Hunger, waiting time and transport costs: Time to confront challenges to ART adherence in Africa

International audienceAdherence levels in Africa have been found to be better than those in the US. However around one out of four ART users fail to achieve optimal adherence, risking drug resistance and negative treatment outcomes. A high demand for 2nd line treatments (currently ten times more expensive than 1st line ART) undermines the sustainability of African ART programs. There is an urgent need to identify context-specific constraints to adherence and implement interventions to address them. We used rapid appraisals (involving mainly qualitative methods) to find out why and when people do not adhere to ART in Uganda, Tanzania and Botswana. Multidisciplinary teams of researchers and local health professionals conducted the studies, involving a total of 54 semi-structured interviews with health workers, 73 semi-structured interviews with ART users and other key informants, 34 focus group discussions, and 218 exit interviews with ART users. All the facilities studied in Botswana, Tanzania and Uganda provide ARVs free of charge, but ART users report other related costs (e.g. transport expenditures, registration and user fees at the private health facilities, and lost wages due to long waiting times) as main obstacles to optimal adherence. Side effects and hunger in the initial treatment phase are an added concern. We further found that ART users find it hard to take their drugs when they are among people to whom they have not disclosed their HIV status, such as co-workers and friends. The research teams recommend that (i) health care workers inform patients better about adverse effects; (ii) ART programmes provide transport and food support to patients who are too poor to pay; (iii) recurrent costs to users be reduced by providing three-months, rather than the one-month refills once optimal adherence levels have been achieved; and (iv) pharmacists play an important role in this follow-up care

Maternal Latent Mycobacterium tuberculosis Does Not Affect the Infant Immune Response Following BCG at Birth: An Observational Longitudinal Study in Uganda

Background: BCG has low efficacy in tropical countries. We hypothesized that maternal latent Mycobacterium tuberculosis (M.tb) infection (LTBI) results in fetal tolerance to mycobacterial antigens and impaired responses to BCG immunization. Methods: We enrolled 132 LTBI-positive and 150 LTBI-negative mothers and their babies in Entebbe, Uganda. Infants were BCG-immunized at birth. Cord blood and samples at weeks 1, 4, 6, 10, 14, 24, and 52 were analyzed for cytokine/chemokine responses to M.tb antigens by Luminex 17-plex assay in 6-day whole blood cultures and antibody responses by ELISA. Of the 17 Luminex analytes, seven (IL-2, IL-5, IL-10, IL-13, IL-17A, TNF, and IFN-γ) were included in the main analysis as they were considered most likely to represent T cell responses. Immune sensitization was defined as a detectable cord blood cytokine response to PPD for any of the seven cytokines. Patterns of cytokine and antibody responses were compared between infants of mothers with and without LTBI using linear mixed models adjusting for confounders. Results: Most infants (73%) were sensitized in utero to M.tb antigens, with no overall difference seen between infants born to mothers with or without LTBI. Patterns of post-BCG cytokine and antibody responses to mycobacterial antigens were similar between the two infant groups. Conclusions: Our data do not support the hypothesis that maternal LTBI results in an impaired response to BCG immunization, in Ugandan infants. BCG vaccination at or shortly after birth is likely to be beneficial to all infants, irrespective of maternal LTBI status.UK Medical Research Council; DELTAS Africa Initiative SSACAB; DELTAS Initiative MUIIplus; Commonwealth Scholarships Commission; MRC/UVRI and LSHTM Uganda Research Unit; EU Horizon 2020 programme; MRC London Intercollegiate Doctoral Training Partnership; MRC; UK Medical Research Council (MRC); UK Department for International Development (DFID)

Effect of birth weight, exclusive breastfeeding and growth in infancy on fat mass and fat free mass indices in early adolescence: an analysis of the Entebbe Mother and Baby Study (EMaBs) cohort [version 1; peer review: 1 approved, 2 approved with reservations]

