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We present a framework for identifying when conditions are favourable for transmission of vector-borne diseases between communities by incorporating predicted disease prevalence mapping with landscape analysis of sociological, environmental and host/parasite genetic data. We explored the relationship between environmental features and gene flow of a filarial parasite of humans, Onchocerca volvulus, and its vector, blackflies in the genus Simulium. We generated a baseline microfilarial prevalence map from point estimates from 47 locations in the ecological transition separating the savannah and forest in Ghana, where transmission of O. volvulus persists despite onchocerciasis control efforts. We generated movement suitability maps based on environmental correlates with mitochondrial population structure of 164 parasites from 15 communities and 93 vectors from only four sampling sites, and compared these to the baseline prevalence map. Parasite genetic distance between sampling locations was significantly associated with elevation (r = .793, p = .005) and soil moisture (r = .507, p = .002), while vector genetic distance was associated with soil moisture (r = .788, p = .0417) and precipitation (r = .835, p = .0417). The correlation between baseline prevalence and parasite resistance surface maps was stronger than that between prevalence and vector resistance surface maps. The centre of the study area had high prevalence and suitability for parasite and vector gene flow, potentially contributing to persistent transmission and suggesting the importance of re-evaluating transmission zone boundaries. With suitably dense sampling, this framework can help delineate transmission zones for onchocerciasis and would be translatable to other vector-borne diseases.
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Flujo Génico , Insectos Vectores , Onchocerca volvulus , Oncocercosis , Simuliidae , Animales , Oncocercosis/transmisión , Oncocercosis/epidemiología , Insectos Vectores/genética , Insectos Vectores/parasitología , Simuliidae/genética , Simuliidae/parasitología , Humanos , Ghana/epidemiología , Onchocerca volvulus/genética , Prevalencia , Genética de Población , AmbienteRESUMEN
The impact of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) (initiated in 2000 in Ghana and ran for 12 years) in mitigating soil-transmitted helminth (STH) infections in LF-endemic areas is unknown. During a 1-year hiatus which ensued between 2011 and 2012, a longitudinal study was conducted to determine GPELF effect on hookworm infections in selected communities involved in the programme since its inception, while measuring the effectiveness of biannual ALB treatments on schoolchildren living in such communities. A total of 399 school children aged 3 to 18 years were randomly selected from four communities in the Kpandai district of northern Ghana. Each presented a single stool sample at baseline, 21 days post-treatment, at the 3rd and 6th months, 21 days post-second intervention (i.e. following sample collection and treatment with ALB in the 6th month), and in the ninth month of the study period. Haemoglobin (hb) levels were also measured at all time points using finger prick blood samples and a URIT digital test kit. Each participant submitting a sample, was treated with a single-dose ALB (400mg) at baseline and in the sixth month. Stool samples were processed by preparing duplicate Kato-Katz slides per sample, and examined by microscopy. The Body Mass Index-for-age z-scores (BAZ) of participants were assessed following the determination of BMIs at each time point by measuring their height and weight with a stadiometer and weighing scale. Overall hookworm prevalences were 25.68% (95% CI = 20.51-31.75) at baseline, 11.18% (95% CI = 7.87-15.41) 21 days post-treatment, 11.78% (95% CI = 8.38-16.11) and 6.95% (95% CI = 4.41-10.43) in the 3rd and 6th months, 0.91% (95% CI = 0.19-2.65) 21 days post-second intervention, and 8.46% (95% CI = 5.62-12.23) in the ninth month. Observed overall faecal egg count reduction rates (ERRs) were 94.21% (95% CI = 81.50%- 100.00%) 21 days after baseline treatment, 97.70% (95% CI = 85.08-100.00) and 96.95% (95% CI = 84.18%- 100.00%) in the 3rd and 6th months, 99.98% (95% CI = 86.42%- 100.00%) 21 days post-second intervention, and 17.18% (95% CI = 14.07%- 20.67%) in the 9th month. Respective cure rates (CRs) were 62.35% (95% CI = 46.71-81.56%), 85.88% (95% CI = 67.32-100.00%), 87.06% (95% CI = 68.36%- 100.00%), 98.82% (95% CI = 78.83%- 100.00%), and 36.36% (95% CI = 9.91%- 93.11%). Additionally, increases in the percent frequency of 'normal hb' (p < 0.01) were observed across the study time points, whilst 'normal BAZ' cases remained high (from 94.87% to 98.87%) throughout the study period. These findings primarily indicate satisfactory effectiveness of ALB which may be maintainable in mass drug administration programmes by the modification of treatment strategies from annual to bi-annual regimes. This could minimize the likelihood of emerging poorly-responding hookworm phenotypes in Ghana. Additionally, a positive impact of bi-annual treatment on participant anaemia status is herein indicated with particular regard to the school children in our cohort.
