Spatial and temporal diversity of Simulium damnosum s.l. gut microbiota and association with Onchocerca volvulus infection in Cameroon.

Arthropod microbiota plays an important role in host physiology, and there is growing interest in using vector symbionts to modify vector competence and control parasite transmission. This study aims to characterise the blackfly Simulium damnosum s.l. gut microbiota and to explore possible associations with various bio-ecological determinants of the Onchocerca volvulus establishment and the transmission in blackfly. Adult female blackflies were caught in three Cameroonian health districts belonging to different bioecological zones endemic for onchocerciasis. Flies were dissected and qPCR screened for Onchocerca volvulus infection. The diversity of the blackflies gut microbiota was assessed by high-throughput sequencing of the V3-V4 hypervariable region of the bacterial 16S ribosomal RNA. Subsequent metataxo-genomic, multivariate, and association analysis were used to investigate the variables that influence the microbiota diversity. Transmission index rates ranging from 20.7 to 6.0 % and 6.2-2.0 % for infection and infectivity rates, respectively, indicate ongoing transmission of onchocerciasis across all surveyed health districts. The identified bacterial taxa were clustered into four phyla, five classes, and 23 genera. The S. damnosum s.l. gut microbiota was dominated by Wolbachia and by Rosenbergiella in Wolbachia-free Simulium. Significant differences were observed in the diversity of S. damnosum s.l. microbiota concerning parity status (P = 0.007), health district of origin (P = 0.001), and the presence of the Onchocerca volvulus. Simulium from the Bafia health district also showed increased bacterial diversity between two consecutive years (P = 0.001). Four bacterial taxa, including Serratia, were associated with the absence of the O. volvulus infection. These results indicate that S. damnosum s.l. from different onchocerciasis foci in Cameroon, exhibit distinguishable gut microbial compositions which are dynamic over time. Some bacterial species are associated with the O. volvulus infection and could be further investigated as biological target/tool for vector modified-based onchocerciasis control.

Persistent transmission of soil-transmitted helminths despite 16 years of uninterrupted Mebendazole- and ivermectin-based preventive chemotherapy in the Lomie Health District (East Region, Cameroon): The emergency of complementary control strategies.

BACKGROUND: The control of the Soil-Transmitted Helminths (STH) infections primarily relies on the school-based Preventive Chemotherapy (PCT) with mebendazole. Given the efficacy of ivermectin on STH, the control of the latter is expected to be potentialized in areas where ivermectin is also distributed for onchocerciasis and/or lymphatic filariasis control/elimination. This study aimed to assess the prevalence and intensity of STH in the Lomie Health District where annual school-based deworming campaigns and community-directed treatments with Ivermectin have been underway for almost two decades. METHODOLOGY/PRINCIPAL FINDINGS: A quantitative cross-sectional study was conducted in 10 schools of the Lomie Health District, East Region, Cameroon. Stool samples were collected from school-aged children and analysed using the Kato-Katz technique. Semi-structured questionnaires were administered to enrolees to assess compliance with water, sanitation, and hygiene (WASH). Of the 491 children (median age: 9 years; IQR: 7-10) enrolled, 83.9% (95% CI: 80.3-87.1) were infected with at least one STH species. Trichuris trichiura was the predominant species (78.5%), and no hookworm was found. The prevalence trend slightly decreased between 1987 and 2010 (~8%) and remained unchanged since 2010 (p-value = 0.05). Overall, 46.8% and 41.8% of children were heavy-to-moderately infected with Ascaris lumbricoides and T. trichiura. Poor hand hygiene (OR: 2.24, 95% IC: 1.4-3.4, p-value = 0.0002) and the use of river as a source of drinking water (OR: 14.8, 95% IC: 6.9-33.3, p-value = 0.0001) were the main risk factors associated with the STH infection in Lomie Health District. CONCLUSIONS/SIGNIFICANCE: The persistent high prevalence and intensity of STH infection despite 16 years of mebendazole-based PCT and expected collateral impact of ivermectin mass distribution, points to plausible implementation gaps, poor compliance to WASH or sub-optimal efficacy of the anthelminthics used. This study highlights the need to further assess the cause of the persistent high prevalence and implement context-adapted control measures in order to curb STH transmission.

