HIV prevalence among children admitted with severe acute malnutrition and associated factors with mother-to-child HIV transmission at Mulago Hospital, Uganda: A mixed methods study.

BACKGROUND: Despite global efforts to eliminate mother-to-child-transmission of HIV (MTCT), many children continue to become infected. We determined the prevalence of HIV among children with severe acute malnutrition (SAM) and that of their mothers, at admission to Mwanamugimu Nutrition Unit, Mulago Hospital, Uganda. We also assessed child factors associated with HIV-infection, and explored factors leading to HIV-infection among a subset of the mother-child dyads that tested positive. METHODOLOGY: We conducted a cross-sectional evaluation within the REDMOTHIV (Reduce mortality in HIV) clinical trial that investigated strategies to reduce mortality among HIV-infected and HIV-exposed children admitted with SAM at the Nutrition Unit. From June 2021 to December 2022, we consecutively tested children aged 1 month to 5 years with SAM for HIV, and the mothers who were available, using rapid antibody testing upon admission to the unit. HIV-antibody positive children under 18 months of age had a confirmatory HIV-DNA PCR test done. In-depth interviews (IDIs) were conducted with mothers of HIV positive dyads, to explore the individual, relationship, social and structural factors associated with MTCT, until data saturation. Quantitative data was analyzed using descriptive statistics and logistic regression in STATAv14, while a content thematic approach was used to analyze qualitative data. RESULTS: Of 797 children tested, 463(58.1%) were male and 630(79.1%) were ≤18months of age; 76 (9.5%) tested positive. Of 709 mothers, median (IQR) age 26 (22, 30) years, 188(26.5%) were HIV positive. Sixty six of the 188 mother-infant pairs with HIV exposure tested positive for HIV, an MTCT rate of 35.1% (66/188). Child age >18 months was marginally associated with HIV-infection (crude OR = 1.87,95% CI: 1.11-3.12, p-value = 0.02; adjusted OR = 1.72, 95% CI: 0.96, 3.09, p-value = 0.068). The IDIs from 16 mothers revealed associated factors with HIV transmission at multiple levels. Individual level factors: inadequate information regarding prevention of MTCT(PMTCT), limited perception of HIV risk, and fear of antiretroviral drugs (ARVs). Relationship level factors: lack of family support and unfaithfulness (infidelity) among sexual partners. Health facility level factors: negative attitude of health workers and missed opportunities for HIV testing. Community level factors: poverty and health service disruptions due to the COVID-19 pandemic. CONCLUSION: In this era of universal antiretroviral therapy for PMTCT, a 10% HIV prevalence among severely malnourished children is substantially high. To eliminate vertical HIV transmission, more efforts are needed to address challenges mothers living with HIV face intrinsically and within their families, communities and at health facilities.

Strategies to Reduce Mortality Among Children Living With HIV and Children Exposed to HIV but Are Uninfected, Admitted With Severe Acute Malnutrition at Mulago Hospital, Uganda (REDMOTHIV): A Mixed Methods Study.

Background: Children living with HIV (CLHIV) and children who are exposed to HIV but uninfected (CHEU) are at increased risk of developing malnutrition. Severely malnourished children have high mortality rates, but mortality is higher in CLHIV/CHEU. This study aims to investigate whether empiric use of an antibiotic with greater antimicrobial sensitivity (ceftriaxone) than standard-of-care (ampicillin plus gentamicin) will reduce mortality among CLHIV/CHEU admitted with severe acute malnutrition. Methods: This is an open label randomized controlled trial involving 300 children; 76 CLHIV and 224 CHEU. The participants are being randomized to receive 1 week of ceftriaxone (n = 150) or standard-of-care (ampicillin/gentamicin) (n = 150), in addition to other routine care. The trial's primary outcome is in-hospital mortality. Secondary outcomes are: length of hospitalization; weight-for-height, weight-for-age and height-for-age z-scores; and pattern/antimicrobial sensitivity of pathogens. In addition, 280 severely malnourished children of unknown serostatus will be tested for HIV at admission to determine the prevalence and factors associated with HIV-infection. Furthermore, all the CLHIV on LPV/r will each provide sparse pharmacokinetic (PK) samples to evaluate the PK of LPV/r among malnourished children. In this PK sub-study, geometric means of steady-state LPV PK parameters [Area Under the Curve (AUC) 0-12h , maximum concentration (Cmax) and concentration at 12 h after dose (C12h)] will be determined. They will then be put in pharmacokinetic-pharmacodynamic (PK-PD) models to determine optimal doses for the study population. Discussion: This study will ascertain whether antibiotics with higher sensitivity patterns to common organisms in Uganda and similar settings, will produce better treatment outcomes. The study will also provide insights into the current pattern of organisms isolated from blood cultures and their antimicrobial sensitivities, in this population. In addition, the study will ascertain whether there has been a significant change in the prevalence of HIV-infection among children presenting with severe malnutrition in the WHO recommended option B plus era, while determining the social/structural factors associated with HIV-infection. There will also be an opportunity to study PK parameters of antiretroviral drugs among severely malnourished children which is rarely done, and yet it is very important to understand the dosing requirements of this population. Trial Registration: ClinicalTrials.gov, identifier: NCT05051163.

