Dataset Information

Ongoing Transmission of Onchocerca volvulus after 25 Years of Annual Ivermectin Mass Treatments in the Vina du Nord River Valley, in North Cameroon.

ABSTRACT: BACKGROUND:Recent reports of transmission interruption of Onchocerca volvulus, the causing agent of river blindness, in former endemic foci in the Americas, and more recently in West and East Africa, raise the question whether elimination of this debilitating disease is underway after long-term treatment of the population at risk with ivermectin. The situation in Central Africa has not yet been clearly assessed. METHODS AND FINDINGS:Entomologic data from two former endemic river basins in North Cameroon were generated over a period of 43 and 48 months to follow-up transmission levels in areas under prolonged ivermectin control. Moreover, epidemiologic parameters of animal-borne Onchocerca spp. transmitted by the same local black fly vectors of the Simulium damnosum complex were recorded and their impact on O. volvulus transmission success evaluated. With mitochondrial DNA markers we unambiguously confirmed the presence of infective O. volvulus larvae in vectors from the Sudan savannah region (mean Annual Transmission Potential 2009-2012: 98, range 47-221), but not from the Adamawa highland region. Transmission rates of O. ochengi, a parasite of Zebu cattle, were high in both foci. CONCLUSIONS/SIGNIFICANCE:The high cattle livestock density in conjunction with the high transmission rates of the bovine filaria O. ochengi prevents the transmission of O. volvulus on the Adamawa plateau, whereas transmission in a former hyperendemic focus was markedly reduced, but not completely interrupted after 25 years of ivermectin control. This study may be helpful to gauge the impact of the presence of animal-filariae for O. volvulus transmission in terms of the growing human and livestock populations in sub-Saharan countries.

SUBMITTER: Eisenbarth A

PROVIDER: S-EPMC4771805 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Ongoing Transmission of Onchocerca volvulus after 25 Years of Annual Ivermectin Mass Treatments in the Vina du Nord River Valley, in North Cameroon.

Eisenbarth Albert A Achukwi Mbunkah Daniel MD Renz Alfons A

PLoS neglected tropical diseases 20160229 2

<h4>Background</h4>Recent reports of transmission interruption of Onchocerca volvulus, the causing agent of river blindness, in former endemic foci in the Americas, and more recently in West and East Africa, raise the question whether elimination of this debilitating disease is underway after long-term treatment of the population at risk with ivermectin. The situation in Central Africa has not yet been clearly assessed.<h4>Methods and findings</h4>Entomologic data from two former endemic river b ...[more]

PMID: 26926855

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Project description:BackgroundThe onchocerciasis focus surrounding the lower Mbam and Sanaga rivers, where Onchocerca volvulus is transmitted by Simulium damnosum s.l. (Diptera: Simuliidae), was historically the largest in the southern regions of Cameroon. Annual community-directed treatment with ivermectin (CDTI) has been taking place since 2000, but recent studies have shown that new infections are occurring in children. We aimed to investigate blackfly biting and O. volvulus transmission rates along the lower Mbam river 16 years after the formal onset of annual CDTI.MethodsBlack flies were collected for three consecutive days each month between July 2016 and June 2017 at two riverside villages and two inland sites situated 4.9 km and 7.9 km from the riverside. Specimens collected at each site were dissected on one of the three collection days each month to estimate parity rates and O. volvulus infection rates, while the remaining samples were preserved for pool screening.ResultsIn total, 93,573 S. damnosum s.l. black flies were recorded biting humans and 9281 were dissected. Annual biting rates of up to 606,370 were estimated at the riverside, decreasing to 20,540 at 7.9 km, while, based on dissections, annual transmission potentials of up to 4488 were estimated at the riverside, decreasing to 102 and 0 at 4.9 km and 7.9 km, respectively. However, pool screening showed evidence of infection in black flies at the furthest distance from the river. Results of both methods demonstrated the percentage of infective flies to be relatively low (0.10-0.36%), but above the WHO threshold for interruption of transmission. In addition, a small number of larvae collected during the dry season revealed the presence of Simulium squamosum E. This is the first time S. squamosum E has been found east of Lake Volta in Ghana, but our material was chromosomally distinctive, and we call it S. squamosum E2.ConclusionsRelatively low O. volvulus infection rates appear to be offset by extremely high densities of biting black flies which are sustaining transmission along the banks of the lower Mbam river.

