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1.
BMJ Open ; 11(3): e042544, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33674370

RESUMO

INTRODUCTION: Investing in children during the critical period between birth and age 5 years can have long-lasting benefits throughout their life. Children in Kenya's urban informal settlements, face significant challenges to healthy development, particularly when their families need to earn a daily wage and cannot care for them during the day. In response, informal and poor quality child-care centres with untrained caregivers have proliferated. We aim to co-design and test the feasibility of a supportive assessment and skills-building for child-care centre providers. METHODS AND ANALYSIS: A sequential mixed-methods approach will be used. We will map and profile child-care centres in two informal settlements in Nairobi, and complete a brief quality assessment of 50 child-care centres. We will test the feasibility of a supportive assessment skills-building system on 40 child-care centres, beginning with assessing centre-caregivers' knowledge and skills in these centres. This will inform the subsequent co-design process and provide baseline data. Following a policy review, we will use experience-based co-design to develop the supportive assessment process. This will include qualitative interviews with policymakers (n=15), focus groups with parents (n=4 focus group discussions (FGDs)), child-care providers (n=4 FGDs) and joint workshops. To assess feasibility and acceptability, we will observe, record and cost implementation for 6 months. The knowledge/skills questionnaire will be repeated at the end of implementation and results will inform the purposive selection of 10 child-care providers and parents for qualitative interviews. Descriptive statistics and thematic framework approach will respectively be used to analyse quantitative and qualitative data and identify drivers of feasibility. ETHICS AND DISSEMINATION: The study has been approved by Amref Health Africa's Ethics and Scientific Review Committee (Ref: P7802020 on 20th April 2020) and the University of York (Ref: HSRGC 20th March 2020). Findings will be published and continual engagement with decision-makers will embed findings into child-care policy and practice.

2.
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.

3.
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.

4.
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.

5.
PLoS One ; 15(7): e0236488, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32716925

RESUMO

BACKGROUND: Long term outcomes of children with neurodevelopmental disability are influenced by the condition itself, available health services and caretakers' coping ability to nurture the children which may be related to their beliefs and experiences. Most children with neurodevelopmental disabilities live in resource constrained settings. To inform design of contextually appropriate interventions, this study explored health workers' and caretakers' experiences in caring for infants with neurodevelopmental disability in rural eastern Uganda. METHODS: A qualitative case study was carried out in December 2017 and involved in-depth interviews with 14 caretakers of infants with severe neurodevelopmental disability, and five health workers in Iganga/Mayuge Demographic Surveillance Site in eastern Uganda. The interviews with caretakers were conducted in Lusoga, the local language, and in English for the health workers, using a pre-determined open-ended interview guide. Data were analyzed using latent content analysis. RESULTS: Caretakers described the experience of caring for children with neurodevelopmental disability as impoverishing and 'imprisoning' due to high care costs, inability to return to income generating activities and nursing challenges. The latter resulted from failure in body control and several aspects of nutrition and maintaining vital functions, coupled with limited support from the community and the health system. Many caretakers expressed beliefs in supernatural causes of neurodevelopmental disability though they reported about complications during and shortly after the birth of the affected child. Care-seeking was often challenging and impeded by costs and the feeling of lack of improvement. The health care system was also found to be incapable of adequately addressing the needs of such children due to lack of commodities, and human resource limitations. CONCLUSION: The caretakers expressed a feeling of emotional stress due to being left alone with a high nursing burden. Improvement in the health services including a holistic approach to care, improved community awareness and parental support could contribute to nursing of children with NDD.


Assuntos
Cuidadores , Cuidado da Criança , Pessoas com Deficiência , Pessoal de Saúde , Transtornos do Neurodesenvolvimento/terapia , População Rural , Criança , Comunicação , Seguimentos , Humanos , Percepção , Apoio Social , Uganda
6.
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.

