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1.
Artigo em Inglês | PAHO-IRIS | ID: phr-53192

RESUMO

[ABSTRACT]. Objective. To confirm the absence of Wuchereria bancrofti autochthonous cases in Manaus, a former focus of lymphatic filariasis in the Western Brazilian Amazon. Methods. A field survey was carried out in 2016 using immunochromatographic rapid tests (ICT card) for the detection of circulating filarial antigens in blood. The sample included a group of 3 000 schoolchildren aged 6 to 10 years enrolled in schools from different urban areas of Manaus (including the former lymphatic filariasis focus in the city) and a group of 709 adolescents and adults, between the ages of 11 and 85 years, born and raised in different areas of Manaus. Results. All of the individuals tested negative for W. bancrofti antigen. Conclusions. Although Manaus was once considered endemic, this focus no longer seems to be active for lymphatic filariasis transmission. The results of this study could support the certification by the World Health Organization of the lymphatic filariasis transmission elimination exercise in Brazil.


[RESUMEN]. Objetivo. Confirmar la ausencia de casos autóctonos de Wuchereria bancrofti en Manaos, anteriormente un foco de filariasis linfática en la Amazonia occidental de Brasil. Métodos. En el 2016 se llevó a cabo una encuesta en el terreno con pruebas rápidas inmunocromatográficas (tiras inmunocromatográficas) para detectar antígenos filáricos circulantes en sangre. La muestra constó de un grupo de 3 000 escolares de 6 a 10 años matriculados en escuelas de diferentes zonas urbanas de Manaos (incluida la zona que anteriormente era el foco de filariasis linfática en la ciudad) y de un grupo de 709 adolescentes y adultos, de edades comprendidas entre 11 y 85 años, nacidos y criados en diferentes áreas de Manaos. Resultados. Todas las personas dieron negativo en la prueba de antígeno de Wuchereria bancrofti. Conclusiones. Aunque hubo un tiempo en que Manaos se consideraba zona endémica, parece que este foco de transmisión de la filariasis linfática ya no está activo. Los resultados de este estudio podrían brindar apoyo a la certificación de la Organización Mundial de la Salud respecto de los esfuerzos realizados en Brasil para eliminar la transmisión de la filariasis linfática.


[RESUMO]. Objetivo. Confirmar a ausência de casos autóctones de Wuchereria bancrofti em Manaus, anteriormente um foco da filariose linfática na parte leste da Amazônia brasileira. Métodos. Uma pesquisa de campo foi realizada em 2016 com o uso de teste rápido por imunocromatografia (cartão ICT) para detecção de antígenos de microfilárias circulantes no sangue. A amostra estudada consistiu de um grupo de 3 000 crianças escolares entre 6 e 10 anos de idade matriculados em escolas de diferentes áreas da zona urbana de Manaus (englobando a área anteriormente com o foco de filariose linfática) e um grupo de 709 adolescentes e adultos entre 11 e 85 anos de idade nascidos e crescidos em diferentes áreas de Manaus. Resultados. Todos os indivíduos pesquisados tiveram teste negativo para o antígeno da W. bancrofti. Conclusões. Apesar de Manaus ter sido anteriormente uma área endêmica, parece que não existe mais foco ativo de transmissão da filariose linfática na cidade. Os resultados deste estudo podem servir para embasar a certificação pela Organização Mundial da Saúde da eliminação da transmissão da filariose linfática no Brasil.


Assuntos
Wuchereria bancrofti , Filariose Linfática , Brasil , Filariose Linfática , Brasil , Filariose Linfática
3.
Int Health ; 13(Supplement_1): S55-S59, 2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33349882

RESUMO

Since the launch of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) in 2000, more than 910 million people have received preventive chemotherapy for lymphatic filariasis (LF) and many thousands have received care for chronic manifestations of the disease. To achieve this, millions of community drug distributors (CDDs), community members and health personnel have worked together each year to ensure that at-risk communities receive preventive chemotherapy through mass drug administration (MDA). The successes of 20 y of partnership with communities is celebrated, including the application of community-directed treatment, the use of CDDs and integration with other platforms to improve community access to healthcare. Important challenges facing the GPELF moving forward towards 2030 relate to global demographic, financing and programmatic changes. New innovations in research and practice present opportunities to encourage further community partnership to achieve the elimination of LF as a public health problem. We stress the critical need for community ownership in the current Covid-19 pandemic, to counter concerns in relaunching MDA programmes for LF.