Project description:BACKGROUND/OBJECTIVE: Ivermectin has been the keystone of onchocerciasis control for the last 25 years. Sub-optimal responses to the drug have been reported in Ghanaian communities under long-term treatment. We assessed, in two Cameroonian foci, whether the microfilaricidal and/or embryostatic effects of ivermectin on Onchocerca volvulus have been altered after several years of drug pressure. METHODS: We compared the dynamics of O. volvulus skin microfilarial densities after ivermectin treatment in two cohorts with contrasting exposure to this drug: one received repeated treatment for 13 years whereas the other had no history of large-scale treatments (referred to as controls). Microfilarial densities were assessed 15, 80 and 180 days after ivermectin in 122 multiply treated and 127 ivermectin-naïve individuals. Comparisons were adjusted for individual factors related to microfilarial density: age and number of nodules. FINDINGS: Two weeks post ivermectin, microfilarial density dropped equally (98% reduction) in the ivermectin-naïve and multiply treated groups. Between 15 and 180 days post ivermectin, the proportion of individuals with skin microfilariae doubled (from 30.8% to 67.8%) in controls and quadrupled (from 19.8% to 76.9%) in multiply treated individuals but the mean densities remained low in both sites. In fact, between 15 and 80 days, the repopulation rate was significantly higher in the multiply treated individuals than in the controls but no such difference was demonstrated when extending the follow-up to 180 days. The repopulation rate by microfilariae was associated with host factors: negatively with age and positively with the number of nodules. CONCLUSION: These observations may indicate that the worms from the multi-treated area recover mf productivity earlier but would be less productive than the worms from the ivermectin-naïve area between 80 and 180 days after ivermectin. Moreover, they do not support the operation of a strong cumulative effect of repeated treatments on the fecundity of female worms as previously described.

Project description:BackgroundIvermectin (IVM) has been used in Ghana for over two decades for onchocerciasis control. In recent years there have been reports of persistent microfilaridermias despite multiple treatments. This has necessitated a reexamination of its microfilaricidal and suppressive effects on reproduction in the adult female Onchocerca volvulus. In an initial study, we demonstrated the continued potent microfilaricidal effect of IVM. However, we also found communities in which the skin microfilarial repopulation rates at days 90 and 180 were much higher than expected. In this follow up study we have investigated the reproductive response of female worms to multiple treatments with IVM.Methods and findingsThe parasitological responses to IVM in two hundred and sixty-eight microfilaridermic subjects from nine communities that had received 10 to 19 annual doses of IVM treatment and one pre-study IVM-naïve community were followed. Skin snips were taken 364 days after the initial IVM treatment during the study to determine the microfilaria (mf) recovery rate. Nodules were excised and skin snips taken 90 days following a second study IVM treatment. Nodule and worm density and the reproductive status of female worms were determined. On the basis of skin mf repopulation and skin mf recovery rates we defined three categories of response--good, intermediate and poor--and also determined that approximately 25% of subjects in the study carried adult female worms that responded suboptimally to IVM. Stratification of the female worms by morphological age and microfilarial content showed that almost 90% of the worms were older or middle aged and that most of the mf were produced by the middle aged and older worms previously exposed to multiple treatments with little contribution from young worms derived from ongoing transmission.ConclusionsThe results confirm that in some communities adult female worms were non-responsive or resistant to the anti-fecundity effects of multiple treatments with IVM. A scheme of the varied responses of the adult female worm to multiple treatments is proposed.