Background: There is limited data from Africa on the effect of pre- and post-natal growth and infant feeding on later body composition. This study's aim was to investigate the effect of birth weight, exclusive breastfeeding and infant growth on adolescent body composition, using data from a Ugandan birth cohort. / Methods: Data was collected prenatally from pregnant women and prospectively from their resulting live offspring. Data on body composition (fat mass index [FMI] and fat free mass index [FFMI]) was collected from 10- and 11-year olds. Linear regression was used to assess the effect of birth weight, exclusive breastfeeding and infant growth on FMI and FFMI, adjusting for confounders. / Results: 177 adolescents with a median age of 10.1 years were included in analysis, with mean FMI 2.9 kg/m2 (standard deviation (SD) 1.2), mean FFMI 12.8 kg/m2 (SD 1.4) and mean birth weight 3.2 kg (SD 0.5). 90 (50.9%) were male and 110 (63.2%) were exclusively breastfeeding at six weeks of age. Birth weight was associated with FMI in adolescence (regression coefficient β= 0.66 per kg increase in birth weight, 95% confidence interval (CI) (0.04, 1.29), P=0.02), while exclusive breastfeeding (β= -0.43, 95% CI (-1.06, 0.19), P=0.12), growth 0-6 months (β= 0.24 95% CI (-0.43, 0.92), P=0.48) and growth 6-12 months (β= 0.61, 95% CI (-0.23, 1.46), P=0.11) were not associated with FMI among adolescents. Birth weight (β= 0.91, 95% CI (0.17, 1.65), P=0.01) was associated with FFMI in adolescence. Exclusive breastfeeding (β= 0.17, 95% CI (-0.60, 0.94), P=0.62), growth 0-6 months (β= 0.56, 95% CI (-0.20, 1.33), P= 0.10), and growth 6-12 months (β= -0.02, 95% CI (-1.02, 0.99), P=0.97) were not associated with FFMI. / Conclusions: Birth weight predicted body composition parameters in Ugandan early adolescents, however, exclusive breastfeeding at six weeks of age and growth in infancy did not

Effect of birth weight, exclusive breastfeeding and growth in infancy on fat mass and fat free mass indices in early adolescence: an analysis of the Entebbe Mother and Baby Study (EMaBs) cohort [version 2; peer review: 1 approved, 2 approved with reservations]

Background: There is limited data from Africa on the effect of pre- and post-natal growth and infant feeding on later body composition. This study's aim was to investigate the effect of birth weight, exclusive breastfeeding and infant growth on adolescent body composition, using data from a Ugandan birth cohort. / Methods: Data was collected prenatally from pregnant women and prospectively from their resulting live offspring. Data on body composition (fat mass index [FMI] and fat free mass index [FFMI]) was collected from 10- and 11-year olds. Linear regression was used to assess the effect of birth weight, exclusive breastfeeding and infant growth on FMI and FFMI, adjusting for confounders. / Results: 177 adolescents with a median age of 10.1 years were included in analysis, with mean FMI 2.9 kg/m 2 (standard deviation (SD) 1.2), mean FFMI 12.8 kg/m 2 (SD 1.4) and mean birth weight 3.2 kg (SD 0.5). 90 (50.9%) were male and 110 (63.2%) were exclusively breastfeeding at six weeks of age. Birth weight was associated with FMI in adolescence (regression coefficient β= 0.66 per kg increase in birth weight, 95% confidence interval (CI) (0.04, 1.29), P=0.02), while exclusive breastfeeding (β= -0.43, 95% CI (-1.06, 0.19), P=0.12), growth 0-6 months (β= 0.24 95% CI (-0.43, 0.92), P=0.48) and growth 6-12 months (β= 0.61, 95% CI (-0.23, 1.46), P=0.11) were not associated with FMI among adolescents. Birth weight (β= 0.91, 95% CI (0.17, 1.65), P=0.01) was associated with FFMI in adolescence. Exclusive breastfeeding (β= 0.17, 95% CI (-0.60, 0.94), P=0.62), growth 0-6 months (β= 0.56, 95% CI (-0.20, 1.33), P= 0.10), and growth 6-12 months (β= -0.02, 95% CI (-1.02, 0.99), P=0.97) were not associated with FFMI. / Conclusions: Birth weight predicted body composition parameters in Ugandan early adolescents, however, exclusive breastfeeding at six weeks of age and growth in infancy did not

