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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 SD, Nana-Djeunga HC, Kamgno J, Tendongfor N, Wanji S, Njiokou F, Prichard RK, Boussinesq M - PLoS Negl Trop Dis (2013)

Bottom Line: Two weeks post ivermectin, microfilarial density dropped equally (98% reduction) in the ivermectin-naïve and multiply treated groups.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.Moreover, they do not support the operation of a strong cumulative effect of repeated treatments on the fecundity of female worms as previously described.

View Article: PubMed Central - PubMed

Affiliation: UMI 233, Institut de Recherche pour le Développement (IRD) and University of Montpellier 1, Montpellier, France. sebastien.pion@ird.fr

ABSTRACT

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.

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Evolution of Onchocerca volvulus microfilarial density (mf/mg) between 15 and 80 days after ivermectin treatment.Microfilarial density at D80 is plotted against density at D15 (scatterplots), for each individual, in ivermectin-naïve and multiply treated subjects. Distribution of individual variation between 15 and 80 days post-treatment is also given (histograms) for the ivermectin-naïve and multiply treated subjects (positive difference means an increase between D15 and D80). Lines in scatterplots represent slope = 1, i.e no change in microfilarial density. X-axis below histograms indicates central values of 2 mf/mg width bins (e.g. 0 indicates microfilarial density between −1 and 1).
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pntd-0002084-g002: Evolution of Onchocerca volvulus microfilarial density (mf/mg) between 15 and 80 days after ivermectin treatment.Microfilarial density at D80 is plotted against density at D15 (scatterplots), for each individual, in ivermectin-naïve and multiply treated subjects. Distribution of individual variation between 15 and 80 days post-treatment is also given (histograms) for the ivermectin-naïve and multiply treated subjects (positive difference means an increase between D15 and D80). Lines in scatterplots represent slope = 1, i.e no change in microfilarial density. X-axis below histograms indicates central values of 2 mf/mg width bins (e.g. 0 indicates microfilarial density between −1 and 1).

Mentions: Between 15 and 80 days after ivermectin, the proportions of subjects with mf increased by a third to 40.2%, and doubled to 41.1% in the control and multiply treated group, respectively. The mean microfilarial density continued to decrease in the control group but showed an increase in the multiply treated group. However, due to the high variability in microfilarial density, mean values are poorly representative of the panel of actual individual responses and, as shown in Figure 2, from D15 to D80, the subjects showed different profiles of evolution of their microfilarial density. In the multiply treated group, a higher proportion of participants showed an increase in microfilarial density than in the control group (38.7% vs 26.7%) (Table 2). At the same time, a higher proportion of subjects showed a decrease in the control group than in the multiply treated group (22.1% vs 11.3%) (Table 2). However, comparison of distribution of individual variations from 15 to 80 days post treatment between the two groups did not yield a significant difference (Kolmogorov-Smirnov test, p = 0.171).


Dynamics of Onchocerca volvulus microfilarial densities after ivermectin treatment in an ivermectin-naïve and a multiply treated population from Cameroon.

Pion SD, Nana-Djeunga HC, Kamgno J, Tendongfor N, Wanji S, Njiokou F, Prichard RK, Boussinesq M - PLoS Negl Trop Dis (2013)

Evolution of Onchocerca volvulus microfilarial density (mf/mg) between 15 and 80 days after ivermectin treatment.Microfilarial density at D80 is plotted against density at D15 (scatterplots), for each individual, in ivermectin-naïve and multiply treated subjects. Distribution of individual variation between 15 and 80 days post-treatment is also given (histograms) for the ivermectin-naïve and multiply treated subjects (positive difference means an increase between D15 and D80). Lines in scatterplots represent slope = 1, i.e no change in microfilarial density. X-axis below histograms indicates central values of 2 mf/mg width bins (e.g. 0 indicates microfilarial density between −1 and 1).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585010&req=5

pntd-0002084-g002: Evolution of Onchocerca volvulus microfilarial density (mf/mg) between 15 and 80 days after ivermectin treatment.Microfilarial density at D80 is plotted against density at D15 (scatterplots), for each individual, in ivermectin-naïve and multiply treated subjects. Distribution of individual variation between 15 and 80 days post-treatment is also given (histograms) for the ivermectin-naïve and multiply treated subjects (positive difference means an increase between D15 and D80). Lines in scatterplots represent slope = 1, i.e no change in microfilarial density. X-axis below histograms indicates central values of 2 mf/mg width bins (e.g. 0 indicates microfilarial density between −1 and 1).
Mentions: Between 15 and 80 days after ivermectin, the proportions of subjects with mf increased by a third to 40.2%, and doubled to 41.1% in the control and multiply treated group, respectively. The mean microfilarial density continued to decrease in the control group but showed an increase in the multiply treated group. However, due to the high variability in microfilarial density, mean values are poorly representative of the panel of actual individual responses and, as shown in Figure 2, from D15 to D80, the subjects showed different profiles of evolution of their microfilarial density. In the multiply treated group, a higher proportion of participants showed an increase in microfilarial density than in the control group (38.7% vs 26.7%) (Table 2). At the same time, a higher proportion of subjects showed a decrease in the control group than in the multiply treated group (22.1% vs 11.3%) (Table 2). However, comparison of distribution of individual variations from 15 to 80 days post treatment between the two groups did not yield a significant difference (Kolmogorov-Smirnov test, p = 0.171).

Bottom Line: Two weeks post ivermectin, microfilarial density dropped equally (98% reduction) in the ivermectin-naïve and multiply treated groups.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.Moreover, they do not support the operation of a strong cumulative effect of repeated treatments on the fecundity of female worms as previously described.

View Article: PubMed Central - PubMed

Affiliation: UMI 233, Institut de Recherche pour le Développement (IRD) and University of Montpellier 1, Montpellier, France. sebastien.pion@ird.fr

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus