RESUMO
BACKGROUND: Lymphatic filariasis (LF) affects more than 120 million people globally. In Tanzania, nearly six million people are estimated to live with clinical manifestations of the disease. The National LF control program was established in 2000 using Mass drug administration (MDA) of Ivermectin and Albendazole to individuals aged 5years and above. This study assessed the infection status in individuals aged 15 years and above who are eligible for participation in MDA. The level of compliance to MDA and the reasons for non-compliance to MDA were also assessed. METHODS: A community based cross-sectional study was conducted in two villages of Masasi District. A total of 590 participants aged 15 years and above were screened for the circulating filarial antigen (CFA) using the rapid diagnostic test. Night blood samples from CFA positive individuals were further analyzed for detection and quantification of Wuchereria bancrofti microfilaria (Mf) using the counting chamber technique. A pre-tested questionnaire was administered to collect information on compliance to MDA and the factors affecting continued transmission. Data were analyzed using SPSS Version 20. Chi-square test was used to compare the prevalence of CFA by gender and village where a P-value ≤0.05 was considered statistically significant. RESULTS: Out of 590 participants, 30 (5.1%) were positive for CFA and one (0.2%) was found positive for microfilaria of Wuchereria bancrofti. Compliance during the last round of MDA, in the year 2019 was 56% which is below the minimum coverage recommended by WHO. Absence from home during MDA and perceptions of being free from hydrocele or elephantiasis were the major reasons for non-compliance. CONCLUSION: There is a significant decline in LF transmission in Masasi District after seven rounds of MDA. However, the presence of individuals who are persistently non-compliant may delay elimination of LF in the District.
Assuntos
Filariose Linfática/epidemiologia , Filaricidas/uso terapêutico , Administração Massiva de Medicamentos/métodos , Adolescente , Adulto , Idoso , Albendazol/uso terapêutico , Animais , Antígenos de Helmintos/uso terapêutico , Estudos Transversais , Erradicação de Doenças/métodos , Filariose Linfática/tratamento farmacológico , Filariose Linfática/transmissão , Feminino , Filaricidas/administração & dosagem , Humanos , Ivermectina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prevalência , Tanzânia/epidemiologia , Wuchereria bancrofti/patogenicidadeRESUMO
The global elimination of lymphatic filariasis (LF) is a major focus of the World Health Organization. One key challenge is locating residual infections that can perpetuate the transmission cycle. We show how a targeted sampling strategy using predictions from a geospatial model, combining random forests and geostatistics, can improve the sampling efficiency for identifying locations with high infection prevalence. Predictions were made based on the household locations of infected persons identified from previous surveys, and environmental variables relevant to mosquito density. Results show that targeting sampling using model predictions would have allowed 52% of infections to be identified by sampling just 17.7% of households. The odds ratio for identifying an infected individual in a household at a predicted high risk compared to a predicted low risk location was 10.2 (95% CI 4.2-22.8). This study provides evidence that a 'one size fits all' approach is unlikely to yield optimal results when making programmatic decisions based on model predictions. Instead, model assumptions and definitions should be tailored to each situation based on the objective of the surveillance program. When predictions are used in the context of the program objectives, they can result in a dramatic improvement in the efficiency of locating infected individuals.
Assuntos
Filariose Linfática/epidemiologia , Filariose Linfática/prevenção & controle , Filariose Linfática/transmissão , Aedes , Animais , Anticorpos Anti-Helmínticos/análise , Anticorpos Anti-Helmínticos/imunologia , Antígenos de Helmintos/análise , Antígenos de Helmintos/imunologia , Brugia Malayi/patogenicidade , Reservatórios de Doenças , Monitoramento Epidemiológico , Características da Família , Humanos , Insetos Vetores , Aprendizado de Máquina , Prevalência , Samoa/epidemiologia , Wuchereria bancrofti/patogenicidadeRESUMO
BACKGROUND: The control of lymphatic filariasis (LF) caused by Wuchereria bancrofti in the Central African Region has been hampered by the presence of Loa loa due to severe adverse events that arise in the treatment with ivermectin. The immunochromatographic test (ICT) cards used for mapping LF demonstrated cross-reactivity with L. loa and posed the problem of delineating the LF map. To verify LF endemicity in forest areas of Cameroon where mass drug administration (MDA) has not been ongoing, we used the recently developed strategy that combined serology, microscopy and molecular techniques. METHODS: This study was carried out in 124 communities in 31 health districts (HDs) where L. loa is present. At least 125 persons per site were screened. Diurnal blood samples were investigated for circulating filarial antigen (CFA) by FTS and for L. loa microfilariae (mf) using TBF. FTS positive individuals were further subjected to night blood collection for detecting W. bancrofti. qPCR was used to detect DNA of the parasites. RESULTS: Overall, 14,446 individuals took part in this study, 233 participants tested positive with FTS in 29 HDs, with positivity rates ranging from 0.0 to 8.2%. No W. bancrofti mf was found in the night blood of any individuals but L. loa mf were found in both day and night blood of participants who were FTS positive. Also, qPCR revealed that no W. bancrofti but L.loa DNA was found with dry bloodspot. Positive FTS results were strongly associated with high L. loa mf load. Similarly, a strong positive association was observed between FTS positivity and L loa prevalence. CONCLUSIONS: Using a combination of parasitological and molecular tools, we were unable to find evidence of W. bancrofti presence in the 31 HDs, but L. loa instead. Therefore, LF is not endemic and LF MDA is not required in these districts.
