Prevalence and predictors of vitamin D deficiency in young African children.

BACKGROUND: Children living in sub-Saharan Africa have a high burden of rickets and infectious diseases, conditions that are linked to vitamin D deficiency. However, data on the vitamin D status of young African children and its environmental and genetic predictors are limited. We aimed to examine the prevalence and predictors of vitamin D deficiency in young African children. METHODS: We measured 25-hydroxyvitamin D (25(OH)D) and typed the single nucleotide polymorphisms, rs4588 and rs7041, in the GC gene encoding the vitamin D binding protein (DBP) in 4509 children aged 0-8 years living in Kenya, Uganda, Burkina Faso, The Gambia and South Africa. We evaluated associations between vitamin D status and country, age, sex, season, anthropometric indices, inflammation, malaria and DBP haplotypes in regression analyses. RESULTS: Median age was 23.9 months (interquartile range [IQR] 12.3, 35.9). Prevalence of vitamin D deficiency using 25(OH)D cut-offs of < 30 nmol/L and < 50 nmol/L was 0.6% (95% CI 0.4, 0.9) and 7.8% (95% CI 7.0, 8.5), respectively. Overall median 25(OH)D level was 77.6 nmol/L (IQR 63.6, 94.2). 25(OH)D levels were lower in South Africa, in older children, during winter or the long rains, and in those with afebrile malaria, and higher in children with inflammation. 25(OH)D levels did not vary by stunting, wasting or underweight in adjusted regression models. The distribution of Gc variants was Gc1f 83.3%, Gc1s 8.5% and Gc2 8.2% overall and varied by country. Individuals carrying the Gc2 variant had lower median 25(OH)D levels (72.4 nmol/L (IQR 59.4, 86.5) than those carrying the Gc1f (77.3 nmol/L (IQR 63.5, 92.8)) or Gc1s (78.9 nmol/L (IQR 63.8, 95.5)) variants. CONCLUSIONS: Approximately 0.6% and 7.8% of young African children were vitamin D deficient as defined by 25(OH)D levels < 30 nmol/L and < 50 nmol/L, respectively. Latitude, age, season, and prevalence of inflammation and malaria should be considered in strategies to assess and manage vitamin D deficiency in young children living in Africa.

Estimating the burden of iron deficiency among African children.

BACKGROUND: Iron deficiency (ID) is a major public health burden in African children and accurate prevalence estimates are important for effective nutritional interventions. However, ID may be incorrectly estimated in Africa because most measures of iron status are altered by inflammation and infections such as malaria. Through the current study, we have assessed different approaches to the prediction of iron status and estimated the burden of ID in African children. METHODS: We assayed iron and inflammatory biomarkers in 4853 children aged 0-8 years from Kenya, Uganda, Burkina Faso, South Africa, and The Gambia. We described iron status and its relationship with age, sex, inflammation, and malaria parasitemia. We defined ID using the WHO guideline (ferritin < 12 µg/L or < 30 µg/L in the presence of inflammation in children < 5 years old or < 15 µg/L in children ≥ 5 years old). We compared this with a recently proposed gold standard, which uses regression-correction for ferritin levels based on the relationship between ferritin levels, inflammatory markers, and malaria. We further investigated the utility of other iron biomarkers in predicting ID using the inflammation and malaria regression-corrected estimate as a gold standard. RESULTS: The prevalence of ID was highest at 1 year of age and in male infants. Inflammation and malaria parasitemia were associated with all iron biomarkers, although transferrin saturation was least affected. Overall prevalence of WHO-defined ID was 34% compared to 52% using the inflammation and malaria regression-corrected estimate. This unidentified burden of ID increased with age and was highest in countries with high prevalence of inflammation and malaria, where up to a quarter of iron-deficient children were misclassified as iron replete. Transferrin saturation < 11% most closely predicted the prevalence of ID according to the regression-correction gold standard. CONCLUSIONS: The prevalence of ID is underestimated in African children when defined using the WHO guidelines, especially in malaria-endemic populations, and the use of transferrin saturation may provide a more accurate approach. Further research is needed to identify the most accurate measures for determining the prevalence of ID in sub-Saharan Africa.

