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1.
Glob Health Action ; 17(1): 2297513, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38323339

RESUMEN

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.


Asunto(s)
Diabetes Mellitus , Enfermedades no Transmisibles , Embarazo , Adulto , Humanos , Femenino , Ghana/epidemiología , Prevalencia , Diabetes Mellitus/epidemiología , Factores de Riesgo
2.
J Infect ; 85(6): 683-692, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36152736

RESUMEN

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.


Asunto(s)
Virus de la Fiebre Hemorrágica de Crimea-Congo , Fiebre Hemorrágica de Crimea , Ixodidae , Rhipicephalus , Humanos , Animales , Bovinos , Fiebre Hemorrágica de Crimea/epidemiología , Fiebre Hemorrágica de Crimea/diagnóstico , Estudios Transversales , Estudios Seroepidemiológicos , Uganda/epidemiología
3.
Nutrients ; 14(7)2022 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-35405984

RESUMEN

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.


Asunto(s)
Deficiencias de Hierro , Deficiencia de Vitamina D , Biomarcadores , Niño , Humanos , Inflamación/epidemiología , Hierro , Prevalencia , Sudáfrica , Vitamina D , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiología , Vitaminas
4.
PLoS Negl Trop Dis ; 16(3): e0010233, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35333856

RESUMEN

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.


Asunto(s)
Salud Única , Fiebre del Valle del Rift , Virus de la Fiebre del Valle del Rift , Animales , Brotes de Enfermedades , Humanos , Fiebre del Valle del Rift/epidemiología , Síndrome , Zoonosis/epidemiología
5.
J Hum Hypertens ; 36(11): 1021-1026, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-34537817

RESUMEN

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.


Asunto(s)
Enfermedades del Sistema Nervioso Autónomo , Hipertensión , Niño , Adulto , Humanos , Masculino , Femenino , Lactante , Presión Sanguínea/fisiología , Estudios Transversales , Índice de Masa Corporal , Uganda/epidemiología , Hipertensión/diagnóstico , Hipertensión/epidemiología , Hipertensión/etiología , Población Rural , Obesidad/complicaciones , Prevalencia , Factores de Riesgo
6.
Elife ; 102021 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-34550875

RESUMEN

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).


Asunto(s)
Enfermedades Transmisibles/epidemiología , Hipersensibilidad/epidemiología , Factores de Edad , Niño , Preescolar , Enfermedades Transmisibles/diagnóstico , Enfermedades Transmisibles/inmunología , Femenino , Humanos , Hipersensibilidad/diagnóstico , Hipersensibilidad/inmunología , Hipersensibilidad/prevención & control , Lactante , Recién Nacido , Análisis de Clases Latentes , Masculino , Prevalencia , Factores Protectores , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de Riesgo , Uganda/epidemiología
7.
Sci Rep ; 11(1): 16503, 2021 08 13.
Artículo en Inglés | MEDLINE | ID: mdl-34389769

RESUMEN

Dyslipidaemia in adolescence tracks into adulthood and is an important risk factor for cardiovascular disease. Little is known about the effects of environmental exposures and early-life exposure to infectious diseases common to tropical regions on lipids. In 1119 early adolescent participants in the Entebbe Mother and Baby Study, we used linear regression to examine whether prenatal, childhood or adolescent factors are associated with lipid levels. Reduced high-density lipoprotein (HDL) and elevated triglyceride levels were common (prevalence 31% and 14%, respectively), but elevated low-density lipoprotein (LDL) or total cholesterol (TC) were rare. Current malaria infection was associated with lower mean LDL (adjusted ß - 0.51; 95% CI - 0.81, - 0.21), HDL (adjusted ß - 0.40; 95% CI - 0.56, - 0.23), and TC levels (adjusted ß - 0.62; 95% CI - 0.97, - 0.27), but higher mean triglyceride levels (geometric mean ratio (GMR) 1.47; 95% CI 1.18-1.84). Early-life asymptomatic malaria was associated with modest reductions in HDL and TC. Body mass index (BMI) was positively associated with LDL, TC, and triglycerides. No associations with helminth infection were found. Our findings suggest that early-life factors have only marginal effects on the lipid profile. Current malaria infection and BMI are strongly associated with lipids and important to consider when trying to improve the lipid profile.


