Publications
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Whittaker C, Walker M, Pion SDS, et al., 2018, Loa loa: more than meets the eye?, Trends in Parasitology, Vol: 34, Pages: 261-262, ISSN: 0169-4758
Whittaker C, Walker M, Pion SDS, et al., 2018, The population biology and transmission dynamics of Loa loa, Trends in Parasitology, Vol: 34, Pages: 335-350, ISSN: 1471-5007
Endemic to Central Africa, loiasis – or African eye worm (caused by the filarial nematode Loa loa) – affects more than 10 million people. Despite causing ocular and systemic symptoms, it has typically been considered a benign condition, only of public health relevance because it impedes mass drug administration-based interventions against onchocerciasis and lymphatic filariasis in co-endemic areas. Recent research has challenged this conception, demonstrating excess mortality associated with high levels of infection, implying that loiasis warrants attention as an intrinsic public health problem. This review summarises available information on the key parasitological, entomological, and epidemiological characteristics of the infection and argues for the mobilisation of resources to control the disease, and the development of a mathematical transmission model to guide deployment of interventions.
Colebunders R, Basanez M-G, Siling K, et al., 2018, From river blindness control to elimination: bridge over troubled water, INFECTIOUS DISEASES OF POVERTY, Vol: 7, ISSN: 2095-5162
BackgroundAn estimated 25 million people are currently infected with onchocerciasis (a parasitic infection caused by the filarial nematode Onchocerca volvulus and transmitted by Simulium vectors), and 99% of these are in sub-Saharan Africa. The African Programme for Onchocerciasis Control closed in December 2015 and the World Health Organization has established a new structure, the Expanded Special Project for the Elimination of Neglected Tropical Diseases for the coordination of technical support for activities focused on five neglected tropical diseases in Africa, including onchocerciasis elimination.AimsIn this paper we argue that despite the delineation of a reasonably well-defined elimination strategy, its implementation will present particular difficulties in practice. We aim to highlight these in an attempt to ensure that they are well understood and that effective plans can be laid to solve them by the countries concerned and their international partners.ConclusionsA specific concern is the burden of disease caused by onchocerciasis-associated epilepsy in hyperendemic zones situated in countries experiencing difficulties in strengthening their onchocerciasis control programmes. These difficulties should be identified and programmes supported during the transition from morbidity control to interruption of transmission and elimination.
Colebunders R, Mandro M, Njamnshi AK, et al., 2018, Report of the first international workshop on onchocerciasis-associated epilepsy, Infectious Diseases of Poverty, Vol: 7, ISSN: 2095-5162
Background:Recently, several epidemiological studies performed in Onchocerca volvulus-endemic regions have suggested that onchocerciasis-associated epilepsy (OAE) may constitute an important but neglected public health problem in many countries where onchocerciasis is still endemic.Main text:On October 12–14th 2017, the first international workshop on onchocerciasis-associated epilepsy (OAE) was held in Antwerp, Belgium. The workshop was attended by 79 participants from 20 different countries. Recent research findings strongly suggest that O. volvulus is an important contributor to epilepsy, particularly in meso- and hyperendemic areas for onchocerciasis. Infection with O. volvulus is associated with a spectrum of epileptic seizures, mainly generalised tonic-clonic seizures but also atonic neck seizures (nodding), and stunted growth. OAE is characterised by an onset of seizures between the ages of 3–18 years. Multidisciplinary working groups discussed topics such as how to 1) strengthen the evidence for an association between onchocerciasis and