Iron Status and Associated Malaria Risk Among African Children.

BACKGROUND: It remains unclear whether improving iron status increases malaria risk, and few studies have looked at the effect of host iron status on subsequent malaria infection. We therefore aimed to determine whether a child's iron status influences their subsequent risk of malaria infection in sub-Saharan Africa. METHODS: We assayed iron and inflammatory biomarkers from community-based cohorts of 1309 Kenyan and 1374 Ugandan children aged 0-7 years and conducted prospective surveillance for episodes of malaria. Poisson regression models were fitted to determine the effect of iron status on the incidence rate ratio (IRR) of malaria using longitudinal data covering a period of 6 months. Models were adjusted for age, sex, parasitemia, inflammation, and study site. RESULTS: At baseline, the prevalence of iron deficiency (ID) was 36.9% and 34.6% in Kenyan and Ugandan children, respectively. ID anemia (IDA) affected 23.6% of Kenyan and 17.6% of Ugandan children. Malaria risk was lower in children with ID (IRR, 0.7; 95% confidence interval [CI], 0.6, 0.8; P < .001) and IDA (IRR, 0.7; 95% CI, 0.6, 0.9; P = .006). Low transferrin saturation (<10%) was similarly associated with lower malaria risk (IRR, 0.8; 95% CI, 0.6, 0.9; P = .016). However, variation in hepcidin, soluble transferrin receptors (sTfR), and hemoglobin/anemia was not associated with altered malaria risk. CONCLUSIONS: ID appears to protect against malaria infection in African children when defined using ferritin and transferrin saturation, but not when defined by hepcidin, sTfR, or hemoglobin. Additional research is required to determine causality. CLINICAL TRIALS REGISTRATION: ISRCTN32849447.

Life-course of atopy and allergy-related disease events in tropical sub-Saharan Africa: A birth cohort study.

BACKGROUND: In high-income countries, allergy-related diseases (ARDs) follow a typical sequence, the 'Atopic March'. Little is known about the life-course of ARDs in the markedly different, low-income, tropical environment. We describe ARDs in a tropical, African birth cohort. METHODS: Ugandan children were followed from birth to 9 years. ISAAC questionnaires were completed at intervals; doctor-diagnosed ARDs were recorded throughout follow-up. Skin prick tests (SPTs) were performed at 3 and 9 years. Atopy was defined as ≥1 positive SPT. RESULTS: Of the 2345 live-born children, 1214 (52%) were seen at 9 years. Wheeze and eczema were common in infancy, but by 9 years, only 4% reported recent wheeze, 5% eczema and 5% rhinitis. Between 3 and 9 years, atopy prevalence increased from 19% to 25%. Atopy at 3 or 9 years was associated with reported ARD events at 9 years, for example OR = 5.2 (95% CI 2.9-10.7) for atopy and recent wheeze at 9 years. Reported or doctor-diagnosed ARD events in early childhood were associated with the same events in later childhood, for example OR = 4.4 (2.3-8.4) for the association between reported wheeze before 3 years with reported recent wheeze at 9 years, but progression from early eczema to later rhinitis or asthma was not observed. CONCLUSION: Allergen sensitization started early in childhood and increased with age. Eczema and wheeze were common in infancy and declined with age. Atopy was strongly associated with ARD among the few affected children. The typical Atopic March did not occur. Environmental exposures during childhood may dissociate atopy and ARD.

Effects of treating helminths during pregnancy and early childhood on risk of allergy-related outcomes: Follow-up of a randomized controlled trial.

