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The epidemiology of lymphatic filariasis in Ghana, explained by the possible existence of two strains of Wuchereria bancrofti.

ABSTRACT: INTRODUCTION:Lymphatic filariasis is a debilitating disease caused by the filarial worm Wuchereria bancrofti. It is earmarked for elimination by the year 2020 through the Global Program for the Elimination of LF (GPELF). In Ghana, mass treatment has been on-going since the year 2000. Earlier studies have revealed differing epidemiology of LF in the North and South of Ghana. This study was therefore aimed at understanding the possible impacts of W. bancrofti diversity on the epidemiology and control of LF in Ghana. METHODS:The Mitochondrial, Cytochrome C Oxidase I gene of W. bancrofti samples was sequenced and analyzed. The test sequences were grouped into infrapopulations, and pairwise differences (?) and mutation rates (?) were computed. The amount of variance within and among populations was also computed using the AMOVA. The evolutionary history was inferred using the Maximum Parsimony method. RESULTS:Seven samples from the South and 15 samples from the North were sequenced, and submitted to GenBank with accession numbers GQ479497- GQ479518. The results revealed higher mutation frequencies in the southern population, compared to the northern population. Haplotype analyses revealed a total of 11 haplotypes (Hap) in all the 22 DNA sequences, with high genetic variation and polymorphisms within the southern samples. CONCLUSION:This study showed that there is considerable genetic variability within W. bancrofti populations in Ghana, differences that might explain the observed epidemiology of LF. Further studies are however required for an in-depth understanding of LF epidemiology and control.

SUBMITTER: de Souza DK

PROVIDER: S-EPMC4218648 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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The epidemiology of lymphatic filariasis in Ghana, explained by the possible existence of two strains of Wuchereria bancrofti.

de Souza Dziedzom Komi DK Osei-Poku Jewelna J Blum Julia J Baidoo Helena H Brown Charles Addoquaye CA Lawson Bernard Walter BW Wilson Michael David MD Bockarie Moses John MJ Boakye Daniel Adjei DA

The Pan African medical journal 20140226

<h4>Introduction</h4>Lymphatic filariasis is a debilitating disease caused by the filarial worm Wuchereria bancrofti. It is earmarked for elimination by the year 2020 through the Global Program for the Elimination of LF (GPELF). In Ghana, mass treatment has been on-going since the year 2000. Earlier studies have revealed differing epidemiology of LF in the North and South of Ghana. This study was therefore aimed at understanding the possible impacts of W. bancrofti diversity on the epidemiology ...[more]

PMID: 25374638

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Project description:BackgroundLymphatic filarial parasites survive within the lymphatic vessels for years despite the complex immune environment surrounding them. Parasites possibly accomplish this by adopting various immunomodulatory strategies, which include release of glutathione-S-transferases (GSTs) that counteract the oxidative free radicals produced by the host. Since GSTs produced by parasites appear to be critical for the survival of parasites in the host, several studies evaluated the potential of parasite GSTs as vaccine candidates especially against schistosomiasis, fascioliasis and Seteria cervi. However, vaccine potential of GSTs of lymphatic filarial parasites has not been evaluated before.Methods/principal findingsIn the present study, the GST gene was cloned from the third stage larval (L3) cDNA libraries of Wuchereria bancrofti, and recombinant GST (WbGST) was expressed and purified. Serum samples from individuals living in an endemic area were analyzed for their reactivity with rWbGST. These findings showed that sera from endemic normal individuals (EN) carry significant levels of anti-WbGST IgG antibodies compared to subjects who are microfilaraemic (Mf) or show symptoms of clinical pathology (CP). Isotype analysis of the anti-WbGST IgG antibodies showed a predominance of IgG1 and IgG3 antibodies in EN individuals. Subsequent functional analysis of the rWbGST showed that the rWbGST protein retained the enzymatic activity of GST and the antibodies in EN sera could inhibit this enzymatic activity. Similar results were obtained when anti-rWbGST antibodies raised in mice were used in the neutralization assay. Brugia malayi GST and WbGST show significant sequence similarity. Therefore, to evaluate the vaccine potential of rWbGST, we used B. malayi L3 as challenge parasites. Vaccine potential of rWbGST was initially evaluated by confirming the role of human and mice WbGST antibodies in an antibody dependent cellular cytotoxicity (ADCC) assay. Subsequent vaccination studies in a jird model showed that approximately 61% protection could be achieved against a B. malayi L3 challenge infection in jirds immunized with rWbGST.ConclusionsResults of this study show that rWbGST is a potential vaccine candidate against lymphatic filariasis. Nearly 61% protection can be achieved against a B. malayi challenge infection in a jird model. The study also showed that the WbGST protein retained the enzymatic activity of GST and this enzymatic activity appears to be critical for the survival of the parasite in the host.

