Programmatic factors associated with the limited impact of Community-Directed Treatment with Ivermectin to control Onchocerciasis in three drainage basins of South West Cameroon

<div><p>Introduction</p><p>The CDTI model is known to have enhanced community participation in planning and resource mobilization toward the control of onchocerciasis. These effects were expected to translate into better individual acceptance of the intervention and hence high Treatment Coverage, leading to a sustainable community-led strategy and reduction in the disease burden. A survey revealed that after 10–12 rounds of treatment, prevalence of onchocerciasis was still high in three drainage basins of South West Cameroon and transmission was going on.</p><p>Methods</p><p>We designed a three (3)-year retrospective (2012, 2013 and 2014), descriptive cross-sectional study to explore the roles of operational challenges in the failure of CDTI to control the disease as expected. We administered 83 semi-structured questionnaires and conducted 12 in-depth interviews with Chiefs of Bureau Health, Chiefs of Centers, CDDs and Community Heads. Descriptive statistics was used to explore indicators of performance which were supported with views from in-depth interviews.</p><p>Results</p><p>We found that community participation was weak; communities were not deciding time and mode of distributions. Only 6 (15.0%) of 40 Community Drug Distributors reported they were selected at general community meetings as required. The health service was not able to meet and discuss Community-Directed Treatment with Ivermectin activities with individual communities partly due to transportation challenges; this was mostly done through letters. Funding was reported to be inadequate and not timely. Funds were not available to conduct Community-Self Monitoring after the 2014 Mass Drug Administration. There was inadequate health staff at the frontline health facility levels, and some Chiefs of Center reported that Community-Directed Treatment with Ivermectin work was too much for them. The mean operational Community Drug Distributor-population ratio was 1 Community Drug Distributor per 317 populations (range: 194–464, expected is 1:250). Community Drug Distributor attrition rate was 14% (2012), 11% (2013) and 12% (2014) of total Community Drug Distributors trained in the region. Lack of incentive for Community Drug Distributor was primary reason for Community Drug Distributor attrition. Number of Community Drug Distributors trained together by health area ranged from 14 to 127 (mean ± SD = 51 ±32) with duration of training ranging from 4–7 hours (mean ± SD = 5.05 ± 1.09). The trainings were conducted at the health centers. Community Drug Distributors always conducted census during the past three distributions (Mean ± SD = 2.85 ± 0.58). Community-Self Monitoring was facing challenge. Several of the community heads, Chiefs of Bureau Health and Chiefs of Center agreed that Community-Self Monitoring was not being carried out effectively due to lack of incentives for monitors in the communities.</p><p>Conclusion</p><p>Inadequate human resource, funding issues and transportation challenges during distribution periods reduced the ability of the health service to thoroughly sensitize communities and supervise CDTI activities. This resulted in weak community understanding, acceptance and participation in the process. CDTI in our study area did not achieve sustainable community-led campaign and this may have led to the reduced impact on Onchocerciasis.</p></div

Elevated frequencies of CD3^-CD16⁺CD56⁺ natural killer cells in peripheral blood of <i>M</i>. <i>perstans</i>-microfilaremic individuals.

<p>Using flow cytometry, peripheral whole blood cells from <i>M</i>. <i>perstans</i> microfilaremic (Mp MF+; n = 11) and amicrofilaremic (Mp MF-; n = 10) individuals were analyzed for frequencies (%) of (<b>A</b>) CD3⁺ T cells co-expressing CD16 and CD56 for NKT cells and (<b>B</b>) CD3^- cells co-expressing CD16 and CD56 to determine NK populations. Graphs show box whiskers with median, interquartile ranges and outliers. Statistical significances between the indicated groups were obtained using the Mann-Whitney-U-test.</p

The experiences of COCs with Ivermectin distribution over the past three years.

<p>The experiences of COCs with Ivermectin distribution over the past three years.</p

<i>Mansonella perstans</i> microfilaremic individuals are characterized by enhanced type 2 helper T and regulatory T and B cell subsets and dampened systemic innate and adaptive immune responses