Assuntos
Filariose Linfática/diagnóstico , Filariose Linfática/epidemiologia , Ivermectina/uso terapêutico , Adolescente , Adulto , Animais , Antígenos de Helmintos/sangue , Camarões/epidemiologia , Reações Cruzadas , Estudos Transversais , Feminino , Florestas , Humanos , Imunoensaio , Loa/imunologia , Loa/patogenicidade , Masculino , Administração Massiva de Medicamentos , Pessoa de Meia-Idade , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Wuchereria bancrofti/imunologia , Wuchereria bancrofti/patogenicidade , Adulto JovemRESUMO
Endemic countries with lymphatic filariasis are striving towards the Global Program to Eliminate Lymphatic Filariasis (GPELF) by 2020. Efficient and cost-effective diagnostic tools to assess active filarial infection are critical to eradicate lymphatic filariasis. Detection of circulating filarial antigens in sera is one of the precise methods to identify this infection. Monoclonal antibodies and single chain fragment variable (scFv) against Wuchereria bancrofti antigen SXP1 have been developed for antigen detection. Molecular cloning of scFv for recombinant expression has laid a platform for developing novel genetic constructs with enhanced reactivity. In this study, a simple procedure is developed to create diverse libraries of scFv based on a single DNA framework with all the requisites for an in vitro protein synthesis and ribosomal display. Error Prone-PCR was performed to incorporate random mutations and screened by ribosome display technique to isolate evolved scFv. Evolved scFv with six mutations showed tenfold increase in affinity compared to wild-type scFv for rWbSXP1. In silico studies showed that four mutations introduced unique molecular interactions between the evolved scFv and SXP1. Reactivity with asserted clinical samples of endemic normals (EN), microfilariaemic (MF), chronic pathology (CP) and non-endemic normals (NEN) showed significant augment (59.69%, p < 0.0001) in reactivity to MF samples with evolved scFv in comparison to wild-type scFv. Sensitivity of scFv was increased from 15.62 ng to 195 pg by evolved scFv in serum samples. This evolutionary method coupled with ribosome display has facilitated us to improve the reactivity of the ScFv without diminishing the specificity.
Assuntos
Filariose Linfática/diagnóstico , Anticorpos de Cadeia Única/genética , Animais , Anticorpos Monoclonais/imunologia , Antígenos de Helmintos/imunologia , Filariose Linfática/genética , Ensaio de Imunoadsorção Enzimática/métodos , Evolução Molecular , Proteínas de Helminto/imunologia , Engenharia de Proteínas/métodos , Anticorpos de Cadeia Única/metabolismo , Wuchereria bancrofti/imunologia , Wuchereria bancrofti/patogenicidadeRESUMO
Culex quinquefasciatus plays an important role in transmission of vector-borne diseases of public health importance, including lymphatic filariasis (LF), as well as many arboviral diseases. Currently, efforts to tackle C. quinquefasciatus vectored diseases are based on either mass drug administration (MDA) for LF, or insecticide-based interventions. Widespread and intensive insecticide usage has resulted in increased resistance in mosquito vectors, including C. quinquefasciatus. Herein, the transcriptome profile of Ugandan bendiocarb-resistant C. quinquefasciatus was explored to identify candidate genes associated with insecticide resistance. High levels of insecticide resistance were observed for five out of six insecticides tested, with the lowest mortality (0.97%) reported to permethrin, while for DDT, lambdacyhalothrin, bendiocarb and deltamethrin the mortality rate ranged from 1.63-3.29%. Resistance to bendiocarb in exposed mosquitoes was marked, with 2.04% mortality following 1 h exposure and 58.02% after 4 h. Genotyping of the G119S Ace-1 target site mutation detected a highly significant association (p < 0.0001; OR = 25) between resistance and Ace1-119S. However, synergist assays using the P450 inhibitor PBO, or the esterase inhibitor TPP resulted in markedly increased mortality (to ≈80%), suggesting a role of metabolic resistance in the resistance phenotype. Using a novel, custom 60 K whole-transcriptome microarray 16 genes significantly overexpressed in resistant mosquitoes were detected, with the P450 Cyp6z18 showing the highest differential gene expression (>8-fold increase vs unexposed controls). These results provide evidence that bendiocarb resistance in Ugandan C. quinquefasciatus is mediated by both target-site mechanisms and over-expression of detoxification enzymes.