Asunto(s)
Lípidos/sangre , Adolescente , Colesterol/sangre , LDL-Colesterol/sangre , Dislipidemias/epidemiología , Dislipidemias/etiología , Femenino , Infecciones por Uncinaria/complicaciones , Humanos , Modelos Lineales , Lipoproteínas HDL/sangre , Malaria/complicaciones , Masculino , Factores de Riesgo , Factores Socioeconómicos , Triglicéridos/sangre , Uganda/epidemiología
8.
BMC Med ; 19(1): 115, 2021 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-34011341

RESUMEN

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.


Asunto(s)
Deficiencia de Vitamina D , Adulto , Niño , Preescolar , Haplotipos , Humanos , Prevalencia , Estaciones del Año , Sudáfrica , Vitamina D , Deficiencia de Vitamina D/diagnóstico , Deficiencia de Vitamina D/epidemiología , Proteína de Unión a Vitamina D/genética , Adulto Joven
10.
Nat Med ; 27(4): 653-658, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33619371

RESUMEN

Malaria and iron deficiency (ID) are common and interrelated public health problems in African children. Observational data suggest that interrupting malaria transmission reduces the prevalence of ID1. To test the hypothesis that malaria might cause ID, we used sickle cell trait (HbAS, rs334 ), a genetic variant that confers specific protection against malaria2, as an instrumental variable in Mendelian randomization analyses. HbAS was associated with a 30% reduction in ID among children living in malaria-endemic countries in Africa (n = 7,453), but not among individuals living in malaria-free areas (n = 3,818). Genetically predicted malaria risk was associated with an odds ratio of 2.65 for ID per unit increase in the log incidence rate of malaria. This suggests that an intervention that halves the risk of malaria episodes would reduce the prevalence of ID in African children by 49%.


Asunto(s)
Deficiencias de Hierro , Malaria/complicaciones , Absorción Fisiológica , Adolescente , África , Niño , Preescolar , Femenino , Geografía , Hepcidinas/metabolismo , Humanos , Lactante , Masculino , Análisis de la Aleatorización Mendeliana , Rasgo Drepanocítico/complicaciones
11.
BMJ Glob Health ; 5(12)2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33293291

RESUMEN

OBJECTIVE: To investigate the relationship between social risk factors and latent tuberculosis infection (LTBI) among individuals who are eligible for LTBI screening in the United Kingdom (UK). METHODS: This cross-sectional study used data collected in the UK Prognostic Evaluation of Diagnostic Interferon-Gamma Release Assays (IGRAs) Consortium Study which enrolled 9176 recent tuberculosis (TB) contacts and migrants at National Health Service (NHS) facilities and community settings in the UK. The study outcome was LTBI (positive IGRA test (QuantiFERON-TB Gold In-Tube or T-SPOT.TB)). The main exposures were history of smoking, history of substance misuse, homelessness, prison stay and socioeconomic deprivation. RESULTS: 4914 (56.2%) individuals resided in the most deprived areas and 2536 (27.6%) had LTBI. In the multivariable analysis (adjusting for age, gender, place of birth, ethnicity, HIV status, BCG vaccination and recent TB contact) living in the least deprived areas compared with living in the most deprived areas was associated with reduced odds of LTBI (odds ratio (OR)=0.68, 95% CI: 0.51 to 0.90) while ever been homeless (OR=1.50, 95% CI: 1.02 to 2.21) was associated with increased odds of LTBI. Smoking, homelessness and substance misuse were not associated with LTBI. CONCLUSION: Social deprivation could be an important risk factor for LTBI, highlighting the social inequality in the burden of TB infection in the UK. Migrants and TB contacts who were socially deprived or homeless were at a significantly higher risk for LTBI, thus tailored intense public health interventions to these groups may help to reduce the risk of future TB disease. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT01162265).