Assuntos
Participação da Comunidade , Erradicação de Doenças/organização & administração , Filariose Linfática/prevenção & controle , Saúde Global , Erradicação de Doenças/tendências , Filariose Linfática/epidemiologia , Filaricidas/uso terapêutico , Previsões , Humanos , Administração Massiva de Medicamentos
5.
PLoS Negl Trop Dis ; 14(9): e0008499, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32936792

RESUMO

Since the prioritization of Lymphatic Filariasis (LF) elimination in 1997, progress has been made in reducing disease transmission and burden. Validation of elimination through Transmission Assessment Surveys (TAS) in implementation units (IUs) that have received at least 5 rounds of mass drug administration (MDA) and achieved minimum threshold of 65% treatment coverage is required. There are IUs that do not qualify for TAS due to achievement of low treatment coverage. This study sought to identify barriers of community participation and access to MDA, develop and test strategies to be recommended for improved uptake. Two wards in Kaloleni sub-county, Kilifi county with an average treatment coverage of 56% in 2015, 50.5% in 2016 were purposively sampled and a quasi-experimental study conducted. Through systematic random sampling, 350 (pre-intervention) and 338 (post-intervention) household heads were selected and interviewed for quantitative data. For qualitative data, 16 Focus Group Discussions (FGDs) with purposively selected community groups were conducted. Participatory meetings were held with county stakeholders to agree on strategies for improved community participation in MDA. The quantitative data were analyzed using STATA version 14.1, statistical significance assessed by chi square test and qualitative data by QSR NVIVO version 10. The identified strategies were tested in experimental sites during the 2018 MDA and the usual MDA strategies applied in control sites. The results showed an increase in community participation and access to MDA in both sites 80.6% (pre-intervention), 82.9% (post-intervention). The proportion of participants who considered the treatment as necessary significantly (p = 0.001) increased to 96.2% from 88.3% and significantly dropped for those with drug swallowing problems associated with: size (p<0.001), number (p<0.027) and taste (p = 0.001). The implemented strategies may have contributed to increased participation and access to MDA and should be applied for improved treatment uptake. Health education on disease aetiology and importance of drug uptake in all rounds is key to program's success.


Assuntos
Participação da Comunidade/métodos , Filariose Linfática/tratamento farmacológico , Educação em Saúde , Administração Massiva de Medicamentos/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos de Deglutição , Filariose Linfática/prevenção & controle , Características da Família , Feminino , Filaricidas/uso terapêutico , Grupos Focais , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Quênia , Masculino , Pessoa de Meia-Idade
6.
PLoS Negl Trop Dis ; 14(9): e0008511, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32976499

RESUMO

BACKGROUND: Soil-transmitted helminthiasis (STH) is endemic in Fiji but its prevalence is not known and likely to have changed after a decade of mass drug administration (MDA) for lymphatic filariasis (LF). By linking with LF transmission assessment surveys (LF-TAS), we undertook the first nation-wide assessment of STH in Fijian primary schools, as well as an analysis of factors associated with STH infections. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional assessment for STH was conducted in all four Divisions of Fiji from 2014 to 2015. In the Western, Central, and Northern Divisions, schools were sub-sampled after LF-TAS, while, in the Eastern Division, schools were selected via simple random sampling. For the diagnosis of STH, stool samples were examined by coproscopy with a single Kato-Katz thick smear (KK) and the formol-ether-acetate concentration technique, except for the samples from the Eastern Division where only KK was used. Mean prevalence of any STH among class 1-2 students at the national level was 10.5% (95% CI: 6.9-15.5). Across the three Divisions via LF-TAS, the prevalence levels for ascariasis were 8.7% (95% CI: 4.3-16.6), hookworm 3.9% (95% CI: 2.3-6.6) and trichuriasis 0%. In the Eastern Division, ascariasis prevalence was 13.3% (95% CI: 6.4-25.6), and hookworm 0.7% (95% CI: 0.2-2.5), with one case of trichuriasis. Among class 3-8 students, ascariasis prevalence was lower. Lower risk of any STH was associated with wearing shoes (adjusted OR 0.54, 95% CI: 0.32-0.90) and having piped water from the Fiji Water Authority at home (adjusted OR 0.48, 95% CI: 0.25-0.92). CONCLUSIONS: After a decade of community-based LF-MDA, STH in school-age children in Fiji is now close to 10%, but localities of endemicity remain. Preventive chemotherapy should be maintained in areas with elevated STH prevalence alongside targeted delivery of integrated WASH interventions. LF-TAS has provided an opportunity to develop future public health surveillance platforms.


Assuntos
Ascaríase/epidemiologia , Infecções por Uncinaria/epidemiologia , Tricuríase/epidemiologia , Adolescente , Ancylostomatoidea/isolamento & purificação , Animais , Ascaris/isolamento & purificação , Criança , Pré-Escolar , Estudos Transversais , Filariose Linfática/epidemiologia , Feminino , Fiji/epidemiologia , Helmintíase/epidemiologia , Humanos , Masculino , Contagem de Ovos de Parasitas , Prevalência , Sapatos , Estudantes , Inquéritos e Questionários , Trichuris/isolamento & purificação , Abastecimento de Água
7.
PLoS One ; 15(9): e0238622, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32946536

