Update on the biology and ecology of Culicoides species in the South-West region of Cameroon with implications on the transmission of Mansonella perstans.

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 between 10 and 11 pm.

Comparative analysis of IgG and IgG subclasses against Plasmodium falciparum MSP-119 in children from five contrasting bioecological zones of Cameroon.

BACKGROUND: Studies reporting the natural immune responses against malaria in children from different geographical settings in endemic areas are not readily available. This study was aimed at comparing the immune responses against Plasmodium falciparum MSP-119 antigen in children from five contrasting bioecological zones in Cameroon. METHODS: In a cross-sectional survey, children between 2 and 15 years, were enrolled from five ecological strata including the south Cameroonian equatorial forest, sudano-sahelian, high inland plateau, high western plateau, and the coastal strata. The children were screened for clinical malaria (defined by malaria parasitaemia ≥ 5000 parasites/µl plus axillary temperature ≥ 37.5 °C). Their antibody responses were measured against P. falciparum MSP-119 antigen using standard ELISA technique. RESULTS: In all, 415 children comprising 217 (52.3%) males participated. Total IgG and IgG1-IgG4 titres were observed to increase with age in all the strata except in the sudano-sahelian and high inland plateau strata. Total IgG and IgG1-IgG4 titres were significantly higher in the coastal strata and lowest in the high inland plateau (for IgG1 and IgG2) and sudano-sahelian strata (for IgG3 and IgG4). Titres of the cytophilic antibodies (IgG1 and IgG3) were significantly higher than the non-cytophilic antibodies (IgG2 and IgG4) in all the strata except in the sudano-sahelian and high inland plateau strata. Total IgG and IgG subclass titres were significantly higher in children positive for clinical malaria compared to negative children in all study sites except in the high western plateau and coastal (for IgG1 and IgG3), and the sudano-sahelian strata (for all antibodies). Furthermore, a significant positive correlation was observed between parasite density and IgG2 or IgG4 titres in all study sites except in the south Cameroonian equatorial forest and sudano-sahelian strata. CONCLUSIONS: This study showed that antibody responses against MSP-119 vary considerably in children from the different bioecological strata in Cameroon and could be linked to the differential exposure to malaria in the different strata. Furthermore, the rate of antibody acquisition was not observed to increase in an age-dependent manner in low transmission settings.

Mansonella perstans 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.

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-1ß 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.

Successful long-term maintenance of Mansonella perstans in an in vitro culture system.

BACKGROUND: Approximately 114 million people are infected with Mansonella perstans in large proportions of Africa. In contrast to other filariae that infect humans, M. perstans-infected individuals show no distinct pathology or specific clinical picture, indicating a well-tuned adaptation to the host. In addition, since M. perstans adult worms reside in serous cavities which are difficult to access, research has been hindered and there is a paucity of knowledge about the biology of M. perstans, especially the development of the different life stages as well as M. perstans-driven immune responses. Thus in this study, an in vitro culture system was developed which allows an in-depth analysis of M. perstans. RESULTS: Culicoides species were caught in Ediki (Kumba), Southwest Region within Cameroon following a blood meal on a microfilaremic donor that had 1500 microfilariae/ml of peripheral blood and kept in captivity for 12 days at 23 °C. In a pilot experiment, 15 infective larvae were obtained from the midges and co-cultured with a confluent monolayer of monkey kidney epithelial cells (LLC-MK2) in DMEM medium supplemented with 10% FBS for up to 77 days. The resulting survival rates of 33% revealed that the cell-conditioned medium was suitable for long-term maintenance of M. perstans worms. To confirm these preliminary observations, 249 infective larvae were cultured for 50 days and their development was monitored daily and microscopically graded for motility. In total, 170 (68.3%) filariae survived and 124 (49.8%) larvae moulted between days 21-30 to become L5 stage larvae which were motile and showed continuous vigorous movement. CONCLUSION: We have established an in vitro culture system for the generation and long-term maintenance of viable M. perstans worms. This technique will be an important tool to study parasite biology and development, the role in host immunity, and might be helpful to discover novel treatment strategies against this filariae.

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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Epidemiological and clinical profile of paediatric malaria: a cross sectional study performed on febrile children in five epidemiological strata of malaria in Cameroon.