Assuntos
Culex/efeitos dos fármacos , Filariose Linfática/prevenção & controle , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Mosquitos Vetores/efeitos dos fármacos , Acetilcolinesterase/genética , Animais , Culex/genética , Culex/parasitologia , Filariose Linfática/parasitologia , Filariose Linfática/transmissão , Feminino , Perfilação da Expressão Gênica , Genes de Insetos/genética , Técnicas de Genotipagem , Humanos , Proteínas de Insetos/genética , Controle de Mosquitos/métodos , Mosquitos Vetores/genética , Mosquitos Vetores/parasitologia , Mutação , Análise de Sequência com Séries de Oligonucleotídeos , Uganda , Wuchereria bancrofti/patogenicidadeRESUMO
Filariasis and Strongyloidiasis are two endemic parasitic infections seen in any tropical country. Filariasis, commonly caused by Wuchereria bancrofti, Brugia malayi, and Brugia timori is seen often in peripheral blood and lymphoid tissue. But it can be isolated from wide variety of soft tissue sites in the body like soft tissue lumps, breast, thyroid, body fluids. Strongyloides stercoralis, a helminthic infection, usually affects the respiratory and gastrointestinal (GI) tract, and frequently picked up in GI biopsies. However, in cases of hyper infection and patients with altered immunity, it can be isolated from other rare sites like body fluid samples. Accurate morphological Identification and confirmation are important for specific management. We report a case of microfilaria isolated from cerebrospinal fluid and a case of Strongyloides larva isolated from ascitic fluid in clinically unsuspected cases of these two parasitic infestations. We have also added a brief discussion on morphological differences between the two larval forms.
Assuntos
Ascite/patologia , Filariose/líquido cefalorraquidiano , Estrongiloidíase/líquido cefalorraquidiano , Adulto , Animais , Ascite/parasitologia , Feminino , Filariose/parasitologia , Filariose/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Strongyloides stercoralis/patogenicidade , Estrongiloidíase/parasitologia , Estrongiloidíase/patologia , Wuchereria bancrofti/patogenicidadeRESUMO
Interaction between innate immune cells and parasite plays a key role in the immunopathogenesis of lymphatic filariasis. Despite being professional antigen presenting cells critical for the pathogen recognition, processing and presenting the antigens for mounting T cell responses, the dendritic cell response and its role in initiating CD4+ T cell response to filaria, in particular Wuchereria bancrofti, the most prevalent microfilaria is still not clear. Herein, we demonstrate that a 70 kDa phosphorylcholine-binding W. bancrofti sheath antigen induces human dendritic cell maturation and secretion of several pro-inflammatory cytokines. Further, microfilarial sheath antigen-stimulated dendritic cells drive predominantly Th1 and regulatory T cell responses while Th17 and Th2 responses are marginal. Mechanistically, sheath antigen-induced dendritic cell maturation, and Th1 and regulatory T cell responses are mediated via toll-like receptor 4 signaling. Our data suggest that W. bancrofti sheath antigen exploits dendritic cells to mediate distinct CD4+ T cell responses and immunopathogenesis of lymphatic filariasis.
Assuntos
Células Dendríticas/imunologia , Interações Hospedeiro-Parasita/imunologia , Microfilárias/imunologia , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Receptor 4 Toll-Like/genética , Wuchereria bancrofti/imunologia , Animais , Apresentação de Antígeno , Antígenos de Helmintos/genética , Antígenos de Helmintos/imunologia , Antígenos de Helmintos/farmacologia , Diferenciação Celular , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/parasitologia , Filariose Linfática/genética , Filariose Linfática/imunologia , Filariose Linfática/parasitologia , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/imunologia , Regulação da Expressão Gênica , Humanos , Imunidade Inata , Interferon gama/genética , Interferon gama/imunologia , Interleucina-17/genética , Interleucina-17/imunologia , Ativação Linfocitária , Microfilárias/genética , Microfilárias/patogenicidade , Transdução de Sinais , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/parasitologia , Células Th1/efeitos dos fármacos , Células Th1/parasitologia , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Células Th17/parasitologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Células Th2/parasitologia , Receptor 4 Toll-Like/imunologia , Wuchereria bancrofti/genética , Wuchereria bancrofti/patogenicidadeRESUMO
Lymphatic filariasis, a chronic disfiguring disease exhibits complex pathology. Based on different clinical manifestations, infected individuals are categorized into asymptomatic-carriers and chronic-patients. The mechanism behind differential clinical outcomes remains unclear. Roles of filaria-specific B cell responses in filariasis have been documented, whereas the contribution of B1 cell response and poly-specific IgG and IgA in the context of clinical filariasis is not deciphered. In this study, we measured the poly-specific IgG and IgA levels in different clinical categories of filariasis. Asymptomatic-carriers exhibited increased IgG4 antibodies against both filarial-antigens as well as auto-antigens compared to other clinical categories, although IgG against these auto-antigens remained lower. IgA levels against both filarial and auto-antigens were decreased in asymptomatic-carriers. A positive correlation between anti-filarial IgG4 and IgG4 against auto-antigens were observed, suggesting the synergistic role of poly-specific natural IgG4 with anti-filarial IgG4 in blocking the pathogenesis in asymptomatic microfilarial cases.
