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1.
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
2.
BMJ Open ; 11(2): e040426, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33593768

RESUMO

INTRODUCTION: Several licensed and investigational vaccines have lower efficacy, and induce impaired immune responses, in low-income versus high-income countries and in rural, versus urban, settings. Understanding these population differences is essential to optimising vaccine effectiveness in the tropics. We suggest that repeated exposure to and immunomodulation by chronic helminth infections partly explains population differences in vaccine response. METHODS AND ANALYSIS: We have designed an individually randomised, parallel group trial of intensive versus standard praziquantel (PZQ) intervention against schistosomiasis, to determine effects on vaccine response outcomes among school-going adolescents (9-17 years) from rural Schistosoma mansoni-endemic Ugandan islands. Vaccines to be studied comprise BCG on day 'zero'; yellow fever, oral typhoid and human papilloma virus (HPV) vaccines at week 4; and HPV and tetanus/diphtheria booster vaccine at week 28. The intensive arm will receive PZQ doses three times, each 2 weeks apart, before BCG immunisation, followed by a dose at week 8 and quarterly thereafter. The standard arm will receive PZQ at week 8 and 52. We expect to enrol 480 participants, with 80% infected with S. mansoni at the outset.Primary outcomes are BCG-specific interferon-γ ELISpot responses 8 weeks after BCG immunisation and for other vaccines, antibody responses to key vaccine antigens at 4 weeks after immunisation. Secondary analyses will determine the effects of intensive anthelminthic treatment on correlates of protective immunity, on waning of vaccine response, on priming versus boosting immunisations and on S. mansoni infection status and intensity. Exploratory immunology assays using archived samples will enable assessment of mechanistic links between helminths and vaccine responses. ETHICS AND DISSEMINATION: Ethics approval has been obtained from relevant ethics committes of Uganda and UK. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications. TRIAL REGISTRATION NUMBER: ISRCTN60517191.


Assuntos
Esquistossomose , Adolescente , Animais , Humanos , Imunidade , Ilhas , Praziquantel , Ensaios Clínicos Controlados Aleatórios como Assunto , Uganda
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.


Assuntos
Anti-Helmínticos/administração & dosagem , Administração Massiva de Medicamentos/estatística & dados numéricos , Esquistossomose/tratamento farmacológico , Esquistossomose/epidemiologia , Recusa do Paciente ao Tratamento/estatística & dados numéricos , Adolescente , Adulto , Albendazol/administração & dosagem , Animais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Lagos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Praziquantel/administração & dosagem , Prevalência , Características de Residência , Uganda/epidemiologia , Adulto Jovem
4.
Open Forum Infect Dis ; 7(4): ofaa091, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32296727

RESUMO

BACKGROUND: Praziquantel mass drug administration (MDA) is recommended in schistosomiasis-endemic areas. Animal models demonstrate Schistosoma parasite resistance to praziquantel after repeated exposure. METHODS: We conducted a parasitological survey in 26 fishing communities in Uganda after 4 years of quarterly (13 communities) or annual (13 communities) praziquantel MDA, with Schistosoma infection detected by single-stool-sample Kato-Katz. A test of cure was done in participants who were positive on both urine circulating cathodic antigen test and 3-sample Kato-Katz. We calculated cure rates (CRs) and egg reduction rates (ERRs) based on 3-sample Kato-Katz and infection intensity using worm-specific circulating anodic antigen (CAA) in blood, comparing these between quarterly and annually treated participants. RESULTS: Single-sample Kato-Katz Schistosoma mansoni prevalence was 22% in 1,056 quarterly treated participants and 34% in 1,030 annually treated participants (risk ratio, 0.62; 95% confidence interval [CI], 0.40 to 0.94). Among 110 test-of-cure participants, CRs were 65% and 51% in annually and quarterly treated villages, respectively (odds ratio, 0.65; 95% CI, 0.27 to 1.58); ERRs were 94% and 81% (difference, -13%; 95% CI, -48% to 2%). There was no impact of quarterly vs annual praziquantel on S. mansoni by CAA. CONCLUSIONS: In this schistosomiasis hot spot, there was little evidence of decreased praziquantel efficacy. However, in the absence of alternative therapies, there remains a need for continued vigilance of praziquantel efficacy in the MDA era.

5.
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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