RESUMO

BACKGROUND: Assessing the quality of mass drug administration (MDA) rounds is a key component of lymphatic filariasis (LF) elimination programs. Routine collection of administrative coverage is unreliable, especially when pockets with low program coverage exist. To address this gap, we used lot quality assurance sampling (LQAS) following the 10th annual LF-MDA round in Fiji to explore whether there was any area in which target coverage was not reached. We also assessed the level of drug compliance and satisfaction with the LF-MDA implementation strategy. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cross-sectional household survey in 3 divisions of Fiji. For LQAS, we defined 19 lots in 7 medical areas of the Suva sub-division and another 12 sub-divisions in the Central, Northern, and Eastern Divisions. A sample of 16 randomly selected household members was taken un each lot. We defined our decision rule as follows: if more than 1 person in a given lot did not swallow the medication, coverage was considered inadequate, i.e. less than 80%. Of the 7 lots in Suva sub-division and 12 lots in the 3 divisions, five and two lots, respectively, were identified as having inadequate coverage. The overall program coverage estimated from 304 samples was 92%, which was higher than the reported administrative coverage of 82%. About 98% of interviewees were offered the medication and 96% swallowed it. Non-participation arose from insufficient information on how to obtain the drugs. At least 92% were satisfied with the LF-MDA implementation strategy. CONCLUSIONS: Areas of low program coverage with results discordant with the reported administrative coverage existed in both urban and rural settings. Drug compliance and satisfaction were high, even after repeated rounds. We recommend increasing efforts to deliver the service in those areas with inadequate program coverage, as well as conducting timely coverage assessment through LQAS for corrective action.


Assuntos
Filariose Linfática/tratamento farmacológico , Amostragem para Garantia da Qualidade de Lotes , Administração Massiva de Medicamentos , Adolescente , Adulto , Criança , Características da Família , Feminino , Fiji , Geografia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Inquéritos e Questionários , Adulto Jovem
8.
PLoS Negl Trop Dis ; 14(9): e0008642, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32976514

RESUMO

Mass Drug Administration (MDA) programs to eliminate Lymphatic Filariasis (LF) in western Africa use the anthelminthics ivermectin plus albendazole. These drugs have the potential to impact also Soil-Transmitted Helminth (STH) infections, since the drugs have a broad range of anthelminthic activity. Integration of preventive chemotherapy efforts for LF, onchocerciasis and STH is recommended by the World Health Organization (WHO) in order to avoid duplication of MDA and to reduce costs. The objective of the current study was to determine whether five semi-annual rounds of community-wide MDA to eliminate LF and onchocerciasis have a greater impact on STH than three annual rounds of MDA with similar compliance. The effects of MDA using ivermectin (IVM, 0.2 mg/kg) combined with albendazole (ALB, 400 mg) on the prevalence and intensity of hookworm infection were evaluated in the Abengourou (annual MDA) and Akoupé (semi-annual MDA) health Districts in eastern Côte d'Ivoire from 2014 to 2017. A cross-sectional approach was used together with mixed logistic regression, and mixed linear models. Subjects were tested for STH using the Kato-Katz technique before the first round of MDA and 12, 24, and 36 months after the first round of MDA. The mean self-reported MDA compliance assessed during the survey was 65%, and no difference was observed between treatment areas. These results were confirmed by an independent coverage survey as recommended by WHO. Hookworm was the most prevalent STH species in both areas (23.9% vs 12.4%) and the prevalence of other STH species was less than 1%. The crude prevalence of hookworm dropped significantly, from 23.9% to 5.5% (p <0.001, 77% reduction) in the annual MDA treatment area and from 12.4% to 1.9% (p <0.001, 85% reduction) in the semi-annual treatment area. The average intensity of hookworm infection decreased in the annual MDA area (406.2 epg to 118.3 epg), but not in the semi-annual MDA area (804.9 epg to 875.0 epg). Moderate and heavy infections (1% and 1.3% at baseline) were reduced to 0% and 0.4% in the annual and semi-annual treatment areas, respectively. Using a mixed logistic regression model, and after adjusting for baseline prevalence, only the year 2 re-examination showed a difference in prevalence between treatments (OR: 2.26 [95% CI: 1.03, 4.98], p = 0.043). Analysis of intensity of hookworm infection indicated also that treatment differences varied by follow-up visit. In conclusion twelve months after the last treatment cycle, three annual and five semi-annual rounds of community-wide MDA with the combination of IVM and ALB showed strong, but similar impact on hookworm prevalence and intensity in eastern Côte d'Ivoire. Therefore, an annual MDA regimen seems to be an efficient strategy to control hookworm infection in endemic areas with low and moderate infection prevalence. Trial registration: The study was registered at ClinicalTrial.gov under the number NTC02032043.


