Blood pressure in primary school children in Uganda: a cross-sectional survey.

BACKGROUND: Non-communicable diseases are an emerging concern in sub-Saharan Africa, and risks for these conditions are often based on exposures in early life, with premonitory signs developing during childhood. The prevalence of hypertension has been reported to be high in African adults, but little is known about blood pressure in African children. We studied prevalence and risk factors for high blood pressure (HBP) among school children in central Uganda. METHODS: Two urban and five rural schools were randomly selected from government schools in Wakiso district, Uganda. Questionnaires were administered and anthropometric measures taken. Blood pressure (BP) was measured three times in one sitting (on day 1) and the average compared to internationally-used normograms. Children with BP >95th percentile were re-tested at two additional sittings (day 2 and day 3) within one week, and at two further follow up visits over a period of six months. Those with sustained HBP were referred for further investigation. RESULTS: Of 552 students included, 539 completed the initial assessments (days 1-3) of whom 92 (17.1%) had HBP at the initial sitting. Age (adjusted odds ratio (aOR) 1.29 (95% confidence interval 1.14, 1.47), p< 0.001), body mass index (1.70 (1.25-2.31) p = 0.001) and soil-transmitted helminths (2.52 (1.04-6.11), 0.04) were associated with increased prevalence of HBP at the initial sitting. After further investigation, sustained HBP was seen in 14 children, yielding an estimated prevalence of 3.8% allowing for losses to follow up. Four children required treatment. CONCLUSION: It is feasible to measure blood pressure accurately in the school setting. A high HBP prevalence on initial readings gave cause for concern, but follow up suggested a true HBP prevalence commensurate with international normograms. Extended follow up is important for accurate assessment of blood pressure among African children

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

Impact of Anthelminthic Treatment in Pregnancy and Childhood on Immunisations, Infections and Eczema in Childhood:A Randomised Controlled Trial

Helminth infections may modulate immune responses to unrelated pathogens and allergens; these effects may commence prenatally. We addressed the hypothesis that anthelminthic treatment in pregnancy and early childhood would improve responses to immunisation and modulate disease incidence in early childhood with both beneficial and detrimental effects.A randomised, double-blind, placebo-controlled trial was conducted in Entebbe, Uganda [ISRCTN32849447]. In three independent randomisations, 2507 pregnant women were allocated to receive single-dose albendazole or placebo, and praziquantel or placebo; 2016 of their offspring were randomised to receive quarterly single-dose albendazole or placebo from age 15 months to 5 years. Primary outcomes were post-immunisation recall responses to BCG and tetanus antigens, and incidence of malaria, diarrhoea, and pneumonia; incidence of eczema was an important secondary outcome. Analysis was by intention-to-treat. Of 2345 live births, 1622 (69%) children remained in follow-up at age 5 years. 68% of mothers at enrolment, and 11% of five-year-olds, had helminth infections. Maternal hookworm and Schistosoma mansoni were effectively treated by albendazole and praziquantel, respectively; and childhood hookworm and Ascaris by quarterly albendazole. Incidence rates of malaria, diarrhoea, pneumonia, and eczema were 34, 65, 10 and 5 per 100 py, respectively. Albendazole during pregnancy caused an increased rate of eczema in the children (HR 1.58 (95% CI 1.15–2.17), p = 0.005). Quarterly albendazole during childhood was associated with reduced incidence of clinical malaria (HR 0.85 (95% CI 0.73–0.98), p = 0.03). There were no consistent effects of the interventions on any other outcome.Routine use of albendazole in pregnancy may not always be beneficial, even in tropical developing countries. By contrast, regular albendazole treatment in preschool children may have an additional benefit for malaria control where helminths and malaria are co-endemic. Given the low helminth prevalence in our children, the effect of albendazole on malaria is likely to be direct.Current Controlled Trials ISRCTN3284944

The effect of anthelminthic treatment during pregnancy on incidence of malaria, diarrhoea, pneumonia and eczema during early childhood (from birth to 5 years).

<p>There was no evidence of interaction between maternal albendazole and praziquantel treatments, therefore the effects of each treatment were examined independently.</p

Effect of quarterly albendazole from age 15 months to 5 years on infectious disease incidence in children.

<p>Kaplan-Meier survival estimates for time to first (or only episode) of (a) malaria, (b) diarrhoea and (c) pneumonia during the intervention period, comparing children who received quarterly albendazole with those who received placebo. Numbers shown in the tables are number of events (in brackets) and number of children at risk.</p

The effect of quarterly albendazole during childhood on asymptomatic malaria parasitaemia, haemoglobin and growth.

<p>Malaria parasitaemia results were missing for 39, 53, 52 and 38 children at ages 2, 3, 4 and 5 years, respectively; haemoglobin results were missing for 17, 28, 658^b and 13 children at ages 2, 3, 4 and 5 years, respectively; weight-for-age z-scores were missing for 2, 0, 1 and 4 children at ages 2, 3, 4 and 5 years, respectively; height-for-age z-scores were missing for 12, 2, 9 and 12 children at ages 2, 3, 4 and 5 years, respectively; weight-for-height z-scores were missing for 16, 4, 11 and 184^c children at ages 2, 3, 4 and 5 years, respectively.</p>a<p>The effect of quarterly albendazole on asymptomatic malaria parasitaemia changed with time (interaction p = 0.02), therefore the overall effect of the intervention on this outcome is not presented.</p>b<p>Haemoglobin was not measured for four-year olds from 22^nd January 2009 onwards due to budget constraints.</p>c<p>Weight-for-height z-scores could not be calculated using WHO Anthro software for children who were aged >5 years and 1 month.</p

The prevalence of helminth infection at each routine annual visit, by childhood treatment group.

1<p>For each annual visit, denominators are slightly lower than in Web <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050325#pone-0050325-t003" target="_blank">Table 3</a> due to excluding children who were first randomised at that annual visit.</p