Safety and Short-term Efficacy of a Single Dose of 2†mg Moxidectin in Loa loa-Infected Individuals: A Double-Blind, Randomized Ivermectin-Controlled Trial With Ascending Microfilarial Densities.

Background: In 2018, the US Food and Drug Administration approved the macrocylic lactone moxidectin (MOX) at 8 mg dosage for onchocerciasis treatment in individuals aged ≥12 years. Severe adverse reactions have occurred after ivermectin (IVM), also a macrocyclic lactone, in individuals with high Loa microfilarial density (MFD). This study compared the safety and efficacy of a 2 mg MOX dose and the standard 150 µg/kg IVM dose in individuals with low L loa MFD. Methods: A double-blind, randomized, ivermectin-controlled trial of a 2 mg moxidectin dose was conducted in Cameroon between May and July 2022. It enrolled 72 adult men with L loa MFD between 5 and 1000 microfilariae/mL. Outcomes were occurrence of adverse events (AEs) and L loa MFD reduction rate during the first month off treatment. Results: No serious or severe AEs occurred among the 36 MOX- or the 36 IVM-treated individuals. Forty-nine AEs occurred in the MOX arm versus 59 AEs in the IVM arm. Grade 2 AE incidence was higher among IVM- than MOX-treated participants (38.5% and 14.3%, respectively, P = .043). Median MFD reduction rates were significantly higher after IVM than MOX at day 3 (70.2% vs 48.5%), day 7 (76.4% vs 50.0%), and day 30 (79.8% vs 48.1%). Conclusions: A single 2 mg MOX dose is as safe as 150 µg/kg IVM in patients with low L loa MFD. Further studies with higher MOX doses and in patients with higher MFD are warranted. Clinical Trials Registration: NCT04049851.

Impact of short-term discontinuation of ivermectin-based chemoprevention on onchocerciasis transmission in endemic settings with long history of mass drug administration.

BACKGROUND: The control of onchocerciasis currently relies on annual distribution of single dose ivermectin. Because ivermectin has minimal effects on the adult parasite, mass drug administration (MDA) campaigns against onchocerciasis require at least 15 years of annual uninterrupted ivermectin distribution. Mathematical models have predicted that short-term disruption of MDA (as was seen during COVID-19) could impacted the microfilaridermia prevalence depending on the pre-control endemicity and the histories of treatment, requiring corrective measures (such as biannual MDA) to mitigate the effect on onchocerciasis elimination. Field evidence supporting this prediction, however, has yet to be gathered. This study aimed to assess the impact of ~2 years disruption of MDA on onchocerciasis transmission indicators. METHODOLOGY: A cross-sectional survey was carried out in 2021 in seven villages of Bafia and Ndikinimeki, two health districts located in the Centre Region, Cameroon, where MDA has been ongoing for two decades, but interrupted in 2020 as a response to the COVID-19 pandemic. Volunteers aged 5 years and above were enrolled for clinical and parasitological examinations for onchocerciasis. Data were compared with pre-COVID-19 prevalence and intensity of infection from the same communities to measure changes over time. PRINCIPAL FINDINGS: A total of 504 volunteers (50.3% males), aged 5-99 years (Median: 38; IQR: 15-54) was enrolled in the two health districts. The overall prevalence of microfilaridermia in 2021 was similar in Ndikinimeki health district (12.4%; 95% CI: 9.7-15.6) and Bafia health district (15.1%; 95% CI: 11.1-19.8) (p-value = 0.16). Microfilaridermia prevalences were either similar between 2018 and 2021 in the communities of Ndikinimeki health district (19.3% vs 12.8% (p = 0.057) for Kiboum 1; and 23.7% vs 21.4% (p = 0.814) for Kiboum 2), or higher in 2019 compared to 2021 in the communities of Bafia health district (33.3% vs 20.0% (p = 0.035) for Biatsota). The mean microfilarial densities in these communities dropped from 5.89 (95% CI: 4.77-7.28) mf/ss to 2.4 (95% CI: 1.68-3.45) mf/ss (p-value < 0.0001), and from 4.81 (95% CI: 2.77-8.31) mf/ss to 4.13 (95% CI: 2.49-6.86) mf/ss (p-value < 0.02) in Bafia and Ndikinimeki health districts, respectively. Community Microfilarial Load (CMFL) dropped from 1.08-1.33 mf/ss in 2019 to 0.052-0.288 mf/ss in 2021 in Bafia health district while remaining stable in the Ndikinimeki health district. CONCLUSION/SIGNIFICANCE: The continued decline in prevalence and CMFL observed ~2 years after MDA disruption is consistent with mathematical predictions (ONCHOSIM) and shows that additional efforts and resources are not needed to mitigate the effects of short-term MDA disruption in highly endemic settings prior to intervention with long treatment histories.