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Anemia , Antihelmínticos , Filariasis Linfática , Helmintiasis , Infecciones por Uncinaria , Niño , Humanos , Albendazol/uso terapéutico , Índice de Masa Corporal , Ghana/epidemiología , Estudios Longitudinales , Infecciones por Uncinaria/tratamiento farmacológico , Infecciones por Uncinaria/epidemiología , Anemia/tratamiento farmacológico , Anemia/epidemiología , Heces , Antihelmínticos/uso terapéutico , SueloRESUMEN
Introduction: Alzheimer's disease (AD) is a neurodegenerative disorder with no conclusive remedy. Yohimbine, found in Rauwolfia vomitoria, may reduce brain inflammation by targeting tumour necrosis factor-alpha (TNFα), implicated in AD pathogenesis. Metoserpate, a synthetic compound, may inhibit TNFα. The study is aimed at assessing the potential utility of repurposing metoserpate for TNFα inhibition to reduce neuronal damage and inflammation in AD. The development of safe and effective treatments for AD is crucial to address the growing burden of the disease, which is projected to double over the next two decades. Methods: Our study repurposed an FDA-approved drug as TNFα inhibitor for AD management using structural similarity studies, molecular docking, and molecular dynamics simulations. Yohimbine was used as a reference compound. Molecular docking used SeeSAR, and molecular dynamics simulation used GROMACS. Results: Metoserpate was selected from 10 compounds similar to yohimbine based on pharmacokinetic properties and FDA approval status. Molecular docking and simulation studies showed a stable interaction between metoserpate and TNFα over 100 ns (100000 ps). This suggests a reliable and robust interaction between the protein and ligand, supporting the potential utility of repurposing metoserpate for TNFα inhibition in AD treatment. Conclusion: Our study has identified metoserpate, a previously FDA-approved antihypertensive agent, as a promising candidate for inhibiting TNFα in the management of AD.
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Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/metabolismo , Simulación del Acoplamiento Molecular , Factor de Necrosis Tumoral alfa , Reposicionamiento de Medicamentos , Simulación de Dinámica Molecular , Yohimbina/farmacología , Yohimbina/uso terapéuticoRESUMEN
National programs in Africa have expanded their objectives from control of onchocerciasis (river blindness) as a public health problem to elimination of parasite transmission, motivated by the reduction of Onchocerca volvulus infection prevalence in many African meso- and hyperendemic areas due to mass drug administration of ivermectin (MDAi). Given the large, contiguous hypo-, meso-, and hyperendemic areas, sustainable elimination of onchocerciasis in sub-Saharan Africa requires delineation of geographic boundaries for parasite transmission zones, so that programs can consider the risk of parasite re-introduction through vector or human migration from areas with ongoing transmission when making decisions to stop MDAi. We propose that transmission zone boundaries can be delineated by characterising the parasite genetic population structure within and between potential zones. We analysed whole mitochondrial genome sequences of 189 O. volvulus adults to determine the pattern of genetic similarity across three West African countries: Ghana, Mali, and Côte d'Ivoire. Population genetic structure indicates that parasites from villages near the Pru, Daka, and Black Volta rivers in central Ghana belong to one parasite population, indicating that the assumption that river basins constitute individual transmission zones is not supported by the data. Parasites from Mali and Côte d'Ivoire are genetically distinct from those from Ghana. This research provides the basis for developing tools for elimination programs to delineate transmission zones, to estimate the risk of parasite re-introduction via vector or human movement when intervention is stopped in one area while transmission is ongoing in others, to identify the origin of infections detected post-treatment cessation, and to investigate whether persisting prevalence despite ongoing interventions in one area is due to parasites imported from others.
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Genoma Mitocondrial , Indanos , Onchocerca volvulus , Oncocercosis , Adulto , Animales , Humanos , Oncocercosis/epidemiología , Oncocercosis/prevención & control , Onchocerca volvulus/genética , África Occidental , Ivermectina/uso terapéuticoRESUMEN
With safely managed water accessible to only 19% of the population in Ghana, the majority of its residents are at risk of drinking contaminated water. Furthermore, this water could be a potential vehicle for the transmission of antimicrobial-resistant bacteria. This study assessed the presence of bacteria and the antibiotic resistance profile of Escherichia coli and Pseudomonas aeruginosa in drinking-water sources using membrane filtration and Kirby-Bauer disc diffusion methods. A total of 524 water samples were analyzed for total coliforms, total heterotrophic bacteria, E. coli and P. aeruginosa. Samples included sachets, bottled water, tap water, borehole and well water. Most of the sachet and bottled water samples were within the limits of Ghana's standards for safe drinking water for the parameters tested. Over 50% of tap and borehole water was also free of E. coli and P. aeruginosa. Overall, of 115 E. coli isolates from tap and ground water samples, most were resistant to cefuroxime (88.7%), trimethoprim-sulfamethoxazole (62.6%) and amoxicillin-clavulanate (52.2%). P. aeruginosa isolates were most resistant to aztreonam (48%). Multidrug resistance was predominantly seen among E. coli isolates (58%). Evidence from this study calls for routine antimicrobial resistance surveillance in drinking water across the country and additional treatment of water sources at household levels.