BACKGROUND: Helminth infections, common in low-income countries, may protect against allergy-related disease. Early exposure may be a key. In the Entebbe Mother and Baby Study, treating helminths during pregnancy resulted in increased eczema rates in early childhood. We followed the cohort to determine whether this translated to increased asthma rates at school age. METHODS: This randomized, double-blind, placebo-controlled trial, conducted in Entebbe, Uganda, had three interventions. During pregnancy, women were randomized, simultaneously, to albendazole vs placebo and to praziquantel vs placebo. Their children were independently randomized to quarterly albendazole vs placebo from age 15 months to 5 years. We here report follow-up to age 9 years. Primary outcomes at 9 years were recent reported wheeze, skin prick test positivity (SPT) to common allergens and allergen-specific IgE positivity to dust mite or cockroach. Secondary outcomes were doctor-diagnosed asthma and eczema rates between 5 and 9 years, recent eczema, rhinitis and urticaria at 9 years, and SPT and IgE responses to individual allergens. RESULTS: 2507 pregnant women were enrolled; 1215 children were seen at age nine, of whom 1188 are included in this analysis. Reported wheeze was rare at 9 years (3.7%) while SPT positivity (25.0%) and IgE positivity (44.1%) were common. There was no evidence of a treatment effect for any of the three interventions on any of the primary outcomes. CONCLUSIONS: Prenatal and early-life treatment of helminths, in the absence of change in other exposures, is unlikely to increase the risk of atopic diseases later in childhood in this tropical, low-income setting.

Maternal hookworm modifies risk factors for childhood eczema: results from a birth cohort in Uganda.

BACKGROUND: Worms may protect against allergy. Early-life worm exposure may be critical, but this has not been fully investigated. OBJECTIVES: To investigate whether worms in pregnancy and in early childhood are associated with childhood eczema incidence. METHODS: The Entebbe Mother and Baby Study, an anthelminthic treatment trial, enrolled pregnant women between 2003 and 2005 in Uganda. Mothers were investigated for worms during pregnancy and children annually. Eczema was doctor-diagnosed from birth to age five years. A planned observational analysis was conducted within the trial cohort to investigate associations between worms and eczema. RESULTS: Data for 2345 live-born children were analysed. Hookworm was the most prevalent maternal worm (45%). Childhood worms were less prevalent. Eczema incidence was 4.68/100 person-years. Maternal hookworm was associated with reduced eczema incidence [adjusted hazard ratio (95% confidence interval), p-value: 0.71(0.51-0.99), 0.04] and modified effects of known risk factors for eczema: Dermatophagoides-specific IgE in children was positively associated with eczema incidence if the mother had no hookworm [2.72(1.11-6.63), 0.03], but not if the mother had hookworm [0.41(0.10-1.69), 0.22], interaction p-value = 0.03. Similar interactions were seen for maternal history of eczema {[2.87(1.31-6.27, 0.008) vs. [0.73(0.23-2.30), 0.60], interaction p-value = 0.05}, female gender {[1.82(1.22-2.73), 0.004 vs. [0.96(0.60-1.53), 0.87], interaction p-value = 0.04} and allergen-specific IgE. Childhood Trichuris trichiura and hookworm were inversely associated with eczema. CONCLUSIONS: Maternal hookworm modifies effects of known risk factors for eczema. Mechanisms by which early-life worm exposures influence allergy need investigation. Worms or worm products, and intervention during pregnancy have potential for primary prevention of allergy.

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.

Associations between maternal helminth and malaria infections in pregnancy and clinical malaria in the offspring: a birth cohort in entebbe, Uganda.