Prevalence of epilepsy in Ndom Health District (Littoral Region, Cameroon) after long-term ivermectin-based preventive chemotherapy for the control of onchocerciasis.

Assuming the causality relationship between Onchocerca volvulus infection and epilepsy onset, preventive chemotherapy for the control onchocerciasis can result to a significant impact on epilepsy burden. This study aimed at assessing the prevalence of epilepsy in an onchocerciasis endemic area under annual CDTI for 16 years. A cross-sectional survey was conducted in two communities (Kelleng and Nkonkwalla) located in the Ndom Health District (Littoral Region, Cameroon) to assess the prevalence of epilepsy using a standardized questionnaire for non-specialists in tropical areas. Data on the nuisance of onchocerciasis vector and distance of surveyed households to the river were also collected. Epilepsy status was collected from 367 participants (sex ratio (M/F): 1.13). The crude prevalence of epilepsy was estimated at 8.4 % (95 % CI: 5.8-11.8); the highest prevalence was found in females (13.8 %; 95 % CI: 8.8-20.3) compared to males (5.0 %; 95 % CI: 2.4-9.04)) (p-value = 0.02) and in Nkonkwalla (9.0 %; 95 % CI: 5.5-13.6) (p-value = 0.82) compared to Kelleng (7.7 %; 95 % CI: 4.06-13.13). After 16 years of CDTI in Kelleng, crude prevalence of epilepsy decreased from 10.2 % to 7.2 % (p-value = 0.19), whereas the age sex-standardized prevalence dropped from 13.5 % to 7.7 % between 2004 and 2020 (p-value = 0.05). The median age of epilepsy cases shifted from 24 (IQR: 20-30) in 2004 to 28 years (IQR: 23-34) in 2020. The shift in age-specific prevalence over the years suggests a decreasing incidence of epilepsy in areas under long-term CDTI and a significant impact of onchocerciasis control on the prevalence of epilepsy.

High infection rates for onchocerciasis and soil-transmitted helminthiasis in children under five not receiving preventive chemotherapy: a bottleneck to elimination.