7.
Nutrients ; 12(6)2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32503251

RESUMO

Vitamin D deficiency is common worldwide and young children are among the most affected groups. Animal studies suggest a key role for vitamin D in brain development. However, studies investigating the effects of vitamin D on neurobehavioural outcomes in children are inconclusive and evidence is limited in sub-Saharan Africa. We evaluated the effect of vitamin D status on cognitive and motor outcomes using prospective data from the Entebbe Mother and Baby Study birth cohort. We analysed data from 302 Ugandan children with 25-hydroxyvitamin D (25(OH)D) measurements below five years and developmental measures at five years of age. We used multivariable linear regression, adjusted for potential confounders, to estimate the effect of 25(OH)D on cognitive and motor outcomes. Of 302 children, eight (2.7%) had 25(OH)D levels <50 nmol/L, 105 (35.8%) had levels 50-75 nmol/L and 189 (62.6%) had levels >75 nmol/L. There was no evidence that earlier vitamin D status was associated with cognitive and motor outcomes in five-year-old Ugandan children. This study adds to the sparse literature and highlights the need for further longitudinal studies on vitamin D and neurobehavioural outcomes in children living in sub-Saharan Africa.

8.
Parasitol Int ; 78: 102132, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32387542

RESUMO

Several vaccines elicit lower efficacy or impaired immune responses in rural compared to urban settings, and in tropical low-income countries compared to high-income countries. An unresolved hypothesis is that immunomodulation by parasitic infections such as helminths (prevalent in rural tropical settings) contributes to suppression of vaccine responses. Among 1-17-year-old Ugandan residents of rural Schistosoma mansoni (Sm)-endemic islands and proximate urban communities with lower helminth exposure, we assessed plasma antibody and whole blood assay cytokine responses to tetanus toxoid (TT) and purified protein derivative of Mycobacterium tuberculosis (PPD). These were taken to represent recall responses to tetanus and BCG vaccination in infancy. PPD-specific responses are additionally induced by tuberculous and non-tuberculous mycobacterial exposure. Urban-rural comparisons showed that PPD-specific IFN-γ and IL-13 and TT-specific IL-13 and IgG concentrations were lower in the rural setting, but that PPD-specific IgE concentrations were higher. Among rural participants, Sm infection was inversely associated with PPD-specific IFN-γ, while nematode infection was positively associated with PPD-specific IgG. Among urban participants, Sm infection was positively associated with PPD-specific responses but inversely associated with TT-specific responses, while nematode infection was inversely associated with TT-specific IgG and IgG4, but no associations were observed with PPD-specific responses. Despite these associations, for the urban-rural comparisons there were no notable changes in test statistics after adjusting for current helminth infections, suggesting that helminths were not the sole explanation for the urban-rural differences observed. Helminths likely work in concert with other environmental exposures and operational factors to influence vaccine response.

9.
BMJ Open ; 9(10): e032705, 2019 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-31601606

RESUMO

INTRODUCTION: Early intervention programmes (EIPs) for infants with neurodevelopmental impairment have been poorly studied especially in low-income settings. We aim to evaluate the feasibility and acceptability of a group participatory EIP, the 'ABAaNA EIP', for young children with neurodevelopmental impairment in Uganda. METHODS AND ANALYSIS: We will conduct a pilot feasibility, single-blinded, randomised controlled trial comparing the EIP with standard care across two study sites (one urban, one rural) in central Uganda. Eligible infants (n=126, age 6-11 completed months) with neurodevelopmental impairment (defined as a developmental quotient <70 on Griffiths Scales of Mental Development, and, or Hammersmith Infant Neurological Examination score <60) will be recruited and randomised to the intervention or standard care arm. Intervention arm families will receive the 10-modular, peer-facilitated, participatory, community-based programme over 6 months. Recruited families will be followed up at 6 and 12 months after recruitment, and assessors will be blinded to the trial allocation. The primary hypothesis is that the ABAaNA EIP is feasible and acceptable when compared with standard care. Primary outcomes of interest are feasibility (number recruited and randomised at baseline) and acceptability (protocol violation of arm allocation and number of sessions attended) and family and child quality of life. Guided by the study aim, the qualitative data analysis will use a data-led thematic framework approach. The findings will inform scalability and sustainability of the programme. ETHICS AND DISSEMINATION: The trial protocol has been approved by the relevant Ugandan and UK ethics committees. Recruited families will give written informed consent and we will follow international codes for ethics and good clinical practice. Dissemination will be through peer-reviewed publications, conference presentations and public engagement. TRIAL REGISTRATION NUMBER: ISRCTN44380971; protocol version 3.0, 19th February 2018.