Physical activity level among children recovering from severe acute malnutrition.

OBJECTIVE: To assess the level and predictors of physical activity at discharge among children recovering from severe acute malnutrition (SAM). METHODS: We conducted a prospective study among 69 children 6-59 months of age admitted with SAM for nutritional rehabilitation at Mulago National Referral Hospital, Uganda. Using hip-mounted triaxial accelerometers, we measured physical activity expressed as counts per minute (cpm) during the last three days of hospital treatment. As potential predictors, we assessed clinical and background characteristics, duration to transition phase and duration of hospitalisation, serum C-reactive protein and whole-blood docosahexaenoic acid (DHA). Multiple linear regression analyses were used to identify predictors of physical activity. RESULTS: The median (IQR) age was 15.5 (12.6; 20.5) months. At discharge, the mean (SD) movement was 285 (126) cpm. Physical activity was 43 (19; 67) cpm higher for each unit increase in weight-for-height z-score (WHZ) and 72 (36; 108) cpm higher for each centimetre increase in MUAC. Whole-blood DHA on admission was also a positive predictor of physical activity, whereas duration to transition phase and duration of hospitalisation were both negative predictors. CONCLUSION: The level of physical activity at discharge among children treated for SAM was low. WHZ, MUAC and DHA on admission were positive predictors of physical activity, whereas duration of stabilisation and hospitalisation was negative predictors of physical activity. These results suggest that assessment of physical activity may be used as a marker of recovery.

Risk factors for death in children during inpatient treatment of severe acute malnutrition: a prospective cohort study.

BACKGROUND: Children who receive in-hospital treatment of severe acute malnutrition often have high mortality rates, and the reasons are not well understood. OBJECTIVE: We assessed risk factors for death in children who were treated for malnutrition in a hospital. DESIGN: In a prospective observational study of 120 children who were receiving in-hospital treatment of severe acute malnutrition in Uganda with therapeutic formulas F-75 and F-100, we collected data on symptoms, clinical findings, plasma markers of refeeding syndrome (electrolytes and phosphate), and acute phase reactants, and recorded the nutritional therapy given in hospital. RESULTS: Seventeen children (14%) died. Clinical risk factors for death were the presence of oral thrush (HR: 5.0; 95% CI: 1.6, 15.2), a caretaker-reported severity of illness on a visual analog scale (HR: 1.7; 95% CI: 1.1, 2.6), impaired consciousness (HR: 16.7; 95% CI: 3.1, 90.4), and a capillary refill time >2 s (HR: 3.9; 95% CI: 1.4, 11.3). HIV infection was not associated with mortality (HR: 3.0; 95% CI: 0.7, 12.4), which was most likely due to low power. Biochemical risk factors were a plasma C-reactive protein concentration >15 mg/L on admission and low plasma phosphate that was measured on day 2 (HR: 8.7; 95% CI: 2.5, 30.1), particularly in edematous children. The replacement of F-75 with unfortified rice porridge to ameliorate diarrhea was associated with a higher risk of death, particularly if given during the first 2 d (HR: 5.0; 95% CI: 1.9, 13.3), which was an association that remained after adjustment for potential confounders (HR: 69.5; 95% CI: 7.0, 694.6). CONCLUSIONS: Refeeding syndrome may occur in children who are treated for malnutrition, even with moderately low plasma phosphate, and, in particular, in children with edematous malnutrition. The replacement of F-75 with unfortified rice porridge is associated with increased risk of death, which is possibly mediated by lowering plasma phosphate. The identified clinical risk factors may potentially improve the triage of children with malnutrition. This trial was registered at www.isrctn.com as ISRCTN55092738.

Changes in whole-blood PUFA and their predictors during recovery from severe acute malnutrition.

