Browsing by Author "Kamgno, J."
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Item Evaluating the impact of alternative intervention strategies in accelerating onchocerciasis elimination in an area of persistent transmission in the West Region of Cameroon(PLOS NEGLECTED TROPICAL DISEASES, 2022) Atekem, K.; Dixon, R.; Wilhelm, A.; Biholong, B.; Oye, J.; Djeunga, H.N.; Nwane4, P.; Ayisi, F.; Boakye, D.; Kamgno, J.; Schmidt, E.; Nditanchou, R.; Senyonjo, L.Background Alternative strategies are recommended to accelerate onchocerciasis elimination in problematic areas including areas where annual ivermectin (IVM) distributions are unable to interrupt transmission. The aim of this study was to accelerate progress towards elimination in the Massangam health district, West Region of Cameroon where impact evaluations demonstrated ongoing transmission of onchocerciasis infection and high microfilaria (mf) prevalence despite more than 20 years of annual IVM distribution. Methodology/Principal findings Parasitological, entomological, and breeding site surveys were conducted in 2015 delineating a focus of high transmission and identified three communities with high mf prevalence. Individuals in these communities were screened for mf yearly for a period of two years and those positive treated each year with doxycycline 100mg daily for five weeks. In addition, surrounding communities were given biannual IVM. Temephos-based applications were performed once a week for 10 consecutive weeks on Simulium damnosum s.l. breeding sites. Parasitological and entomological assessments were conducted after two years of implementation and findings compared with 2015 baseline. Alternative strategies accelerated progress towards elimination through a significant mf reduction (χ2: 40.1; p<0.001) from 35.7% (95%CI: 29.0–42.8) to 12.3% (95%CI, 9.0–16.4). Reductions were furthermore recorded over a longer period, with a reduction of prevalence of 29.0% under AIS in 2017– 2019 compared to 14.6% with IVM in 2011–2015; and by 23.2% following the two years of alternative strategies compared to 20.3% reduction over 15 years of treatment with IVM (1996–2011). Entomological assessment demonstrates that transmission is still ongoing despite the reduction in mf which is expected in an environment with complex breeding sites and open transmission zones, i.e., where migration of flies or humans to and from neigh bouring areas is common. Conclusion/Significance This study provides evidence that alternative strategies are feasible and effective and should be considered in areas where transmission is sustained throughout long term unin terrupted MDA with IVM. However, there is need to consider wider transmission zones, and further explore optimal timing of larviciding with treatment to impact transmissionItem Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity(Public Library of Science, 2017) Doyle, S.R.; Bourguinat, C.; Nana-Djeunga, H.C.; Kengne-Ouafo, J.A.; Pion, S.D.S.; Bopda, J.; Kamgno, J.; Wanji, S.; Che, H.; Kuesel, A.C.; Walker, M.; Basáñez, M.G.; Boakye, D.A.; Osei-Atweneboana, M.Y.; Boussinesq, M.; Prichard, R.K.; Grant, W.N.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. © 2017 Doyle et al.Item 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, 2017) Doyle, S. R.; Bourguinat, C; Nana-Djeunga, H. C.; Kengne-Ouafo, J. A.; Bopda, J.; Kamgno, J.; Wanji, S.; Kuesel, A. C.; Walker, M.; Boakye, D.A.; Osei-Atweneboana, M.Y.; Boussinesq, M.; Prichard, R.K.; Grant, W.N.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. © 2017 Doyle et al.Item Ivermectin and doxycycline treatments against Onchocerciasis: Adaptations and impact among semi-nomadic population in Massangam Health District, Cameroon(PLOS Neglected Tropical Diseases, 2023) NditanchouI, R; Dixon, R.; Kamgno, J.; et al.We trialed strategies to reach semi-nomadic population with interventions targeting oncho cerciasis including a combination of community knowledge and Geographical Information System (GIS) technology; nomad-specific sensitization; and mobile outreach. The interven tions included ivermectin (ivm) mass drug administration (MDA) and treating infected indi viduals (found upon skin snip microscopy test) with doxycycline for 35 days. Microscopy negative snips were further tested by Polymerase Chain Reaction (PCR). After 8 months, individuals immigrating or emigrating constituted 47% of the initial population; 59% of indi viduals not born in the area have immigrated during the last five years; 28% (age>9) report edly never taken ivm; 72% (compared to 51% previously) of eligible population (age 5 years) took ivm; and 47% (age > 8, not pregnant, not breastfeeding, not severely ill,) partici pated in the test. A high prevalence of onchocerciasis,15.1%, was found upon microscopy & PCR test; 9/10 tested by skin snip microscopy and PCR at follow-up were all negative. Microfilaria prevalence and intensity upon skin snip microscopy reduced significantly from baseline following the intervention (8.9% to 4.1%, p = 0.032; 0.18 to 0.16, p = 0.013, respec tively). The strategies considerably increased reach to nomadic camps. Treating with doxy cycline in combination with ivm is feasible and has led to a significant reduction in infection level within one year among the semi-nomads. Being potentially curative in one intervention round, this combination should be considered for population group faced with challenges of achieving adequate coverage and adhesion to ivm MDA over prolonged period (>10 years).