BACKGROUND: Helminth and malaria coinfections are common in the tropics. We investigated the hypothesis that prenatal exposure to these parasites might influence susceptibility to malaria in childhood. METHODS: In a birth cohort of 2345 mother-child pairs in Uganda, maternal helminth and malaria infection status was determined during pregnancy, and childhood malaria episodes were recorded from birth to age 5 years. We examined associations between maternal infections and malaria in the offspring. RESULTS: Common maternal infections were hookworm (45%), Mansonella perstans (21%), Schistosoma mansoni (18%), and Plasmodium falciparum (11%). At age 5 years, 69% of the children were still under follow-up. The incidence of malaria was 34 episodes per 100 child-years, and the mean prevalence of asymptomatic malaria at annual visits was 5.4%. Maternal hookworm and M. perstans infections were associated with an increased rate of childhood clinical malaria (adjusted hazard ratio [aHR], 1.24, 95% confidence interval [CI], 1.10-1.41; aHR, 1.20, 95% CI, 1.05-1.38, respectively). S. mansoni infection had no consistent association with childhood malaria. CONCLUSIONS: This is the first report of an association between helminth infections in pregnancy and malaria in the offspring and indicates that helminth infections in pregnancy may increase the burden of childhood malaria morbidity.

The contextual awareness, response and evaluation (CARE) diabetes project: study design for a quantitative survey of diabetes prevalence and non-communicable disease risk in Ga Mashie, Accra, Ghana.

Diabetes is estimated to affect between 3.3% and 8.3% of adults in Ghana, and prevalence is expected to rise. The lack of cost-effective diabetes prevention programmes designed specifically for the Ghanaian population warrants urgent attention. The Contextual Awareness, Response and Evaluation (CARE): Diabetes Project in Ghana is a mixed methods study that aims to understand diabetes in the Ga Mashie area of Accra, identify opportunities for community-based intervention and inform future diabetes prevention and control strategies. This paper presents the study design for the quantitative survey within the CARE project. This survey will take place in the densely populated Ga Mashie area of Accra, Ghana. A household survey will be conducted using simple random sampling to select households from 80 enumeration areas identified in the 2021 Ghana Population and Housing Census. Trained enumerators will interview and collect data from permanent residents aged ≥ 25 years. Pregnant women and those who have given birth in the last six months will be excluded. Data analysis will use a combination of descriptive and inferential statistics, and all analyses will account for the cluster sampling design. Analyses will describe the prevalence of diabetes, other morbidities, and associated risk factors and identify the relationship between diabetes and physical, social, and behavioural parameters. This survey will generate evidence on drivers and consequences of diabetes and facilitate efforts to prevent and control diabetes and other NCDs in urban Ghana, with relevance for other low-income communities.

Maternal HIV infection and other factors associated with growth outcomes of HIV-uninfected infants in Entebbe, Uganda.

OBJECTIVE: To assess the associations between maternal HIV infection and growth outcomes of HIV-exposed but uninfected infants and to identify other predictors for poor growth among this population. DESIGN: Within a trial of de-worming during pregnancy, the cohort of offspring was followed from birth. HIV status of the mothers and their children was investigated and growth data for children were obtained at age 1 year. Length-for-age, weight-for-age and weight-for-length Z-scores were calculated for each child; Z-scores ,22 were defined as stunting, underweight and wasting, respectively. SETTING: The study was conducted in Entebbe municipality and Katabi subcounty, Uganda. SUBJECTS: The sample consisted of 1502 children aged 1 year: HIV-unexposed (n 1380) and HIV-exposed not infected (n 122). RESULTS: Prevalence of stunting, underweight and wasting was 14.2%, 8.0% and 3.9%, respectively. There was evidence for an association between maternal HIV infection and odds of being underweight (adjusted OR52.32; 95% CI 1.32, 4.09; P=0.006) but no evidence for an association with stunting or with wasting. Young maternal age, low maternal education, low birth weight, early weaning and experiencing a higher number of episodes of malaria during infancy were independent predictors for stunting and underweight. A higher number of living children in the family was associated with wasting. CONCLUSIONS: Maternal HIV infection was associated with being underweight in HIV-exposed uninfected infants. The success of programmes for prevention of mother-to-child HIV transmission means that an increasing number of infants will be born to HIV-infected women without acquiring HIV. Therefore, viable nutritional interventions need to be identified for this population.

Factors affecting the infant antibody response to measles immunisation in Entebbe-Uganda.