BACKGROUND: In the wake of a decline in global malaria, it is imperative to describe the epidemiology of malaria in a country to inform control policies. The purpose of this study was to describe the epidemiological and clinical profile of paediatric malaria in five epidemiological strata of malaria in Cameroon including: the Sudano-sahelian (SS) strata, the High inland plateau (HIP) strata, the South Cameroonian Equatorial forest (SCEF) strata, the High western plateau (HWP) strata, and the Coastal (C) strata. METHODS: This study involved 1609 febrile children (≤15 years) recruited using reference hospitals in the five epidemiological strata. Baseline characteristics were determined; blood glucose level was measured by a glucometer, malaria parasitaemia was assessed by Giemsa microscopy, and complete blood count was performed using an automated hematology analyser. Severe malaria was assessed and categorized based on WHO criteria. RESULTS: An overall prevalence of 15.0% (95% CI: 13.3-16.9) for malaria was observed in this study. Malaria prevalence was significantly higher in children between 60 and 119 months (p < 0.001) and in Limbe (C strata) (p < 0.001). The overall rate of severe malaria (SM) attack in this study was 29.3%; SM was significantly higher in children below 60 months (p < 0.046). Although not significant, the rate of SM was highest in Maroua (SS strata) and lowest in Limbe in the C strata. The main clinical phenotypes of SM were hyperparasitaemia, severe malaria anaemia and impaired consciousness. The majority (73.2%) of SM cases were in group 1 of the WHO classification of severe malaria (i.e. the most severe form). The malaria case-fatality rate was 5.8%; this was higher in Ngaoundere (HIP strata) (p = 0.034). CONCLUSION: In this study, malaria prevalence decreased steadily northward, from the C strata in the South to the SS strata in the North of Cameroon, meanwhile the mortality rate associated with malaria increased in the same direction. On the contrary, the rate of severe malaria attack was similar across the different epidemiological strata. Immunoepidemiological studies will be required to shed more light on the observed trends.

Identification of the Plasmodium species in clinical samples from children residing in five epidemiological strata of malaria in Cameroon.

BACKGROUND: Malaria in Cameroon was previously known to be caused solely by Plasmodium falciparum but today, evidence points to other Plasmodium species including P. vivax, P. ovale and P. malariae. The purpose of this study was to identify the Plasmodium species in clinical samples from children residing in five epidemiological strata of malaria in Cameroon, so as to advise control policies. METHODS: One thousand six hundred nine febrile children (≤15 years) were recruited from five epidemiological strata of malaria including the Sudano-sahelian (SS) strata, the High inland plateau (HIP) strata, the South Cameroonian Equatorial forest (SCEF) strata, the High western plateau (HWP) strata and the Coastal (C) strata. Malaria parasites were detected by Giemsa microscopy (GM) while a multiplex polymerase chain reaction (PCR) was used to identify the Plasmodium species. Statistical analysis performed included the Pearson chi-square test, and statistical significance was set at p < 0.05. RESULTS: The PCR-adjusted prevalence of malaria was 17.6%. The detection rate of PCR was higher than GM (p = 0.05). However, GM demonstrated a high sensitivity (85.5%) and specificity (100%) and, overall, a perfectly correlated agreement with PCR (97.5%). The prevalence of malaria was significantly higher in children between 60 and 119 months (p < 0.001) and in Limbe (in the Coastal strata) (p < 0.001). Contrariwise, the prevalence of malaria was not associated with gender (p = 0.239). P. falciparum was identified in all (100%) the cases of malaria; P. ovale, P. vivax, P. malariae and P. knowlesi were all absent. No case of mixed infection was identified. CONCLUSIONS: P. falciparum was the only species causing clinical malaria in the target population, which is contrary to studies that have reported P. vivax, P. malariae and P. ovale as causing clinical malaria in Cameroon.

Anaemia and its association with month and blood phenotype in blood donors in Fako division, Cameroon.