Assuntos
Filariose Linfática/tratamento farmacológico , Infecções por Uncinaria/tratamento farmacológico , Administração Massiva de Medicamentos/métodos , Oncocercose/tratamento farmacológico , Adolescente , Adulto , Albendazol/administração & dosagem , Albendazol/uso terapêutico , Ancylostomatoidea , Animais , Criança , Costa do Marfim/epidemiologia , Estudos Transversais , Combinação de Medicamentos , Filariose Linfática/epidemiologia , Feminino , Infecções por Uncinaria/epidemiologia , Humanos , Ivermectina/administração & dosagem , Ivermectina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oncocercose/epidemiologia , Prevalência , Adulto Jovem
9.
Lancet Glob Health ; 8(9): e1186-e1194, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32827480

RESUMO

BACKGROUND: Lymphatic filariasis is a neglected tropical disease that can cause permanent disability through disruption of the lymphatic system. This disease is caused by parasitic filarial worms that are transmitted by mosquitos. Mass drug administration (MDA) of antihelmintics is recommended by WHO to eliminate lymphatic filariasis as a public health problem. This study aims to produce the first geospatial estimates of the global prevalence of lymphatic filariasis infection over time, to quantify progress towards elimination, and to identify geographical variation in distribution of infection. METHODS: A global dataset of georeferenced surveyed locations was used to model annual 2000-18 lymphatic filariasis prevalence for 73 current or previously endemic countries. We applied Bayesian model-based geostatistics and time series methods to generate spatially continuous estimates of global all-age 2000-18 prevalence of lymphatic filariasis infection mapped at a resolution of 5 km2 and aggregated to estimate total number of individuals infected. FINDINGS: We used 14 927 datapoints to fit the geospatial models. An estimated 199 million total individuals (95% uncertainty interval 174-234 million) worldwide were infected with lymphatic filariasis in 2000, with totals for WHO regions ranging from 3·1 million (1·6-5·7 million) in the region of the Americas to 107 million (91-134 million) in the South-East Asia region. By 2018, an estimated 51 million individuals (43-63 million) were infected. Broad declines in prevalence are observed globally, but focal areas in Africa and southeast Asia remain less likely to have attained infection prevalence thresholds proposed to achieve local elimination. INTERPRETATION: Although the prevalence of lymphatic filariasis infection has declined since 2000, MDA is still necessary across large populations in Africa and Asia. Our mapped estimates can be used to identify areas where the probability of meeting infection thresholds is low, and when coupled with large uncertainty in the predictions, indicate additional data collection or intervention might be warranted before MDA programmes cease. FUNDING: Bill & Melinda Gates Foundation.


Assuntos
Filariose Linfática/epidemiologia , Saúde Global/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Análise Espacial , Adulto Jovem
10.
11.
PLoS Negl Trop Dis ; 14(8): e0008616, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32853202

RESUMO

Podoconiosis is a type of tropical lymphedema that causes massive swelling of the lower limbs. The disease is associated with both economic insecurity, due to long-term morbidity-related loss of productivity, and intense social stigma. The geographical distribution and burden of podoconiosis in Africa are uncertain. We applied statistical modelling to the most comprehensive database compiled to date to predict the environmental suitability of podoconiosis in the African continent. By combining climate and environmental data and overlaying population figures, we predicted the environmental suitability and human population at risk of podoconiosis in Africa. Environmental suitability for podoconiosis was predicted in 29 African countries. In the year 2020, the total population in areas suitable for podoconiosis is estimated at 114.5 million people, (95% uncertainty interval: 109.4-123.9) with 16.9 million in areas suitable for both lymphatic filariasis and podoconiosis. Of the total 5,712 implementation units (typically second administrative-level units, such as districts) defined by the World Health Organization in Africa, 1,655 (29.0%) were found to be environmentally suitable for podoconiosis. The majority of implementation units with high environmental suitability are located in Angola (80, 4.8%), Cameroon (170, 10.3%), the DRC (244, 14.7%), Ethiopia (495, 29.9%), Kenya (217, 13.1%), Uganda (116, 7.0%) and Tanzania (112, 6.8%). Of the 1,655 environmentally suitable implementation units, 960 (58.0%) require more detailed community-level mapping. Our estimates provide key evidence of the population at risk and geographical extent of podoconiosis in Africa, which will help decision-makers to better plan more integrated intervention programmes.


Assuntos
Elefantíase/epidemiologia , África/epidemiologia , Angola/epidemiologia , Camarões/epidemiologia , Bases de Dados Factuais , República Democrática do Congo/epidemiologia , Filariose Linfática/epidemiologia , Etiópia/epidemiologia , Previsões , Geografia , Humanos , Quênia/epidemiologia , Morbidade , Prevalência , Fatores de Risco , Tanzânia/epidemiologia , Uganda/epidemiologia
12.
PLoS Negl Trop Dis ; 14(8): e0007009, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32804967

RESUMO

Ghana has been implementing Mass Drug Administration (MDA) since the year 2001, and Lymphatic Filariasis transmission has been interrupted in 76 out of the 98 targeted districts. The remaining districts have a microfilaria prevalence above the 1% threshold needed for the interruption of transmission. This study assesses the level of lymphatic filariasis MDA coverage and explored factors affecting the quality of implementation of the MDA in the Bole and Central Gonja Districts of Northern Ghana. A concurrent mixed methods study design approach was used to provide both a quantitative and qualitative insight. A descriptive analysis was carried out, and the results are presented in tables and charts. The transcripts of the qualitative interviews were imported into Nvivo and framework methods of analysis were used. The results were summarized based on the themes and buttressed with narratives with key quotes presented within the texts. The overall MDA coverage in Central Gonja is 89.3% while that of Bole district is 82.9%. Refusal to ingest the drug and adverse drug reactions were higher in Bole district than the Central Gonja District. The persistent transmission of lymphatic filariasis in Bole District was characterized by poor community mobilization and sensitization, nonadherence to the directly observed treatment strategy, refusal to ingest the drug due to the fear of adverse drug reactions, inadequate knowledge and misconceptions about the disease. Reported mass drug administration coverage will not necessarily result into interruption of transmission of the disease without strict compliance to the directly observed treatment strategy, strong stakeholder engagement coupled with evidence-based context-specific multi-channel community education strategies with key educational messages on the cause of the disease and adverse drug reactions. While the clock for the elimination of lymphatic filariasis by the year 2020 and meeting of the Sustainable Development Goal 3 target 3.3 by 2030 is ticking, there is an urgent need for a concerted effort to improve the fidelity of the ongoing lymphatic filariasis MDA campaigns in the Bole District of Northern Ghana.


Assuntos
Filariose Linfática/prevenção & controle , Filaricidas/uso terapêutico , Administração Massiva de Medicamentos/estatística & dados numéricos , Adulto , Erradicação de Doenças/métodos , Erradicação de Doenças/normas , Feminino , Filaricidas/administração & dosagem , Filaricidas/efeitos adversos , Gana/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Administração Massiva de Medicamentos/efeitos adversos , Administração Massiva de Medicamentos/métodos , Pessoa de Meia-Idade , Recusa do Paciente ao Tratamento/estatística & dados numéricos
13.
Am J Trop Med Hyg ; 103(1): 295-302, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32653050

RESUMO

Lymphatic filariasis (LF) is endemic in 72 countries; 15 million persons live with chronic filarial lymphedema. It can be a disabling condition, frequently painful, leading to reduced mobility, social exclusion, and depression. The Global Program to Eliminate Lymphatic Filariasis aims to stop new infections and care for affected persons, but morbidity management has been initiated in only 38 countries. We examine economic costs and benefits of alleviating chronic lymphedema and its effects through simple limb care. We use economic and epidemiological data from 12 Indian states in which 99% of Indians with filariasis reside. Using census data, we calculate the age distribution of filarial lymphedema and predict the burden of morbidity of infected persons. We estimate lifetime medical costs and lost earnings due to lymphedema and acute dermatolymphangioadenitis (ADLA) with and without community-based limb-care programs. Programs of community-based limb care in all Indian endemic areas would reduce costs of disability by 52%, saving a per person average of US$2,721, equivalent to 703 workdays. Per-person savings are 185 times the program's per-person cost. Chronic lymphedema and ADLA impose a substantial physical and economic burden in filariasis-endemic areas. Low-cost programs for lymphedema management based on limb washing and topical medication are effective in reducing the number of ADLA episodes and stopping progression of disabling lymphedema. With reduced disability, people can work longer hours per day, more days per year, and in more strenuous, higher paying jobs, resulting in important economic benefits to themselves, their families, and their communities.


Assuntos
Filariose Linfática/economia , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Efeitos Psicossociais da Doença , Análise Custo-Benefício , Progressão da Doença , Filariose Linfática/epidemiologia , Filariose Linfática/terapia , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Política de Saúde , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
PLoS Comput Biol ; 16(7): e1007506, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32692741

RESUMO

Although there is increasing importance placed on the use of mathematical models for the effective design and management of long-term parasite elimination, it is becoming clear that transmission models are most useful when they reflect the processes pertaining to local infection dynamics as opposed to generalized dynamics. Such localized models must also be developed even when the data required for characterizing local transmission processes are limited or incomplete, as is often the case for neglected tropical diseases, including the disease system studied in this work, viz. lymphatic filariasis (LF). Here, we draw on progress made in the field of computational knowledge discovery to present a reconstructive simulation framework that addresses these challenges by facilitating the discovery of both data and models concurrently in areas where we have insufficient observational data. Using available data from eight sites from Nigeria and elsewhere, we demonstrate that our data-model discovery system is able to estimate local transmission models and missing pre-control infection information using generalized knowledge of filarial transmission dynamics, monitoring survey data, and details of historical interventions. Forecasts of the impacts of interventions carried out in each site made by the models estimated using the reconstructed baseline data matched temporal infection observations and provided useful information regarding when transmission interruption is likely to have occurred. Assessments of elimination and resurgence probabilities based on the models also suggest a protective effect of vector control against the reemergence of LF transmission after stopping drug treatments. The reconstructive computational framework for model and data discovery developed here highlights how coupling models with available data can generate new knowledge about complex, data-limited systems, and support the effective management of disease programs in the face of critical data gaps.


Assuntos
Erradicação de Doenças/estatística & dados numéricos , Filariose Linfática , Modelos Biológicos , Modelos Estatísticos , Antígenos de Helmintos/sangue , Biologia Computacional , Bases de Dados Factuais , Filariose Linfática/tratamento farmacológico , Filariose Linfática/epidemiologia , Filariose Linfática/parasitologia , Filaricidas/administração & dosagem , Filaricidas/uso terapêutico , Humanos , Ivermectina/administração & dosagem , Ivermectina/uso terapêutico , Nigéria
15.
PLoS Negl Trop Dis ; 14(7): e0008427, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32628671

RESUMO

A major impediment to eliminate lymphatic filariasis and onchocerciasis is the lack of effective short-course macrofilaricidal drugs or regimens that are proven to be safe for both infections. In this study we tested oxfendazole, an anthelmintic shown to be well tolerated in phase 1 clinical trials. In vitro, oxfendazole exhibited modest to marginal motility inhibition of adult worms of Onchocerca gutturosa, pre-adult worms of Onchocerca volvulus and Onchocerca lienalis microfilariae. In vivo, five days of oral treatments provided sterile cure with up to 100% macrofilaricidal efficacy in the murine Litomosoides sigmodontis model of filariasis. In addition, 10 days of oral treatments with oxfendazole inhibited filarial embryogenesis in patent L. sigmodontis-infected jirds and subsequently led to a protracted but complete clearance of microfilaremia. The macrofilaricidal effect observed in vivo was selective, as treatment with oxfendazole of microfilariae-injected naïve mice was ineffective. Based on pharmacokinetic analysis, the driver of efficacy is the maintenance of a minimal efficacious concentration of approximately 100 ng/ml (based on subcutaneous treatment at 25 mg/kg in mice). From animal models, the human efficacious dose is predicted to range from 1.5 to 4.1 mg/kg. Such a dose has already been proven to be safe in phase 1 clinical trials. Oxfendazole therefore has potential to be efficacious for treatment of human filariasis without causing adverse reactions due to drug-induced microfilariae killing.


Assuntos
Benzimidazóis/farmacologia , Filariose Linfática/tratamento farmacológico , Filarioidea/efeitos dos fármacos , Animais , Anti-Helmínticos/uso terapêutico , Modelos Animais de Doenças , Filariose Linfática/parasitologia , Feminino , Filarioidea/embriologia , Gerbillinae/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Microfilárias/efeitos dos fármacos , Onchocerca/efeitos dos fármacos , Onchocerca volvulus/efeitos dos fármacos , Oncocercose/tratamento farmacológico
16.
Nat Commun ; 11(1): 2685, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32483209

RESUMO

Lymphatic filariasis and onchocerciasis are neglected tropical diseases (NTDs) targeted for elimination by mass (antifilarial) drug administration. These drugs are predominantly active against the microfilarial progeny of adult worms. New drugs or combinations are needed to improve patient therapy and to enhance the effectiveness of interventions in persistent hotspots of transmission. Several therapies and regimens are currently in (pre-)clinical testing. Clinical trial simulators (CTSs) project patient outcomes to inform the design of clinical trials but have not been widely applied to NTDs, where their resource-saving payoffs could be highly beneficial. We demonstrate the utility of CTSs using our individual-based onchocerciasis transmission model (EPIONCHO-IBM) that projects trial outcomes of a hypothetical macrofilaricidal drug. We identify key design decisions that influence the power of clinical trials, including participant eligibility criteria and post-treatment follow-up times for measuring infection indicators. We discuss how CTSs help to inform target product profiles.


Assuntos
Ensaios Clínicos como Assunto/métodos , Filariose Linfática/tratamento farmacológico , Filaricidas/uso terapêutico , Oncocercose/tratamento farmacológico , Protocolos de Ensaio Clínico como Assunto , Ensaios Clínicos como Assunto/estatística & dados numéricos , Simulação por Computador , Avaliação de Medicamentos/métodos , Avaliação de Medicamentos/estatística & dados numéricos , Humanos , Ivermectina/uso terapêutico , Modelos Biológicos , Oncocercose/parasitologia , Oncocercose/transmissão
17.
PLoS Biol ; 18(6): e3000723, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32511224