BACKGROUND: Vaccine failure is an important concern in the tropics with many contributing elements. Among them, it has been suggested that exposure to natural infections might contribute to vaccine failure and recurrent disease outbreaks. We tested this hypothesis by examining the influence of co-infections on maternal and infant measles-specific IgG levels. METHODS: We conducted an observational analysis using samples and data that had been collected during a larger randomised controlled trial, the Entebbe Mother and Baby Study (ISRCTN32849447). For the present study, 711 pregnant women and their offspring were considered. Helminth infections including hookworm, Schistosoma mansoni and Mansonella perstans, along with HIV, malaria, and other potential confounding factors were determined in mothers during pregnancy and in their infants at age one year. Infants received their measles immunisation at age nine months. Levels of total IgG against measles were measured in mothers during pregnancy and at delivery, as well as in cord blood and from infants at age one year. RESULTS: Among the 711 pregnant women studied, 66% had at least one helminth infection at enrolment, 41% had hookworm, 20% M. perstans and 19% S. mansoni. Asymptomatic malaria and HIV prevalence was 8% and 10% respectively. At enrolment, 96% of the women had measles-specific IgG levels considered protective (median 4274 mIU/ml (IQR 1784, 7767)). IgG levels in cord blood were positively correlated to maternal measles-specific IgG levels at delivery (r = 0.81, p < 0.0001). Among the infants at one year of age, median measles-specific IgG levels were markedly lower than in maternal and cord blood (median 370 mIU/ml (IQR 198, 656) p < 0.0001). In addition, only 75% of the infants had measles-specific IgG levels considered to be protective. In a multivariate regression analysis, factors associated with reduced measles-specific antibody levels in infancy were maternal malaria infection, infant malaria parasitaemia, infant HIV and infant wasting. There was no association with maternal helminth infection. CONCLUSION: Malaria and HIV infection in mothers during pregnancy, and in their infants, along with infant malnutrition, may result in reduction of the antibody response to measles immunisation in infancy. This re-emphasises the importance of malaria and HIV control, and support for infant nutrition, as these interventions may have benefits for vaccine efficacy in tropical settings.

Maternal recall of birthweight and birth size in Entebbe, Uganda.

OBJECTIVES: To assess the reliability of maternally recalled birthweight and size in Entebbe, Uganda. METHODS: The study population comprised 404 mothers, who were participants in the Entebbe Mother and Baby Study (EMaBS). Mothers were recruited to EMaBS during antenatal care, maternal characteristics were recorded during pregnancy, and birthweight was recorded at delivery. Four to seven years after delivery, mothers were asked to recall the child's birthweight and size. Their responses were compared with the birthweight recorded in the EMaBS database. RESULTS: Of 404 interviewed mothers, 303 (75%) were able to give an estimate of birthweight and for 265 of these EMaBS data on recorded birthweights were available. Women who were educated and whose children had low birth order were more likely to be able to give an estimate: 37 (14%) recalled the exact recorded birthweight; a further 52 (20%) were accurate to within 0.1 kg of the recorded weight. On average, mothers overestimated birthweight by 0.06 kg (95% CI: 0.00-0.13 kg, P = 0.04). Recalled and recorded birthweights showed moderate agreement with an intraclass correlation coefficient of 0.64. Four hundered mothers gave an estimate of birth size: the sensitivity and specificity of recalled birth size for classifying low birthweight were 76% (95% CI: 50-93%) and 70% (95% CI: 65-75%), respectively. CONCLUSIONS: Mothers' recall of birthweight was not precise but in absence of other data, recall of birthweight and size may have some value in epidemiological studies in these settings.

Effects of maternal worm infections and anthelminthic treatment during pregnancy on infant motor and neurocognitive functioning.