BACKGROUND: Anaemia is one of the main factors in the deferral (disqualification) of blood donors following haematological screening. There is paucity of data on the prevalence of anaemia in blood donors in Sub-Saharan Africa. This study was undertaken to determine the prevalence of anaemia and its association with month and blood phenotype in blood donors in Fako division of Cameroon. METHODS: Blood donors were recruited between the 1st of January and 31st of December 2014, and their haemoglobin concentration (Hb) was determined using a haemoglobinometer. Anaemia was considered as Hb < 12 g/dl for females and Hb < 13 g/dl for males. The ABO and Rhesus blood groups were determined using standard techniques with monoclonal antibodies and the Coombs' test. The Pearson's chi-square, Pearson's correlation, student T test, ANOVA, univariate and multivariable logistic regression analyses adjusting for gender and age as categorical variable were all performed as part of the statistical analysis. RESULTS: A total of 1896 blood donors predominantly males (91.35%) took part in the study. The mean age of the donors was 32 ± 7.81 years. On average, donors had donated blood 5.07 ± 3.54 times in their lifetime. The prevalence of anaemia observed in this study was 31.44% (95% CI: 29.35-33.58). The prevalence of anaemia was higher in females (p ≤ 0.0001) and in participants of age 20 years and below (p = 0.001). A marginal association was observed between prevalence of anaemia and season (p = 0.051). Furthermore, a significant association was observed between prevalence of anaemia and the blood group AB (p = 0.001). The risk of developing anaemia was higher in females compared to males (OR = 2.7, p < 0.0001). The mean Hb observed in this study was 13.42 ± 1.65; the mean Hb was not observed to be associated with the month or season adjusting for age and gender. CONCLUSION: This study revealed a high prevalence of anaemia which translates to a high rate of donor deferral as a result of anaemia in the study area. The prevalence of anaemia was observed to be associated with the blood phenotype and the month, but not the season (dry or rainy). Further studies will be needed to ascertain the aetiology and associated factors for anaemia in blood donors in the study area.

Update on the distribution of Mansonella perstans in the southern part of Cameroon: influence of ecological factors and mass drug administration with ivermectin.

BACKGROUND: Mansonellosis remains one of the most neglected of tropical diseases and its current distribution in the entire forest block of southern Cameroon is unknown. In order to address this issue, we have surveyed the distribution of Mansonella perstans in different bioecological zones and in addition, elucidated the influence of multiple rounds of ivermectin (IVM) based mass drug administration (MDA). METHODS: A mixed design was used. Between 2000 and 2014, both cross-sectional and longitudinal surveys were carried out in 137 communities selected from 12 health districts belonging to five main bioecological zones of the southern part of Cameroon. The zones comprised of grassland savanna (GS), mosaic forest savanna (MFS), forested savanna (FS), deciduous equatorial rainforest (DERF) and the dense humid equatorial rainforest (DHERF). The survey was carried out in some areas with no treatment history as well as those currently under IVM MDA. Individuals within the participatory communities were screened for the presence of M. perstans microfilariae (mf) in peripheral blood by the calibrated thick film method to determine both prevalence and geometric mean intensities at the community level. RESULTS: Apart from sporadic cases in savanna areas, distribution of M. perstans was strongly linked to the equatorial rainforest zones. Before CDTI, the highest mean prevalence (70.0 %) and intensity (17,382.2 mf/ml) were obtained in communities in Mamfes' DHERF areas followed by communities in the DHERF zone of Lolodorf (53.8 % and 7,814.8 mf/ml, respectively). A longitudinal survey in Mamfe further showed that M. perstans infections had reduced by 34.5 % in DERF (P < 0.001) but not DHERF zones after ten years of IVM MDA. Further data from the cross-sectional study revealed that there was a decrease in prevalence in DHERF zones only after ten years of MDA. In DERF zones however, the infection was relatively lower after four years of MDA. CONCLUSIONS: The distribution of M. perstans in the southern part of Cameroon varies with bioecological zones and IVM MDA history. The zones with high prevalence and intensities lie in forested areas while those with low endemicity are in the savanna areas. MDA with ivermectin induced significant reduction in the endemicity of mansonellosis in the decidious equatorial rainforest. In contrast, the prevalence and intensity remained relatively high and stable in the dense humid equatorial rainforest zones even after a decade of mass drug administration with ivermectin. Since it is known that M. perstans down-regulates host's immune system, the findings from this work would be useful in designing studies to understand the impact of M. perstans on host immune response to vaccination and co-infection with other pathogens such as Mycobacterium spp. and Plasmodium spp. in areas of contrasting endemicities.

Cross-Reactivity of Filariais ICT Cards in Areas of Contrasting Endemicity of Loa loa and Mansonella perstans in Cameroon: Implications for Shrinking of the Lymphatic Filariasis Map in the Central African Region.

BACKGROUND: Immunochromatographic 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 FINDINGS: A 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/SIGNIFICANCE: This 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.

Coinfection with malaria and intestinal parasites, and its association with anaemia in children in Cameroon.

