Effect of immunitum supplementation on prevention of recurrent infectious episodes in children with moderate malnutrition: a randomised, double-blind, placebo-controlled trial

INTERVENTION: Participants are randomly allocated to one of two groups using a 1:1 randomisation at the time of enrolment to allocate five participants in each arm for every round of ten enrollments. The study is double‐bling, with the study and control products being indistinugishable in shape, size, colour and taste. They are pre‐labeled for the entire study by a third‐party person who does not play a role in the study implementation. Group 1: Participants in this group receive an oral capsule of immunitum twice daily. Group 2: Participants receive the placebo oral capsule which is taken twice daily. Participants in both groups receive the treatment for 12 months. Clinical follow up and study visits are the same for both groups, with the study product given at the time of enrollment and randomisation and then participants are seen monthly for a clinical follow‐up, nutritional status and treatment compliance until month 12. CONDITION: Recurrent infectious diseases in children with malnutrition: 1. ENT sphere infections 2. Broncho‐pulmonary infections 3. Gastrointestinal tract infections 4. Malaria ; Infections and Infestations ; 1. ENT sphere infections 2. Broncho‐pulmonary infections 3. Gastrointestinal tract infections 4. Malaria PRIMARY OUTCOME: 1. Incidence of infectious diseases (e.g., ENT sphere infections, broncho‐pulmonary infections, gastrointestinal tract infections, and malaria) common in children (12‐59 months) with moderate malnutrition as defined by WHOis assessed by a trained general medical doctor with experience in pediatric case management in district hospitals (supervised daily and closely by an experienced pediatrician) Each enrolled participant was discussed together at her arrival at health center, on regular appointments, and every time a family called saying that the child has a health problem. In addition, when recruited children arrived to health centers, they were seen by a trained nurse working regularly in PCIME or IMCI (Integrated Management of Childhood Illness), who records the case in a dedicated register and reported the case immediately on phone when urgent or complicated situations. Otherwise the case was reported to the study team during the following monthly visit.; 2. Severity and length (in days) of each infectious episode is measured by the medical doctor who is assigned to see participants from the beginning of the disease and follow participant till the end of episode of the disease. Symptoms notified at the beginning are verified every day by a community health worker who see the participant twice a day for giving the immunitum/placebo and asks questions about the signs and symptoms of the disease at each visit then records in the trial notebook which is presented to the medical doctor at the regular visit at the health center or for severe cases at the district hospital, when the child is hospitalized. INCLUSION CRITERIA: 1. Children aged 12 to 59 months 2. Moderate malnutrition as per WHO criteria 3. History of recurrent infectious episodes of upper and lower respiratory tract and gastrointestinal tract SECONDARY OUTCOME: 1. Weight and height are measured using standard anthropomorphic techniques at health center during each monthly visit for 12 months; 2. General vitality is assessed using the general vitality questionnaire that measures apathy, sleep, feeding and fatigue; at health center during each monthly visit for 12 months; 3. Tolerance and compliance is assessed by the assigned community health worker at home, and then by the study team at health center during each monthly visit for 12 months; 4. Proteinemia is measured using spectrophotometry, transferrin is measured by turbidimetry, CRP is measured by ELISA, blood sugar is measured by spectrometry, hemoglobin is measured by spectrometry, erythrocyte sedimentation rate, RBC, WBC, thick blood smear, HIV, stool (for parasites and culture when child has diarrhea, one of the stool sample taken at 12 months will be analysed for microbiome composition) are measured using sample analysis by specific lab techniques for each lab exam and following well defined lab protocols at baseline, six and 12 months; 5. Levels of vitamins A, B1, B2, B9, B12, C, D, E, PP are measured using high‐performance liquid chromatography at baseline, six and 12 months; 6. Levels of iodine will be determined by mass spectrometry, sodium, potassium and chlorine by ion‐selective electrode (ISE), selenium by atomic absorption spectroscopy, zinc by atomic absorption spectrophotometry, and iron by spectrophotometric assay at baseline, six and 12 months; 7. Genomic analyses will be done by single nucleotide polymorphism and proteomics by electrophoresis at baseline, six and 12 months;