Population

Children with severe acute malnutrition:

• Children who are more than 6 months of age with a weight for height <−2 Z-score, or
• Children who are 6–59 months of age, with a mid-upper arm circumference <125 mm
• Urban/rural
• Camp/no camps
• Oedema/no oedema
• Prevalence of oedema
• Emergency/non-emergency
• Community/health-care facilities
• Active screening/passive screening.
• HIV/TB prevalence
• HIV/TB individual status

Intervention

• Standard treatment targeting children with low mid-upper arm circumference

Control

• Standard treatment targeting children with low weight-for-height

Outcomes

• Response to treatment assessed by standard outcome for severe and moderate acute malnutrition

Settings

• Programmatic setting in populations with moderate acute malnutrition prevalence >5%

Population

Children above 6 months of age with severe acute malnutrition:

• HIV positive/HIV negative/unknown
• HIV-endemic settings/non-HIV-endemic settings

Intervention

• For programme using mid-upper arm circumference: mid-upper arm circumference ≥125 mm or any other discharge criteria

Control

• For programme using mid-upper arm circumference: weight gain of 15–20% after oedema disappears
• For programme using weight-for-height: weight-for-height >−11 standard deviation or weight gain of 15–20% after oedema disappears.

Outcomes

1. Mortality
2. Relapse
3. Adverse effects
4. Cost of treatment per child treated

Settings

• All settings

Population

Children who are under 5 years of age with severe acute malnutrition:

• Presence of oedema/no presence of oedema
• Presence of eye signs/no eye signs
• HIV positive/HIV negative/unknown
• HIV-endemic settings/non-HIV-endemic settings
• Prevalence of vitamin a deficiency in the population
• (+/− other sources of vitamin A, as national/local programmes of supplementation/fortification of vitamin A)
• Under 6 months/above 6 months of age
• Measles diagnosis (outbreak)

Intervention

Vitamin A single mega dose:

• Admission/rehabilitation/discharge

Control

• Daily low doses (including therapeutic foods)

Outcomes

1. Mortality rate
2. Adverse effects (to be specified); morbidity
3. Recovery rate
4. Relapse
5. Time to recover; weight gain

Settings

• Low-resource countries

Population

Children who are under 5 years of age with severe acute malnutrition and diarrhoea, defined as:

• Diarrhoea based on the mother recall or other definitions
• With vomiting/without vomiting
• Presence of oedema/no presence of oedema
• Under 6 months/above 6 months of age
• Persistent diarrhoea defined as more than 2 weeks
• HIV positive/HIV negative/unknown
• HIV-endemic settings/non-HIV-endemic settings
• Breastfed/ non-breastfed

Intervention

• Other foods

Control

• Ready-to-use therapeutic food

Outcomes

1. Referral to hospitals
2. Recovery from diarrhoea
3. Adverse effects
4. Time to recover from diarrhoea

Settings

• Outpatient

Population

Children who are 5 years of age with severe acute malnutrition and diarrhoea, defined as:

• Diarrhoea based on the mother recall or other definitions
• With vomiting/without vomiting
• Presence of oedema/no presence of oedema
• Under 6 months/above 6 months of age
• Persistent diarrhoea defined as more than 2 weeks
• HIV positive/HIV negative/unknown
• HIV-endemic settings/non-HIV-endemic settings
• Breastfed/ non-breastfed

Intervention

• Other recipes (e.g. lactose-free F-75 formulation)

Control

• Cooked cereal-based F-75 or glucose-polymer-based F-75

Outcomes

1. Use of intravenous fluids
2. Recovery from diarrhoea; duration of diarrhoea
3. Adverse effects

Settings

• Inpatient

Population

Children who are 6–59 months of age with severe acute malnutrition and return of appetite and most/all oedema disappeared:

• Presence of oedema/no presence of oedema on admission
• HIV positive/HIV negative/unknown
• HIV-endemic settings/non-HIV-endemic settings

Intervention

• Combination of F-75/ready-to-use therapeutic food with/without energy restriction, or F-100/ ready-to-use therapeutic food with/without energy restriction, or F-100 without energy restriction, or ready-to-use therapeutic food with/without energy restriction

Control

• F-100: 130 mL/kg/day increasing 10 mL/kg/ feed if eaten until drinking 200 mL/kg/day

Outcomes

1. Mortality rate; recovery rate
2. Cardiac embarrassment
3. Adverse effect (refeeding syndrome)
4. Relapse

Settings

• Inpatient

Population

Children who are 5 years of age with severe acute malnutrition:

• Dehydration based on the mother recall of watery diarrhoea or other definitions
• With vomiting/without vomiting
• Presence of oedema/no presence of oedema
• Under 6 months/above 6 months of age
• Severe watery diarrhoea without signs of shock (e.g. cholera) or hyponatraemia

Intervention

Treatment with Different rehydration solutions:

• Oral/parenteral/other (F-75/breastfeeding)

Control

• Treatment with ReSoMal

Outcomes

1. Use of intravenous fluids
2. Recovery from dehydration
3. Time to recover from dehydration
4. Adverse effects (convulsions, hyponatraemia, oedema, cardiac embarrassment, shock)

Settings

• All settings

Population

Children who are under 5 years of age with severe acute malnutrition and shock:

• By definition of shock, as:

  —

  Lethargy or unconsciousness and cold hands plus either slow capillary refill or weak or fast pulse

