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1.
Front Immunol ; 12: 637114, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33815390

RESUMO

Introduction: The immunogenicity of BCG vaccination in infants differs between populations. We hypothesized that prenatal exposure to mycobacterial antigens might explain the differences in immune responses to BCG seen in other studies of infants in Africa and the United Kingdom (UK) and we explored this in birth cohorts in Uganda and the UK. Materials and Methods: Blood samples were obtained from BCG-immunized infants of mothers with (n = 110) and without (n = 121) latent Mycobacterium tuberculosis infection (LTBI) in Uganda and BCG-immunized infants of mothers without LTBI (n = 25) in the UK at 10 and 52 weeks after birth. Cytokine and chemokine responses to PPD were measured to assess responses to BCG immunization, and to ESAT6/CFP10 to assess exposure to or infection with M. tuberculosis or non-tuberculous mycobacteria (NTM) in 6-day whole blood culture supernatants by a 17-plex Luminex assay. Median responses were compared between Ugandan infants (together, and separated by maternal LTBI status) and UK infants. Results: The IFN-γ response to BCG vaccination was similar between Ugandan and UK infants at 10 and 52 weeks. At week 52, TNF production was marginally higher in Ugandan infants, but after adjusting for multiple comparisons this difference was not significant. At weeks 10 and 52, stimulation of blood with ESAT6/CFP10 produced significantly higher IFN-γ, TNF, IL-12p40, IL-1α, IL-1ß, IL-1Ra, IP-10, MIP-1α, MIP-1ß, and GM-CSF in Ugandan compared to UK infants. Stimulation of blood with ESAT6/CFP10 produced significantly higher amounts of IL-8 (p = 0.0001), IL-10 (p = 0.0022), and IL-13 (p = 0.0020) in the UK than in Ugandan infants of mothers without LTBI at week 10, but not at week 52. Conclusions: Immune responses to mycobacterial antigens following BCG immunization are similar for PPD, but differ for ESAT6/CFP10, between infants in Uganda and the UK. Neither maternal LTBI nor infant exposure to or infection with mycobacteria impacts the response to BCG. The observed global differences in immune response to BCG immunization are likely to be due to other causes.

2.
Front Immunol ; 12: 620657, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33737927

RESUMO

HIV-1 infection disproportionately affects women in sub-Saharan Africa, where areas of high HIV-1 prevalence and Schistosoma haematobium endemicity largely overlap. Female genital schistosomiasis (FGS), an inflammatory disease caused by S. haematobium egg deposition in the genital tract, has been associated with prevalent HIV-1 infection. Elevated levels of the chemokines MIP-1α (CCL-3), MIP-1ß (CCL-4), IP-10 (CXCL-10), and IL-8 (CXCL-8) in cervicovaginal lavage (CVL) have been associated with HIV-1 acquisition. We hypothesize that levels of cervicovaginal cytokines may be raised in FGS and could provide a causal mechanism for the association between FGS and HIV-1. In the cross-sectional BILHIV study, specimens were collected from 603 female participants who were aged 18-31 years, sexually active, not pregnant and participated in the HPTN 071 (PopART) HIV-1 prevention trial in Zambia. Participants self-collected urine, and vaginal and cervical swabs, while CVLs were clinically obtained. Microscopy and Schistosoma circulating anodic antigen (CAA) were performed on urine. Genital samples were examined for parasite-specific DNA by PCR. Women with FGS (n=28), defined as a positive Schistosoma PCR from any genital sample were frequency age-matched with 159 FGS negative (defined as negative Schistosoma PCR, urine CAA, urine microscopy, and colposcopy imaging) women. Participants with probable FGS (n=25) (defined as the presence of either urine CAA or microscopy in combination with one of four clinical findings suggestive of FGS on colposcope-obtained photographs) were also included, for a total sample size of 212. The concentrations of 17 soluble cytokines and chemokines were quantified by a multiplex bead-based immunoassay. There was no difference in the concentrations of cytokines or chemokines between participants with and without FGS. An exploratory analysis of those women with a higher FGS burden, defined by ≥2 genital specimens with detectable Schistosoma DNA (n=15) showed, after adjusting for potential confounders, a higher Th2 (IL-4, IL-5, and IL-13) and pro-inflammatory (IL-15) expression pattern in comparison to FGS negative women, with differences unlikely to be due to chance (p=0.037 for IL-4 and p<0.001 for IL-5 after adjusting for multiple testing). FGS may alter the female genital tract immune environment, but larger studies in areas of varying endemicity are needed to evaluate the association with HIV-1 vulnerability.