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Agua Potable , Amoxicilina , Antibacterianos/farmacología , Aztreonam , Bacterias , Cefuroxima , Ácido Clavulánico , Estudios Transversales , Agua Potable/microbiología , Escherichia coli , Ghana/epidemiología , Combinación Trimetoprim y SulfametoxazolRESUMEN
INTRODUCTION: Safety of the environment in which vegetables are grown, marketed and consumed is paramount as most are eaten raw. Irrigation sources include open drains and streams, which are often contaminated with human and animal waste due to poor sanitation infrastructure. In irrigated vegetable farms using such sources in Ghana, we assessed Escherichia coli counts, antibiotic resistance patterns and resistant genes on irrigated lettuce. METHODS: A cross-sectional study was conducted between January-May 2022, involving five major vegetable farms in Ghana. RESULTS: Escherichia coli was found in all 25 composite lettuce samples analyzed. Counts expressed in CFU/g ranged from 186 to 3000, with the highest counts found in lettuce irrigated from open drains (1670) and tap water using hose pipes (3000). Among all bacterial isolates, resistance ranged between 49% and 70% for the Watch group of antibiotics, 59% for the Reserved group and 82% were multidrug-resistant. Of 125 isolates, 60 (48%) were extended-spectrum beta-lactamase-producing, of which five (8%) had the blaTEM-resistant gene. CONCLUSIONS: Lettuce was contaminated with Escherichia coli with high levels of antibiotic resistance. We call on the Ghana Ministry of Food and Agriculture, Food and Drugs Authority and other stakeholders to support farmers to implement measures for improving vegetable safety.
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Infecciones por Escherichia coli , Ensaladas , Animales , Antibacterianos/farmacología , Estudios Transversales , Farmacorresistencia Microbiana , Escherichia coli , Ghana , Humanos , Lactuca , Verduras/microbiología , Agua , beta-Lactamasas/genéticaRESUMEN
Alzheimer's disease (AD), which is a progressive neurodegenerative disorder is the most common form of dementia globally. Several studies have suggested alteration in the gut microbiota and HSV-1 infection as contributing factors to the development of the disease. As at now, there are no AD attenuating agents and AD pharmacotherapy is focused on managing symptoms while plants used in ethnomedicine remain potential sources of drugs for the treatment of the condition. Here, we reviewed published databases for African ethnomedicinal plants and functional foods of African origin that are used in the management of AD-related phenotypes, treatment of herpes simplex virus -1 (HSV-1) and/or improvement of gut microbiota. A total of 101 unique plant species and 24 different types of traditionally prepared African functional foodstuff were identified. Of the 101 identified plant species, 50 species serve as functional foodstuffs. Twenty-three (23) of the ethnomedicinal plant families were successfully identified for the treatment and management of AD-related phenotypes and age-related dementia. Eighteen (18) African plant species from 15 families were also identified as potent remedies for HSV-1; while many African wild fruits (3 species), roots and tubers (7 species), leafy vegetables (14 species), and seaweeds (26 species) were functional foods for modifying AD-related phenotypes. It was concluded that African medicinal plants are potential sources of both AD attenuating agents and phytocompounds that may be used against HSV-1 infection and alteration of gut microbiota. Additionally, a number of African functional foods are important sources of prebiotics and probiotics.
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Enfermedad de Alzheimer , Microbioma Gastrointestinal , Herpes Simple , Herpesvirus Humano 1 , Plantas Medicinales , Enfermedad de Alzheimer/tratamiento farmacológico , Alimentos Funcionales , Herpes Simple/tratamiento farmacológico , FenotipoRESUMEN
The modern and rapid avenue for detecting pathogens provided by molecular genetic techniques including polymerase chain reaction (PCR) was explored in the present study to identify prevalent disease pathogens, from six aquaculture farms and in two commonly cultured fish in Ghana. The specific detection was carried out directly on clinical samples of naturally infected fish (O. niloticus and C. gariepinus) based on syber-mix reaction protocol in traditional PCR. Molecular diagnostic techniques allowed the detection of the six most common and important bacterial pathogens in aquaculture farms in Ghana. Also, three of the pathogens (Streptococcus agalactiae, Streptococcus iniae, and Staphylococcus aureus) were simultaneously isolated in a multiplex reaction. The results indicated 90-100% sensitivity and specificity for each of the six bacterial pathogens tested. Streptococcosis and motile aeromonad septicemia were found to be highly prevalent in most aquaculture farms in Ghana with severity in infections traced to the 85.7% and 14.9% co-infections with all six target pathogens in catfish and tilapia respectively. The prevalence rate of infections significantly correlated with variations in salinity, conductivity, and dissolved oxygen concentrations in the thermal stressed condition of the culture water. Multiplex techniques employed in this study represent one of the first to be used by a fish health laboratory in Ghana for rapid detection of pathogens in diseased fish and could be a useful alternative to the culture-based method for routine diagnosis of fish diseases in Ghana.