Children with severe acute malnutrition (SAM) with complications require in-patient management including therapeutic feeding. Little attention has been given to the effects of these feeds on the essential fatty acid status of children with SAM. The objective of this study was to describe changes in the PUFA composition in whole blood in children with SAM during treatment and to determine predictors of change. This prospective study took place in a paediatric nutrition rehabilitation unit in Kampala, Uganda, and assessed whole-blood fatty acid composition of children with SAM at admission, transition, discharge and follow-up (8 and 16 weeks). ANCOVA was used to identify predictors of change in whole-blood PUFA. The study included 120 children with SAM and twenty-nine healthy control children of similar age and sex. Among the SAM children, 38 % were female and 64 % had oedema. Whole-blood n-6 PUFA proportions increased from admission to follow-up, except for arachidonic acid, which decreased by 0·79 (95 % CI 0·46, 1·12) fatty acid percentage (FA%) from admission to transition and 0·10 (95 % CI 0·23, 0·44) FA% at discharge. n-3 Long-chain (LC) PUFA decreased by 0·21 (95 % CI 0·03, 0·40) FA% at discharge and 0·22 (95 % CI 0·01, 0·42) FA% at 8 weeks of follow-up. This decrease was greater in children from families with recent fish intake and those with nasogastric tube feeding. Current therapeutic feeds do not correct whole-blood levels of LCPUFA, particularly n-3 LCPUFA, in children with SAM. Increased attention is needed to the contents of n-3 LCPUFA in therapeutic feeds.

Changes in plasma phosphate during in-patient treatment of children with severe acute malnutrition: an observational study in Uganda.

BACKGROUND: Children treated for severe acute malnutrition (SAM) are at risk of refeeding hypophosphatemia. Therapeutic diets have only recently become fortified with phosphorus to meet United Nations (UN) specifications, but to our knowledge no studies have investigated the effect. OBJECTIVE: The aim was to assess concentrations and correlates of plasma phosphate (P-phosphate) at admission and during treatment and to identify correlates of changes in P-phosphate. DESIGN: This was a prospective observational study in 6- to 59-mo-old children admitted for treatment of SAM to Mulago Hospital, Uganda. P-phosphate was measured at admission, on the second day of treatment with a therapeutic formula containing 75 kcal/100 mL and 560 mg phosphorus/L (F-75, Nutriset), at the start of the transition to a therapeutic formula containing 100 kcal/100 mL and 579 mg phosphorus/L (F-100; Nutriset), at day 2 of transition, and at discharge. RESULTS: Among 120 children, mean ± SD P-phosphate at admission was 1.04 ± 0.31 mmol/L and increased by 0.43 (95% CI: 0.35, 0.52) mmol/L during the first 2 d and more slowly toward discharge. Most (79%) children experienced their lowest P-phosphate concentration at admission, and none developed severe hypophosphatemia. P-phosphate was lowest in children with edema and with elevated C-reactive protein, and a lower increase was seen with increasing caretaker-reported severity of illness. Partially or fully replacing F-75 with rice porridge (i.e., a local practice to reduce diarrhea) during the first 2 d of stabilization was associated with a 0.34-mmol/L (95% CI: 0.18, 0.50 mmol/L) lower increase in P-phosphate during the same first 2 d. CONCLUSIONS: F-75, which complies with UN specifications and provides 73 mg phosphorus · kg(-1) · d(-1) (130 mL · kg(-1) · d(-1)), seems to prevent refeeding hypophosphatemia in children with SAM. Replacing this formula with rice porridge during the first days of treatment to manage diarrhea may have an adverse effect on P-phosphate concentrations. This study was registered at http://www.isrctn.com as ISRCTN55092738.

Essential fatty acid composition and correlates in children with severe acute malnutrition.