epilepsy, 2) determine the burden of disease caused by OAE, 3) prevent OAE, 4) improve the treatment/care for persons with OAE and affected families, 5) identify the pathophysiological mechanism of OAE, and 6) deal with misconceptions, stigma, discrimination and gender violence associated with OAE.An OAE Alliance was created to increase awareness about OAE and its public health importance, stimulate research and disseminate research findings, and create partnerships between OAE researchers, communities, advocacy groups, ministries of health, non-governmental organisations, the pharmaceutical industry and funding organizations.Conclusions:Although the exact pathophysiological mechanism underlying OAE remains unknown, there is increasing evidence that by controlling and eliminating onchocerciasis, OAE will also disappear. Therefore, OAE constitutes an additional argument for strengthening onchocerciasis elimination
Cano J, Basáñez M-G, O'Hanlon SJ, et al., 2018, Identifying co-endemic areas for major filarial infections in sub-Saharan Africa: seeking synergies and preventing severe adverse events during mass drug administration campaigns, Parasites & Vectors, Vol: 11, Pages: 70-70, ISSN: 1756-3305
BACKGROUND: Onchocerciasis and lymphatic filariasis (LF) are major filarial infections targeted for elimination in most endemic sub-Saharan Africa (SSA) countries by 2020/2025. The current control strategies are built upon community-directed mass administration of ivermectin (CDTI) for onchocerciasis, and ivermectin plus albendazole for LF, with evidence pointing towards the potential for novel drug regimens. When distributing microfilaricides however, considerable care is needed to minimise the risk of severe adverse events (SAEs) in areas that are co-endemic for onchocerciasis or LF and loiasis. This work aims to combine previously published predictive risk maps for onchocerciasis, LF and loiasis to (i) explore the scale of spatial heterogeneity in co-distributions, (ii) delineate target populations for different treatment strategies, and (iii) quantify populations at risk of SAEs across the continent. METHODS: Geographical co-endemicity of filarial infections prior to the implementation of large-scale mass treatment interventions was analysed by combining a contemporary LF endemicity map with predictive prevalence maps of onchocerciasis and loiasis. Potential treatment strategies were geographically delineated according to the level of co-endemicity and estimated transmission intensity. RESULTS: In total, an estimated 251 million people live in areas of LF and/or onchocerciasis transmission in SSA, based on 2015 population estimates. Of these, 96 million live in areas co-endemic for both LF and onchocerciasis, providing opportunities for integrated control programmes, and 83 million live in LF-monoendemic areas potentially targetable for the novel ivermectin-diethylcarbamazine-albendazole (IDA) triple therapy. Only 4% of the at-risk population live in areas co-endemic with high loiasis transmission, representing up to 1.2 million individuals at high risk of experiencing SAEs if treated with ivermectin. In these areas, alternative treatment strategies should be ex
Veriegh F, Basanez M-G, Baidoo P, et al., 2018, GEO-STATISTICAL ANALYSIS OF CONTINUAL ONCHOCERCIASIS TRANSMISSION IN AND AROUND AREAS RECEIVING BI-ANNUAL IVERMECTIN TREATMENT REGIMENS, 67th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTHM), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 36-37, ISSN: 0002-9637
Buell K, Whittaker C, Chesnais C, et al., 2018, FROM INFECTION TO DISEASE IN LOIASIS: A SYSTEMATIC REVIEW OF CLINICO-EPIDEMIOLOGICAL CASE REPORTS, 67th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTHM), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 385-385, ISSN: 0002-9637
Nouvellet P, Cucunuba Z, Rodriguez-Barraquer I, et al., 2018, CHARACTERIZATION OF POPULATION EXPOSURE (SEROPREVALENCE) TO ARBOVIRUSES AFTER RECENT OUTBREAKS IN COLOMBIA: DENGUE, CHIKUNGUNYA AND ZIKA, 67th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTHM), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 296-296, ISSN: 0002-9637