<div><p>The filarial nematode <i>Mansonella perstans</i> is endemic throughout Africa, northern South America and the Caribbean. Interestingly, <i>M</i>. <i>perstans</i>-infected individuals present no distinct clinical picture associated with certain pathology. Due to its relatively silent nature, research on this tropical disease has been neglected, especially <i>M</i>. <i>perstans</i>-driven immune responses. A hindrance in obtaining data on <i>M</i>. <i>perstans</i>-specific responses has been the inability to obtain adult worms since their habitats in serous cavities are difficult to access. Thus, in this study, for the first time, we used <i>Mansonella perstans</i> worm antigen extract as stimulant to obtain filarial-specific recall and immunoglobulin responses from <i>M</i>. <i>perstans</i> microfilaremic individuals (Mp MF+) from Cameroon. Moreover, systemic immune profiles in sera and immune cell composition in peripheral blood from Mp MF+ and amicrofilaremic individuals (Mp MF-) were obtained. Our data reveal that Mp MF+ individuals showed significantly reduced cytokine (IL-4, IL-6 and IL-12p70) and chemokine levels (IL-8 and RANTES), but significantly higher MIP-1β as well as increased <i>M</i>. <i>perstans</i>-specific IgG4 levels compared to Mp MF- individuals. In contrast, upon re-stimulation with worm antigen extract, IFN-γ, IL-13, IL-10 and IL-17A secretion was enhanced in cell cultures from Mp MF+ individuals when compared to those from cultures of healthy European individuals. Moreover, analysis of immune cell composition in peripheral blood from Mp MF+ individuals revealed increased type 2 helper T (Th2), natural killer (NK), regulatory B and T cell (Breg and Treg) subsets but decreased type 1 regulatory T (Tr1) cells. In summary, this study deciphers for the first time, <i>M</i>. <i>perstans</i>-specific immune responses using worm antigen extract and shows that patent <i>M</i>. <i>perstans</i> infections have distinct Th2, Breg and Treg subsets accompanied with reduced systemic innate and adaptive immune responses and dominant filarial-specific IgG4 levels.</p></div

Increased frequencies of regulatory T and B cells (Tregs and Bregs) but decreased type 1 regulatory T (Tr1) cell populations in <i>M</i>. <i>perstans</i> microfilaremic individuals.

<p>Using flow cytometry, peripheral whole blood cells from <i>M</i>. <i>perstans</i> microfilaremic (Mp MF+; n = 11) and amicrofilaremic (Mp MF-; n = 10) individuals were analyzed for frequencies (%) of (<b>A</b>) CD4⁺CD127⁺ expressing CD25^high Tregs, (<b>B</b>) CD4+α/βTCR⁺ expressing CD49b and LAG3 Tr1 cells and (<b>C</b>) CD19⁺CD24^highCD38^high expressing CD1d^high Bregs. Graphs show box whiskers with median, interquartile ranges and outliers. Statistical significances between the indicated groups were obtained using the Mann-Whitney-U-test.</p

Reduced systemic IL-13, IL-4 and IL-17A levels in <i>M</i>. <i>perstans</i> microfilaremic individuals.

<p>Sera from <i>M</i>. <i>perstans</i>-microfilaremic (Mp MF+, n = 11) and amicrofilaremic (Mp MF-; n = 28) individuals were analyzed for the contents of (<b>A</b>) IFN-γ, (<b>B</b>) IL-5, (<b>C</b>) IL-13, (<b>D</b>) IL-4, (<b>E</b>) IL-10 and (<b>F</b>) IL-17A using luminex technology. Graphs show box whiskers with median, interquartile ranges and outliers. Statistical significances between the indicated groups were obtained using the Mann-Whitney-U-tests.</p

Level of Community heads awareness of community roles in the CDTI process.

<p>Level of Community heads awareness of community roles in the CDTI process.</p

Dominant <i>M</i>. <i>perstans</i>-specific IL-10, IFN-γ, IL-13 and IL-17A production by peripheral cells from <i>M</i>. <i>perstans</i> microfilaremic individuals.

<p>Freshly isolated peripheral whole blood cells (100μl/well) from <i>M</i>. <i>perstans</i> microfilaremic individuals (Mp MF+; n = 9) and healthy European non-endemic normals (NEN; n = 4) were cultivated in 10% BCS/RPMI-1640 medium (100μl/well) and left either un-stimulated (Cntl) or cultured with <i>M</i>. <i>perstans</i>-derived worm antigen extract (Mp Ag, 50μg/ml) at 37°C for 72 hours. Thereafter, culture supernatants were analysed for levels of (<b>A</b>) IFN-γ, (<b>B</b>) IL-4, (<b>C</b>) IL-5 (<b>D</b>) IL-13, (<b>E</b>) IL-10 and (<b>F</b>) IL-17A by ELISA. Graphs show box whiskers with median, interquartile ranges and outliers. Statistical significances between the indicated groups were obtained using the Kruskal-Wallis-test and, if significant, followed by a Dunn`s multiple comparison test for further comparison of the groups.</p

Characteristics of CDD training for the past three distributions in our study area.

<p>Characteristics of CDD training for the past three distributions in our study area.</p

Mode of selection of CDDs in the study communities.

<p>Mode of selection of CDDs in the study communities.</p