Studies on the macrofilarial population of Onchocerca volvulus in hyper-endemic villages of the Central province of Cameroon

Boussinesq, Michel; Gardon, Jacques; Kamgno, Joseph; Demanga-Ngangue,; Pion, S. D. S.; Duke, B. O. L.

doi:10.1080/00034980120064337

Cited by 7 publications

(3 citation statements)

References 7 publications

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“…Specifically, the number of nodules seems to have a strong effect on the post-ivermectin microfilarial density, with any increase in one nodule associated with a 14.9% increase (conditionally on average values of other covariates) in microfilarial density during the period of follow-up (D15–D180). During a previous study conducted in the Mbam area, we observed that the number of worms per nodule was fairly constant and independent of the number of palpable nodules [33]. Therefore, we can assume that the number of palpable nodules is positively correlated with the number of adult worms actually present in the host.…”

Section: Discussionmentioning

confidence: 73%

“…Indeed, in Liberia, it has been observed that the proportions of old and dead female worms were generally higher in hypo-endemic villages (28% and 18%, respectively) than in hyper-endemic ones (7% and 12%) [32]. We analyzed the population of adult worms collected in the Mbam valley at the outset of the 1994–1998 clinical trial [33]. In this study, the mean number of fecund female worms per nodule was similar in the four groups of villages defined by endemicity level (0.99, 0.90, 0.97 and 0.99 female/nodule in the respective community microfilarial load classes 10–40, 41–60, 61–70 and >70 mf/skin snip).…”

Section: Discussionmentioning

confidence: 99%

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Dynamics of Onchocerca volvulus Microfilarial Densities after Ivermectin Treatment in an Ivermectin-naïve and a Multiply Treated Population from Cameroon

Pion

Nana-Djeunga

Kamgno³

et al. 2013

PLoS Negl Trop Dis

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Background/ObjectiveIvermectin 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.MethodsWe 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.FindingsTwo 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.ConclusionThese 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.

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Dynamics of Onchocerca volvulus Microfilarial Densities after Ivermectin Treatment in an Ivermectin-naïve and a Multiply Treated Population from Cameroon

Pion

Nana-Djeunga

Kamgno³

et al. 2013

PLoS Negl Trop Dis

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“…Dead O. volvulus are not rapidly resorbed and can be readily found in nodules [20,23]. In the study area before treatment, 15.2% of adult female worms found in nodules were moribund or dead [24]. After treatment, the proportion of non-genotyped parasites was higher ( p = 0.024), which could be due to the macrofilaricidal effect of IVM [3,25,26].…”

Section: Discussionmentioning

confidence: 99%

Genetic Selection of Low Fertile Onchocerca volvulus by Ivermectin Treatment

et al. 2007

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Background Onchocerca 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 Findings O. 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 µg/kg or 800 µg/kg. Genotype frequencies were determined in β-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 β-tubulin genotype and female parasite fertility. We found a significant selection for β-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 β-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 β-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.

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Individual host factors associated with Onchocerca volvulus microfilarial densities 15, 80 and 180 days after a first dose of ivermectin

et al. 2011

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Reduction in Onchocerca volvulus skin microfilarial densities after treatment with ivermectin shows wide between-host variation. Data from two separate studies conducted in Cameroon on onchocerciasis patients treated for the first time with ivermectin were analyzed to identify host factors associated with microfilarial density at different time-points after treatment. In one site (Nkam valley), the dataset included 103 adult males for whom age, number of palpable onchocercal nodules and microfilarial densities on D0 (pre-treatment), D15, D80 and D180 were available. In the other site (Vina valley), analyses were conducted on 965 individuals of both sexes aged 5 years and over; in this dataset, available information included age, gender, exact dose of ivermectin received, onchocerciasis endemicity level in the village of residence and microfilarial densities on D0 and D180. Negative binomial regression models of microfilarial density at the different intervals post-treatment were fitted, using maximum likelihood, with the available independent variables. Gender and age were found to be associated with microfilarial density on D180. The initial microfilarial density influenced post-treatment densities at all the time-points. All other things being equal, microfilarial densities on D180 were higher in individuals harbouring a higher number of nodules or living in communities with high endemicity levels. This study demonstrates that O. volvulus microfilarial density measured after a first treatment with ivermectin, and thus probably the rate of skin repopulation by microfilariae (mf) varies according to several host factors. Should such factors also influence ivermectin efficacy after repeated treatment, then they should be taken into account to determine whether sub-optimal responses to treatment reported from various areas in Africa are actually due to parasite-related factors, particularly to the emergence of resistant populations.

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Studies on the macrofilarial population of Onchocerca volvulus in hyper-endemic villages of the Central province of Cameroon

Cited by 7 publications

References 7 publications

Dynamics of Onchocerca volvulus Microfilarial Densities after Ivermectin Treatment in an Ivermectin-naïve and a Multiply Treated Population from Cameroon

Dynamics of Onchocerca volvulus Microfilarial Densities after Ivermectin Treatment in an Ivermectin-naïve and a Multiply Treated Population from Cameroon

Genetic Selection of Low Fertile Onchocerca volvulus by Ivermectin Treatment

Individual host factors associated with Onchocerca volvulus microfilarial densities 15, 80 and 180 days after a first dose of ivermectin

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