3.
Pediatr Res ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33674741

RESUMO

BACKGROUND: Neonatal encephalopathy (NE) contributes substantially to child mortality and disability globally. We compared cytokine profiles in term Ugandan neonates with and without NE, with and without perinatal infection or inflammation and identified biomarkers predicting neonatal and early childhood outcomes. METHODS: In this exploratory biomarker study, serum IL-1α, IL-6, IL-8, IL-10, TNFα, and VEGF (<12 h) were compared between NE and non-NE infants with and without perinatal infection/inflammation. Neonatal (severity of NE, mortality) and early childhood (death or neurodevelopmental impairment to 2.5 years) outcomes were assessed. Predictors of outcomes were explored with multivariable linear and logistic regression and receiver-operating characteristic analyses. RESULTS: Cytokine assays on 159 NE and 157 non-NE infants were performed; data on early childhood outcomes were available for 150 and 129, respectively. NE infants had higher IL-10 (p < 0.001), higher IL-6 (p < 0.017), and lower VEGF (p < 0.001) levels. Moderate and severe NE was associated with higher IL-10 levels compared to non-NE infants (p < 0.001). Elevated IL-1α was associated with perinatal infection/inflammation (p = 0.013). Among NE infants, IL-10 predicted neonatal mortality (p = 0.01) and adverse early childhood outcome (adjusted OR 2.28, 95% CI 1.35-3.86, p = 0.002). CONCLUSIONS: Our findings support a potential role for IL-10 as a biomarker for adverse outcomes after neonatal encephalopathy. IMPACT: Neonatal encephalopathy is a common cause of child death and disability globally. Inflammatory cytokines are potential biomarkers of encephalopathy severity and outcome. In this Ugandan health facility-based cohort, neonatal encephalopathy was associated with elevated serum IL-10 and IL-6, and reduced VEGF at birth. Elevated serum IL-10 within 12 h after birth predicted severity of neonatal encephalopathy, neonatal mortality, and adverse early childhood developmental outcomes, independent of perinatal infection or inflammation, and provides evidence to the contribution of the inflammatory processes. Our findings support a role for IL-10 as a biomarker for adverse outcomes after neonatal encephalopathy in a sub-Saharan African cohort.

4.
Lancet Infect Dis ; 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33609457

RESUMO

BACKGROUND: Trials done in infants with low birthweight in west Africa suggest that BCG vaccination reduces all-cause mortality in the neonatal period, probably because of heterologous protection against non-tuberculous infections. This study investigated whether BCG alters all-cause infectious disease morbidity in healthy infants in a different high-mortality setting, and explored whether the changes are mediated via trained innate immunity. METHODS: This was an investigator-blind, randomised, controlled trial done at one hospital in Entebbe, Uganda. Infants who were born unwell (ie, those who were not well enough to be discharged directly home from the labour ward because they required medical intervention), with major congenital malformations, to mothers with HIV, into families with known or suspected tuberculosis, or for whom cord blood samples could not be taken, were excluded from the study. Any other infant well enough to be discharged directly from the labour ward was eligible for inclusion, with no limitation on gestational age or birthweight. Participants were recruited at birth and randomly assigned (1:1) to receive standard dose BCG 1331 (BCG-Danish) on the day of birth or at age 6 weeks (computer-generated randomisation, block sizes of 24, stratified by sex). Investigators and clinicians were masked to group assignment; parents were not masked. Participants were clinically followed up to age 10 weeks and contributed blood samples to one of three immunological substudies. The primary clinical outcome was physician-diagnosed non-tuberculous infectious disease incidence. Primary immunological outcomes were histone trimethylation at the promoter region of TNF, IL6, and IL1B; ex-vivo production of TNF, IL-6, IL-1ß, IL-10, and IFNγ after heterologous stimulation; and transferrin saturation and hepcidin levels. All outcomes were analysed in the modified intention-to-treat population of all randomly assigned participants except those whose for whom consent was withdrawn. This trial is registered with the International Standard Randomised Controlled Trial Number registry (#59683017). FINDINGS: Between Sept 25, 2014, and July 31, 2015, 560 participants were enrolled and randomly assigned to receive BCG at birth (n=280) or age 6 weeks (n=280). 12 participants assigned to receive BCG at birth and 11 participants assigned to receive BCG at age 6 weeks were withdrawn from the study by their parents shortly after randomisation and were not included in analyses. During the first 6 weeks of life before the infants in the delayed vaccination group received BCG vaccination, physician-diagnosed non-tuberculous infectious disease incidence was lower in infants in the BCG at birth group than in the delayed group (98 presentations in the BCG at birth group vs 129 in the delayed BCG group; hazard ratio [HR] 0·71 [95% CI 0·53-0·95], p=0·023). After BCG in the delayed group (ie, during the age 6-10 weeks follow-up), there was no significant difference in non-tuberculous infectious disease incidence between the groups (88 presentations vs 76 presentations; HR 1·10 [0·87-1·40], p=0·62). BCG at birth inhibited the increase in histone trimethylation at the TNF promoter in peripheral blood mononuclear cells occurring in the first 6 weeks of life. H3K4me3 geometric mean fold-increases were 3·1 times lower at the TNF promoter (p=0·018), 2·5 times lower at the IL6 promoter (p=0·20), and 3·1 times lower at the IL1B promoter (p=0·082) and H3K9me3 geometric mean fold-increases were 8·9 times lower at the TNF promoter (p=0·0046), 1·2 times lower at the IL6 promoter (p=0·75), and 4·6 times lower at the IL1B promoter (p=0·068), in BCG-vaccinated (BCG at birth group) versus BCG-naive (delayed BCG group) infants. No clear effect of BCG on ex-vivo production of TNF, IL-6, IL-1ß, IL-10, and IFNγ after heterologous stimulation, or transferrin saturation and hepcidin concentration, was detected (geometric mean ratios between 0·68 and 1·68; p≥0·038 for all comparisons). INTERPRETATION: BCG vaccination protects against non-tuberculous infectious disease during the neonatal period, in addition to having tuberculosis-specific effects. Prioritisation of BCG on the first day of life in high-mortality settings might have significant public-health benefits through reductions in all-cause infectious morbidity and mortality. FUNDING: Wellcome Trust. TRANSLATIONS: For the Luganda and Swahili translations of the abstract see Supplementary Materials section.

5.
BMC Infect Dis ; 21(1): 178, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33588804

RESUMO

BACKGROUND: Tuberculosis (TB) control relies on early diagnosis and treatment. International guidelines recommend systematic TB screening at health facilities, but implementation is challenging. We investigated completion of recommended TB screening steps in Blantyre, Malawi. METHODS: A prospective cohort recruited adult outpatients attending Bangwe primary clinic. Entry interviews were linked to exit interviews. The proportion of participants progressing through each step of the diagnostic pathway were estimated. Factors associated with request for sputum were investigated using multivariable logistic regression. RESULTS: Of 5442 clinic attendances 2397 (44%) had exit interviews. In clinically indicated participants (n = 445) 256 (57.5%) were asked about cough, 36 (8.1%) were asked for sputum, 21 (4.7%) gave sputum and 1 (0.2%) received same-day results. Significant associations with request for sputum were: any TB symptom (aOR:3.20, 95%CI:2.02-5.06), increasing age (aOR:1.02, 95%CI:1.01-1.04 per year) and for HIV-negative participants only, a history of previous TB (aOR:3.37, 95%CI:1.45-7.81). Numbers requiring sputum tests (26/day) outnumbered diagnostic capacity (8-12/day). CONCLUSIONS: Patients were lost at every stage of the TB care cascade, with same day sputum submission following all steps of the diagnosis cascade achieved in only 4.7% if clinically indicated. Infection control strategies should be implemented, with reporting on early steps of the TB care cascade formalised. High-throughput screening interventions, such as digital CXR, that can achieve same-day TB diagnosis are urgently needed to meet WHO End TB goals.


Assuntos
Programas de Rastreamento/estatística & dados numéricos , Tuberculose/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Instituições de Assistência Ambulatorial , Feminino , Humanos , Entrevistas como Assunto/estatística & dados numéricos , Modelos Logísticos , Malaui/epidemiologia , Masculino , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Estudos Prospectivos , Escarro/microbiologia , Tuberculose/epidemiologia , Tuberculose/prevenção & controle , Adulto Jovem
6.
Nat Med ; 27(4): 653-658, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33619371

RESUMO

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%.

7.
Clin Exp Allergy ; 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33512036

RESUMO

BACKGROUND: Serum inhibition of allergen-specific IgE has been associated with competing IgG4 and non-specific polyclonal IgE. In allergen immunotherapy, beneficial responses have been associated with high IgG4/IgE ratios. Helminths potentiate antibody class switching to IgG4 and stimulate polyclonal IgE synthesis; therefore, we hypothesized a role for helminth-associated IgG4 and total IgE in protection against atopic sensitization and clinical allergy (asthma) in tropical low-income countries. METHODS: Among community residents of Ugandan rural Schistosoma mansoni (Sm)-endemic islands and a mainland urban setting with lower helminth exposure, and among urban asthmatic schoolchildren and non-asthmatic controls, we measured total, Schistosoma adult worm antigen (SWA)-specific, Schistosoma egg antigen (SEA)-specific and allergen (house dust mite [HDM] and German cockroach)-specific IgE and IgG4 by ImmunoCAP® and/or ELISA. We assessed associations between these antibody profiles and current Sm infection, the rural-urban environment, HDM and cockroach skin prick test (SPT) reactivity, and asthma. RESULTS: Total IgE, total IgG4 and SWA-, SEA- and allergen-specific IgE and IgG4 levels were significantly higher in the rural, compared to the urban setting. In both community settings, both Sm infection and SPT reactivity were positively associated with allergen-specific and total IgE responses. SPT reactivity was inversely associated with Schistosoma-specific IgG4, allergen-specific IgG4/IgE ratios and total IgE/allergen-specific IgE ratios. Asthmatic schoolchildren, compared with non-asthmatic controls, had significantly higher levels of total and allergen-specific IgE, but lower ratios of allergen-specific IgG4/IgE and total IgE/allergen-specific IgE. CONCLUSIONS AND CLINICAL RELEVANCE: Our immuno-epidemiological data support the hypothesis that the IgG4-IgE balance and the total IgE-allergen-specific IgE balance are more important than absolute total, helminth- or allergen-specific antibody levels in inhibition of allergies in the tropics.

8.
Glob Public Health ; : 1-17, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33460355

RESUMO

We investigated patterns and drivers of alcohol misuse and illicit drug use among young fisherfolk. We undertook this study in fishing communities on Koome Island, Lake Victoria, Uganda, from December 2017-July 2018. We conducted six group discussions with men (3) and women (3) and 33 in-depth interviews with: young people [users (n = 10); non-users (n = 2)], local leaders (n = 3), health workers (n = 2), parents (n = 5), alcohol/illicit drugs sellers/distributors (n = 5), law enforcement officers (n = 5). We sampled participants using purposive and snowball strategies. Interview themes included: knowledge, experiences and perceptions of alcohol use/illicit drug use, HIV risk behaviour and harm reduction. We mapped alcohol/illicit drug use outlets using a Geographic Information System to capture density, distribution and proximity to young people's homes. We coded and analysed qualitative data using thematic content analysis. Motivations for heavy drinking and illicit drug use were multifaceted and largely beyond individual control. Key contextual determinants included social norms around consumption (acceptability), price (affordability), and ease of purchase (availability). Prevention and harm reduction interventions to tackle alcohol misuse and illicit drug use should be aimed at the structural rather than individual level and must be conducted in tandem with strategies to control poverty and HIV.

9.
Malar J ; 20(1): 56, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33478507

RESUMO

BACKGROUND: Access and adherence to artemisinin-based combination therapy (ACT) are key challenges to effective malaria treatment. A secondary analysis of the Sierra Leone malaria Knowledge, Attitudes, and Practices (mKAP) survey was conducted to investigate access and adherence to ACT for the treatment of fever in children under-five. METHODS: The mKAP was a nationally representative, two-stage cluster-sample survey, conducted in 2012. Thirty primary sampling units per district were randomly selected using probability proportionate to size, based on national census estimates; 14 households were subsequently randomly selected and enrolled per sampling unit. The analysis was restricted to children under-five with fever in the past two weeks. Factors associated with access and adherence were assessed using multivariate logistic regression. RESULTS: Of 5169 enrolled households, 1456 reported at least one child under-five with fever in the past two weeks. Of the 1641 children from these households, 982 (59.8%) received any treatment for fever and were analysed for access to ACT; 469 (47.6%) received ACT and 466 were analysed for treatment adherence. Only 222 (47.4%) febrile children received ACT and completed 3-day treatment. In an adjusted analysis, factors associated with ACT access included knowledge of ACT (odds ratio [OR] 2.78, 95% CI 2.02-3.80; p < 0.001), knowledge of insecticide-treated nets (ITNs) (OR 1.84, 95% CI 1.29-2.63; p = 0.001), source of care (public health facility vs. other; OR 1.86, 95% CI 1.27-2.72, p = 0.001), geographic region (East vs. West; OR 2.30, 95% CI 1.20-4.44; p = 0.025), and age (24-59 vs. 0-23 months; OR 1.45, 95% CI 1.07-1.96; p = 0.016). The only factor associated with ACT adherence was time to treatment; children treated within 24 h were less likely to adhere (OR 0.55, 95% CI 0.34-0.89; p = 0.015). CONCLUSIONS: In 2012, access and adherence to ACT remained low in Sierra Leone. Knowledge of ACT and ITNs, and seeking care in the public sector, were most strongly associated with ACT access. National surveys provide important information on anti-malarial access and could be expanded to measure treatment adherence.

