Are there regional differences in the response to, and safety of, vitamin A supplementation in children with severe acute malnutrition?
5. Therapeutic feeding approaches in the management of severe acute malnutrition in children who are 6–59 months of age
Priority issues
What are the efficacy and effectiveness of different ready-to-use therapeutic foods that comply with WHO specifications and are made from different ingredients in different regions of the world (using commercially produced ready-to-use therapeutic food as the comparison)?
What is the comparative effectiveness of ready-to-use therapeutic food and F-100 for recovery of children with severe acute malnutrition who have diarrhoea?
Other issues (no specific order)
What are the most effective approaches for managing the transition from F-75 to ready-to-use therapeutic food, or from F-100 to ready-to-use therapeutic food, in children with severe acute malnutrition before discharge from hospital to continued treatment as outpatients?
What is the impact of different feeding approaches to management of severe acute malnutrition in integrated severe acute malnutrition services?
What is the comparative efficacy (in terms of physiological, immunological and body composition recovery) and effectiveness of therapeutic foods made from locally produced food and ready-to-use therapeutic food for management of severe acute malnutrition of children in outpatient care?
What body composition and physiological changes follow management of severe acute malnutrition using different durations of feeding with ready-to-use therapeutic food in children of different ages and according to different criteria for stopping ready-to-use therapeutic food (see Recommendations)?
What is the relative cost effectiveness of managing severe acute malnutrition in children in hospital and community settings, taking into consideration coverage and effectiveness of services at scale?
What are the key indicators of performance for integrated services for the management of severe acute malnutrition? What is an appropriate cost-effective system for standardized and minimal monitoring and reporting of performance of integrated services for the management of severe acute malnutrition? What is an appropriate and cost-effective integrated system for monitoring coverage, barriers to access and service uptake?
What is a cost-effective system to integrate the management of severe acute malnutrition into routine heath systems and monitor this integration with a health-system-strengthening approach?
6. Fluid management of children with severe acute malnutrition
Priority issues
What is the efficacy and safety of ReSoMal compared with that of 75 mosmol/L oral rehydration solution in severely malnourished dehydrated children with non-cholera diarrhoea?
What are the most effective ways to assess and monitor the hydration status of children with severe acute malnutrition who present with some dehydration (but no shock)?
What are the most appropriate fluid strategy (type, volumes, rate) and monitoring approaches for managing children with severe acute malnutrition, with or without oedema, who present with severe dehydration or shock?
How can the diagnosis and severity of dehydration in children with severe acute malnutrition be improved and how can the types of shock, especially hypovolaemic, septic and cardiogenic, be differentiated better, in order to guide the most appropriate management?
What is the best way to monitor the clinical condition in response to resuscitation for severe dehydration or shock in children with severe acute malnutrition?
What is the role of blood transfusions in the management of children with severe malnutrition, with or without shock?
7. Management of HIV-infected children with severe acute malnutrition
Priority issues
Does early initiation of antiretroviral drug treatment (as soon as metabolic complications are stabilized and sepsis is treated) in HIV-infected children with severe acute malnutrition improve outcomes and reduce adverse events such as immune reconstitution inflammatory syndrome or dyslipidaemia, compared with later initiation?
Are the pharmacokinetic characteristics of HIV-infected children with severe acute malnutrition being started on antiretroviral drug treatment different from those of HIV-infected children who do not have severe acute malnutrition? Is there any need to modify the dose of antiretroviral drugs in HIV-infected children who are severely malnourished, to either avoid toxicity or ensure adequate therapeutic levels?
Are the pharmacokinetic characteristics of HIV-infected children with severe acute malnutrition receiving other drugs, such as isoniazid, different from those of HIV-infected children who do not have severe acute malnutrition?
What is the optimal dosing of antiretroviral drug treatment in HIV-infected children with severe acute malnutrition, to optimize clinical recovery and viral suppression and avoid the development of metabolic complications such as immune reconstitution inflammatory syndrome?
What is the most effective therapeutic feeding approach for HIV-infected children with severe acute malnutrition who have persistent diarrhoea?
Are the pathophysiological abnormalities of HIV-infected children with severe acute malnutrition, with or without oedema, the same as those of children with severe acute malnutrition but without HIV?
8. Identifying and managing infants who are less than 6 months of age with severe acute malnutrition
Priority issues
In infants who are less than 6 months of age, what is the predictive value of population-derived thresholds for weight-for-height, mid-upper arm circumference and reduced growth velocity (weight-for-age) with or without oedema to identify infants at high risk of mortality?
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Consider analysis of published or other existing data.
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Consider the feasibility of each assessment.
What are the most effective and safest therapeutic feeding approaches, including different food “recipes” in addition to breastfeeding, for infants who are less than 6 months of age with severe acute malnutrition?
How is breastfeeding most effectively re-established among infants with a low weight-for-height/poor weight gain?
Other issues (no specific order)
Do infants who are less than 6 months of age with weight-for-length less than −3 Z-score also have reduced growth velocity and is there any difference according to epidemiological setting such as African, South Asian and South-East Asian sites?
In infants who are less than 6 months of age, what is the feasibility and accuracy of using weight-for-height, mid-upper arm circumference and reduced growth velocity (weight-for-age) with or without oedema to identify infants in need of therapeutic management?
What criteria most effectively identify infants who are less than 6 months of age with the metabolic abnormalities/adaptations associated with severe acute malnutrition in older children?
What is the effectiveness, tolerance and safety of ready-to-use therapeutic food as an adjuvant to breastfeeding in infants who are less than 6 months of age with severe acute malnutrition?
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Consider specific subgroups, e.g. with oedema, 4–6months old, those with underlying diseases such as HIV.
What is the recommended folic acid supplementation for infants who are less than 6 months of age with severe acute malnutrition?
Are there adjustments in the drug dosage or selection of drugs required when managing infants who are less than 6 months of age with severe acute malnutrition?
Is there any reason to expect that the efficacy of vitamin A supplementation for infants who are less than 6 month of age with severe acute malnutrition is different from that observed in infants who are 1 to 5 months of age without severe acute malnutrition?