Assuntos
Anticorpos Anti-Helmínticos/genética , Autoanticorpos/genética , Autoantígenos/genética , Filariose Linfática/imunologia , Imunoglobulina A/genética , Imunoglobulina G/genética , Wuchereria bancrofti/imunologia , Actinas/genética , Actinas/imunologia , Adulto , Animais , Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/sangue , Antígenos de Helmintos/genética , Doenças Assintomáticas , Autoanticorpos/sangue , Autoantígenos/imunologia , Linfócitos B/imunologia , Linfócitos B/parasitologia , DNA de Cadeia Simples/genética , DNA de Cadeia Simples/imunologia , Filariose Linfática/genética , Filariose Linfática/parasitologia , Filariose Linfática/patologia , Feminino , Expressão Gênica , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Miosinas/genética , Miosinas/imunologia , Índice de Gravidade de Doença , Wuchereria bancrofti/patogenicidadeRESUMO
We compared the impact of annual and semiannual mass drug administration (MDA) on the prevalence of Brugia timori and Wuchereria bancrofti in Flores Island. Two villages (Paga, B. timori only; Lewomada, co-endemic) received annual MDA with diethylcarbamazine/albendazole and a larger village (Pruda, co-endemic) received semiannual MDA. Infection parameters (microfilariae [Mf], antibodies to recombinant filarial antigen BmR1 [Brugia Rapid (BR)], and a test for W. bancrofti antigenemia [immunochromatographic test (ICT)]) were assessed before and after treatment. The crude Mf prevalence in Pruda decreased after five semiannual treatments from 14.2% to 1.2%, whereas the Mf prevalence in the other two villages decreased after three annual treatments from 3.9% to 0% and from 5% to 0.3%, respectively. ICT positivity prevalence in Pruda and Lewomada decreased from 22.9% and 6.5% to 7% and 0.8%, respectively, whereas BR antibody prevalence in Pruda, Lewomada, and Paga decreased from 28.9%, 31.7%, and 12.5% to 3.6%, 4.1%, and 1.8%, respectively. Logistic regression analysis indicated that that Mf, BR, and ICT prevalence decreased significantly over time and that for the Mf and ICT outcomes the semiannual treatment had higher odds of positivity. Model-adjusted prevalence estimates revealed that apparent differences in treatment effectiveness were driven by differences in baseline prevalence and that adjusted prevalence declined more rapidly in the semiannual treatment group. We conclude that in this setting, annual MDA was sufficient to reduce Mf prevalence to less than 1% in areas with low to moderate baseline prevalence. Semiannual MDA was useful for rapidly reducing Mf prevalence in an area with higher baseline endemicity.
Assuntos
Albendazol/uso terapêutico , Brugia/efeitos dos fármacos , Dietilcarbamazina/uso terapêutico , Filariose Linfática/tratamento farmacológico , Filaricidas/uso terapêutico , Administração Massiva de Medicamentos/métodos , Wuchereria bancrofti/efeitos dos fármacos , Adolescente , Adulto , Idoso , Animais , Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/sangue , Brugia/crescimento & desenvolvimento , Brugia/patogenicidade , Criança , Pré-Escolar , Esquema de Medicação , Combinação de Medicamentos , Filariose Linfática/epidemiologia , Filariose Linfática/parasitologia , Feminino , Humanos , Indonésia/epidemiologia , Ilhas , Masculino , Pessoa de Meia-Idade , Prevalência , Wuchereria bancrofti/crescimento & desenvolvimento , Wuchereria bancrofti/patogenicidadeRESUMO
Scabies was recently added to the World Health Organization list of neglected tropical diseases. The ability to treat scabies with oral ivermectin makes a mass drug administration (MDA) campaign a feasible option for scabies control. Ivermectin MDA in communities endemic for lymphatic filariasis (LF) or onchocerciasis may already be having an impact on scabies. We examined the effect of ivermectin MDA for LF on scabies prevalence over 4 years in eight Tanzanian villages. At baseline, 4.4% (95% confidence interval [CI]: 3.7-5.4) of individuals tested positive for scabies, decreasing to 0.84% (95% CI: 0.51-1.4) after one round of ivermectin MDA but increased in Year 3 (2.5% [95% CI: 1.9-3.3]) and Year 4 (2.9% [95% CI: 2.2-3.8]). Most scabies cases were seen in children younger than 15 years. The data suggest that single-dose ivermectin MDA may not be effective in attaining long-term decreases when scabies prevalence is less than 5%.
