BackgroundImmunochromatographic card test (ICT) is a tool to map the distribution of Wuchereria bancrofti. In areas highly endemic for loaisis in DRC and Cameroon, a relationship has been envisaged between high L. loa microfilaria (Mf) loads and ICT positivity. However, similar associations have not been demonstrated from other areas with contrasting levels of L. loa endemicity. This study investigated the cross-reactivity of ICT when mapping lymphatic filariasis (LF) in areas with contrasting endemicity levels of loiasis and mansonellosis in Cameroon.Methodology/Principal FindingsA cross-sectional study to assess the prevalence and intensity of W. bancrofti, L. loa and M. perstans was carried out in 42 villages across three regions (East, North-west and South-west) of the Cameroon rainforest domain. Diurnal blood was collected from participants for the detection of circulating filarial antigen (CFA) by ICT and assessment of Mf using a thick blood smear. Clinical manifestations of LF were also assessed. ICT positives and patients clinically diagnosed with lymphoedema were further subjected to night blood collection for the detection of W. bancrofti Mf. Overall, 2190 individuals took part in the study. Overall, 24 individuals residing in 14 communities were tested positive by ICT, with prevalence rates ranging from 0% in the South-west to 2.1% in the North-west. Lymphoedema were diagnosed in 20 individuals with the majority of cases found in the North-west (11/20), and none of them were tested positive by ICT. No Mf of W. bancrofti were found in the night blood of any individual with a positive ICT result or clinical lymphoedema. Positive ICT results were strongly associated with high L. loa Mf intensity with 21 subjects having more than 8,000 L. loa Mf ml/blood (Odds ratio = 15.4; 95%CI: 6.1–39.0; p < 0.001). Similarly, a strong positive association (Spearman’s rho = 0.900; p = 0.037) was observed between the prevalence of L. loa and ICT positivity by area: a rate of 1% or more of positive ICT results was found only in areas with an L. loa Mf prevalence above 15%. In contrast, there was no association between ICT positivity and M. perstans prevalence (Spearman’s rho = - 0.200; p = 0.747) and Mf density (Odds ratio = 1.8; 95%CI: 0.8–4.2; p = 0.192).Conclusions/SignificanceThis study has confirmed the strong association between the ICT positivity and L. loa intensity (Mf/ml of blood) at the individual level. Furthermore, the study has demonstrated that ICT positivity is strongly associated with high L. loa prevalence. These results suggest that the main confounding factor for positive ICT test card results are high levels of L. loa. The findings may indicate that W. bancrofti is much less prevalent in the Central African region where L. loa is highly endemic than previously assumed and accurate re-mapping of the region would be very useful for shrinking of the map of LF distribution.

Elimination of the helminth disease, river blindness, remains challenging due to ivermectin treatment-associated adverse reactions in loiasis co-infected patients. Here, we address a deficit in preclinical research tools for filarial translational research by developing Loa loa mouse infection models. We demonstrate that adult Loa loa worms in subcutaneous tissues, circulating microfilariae (mf) and presence of filarial biomarkers in sera occur following experimental infections of lymphopenic mice deficient in interleukin (IL)-2/7 gamma-chain signaling. A microfilaraemic infection model is also achievable, utilizing immune-competent or -deficient mice infused with purified Loa mf. Ivermectin but not benzimidazole treatments induce rapid decline (>90%) in parasitaemias in microfilaraemic mice. We identify up-regulation of inflammatory markers associated with allergic type-2 immune responses and eosinophilia post-ivermectin treatment. Thus, we provide validation of murine research models to identify loiasis biomarkers, to counter-screen candidate river blindness cures and to interrogate the inflammatory etiology of loiasis ivermectin-associated adverse reactions.

IntroductionThe 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.MethodsWe 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.ResultsWe 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.ConclusionInadequate human resource, funding issues and transportation challenges during distribution periods reduced the ability of the health service to thoroughly sensitize communities and supervis...

The filarial nematode Mansonella perstans is endemic throughout Africa, northern South America and the Caribbean. Interestingly, M. perstans-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 M. perstans-driven immune responses. A hindrance in obtaining data on M. perstans-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 Mansonella perstans worm antigen extract as stimulant to obtain filarial-specific recall and immunoglobulin responses from M. perstans 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 M. perstans-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, M. perstans-specific immune responses using worm antigen extract and shows that patent M. perstans infections have distinct Th2, Breg and Treg subsets accompanied with reduced systemic innate and adaptive immune responses and dominant filarial-specific IgG4 levels.

Background Culicoides (Diptera; Ceratoponidae) are tiny, stout, blood-sucking flies with a near worldwide distribution. When present, they are often considered a biting nuisance but in addition, they are involved in the transmission of pathogens to humans, domestic and wild animals. Data on Culicoides species in the South-West region of Cameroon dates back to the 1950s. Over the decades, ecological transformation due to agriculture and deforestation may have affected the population dynamics of Culicoides and therefore our study provides an update of their bio-ecology in the region. Furthermore, the role of various Culicoides species in the transmission of parasitic filariae of the genus Mansonella remains inconclusive in this region. This study was designed to address these unknown issues and expand on current scientific knowledge. Results Eight species of Culicoides ( C. bedfordi , C. inornatipennis , C. fulvithorax , C. grahamii , C. imicola , C. milnei , C. neavei and C. kumbaensis ) were collected using light traps and human baits. Culicoides grahamii was the most abundant species, followed closely by C. milnei . Three species ( C. milnei , C. grahamii and C. inornatipennis ) were common in all observed larval development sites. Only four species ( C. inornatipennis , C. fulvithorax , C. grahamii and C. milnei ) were collected on humans. Anthropophilic species were more abundant ( P < 0.001) in the evening (4–7 pm) when compared to the morning collections (6–9 am). After overnight fly collections using a drop trap with a human microfilaremic donor, C. milnei emerged as the potential host for transmitting Mansonella perstans . Substantial heterogeneity was observed between the trap visiting cycles of the various species ( P < 0.001). The biting cycle of the main vector, C. milnei , showed two peaks (10–11 pm and 4–5 am), the highest being 10–11 pm. Conclusions The Culicoides fauna of the South-West region of Cameroon has not changed significantly since the 1950s. Culicoides milnei was demonstrated to be the major vector of M. perstans in this part of Cameroon. It is essentially a nocturnal species which peaks in abundance bet...