BACKGROUND: Severe acute malnutrition (SAM) is a common condition in children living in low-income countries and may be associated with reduced polyunsaturated fatty acids (PUFA) blood levels. The purpose of this study was to describe whole blood fatty acid composition and correlates of PUFA in children admitted with SAM. METHODS: We conducted a cross-sectional study among children admitted with SAM at Mulago National Referral Hospital and healthy controls. Whole blood fatty acid composition was measured and correlated with clinical data such as oedema, levels of haemoglobin, C-reactive protein and HIV-infection status. Multiple linear regression analyses were used to identify correlates of PUFA. RESULTS: The relative contribution of saturated fatty acid to the fatty acids in whole blood (FA%) were lower in 108 children with SAM compared to 24 well-nourished controls whereas most monounsaturated fatty acids were higher in children with SAM. Total and all n-6 PUFA including linoleic (18:2n-6, LA) and arachidonic acid (20:4n-6, AA), as well as total n-3 PUFA and docosahexaenoic acid (22:6n-3, DHA) were lower in children with SAM. The n-6:n-3 PUFA ratio was also lower in the children with SAM. Haemoglobin was a positive correlate of AA, n-3 docosapentaenoic acid (22:5n-3, n-3 DPA), DHA, total n-6 long chain (LC) PUFA and total n-3 LCPUFA. HIV infected children had 0.87 (0.47; 1.58) %-points less n-6 LCPUFA and 0.61 (0.03; 1.19) %-points less AA than the un-infected children. CONCLUSION: Children with SAM presented with lower FA% of LCPUFA. HIV infection and low haemoglobin were also associated with lower FA% of LCPUFA, which may be related to lower numbers of blood cells. Nutrition rehabilitation interventions need to pay more attention to the intake of PUFA.

Social, dietary and clinical correlates of oedema in children with severe acute malnutrition: a cross-sectional study.

BACKGROUND: Severe acute malnutrition is a serious public health problem, and a challenge to clinicians. Why some children with malnutrition develop oedema (kwashiorkor) is not well understood. The objective of this study was to investigate socio-demographic, dietary and clinical correlates of oedema, in children hospitalised with severe acute malnutrition. METHODS: We recruited children with severe acute malnutrition admitted to Mulago Hospital, Uganda. Data was collected using questionnaires, clinical examination and measurement of blood haemoglobin, plasma c-reactive protein and α1-acid glycoprotein. Correlates of oedema were identified using multiple logistic regression analysis. RESULTS: Of 120 children included, 77 (64%) presented with oedematous malnutrition. Oedematous children were slightly older (17.7 vs. 15.0 months, p = 0.006). After adjustment for age and sex, oedematous children were less likely to be breastfed (odds ratio (OR): 0.19, 95%-confidence interval (CI): 0.06; 0.59), to be HIV-infected (OR: 0.10, CI: 0.03; 0.41), to report cough (OR: 0.33, CI: 0.13; 0.82) and fever (OR: 0.22, CI: 0.09; 0.51), and to have axillary temperature > 37.5 °C (OR: 0.28 CI: 0.11; 0.68). Household dietary diversity score was lower in children with oedema (OR: 0.58, CI: 0.40; 85). No association was found with plasma levels of acute phase proteins, household food insecurity or birth weight. CONCLUSION: Children with oedematous malnutrition were less likely to be breastfed, less likely to have HIV infection and had fewer symptoms of other infections. Dietary diversity was lower in households of children who presented with oedema. Future research may confirm whether a causal relationship exists between these factors and nutritional oedema.

Bacteraemia in severely malnourished children in an HIV-endemic setting.

BACKGROUND: HIV infection predisposes children with malnutrition to recurrent bacterial infections and a high risk of bacteraemia. METHODS: A cross-sectional descriptive study to determine the prevalence, causative organisms, antibiotic sensitivity and factors associated with bacteraemia in malnourished children was undertaken at Mulago Hospital, Kampala. The prevalence of HIV infection was also determined. A total of 134 children aged 6-59 months with severe malnutrition were recruited. RESULTS: Sixty-one (45.5%) had oedematous malnutrition and 73 (54.5%) had severe wasting. Fifty-nine (44.0%) were HIV-infected. The prevalence of bacteraemia was 22%. The predominant organisms isolated were gram-negative enteric bacilli (77%) with Salmonella species and E. coli contributing 67% of the isolates. Hypoglycaemia was significantly associated with bacteraemia (p=0.007). Most organisms were resistant to cotrimaxazole (93.3%), ampicillin (76.7%), gentamicin (66.7%) and chloramphenicol (60%). All isolates were sensitive to ceftriaxone. Sensitivity to ciprofloxacin was 97%. There was no strong association between HIV infection and bacteraemia. The relative risk of death in malnourished children with bacteraemia was ten times higher than in those without bacteraemia. CONCLUSIONS: Nearly a quarter (22%) of children admitted with severe malnutrition had bacteraemia and gram-negative organisms were the predominant cause. Forty-four per cent were HIV-infected. Most of the bacteria were sensitive to ceftriaxone and ciprofloxacin and resistant to commonly used antibiotics. In the absence of culture and sensitivity, ciprofloxacin or ceftriaxone should be considered as first-line antibiotics for severely malnourished children.