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Enfermedades de los Peces , Infecciones Estreptocócicas , Animales , Bacterias/genética , Enfermedades de los Peces/diagnóstico , Enfermedades de los Peces/epidemiología , Enfermedades de los Peces/microbiología , Peces , Ghana/epidemiología , Reacción en Cadena de la Polimerasa Multiplex/métodos , Prevalencia , Infecciones Estreptocócicas/diagnóstico , Infecciones Estreptocócicas/epidemiología , Infecciones Estreptocócicas/veterinaria , Streptococcus agalactiae/genéticaRESUMEN
The COVID-19 pandemic is one of the fastest evolving pandemics in recent history. As such, the SARS-CoV-2 viral evolution needs to be continuously tracked. This study sequenced 1123 SARS-CoV-2 genomes from patient isolates (121 from arriving travellers and 1002 from communities) to track the molecular evolution and spatio-temporal dynamics of the SARS-CoV-2 variants in Ghana. The data show that initial local transmission was dominated by B.1.1 lineage, but the second wave was overwhelmingly driven by the Alpha variant. Subsequently, an unheralded variant under monitoring, B.1.1.318, dominated transmission from April to June 2021 before being displaced by Delta variants, which were introduced into community transmission in May 2021. Mutational analysis indicated that variants that took hold in Ghana harboured transmission enhancing and immune escape spike substitutions. The observed rapid viral evolution demonstrates the potential for emergence of novel variants with greater mutational fitness as observed in other parts of the world.
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COVID-19 , SARS-CoV-2 , COVID-19/epidemiología , Genoma Viral/genética , Ghana/epidemiología , Humanos , Mutación , Pandemias , Filogenia , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/genéticaRESUMEN
BACKGROUND: In onchocerciasis endemic areas in Africa, heterogenous biting rates by blackfly vectors on humans are assumed to partially explain age- and sex-dependent infection patterns with Onchocerca volvulus. To underpin these assumptions and further improve predictions made by onchocerciasis transmission models, demographic patterns in antibody responses to salivary antigens of Simulium damnosum s.l. are evaluated as a measure of blackfly exposure. METHODOLOGY/PRINCIPAL FINDINGS: Recently developed IgG and IgM anti-saliva immunoassays for S. damnosum s.l. were applied to blood samples collected from residents in four onchocerciasis endemic villages in Ghana. Demographic patterns in antibody levels according to village, sex and age were explored by fitting generalized linear models. Antibody levels varied between villages but showed consistent patterns with age and sex. Both IgG and IgM responses declined with increasing age. IgG responses were generally lower in males than in females and exhibited a steeper decline in adult males than in adult females. No sex-specific difference was observed in IgM responses. CONCLUSIONS/SIGNIFICANCE: The decline in age-specific antibody patterns suggested development of immunotolerance or desensitization to blackfly saliva antigen in response to persistent exposure. The variation between sexes, and between adults and youngsters may reflect differences in behaviour influencing cumulative exposure. These measures of antibody acquisition and decay could be incorporated into onchocerciasis transmission models towards informing onchocerciasis control, elimination, and surveillance.