We tested the hypothesis that maternal worm infections in pregnancy affect infant motor and neurocognitive development, and that anthelminthic treatment during pregnancy can reverse these effects. We used measures which examine infant motor, cognitive and executive function, including inhibition. We assessed 983 Ugandan infants aged 15 months, using locally appropriate measures within the Entebbe Mother and Baby Study, a trial of anthelminthic treatment during pregnancy. Key exposures were maternal worm infections and anthelminthic treatment during pregnancy. Effects of other health and social factors were controlled for statistically. Of the five major worm species found in the pregnant women, two had influences on the developmental measures: Maternal Mansonella perstans and Strongyloides stercoralis infections showed negative associations with the A-not B-task, and Language, respectively. Performance on other psychomotor and cognitive measures was associated with illnesses during infancy and infants' behavior during assessment, but not with maternal worm infections. There were no positive effects of maternal anthelminthic treatment on infant abilities. Mansonella perstans and Strongyloides stercoralis infection during pregnancy seem associated with impaired early executive function and language, respectively, but single-dose anthelminthic treatment during pregnancy was not beneficial. The biological mechanisms that could underlie these neurocognitive effects are discussed.

Clinical manifestations of Rift Valley fever in humans: Systematic review and meta-analysis.

BACKGROUND: Rift Valley fever (RVF) is an emerging, neglected, mosquito-borne viral zoonosis associated with significant morbidity, mortality and expanding geographical scope. The clinical signs and symptoms in humans are non-specific and case definitions vary. We reviewed and analysed the clinical manifestations of RVF in humans. METHODS: In this systematic review and meta-analysis we searched on different dates, the Embase (from 1947 to 13th October 2019), Medline (1946 to 14th October 2019), Global Health (1910 to 15th October 2019), and Web of Science (1970 to 15th October 2019) databases. Studies published in English, reporting frequency of symptoms in humans, and laboratory confirmed RVF were included. Animal studies, studies among asymptomatic volunteers, and single case reports for which a proportion could not be estimated, were excluded. Quality assessment was done using a modified Hoy and Brooks et al tool, data was extracted, and pooled frequency estimates calculated using random effects meta-analysis. RESULTS: Of the 3765 articles retrieved, less than 1% (32 articles) were included in the systematic review and meta-analysis. Nine RVF clinical syndromes were reported including the general febrile, renal, gastrointestinal, hepatic, haemorrhagic, visual, neurological, cardio-pulmonary, and obstetric syndromes. The most common clinical manifestations included fever (81%; 95% Confidence Interval (CI) 69-91; [26 studies, 1286 patients]), renal failure (41%; 23-59; [4, 327]), nausea (38%; 12-67; [6, 325]), jaundice (26%; 16-36; [15, 393]), haemorrhagic disease (26%; 17-36; [16, 277]), partial blindness (24%; 7-45; [11, 225]), encephalitis (21%; 11-33; [4, 327]), cough (4%; 0-17; [4, 11]), and miscarriage (54%) respectively. Death occurred in 21% (95% CI 14-29; [16 studies, 328 patients]) of cases, most of whom were hospitalised. DISCUSSION: This study delineates the complex symptomatology of human RVF disease into syndromes. This approach is likely to improve case definitions and detection rates, impact outbreak control, increase public awareness about RVF, and subsequently inform 'one-health' policies. This study provides a pooled estimate of the proportion of RVF clinical manifestations alongside a narrative description of clinical syndromes. However, most studies reviewed were case series with small sample sizes and enrolled mostly in-patients and out-patients, and captured symptoms either sparsely or using broad category terms.

Blood pressure levels among children in rural Uganda: results from 1913 children in a general population survey.