Asunto(s)
Tuberculosis Latente , Estudios Transversales , Inglaterra/epidemiología , Humanos , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/epidemiología , Estudios Prospectivos , Factores de Riesgo , Medicina Estatal , Prueba de Tuberculina , Reino Unido/epidemiología
12.
13.
Vaccine ; 38(33): 5077-5081, 2020 07 14.
Artículo en Inglés | MEDLINE | ID: mdl-32417140

RESUMEN

Smallpox eradication, coordinated by the WHO and certified 40 years ago, led to the cessation of routine smallpox vaccination in most countries. It is estimated that over 70% of the world's population is no longer protected against smallpox, and through cross-immunity, to closely related orthopox viruses such as monkeypox. Monkeypox is now a re-emerging disease. Monkeypox is endemic in as yet unconfirmed animal reservoirs in sub-Saharan Africa, while its human epidemiology appears to be changing. Monkeypox in small animals imported from Ghana as exotic pets was at the origin of an outbreak of human monkeypox in the USA in 2003. Travellers infected in Nigeria were at the origin of monkeypox cases in the UK in 2018 and 2019, Israel in 2018 and Singapore in2019. Together with sporadic reports of human infections with other orthopox viruses, these facts invite speculation that emergent or re-emergent human monkeypox might fill the epidemiological niche vacated by smallpox. An ad-hoc and unofficial group of interested experts met to consider these issues at Chatham House, London in June 2019, in order to review available data and identify monkeypox-related research gaps. Gaps identified by the experts included:The experts further agreed on the need for a better understanding of the genomic evolution and changing epidemiology of orthopox viruses, the usefulness of in-field genomic diagnostics, and the best disease control strategies, including the possibility of vaccination with new generation non-replicating smallpox vaccines and treatment with recently developed antivirals.


Asunto(s)
Mpox , Vacuna contra Viruela , Viruela , Ghana , Humanos , Israel , Londres , Mpox/epidemiología , Mpox/prevención & control , Monkeypox virus , Nigeria , Singapur , Viruela/epidemiología , Viruela/prevención & control , Vacuna contra Viruela/efectos adversos
15.
BMC Med ; 18(1): 31, 2020 02 27.
Artículo en Inglés | MEDLINE | ID: mdl-32102669

RESUMEN

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.


Asunto(s)
Anemia Ferropénica/epidemiología , África , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino
17.
Sci Adv ; 5(9): eaaw0109, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31517041

RESUMEN

Iron acquisition is critical for life. Ferroportin (FPN) exports iron from mature erythrocytes, and deletion of the Fpn gene results in hemolytic anemia and increased fatality in malaria-infected mice. The FPN Q248H mutation (glutamine to histidine at position 248) renders FPN partially resistant to hepcidin-induced degradation and was associated with protection from malaria in human studies of limited size. Using data from cohorts including over 18,000 African children, we show that the Q248H mutation is associated with modest protection against anemia, hemolysis, and iron deficiency, but we found little evidence of protection against severe malaria or bacteremia. We additionally observed no excess Plasmodium growth in Q248H erythrocytes ex vivo, nor evidence of selection driven by malaria exposure, suggesting that the Q248H mutation does not protect from malaria and is unlikely to deprive malaria parasites of iron essential for their growth.


Asunto(s)
Anemia/genética , Proteínas de Transporte de Catión/genética , Deficiencias de Hierro , Mutación Missense , Sustitución de Aminoácidos , Anemia/metabolismo , Bacteriemia/genética , Bacteriemia/metabolismo , Proteínas de Transporte de Catión/metabolismo , Eritrocitos/metabolismo , Femenino , Humanos , Lactante , Recién Nacido , Hierro/metabolismo , Malaria/genética , Malaria/metabolismo , Masculino
18.
Mol Genet Genomic Med ; 7(10): e00950, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31469255

RESUMEN

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 < 5.0 × 10-8 ) in published BP GWASs were replicated in our study. RESULTS: Of the 14 million variants analyzed among 815 adolescents, none reached genome-wide significance (p < 5.0×10-8 ) for association with systolic or diastolic BP. The most strongly associated variants were rs181430167 (p = 6.8 × 10-7 ) for systolic BP and rs12991132 (p = 4.0 × 10-7 ) for diastolic BP. Thirty-three (17 single nucleotide polymorphisms (SNPs) for systolic BP, 15 SNPs for diastolic BP and one SNP for both) of 330 variants previously identified as associated with BP were replicated in this study, but none remained significant after accounting for multiple testing. 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.