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Whittaker C, Walker M, Pion S, et al., 2018, EVALUATING THE IMPACT OF ANTHELMINTIC-BASED INTERVENTION STRATEGIES FOR CONTROLLING <it>LOA LOA</it>: A MATHEMATICAL MODELLING STUDY USING EPILOA, 67th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTHM), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 16-16, ISSN: 0002-9637
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Dixon M, Braae U, Winskill P, et al., 2018, TOWARDS THE DESIGN AND OPTIMIZATION OF INTERVENTION STRATEGIES AGAINST <it>TAENIA SOLIUM</it> TAENIOSIS/CYSTICERCOSIS BY MULTI-MODEL COMPARISON, 67th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTHM), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 151-151, ISSN: 0002-9637
Halder J, Prociuk D, Nouvellet P, et al., 2018, DECREASING THE IMPACT OF CHAGAS DISEASE THROUGH MODELLING: THE DICTUM FRAMEWORK FOR RETRIEVING, COLLATING, AND ANALYSING SEROSURVEY DATA FOR CHAGAS DISEASE ACROSS LATIN AMERICA, 67th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTHM), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 625-625, ISSN: 0002-9637
Jewell P, Abraham A, Schmidt V, et al., 2018, TREATMENT OF INDIVIDUALS LIVING WITH NEUROCYSTICERCOSIS AND HIV/AIDS: A SCOPING REVIEW, 67th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTHM), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 151-151, ISSN: 0002-9637
Assoum M, Ortu G, Basanez M-G, et al., 2017, Spatiotemporal distribution and population at risk of soil-transmitted helminth infections following an eight-year school-based deworming programme in Burundi, 2007-2014, Parasites & Vectors, Vol: 10, ISSN: 1756-3305
Background: Investigating the effect of successive annual deworming rounds on the spatiotemporal distribution ofinfection prevalence and numbers at risk for soil-transmitted helminths (STHs) can help identify communitiesnearing elimination and those needing further interventions. In this study, we aim to quantify the impact ofan 8-year mass drug administration (MDA) programme (from 2007 to 2014) on the spatiotemporal distribution ofprevalence of STH infections and to estimate the number of school-aged children infected with STHs in Burundi.Methods: During annual longitudinal school-based surveys in Burundi between 2007 and 2011, STH infection andanthropometric data for a total of 40,656 children were collected; these data were supplemented with data froma national survey conducted in 2014. Bayesian model based geostatistics (MBG) were used to generate predictiveprevalence maps for each STH species and year. The numbers of children at-risk of infection per district between2008 and 2014 were estimated as the product of the predictive prevalence maps and population density maps.Results: Overall, the degree of spatial clustering of STH infections decreased between 2008 and 2011; in 2014 thegeographical clusters of all STH infections reappeared. The reduction in prevalence was small for Ascaris lumbricoidesand Trichuris trichiura in the centre and central north of the country. Our predictive prevalence maps for hookwormindicate a reduction in prevalence along the periphery of the country. The predicted number of children infected withany STH species decreased substantially between 2007 and 2011, but in 2014 there was an increase in the predictednumber of children infected with A. lumbricoides and T. trichiura. In 2014, the districts with the highest predictednumber of children infected with A. lumbricoides, T. trichiura and hookworms were Kibuye district (n = 128,903),Mabayi district (n = 35,302) and Kiremba (n = 87,511), respectively.Conclusions: While the MDA programme
Walker M, Stolk WA, Dixon M, et al., 2017, ELIMINATION OF ONCHOCERCIASIS WITH IVERMECTIN: A VALIDATION OF THE EPIONCHO AND ONCHOSIM MODELS USING DATA FROM MALI AND SENEGAL, 65th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 154-154, ISSN: 0002-9637