Assuntos
Intervenção Médica Precoce , Transtornos do Neurodesenvolvimento/terapia , Estudos de Viabilidade , Humanos , Lactente , Projetos Piloto , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Uganda
10.
BMC Pediatr ; 19(1): 379, 2019 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-31651279

RESUMO

BACKGROUND: Neurodevelopmental disability (NDD) is increasingly acknowledged as one of the important causes of disease burden in low income countries. None the less, there is a dearth of data on the burden of NDD and its determinants in these settings. We aimed to establish the prevalence and factors associated with NDD among infants in Eastern Uganda. METHODS: We assessed 487 infants aged 9-12 months within Iganga-Mayuge Health Demographic Surveillance Site in Eastern Uganda using the Malawi Developmental Assessment Tool. The tool has four domains: gross motor, fine motor, language and social domains. An infant failed a domain if she/he failed more than two parameters of the expected at his/her age. We interviewed mothers on factors that could influence the infants' neurodevelopmental outcomes. Data were analysed using STATA version 14. We used odds ratios and 95% confidence intervals to assess statistical significance of associations. RESULTS: Of the 487 infants, 62(12.7%) had an NDD in at least one of the domains. The most affected was social behaviour where 52(10.7%) infants had an NDD. Severe impairment was seen among 9(1.8%) infants with NDD in either three or four domains. Factors associated with NDD at multivariate logistic regression included: parity of more than three children (aOR = 1.8, 95% CI: 1.02-3.18); failure to cry at birth (aOR = 3.6, 95% CI: 1.46-9.17) and post-neonatal complications (aOR = 4.15, 95% CI: 1.22-14.10). Low birth weight, immediate and exclusive breast feeding were not significantly associated with NDD. CONCLUSION: We found a high NDD burden among infants particularly in the social behaviour domain. To optimise the socio-neural development of infants, programs are needed to educate and work with families on how to engage and stimulate infants. Existing immunisation clinics and community health worker strategies provide an excellent opportunity for stemming this burden.

11.
Trop Doct ; 49(3): 170-177, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30885057

RESUMO

Major depressive disorder (MDD) is a major global health challenge and postnatal women may be at an increased risk for this disorder. Very few studies have tested this hypothesis in sub-Saharan Africa (SSA), so it is uncertain whether risk factors implicated elsewhere in the world are relevant in SSA. We explored prevalence and risk factors for MDD and depressive symptomatology among postnatal mothers in Kampala. Three hundred postnatal mothers at Nsambya Hospital were assessed for MDD using the DSM IV-based MINI; prevalence and risk factors were determined using frequencies and regressions, respectively. Four women (1.33%) had MDD; however, 94 (31%) had 'sub-threshold' or depressive symptomatology, with which partner violence is particularly associated. MDD is rare among postnatal women in a paying hospital in Kampala; however, the high prevalence of depressive symptomatology suggests susceptibility to MDD. Longitudinal studies should investigate this hypothesis and the susceptibility due to partner violence should guide appropriate interventions.


Assuntos
Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/psicologia , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/psicologia , Adulto , Depressão Pós-Parto/diagnóstico , Transtorno Depressivo Maior/diagnóstico , Feminino , Humanos , Violência por Parceiro Íntimo/estatística & dados numéricos , Mães/psicologia , Mães/estatística & dados numéricos , Prevalência , Fatores de Risco , Uganda/epidemiologia
12.
Sci Rep ; 9(1): 3522, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30837526

RESUMO

Core ß-1,2-xylose and α-1,3-fucose are antigenic motifs on schistosome N-glycans, as well as prominent IgE targets on some plant and insect glycoproteins. To map the association of schistosome infection with responses to these motifs, we assessed plasma IgE and IgG reactivity using microarray technology among Ugandans from rural Schistosoma mansoni (Sm)-endemic islands (n = 209), and from proximate urban communities with lower Sm exposure (n = 62). IgE and IgG responses to core ß-1,2-xylose and α-1,3-fucose modified N-glycans were higher in rural versus urban participants. Among rural participants, IgE and IgG to core ß-1,2-xylose were positively associated with Sm infection and concentration peaks coincided with the infection intensity peak in early adolescence. Responses to core α-1,3-fucose were elevated regardless of Sm infection status and peaked before the infection peak. Among urban participants, Sm infection intensity was predominantly light and positively associated with responses to both motifs. Principal component and hierarchical cluster analysis reduced the data to a set of variables that captured core ß-1,2-xylose- and α-1,3-fucose-specific responses, and confirmed associations with Sm and the rural environment. Responses to core ß-1,2-xylose and α-1,3-fucose have distinctive relationships with Sm infection and intensity that should further be explored for associations with protective immunity, and cross-reactivity with other exposures.


