<i>Onchocerca volvulus</i> infection and serological prevalence, ocular onchocerciasis and parasite transmission in northern and central Togo after decades of <i>Simulium damnosum</i> s.l. vector control and mass drug administration of ivermectin

<div><p>Background</p><p>Mass drug administration (MDA) of ivermectin has become the main intervention to control onchocerciasis or “river blindness”. In Togo, after many years of MDA, <i>Onchocerca volvulus</i> infection has declined dramatically, and elimination appears achievable, but in certain river basins the current situation remains unknown. We have conducted parasitological, serological, ophthalmological, and entomological assessments in northern and central Togo within the river basins of Ôti, Kéran and Mô.</p><p>Methodology/Principal findings</p><p>Examinations were completed in 1,455 participants from 11 onchocerciasis sentinel villages, and <i>O</i>. <i>volvulus</i> transmission by <i>Simulium damnosum</i> sensu lato (s.l.) was evaluated. In children (aged 1–10 years), the prevalence of microfilariae (Mf) was 2.3% and in adults it ranged from 5.1 to 13.3%. Positive IgG4 responses to <i>O</i>. <i>volvulus</i> adult (crude) worm antigen (OvAg) and the recombinant Ov16 antigen were in all-ages 48.7% and 34.4%, and 29.1% and 14.9% in children, respectively. In the river basin villages of Kéran, Mô and Ôti, the IgG4 seroprevalences to OvAg in children were 51.7%, 23.5% and 12.7%, respectively, and to the Ov16 antigen 33.3% (Kéran) and 5.2% (Ôti). Onchocerciasis ocular lesions (punctate keratitis, evolving iridocyclitis and chorioretinitis) were observed in children and young adults. <i>O</i>. <i>volvulus</i>-specific DNA (Ov150) was detected by poolscreen in vector samples collected from Tchitchira/Kéran(22.8%), Bouzalo/Mô(11.3%), Baghan/Mô(2.9%) and Pancerys/Ôti(4.9%); prevalences of <i>O</i>. <i>volvulus</i> infection in <i>S</i>. <i>damnosum</i> s.l. were, respectively, 1%, 0.5%, 0.1% and 0.2%.</p><p>Conclusions/Significance</p><p>In the northern and central river basins in Togo, interruption of <i>O</i>. <i>volvulus</i> transmission has not yet been attained. Patent <i>O</i>. <i>volvulus</i> infections, positive antibody responses, progressive ocular onchocerciasis were diagnosed, and parasite transmission by <i>S</i>. <i>damnosum</i> s.l. occurred close to the survey locations. Future interventions may require approaches selectively targeted to non-complying endemic populations, to the seasonality of parasite transmission and national onchocerciasis control programs should harmonize cross-border MDA as a coordinated intervention.</p></div

Locations of the villages surveyed and the <i>Simulium</i> collection sites in the three river basins (Ôti, Kéran, Mô) in Savanes, Kara and central regions in Togo.

<p>For an explanation of the control measures and their timings in the northern and central areas of Togo, including SIZ, see legend of <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006312#pntd.0006312.g001" target="_blank">Fig 1</a>.</p

<i>Onchocerca volvulus</i> microfilarial prevalence (% Mf-positive) by age and sex groups in the survey participants from NOCP sentinel villages in central and northern Togo.

<p>The number of examined participants, the Mf-positive status and the percentage of Mf-positive individuals are shown. From n = 41 study participants the age is missing. The 95% confidence intervals (95% CI, Wilson score interval) of the prevalence values are indicated in square brackets. (* significant differences between female and male survey participation).</p

Collection of <i>Simulium damnosum</i> s.l. at the catch point at the Mô river (village of Bouzalo) caught per person (one day per week).

<p>The annual biting rate (ABR) from January 2016 until December 2016 was calculated by multiplying the number of blackflies caught daily by the number of days per week for each month to add up to 12 months. Collections were conducted from 7am to 6pm with alternating fly catchers every two hours as described in Material and Methods.</p

Ocular pathologies and visual acuity in study participants (n = 1,172) according to age.

<p>The ocular pathologies, their grades of evolution and extent were classified as described previously [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006312#pntd.0006312.ref012" target="_blank">12</a>].</p

Spearman’s rank correlation analyses of ocular pathologies and visual acuity of the right eye (RE) in the survey participants and significant associations (p<0.05).

<p>Spearman’s rank correlation analyses of ocular pathologies and visual acuity of the right eye (RE) in the survey participants and significant associations (p<0.05).</p

Prevalence of microfilariae (Mf) of <i>Onchocerca volvulus</i> in sentinel villages (n = 363) of the National Onchocerciasis Control Programme (NOCP) in Togo.

<p>Regular epidemiological surveys (n = 957) were conducted by the NOCP over a 37-year period (1976–2014) in onchocerciasis endemic villages, and from each participant (n = 193,742) a skin biopsy was taken from the left and right iliac crest and the emerging Mf were counted after snip incubation. The graph shows the microfilarial prevalence (median, minimum, maximum, in %) as detected during the annual surveys. Anti-vectorial interventions were applied since 1976, whereas the central regions were incorporated into the Programme in 1987. Since 1988, vector control measures were supplemented by MDA with ivermectin. Initially MDA was applied mainly by mobile teams; during some years of the early 1990’s, aerial larvicide application was suspended in several river basins. In the northern territories (SIZ) vector control and intensified ivermectin distribution was continued after OCP’s closure in 2002. Special interventions in the post-OCP period included continued aerial larvicide application for five additional years (2003–2007) and biannual ivermectin MDA until the end of 2012.</p

Ocular pathologies in study participants (n = 1,183) from onchocerciasis endemic villages situated in the river basins of Kéran, Mô and Ôti in northern and central Togo.

<p>The village populations have been treated annually via CDTI. The ocular pathologies, their grades of evolution and extent were classified as described previously [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006312#pntd.0006312.ref012" target="_blank">12</a>] and are indicated for the right and left eye (RLE), the left eye (LE) and the right eye (RE). Chi-Square tests were applied to compare ocular pathologies of the right eye (RE) between female and male patients. One-sided Fisher exact test was used to evaluate differences in the prevalence of ocular pathologies in patients from the Ôti, Kéran and Mô river basins, and significant differences are indicated by p<0.05. Spearman’s rank correlation analyses of ocular pathologies of the right eye (RE) and age were conducted; the correlation coefficient ρ and the significant associations (p<0.05) are shown.</p

Ov150 rt-PCR (Poolscreen) testing of <i>Simulium damnosum</i> s.l. black flies collected at sentinel catch points in northern and central Togo in 2015.

<p>Each pool consists of 25 blackflies and is listed with the total number of tested flies by catch point, and the number of Ov150-positive pools. The prevalence (in % with 95% confidence intervals) of <i>O</i>. <i>volvulus</i> in <i>S</i>. <i>damnosum</i> s.l. is calculated according to Katholi et al. 1995 [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006312#pntd.0006312.ref016" target="_blank">16</a>]. Fisher’s exact test was applied to evaluate differences in infection rates between pools.</p

<i>Onchocerca volvulus</i> adult worm (OvAg) and recombinant Ov16 antigen-specific IgG4 reactivity (optical densities; OD) in participants and positive and negative IgG4 responses in age groups.

<p>In A and C the data on antigen-specific IgG4 reactivity are shown as mean optical densities (ODs) with 95% confidence intervals for the means (diamonds). The data presented in box plots show the median OD per age group with the 25% and 75% quartiles and the 1.5x of the interquartile range. In B and D the antigen-specific-IgG4 positive and negative responses in age groups are indicated (in %).</p