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Anticuerpos/sangre , Mordeduras y Picaduras de Insectos/epidemiología , Saliva/inmunología , Simuliidae/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Niño , Preescolar , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Insectos Vectores/inmunología , Insectos Vectores/parasitología , Masculino , Persona de Mediana Edad , Onchocerca volvulus/crecimiento & desarrollo , Oncocercosis/epidemiología , Oncocercosis/transmisión , Simuliidae/parasitología , Adulto JovenRESUMEN
BACKGROUND: Simulium damnosum sensu lato (s.l.) blackflies transmit Onchocerca volvulus, a filarial nematode that causes human onchocerciasis. Human landing catches (HLCs) is currently the sole method used to estimate blackfly biting rates but is labour-intensive and questionable on ethical grounds. A potential alternative is to measure host antibodies to vector saliva deposited during bloodfeeding. In this study, immunoassays to quantify human antibody responses to S. damnosum s.l. saliva were developed, and the salivary proteome of S. damnosum s.l. was investigated. METHODOLOGY/PRINCIPAL FINDINGS: Blood samples from people living in onchocerciasis-endemic areas in Ghana were collected during the wet season; samples from people living in Accra, a blackfly-free area, were considered negative controls and compared to samples from blackfly-free locations in Sudan. Blackflies were collected by HLCs and dissected to extract their salivary glands. An ELISA measuring anti-S. damnosum s.l. salivary IgG and IgM was optimized and used to quantify the humoral immune response of 958 individuals. Both immunoassays differentiated negative controls from endemic participants. Salivary proteins were separated by gel-electrophoresis, and antigenic proteins visualized by immunoblot. Liquid chromatography mass spectrometry (LC-MS/MS) was performed to characterize the proteome of S. damnosum s.l. salivary glands. Several antigenic proteins were recognized, with the major ones located around 15 and 40 kDa. LC-MS/MS identified the presence of antigen 5-related protein, apyrase/nucleotidase, and hyaluronidase. CONCLUSIONS/SIGNIFICANCE: This study validated for the first time human immunoassays that quantify humoral immune responses as potential markers of exposure to blackfly bites. These assays have the potential to facilitate understanding patterns of exposure as well as evaluating the impact of vector control on biting rates. Future studies need to investigate seasonal fluctuations of these antibody responses, potential cross-reactions with other bloodsucking arthropods, and thoroughly identify the most immunogenic proteins.
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Mordeduras y Picaduras de Insectos/epidemiología , Insectos Vectores/fisiología , Saliva , Simuliidae/fisiología , Adolescente , Adulto , Anciano , Animales , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Femenino , Ghana , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Mordeduras y Picaduras de Insectos/inmunología , Masculino , Persona de Mediana Edad , Oncocercosis , SudánRESUMEN
Wastewater treatment plants receive sewage containing high concentrations of bacteria and antibiotics. We assessed bacterial counts and their antibiotic resistance patterns in water from (a) influents and effluents of the Legon sewage treatment plant (STP) in Accra, Ghana and (b) upstream, outfall, and downstream in the recipient Onyasia stream. We conducted a cross-sectional study of quality-controlled water testing (January-June 2018). In STP effluents, mean bacterial counts (colony-forming units/100 mL) had reduced E. coli (99.9% reduction; 102,266,667 to 710), A. hydrophila (98.8%; 376,333 to 9603), and P. aeruginosa (99.5%; 5,666,667 to 1550). Antibiotic resistance was significantly reduced for tetracycline, ciprofloxacin, cefuroxime, and ceftazidime and increased for gentamicin, amoxicillin/clavulanate, and imipenem. The highest levels were for amoxicillin/clavulanate (50-97%) and aztreonam (33%). Bacterial counts increased by 98.8% downstream compared to the sewage outfall and were predominated by E. coli, implying intense fecal contamination from other sources. There was a progressive increase in antibiotic resistance from upstream, to outfall, to downstream. The highest resistance was for amoxicillin/clavulanate (80-83%), cefuroxime (47-73%), aztreonam (53%), and ciprofloxacin (40%). The STP is efficient in reducing bacterial counts and thus reducing environmental contamination. The recipient stream is contaminated with antibiotic-resistant bacteria listed as critically important for human use, which needs addressing.
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BACKGROUND: Schistosomiasis remains a major public health issue with over 90% of the prevalence rates recorded in Sub-Saharan Africa. In this study, the relationships between different interleukin gene polymorphisms (IL-13-591A/G, IL-13-1055C/T, IL-13-1258A/G) and Schistosoma haematobium infection levels were evaluated; as well as the host plasma antibodies and cytokine profiles associated with schistosomiasis infection. METHODOLOGY: A total of 469 school children aged 6 to 19 years from four schistosomiasis-endemic communities in Ghana were involved. Single urine and stool samples were obtained from each pupil, processed via sedimentation and Kato-Katz, and examined via microscopy for Schistosoma and soil-transmitted helminth (STH) eggs. Next, venous blood samples were drawn from 350 healthy pupils, and used to measure antibody and plasma cytokine levels by ELISA. Single nucleotide polymorphisms in the IL-13 gene were genotyped on 71 selected blood samples using the Mass Array technique. PRINCIPAL FINDINGS AND CONCLUSION: The overall prevalence of urinary schistosomiasis was 21.11%. Community-level prevalences were 17.12%, 32.11%, 20.80%, and 15.32% for Asempaneye, Barikumah, Eyan Akotoguah, and Apewosika respectively. Generally, higher S. haematobium infection prevalence and intensity were recorded for participants with genotypes bearing the IL13-1055C allele, the IL13-591A, and the IL13-1258A alleles. Also, higher S. haematobium infection prevalence was observed among participants in the 12-14-year age group with the IL13-1055C, IL13-591A, and IL13-1258A alleles. Interestingly, higher STH prevalence was also observed among participants with the IL13-1055C, IL13-591A, and IL13-1258A alleles. Furthermore, the age-associated trends of measured antibodies and cytokines of S. haematobium-infected school-children depicted a more pro-inflammatory immune profile for pupils aged up to 1l years, and an increasingly anti-inflammatory profile for pupils aged 12 years and above. This work provides insight into the influence of IL-13 gene polymorphisms on S. haematobium, and STH infections, in school-aged children (SAC).