Pearson I, Halder JB, Basanez M-G, et al., 2017, THE EFFICACY OF PREVENTATIVE CHEMOTHERAPY DRUGS FOR THE TREATMENT OF LYMPHATIC FILARIASIS: A SYSTEMATIC REVIEW AND MODEL-BASED META-ANALYSIS, 65th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 344-345, ISSN: 0002-9637
Cucunuba ZM, Sicuri E, Diaz D, et al., 2017, ESTIMATING THE COSTS AND COST-EFFECTIVENESS OF EARLY DIAGNOSIS AND TREATMENT OF CHAGAS DISEASE IN COLOMBIA, 65th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 364-364, ISSN: 0002-9637
Halder JB, Jule AM, Vaillant M, et al., 2017, SYSTEMATIC REVIEW AND META-ANALYSIS OF SOIL-TRANSMITTED HELMINTH TREATMENT EFFICACY STUDIES AND THE CASE FOR SHARING INDIVIDUAL PATIENT DATA, 65th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 542-542, ISSN: 0002-9637
Walker M, Halder JB, Awadzi K, et al., 2017, DEFINING AND DETECTING SUBOPTIMAL RESPONSES TO IVERMECTIN IN PATIENTS WITH ONCHOCERCIASIS, 65th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 344-344, ISSN: 0002-9637
Deol AK, French MD, Walker M, et al., 2017, COMMUNITY-WIDE PATTERNS OF INFECTION AFTER MORE THAN TEN YEARS OF PREVENTIVE CHEMOTHERAPY FOR SCHISTOSOMIASIS AND SOIL-TRANSMITTED HELMINTH INFECTION IN UGANDA: ARE WE READY TO MOVE BEYOND MORBIDITY CONTROL?, 65th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 558-558, ISSN: 0002-9637
Cucunuba Z, Nouvellet P, Okuwoga O, et al., 2017, PROGRESSION AND MORTALITY RATES FOR MODELLING THE BURDEN OF CHAGAS DISEASE, 65th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 206-207, ISSN: 0002-9637
Assoum M, Magalhaes RS, Ortu G, et al., 2017, PREDICTING INFECTION DISTRIBUTION AND BURDEN OF DISEASE USING SPATIOTEMPORAL MODELS FOLLOWING A SEVEN YEAR MASS DRUG ADMINISTRATION PROGRAM AND LONGITUDINAL STUDY IN BURUNDI: 2008-2014, 65th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 543-543, ISSN: 0002-9637
Jule AM, Halder JB, Vaillant M, et al., 2017, SYSTEMATIC REVIEW OF ANTISCHISTOSOMAL TREATMENT EFFICACY STUDIES AND THE SIGNIFICANCE OF INDIVIDUALLEVEL PARTICIPANT DATA FOR META-ANALYSES, 65th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 371-371, ISSN: 0002-9637
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Halder JB, Benton J, Julé AM, et al., 2017, Systematic review of studies generating individual participant data on the efficacy of drugs for treating soil-transmitted helminthiases and the case for data-sharing., PLoS Neglected Tropical Diseases, Vol: 11, ISSN: 1935-2727
BACKGROUND: Preventive chemotherapy and transmission control (PCT) by mass drug administration is the cornerstone of the World Health Organization (WHO)'s policy to control soil-transmitted helminthiases (STHs) caused by Ascaris lumbricoides (roundworm), Trichuris trichiura (whipworm) and hookworm species (Necator americanus and Ancylostama duodenale) which affect over 1 billion people globally. Despite consensus that drug efficacies should be monitored for signs of decline that could jeopardise the effectiveness of PCT, systematic monitoring and evaluation is seldom implemented. Drug trials mostly report aggregate efficacies in groups of participants, but heterogeneities in design complicate classical meta-analyses of these data. Individual participant data (IPD) permit more detailed analysis of drug efficacies, offering increased sensitivity to identify atypical responses potentially caused by emerging drug resistance. METHODOLOGY: We performed a systematic literature review to identify studies concluding after 2000 that collected IPD suitable for estimating drug efficacy against STH. We included studies that administered a variety of anthelmintics with follow ups less than 60 days after treatment. We estimated the number of IPD and extracted cohort- and study-level meta-data. PRINCIPAL FINDINGS: We estimate that there exist individual data on approximately 35,000 participants from 129 studies conducted in 39 countries, including 34 out of 103 countries where PCT is recommended. We find significant heterogeneity in diagnostic methods, times of outcome assessment, and the reported measure of efficacy. We also quantify cohorts comprising pre-school age children, pregnant women, and co-infected participants, including with HIV. CONCLUSIONS: We argue that establishing a global IPD repository would improve the capacity to monitor and evaluate the efficacy of anthelmintic drugs, respond to changes and safeguard the ongoing effectiveness of PCT. Establishing a fair, tran