Despite increasing levels of adult hypertension in sub-Saharan Africa (SSA), there is limited information on elevated blood pressure among children in SSA. We described the distribution of blood pressure among children in rural Uganda and estimated hypertension prevalence. We conducted a cross-sectional study in south-western Uganda, collecting demographic, anthropometric and blood pressure measurements from children aged 6-12 years. Children with elevated blood pressure (systolic and/or diastolic blood pressure greater or equal to the 95th percentile for age, height and sex) were invited for two further assessments 6-18 months later. We described blood pressure distribution at first assessment, assessed associations with demographic and anthropometric characteristics and estimated prevalence of hypertension as defined by having elevated blood pressure on three separate occasions months apart. Blood pressure (BP) was measured in 1913 children (50% male, 3% overweight or obese, 22% stunted) at the first assessment. Mean (SD) systolic and diastolic BP at first assessment was 113.4 mmHg (±10.8) and 69.5 mmHg (±8.3), respectively, and 44.2% had elevated BP. Older age, higher BMI, and being female were associated with higher BP, and stunted height was associated with lower BP. An estimated 7.8% [95% CI:(6.6-9.1)], (males: 6.8%, females: 9.0%), had elevated BP on three separate occasions, and were considered hypertensive. High blood pressure levels among adults in SSA may be set early in life. In this study, obesity (a common lifestyle modifiable risk factor in other settings) was largely irrelevant. More research is needed to understand the main drivers for elevated blood pressure in SSA further.

Widespread exposure to Crimean-Congo haemorrhagic fever in Uganda might be driven by transmission from Rhipicephalus ticks: Evidence from cross-sectional and modelling studies.

BACKGROUND: Crimean-Congo haemorrhagic fever (CCHF) is a widespread tick-borne viral infection, present across Africa and Eurasia, which might pose a cryptic public health problem in Uganda. We aimed to understand the magnitude and distribution of CCHF risk in humans, livestock and ticks across Uganda by synthesising epidemiological (cross-sectional) and ecological (modelling) studies. METHODS: We conducted a cross-sectional study at three urban abattoirs receiving cattle from across Uganda. We sampled humans (n = 478), livestock (n = 419) and ticks (n = 1065) and used commercially-available kits to detect human and livestock CCHF virus (CCHFV) antibodies and antigen in tick pools. We developed boosted regression tree models to evaluate the correlates and geographical distribution of expected tick and wildlife hosts, and of human CCHF exposures, drawing on continent-wide data. FINDINGS: The cross-sectional study found CCHFV IgG/IgM seroprevalence in humans of 10·3% (7·8-13·3), with antibody detection positively associated with reported history of tick bite (age-adjusted odds ratio = 2·09 (1·09-3·98)). Cattle had a seroprevalence of 69·7% (65·1-73·4). Only one Hyalomma tick (CCHFV-negative) was found. However, CCHFV antigen was detected in Rhipicephalus (5·9% of 304 pools) and Amblyomma (2·9% of 34 pools) species. Modelling predicted high human CCHF risk across much of Uganda, low environmental suitability for Hyalomma, and high suitability for Rhipicephalus and Amblyomma. INTERPRETATION: Our epidemiological and ecological studies provide complementary evidence that CCHF exposure risk is widespread across Uganda. We challenge the idea that Hyalomma ticks are consistently the principal reservoir and vector for CCHFV, and postulate that Rhipicephalus might be important for CCHFV transmission in Uganda, due to high frequency of infected ticks and predicted environmental suitability. FUNDING: UCL Global Challenges Research Fund (GCRF) and Pan-African Network on Emerging and Re-Emerging Infections (PANDORA-ID-NET) funded by the European and Developing Countries Clinical Trials Partnership (EDCTP) under the EU Horizon 2020 Framework Programme for Research and Innovation.

Vitamin D Deficiency and Its Association with Iron Deficiency in African Children.

Vitamin D regulates the master iron hormone hepcidin, and iron in turn alters vitamin D metabolism. Although vitamin D and iron deficiency are highly prevalent globally, little is known about their interactions in Africa. To evaluate associations between vitamin D and iron status we measured markers of iron status, inflammation, malaria parasitemia, and 25-hydroxyvitamin D (25(OH)D) concentrations in 4509 children aged 0.3 months to 8 years living in Kenya, Uganda, Burkina Faso, The Gambia, and South Africa. Prevalence of iron deficiency was 35.1%, and prevalence of vitamin D deficiency was 0.6% and 7.8% as defined by 25(OH)D concentrations of <30 nmol/L and <50 nmol/L, respectively. Children with 25(OH)D concentrations of <50 nmol/L had a 98% increased risk of iron deficiency (OR 1.98 [95% CI 1.52, 2.58]) compared to those with 25(OH)D concentrations >75 nmol/L. 25(OH)D concentrations variably influenced individual markers of iron status. Inflammation interacted with 25(OH)D concentrations to predict ferritin levels. The link between vitamin D and iron status should be considered in strategies to manage these nutrient deficiencies in African children.