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Predisposición Genética a la Enfermedad , Factores Inmunológicos/metabolismo , Interleucina-13/genética , Esquistosomiasis Urinaria/epidemiología , Esquistosomiasis Urinaria/genética , Adolescente , Animales , Anticuerpos Antihelmínticos/química , Niño , Heces/parasitología , Femenino , Ghana/epidemiología , Humanos , Factores Inmunológicos/genética , Interleucina-13/sangre , Masculino , Recuento de Huevos de Parásitos , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple , Schistosoma haematobium , Esquistosomiasis Urinaria/orina , Adulto JovenRESUMEN
BACKGROUND: In Ghana, pre-school-aged children (PSAC) are at risk of intestinal schistosomiasis and are living in need of praziquantel treatment. To better assess the infection burden within this vulnerable demographic group, we have provided a comparative assessment of the prevalence of Schistosoma mansoni in pre-school-aged children by urine circulating cathodic antigen (CCA) dipsticks, real-time PCR Taqman® faecal assays and Kato-Katz coproscopy. METHODS: In all, 190 pre-school-aged children were sampled from three endemic communities (viz. Tomefa, Torgahkope/Adakope, and Manheam) around Weija dam, Southern Ghana. Fresh stool and urine samples were collected from all participants for diagnosis. RESULTS: Among all the three communities, the urine-CCA assay recorded the highest prevalence values of 90.5% (95% CI 80.4-96.4), 87.9% (95% CI 76.7-95), and 81.2% (95% CI 69.9-89.6) in Tomefa, Torgahkope/Adakope, and Manheam respectively. Prevalence by real-time PCR was 50% (95% CI 35.5-64.5), 8% (95% CI 2.2-19.2) and 16.7% (95% CI 8.3-28.5), while by Kato-Katz was 55.6% (95% CI 42.5-68.1), 8.6% (95% CI 2.9-19) and 11.6% (95% CI 5.1-21.6) respectively. Children aged 1 year and over were found to be positive with the urine-CCA assay; by the ages of 3-4, over 50% were urine-CCA patent. The sensitivity and specificity of the POC-CCA dipsticks, when compared against the combined results of Kato-Katz/TaqMan results was found to be 84.1% (95% CI = 72.7-92.1) and 12.9% (95% CI = 6.6-22) respectively. CONCLUSIONS: We propose that the urine-CCA dipstick may be a useful rapid diagnostic tool to estimate the prevalence of intestinal schistosomiasis in PSAC, particularly in rapid identification of at-risk areas. However, our assessment has shown that it possible to record false positives when compared to combined Kato-Katz and qPCR results. To guide PSAC praziquantel treatment needs, we propose the urine CCA assay should be included in routine surveillance of intestinal schistosomiasis alongside other diagnostics such as Kato-Katz and urine filtration.
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Antígenos Helmínticos/orina , Pruebas Diagnósticas de Rutina/métodos , Heces/parasitología , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Esquistosomiasis mansoni/diagnóstico , Urinálisis/métodos , Animales , Antígenos Helmínticos/análisis , Bioensayo/métodos , Líquidos Corporales/química , Líquidos Corporales/inmunología , Líquidos Corporales/parasitología , Preescolar , Heces/química , Femenino , Ghana/epidemiología , Humanos , Lactante , Masculino , Sistemas de Atención de Punto , Praziquantel/uso terapéutico , Prevalencia , Schistosoma mansoni/genética , Schistosoma mansoni/inmunología , Schistosoma mansoni/aislamiento & purificación , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomiasis mansoni/parasitología , Esquistosomiasis mansoni/orina , Sensibilidad y EspecificidadRESUMEN
To eliminate soil-transmitted helminth (STH) infections as a public health problem, the administration of benzimidazole (BZ) drugs to children has recently intensified. But, as drug pressure increases, the development of anthelmintic drug resistance (AR) becomes a major concern. Currently, there is no global surveillance system to monitor drug efficacy and the emergence of AR. Consequently, it is unclear what the current efficacy of the used drugs is and whether AR is already present. The aim of this study is to pilot a global surveillance system to assess anthelmintic drug efficacy and the emergence of AR in STH control programs. For this, we will incorporate drug efficacy trials into national STH control programs of eight countries (Bangladesh, Cambodia, Lao PDR, Vietnam, Ghana, Rwanda, Senegal and a yet to be defined country in the Americas). In each country, one trial will be performed in one program implementation unit to assess the efficacy of BZ drugs against STHs in school-aged children by faecal egg count reduction test. Stool samples will be collected before and after treatment with BZs for Kato-Katz analysis and preserved to purify parasite DNA. The presence and frequency of known single nucleotide polymorphisms (SNPs) in the ß-tubulin genes of the different STHs will subsequently be assessed. This study will provide a global pattern of drug efficacy and emergence of AR in STH control programs. The results will provide complementary insights on the validity of known SNPs in the ß-tubulin gene as a marker for AR in human STHs as well as information on the technical and financial resources required to set up a surveillance system. Finally, the collected stool samples will be an important resource to validate different molecular technologies for the detection of AR markers or to identify novel potential molecular markers associated with AR in STH.