Assuntos
Filariose Linfática/epidemiologia , Filaricidas/uso terapêutico , Ivermectina/uso terapêutico , Administração Massiva de Medicamentos/estatística & dados numéricos , Oncocercose/epidemiologia , Escabiose/epidemiologia , Adolescente , Animais , Criança , Pré-Escolar , Estudos Transversais , Esquema de Medicação , Filariose Linfática/tratamento farmacológico , Filariose Linfática/parasitologia , Feminino , Humanos , Lactente , Masculino , Onchocerca/efeitos dos fármacos , Onchocerca/patogenicidade , Onchocerca/fisiologia , Oncocercose/tratamento farmacológico , Oncocercose/parasitologia , Prevalência , População Rural , Sarcoptes scabiei/efeitos dos fármacos , Sarcoptes scabiei/patogenicidade , Sarcoptes scabiei/fisiologia , Escabiose/parasitologia , Escabiose/prevenção & controle , Tanzânia/epidemiologia , Wuchereria bancrofti/efeitos dos fármacos , Wuchereria bancrofti/patogenicidade , Wuchereria bancrofti/fisiologiaRESUMO
OBJECTIVE: To establish clinical and laboratory data of individuals presenting chyluria in endemic areas. RESULTS: 75 individuals were studied. The majority were females with an average age of 45 years residing in the Metropolitan Region of Recife. The mean time between the beginning of the presentation of chyluria and the first care service in the Serviço de Referencia Nacional em Filarioses was approximately 5 years. The most frequent urinalysis changes were hematuria (27.6%), leukocytes (21.9%) and proteinuria (10.5%). The Addis test showed mean values of 155.43 E/min/mL of cylinders, 52,892 E/min/mL of erythrocytes and 291,660 E/min/mL of leukocytes. Among recorded cases, proteinuria had a mean value of 1372.80 mg/dL in 24 h, and the presence of lymphocytes in the urine was positive in 68.3%. Among lymphatic filariasis tests, immunochromatography was positive in 16.7%, there was circulating filarial antigen determined by detection of OG4C3 antibodies in 7.7% and microfilaremia in only 1/55.
Assuntos
Filariose Linfática/urina , Transtornos Urinários/urina , Wuchereria bancrofti/patogenicidade , Adolescente , Adulto , Idoso , Animais , Brasil , Filariose Linfática/complicações , Filariose Linfática/parasitologia , Doenças Endêmicas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transtornos Urinários/etiologia , Adulto JovemRESUMO
BACKGROUND: Lymphedema (LE) is a chronic clinical manifestation of filarial nematode infections characterized by lymphatic dysfunction and subsequent accumulation of protein-rich fluid in the interstitial space-lymphatic filariasis. A number of studies have identified single nucleotide polymorphisms (SNPs) associated with primary and secondary LE. To assess SNPs associated with LE caused by lymphatic filariasis, a cross-sectional study of unrelated Ghanaian volunteers was designed to genotype SNPs in 285 LE patients as cases and 682 infected patients without pathology as controls. One hundred thirty-one SNPs in 64 genes were genotyped. The genes were selected based on their roles in inflammatory processes, angiogenesis/lymphangiogenesis, and cell differentiation during tumorigenesis. RESULTS: Genetic associations with nominal significance were identified for five SNPs in three genes: vascular endothelial growth factor receptor-3 (VEGFR-3) rs75614493, two SNPs in matrix metalloprotease-2 (MMP-2) rs1030868 and rs2241145, and two SNPs in carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM-1) rs8110904 and rs8111171. Pathway analysis revealed an interplay of genes in the angiogenic/lymphangiogenic pathways. Plasma levels of both MMP-2 and CEACAM-1 were significantly higher in LE cases compared to controls. Functional characterization of the associated SNPs identified genotype GG of CEACAM-1 as the variant influencing the expression of plasma concentration, a novel finding observed in this study. CONCLUSION: The SNP associations found in the MMP-2, CEACAM-1, and VEGFR-3 genes indicate that angiogenic/lymphangiogenic pathways are important in LE clinical development.