Assuntos
Imunoglobulina E/sangue , Imunoglobulina G/sangue , Polissacarídeos/imunologia , Schistosoma mansoni/imunologia , Esquistossomose mansoni/patologia , Adolescente , Adulto , Animais , Criança , Pré-Escolar , Feminino , Glicosilação , Humanos , Masculino , Análise em Microsséries , Análise de Componente Principal , População Rural , Schistosoma mansoni/isolamento & purificação , Esquistossomose mansoni/epidemiologia , Esquistossomose mansoni/parasitologia , Uganda , População Urbana , Adulto Jovem
13.
J Hum Hypertens ; 33(9): 679-692, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30804461

RESUMO

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.


Assuntos
Pressão Sanguínea , Hipertensão/epidemiologia , Fatores Etários , Índice de Massa Corporal , Criança , Escolaridade , Feminino , Ganho de Peso na Gestação , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Estudos Longitudinais , Malária/epidemiologia , Masculino , Linhagem , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Uganda/epidemiologia
14.
Clin Exp Allergy ; 49(5): 663-676, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30633850

RESUMO

BACKGROUND: It is proposed that helminth exposure protects against allergy-related disease, by mechanisms that include disconnecting risk factors (such as atopy) from effector responses. OBJECTIVE: We aimed to assess how helminth exposure influences rural-urban differences in risk factors for allergy-related outcomes in tropical low- and middle-income countries. METHODS: In cross-sectional surveys in Ugandan rural Schistosoma mansoni (Sm)-endemic islands, and in nearby mainland urban communities with lower helminth exposure, we assessed risk factors for atopy (allergen-specific skin prick test [SPT] reactivity and IgE [asIgE] sensitization) and clinical allergy-related outcomes (wheeze, urticaria, rhinitis and visible flexural dermatitis), and effect modification by Sm exposure. RESULTS: Dermatitis and SPT reactivity were more prevalent among urban participants, urticaria and asIgE sensitization among rural participants. Pairwise associations between clinical outcomes, and between atopy and clinical outcomes, were stronger in the urban survey. In the rural survey, SPT positivity was inversely associated with bathing in lakewater, Schistosoma-specific IgG4 and Sm infection. In the urban survey, SPT positivity was positively associated with age, non-Ugandan maternal tribe, being born in a city/town, BCG scar and light Sm infection. Setting (rural vs urban) was an effect modifier for risk factors including Sm- and Schistosoma-specific IgG4. In both surveys, the dominant risk factors for asIgE sensitization were Schistosoma-specific antibody levels and helminth infections. Handwashing and recent malaria treatment reduced odds of asIgE sensitization among rural but not urban participants. Risk factors for clinical outcomes also differed by setting. Despite suggestive trends, we did not find sufficient evidence to conclude that helminth (Sm) exposure explained rural-urban differences in risk factors. CONCLUSIONS AND CLINICAL RELEVANCE: Risk factors for allergy-related outcomes differ between rural and urban communities in Uganda but helminth exposure is unlikely to be the sole mechanism of the observed effect modification between the two settings. Other environmental exposures may contribute significantly.