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(1) Background: Current international policy for schistosomiasis and soil-transmitted helminthiasis (STH) control emphasises mass administration of deworming drugs in school-based programmes. However, this approach is insufficient to control the transmission of these diseases, and their burden in non-school cohorts is recognised, albeit under-researched. This research will investigate the feasibility and acceptability of expanding access to praziquantel (PZQ) against schistosomiasis, and albendazole (ALB) against STH, to communities in selected transmission settings in Ghana. (2) Methods: A three-site longitudinal study will be implemented to investigate the effectiveness of expanding treatment strategies for PZQ and ALB to community members. In the context of community mass drug administration (to preschool children, school non-attending children, and adults, including pregnant women), the intervention will be assessed in a random sample of community members, at baseline with follow-up at 6, 12, and 18 months. In each community, 658 participants will be enrolled, and 314 followed up at each time point. The primary outcome measure is the prevalence of infection of Schistosoma haematobium and/or S. mansoni at study endpoint, as assessed by longitudinal surveys. Secondary outcomes are to quantify the infection of schistosomiasis and STH infections in non-treated cohorts, reductions in prevalence of STH, and intensity of schistosomiasis and STH, and treatment coverage. Nested within this study will be qualitative, cost-benefit, and cost-effectiveness evaluations that will explore accessibility, feasibility, and economic impact of expanded treatment from different complementary perspectives. (3) Discussion: Using a multidisciplinary approach, this study will generate evidence for improved availability, acceptability, affordability, and accessibility to deworming drugs against schistosomiasis and STH to individuals and communities in Ghana. This is likely to have considerable research, programmatic, and political value to contribute evidence for national programme policy development within Ghana, and, more broadly, World Health Organization policy development.
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BACKGROUND: Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment-have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread. METHODOLOGY/PRINCIPAL FINDINGS: Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR. CONCLUSIONS/SIGNIFICANCE: This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different parasite populations. Furthermore, we propose that genetic drift rather than genetic selection of SOR is the underlying driver of population differentiation, which has significant implications for the emergence and potential spread of SOR within and between these parasite populations.
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Antiparasitarios/farmacología , Resistencia a Medicamentos , Perfilación de la Expresión Génica , Flujo Genético , Ivermectina/farmacología , Onchocerca volvulus/efectos de los fármacos , Onchocerca volvulus/genética , Animales , Camerún , Femenino , Variación Genética , Genotipo , Ghana , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Onchocerca volvulus/clasificación , Oncocercosis/parasitología , Sitios de Carácter CuantitativoRESUMEN
BACKGROUND: Wolbachia are intracellular bacteria found in arthropods and several filarial nematode species. The filarial Wolbachia have been proposed to be involved in the immunopathology associated with onchocerciasis. Higher Wolbachia-to-nematode ratios have been reported in the savannah-ecotype compared to the forest-ecotype, and have been interpreted as consistent with a correlation between Wolbachia density and disease severity. However, factors such as geographic stratification and ivermectin drug exposure can lead to significant genetic heterogeneity in the nematode host populations, so we investigated whether Wolbachia copy number variation is also associated with these underlying factors. METHODS: Genomic DNA was prepared from single adult nematodes representing forest and savannah ecotypes sampled from Togo, Ghana, Côte d'Ivoire and Mali. A qPCR assay was developed to measure the number of Wolbachia genome(s) per nematode genome. Next-generation sequencing (NGS) was also used to measure relative Wolbachia copy number, and independently verify the qPCR assay. RESULTS: Significant variation was observed within the forest (range: 0.02 to 452.99; median: 10.58) and savannah (range: 0.01 to 1106.25; median: 9.10) ecotypes, however, no significant difference between ecotypes (P = 0.645) was observed; rather, strongly significant Wolbachia variation was observed within and between the nine study communities analysed (P = 0.021), independent of ecotype. Analysis of ivermectin-treated and untreated nematodes by qPCR showed no correlation (P = 0.869); however, an additional analysis of a subset of the nematodes by qPCR and NGS revealed a correlation between response to ivermectin treatment and Wolbachia copy number (P = 0.020). CONCLUSIONS: This study demonstrates that extensive within and between population variation exists in the Wolbachia content of individual adult O. volvulus. The origin and functional significance of such variation (up to ~ 100,000-fold between worms; ~10 to 100-fold between communities) in the context of the proposed mutualistic relationship between the worms and the bacteria, and between the presence of Wolbachia and clinical outcome of infection, remains unclear. These data do not support a correlation between Wolbachia copy number and forest or savannah ecotype, and may have implications for the development of anti-Wolbachia drugs as a macrofilaricidal treatment of onchocerciasis. The biological significance of a correlation between variation in Wolbachia copy number and ivermectin response remains unexplained.