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

Blood pressure risk factors in early adolescents: results from a Ugandan birth cohort

We aimed to investigate life-course factors associated with blood pressure (BP) among Ugandan adolescents. Between 9th April 2003 and 24th November 2005, 2507 pregnant women from Entebbe municipality and Katabi sub-county were enrolled into a deworming trial. The resulting 2345 live-born offspring were followed to age 10 or 11 years, when between 20th May 2014 to 16th June 2016, BP was measured following standard protocols. Factors associated with BP were assessed using multivariable linear regression. BP was measured in 1119 adolescents with a median age of 10.2 years. Mean systolic BP and diastolic BP was 105.9 mmHg (standard deviation (SD) 8.2) and 65.2 mmHg (SD 7.3), respectively. Maternal gestational body mass index (BMI), higher maternal education status and family history of hypertension were positively associated with adolescent BP. Childhood (age ≤5 years) malaria was associated with lower adolescent systolic BP. Factors measured at time of BP measurement positively associated with systolic BP were age, BMI, waist circumference and Trichuris trichiura (whipworm) infection; higher vegetable consumption was associated with lower systolic BP. Results for diastolic BP were similar, except higher fruit, rather than higher vegetable consumption was associated with lower diastolic BP and there was no association with waist circumference or Trichuris trichiura infection. In summary, life-course exposures were associated with adolescent BP in this tropical birth cohort. Malaria early in life could impact later BP. Interventions initiated early in life targeting individuals with family history of hypertension, aiming to reduce adiposity (in pregnancy and adolescence) and promoting fruit and vegetable consumption might contribute to reducing the risk of high BP and subsequent cardiovascular diseases

Adaptation of Western measures of cognition for assessing 5-year-old semi-urban Ugandan children

Background: The majority of available psychometric tests originates from the Western World and was designed to suit the culture, language, and socio-economic status of the respective populations. Few tests have been validated in the developing world despite the growing interest in examining effects of biological and environmental factors on cognitive functioning of children in this setting. Aims: The present study aimed at translating and adapting Western measures of working memory, general cognitive ability, attention, executive function, and motor ability in order to obtain a cognitive instrument suitable for assessing 5-year-old semi-urban Ugandan children. This population represents a particular assessment challenge as school enrolment is highly variable at this age in this setting and many children are unused to a formal educational setting. Methods: Measures of the above domains were selected, translated, and modified to suit the local culture, education, and socio-economic background of the target population. The measures were piloted and then administered to semi-urban Ugandan children aged 4;6-5;6, who included children who had started and not yet started school. Results: Analysis of validity and reliability characteristics showed that 8 (at least one from each domain) out of the 11 measures were successfully adapted on the basis that they showed adequate task comprehension, optimum levels of difficulty to demonstrate individual and group differences in abilities, sensitivity to effects of age and education, and good internal as well as test-retest reliability. Conclusion: Translation and adaptation are realistic and worthwhile strategies for obtaining valid and reliable cognitive measures in a resource-limited setting

A genome‐wide association and replication study of blood pressure in Ugandan early adolescents

Background Genetic association studies of blood pressure (BP) have mostly been conducted in non‐African populations. Using the Entebbe Mother and Baby Study (EMaBS), we aimed to identify genetic variants associated with BP among Ugandan adolescents. Methods Systolic and diastolic BP were measured among 10‐ and 11‐year olds. Whole‐genome genotype data were generated using Illumina omni 2.5M arrays and untyped variants were imputed. Genome‐wide association study (GWAS) was conducted using linear mixed model regression to account for population structure. Linear regression analysis was used to assess whether variants previously associated with BP (p Results Of the 14 million variants analyzed among 815 adolescents, none reached genome‐wide significance (p Conclusion Variants showing suggestive associations are worthy of future investigation. Replication results suggest that variants influencing adolescent BP may overlap somewhat with those already established in previous studies, largely based on adults in Western settings.</p