Assuntos
Helmintíase/epidemiologia , Hipersensibilidade/epidemiologia , Hipersensibilidade/etiologia , População Rural , População Urbana , Alérgenos/imunologia , Estudos Transversais , Feminino , Helmintíase/complicações , Humanos , Hipersensibilidade/diagnóstico , Imunização , Imunoglobulina E/imunologia , Masculino , Razão de Chances , Vigilância da População , Medição de Risco , Fatores de Risco , Testes Cutâneos , Uganda/epidemiologia
15.
Clin Infect Dis ; 68(10): 1665-1674, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-30202872

RESUMO

BACKGROUND: The prevalence of allergy-related diseases is increasing in low-income countries. Parasitic helminths, common in these settings, may be protective. We hypothesized that intensive, community-wide, anthelminthic mass drug administration (MDA) would increase allergy-related diseases, while reducing helminth-related morbidity. METHODS: In an open, cluster-randomized trial (ISRCTN47196031), we randomized 26 high-schistosomiasis-transmission fishing villages in Lake Victoria, Uganda, in a 1:1 ratio to receive community-wide intensive (quarterly single-dose praziquantel plus albendazole daily for 3 days) or standard (annual praziquantel plus 6 monthly single-dose albendazole) MDA. Primary outcomes were recent wheezing, skin prick test positivity (SPT), and allergen-specific immunoglobulin E (asIgE) after 3 years of intervention. Secondary outcomes included helminths, haemoglobin, and hepatosplenomegaly. RESULTS: The outcome survey comprised 3350 individuals. Intensive MDA had no effect on wheezing (risk ratio [RR] 1.11, 95% confidence interval [CI] 0.64-1.93), SPT (RR 1.10, 95% CI 0.85-1.42), or asIgE (RR 0.96, 95% CI 0.82-1.12). Intensive MDA reduced Schistosoma mansoni infection intensity: the prevalence from Kato Katz examinations of single stool samples from each patient was 23% versus 39% (RR 0.70, 95% CI 0.55-0.88), but the urine circulating cathodic antigen test remained positive in 85% participants in both trial arms. Hookworm prevalence was 8% versus 11% (RR 0.55, 95% CI 0.31-1.00). There were no differences in anemia or hepatospenomegaly between trial arms. CONCLUSIONS: Despite reductions in S. mansoni intensity and hookworm prevalence, intensive MDA had no effect on atopy, allergy-related diseases, or helminth-related pathology. This could be due to sustained low-intensity infections; thus, a causal link between helminths and allergy outcomes cannot be discounted. Intensive community-based MDA has a limited impact in high-schistosomiasis-transmission fishing communities, in the absence of other interventions. CLINICAL TRIALS REGISTRATION: ISRCTN47196031.


Assuntos
Anti-Helmínticos/administração & dosagem , Hipersensibilidade/epidemiologia , Esquistossomose/tratamento farmacológico , Esquistossomose/epidemiologia , Adolescente , Adulto , Albendazol/uso terapêutico , Animais , Anti-Helmínticos/uso terapêutico , Criança , Pré-Escolar , Características da Família , Feminino , Helmintíase/tratamento farmacológico , Helmintíase/epidemiologia , Infecções por Uncinaria/tratamento farmacológico , Infecções por Uncinaria/epidemiologia , Humanos , Hipersensibilidade/etiologia , Lactente , Recém-Nascido , Lagos , Masculino , Administração Massiva de Medicamentos , Pessoa de Meia-Idade , Morbidade , Prevalência , Resultado do Tratamento , Uganda/epidemiologia , Adulto Jovem
16.
Int J Epidemiol ; 48(1): 148-156, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29982658

RESUMO

BACKGROUND: In Africa, where low birthweight (LBW), malnutrition and high blood pressure (BP) are prevalent, the relationships between birthweight (BW), weight gain and BP later in life remain uncertain. We examined the effects of early life growth on BP among Ugandan adolescents. METHODS: Data were collected prenatally from women and their offspring were followed from birth, with BP measured following standard protocols in early adolescence. Weight-for-age Z-scores (WAZ) were computed using World Health Organization references. Linear regression was used to relate BW, and changes in WAZ between birth and 5 years, to adolescents' BP, adjusting for confounders. RESULTS: Among 2345 live offspring, BP was measured in 1119 (47.7%) adolescents, with mean systolic BP 105.9 mmHg and mean diastolic BP 65.2 mmHg. There was little evidence of association between BW and systolic [regression coefficient ß = 0.14, 95% confidence interval (CI) (-1.00, 1.27)] or diastolic [ß = 0.43, 95% CI (-0.57, 1.43)] BP. Accelerated weight gain between birth and 5 years was associated with increased BP: systolic ß = 1.17, 95% CI (0.69, 1.66) and diastolic ß = 1.03, 95% CI (0.59, 1.47). Between birth and 6 months of age, effects of accelerated weight gain on adolescent BP were strongest among the LBW (both premature and small-for-gestational-age) children [BW < 2.5 kg: ß = 2.64, 95% CI (0.91, 4.37), BW≥2.5 kg: ß = 0.58, 95% CI (0.01, 1.14), interaction P-value = 0.024]. CONCLUSIONS: Findings from this large tropical birth cohort in Uganda suggest that postnatal weight gain rather than BW is important in the developmental programming of BP, with fast-growing LBW children at particular risk. Efforts to control BP should adopt a life course approach.


Assuntos
Peso ao Nascer , Pressão Sanguínea , Hipertensão/epidemiologia , Recém-Nascido de Baixo Peso/crescimento & desenvolvimento , Ganho de Peso , Adolescente , Criança , Desenvolvimento Infantil , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Modelos Lineares , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Uganda/epidemiologia
17.
Wellcome Open Res ; 3: 152, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30687794

RESUMO

Background: The home environment is reported to contribute significantly to children's developing cognitive skills. However, it is not yet evident whether this role prevails in the context of extreme poverty and frequent ill-health. We therefore investigated the role of the home environment in Ugandan children taking into account the frequent infections and extreme poverty in which they lived. Methods: Cognitive abilities of 163 5-year-old children were assessed. Home environments of these children, their health status and family socioeconomic status (SES) were assessed respectively using the EC-HOME, anthropometry and illnesses, and traditional SES measures. Structural equation analyses compared five models on the influence of the home environment, SES, and child health on the cognitive scores. Results: The model in which the home environment mediates the combined influence of SES and child health on cognitive performance showed a particularly good fit to the data compared with the four alternative models, i.e. those in which the HOME, SES and health independently influence cognitive performance. Conclusions: Home environments providing cognitive stimulation can enable children to overcome effects of major adverse life experiences on cognitive development.

18.
Pediatr Allergy Immunol ; 28(4): 377-383, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28339128

RESUMO

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.


Assuntos
Hipersensibilidade Imediata/epidemiologia , Pobreza , África ao Sul do Saara/epidemiologia , Alérgenos/imunologia , Criança , Pré-Escolar , Estudos de Coortes , Comorbidade , Países em Desenvolvimento , Feminino , Seguimentos , Humanos , Masculino , Prevalência , Sons Respiratórios , Testes Cutâneos , Inquéritos e Questionários , Uganda/epidemiologia
19.
Trop Med Int Health ; 20(9): 1201-1208, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25976017

RESUMO

OBJECTIVES: Recent reports suggest that Schistosoma infection may increase the risk of acquiring human immunodeficiency virus (HIV). We used data from a large cross-sectional study to investigate whether Schistosoma mansoni infection is associated with increased HIV prevalence. METHODS: We conducted a household survey of residents in island fishing communities in Mukono district, Uganda, between October 2012 and July 2013. HIV status was assessed using rapid test kits. Kato-Katz (KK) stool tests and urine-circulating cathodic antigen (CCA) were used to test for Schistosoma infection. Multivariable logistic regression, allowing for the survey design, was used to investigate the association between S. mansoni infection and HIV infection. RESULTS: Data from 1412 participants aged 13 years and older were analysed (mean age 30.3 years, 45% female). The prevalence of HIV was 17.3%. Using the stool Kato-Katz technique on a single sample, S. mansoni infection was detected in 57.2% (719/1257) of participants; urine CCA was positive in 73.8% (478/650) of those tested. S. mansoni infection was not associated with HIV infection. [KK (aOR = 1.04; 95% CI: 0.74-1.47, P = 0.81), CCA (aOR = 1.53; 95% CI: 0.78-3.00, P = 0.19)]. The median S. mansoni egg count per gram was lower in the HIV-positive participants (P = 0.005). CONCLUSIONS: These results add to the evidence that S. mansoni has little effect on HIV transmission, but may influence egg excretion.