A description of congenital anomalies among infants in Entebbe, Uganda.

BACKGROUND: Data on congenital anomalies from developing countries of the sub-Saharan region are scarce. However, it is important to have comprehensive and reliable data on the description and prevalence of congenital anomalies to allow surveillance and the implementation of appropriate public health strategies for prevention and management. In this study, we describe the profile of congenital anomalies seen in a birth cohort in Entebbe, Uganda. METHODS: Congenital anomalies were defined as any structural defect present at birth. Pregnant women were recruited to the cohort between 2003 and 2005. Defects present at birth were recorded by the midwife at delivery and by physicians at the routine six-week postnatal visit and at illness-related visits until 1 year of life. The anomalies were classified by organ system according to the 10th version of the World Health Organization International Classification of Diseases (ICD-10). RESULTS: There were 180 infants with a congenital anomaly among 2365 births. The most commonly affected systems were the musculoskeletal (42.7 per 1000 births) and skin (16.1 per 1000 births). The prevalence of major anomalies was 20.3 per 1000 births; 1.7 per 1000 births for cardiac anomalies and 1.3 per 1000 births for neural system anomalies. Forty (22%) of the congenital anomalies were identified at birth, 131 (73%) at the 6-week postnatal visit, and nine (5%) at illness-related visits. CONCLUSION: Congenital anomalies are common in developing countries. Establishment of comprehensive databases for surveillance would be helpful for surveillance of effects of new exposures, for prevention, management, and health care planning.

Infection-exposure in infancy is associated with reduced allergy-related disease in later childhood in a Ugandan cohort.

Background: Lack of early infection-exposure has been associated with increased allergy-related disease (ARD) susceptibility. In tropical Africa, little is known about which infections contribute to development of ARDs, and at which time. Methods: We used latent class analysis to characterise the early infection-exposure of participants in a Ugandan birth cohort and assessed ARDs in later childhood. Results: Of 2345 live births, 2115 children (90%) had data on infections within the first year of life while 1179 (50%) had outcome data at 9 years. We identified two latent classes of children based on first-year infection-exposure. Class 1 (32% membership), characterised by higher probabilities for malaria (80%), diarrhoea (76%), and lower respiratory tract infections (LRTI) (22%), was associated with lower prevalence of wheeze, eczema, rhinitis, and Dermatophagoides skin prick test (SPT) positivity at 9 years. Based on 5-year cumulative infection experience, class 1 (31% membership), characterised by higher probabilities for helminths (92%), malaria (79%), and LRTI (45%), was associated with lower probabilities of SPT positivity at 9 years. Conclusions: In this Ugandan birth cohort, early childhood infection-exposure, notably to malaria, helminths, LRTI, and diarrhoea, is associated with lower prevalence of atopy and ARDs in later childhood. Funding: This work was supported by several funding sources. The Entebbe Mother and Baby Study (EMaBS) was supported by the Wellcome Trust, UK, senior fellowships for AME (grant numbers 064693, 079110, 95778) with additional support from the UK Medical Research Council. LL is supported by a PhD fellowship through the DELTAS Africa Initiative SSACAB (grant number 107754). ELW received funding from MRC Grant Reference MR/K012126/1. SAL was supported by the PANDORA-ID-NET Consortium (EDCTP Reg/Grant RIA2016E-1609). HM was supported by the Wellcome's Institutional Strategic Support Fund (grant number 204928/Z/16/Z).