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Variaciones en el Número de Copia de ADN , Heterogeneidad Genética , Genoma Bacteriano , Onchocerca volvulus/microbiología , Wolbachia/genética , Animales , Ecotipo , Bosques , Genoma de los Helmintos , Pradera , Secuenciación de Nucleótidos de Alto Rendimiento , Ivermectina/farmacología , Onchocerca volvulus/genética , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Schistosomiasis is a waterborne parasitic disease in sub-Saharan Africa, particularly common in rural populations living in impoverished conditions. With the scale-up of preventive chemotherapy, national campaigns will transition from morbidity- to transmission-focused interventions thus formal investigation of actual or expected declines in environmental transmission is needed as 'end game' scenarios arise. Surprisingly, there are no international or national guidelines to do so in sub-Saharan Africa. Our article therefore provides an introduction to key practicalities and pitfalls in the development of an appropriate environmental surveillance framework. In this context, we discuss how strategies need to be adapted and tailored to the local level to better guide and support future interventions through this transition. As detection of egg-patent infection in people becomes rare, careful sampling of schistosome larvae in freshwater and in aquatic snails with robust species-specific DNA assays will be required. Appropriate metrics, derived from observed prevalence(s) as compared with predetermined thresholds, could each provide a clearer insight into contamination- and exposure-related dynamics. Application could be twofold, first to certify areas currently free from schistosomiasis transmission or second to red-flag recalcitrant locations where extra effort or alternative interventions are needed.
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Monitoreo Epidemiológico , Vigilancia de la Población/métodos , Schistosoma/aislamiento & purificación , Esquistosomiasis/prevención & control , África del Sur del Sahara/epidemiología , Animales , Agua Dulce/parasitología , Humanos , Esquistosomiasis/epidemiología , Esquistosomiasis/parasitología , Esquistosomiasis/transmisión , Caracoles/parasitologíaRESUMEN
BACKGROUND: Vector-biting behaviour is important for vector-borne disease (VBD) epidemiology. The proportion of blood meals taken on humans (the human blood index, HBI), is a component of the biting rate per vector on humans in VBD transmission models. Humans are the definitive host of Onchocerca volvulus, but the simuliid vectors feed on a range of animals and HBI is a key indicator of the potential for human onchocerciasis transmission. Ghana has a diversity of Simulium damnosum complex members, which are likely to vary in their HBIs, an important consideration for parameterization of onchocerciasis control and elimination models. METHODS: Host-seeking and ovipositing S. damnosum (sensu lato) (s.l.) were collected from seven villages in four Ghanaian regions. Taxa were morphologically and molecularly identified. Blood meals from individually stored blackfly abdomens were used for DNA profiling, to identify previous host choice. Household, domestic animal, wild mammal and bird surveys were performed to estimate the density and diversity of potential blood hosts of blackflies. RESULTS: A total of 11,107 abdomens of simuliid females (which would have obtained blood meal(s) previously) were tested, with blood meals successfully amplified in 3,772 (34 %). A single-host species was identified in 2,857 (75.7 %) of the blood meals, of which 2,162 (75.7 %) were human. Simulium soubrense Beffa form, S. squamosum C and S. sanctipauli Pra form were the most anthropophagic (HBI = 0.92, 0.86 and 0.70, respectively); S. squamosum E, S. yahense and S. damnosum (sensu stricto) (s.s.)/S. sirbanum were the most zoophagic (HBI = 0.44, 0.53 and 0.63, respectively). The degree of anthropophagy decreased (but not statistically significantly) with increasing ratio of non-human/human blood hosts. Vector to human ratios ranged from 139 to 1,198 blackflies/person. CONCLUSIONS: DNA profiling can successfully identify blood meals from host-seeking and ovipositing blackflies. Host choice varies according to sibling species, season and capture site/method. There was no evidence that HBI is vector and/or host density dependent. Transmission breakpoints will vary among locations due to differing cytospecies compositions and vector abundances.