10.
Wellcome Open Res ; 5: 61, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33154978

RESUMO

Background: Female genital schistosomiasis (FGS) is a neglected and disabling gynaecological disorder that is difficult to diagnose and is part of the wider spectrum of urogenital disease caused by the waterborne parasite  Schistosoma haematobium. Over 90% of human schistosomiasis cases are found in sub-Saharan Africa with 3.8 million people infected with schistosomes in Zambia. Reported FGS prevalence ranges from 33-75% of those with urinary schistosomiasis in endemic areas, suggesting a potentially high FGS burden in Zambia alone. The Bilharzia and HIV (BILHIV) study evaluated home self-sampling genital collection methods for the diagnosis of FGS. Methods: Eligible participants included non-pregnant, sexually active women aged 18-31 who were previously recruited for the HPTN 071 (PopART) trial in Livingstone, Zambia. Household demographic and symptom questionnaires were administered by community workers. Participants were offered vaginal and cervical self-swabs and a urine cup. Cervicovaginal lavage (CVL) was performed in clinic by midwives. Information was collected from participants on the acceptability and feasibility of genital self-sampling. Results: From January-August 2018, 603 women were enrolled, and 87.3% (527/603) completed clinic follow up. A high proportion of participants indicated that self-collection of specimens was "easy" or "very easy" on a 5-point Likert scale. A high proportion of women would be willing to self-collect all three specimens again in future: vaginal swab 96.7% (583/603), cervical swab 96.5% (582/603), and urine 96.2% (580/603). Home-based self-sampling was preferred over provider-based sampling in the clinic due to greater privacy 58.5% (353/603), convenience 46.3% (279/603) and need for transportation 15.9% (96/603). Conclusions: Home based genital self-sampling for FGS diagnosis is highly acceptable. This scalable method may inform future efforts for community-based diagnosis of FGS.

11.
Clin Exp Allergy ; 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33098716

RESUMO

BACKGROUND: The prevalence of allergy-related diseases (ARDs), including rhinitis, allergic conjunctivitis and eczema, is on the increase globally. The causes of this increase are not well established. OBJECTIVES: To investigate the risk factors associated with ARDs among schoolchildren in Uganda. METHODS: We conducted a secondary data analysis of a large asthma case-control study involving 1700 schoolchildren, 5-17 years, in urban Uganda. ARDs were defined according to the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Skin prick testing (SPT) was conducted using standard procedures and allergen-specific IgE (asIgE) using ImmunoCAP® . We employed inverse probability weighted analysis to generate estimated prevalence data and weighted odds ratios. RESULTS: The lifetime estimated weighted prevalence of reported rhinitis, allergic conjunctivitis and eczema was 43.3%, 39.5% and 13.5%; weighted prevalence in 12 months was 10.1%, 9.1% and 2.3%, respectively. There was overlap of ARDs, with 66.3% of 1193 schoolchildren who reported having ever an ARDs (including asthma) reporting two or more. Risk factors associated with reported rhinitis in the last 12 months were city residence at birth [adjusted odds ratio (95% confidence interval) 2.66 (1.42-4.99) compared to rural]; father's [2.62 (1.79-3.83)] and mother's history of allergic disease [2.12 (1.48-3.02)]; frequent de-worming in the last 12 months [2.01 (1.30-3.11), ≥2 versus none]; current high frequency of 'trucks passing on the street near home' [2.59 (1.48-4.52), 'almost all the time' versus rarely] and positive SPT [1.54 (1.09-2.18)] but not asIgE [1.38 (0.60-3.15)]. The same pattern of risk factors was observed for allergic conjunctivitis and eczema. CONCLUSION: We found extensive multi-morbidity of, and overlap in the risk factors for, rhinitis, conjunctivitis and eczema-similar to asthma risk factors-among schoolchildren in urban Uganda. This suggests a similar underlying cause for all ARDs, associated with exposure to urban lifestyles and environment in Uganda.

12.
PLoS Negl Trop Dis ; 14(10): e0008718, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33075067

RESUMO

BACKGROUND: Mass drug administration (MDA) is a cornerstone of control of parasitic helminths. In schistosomiasis-endemic areas with >50% of school-aged children infected, community-wide MDA with praziquantel is recommended by the World Health Organisation (WHO), with target coverage of >75%. Using data from a cluster-randomised trial of MDA treatment strategies, we aimed to describe the proportion of eligible residents who received MDA and predictors of treatment receipt, and to assess associations with helminth prevalence. METHODS: In the Koome islands of Lake Victoria, Uganda, where baseline schistosomiasis prevalence (by single stool sample, Kato Katz) was 52% overall (all ages) and 67% among school-aged children, we conducted a cluster-randomised trial of community-wide, intensive MDA (quarterly single-dose praziquantel 40mg/kg; triple-dose albendazole 400mg) versus standard, Uganda government intervention (annual single-dose praziquantel 40mg/kg; 6-monthly single-dose albendazole). Twenty-six fishing villages were randomised, 13 per trial arm, for four years. At each treatment round, praziquantel treatment and the first dose of albendazole treatment were directly observed by the study team, registers of village residents were updated and the proportion receiving treatment among those eligible recorded. RESULTS: During the four-year MDA, at each treatment round an average of 13,382 people were registered in the 26 villages (7,153 and 6,229 in standard and intensive intervention villages, respectively). Overall, the proportion of those eligible receiving praziquantel was lower than for albendazole (60% versus 65%), particularly in the standard arm (61% versus 71%) compared to the intensive arm (60% versus 62%). Albendazole receipt was lower when given concurrently with praziquantel. Absence was the commonest reason for non-receipt of treatment (81% albendazole, 77% praziquantel), followed by refusal (14% albendazole, 18% praziquantel). Proportions receiving treatment were lowest among school-aged children, but did not differ by sex. Longitudinal analysis of a subgroup of residents who did not move during the study period found that persistent non-receipt of treatment in this subgroup was rare. Refusal to receive treatment was highest among adults and more common among females. CONCLUSION: In schistosomiasis high-risk communities, a combination of approaches to increasing treatment coverage, such as extended periods of treatment delivery, and the provision of incentives, may be required to achieve WHO targets.