Assuntos
Filariose Linfática/genética , Polimorfismo de Nucleotídeo Único , Wuchereria bancrofti/patogenicidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antígenos CD/sangue , Antígenos CD/genética , Estudos de Casos e Controles , Moléculas de Adesão Celular/sangue , Moléculas de Adesão Celular/genética , Estudos Transversais , Filariose Linfática/etiologia , Feminino , Frequência do Gene , Haplótipos , Interações Hospedeiro-Patógeno , Humanos , Masculino , Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 2 da Matriz/genética , Pessoa de Meia-Idade , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/sangue , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/genéticaRESUMO
BACKGROUND: The Global Programme for the Elimination of Lymphatic Filariasis (GPELF) has been in operation since the year 2000, with the aim of eliminating the disease by the year 2020, following five to six rounds of effective annual mass drug administration (MDA). The treatment regimen is ivermectin (IVM) in combination with diethylcarbamazine (DEC) or albendazole (ALB). In Ghana, MDA has been undertaken since 2001. While the disease has been eliminated in many areas, transmission has persisted in some implementation units that had experienced 15 or more rounds of MDA. Thus, new intervention strategies could eliminate residual infection in areas of persistent transmission and speed up the lymphatic filariasis (LF)-elimination process. This study, therefore, seeks to test the hypothesis that biannual treatment of LF-endemic communities will accelerate the interruption of LF in areas of persistent transmission. METHODS: A cluster randomised trial will be implemented in LF-endemic communities in Ghana. The interventions will be yearly or twice-yearly MDA delivered to entire endemic communities. Allocation to study group will be by clusters identified using the prevalence of LF. Clusters will be randomised to one of two groups: receiving either (1) annual treatment with IVM + ALB or (2) annual MDA with IVM + ALB, followed by an additional MDA 6 months later. The primary outcome measure is the prevalence of LF infection, assessed by four cross-sectional surveys. Entomological assessments will also be undertaken to evaluate the transmission intensity of the disease in the study clusters. Costs and cost-effectiveness will be evaluated. Among a random subsample of participants, microfilaria prevalence will be assessed longitudinally. A nested process evaluation, using semi-structured interviews, focus group discussions and a stakeholder analysis, will investigate the community acceptability, feasibility and scale-up of each delivery system. DISCUSSION: It is expected that this study will add to the existing evidence on the need for alternative intervention strategies for the elimination of LF in Ghana and in other African countries that are facing similar challenges or are at the beginning of their LF-elimination programmes. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03036059 . Registered on 26 January 2017. Pan African Clinical Trials Registry, ID: PACTR201702002012425 . Registered on 23 February 2017.
Assuntos
Albendazol/administração & dosagem , Serviços de Saúde Comunitária , Culicidae/parasitologia , Filariose Linfática/prevenção & controle , Filaricidas/administração & dosagem , Ivermectina/administração & dosagem , Wuchereria bancrofti/efeitos dos fármacos , Albendazol/efeitos adversos , Animais , Protocolos Clínicos , Erradicação de Doenças , Esquema de Medicação , Quimioterapia Combinada , Filariose Linfática/epidemiologia , Filariose Linfática/parasitologia , Filariose Linfática/transmissão , Filaricidas/efeitos adversos , Gana/epidemiologia , Humanos , Ivermectina/efeitos adversos , Administração Massiva de Medicamentos , Prevalência , Projetos de Pesquisa , Fatores de Tempo , Resultado do Tratamento , Wuchereria bancrofti/patogenicidadeRESUMO
Chyluria, commonly seen in south Asian countries, is mainly a manifestation of lymphatic filariasis as a result of infestation with Wuchereria bancrofti, although many other causes can contribute. Many patients can be effectively treated with dietary modifications and drug therapy. The most widely used drug is diethyl carbamazine. The recurrences are common after such treatment. Such patients would benefit from sclerotherapy to obliterate the lympatico-renal fistulae located mainly in the renal pelvicalyceal system. The commonly used sclerosing agent is a combination of 5% povidone-iodine and 50% dextrose instilled through a ureteric catheter. A small percentage of patients who recur after sclerotherapy and those with systemic complications, such as hypoproteinemia and edema, might require surgery in the form of renal hilar lymphatic disconnection. Although it is a major operation, the success rates are >90%. Laparoscopic and robotic techniques have minimized the morbidity related to such surgery. With the advent of the global program for eradication of filariasis initiated by the World Health Organization, the incidence of the disease is decreasing. Mass chemotherapy with diethyl carbamazine is the mainstay of this global program. Many years after eliminating filariasis, chyluria continue to occur in such populations, though in dwindling numbers. Future research should aim at finding more efficacious sclerosing agents with minimal recurrences.
Assuntos
Quilo , Filariose Linfática/terapia , Filaricidas/uso terapêutico , Transtornos Urinários/prevenção & controle , Wuchereria bancrofti/patogenicidade , Animais , Dietilcarbamazina/uso terapêutico , Filariose Linfática/complicações , Filariose Linfática/epidemiologia , Filariose Linfática/parasitologia , Glucose/administração & dosagem , Humanos , Povidona-Iodo/administração & dosagem , Recidiva , Escleroterapia/métodos , Resultado do Tratamento , Transtornos Urinários/epidemiologia , Transtornos Urinários/etiologia , Transtornos Urinários/urina , UrinaRESUMO
BACKGROUND & OBJECTIVES: Different developmental stages of Wuchereria bancrofti, the major causal organism of lymphatic filariasis (LF), are difficult to obtain. Beside this limitation, to obtain complete coding sequence (CDS) of a gene one has to isolate mRNA and perform subsequent cDNA synthesis which is laborious and not successful at times. In this study, an alternative strategy employing polymerase chain reaction (PCR) was optimized and validated, to generate CDS of Macrophage migration Inhibitory Factor-2 (wbMIF-2), a gene expressed in the transition stage between L3 to L4. METHODS: The genomic DNA of W. bancrofti microfilariae was extracted and used to amplify the full length wbMIF-2 gene (4.275 kb). This amplified product was used as a template for amplifying the exons separately, using the overlapping primers, which were then assembled through another round of PCR. RESULTS: A simple strategy was developed based on PCR, which is used routinely in molecular biology laboratories. The amplified CDS of 363 bp of wbMIF-2 generated using genomic DNA splicing technique was devoid of any intronic sequence. INTERPRETATION & CONCLUSIONS: The cDNA of wbMIF-2 gene was successfully amplified from genomic DNA of microfilarial stage of W. bancrofti thus circumventing the use of inaccessible L3-L4 transitional stage of this parasite. This strategy is useful for generating CDS of genes from parasites that have restricted availability.