  —

  Cold hands with capillary refill longer than 3 s and weak and fast pulse

  —

  Other definitions including signs of possible septic shock

• Presence of oedema/no presence of oedema
• Under 6 months/above 6 months of age

Intervention

Treatment with isotonic fluids, colloids fluids or crystalloid fluids:

• Quantity/kg/child
• Speed
• Monitoring: frequent/other schemes

Control

• Treatment with hypotonic fluids as in current guidelines (1)

Outcomes

1. Case-fatality rate
2. Recovery from shock
3. Adverse effects (convulsions, hyponatraemia, hypokalaemia, oedema, cardiac embarrassment)
4. Time to recover from shock

Settings

• All settings

Population

Children who are under 5 years of age with severe acute malnutrition not responding to intravenous fluid treatment of shock:

• By definition of shock, as:

  —

  Lethargy or unconsciousness and cold hands plus either slow capillary refill or weak or fast pulse

  —

  Cold hands with capillary refill longer than 3 s and weak and fast pulse

  —

  Other definitions including signs of possible septic shock

• Presence of oedema/no presence of oedema
• Under 6 months/above 6 months of age

Intervention

Treatment with blood or plasma transfusion:

• Quantity/kg/child
• Speed

Control

• No blood transfusion

Outcomes

1. Case-fatality rate
2. Recovery from shock
3. Adverse effects (convulsions, hyponatraemia, oedema, cardiac embarrassment)
4. Time to recover from shock

Settings

• All settings

Population

Children who are 0–14 years of age with severe acute malnutrition:

• Subgroups:

  —

  Age <6 months, age 6 months to 5 years

  —

  Oedema, no oedema

  —

  TB status: positive/negative/unknown

Intervention

• Start nutritional therapy plus antiretroviral drug treatment concurrently

Control

• Start nutritional therapy and withhold antiretroviral drug treatment for 1 week/2 weeks (within stabilization phase)
• Start nutritional therapy and withhold antiretroviral drug treatment until rehabilitation phase

Outcomes

1. Mortality
2. Markers of nutritional status: lean body mass, height gain, body weight, weight-for-height, weight-for-age, body mass index, mid-upper arm circumference
3. Improvements in CD4 %, CD4 counts, viral load; tolerance of antiretroviral drug treatment (adverse effects)
4. Adherence to antiretroviral drug treatment

Timing

• From time of initiation of services to first 6 months of treatment

Population

Children who are 0–59 months of age with severe acute malnutrition:

• Subgroups:

  —

  Age <6 months, age 6 months to 5 years

  —

  Oedema, no oedema

  —

  TB status: positive/negative/unknown

Intervention

• antiretroviral drug treatment

Comparator

• Compare standard antiretroviral drug treatment doses between children with and without severe acute malnutrition of the same weight
• Compare antiretroviral drug treatment pharmacokinetics (peak levels, clearance) between children of the same age with and without severe acute malnutrition, with weight-appropriate doses

Outcomes

1. Antiretroviral drug treatment tolerance/adverse events
2. Mortality
3. Measures of pharmokinetics
4. Measures of antiretroviral drug treatment absorption
5. Markers of nutritional status: body weight, weight-for-height, weight-for-age, body mass index, mid-upper arm circumference
6. Change in CD4 counts

Timing

• During the first 3 months of antiretroviral drug treatment

Population

Children who are less than 6 months of age with severe acute malnutrition:

• Oedema/no oedema
• 0–2 months/2–6 months
• HIV positive/HIV negative/unknown
• HIV-endemic settings/non-HIV-endemic settings

Intervention

• Admission criteria: mid-upper arm circumference, chest circumference, head circumference, weight loss, breastfeeding failure, weight-for-length different cut-off values
• Discharge criteria: criteria different from those specified for control

Control

• Admission criteria: weight-for-length <−3 standard deviations or visible severe wasting (given the lack of gold standard it is advised to compare different criteria)
• Discharge criteria: there is no standard for this age group; the general recommendation is:

  —

  for programme using mid-upper arm circumference: weight gain of 15–20% after oedema disappears

  —

  for programme using weight-for-height: weight-for-height >−1 standard deviation or weight gain of 15–20% after oedema disappears

Outcomes

1. Short-term mortality
2. Recovery rate; weight gain
3. Adverse effects
4. Time to recover
5. Use of resources
6. Excessive use of breast milk substitute; length gain

Restoration of successful exclusive breastfeeding (added later, not included in the ranking exercise)

Settings

—

Inpatient

Population

Infants less than 6 months of age:

• 0–2 months/2–6 months
• Access to breast milk/no access to breast milk
• Stabilization/rehabilitation
• Presence of oedema/no oedema
• HIV positive/HIV negative/unknown
• HIV-endemic settings/non-HIV-endemic settings

Intervention

• different formulation of F-75 (initiation of treatment), breast milk substitute, breast milk substitute specific for premature infants, F-100, F-100 diluted, expressed breast milk, animal milk
• Supplementary suckling method/cup feeding

Control

• Breast milk if accessible, if not, breast milk substitute

Outcomes

1. Mortality
2. Recovery rate; weight gain
3. Diarrhoea
4. Restoration of successful exclusive breastfeeding
5. Time to recover
6. Length gain
7. Adverse effects
8. Breast milk output

Settings

• Inpatient