Effectiveness of specialized nutritious foods and social and behavior change communication interventions to prevent stunting among children in Badakhshan, Afghanistan: Protocol for a quasi-experimental study

Stunting predominantly occurs during the first 1000 days of life and continues to the age of five years. We will aim to assess the effectiveness of specialized nutritious foods (SNF)and social and behavior change communication (SBCC) strategies during the first 1000 days of life to prevent stunting among children in two rural districts of Badakhshan, Afghanistan. This will be a quasi-experimental pre-post study with the control group utilizing qualitative and quantitative methods. Before launching the program, formative research will be conducted on the acceptability, appropriate use and SBCC strategies needed to support the introduction of intervention package. Repeated cross-sectional baseline and endline surveys will be conducted in both the intervention and the control districts. After the formative research and baseline household survey, an intervention focusing on the provision of SNF, targeting pregnant and lactating women and children 6-23 months, and SBCC strategies will be implemented for at least 12 months. The primary outcome will be a reduction in the prevalence of stunting among children under two years in the intervention group compared to the control group. We will aim to compare the intervention and control group between the pre- and post-intervention assessments to isolate the effect of the intervention by difference-in-differences estimates. The program monitoring and evaluation component will examine the quality of implementation, acceptability of intervention, identification of potential barriers and to learn how to enhance the program\u27s effectiveness through ongoing operational improvements. The results will be beneficial to design interventions to prevent stunting within Afghanistan and other low-middle-income countries

Feasibility and acceptability of undertaking postmortem studies for tuberculosis medical research in a low income country

IntroductionIf we are to break new ground in difficult-to-treat or difficult-to-vaccinate diseases (such as HIV, malaria, or tuberculosis), we must have a better understanding of the immune system at the site of infection in humans. For tuberculosis (TB), the initial site of infection is the lungs, but obtaining lung tissues from subjects suffering from TB has been limited to bronchoalveolar lavage (BAL) or sputum sampling, or surgical resection of diseased lung tissue.MethodsWe examined the feasibility of undertaking a postmortem study for human tuberculosis research at Mulago National Referral Hospital in Kampala, Uganda.ResultsPostmortem studies give us an opportunity to compare TB-involved and -uninvolved sites, for both diseased and non-diseased individuals. We report good acceptability of the next-of-kin to consent for their relative’s tissue to be used for medical research; that postmortem and tissue processing can be undertaken within 8 hours following death; and that immune cells remain viable and functional up to 14 hours after death.DiscussionPostmortem procedures remain a valuable and essential tool both to establish cause of death, and to advance our medical and scientific understanding of infectious diseases

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

Supplemental Material, sj-pdf-1-fnb-10.1177_03795721231190203 - Trends and Determinants of Children’s Wasting and Women’s Thinness in Chad, 2015 to 2021

Supplemental Material, sj-pdf-1-fnb-10.1177_03795721231190203 for Trends and Determinants of Children’s Wasting and Women’s Thinness in Chad, 2015 to 2021 by Sarah Adler, Eleonor Zavala, Edgar Wabyona, Martin Ahimbisibwe, Fanga Haisset and Shannon Doocy in Food and Nutrition Bulletin</p