Assuntos
Filariose Linfática/diagnóstico , Filariose Linfática/genética , Fatores Inibidores da Migração de Macrófagos/genética , Wuchereria bancrofti/genética , Animais , DNA Complementar/genética , DNA Complementar/isolamento & purificação , Filariose Linfática/parasitologia , Éxons/genética , Humanos , Fatores Inibidores da Migração de Macrófagos/isolamento & purificação , Reação em Cadeia da Polimerase , Wuchereria bancrofti/isolamento & purificação , Wuchereria bancrofti/patogenicidadeRESUMO
BACKGROUND: Diagnostic tools for lymphatic filariasis (LF) elimination programs are useful in mapping the distribution of the disease, delineating areas where mass drug administrations (MDA) are required, and determining when to stop MDA. The prevalence and burden of LF have been drastically reduced following mass treatments, and the evaluation of the performance of circulating filarial antigen (CFA)-based assays was acknowledged to be of high interest in areas with low residual LF endemicity rates after multiple rounds of MDA. The objective of this study was therefore to evaluate the immunochromatographic test (ICT) sensitivity in low endemicity settings and, specifically, in individuals with low intensity of lymphatic filariasis infection. METHODS: To perform this study, calibrated thick blood smears, ICT and Og4C3 enzyme-linked immunosorbent assay (ELISA) were carried out by night to identify Wuchereria bancrofti microfilarial and circulating filarial antigen carriers. A threshold determination assay regarding ICT and ELISA was performed using serial plasma dilutions from individuals with positive microfilarial counts. RESULTS: All individuals harbouring microfilariae (positive blood films) were detected by ICT and ELISA, but among individuals positive for ELISA, only 35.7 % of them were detected using ICT (Chi square: 4.57; p-value = 0.03), indicating a moderate agreement between both tests (kappa statistics = 0.49). Threshold determination analyses showed that ELISA was still positive at the last plasma dilution with negative ICT result. CONCLUSIONS: These findings suggest a loss of sensitivity for ICT in low endemicity settings, especially in people exhibiting low levels of circulating filarial antigen, raising serious concern regarding the monitoring and evaluation procedures in the framework of LF elimination program.
Assuntos
Antígenos de Helmintos/sangue , Filariose Linfática/diagnóstico , Imunoensaio/métodos , Animais , Antígenos de Helmintos/imunologia , Camarões/epidemiologia , Filariose Linfática/epidemiologia , Filariose Linfática/prevenção & controle , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Masculino , Sensibilidade e Especificidade , Wuchereria bancrofti/imunologia , Wuchereria bancrofti/patogenicidadeRESUMO
Lymphatic filariasis, a mosquito-borne parasitic disease, affects more than 120 million people worldwide. Vaccination for filariasis by targeting different stages of the parasite will be a boon to the existing MDA efforts of WHO which required repeated administration of the drug to reduce the infection level and sustained transmission. Onset of a filaria-specific immune response achieved through antigen vaccines can act synergistically with these drugs to enhance the parasite killing. Multi-epitope vaccine approach has been proved to be successful against several parasitic diseases as it overcomes the limitations associated with the whole antigen vaccines. Earlier results from our group suggested the protective efficacy of multi-epitope vaccine comprising two immunodominant epitopes from Brugia malayi antioxidant thioredoxin (TRX), several epitopes from transglutaminase (TGA) and abundant larval transcript-2 (ALT-2). In this study, the prophylactic efficacy of the filarial epitope protein (FEP), a chimera of selective epitopes identified from our earlier study, was tested in a murine model (jird) of filariasis with L3 larvae. FEP conferred a significantly (P < 0.0001) high protection (69.5%) over the control in jirds. We also observed that the multi-epitope recombinant construct (FEP) induces multiple types of protective immune responses, thus ensuring the successful elimination of the parasite; this poses FEP as a potential vaccine candidate.