13.
Wellcome Open Res ; 5: 39, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32875121

RESUMO

Background: The burden of cardiometabolic diseases, including cardiovascular diseases and diabetes, is increasing in sub-Saharan Africa and this has been linked to urbanisation. Helminths, through their immunomodulatory properties, may protect against these disorders. We hypothesised that the rural environment protects against cardiometabolic diseases and that helminths may influence rural-urban disparity of cardiometabolic disease risk. Methods: We compared metabolic parameters of individuals aged ≥10 years living in rural, high-helminth-transmission and urban, lower-helminth-transmission settings in Uganda. Cross-sectional surveys were conducted in rural Lake Victoria island communities and in urban sub-wards in Entebbe municipality. Helminth infection and outcomes, including insulin resistance (computed using the homeostatic model assessment of insulin resistance [HOMA-IR]), fasting blood glucose, fasting blood lipids, blood pressure, body mass index (BMI), waist and hip circumference, were assessed. Results: We analysed 1,898 rural and 930 urban participants. Adjusting for BMI, exercise, smoking, alcohol intake, age and sex, urban residents had lower mean fasting glucose (adjusted mean difference [95%CI] -0.13 [-0.24, -0.01] p=0.04) and HOMA-IR (-0.13 [-0.25, -0.01] p=0.04) but higher blood pressure (systolic, 4.64 [3.23, 6.06] p<0.001; diastolic, 1.89 [0.81, 2.97] p=0.001). Current helminth infection did not explain the observed differences. Conclusions: In low-income countries, rural living may protect against hypertension but impair glucose metabolism.

14.
Trials ; 21(1): 707, 2020 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-32778139

RESUMO

An amendment to this paper has been published and can be accessed via the original article.

15.
PLoS One ; 15(8): e0236407, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790669

RESUMO

INTRODUCTION: Patients with tuberculosis (TB) symptoms have high prevalence of HIV, and should be prioritised for HIV testing. METHODS: In a prospective cohort study in Bangwe primary care clinic, Blantyre, Malawi, all adults (18 years or older) presenting with an acute illness were screened for TB symptoms (cough, fever, night sweats, weight loss). Demographic characteristics were linked to exit interview by fingerprint bioidentification. Multivariable logistic regression models were constructed to estimate the proportion completing same-visit HIV testing, comparing between those with and without TB symptoms. RESULTS: There were 5427 adult attendees between 21/5/2018 and 6/9/2018. Exit interviews were performed for 2402 (44%). 276 patients were excluded from the analysis, being already on antiretroviral therapy (ART). Presentation with any TB symptom was common for men (54.6%) and women (57.4%). Overall 27.6% (585/ 2121) attenders reported being offered testing and 21.5% (455/2121) completed provider-initiated HIV testing and counselling (PITC) and received results. The proportions offered testing were similar among participants with and without TB symptoms (any TB symptom: 29.0% vs. 25.7%). This was consistent for each individual symptom; cough, weight loss, fever and night sweats. Multivariable regression models indicated men, younger adults and participants who had previously tested were more likely to complete PITC than women, older adults and those who had never previously tested. CONCLUSIONS: Same-visit completion of HIV testing was suboptimal, especially among groups known to have high prevalence of undiagnosed HIV. As countries approach universal coverage of ART, identifying and prioritising currently underserved groups for HIV testing will be essential.