BACKGROUND: The current mainstay for control/elimination of onchocerciasis and soil-transmitted helminthiasis (STH) relies on ivermectin- and mebendazole/albendazole-based preventive chemotherapies. However, children under five years of age have been excluded in both research activities and control programs, because they were believed to have insignificant infection rates. There is therefore a need for up-to-date knowledge on the prevalence and intensity of STH and onchocerciasis infections in this age group. This study aimed at assessing the rates and intensities of onchocerciasis and STH infections in children under five years of age who are excluded from ivermectin- or mebendazole/albendazole-based preventive chemotherapies. METHODS: A series of cross-sectional surveys was conducted in four Health Districts in the Centre and Littoral Regions of Cameroon between 2018 and 2019. All subjects aged 2 to 4 years, were screened for prevalence (or infection rate) and intensity [number of eggs per gram of stool (epg) or number of microfilariae per skin snip (mf/ss)] of STH and onchocerciasis infections respectively using the Kato-Katz and skin snip methodologies. Chi-square and the non-parametric tests (Mann Whitney and Kruskal Wallis) were used to compare infection rates and intensities of infections between Health Districts and genders, respectively. RESULTS: A total of 421 children were enrolled in this study. The overall prevalence of onchocerciasis was 6.6% [95% confidence interval (CI): 4.3‒9.9], ranging from 3.6% (in the Ntui Health District) to 12.2% (in the Bafia Health District). The intensity of infection ranged from 0.5 to 46 microfilariae per skin snip [median: 5; interquartile range (IQR): 2.25‒8.5]. The overall prevalence of STH was 9.6% (95% CI: 6.5‒13.9), with a high infection rate (29.6%) in the Akonolinga Health District. Two STH species (Ascaris lumbricoides and Trichuris trichiura) were found among infected individuals. The median intensities of STH infections were 1,992 epg (IQR: 210‒28,704) and 96 epg (IQR: 48‒168) for A. lumbricoides and T. trichiura, respectively. CONCLUSIONS: This study reveals that children < 5 years of age are highly infected with STH and onchocerciasis, and could contribute to the spread of these diseases, perpetuating a vicious circle of transmission and hampering elimination efforts. These findings reveal the urgent need to provide (or scale) treatments (likely pediatric formulations) to these preschool-aged children, especially in areas of high transmission, to accelerate efforts to reach WHO 2030 target.

Bacteriome Diversity of Blackflies' Gut and Association with Onchocerca volvulus, the Causative Agent of Onchocerciasis in Mbam Valley (Center Region, Cameroon).

Vector control using larvicides is the main alternative strategy to address limits of preventive chemotherapy using ivermectin for the control of onchocerciasis. However, it remains substantially limited by implementation difficulties, ecological concerns and the resistance of vector populations. Therefore, efficient and environmentally safe alternative control strategies are still needed. This study explores the composition of the blackfly bacteriome and its variability in the presence of Onchocerca volvulus infection, in order to determine their potential as a novel vector control-based approach to fight onchocerciasis. An entomological survey of a collection of samples was performed in the Bafia health district, a historical endemic focus for onchocerciasis in Cameroon. A total of 1270 blackflies were dissected and the infection rate was 10.1%, indicative of ongoing transmission of onchocerciasis in the surveyed communities. Sequencing process of blackflies' gut DNA for bacteria screening revealed 14 phyla and 123 genera, highlighting the diversity of gut blackflies bacterial communities. Eight bacteria formed the core of blackfly bacteriome and Wolbachia was the predominant genus with 73.4% of relative abundance of blackflies' gut bacterial communities. Acidomonas and Roseanomas genera were significantly abundant among infected blackflies (p = 0.01), whereas other genera such as Brevibacterium and Fructobacillus were associated with the absence of infection (p = 0.0009). Differences in gut bacterial distribution of blackflies according to their infection status by the parasite suggest a causal relationship between the bacteriome composition and the onset of blackflies' infection by O. volvulus or vice versa. Blackfly native bacteria are then potentially involved in infection by O. volvulus, either by facilitating or preventing the parasite infestation of the vector. These bacteria represent an interesting potential as a biological tool/target for a novel approach of vector control to fight onchocerciasis.

Support for families of isolated or deceased COVID-19 patients in sub-Saharan Africa.

Aside the direct effect of the COVID-19 on infected patients, this infectious disease outbreak has various psychological consequences. These mental health repercussions pertain to the general population of uninfected individuals, and particularly families of isolated or deceased COVID-19 patients. This aspect is of substantial interest amid sub-Saharan African communities, considering the key place and cultural significance of mourning and funerals in these settings. In this commentary, we discuss on the issue of psychological and social support of COVID-19 patients' families, by taking into account some sub-Saharan African cultural considerations.