Assuntos
Filariose Linfática/prevenção & controle , Epitopos Imunodominantes/administração & dosagem , Vacinas Protozoárias/imunologia , Proteínas Recombinantes de Fusão/administração & dosagem , Animais , Anticorpos Anti-Helmínticos/imunologia , Anticorpos Antiprotozoários/sangue , Antígenos de Helmintos/imunologia , Brugia Malayi/imunologia , Brugia Malayi/patogenicidade , Modelos Animais de Doenças , Gerbillinae , Proteínas de Helminto/imunologia , Humanos , Epitopos Imunodominantes/imunologia , Masculino , Camundongos , Vacinas Protozoárias/administração & dosagem , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes/imunologia , Tiorredoxinas/imunologia , Transglutaminases/imunologia , Vacinação , Wuchereria bancrofti/patogenicidadeRESUMO
In India diurnally subperiodic filariasis (DspWB) is prevalent only in the Nicobar district of Andaman and Nicobar Islands. Studies undertaken at different points of time indicate that this form of filariasis is restricted to a small region in Nancowry group of islands where it is transmitted by mosquito Downsiomyia nivea, a day biting mosquito. Studies on prevalence, distribution, and assessment of endemicity status, vector incrimination, bioecology, host seeking behaviour, population dynamics of the vector, transmission dynamics and clinical epidemiology indicate the prevalence and persistence of this infection in the Nancowry group of islands with perennial transmission. There was no control programme in these islands, until the National programme to eliminate filariasis was launched in 2004. Eight rounds of annual mass drug administration (MDA) with diethyl carbamazine (DEC) + albendazole have been completed. Despite this, microfilaria prevalence remains at above one per cent, the level identified for initiating transmission assessment survey to decide on continuation of MDA further. This necessitates adjunct measures to the ongoing MDA programme in these islands. The vector control options could be an adjunct measure, but the vector is a forest dweller with a unique bio-ecology, therefore, not a technically feasible option. Use of DEC fortified salt for six months to one year could hasten the process of elimination. Although administration of DEC-fortified salt is simple, rapid, safe, and cost-effective, challenges are to be tackled for evolving operationally realistic strategy. Such a strategy requires commitment of all sections of the society, a distribution mechanism that ensures the use of DEC-fortified salt in the Nancowry islands. Here we discuss the plan of action to serve the indigenous communities and operationalizing DEC fortified salt strategy through an inter-sectoral approach involving multiple stakeholders.
Assuntos
Aedes/patogenicidade , Filariose/epidemiologia , Filariose/transmissão , Wuchereria bancrofti/patogenicidade , Animais , Filariose/prevenção & controle , Filaricidas/uso terapêutico , Humanos , Índia/epidemiologia , Insetos Vetores/patogenicidadeRESUMO
After 6 months of a trip to Haiti, a 25-year-old healthy man presented with a 6-week history of a very slow progressive intermittent bilateral testicular pain and swelling. The biopsies in both testicles revealed the presence of a dead filarial parasite. Polymerase chain reaction products of the DNA from the biopsy were shown to have a 100% identity to Wuchereria bancrofti. Despite being uncommon in travelers, this presentation of W. bancrofti highlights the possibility of acquiring W. bancrofti during short-term trips to highly endemic regions of the world (i.e., Haiti).
Assuntos
Filariose Linfática/parasitologia , Testículo/parasitologia , Wuchereria bancrofti/fisiologia , Adulto , Animais , Filariose Linfática/diagnóstico , Filariose Linfática/patologia , Haiti , Humanos , Masculino , Testículo/patologia , Viagem , Wuchereria bancrofti/patogenicidadeRESUMO
BACKGROUND & OBJECTIVES: In India, diurnally sub periodic Wuchereria bancrofti transmitted by Downsiomyia nivea is prevalent only in the Nicobar district of Andaman and Nicobar Islands. The ongoing LF elimination programme aims at transmission interruption by bringing down the microfilarie (mf) load in the community, which has implication on the parasite load in mosquito vector. Therefore, understanding density dependent constraints on transmission assumes significance from control perspective. The present study was undertaken in Teressa Island to understand the density dependent parasite mortality and survival probability of the parasite Do. nivea. METHODS: The entomological data collected from Teressa Island, endemic for the diurnally sub periodic form of W. bancrofti were used to examine the parasite loss and its survival up to infectivity. Patterns of parasite distribution in Do. nivea were examined. RESULTS: Distribution patterns of microfilariae were found to be over dispersed in Do. nivea. The later stages of the parasite in the vector were randomly distributed. Distribution pattern of various filarial larval stages suggested that the loss of parasites occurred as development progressed and was maximal between the first and second stages. Further, both the prevalence of infection and the degree of parasite aggregation in the vector population have fallen significantly with development of parasite stage. INTERPRETATION & CONCLUSIONS: Results indicate the operation of parasite density dependent mortality of vectors or parasite loss or combination of both. The present study with Aedes transmitted filariasis conducted before launching LF elimination programme in the study area indicates a comparable level of parasite regulation in the vector which has similar implications on the transmission threshold. Thus, the consideration of Aedes with Culex in deriving the critical level of antigen positive for making decisions on cessation of mass drug administration (MDA) can be justified. However, with MDA aiming at reducing parasite load in the community, the operation of density dependent factor in the transmission becomes less pronounced in the subsequent rounds of MDA.