Malaria illness mediated by anaemia lessens cognitive development in younger Ugandan children

BACKGROUND: Asymptomatic falciparum malaria is associated with poorer cognitive performance in African schoolchildren and intermittent preventive treatment of malaria improves cognitive outcomes. However, the developmental benefits of chemoprevention in early childhood are unknown. Early child development was evaluated as a major outcome in an open-label, randomized, clinical trial of anti-malarial chemoprevention in an area of intense, year-round transmission in Uganda. METHODS: Infants were randomized to one of four treatment arms: no chemoprevention, daily trimethoprim–sulfamethoxazole, monthly sulfadoxine–pyrimethamine, or monthly dihydroartemisinin–piperaquine (DP), to be given between enrollment (4–6 mos) and 24 months of age. Number of malaria episodes, anaemia (Hb < 10) and neurodevelopment [Mullen Scales of Early Learning (MSEL)] were assessed at 2 years (N = 469) and at 3 years of age (N = 453); at enrollment 70 % were HIV-unexposed uninfected (HUU) and 30 % were HIV-exposed uninfected (HEU). RESULTS: DP was highly protective against malaria and anaemia, although trial arm was not associated with MSEL outcomes. Across all treatment arms, episodes of malarial illness were negatively predictive of MSEL cognitive performance both at 2 and 3 years of age (P = 0.02). This relationship was mediated by episodes of anaemia. This regression model was stronger for the HEU than for the HUU cohort. Compared to HUU, HEU was significantly poorer on MSEL receptive language development irrespective of malaria and anaemia (P = 0.01). CONCLUSIONS: Malaria with anaemia and HIV exposure are significant risk factors for poor early childhood neurodevelopment in malaria-endemic areas in rural Africa. Because of this, comprehensive and cost/effective intervention is needed for malaria prevention in very young children in these settings

Hepatitis C and HIV incidence and harm reduction program use in a conflict setting: an observational cohort of injecting drug users in Kabul, Afghanistan

BACKGROUND: Armed conflict may increase the risk of HIV and other pathogens among injecting drug users (IDUs); however, there are few prospective studies. This study aimed to measure incidence and potential predictors, including environmental events and needle and syringe distribution and collection program (NSP) use, of hepatitis C virus (HCV) and HIV among IDUs in Kabul, Afghanistan. METHODS: Consenting adult IDUs completed interviews quarterly in year 1 and semi-annually in year 2 and HCV and HIV antibody testing semi-annually through the cohort period (November 2007–December 2009). Interviews detailed injecting and sexual risk behaviors, NSP service use, and conflict-associated displacement. Quarters with peak conflict or local displacement were identified based on literature review, and key events, including insurgent attacks and deaths, were reported with simple counts. Incidence and predictors of HCV and HIV were measured with Cox proportional hazards models. RESULTS: Of 483 IDUs enrolled, 385 completed one or more follow-up visits (483.8 person-years (p-y)). All participants were male with a median age of 28 years and a median duration of injecting of 2 years. Reported NSP use among the participants ranged from 59.9 to 70.5 % in the first year and was 48.4 and 55.4 % at 18 and 24 months, respectively. There were 41 confirmed deaths, with a crude death rate of 93.4/1000 p-y (95 % confidence interval (CI) 67.9–125) and overdose as the most common cause. HCV and HIV incidence were 35.6/100 p-y (95 % CI 28.3–44.6) and 1.5/100 p-y (95 % CI 0.6–3.3), respectively. Changing from injecting to smoking was protective for HCV acquisition (adjusted hazard ratio (AHR) = 0.53, 95 % CI 0.31–0.92), while duration of injecting (AHR = 1.09, 95 % CI 1.01–1.18/year) and sharing syringes (AHR = 10.09, 95 % CI 1.01–100.3) independently predicted HIV infection. CONCLUSION: There is high HCV incidence and high numbers of reported deaths among male Kabul IDUs despite relatively consistent levels of harm reduction program use; peak violence periods did not independently predict HCV and HIV risk. Programming should increase awareness of HCV transmission and overdose risks, prepare clients for harm reduction needs during conflict or other causes of displacement, and continue efforts to engage community and police force support

Effect of caregiver training on neurodevelopment of HIV-exposed uninfected children and caregiver mental health: a Ugandan cluster randomized controlled trial

Objective—Early childhood development (ECD) programs typically combine healthy nutrition and cognitive stimulation in an integrated model. We separately delivered these two components in a cluster randomized controlled trial (RCT) to evaluate their comparative effectiveness in promoting healthy child development and caregiver mental health. This is the first study to do so for HIV-affected children and their infected mothers,. Methods—221 HIV-exposed but uninfected (HEU) child (2 to 3 years old) and caregiver dyads in 18 geographic clusters in Eastern Uganda were randomized by cluster to receive biweekly individualized sessions of either 1) Mediational Intervention for Sensitizing Caregivers (MISC) training emphasizing cognitive stimulation, or 2) Uganda Community Based Association for Child Welfare program that delivered (UCOBAC) health and nutrition training. Children were evaluated at baseline, six months, one year (training conclusion), and one-year post-training with the Mullen Scales of Early Learning (MSEL), the Color-Object Association Test (COAT) for memory, the Early Childhood Vigilance Test (ECVT) of attention, and the Behavior Rating Inventory of Executive Function (BRIEF-parent). The Caldwell HOME was completed by observers to gauge caregiving quality after training. Caregiver depression/anxiety (Hopkins Symptom Checklist-25) and functionality (list of activities of daily living) were also evaluated. Data collectors were blinded to trial arm assignment. Results—MISC resulted in significantly better quality of caregiving compared to UCOBAC mid- intervention with an adjusted mean difference (MadjDiff ) of 2.34 (95% CI: 1.54, 3.15, p\u3c0.01), post intervention (MadjDiff=2.43, 95% CI: 1.61, 3.25, p\u3c0.01) and at one year follow-up (MadjDiff=2.07, 95% CI: 1.23, 2.90, p\u3c0.01). MISC caregivers reported more problems on the BRIEF for their child at one-year post-training only (p\u3c0.01). Caregiving quality (HOME) was significantly correlated with MSEL composite performance one-year post training for both the MISC and the UCOBAC trial arms. Likewise, physical growth was significantly related to child development outcomes even though it did not differ between trial arms. Conclusions—Even though MISC demonstrated an advantage of improving caregiving quality, it did not produce better child cognitive outcomes compared to health and nutrition training