Project description:BACKGROUND:Lymphatic filariasis (LF) is widely endemic in Côte d'Ivoire, and elimination as public health problem (EPHP) is based on annual mass drug administration (MDA) using ivermectin and albendazole. To guide EPHP efforts, we evaluated Wuchereria bancrofti infection indices among humans, and mosquito vectors after four rounds of MDA in four cross-border health districts of Côte d'Ivoire. METHODOLOGY:We monitored people and mosquitoes for W. bancrofti infections in the cross-border health districts of Aboisso, Bloléquin, Odienné and Ouangolodougou, Côte d'Ivoire. W. bancrofti circulating filarial antigen (CFA) was identified using filariasis test strips, and antigen-positive individuals were screened for microfilaremia. Moreover, filarial mosquito vectors were sampled using window exit traps and pyrethrum sprays, and identified morphologically at species level. Anopheles gambiae s.l. and Culex quinquefasciatus females were analyzed for W. bancrofti infection using polymerase chain reaction (PCR) technique. PRINCIPAL FINDINGS:Overall, we found a substantial decline in W. bancrofti infection indices after four rounds of MDA compared to pre-MDA baseline data. CFA prevalence fell from 3.38-5.50% during pre-MDA to 0.00-1.53% after MDA interventions. No subjects had detectable levels of CFA in Ouangolodougou. Moreover, post-MDA CFA prevalence was very low, and below the 1% elimination threshold in Aboisso (0.19%) and Odienné (0.49%). Conversely, CFA prevalence remained above 1% in Bloléquin (1.53%). W. bancrofti microfilariae (Mf) were not found in Aboisso, Bloléquin, and Ouangolodougou, except for Odienné with low prevalence (0.16%; n = 613) and microfilaremia of 32.0 Mf/mL. No An. gambiae s.l. and Cx. quinquefasciatus pools were infected with W. bancrofti in Bloléquin and Ouangolodougou, while they exhibited low infection rates in Aboisso (1% and 0.07%), and Odienné (0.08% and 0.08%), respectively. CONCLUSIONS:In cross-border areas of Côte d'Ivoire, LF infection indices in humans and mosquito vectors substantially declined after four rounds of MDA. CFA prevalence fell under the World Health Organization (WHO)-established threshold (1%) in Aboisso, Ouangolodougou and Odienné. Moreover, W. bancrofti prevalence in mosquitoes was lower than WHO-established threshold (2%) in all areas. This might suggest the interruption of W. bancrofti transmission, and possible MDA cessation. However, a formal transmission assessment survey (TAS) and molecular xenomonitoring in mosquito vectors should be implemented before eventual MDA cessation. However, MDA should pursue in Bloléquin where W. bancrofti infection prevalence remained above 1%. Our results provided important ramifications for LF control efforts towards EPHP in Côte d'Ivoire.

Project description:Wuchereria bancrofti (Wb) is the most widely distributed of the three nematodes known to cause lymphatic filariasis (LF), the other two being Brugia malayi and Brugia timori. Current tools available to monitor LF are limited to diagnostic tests targeting DNA repeats, filarial antigens, and anti-filarial antibodies. While these tools are useful for detection and surveillance, elimination programs have yet to take full advantage of molecular typing for inferring infection history, strain fingerprinting, and evolution. To date, molecular typing approaches have included whole mitochondrial genomes, genotyping, targeted sequencing, and random amplified polymorphic DNA (RAPDs). These studies have revealed much about Wb biology. For example, in one study in Papua New Guinea researchers identified 5 major strains that were widespread and many minor strains some of which exhibit geographic stratification. Genome data, while rare, has been utilized to reconstruct evolutionary relationships among taxa of the Onchocercidae (the clade of filarial nematodes) and identify gene synteny. Their phylogeny reveals that speciation from the common ancestor of both B. malayi and Wb occurred around 5-6 millions years ago with shared ancestry to other filarial nematodes as recent as 15 million years ago. These discoveries hold promise for gene discovery and identifying drug targets in species that are more amenable to in vivo experiments. Continued technological developments in whole genome sequencing and data analysis will likely replace many other forms of molecular typing, multiplying the amount of data available on population structure, genetic diversity, and phylogenetics. Once widely available, the addition of population genetic data from genomic studies should hasten the elimination of LF parasites like Wb. Infectious disease control programs have benefited greatly from population genetics data and recently from population genomics data. However, while there is currently a surplus of data for diseases like malaria and HIV, there is a scarcity of this data for filarial nematodes. With the falling cost of genome sequencing, research on filarial nematodes could benefit from the addition of population genetics statistics and phylogenetics especially in dealing with elimination programs. A comprehensive review focusing on population genetics of filarial nematode does not yet exist. Here our goal is to provide a current overview of the molecular epidemiology of W. bancrofti (Wb) the primary causative agent of LF. We begin by reviewing studies utilizing molecular typing techniques with specific focus on genomic and population datasets. Next, we used whole mitochondrial genome data to construct a phylogeny and examine the evolutionary history of the Onchocercidae. Then, we provide a perspective to aid in understanding how population genetic techniques translate to modern epidemiology. Finally, we introduce the concept of genomic epidemiology and provide some examples that will aid in future studies of Wb.

Dataset Information

The epidemiology of lymphatic filariasis in Ghana, explained by the possible existence of two strains of Wuchereria bancrofti.

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The epidemiology of lymphatic filariasis in Ghana, explained by the possible existence of two strains of Wuchereria bancrofti.

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