Assuntos
Infecções por HIV/diagnóstico , Tuberculose/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Infecções por HIV/epidemiologia , Humanos , Malaui/epidemiologia , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Atenção Primária à Saúde , Estudos Prospectivos , Tuberculose/epidemiologia , Cobertura Universal do Seguro de Saúde , Adulto Jovem
16.
PLoS Negl Trop Dis ; 14(7): e0008337, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32663222

RESUMO

BACKGROUND: Given the potentially causal association of female genital schistosomiasis (FGS) with HIV-1 infection, improved diagnostics are urgently needed to scale-up FGS surveillance. The BILHIV (bilharzia and HIV) study assessed the performance of home-based self-collection methods (cervical and vaginal swabs) compared to cervicovaginal lavage (CVL) for the detection of Schistosoma DNA by real-time polymerase chain reaction (PCR). METHODS: Between January and August 2018, a consecutive series of female participants from the Population-Cohort of the previous HIV prevention trial HPTN 071 (PopART), resident in Livingstone, Zambia were invited to take part in BILHIV if they were 18-31 years old, non-pregnant and sexually active. Genital self-collected swabs and a urine specimen were obtained and a questionnaire completed at home visits. CVL was obtained at clinic follow-up. RESULTS: 603 women self-collected genital swabs. Of these, 527 women had CVL performed by a mid-wife during clinic follow-up. Schistosoma DNA was more frequently detected in genital self-collected specimens (24/603, 4.0%) compared to CVL (14/527, 2.7%). Overall, 5.0% (30/603) women had female genital schistosomiasis, defined as a positive PCR by any genital sampling method (cervical swab PCR, vaginal swab PCR, or CVL PCR) and 95% (573/603) did not have a positive genital PCR. The sensitivity of any positive genital self-collected swab against CVL was 57.1% (95% CI 28.9-82.3%), specificity 97.3% (95.5-98.5%). In a subset of participants with active schistosome infection, determined by detectable urine Circulating Anodic Antigen (CAA) (15.1%, 91/601), positive PCR (4.3%, 26/601), or positive microscopy (5.5%, 33/603), the sensitivity of any positive self-collected specimen against CVL was 88.9% (51.8-99.7%). CONCLUSIONS: Genital self-sampling increased the overall number of PCR-based FGS diagnoses in a field setting, compared with CVL. Home-based sampling may represent a scalable alternative method for FGS community-based diagnosis in endemic resource limited settings.


Assuntos
Colo do Útero/parasitologia , Schistosoma/isolamento & purificação , Esquistossomose/parasitologia , Manejo de Espécimes/métodos , Irrigação Terapêutica/métodos , Vagina/parasitologia , Adulto , Animais , Estudos de Coortes , Feminino , Infecções por HIV/virologia , Humanos , Schistosoma/genética , Esquistossomose/diagnóstico , Esquistossomose/epidemiologia , Autoexame , Adulto Jovem , Zâmbia/epidemiologia
17.
Infect Agent Cancer ; 15: 49, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32714434

RESUMO

Kaposi's sarcoma-associated herpesvirus (KSHV) transmission within endemic areas may vary. KSHV seroprevalence has been studied by different groups of researchers using different methods, making it difficult to make direct comparisons. Here we show results on KSHV seroprevalence using the same laboratory method from four different but geographically proximate populations in Uganda. Blood samples from the urban Entebbe Mother and Baby Study (EMaBS), the rural General Population Cohort (GPC), the fishing community Lake Victoria Island Intervention Study on Worms and Allergy related Diseases (LaVIISWA) and the high-risk sexual behaviour Good Health for Women Project (GHWP), were tested for IgG antibody levels to K8.1 and ORF73 recombinant proteins using ELISA. All adult participants of the EMaBS study and the GHWP were women, while the GPC (54% female) and LaVIISWA (52% female) studies had both males and females. EMaBS children were all 5 years of age while their mothers were 14 to 47 years of age. GHWP women were 15 to 45 years old, LaVIISWA participants were 1 to 72 years old while GPC participants were 1 to 103 years old. KSHV seropositivity varied in the different populations. In children aged 5 years, EMaBS had the lowest prevalence of 15% followed by GPC at 35% and LaVIISWA at 54%. In adult women, seropositivity varied from 69% (EMaBS) to 80% (LaVIISWA) to 87% (GPC) to 90% (GHWP). The reasons for the variation in prevalence are unclear but may reflect differences in the prevalence of cofactors between these four geographically proximate populations.