Halder JB, Benton J, Jule AM, et al., 2017, Landscape of studies generating individual participant data on the efficacy of drugs for treating soil-transmitted helminthiasis and the case for data sharing, Publisher: WILEY, Pages: 48-48, ISSN: 1360-2276
Cucunuba Perez ZM, Nouvellet P, Conteh L, et al., 2017, Modelling historical changes in the force-of-infection of Chagas disease to inform control and elimination programmes: application in Colombia, BMJ Global Health, Vol: 2, ISSN: 2059-7908
Background WHO's 2020 milestones for Chagas disease include having all endemic Latin American countries certified with no intradomiciliary Trypanosoma cruzi transmission, and infected patients under care. Evaluating the variation in historical exposure to infection is crucial for assessing progress and for understanding the priorities to achieve these milestones.Methods Focusing on Colombia, all the available age-structured serological surveys (undertaken between 1995 and 2014) were searched and compiled. A total of 109 serosurveys were found, comprising 83 742 individuals from rural (indigenous and non-indigenous) and urban settings in 14 (out of 32) administrative units (departments). Estimates of the force-of-infection (FoI) were obtained by fitting and comparing three catalytic models using Bayesian methods to reconstruct temporal and spatial patterns over the course of three decades (between 1984 and 2014).Results Significant downward changes in the FoI were identified over the course of the three decades, and in some specific locations the predicted current seroprevalence in children aged 0–5 years is <1%. However, pronounced heterogeneity exists within departments, especially between indigenous, rural and urban settings, with the former exhibiting the highest FoI (up to 66 new infections/1000 people susceptible/year). The FoI in most of the indigenous settings remain unchanged during the three decades investigated. Current prevalence in adults in these 15 departments varies between 10% and 90% depending on the dynamics of historical exposure.Conclusions Assessing progress towards the control of Chagas disease requires quantifying the impact of historical exposure on current age-specific prevalence at subnational level. In Colombia, despite the evident progress, there is a marked heterogeneity indicating that in some areas the vector control interventions have not been effective, hindering the possibility of achieving interruption by 2020. A su
Herricks JR, Hotez PJ, Wanga V, et al., 2017, The global burden of disease study 2013: What does it mean for the NTDs?, PLOS NEGLECTED TROPICAL DISEASES, Vol: 11, ISSN: 1935-2735
The Global Burden of Disease Study (GBD) is a landmark initiative that systematically quantifies the prevalence, morbidity, and mortality for hundreds of diseases, injuries, and risk factors of global health importance. For the neglected tropical diseases (NTDs), the GBD 2010 confirmed a high disease burden for the 17 major NTDs prioritized by the World Health Organization (WHO) as well as for selected conditions also recognized as NTDs by PLOS Neglected Tropical Diseases, including amoebiasis, cholera, cryptosporidiosis, typhoid and paratyphoid fevers, trichomoniasis, venomous animal contact, and scabies (referred to here as “additional NTDs”) [1]. The GBD 2013 is intended to be the first in a series of annual updates for the GBD studies, with its initial results published in 2015 in The Lancet [2–4]. Here, we review information on the NTDs published in the GBD 2013 capstone papers [2–4] and present new NTD data and updated burden estimates from the GBD 2013 study and new country-specific estimates. We show key outputs of GBD 2013 including country-specific estimates of prevalence or incidence and health-gap metrics for the aforementioned NTDs.