20.
Trials ; 16: 187, 2015 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-25902705

RESUMO

BACKGROUND: The Hygiene Hypothesis proposes that infection exposure protects against inflammatory conditions. Helminths possess allergen-like molecules and may specifically modulate allergy-related immunological pathways to inhibit responses which protect against them. Mass drug administration is recommended for helminth-endemic communities to control helminth-induced pathology, but may also result in increased rates of inflammation-mediated diseases in resource-poor settings. Immunological studies integrated with implementation of helminth control measures may elucidate how helminth elimination contributes to ongoing epidemics of inflammatory diseases. We present the design of the Lake Victoria Island Intervention Study on Worms and Allergy-related diseases (LaVIISWA), a cluster-randomised trial evaluating the risks and benefits of intensive versus standard anthelminthic treatment for allergy-related diseases and other health outcomes. METHODS/DESIGN: The setting is comprised of island fishing communities in Mukono district, Uganda. Twenty-six communities have been randomised in a 1:1 ratio to receive standard or intensive anthelminthic intervention for a three-year period. Baseline characteristics were collected immediately prior to intervention rollout, commenced in February 2013. Primary outcomes are reported wheeze in the past 12 months and atopy (skin prick test response and allergen-specific immunoglobulin (asIg) E concentration). Secondary outcomes are visible flexural dermatitis, helminth infections, haemoglobin, growth parameters, hepatosplenomegaly, and responses to vaccine antigens. The trial provides a platform for in-depth analysis of clinical and immunological consequences of the contrasting interventions. DISCUSSION: The baseline survey has been completed successfully in a challenging environment. Baseline characteristics were balanced between trial arms. Prevalence of Schistosoma mansoni, hookworm, Strongyloides stercoralis and Trichuris trichiura was 52%, 23%, 13%, and 12%, respectively; 31% of Schistosoma mansoni infections were heavy (>400 eggs/gram). The prevalence of reported wheeze and positive skin prick test to any allergen was 5% and 20%, respectively. Respectively, 77% and 87% of participants had Dermatophagoides- and German cockroach-specific IgE above 0.35 kUA/L. These characteristics suggest that the LaVIISWA study will provide an excellent framework for investigating beneficial and detrimental effects of worms and their treatment, and the mechanisms of such effects. TRIAL REGISTRATION: This trial was registered with Current Controlled Trials (identifier: ISRCTN47196031) on 7 September 2012.


Assuntos
Albendazol/administração & dosagem , Anti-Helmínticos/administração & dosagem , Dermatite Atópica/tratamento farmacológico , Praziquantel/administração & dosagem , Hipersensibilidade Respiratória/tratamento farmacológico , Esquistossomose mansoni/tratamento farmacológico , Estrongiloidíase/tratamento farmacológico , Tricuríase/tratamento farmacológico , Albendazol/efeitos adversos , Animais , Anti-Helmínticos/efeitos adversos , Biomarcadores/sangue , Protocolos Clínicos , Dermatite Atópica/diagnóstico , Dermatite Atópica/imunologia , Dermatite Atópica/parasitologia , Esquema de Medicação , Hemoglobinas/metabolismo , Interações Hospedeiro-Parasita , Humanos , Imunoglobulina E/sangue , Testes Intradérmicos , Praziquantel/efeitos adversos , Projetos de Pesquisa , Hipersensibilidade Respiratória/diagnóstico , Hipersensibilidade Respiratória/imunologia , Hipersensibilidade Respiratória/parasitologia , Sons Respiratórios/efeitos dos fármacos , Sons Respiratórios/imunologia , Schistosoma mansoni/efeitos dos fármacos , Schistosoma mansoni/imunologia , Schistosoma mansoni/patogenicidade , Esquistossomose mansoni/diagnóstico , Esquistossomose mansoni/imunologia , Esquistossomose mansoni/parasitologia , Strongyloides stercoralis/efeitos dos fármacos , Strongyloides stercoralis/imunologia , Strongyloides stercoralis/patogenicidade , Estrongiloidíase/diagnóstico , Estrongiloidíase/imunologia , Estrongiloidíase/parasitologia , Fatores de Tempo , Resultado do Tratamento , Tricuríase/diagnóstico , Tricuríase/imunologia , Tricuríase/parasitologia , Trichuris/efeitos dos fármacos , Trichuris/imunologia , Trichuris/patogenicidade , Uganda
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