RESUMO

Lymphatic filariasis (LF) afflicts over 60 million people worldwide and leads to severe pathological outcomes in chronic cases. The nematode parasites (Nematoda: Filarioidea) that cause LF require both arthropod (mosquito) intermediate hosts and mammalian definitive hosts for their propagation. The invasion and migration of filarial worms through host tissues are complex and critical to survival, yet little is known about the receptors and signaling pathways that mediate directed migration in these medically important species. In order to better understand the role of chemosensory signaling in filarial worm taxis, we employ comparative genomics, transcriptomics, reverse genetics, and chemical approaches to identify putative chemosensory receptor proteins and perturb chemotaxis phenotypes in filarial worms. We find that chemoreceptor family size is correlated with the presence of environmental (extrahost) stages in nematode life cycles, and that filarial worms contain compact and highly diverged chemoreceptor complements and lineage-specific ion channels that are predicted to operate downstream of chemoreceptor activation. In Brugia malayi, an etiological agent of LF, chemoreceptor expression patterns correspond to distinct parasite migration events across the life cycle. To interrogate the role of chemosensation in the migration of larval worms, arthropod and mammalian infectious stage Brugia parasites were incubated in nicotinamide, an agonist of the nematode transient receptor potential (TRP) channel OSM-9. Exposure of microfilariae to nicotinamide alters intramosquito migration, and exposure of L3s reduces chemotaxis toward host-associated cues in vitro. Nicotinamide also potently modulates thermosensory responses in L3s, suggesting a polymodal sensory role for Brugia osm-9. Reverse genetic studies implicate both Brugia osm-9 and the cyclic nucleotide-gated (CNG) channel subunit tax-4 in larval chemotaxis toward host serum, and these ion channel subunits partially rescue sensory defects in Caenorhabditis elegans osm-9 and tax-4 knock-out strains. Together, these data reveal genetic and functional diversification of chemosensory signaling proteins in filarial worms and encourage a more thorough investigation of clade- and parasite-specific facets of nematode sensory receptor biology.


Assuntos
Brugia Malayi/genética , Células Quimiorreceptoras/metabolismo , Culicidae/parasitologia , Filariose Linfática/parasitologia , Variação Genética , Animais , Caenorhabditis elegans/fisiologia , Quimiotaxia , Genoma , Proteínas de Helminto/metabolismo , Larva , Estágios do Ciclo de Vida , Interferência de RNA , RNA de Cadeia Dupla/metabolismo , Canais de Cátion TRPV/agonistas , Canais de Cátion TRPV/metabolismo , Temperatura
18.
PLoS Negl Trop Dis ; 14(6): e0008301, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32479495

RESUMO

Achieving elimination of lymphatic filariasis (LF) as a public health problem requires a minimum of five effective rounds of mass drug administration (MDA) and demonstrating low prevalence in subsequent assessments. The first assessments recommended by the World Health Organization (WHO) are sentinel and spot-check sites-referred to as pre-transmission assessment surveys (pre-TAS)-in each implementation unit after MDA. If pre-TAS shows that prevalence in each site has been lowered to less than 1% microfilaremia or less than 2% antigenemia, the implementation unit conducts a TAS to determine whether MDA can be stopped. Failure to pass pre-TAS means that further rounds of MDA are required. This study aims to understand factors influencing pre-TAS results using existing programmatic data from 554 implementation units, of which 74 (13%) failed, in 13 countries. Secondary data analysis was completed using existing data from Bangladesh, Benin, Burkina Faso, Cameroon, Ghana, Haiti, Indonesia, Mali, Nepal, Niger, Sierra Leone, Tanzania, and Uganda. Additional covariate data were obtained from spatial raster data sets. Bivariate analysis and multilinear regression were performed to establish potential relationships between variables and the pre-TAS result. Higher baseline prevalence and lower elevation were significant in the regression model. Variables statistically significantly associated with failure (p-value ≤0.05) in the bivariate analyses included baseline prevalence at or above 5% or 10%, use of Filariasis Test Strips (FTS), primary vector of Culex, treatment with diethylcarbamazine-albendazole, higher elevation, higher population density, higher enhanced vegetation index (EVI), higher annual rainfall, and 6 or more rounds of MDA. This paper reports for the first time factors associated with pre-TAS results from a multi-country analysis. This information can help countries more effectively forecast program activities, such as the potential need for more rounds of MDA, and prioritize resources to ensure adequate coverage of all persons in areas at highest risk of failing pre-TAS.


Assuntos
Transmissão de Doença Infecciosa/prevenção & controle , Filariose Linfática/epidemiologia , Filariose Linfática/prevenção & controle , Filaricidas/administração & dosagem , Albendazol/administração & dosagem , Dietilcarbamazina/administração & dosagem , Filariose Linfática/tratamento farmacológico , Humanos , Internacionalidade , Administração Massiva de Medicamentos/métodos , Avaliação de Programas e Projetos de Saúde , Saúde Pública , Fatores de Risco
19.
PLoS Negl Trop Dis ; 14(6): e0008298, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32511226