BACKGROUND: The purpose of this study was to determine the prevalence of coinfection with malaria and intestinal parasites, as well as to determine its association with anaemia in children aged 10 years and below in Muyuka, Cameroon. MATERIALS AND METHODS: This was a cross-sectional study. Participants were febrile children who were admitted to the Muyuka district hospital between April and October 2012. Blood and stool samples were collected from those participants who gave consent to take part in the study. Haemoglobin concentration (Hb) and complete blood count (CBC) were performed using an automated haematology analyser (Mindray®, BC-2800). Giemsa-stained blood film was examined to detect malaria parasites, while the formol-ether concentration technique was used to detect intestinal parasitic infections (IPIs). The Pearson's chi-square, Student's T-test and correlation analysis were all performed as part of the statistical analyses. RESULTS: Four hundred and eleven (411) children successfully took part in this study. The prevalence of malaria, IPIs, malaria and IPI coinfection, and anaemia observed were 98.5 %, 11.9 %, 11.9 % and 44.8 %, respectively. Anaemia and IPIs were significantly associated with age; anaemia was more prevalent in children under five years of age (p = 0.000), whereas IPIs were more prevalent in children aged between five and 10 years (p = 0.006). The parasite species isolated included Ascaris lumbricoides (36 [73.5 %]), Entamoeba histolytica/dispar (9 [18.4 %]) and hookworm (4 [8.2 %]). The mean Hb observed was 10.64 g/dl (±1.82). A significant negative correlation was observed between malaria parasite density and Hb. There was no significant difference in the prevalence of anaemia among children infected with malaria, IPIs, or malaria and IPI coinfection, or among non-infected children. Similarly, the mean Hb did not differ among infected and non-infected children. CONCLUSION: This study showed that malaria and IPIs still constitute a major public health problem in the study area despite a lack of any significant association between these infections and anaemia. The findings suggest that there is a need for the implementation of control measures to curb the rate of malaria and IPIs in the study area.

A murine macrofilaricide pre-clinical screening model for onchocerciasis and lymphatic filariasis.

BACKGROUND: New drugs effective against adult filariae (macrofilaricides) would accelerate the elimination of lymphatic filariasis and onchocerciasis. Anti-Onchocerca drug development is hampered by the lack of a facile model. We postulated that SCID mice could be developed as a fmacrofilaricide screening model. METHODS: The filaricides: albendazole (ABZ), diethylcarbamazine (DEC), flubendazole (FBZ), ivermectin (IVM) and the anti-Wolbachia macrofilaricide, minocycline (MIN) were tested in Brugia malayi (Bm)-parasitized BALB/c SCID mice vs vehicle control (VC). Responses were compared to BALB/c wild type (WT). Onchocerca ochengi male worms or onchocercomata were surgically implanted into BALB/c SCID, CB.17 SCID, BALB/c WT mice or Meriones gerbils. Survival was evaluated at 7-15 days. BALB/c SCID were tested to evaluate the responsiveness of pre-clinical macrofilaricides FBZ and rifapentine (RIFAP) against male Onchocerca. RESULTS: WT and SCID responded with >95% efficacy following ABZ or DEC treatments against Bm larvae (P < 0.0001). IVM was partially filaricidal against Bm larvae in WT and SCID (WT; 39.8%, P = 0.0356 and SCID; 56.7%, P = 0.026). SCID responded similarly to WT following IVM treatment of microfilaraemias (WT; 79%, P = 0.0194. SCID; 76%, P = 0.0473). FBZ induced a total macrofilaricidal response against adult Bm in WT and SCID (WT; P = 0.0067, SCID; P = 0.0071). MIN induced a >90% reduction in Bm Wolbachia burdens (P < 0.0001) and a blockade of microfilarial release (P = 0.0215) in SCID. Male Onchocerca survival was significantly higher in SCID vs WT mice, but not gerbils, after +15 days (60% vs 22% vs 39% P = 0.0475). Onchocercoma implants had engrafted into host tissues, with evidence of neovascularisation, after +7 days and yielded viable macro/microfilariae ex vivo. FBZ induced a macrofilaricidal effect in Onchocerca male implanted SCID at +5 weeks (FBZ; 1.67% vs VC; 43.81%, P = 0.0089). Wolbachia loads within male Onchocerca were reduced by 99% in implanted SCID receiving RIFAP for +2 weeks. CONCLUSIONS: We have developed a 'pan-filarial' small animal research model that is sufficiently robust, with adequate capacity and throughput, to screen existing and future pre-clinical candidate macrofilaricides. Pilot data suggests a murine onchocercoma xenograft model is achievable.