Asunto(s)
Presión Sanguínea/genética , Estudio de Asociación del Genoma Completo , Proteínas Adaptadoras Transductoras de Señales/genética , Niño , Sitios Genéticos , Genotipo , Humanos , Modelos Lineales , Polimorfismo de Nucleótido Simple , Factores de Transcripción/genética , Uganda
19.
J Hum Hypertens ; 33(9): 679-692, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-30804461

RESUMEN

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.


Asunto(s)
Presión Sanguínea , Hipertensión/epidemiología , Factores de Edad , Índice de Masa Corporal , Niño , Escolaridad , Femenino , Ganancia de Peso Gestacional , Humanos , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Estudios Longitudinales , Malaria/epidemiología , Masculino , Linaje , Prevalencia , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de Riesgo , Uganda/epidemiología
20.
PLoS Negl Trop Dis ; 13(2): e0007157, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30763405

RESUMEN

BACKGROUND: Schistosoma infection is associated with immune modulation that can influence responses to non-schistosome antigens. Vaccine responses may be impaired in S. mansoni-infected individuals. We investigated effects of S. mansoni infection on responses to childhood measles catch-up immunisation and of praziquantel treatment on this outcome in a randomised trial. METHODOLOGY: The Immune Modulation and Childhood Immunisation (IMoChI) study was based in Entebbe, Uganda. Children aged 3-5 years (193 S. mansoni-infected and 61 uninfected) were enrolled. Infected children were randomised in a 1:1:1 ratio to receive praziquantel 2 weeks before, at time of, or 1 week after, measles catch-up immunisation. Plasma anti-measles IgG was measured at enrolment, 1 week and 24 weeks after measles immunisation. Primary outcomes were IgG levels and percentage of participants with levels considered protective against measles. RESULTS: Anti-measles IgG levels increased following immunisation, but at 1 week post-immunisation S. mansoni-infected, compared to uninfected, children had lower levels of anti-measles IgG (adjusted geometric mean ratio (aGMR) 0.4 [95% CI 0.2-0.7]) and the percentage with protective antibody levels was also lower (adjusted odds ratio 0.1 [0-0.9]). Among S. mansoni-infected children, anti-measles IgG one week post-immunisation was higher among those treated with praziquantel than among those who were not yet treated (treatment before immunisation, aGMR 2.3 [1.5-4.8]; treatment at immunisation aGMR 1.8 [1.1-3.5]). At 24 weeks post-immunisation, IgG levels did not differ between the trial groups, but tended to be lower among previously-infected children who were still S mansoni stool-positive than among those who became stool-negative. CONCLUSIONS AND SIGNIFICANCE: Our findings suggest that S. mansoni infection among pre-school children is associated with a reduced antibody response to catch-up measles immunisation, and that praziquantel treatment improves the response. S. mansoni infection may contribute to impaired vaccine responses in endemic populations; effective schistosomiasis control may be beneficial for vaccine efficacy. This should be further explored. TRIAL REGISTRATION: ISRCTN87107592.


Asunto(s)
Antihelmínticos/uso terapéutico , Anticuerpos Antivirales/sangre , Vacuna Antisarampión/inmunología , Sarampión/prevención & control , Praziquantel/uso terapéutico , Esquistosomiasis mansoni/tratamiento farmacológico , Antihelmínticos/administración & dosificación , Preescolar , Femenino , Humanos , Inmunoglobulina G/sangre , Masculino , Praziquantel/administración & dosificación , Esquistosomiasis mansoni/inmunología
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