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.

Attitudes, Practices and Understanding of health workers and caregivers regarding the relationship between severe pneumonia and malnutrition in children: A Qualitative Study.

Background: Severe Pneumonia is still the leading cause of morbidity and mortality among children worldwide. Many children with severe pneumonia are reported to die in hospital as well as following discharge due to malnutrition. Severe pneumonia is a catabolic illness, which predisposes to severe malnutrition. WHO and United Nations Children's Fund (UNICEF), recommend 'continued' feeding but do not give any specific recommendations for nutritional support. This could influence health workers' and caregivers' attitudes, practices and understanding regarding the topic. This study aimed to explore the attitudes, practices and understanding of health workers regarding the relationship between severe pneumonia and malnutrition. Methods: We conducted an exploratory qualitative study among health workers and caregivers of children hospitalized with severe pneumonia at Mulago National Referral Hospital in Uganda. Data were collected using focus-groups involving caregivers and key informant interviews with health workers and analysed using the content-thematic analysis approach. Both manual coding and Atlas Ti software were used to support the analysis. Results: Some of the health workers and caregivers were aware of the relationship between severe pneumonia and malnutrition to various degrees, citing reduced appetite, difficulty in breathing and persistent vomiting as pathways to malnutrition in patients with severe pneumonia, which called for a balanced diet and more frequent breastfeeding. Suppressed immunity in malnourished children was mentioned as the pathway to severe pneumonia. Some caregivers confessed not knowing anything about the relationship between the two conditions. Conclusion: Attitudes, practices and understanding regarding the deadly relationship between severe pneumonia and malnutrition among care givers could further be improved by health education and mass sensitization. Clarifying practice guidelines could further enhance attitudes and practices of health workers to reduce preventable pneumonia deaths.

Mortality among non-severely under nourished children with pneumonia globally: protocol for a systematic review and meta-analysis.

Background: Pneumonia remains the commonest cause of ill health and mortality among children worldwide. Severe undernutrition increases the mortality risk among children with pneumonia. While children with pneumonia are at increased risk of developing malnutrition, the impact of pneumonia on mortality and nutritional status of non-severely undernourished children is not well described. The impact of nutritional supplementation on mortality and nutritional status in this population is not well understood. This review will collate available evidence on the all-cause mortality and anthropometric indices outcomes following pneumonia, as well as the impact of nutritional supplementation on mortality and anthropometry among non-severely malnourished children with pneumonia. Methods: The review will be done using a priori criteria developed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Data will be obtained from data bases, grey literature, and bibliographies. An experienced librarian will conduct article search in PUBMED, MEDLINE, EMBASE, Web of Science, Google scholar, and Scopus. Retrieved articles will be entered in Endnote ver 9.0, duplicates removed, and transferred to Epi-reviewer for screening and data abstraction. Risk of bias in the included articles will be assessed using standard criteria. Heterogeneity will be assessed using I 2-statistic and sub-group analysis will be done. Data will be analysed using both narrative and quantitative synthesis. Quantitative synthesis will be done using DeSimonian and Laird Random-effects model in STATA ver 15.0. Conclusions: The results will provide baseline information about the mortality and anthropometric outcomes of pneumonia among non-severely malnourished children as well as the potential effect of nutritional supplementation on these outcomes. This will provide a basis to explore the potential for nutritional supplementation improving clinical outcomes like mortality and occurrence of severe acute malnutrition among children with severe pneumonia worldwide. Registration: The review has been registered in PROSPERO (CRD42021257272; 15 July 2021).

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.

Neurocognitive function among HIV-infected children on protease inhibitor -based versus non-protease inhibitor based antiretroviral therapy in Uganda: a pilot study.

BACKGROUND: HIV infection is associated with significant neurocognitive deficits making maximization of cognitive function among children receiving antiretroviral therapy (ART) a public health imperative. Non-protease inhibitors (non-PIs) achieve higher drug levels in the cerebral spinal fluid (CSF) compared to PIs, potentially leading to better neurocognitive function by reducing CSF viral load and inflammation. ART that maximises children's neurodevelopment and school achievement could result in improved quality of life and productivity as adults, but little research to date has examined whether non-PI ART is associated with better neurocognitive outcomes. We compared the neurocognitive function between children living with HIV receiving PI-based and non PI-based ART. METHODS: We recruited a consecutive sample of clinically stable Ugandan children living with HIV aged 5-12 years who received PI-based or non PI-based ART for ≥ 1 year (viral load < 1000 copies). Neurocognitive function was assessed using the Kaufman Assessment Battery for Children, the Test of Variables of Attention, and Bruininks-Oseretsky Test of Motor Proficiency. Age-adjusted neurocognitive z-scores for the two groups were compared using linear regression models in STATA version 13. The Hommel's method was used to adjust for multiple testing. RESULTS: We enrolled 76 children living with HIV; 34 on PI ART and 42 on non-PI ART. Mean (±SD) age was greater in the non-PI vs. PI group (9.5 ± 1.9 vs. 8.5 ± 2.0) years (p = 0.03). Children in the non-PI group had lower socioeconomic scores (5.7 ± 3.3 vs. 7.4 ± 2.8, p = 0.02). There was no difference in neurocognitive function between the groups (adjusted p > 0.05) for KABC and TOVA. Children in the PI group had better total BOT scores than their counterparts (46.07 ± 1.40) vs. 40.51 (1.24), p = 0.03). CONCLUSIONS: We detected no difference in neurocognitive function among children on PI and non PI-based ART therapy based on KABC and TOVA tests. Children on PI based ART had better motor function than their counterparts. We recommend a prospective study with a larger sample size.