Background:The most important risk encountered in distributing Mectizan® for the control of onchocerciasis in areas where Loa loa is co-endemic is the development of an encephalopathic syndrome in people with very high levels of L. loa [> 30,000 microfilariae/milliliter blood (mf/ml)] following treatment with Mectizan®. This syndrome, which occurs rarely, is characterized by symptoms such as confusion, lethargy, coma, and urinary incontinence.The reason this syndrome develops is that Mectizan®, in addition to being an effective drug against the microfilariae of Onchocerca volvulus (the causative agent of onchocerciasis), is also effective against L. loa microfilariae, the rapid killing of which has been associated with this encephalopathy. Like all serious illnesses, this encephalopathy requires prompt medical and nursing care to provide supportive treatment and to prevent nosocomial infections. With competent and timely medical care, patients usually recover fully. The pathogenesis of this encephalopathy remains unknown.L. loa is known, or suspected, to be endemic in humid forest areas of Central and East Africa. The precise distribution of L. loa is still being defined and mapped. Methodologies for mapping include parasitologic surveys, rapid assessment of L. loa based on the restricted definition of eye worm passage (RAPLOA), and predicted prevalence based on environmental factors conducive to the breeding of the vector of L. loa, Chrysops spp.Recent epidemiologic studies have shown that in areas where the prevalence of L. loa microfilaremia in adults exceeds 20%, the percentage of adults with L. loa microfilaremia greater than 30,000 mf/ml is about 1%.1 The threshold for increased community risk of L. loa encephalopathy following Mectizan® treatment has been defined as 20% microfilaremia prevalence which corresponds to a 40% prevalence of history of eye worm passage as measured by RAPLOA.
BackgroundAfter more than a decade of community-directed treatment with ivermectin (CDTI) in Centre and Littoral Regions of Cameroon, onchocerciasis endemicity was still high in some communities according to the 2011 epidemiological evaluations. Some corrective measures were undertaken to improve the CDTI process and therefore reduce the burden of the disease. The objective of the present study was to assess the progress made towards the elimination of onchocerciasis in the Centre 1 and Littoral 2 CDTI projects where the worst performances were found in 2011. To this end, a cross-sectional survey was conducted in April 2015 in eight communities in two health districts (HD), Bafia in Centre 1 and Yabassi in Littoral 2, chosen because assessed at baseline and in 2011. All volunteers living for at least five years in the community, aged five years or more, underwent clinical and parasitological examinations. Individual compliance to ivermectin treatment was also assessed. Analyses of data were weighted proportionally to age and gender distribution in the population.ResultsIn the Bafia and Yabassi HD, 514 and 242 individuals were examined with a mean age of 35.1 (standard deviation, SD: 20.7) and 44.6 (SD: 16.3) years, respectively. In the Bafia HD, the weighted prevalences varied from 24.4 to 57.0 % for microfilaridermia and from 3.6 to 37.4 % for nodule presence across the surveyed communities. The community microfilarial load (CMFL), expressed in microfilariae/skin snip (mf/ss), significantly dropped from 20.84–114.50 mf/ss in 1991 to 0.31–1.62 mf/ss in 2015 in all the surveyed communities. In the Yabassi HD, the weighted prevalences varied from 12.3 to 59.3 % for microfilaridermia and from 1.5 to 3.7 % for nodule presence across the surveyed communities, while a significant drop was observed in CMFL, from 20.40–28.50 mf/ss in 1999 to 0.48–1.74 mf/ss in 2015. The 2014 weighted therapeutic coverage of participants varied from 65.8 % (95 % CI: 58.4–73.2) in Yabassi HD, to 68.0 % (95 % CI: 63.3–72.7) in Bafia HD, with important variations among communities.ConclusionsAfter more than 15 years of CDTI, onchocerciasis is still mesoendemic in the surveyed communities. Further studies targeting therapeutic coverage, socio-anthropological considerations of CDTI implementation and entomological studies would bring more insights to the persistence of the disease as observed in the present study.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1868-8) contains supplementary material, which is available to authorized users.
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 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.
Abstract. The present study analyzed the relationship between the genetic diversity of Plasmodium falciparum and parasitologic/entomologic indices in the Mount Cameroon region by using merozoite surface protein 1 as a genetic marker. Blood samples were collected from asymptomatic children from three altitude zones (high, intermediate, and low). Parasitologic and entomologic indices were determined by microscopy and landing catch mosquito collection/ circumsporozoite protein-enzyme-linked immunosorbent assay, respectively. A total of 142 randomly selected P. falciparum-positive blood samples were genotyped by using a nested polymerase chain reaction-based technique. K-1 polymerase chain reaction products were also sequenced. As opposed to high altitude, the highest malaria prevalence (70.65%) and entomologic inoculation rate (2.43 infective/bites/night) were recorded at a low altitude site. Seven (18.91%), 22 (36.66%), and 19 (42.22%) samples from high, intermediate, and low altitudes, respectively, contained multiclonal infections. A new K-1 polymorphism was identified. This study shows a positive non-linear association between low/intermediate altitude (high malaria transmission) and an increase in P. falciparum merozoite surface protein 1 block 2 polymorphisms.
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