RESUMO

In Haiti, 22 communes still require mass drug administration (MDA) to eliminate lymphatic filariasis (LF) as a public health problem. Several clinical trials have shown that a single oral dose of ivermectin (IVM), diethylcarbamazine (DEC) and albendazole (ALB) (IDA) is more effective than DEC plus ALB (DA) for clearing Wuchereria bancrofti microfilariae (Mf). We performed a cluster-randomized community study to compare the safety and efficacy of IDA and DA in an LF-endemic area in northern Haiti. Ten localities were randomized to receive either DA or IDA. Participants were monitored for adverse events (AE), parasite antigenemia, and microfilaremia. Antigen-positive participants were retested one year after MDA to assess treatment efficacy. Fewer participants (11.0%, 321/2917) experienced at least one AE after IDA compared to DA (17.3%, 491/2844, P<0.001). Most AEs were mild, and the three most common AEs reported were headaches, dizziness and abdominal pain. Serious AEs developed in three participants who received DA. Baseline prevalence for filarial antigenemia was 8.0% (239/3004) in IDA localities and 11.5% (344/2994) in DA localities (<0.001). Of those with positive antigenemia, 17.6% (42/239) in IDA localities and 20.9% (72/344, P = 0.25) in DA localities were microfilaremic. One year after treatment, 84% percent of persons with positive filarial antigen tests at baseline could be retested. Clearance rates for filarial antigenemia were 20.5% (41/200) after IDA versus 25.4% (74/289) after DA (P = 0.3). However, 94.4% (34/36) of IDA recipients and 75.9% (44/58) of DA recipients with baseline microfilaremia were Mf negative at the time of retest (P = 0.02). Thus, MDA with IDA was at least as well tolerated and significantly more effective for clearing Mf compared to the standard DA regimen in this study. Effective MDA coverage with IDA could accelerate the elimination of LF as a public health problem in the 22 communes that still require MDA in Haiti.


Assuntos
Albendazol/administração & dosagem , Antiparasitários/administração & dosagem , Dietilcarbamazina/administração & dosagem , Ivermectina/administração & dosagem , Adolescente , Adulto , Albendazol/efeitos adversos , Animais , Antiparasitários/efeitos adversos , Criança , Pré-Escolar , Dietilcarbamazina/efeitos adversos , Quimioterapia Combinada , Filariose Linfática/tratamento farmacológico , Feminino , Haiti , Humanos , Ivermectina/efeitos adversos , Modelos Logísticos , Masculino , Administração Massiva de Medicamentos/efeitos adversos , Pessoa de Meia-Idade , Prevalência , Resultado do Tratamento , Adulto Jovem
20.
PLoS Negl Trop Dis ; 14(6): e0008322, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32574160

RESUMO

BACKGROUND: The World Health Organization now recommends semiannual mass drug administration (MDA) of albendazole with integrated vector management as an option for eliminating lymphatic filariasis (LF) in areas of loiasis-endemic countries where it may not be safe to use diethylcarbamazine or ivermectin in MDA programs. However, the published evidence base to support this policy is thin, and uptake by national programs has been slow. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a community trial to assess the impact of semiannual MDA on lymphatic filariasis and soil-transmitted helminth infections (STH) in two villages in the Bandundu province of the Democratic Republic of the Congo with moderately high prevalences for LF and hookworm infections. MDA with albendazole was provided every six months from June 2014 to December 2017 with treatment coverages of the eligible population (all ≥ 2 year of age) that ranged between 56% and 88%. No adverse effects were reported during the trial. Evaluation at 48 months, (i.e. 6 months after the 8th round of MDA), showed that W. bancrofti microfilaremia (Mf) prevalence in the study communities had decreased between 2014 to 2018 from 12% to 0.9% (p<0.001). The prevalence of W. bancrofti antigenemia was also significantly reduced from 31.6% to 8.5% (p<0.001). MDA with albendazole also reduced hookworm, Ascaris lumbricoides and Trichuris trichiura infection prevalences in the community from 58.6% to 21.2% (p<0.001), from 14.0% to 1.6% and 4.1% to 2.9%, respectively. Hookworm and Ascaris infection intensities were reduced by 93% (p = 0.02) and 57% (p = 0.03), respectively. In contrast, Trichuris infection intensity was not significantly reduced by MDA (p = 0.61) over this time period. CONCLUSION/SIGNIFICANCE: These results provide strong evidence that semiannual MDA with albendazole alone is a safe and effective strategy for LF elimination in Central Africa. Community MDA also had a major impact on STH infections.


Assuntos
Albendazol/uso terapêutico , Anti-Helmínticos/uso terapêutico , Filariose Linfática/tratamento farmacológico , Helmintíase/tratamento farmacológico , Adolescente , Adulto , Animais , Antígenos de Helmintos/imunologia , Ascaríase/tratamento farmacológico , Ascaríase/epidemiologia , Ascaris lumbricoides/efeitos dos fármacos , Ascaris lumbricoides/isolamento & purificação , Criança , República Democrática do Congo/epidemiologia , Filariose Linfática/epidemiologia , Feminino , Helmintíase/epidemiologia , Helmintíase/parasitologia , Infecções por Uncinaria/tratamento farmacológico , Infecções por Uncinaria/epidemiologia , Humanos , Masculino , Solo/parasitologia , Tricuríase/epidemiologia , Trichuris/efeitos dos fármacos , Trichuris/isolamento & purificação , Wuchereria bancrofti/efeitos dos fármacos , Wuchereria bancrofti/isolamento & purificação , Adulto Jovem
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