18.
Clin Infect Dis ; 2020 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-32507899

RESUMO

BACKGROUND: Iron deficiency (ID) and malaria are common causes of ill-health and disability among children living in sub-Saharan Africa. Although iron is critical for the acquisition of humoral immunity, little is known about the effects of ID on antibody responses to Plasmodium falciparum malaria. METHODS: The study included 1,794 Kenyan and Ugandan children aged 0-7 years. We measured biomarkers of iron and inflammation, and antibodies to P falciparum antigens including apical merozoite antigen 1 (anti-AMA-1) and merozoite surface antigen 1 (anti-MSP-1) in cross-sectional and longitudinal studies. RESULTS: The overall prevalence of ID was 31%. ID was associated with lower anti-AMA-1 and anti-MSP-1 antibody levels in pooled analyses adjusted for age, gender, study site, inflammation and P falciparum parasitemia (adjusted mean difference on a log-transformed scale (ß) -0.46; 95 CI -0.66, -0.25 P <0.0001; ß -0.33; 95 CI -0.50, -0.16 P <0.0001, respectively). Additional covariates for malaria exposure index, previous malaria episodes, and time since last malaria episode, were available for individual cohorts. Meta-analysis was used to allow for these adjustments giving ß -0.34; -0.52, -0.16 for anti-AMA-1 antibodies and ß -0.26; -0.41, -0.11 for anti-MSP-1 antibodies. Low transferrin saturation was similarly associated with reduced anti-AMA1 antibody levels. Lower AMA-1 and MSP-1 specific antibody levels persisted over time in iron-deficient children. CONCLUSIONS: Reduced levels of P. falciparum-specific antibodies in iron-deficient children might reflect impaired acquisition of immunity to malaria and/or reduced malaria exposure. Strategies to prevent and treat ID may influence antibody responses to malaria for children living in sub-Saharan Africa.

19.
Allergy ; 2020 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-32568414

RESUMO

BACKGROUND: In high-income, temperate countries, IgE to allergen extracts is a risk factor for, and mediator of, allergy-related diseases (ARDs). In the tropics, positive IgE tests are also prevalent, but rarely associated with ARD. Instead, IgE responses to ubiquitous cross-reactive carbohydrate determinants (CCDs) on plant, insect and parasite glycoproteins, rather than to established major allergens, are dominant. Because anti-CCD IgE has limited clinical relevance, it may impact ARD phenotyping and assessment of contribution of atopy to ARD. METHODS: Using an allergen extract-based test, a glycan and an allergen (glyco)protein microarray, we mapped IgE fine specificity among Ugandan rural Schistosoma mansoni (Sm)-endemic communities, proximate urban communities, and importantly in asthmatic and nonasthmatic schoolchildren. RESULTS: Overall, IgE sensitization to extracts was highly prevalent (43%-73%) but allergen arrays indicated that this was not attributable to established major allergenic components of the extracts (0%-36%); instead, over 40% of all participants recognized CCD-bearing components. Using glycan arrays, we dissected IgE responses to specific glycan moieties and found that reactivity to classical CCD epitopes (core ß-1,2-xylose, α-1,3-fucose) was positively associated with sensitization to extracts, rural environment and Sm infection, but not with skin reactivity to extracts or sensitization to their major allergenic components. Interestingly, we discovered that reactivity to only a subset of core α-1,3-fucose-carrying N-glycans was inversely associated with asthma. CONCLUSIONS: CCD reactivity is not just an epiphenomenon of parasite exposure hampering specificity of allergy diagnostics; mechanistic studies should investigate whether specific CCD moieties identified here are implicated in the protective effect of certain environmental exposures against asthma.

20.
Wellcome Open Res ; 5: 28, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32399499

RESUMO

Introduction: Vitamin D plays an important role in brain development in experimental studies; however, the effect of vitamin D deficiency on child development remains inadequately characterized. We aimed to estimate the effects of vitamin D deficiency on neurobehavioural outcomes in children up to 18 years of age. Methods: We searched PubMed, EMBASE, PsycINFO, Scopus, Cochrane Library, Web of Science and Open Grey for published studies up to 10th January 2020. We included all studies that assessed the effects of maternal or child vitamin D status or vitamin D supplementation on neurobehavioural outcomes in children. Study findings were synthesized qualitatively as the high level of heterogeneity in study populations and methodologies precluded a quantitative meta-analysis. Results: Our search identified 5,633 studies, of which 31 studies with 31,375 participants from 18 countries were included in the systematic review. Of the studies identified, one was a randomised controlled trial (RCT) of vitamin D supplementation in children, while 30 were observational. The RCT (n=55) reported a beneficial effect of supplementation with lower doses compared to higher doses of vitamin D on motor development. Twelve mother-child studies (n=17,136) and five studies in children (n=1,091) reported an association between low maternal or child 25-hydroxyvitamin D levels and impaired neurobehavioural outcomes in children, while 15 mother-child studies (n=20,778) and eight studies in children (n=7,496) reported no association. Conclusions: Although animal studies point to an effect of vitamin D deficiency on brain development, there are few studies on the effects of vitamin D deficiency on neurobehavioural outcomes in children and their findings are inconsistent. There is a need for well-conducted, adequately powered studies to further determine these effects in children. Registration: PROSPERO ID CRD42018087619; registered on 15 February 2018.

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