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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 80 and 180 days after ivermectin treatment.Microfilarial density at D180 is plotted against density at D80 (scatterplots), for each individual, in ivermectin-naïve and multiply treated subjects. Distribution of individual variation between 80 and 180 days post-treatment is also given (histograms) for the ivermectin-naïve and multiply treated subjects (positive difference means an increase between D80 and D180). 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-g003: Evolution of Onchocerca volvulus microfilarial density (mf/mg) between 80 and 180 days after ivermectin treatment.Microfilarial density at D180 is plotted against density at D80 (scatterplots), for each individual, in ivermectin-naïve and multiply treated subjects. Distribution of individual variation between 80 and 180 days post-treatment is also given (histograms) for the ivermectin-naïve and multiply treated subjects (positive difference means an increase between D80 and D180). 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: From 80 days after ivermectin onwards, reappearance of mf in the skin continued to occur (Table 2, Figure 3). At 180 days post ivermectin, the proportion of subjects with skin mf doubled (increased to 67.8%) in the control group and quadrupled (increased to 76.9%) in the multiply treated one in relation to the values at D15. The mean microfilarial densities remained low in both groups during this time period and reached similar mean values at D180 (2.2 mf/mg in the ivermectin-naïve group vs 2.5 mf/mg in the multiply treated group) (Table 1). At D180, only six (5.0%) and seven (5.8%) individuals had microfilarial densities above 10 mf/mg in the control and multiply treated groups, respectively. The distributions of individual variations from 80 to 180 days post-treatment were similar in the two groups (Kolmogorov-Smirnov test, p = 0.345).


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 80 and 180 days after ivermectin treatment.Microfilarial density at D180 is plotted against density at D80 (scatterplots), for each individual, in ivermectin-naïve and multiply treated subjects. Distribution of individual variation between 80 and 180 days post-treatment is also given (histograms) for the ivermectin-naïve and multiply treated subjects (positive difference means an increase between D80 and D180). 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-g003: Evolution of Onchocerca volvulus microfilarial density (mf/mg) between 80 and 180 days after ivermectin treatment.Microfilarial density at D180 is plotted against density at D80 (scatterplots), for each individual, in ivermectin-naïve and multiply treated subjects. Distribution of individual variation between 80 and 180 days post-treatment is also given (histograms) for the ivermectin-naïve and multiply treated subjects (positive difference means an increase between D80 and D180). 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: From 80 days after ivermectin onwards, reappearance of mf in the skin continued to occur (Table 2, Figure 3). At 180 days post ivermectin, the proportion of subjects with skin mf doubled (increased to 67.8%) in the control group and quadrupled (increased to 76.9%) in the multiply treated one in relation to the values at D15. The mean microfilarial densities remained low in both groups during this time period and reached similar mean values at D180 (2.2 mf/mg in the ivermectin-naïve group vs 2.5 mf/mg in the multiply treated group) (Table 1). At D180, only six (5.0%) and seven (5.8%) individuals had microfilarial densities above 10 mf/mg in the control and multiply treated groups, respectively. The distributions of individual variations from 80 to 180 days post-treatment were similar in the two groups (Kolmogorov-Smirnov test, p = 0.345).

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