Project description:BackgroundOnchocerca volvulus is the causative agent of onchocerciasis, or "river blindness". Ivermectin has been used for mass treatment of onchocerciasis for up to 18 years, and recently there have been reports of poor parasitological responses to the drug. Should ivermectin resistance be developing, it would have a genetic basis. We monitored genetic changes in parasites obtained from the same patients before use of ivermectin and following different levels of ivermectin exposure.Methods and findingsO. volvulus adult worms were obtained from 73 patients before exposure to ivermectin and in the same patients following three years of annual or three-monthly treatment at 150 microg/kg or 800 microg/kg. Genotype frequencies were determined in beta-tubulin, a gene previously found to be linked to ivermectin selection and resistance in parasitic nematodes. Such frequencies were also determined in two other genes, heat shock protein 60 and acidic ribosomal protein, not known to be linked to ivermectin effects. In addition, we investigated the relationship between beta-tubulin genotype and female parasite fertility. We found a significant selection for beta-tubulin heterozygotes in female worms. There was no significant selection for the two other genes. Quarterly ivermectin treatment over three years reduced the frequency of the beta-tubulin "aa" homozygotes from 68.6% to 25.6%, while the "ab" heterozygotes increased from 20.9% to 69.2% in the female parasites. The female worms that were homozygous at the beta-tubulin locus were more fertile than the heterozygous female worms before treatment (67% versus 37%; p = 0.003) and twelve months after the last dose of ivermectin in the groups treated annually (60% versus 17%; p<0.001). Differences in fertility between heterozygous and homozygous worms were less apparent three months after the last treatment in the groups treated three-monthly.ConclusionsThe results indicate that ivermectin is causing genetic selection on O. volvulus. This genetic selection is associated with a lower reproductive rate in the female parasites. We hypothesize that this genetic selection indicates that a population of O. volvulus, which is more tolerant to ivermectin, is being selected. This selection could have implications for the development of ivermectin resistance in O. volvulus and for the ongoing onchocerciasis control programmes.

Project description:BackgroundCommunity Directed Treatment with ivermectin is the cornerstone of current efforts to eliminate onchocerciasis. However recent studies suggest there are foci where long-term annual distribution of the drug alone has failed to ensure elimination thresholds are reached. It is important to achieve high levels of compliance in order to obtain elimination targets. An epidemiological and entomological evaluation conducted in the western region of Cameroon in 2011 revealed that two health districts remained with a high prevalence of infection, despite long-term distribution of ivermectin since 1996. This paper explores potential factors that may have contributed to the non-interruption of transmission, focusing on ivermectin treatment compliance and the importance of systematic non-compliance within the population.Methodology/principal findingsA mixed methods approach was used, including a population-based survey to assess treatment compliance and factors associated and qualitative assessments including focus group discussions and in-depth interviews with key programme stakeholders and drug distributors. Compliance was reported at 71.2% (95%CI: 61.7-79.2%;n = 853/1198). The key factors related to compliance in the most recent round related to either programmatic and delivery issues, primarily absenteeism at the time of the campaign or alternatively individual determinants. An individual's experience of side effects in the past was strongly associated with non-compliance to ivermectin. Other factors included ethnicity, how long lived in the village and age. There was a high percentage of reported systematic non-compliance at 7.4% (95% CI: 4.3-12.3%; n = 86/1165), higher amongst females. This group may be important in facilitating the sustainment of on-going transmission.Conclusions/significanceEfforts to reduce the number of systematic non-compliers and non-compliance in certain groups may be important in ensuring the interruption of transmission in the study area. However, in areas with high pre-control force of transmission, as in these districts, annual distribution with ivermectin, even if sustaining high levels of compliance, may still be inadequate to achieve elimination. Further studies are required to better understand the transmission dynamics and focus of on-going transmission in the study districts.

Project description:Vector control using larvicides is the main alternative strategy to address limits of preventive chemotherapy using ivermectin for the control of onchocerciasis. However, it remains substantially limited by implementation difficulties, ecological concerns and the resistance of vector populations. Therefore, efficient and environmentally safe alternative control strategies are still needed. This study explores the composition of the blackfly bacteriome and its variability in the presence of Onchocerca volvulus infection, in order to determine their potential as a novel vector control-based approach to fight onchocerciasis. An entomological survey of a collection of samples was performed in the Bafia health district, a historical endemic focus for onchocerciasis in Cameroon. A total of 1270 blackflies were dissected and the infection rate was 10.1%, indicative of ongoing transmission of onchocerciasis in the surveyed communities. Sequencing process of blackflies' gut DNA for bacteria screening revealed 14 phyla and 123 genera, highlighting the diversity of gut blackflies bacterial communities. Eight bacteria formed the core of blackfly bacteriome and Wolbachia was the predominant genus with 73.4% of relative abundance of blackflies' gut bacterial communities. Acidomonas and Roseanomas genera were significantly abundant among infected blackflies (p = 0.01), whereas other genera such as Brevibacterium and Fructobacillus were associated with the absence of infection (p = 0.0009). Differences in gut bacterial distribution of blackflies according to their infection status by the parasite suggest a causal relationship between the bacteriome composition and the onset of blackflies' infection by O. volvulus or vice versa. Blackfly native bacteria are then potentially involved in infection by O. volvulus, either by facilitating or preventing the parasite infestation of the vector. These bacteria represent an interesting potential as a biological tool/target for a novel approach of vector control to fight onchocerciasis.

Project description:BackgroundThe tropical disease onchocerciasis (river blindness), caused by Onchocerca volvulus filarial nematodes, is targeted for elimination by mass treatment with nematocidal and antimicrobial drugs. Diagnosis of O. volvulus infections is based on counts of skin-borne microfilariae, but additional diagnostic tools, e.g. worm- or host-derived small RNAs, proteins or metabolites, are required for high-throughput screening. N-acetyltyramine-O,β-glucuronide (NATOG) was suggested as a biomarker for onchocerciasis but its viability as diagnostic tool has been challenged.MethodsWe performed a screening program of urine samples from individuals from Cameroon infected with O. volvulus, Loa loa, Mansonella perstans or a combination thereof. Urine metabolites were measured by liquid chromatography-mass spectrometry (LC-MS). Principle component analysis (PCA) revealed that onchocerciasis causes complex changes of the urine metabolome.ResultsThe mean NATOG content was elevated in urine of O. volvulus-infected compared with non-infected individuals, but NATOG levels showed considerable variation. However, 13.8% of all O. volvulus-infected individuals had high NATOG levels never reached by individuals without filarial infections or only infected with L. loa or M. perstans. Therefore, the identification of individuals with high NATOG levels might be used to screen for the elimination of onchocerciasis after mass drug application. Additional metabolites, including a compound identified as cinnamoylglycine, had high PC1/PC2 loadings in the data set. Mean levels of cinnamoylglycine were increased in O. volvulus-infected individuals, and 17.2% of all O. volvulus individuals had elevated cinnamoylglycine levels not reached by the controls.ConclusionsOn an individual level, NATOG alone had poor discriminative power distinguishing infected from non-infected individuals. However, 13.8% of all O. volvulus-infected individuals had NATOG levels never reached by individuals without filarial infections or infected with only L. loa or M. perstans. Discrimination of O. volvulus infections from controls or individuals suffering from multiple infections was improved by the measurement of additional metabolites, e.g. cinnamoylglycine. Thus, measuring a combination of urine metabolites may provide a way to assess onchocerciasis on the population level. This provides the possibility to design a strategy for large-scale onchocerciasis epidemiological screening programs based on urine rather than invasive techniques.

Dataset Information

Ongoing Transmission of Onchocerca volvulus after 25 Years of Annual Ivermectin Mass Treatments in the Vina du Nord River Valley, in North Cameroon.

Publications

Ongoing Transmission of Onchocerca volvulus after 25 Years of Annual Ivermectin Mass Treatments in the Vina du Nord River Valley, in North Cameroon.

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