Annex 6Questions on the management of severe acute malnutrition in population, intervention, control, outcomes (PICO) format1

Publication Details

1. Admission and discharge criteria for children who are 6–59 months of age with severe acute malnutrition

Admission criteria for children who are 6 to 59 months of age with severe acute malnutrition

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%

Discharge criteria for children who are 6–59 months of age with severe acute malnutrition

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

2. Where to manage children with severe acute malnutrition who have oedema

Population

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

  • Oedema +/oedema++/oedema +++/no oedema

Intervention

  • Good appetite or no medical complications and oedema +/oedema++
  • Marasmic kwashiorkor
  • Children who are above 6 months of age and <4 kg

Control

  • Good appetite or no medical complications as outpatient

Outcomes

  1. Short-term mortality
  2. Recovery rate
  3. Time to recover
  4. Weight gain
  5. Use of resources
  6. Adverse effects
  7. Length gain

Settings

  • Outpatient

3. Use of antibiotics in the management of children with severe acute malnutrition in outpatient care

Population

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

  • HIV positive/HIV negative/unknown
  • HIV-endemic settings/non-HIV-endemic settings
  • Under 6 months/above 6 months of age
  • Clinical signs of infection (to be defined)/no clinical signs of infection
  • Local sensitivity

Intervention

  • Amoxicillin, ampicillin, cephalosporin, chloramphenicol, ciprofloxacin co-trimoxazole, gentamicin, metronidazole

Control

  • No antibiotics, or
  • Different antibiotics

Outcomes

  1. Mortality rate
  2. Recovery rate
  3. Adverse effects; relapse
  4. Time to recover; weight gain

Settings

  • Low-resource countries

4. Vitamin A supplementation in the treatment of children with severe acute malnutrition

Effectiveness and safety of vitamin A supplementation in children with severe acute malnutrition

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

5. Therapeutic feeding approaches in the management of severe acute malnutrition in children who are 6–59 months of age

Feeding outpatient children with severe acute malnutrition and diarrhoea

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

Feeding inpatient children with severe acute malnutrition and diarrhoea

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

Feeding children with severe acute malnutrition in the transition phase

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

6. Fluid management of children with severe acute malnutrition

Management of dehydration without shock due to diarrhoea (and vomiting) in children with severe acute malnutrition

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

Management of shock with intravenous fluids in children with severe acute malnutrition

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

Blood or plasma transfusion in children with shock after failure of intravenous fluid in children with severe acute malnutrition

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

7. Management of HIV-infected children with severe acute malnutrition

What are the implications of severe acute malnutrition on antiretroviral drug treatment initiation and dosing?

In children who are 0–59 months of age with severe acute malnutrition, at which stage in nutritional recovery should antiretroviral drug treatment be commenced?

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

In children with HIV and severe acute malnutrition should antiretroviral drug treatment dosing be adjusted from doses for non-malnourished children?

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

8. Identifying and managing infants who are less than 6 months of age with severe acute malnutrition

Admission and discharge criteria for infants who are less than 6 months of age with severe acute malnutrition

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

Feeding severely malnourished infants who are less than 6 months of age (breastfed or non-breastfed infants)

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

Footnotes

1

In the Outcomes section of each item, the numbering refers to a ranking in order of priority, where 1 is the most critical.