Doyle SR, Bourguinat C, Nana-Djeunga HC, et al., 2017, Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity, PLoS Neglected Tropical Diseases, Vol: 11, ISSN: 1935-2727
BackgroundTreatment 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 findingsPooled 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/SignificanceThis 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 differe
Walker M, Pion SDS, Fang H, et al., 2017, The macrofilaricidal efficacy of repeated doses of ivermectin for the treatment of river blindness, Clinical Infectious Diseases, Vol: 65, Pages: 2026-2034, ISSN: 1537-6591
Background Mass drug administration (MDA) with ivermectin is the cornerstone of efforts to eliminate human onchocerciasis by 2020/2025. The feasibility of elimination crucially depends on the effects of multiple ivermectin doses on Onchocerca volvulus. A single ivermectin (standard) dose clears the skin-dwelling microfilarial progeny of adult worms (macrofilariae) and temporarily impedes the release of such progeny by female macrofilariae, but a macrofilaricidal effect has been deemed minimal. Multiple doses of ivermectin may cumulatively and permanently reduce the fertility and shorten the lifespan of adult females, but rigorous quantification of these effects necessitates interrogating longitudinal data on macrofilariae with suitably powerful analytical techniques.Methods Using a novel mathematical modelling approach, we analysed―at an individual participant level―longitudinal data on viability and fertility of female worms from the single most comprehensive multiple-dose clinical trial of ivermectin, comparing three-monthly with annual treatments administered for three years, in Cameroon.ResultsMultiple doses of ivermectin have a partial macrofilaricidal and a modest permanent sterilising effect after 4 or more consecutive treatments, even at routine MDA doses (150 g/kg) and (annual) frequencies. The life expectancy of adult O. volvulus is reduced by approximately 50% and70% after three years of annual or three-monthly (quarterly) exposures to ivermectin.ConclusionsOur quantification of macrofilaricidal and sterilising effects of ivermectin should be incorporated into transmission models informing onchocerciasis elimination efforts in Africa and residual foci in Latin America. It also provides a framework to assess macrofilaricidal candidate drugs currently under development.
Hotez PJ, Basanez M-G, Acosta-Serrano A, et al., 2017, Venezuela and its rising vector-borne neglected diseases, PLoS Neglected Tropical Diseases, Vol: 11, ISSN: 1935-2727
Crainey JL, Hurst J, Lamberton PHL, et al., 2017, The genomic architecture of novel simulium damnosum Wolbachia prophage sequence elements and implications for onchocerciasis epidemiology, Frontiers in Microbiology, Vol: 8, ISSN: 1664-302X
Research interest in Wolbachia is growing as new discoveries and technical advancements reveal the public health importance of both naturally occurring and artificial infections. Improved understanding of the Wolbachia bacteriophages (WOs) WOcauB2 and WOcauB3 (belonging to a sub-group of four WOs encoding serine recombinases group 1 (sr1WOs)), has enhanced the prospect of novel tools for the genetic manipulation of Wolbachia. The basic biology of sr1WOs, including host range and mode of genomic integration is, however, still poorly understood. Very few sr1WOs have been described, with two such elements putatively resulting from integrations at the same Wolbachia genome loci, about 2 kb downstream from the FtsZ cell-division gene. Here we characterise the DNA sequence flanking the FtsZ gene of wDam, a genetically distinct line of Wolbachia isolated from the West African onchocerciasis vector Simulium squamosum E. Using Roche 454 shot-gun and Sanger sequencing, we have resolved >32 kb of WO prophage sequence into 3 contigs representing three distinct prophage elements. Spanning ≥ 36 distinct WO open reading frame gene sequences, these prophage elements correspond roughly to three different WO modules: a serine recombinase and replication module (sr1RRM), a head and base-plate module and a tail module. The sr1RRM module contains replication genes and a Holliday junction recombinase and is unique to the sr1 group WOs. In the extreme terminal of the tail module there is an SpvB protein homologue—believed to have insecticidal properties and proposed to have a role in how Wolbachia parasitize their insect hosts. We propose that these wDam prophage modules all derive from a single WO genome, which we have named here sr1WOdamA1. The best-match database sequence for all of our sr1WOdamA1-predicted gene sequences was annotated as of Wolbachia or Wolbachia phage sourced from an arthropod. Clear evidence of exchange between sr1WOdamA1 and other Wolbachia WO phage seq
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