To confirm our earlier evidence of a temporal and dose-response relationship between onchocerciasis and epilepsy, we conducted another cohort study in a different setting in Cameroon. Individuals whose Onchocerca volvulus microfilarial density (Ov-MFD) was measured in 1992-1994 when they were children, were revisited in 2019 to determine if they acquired epilepsy. With reference to individuals with no microfilariae in 1992-1994, the relative risks of acquiring epilepsy were 0.96, 2.76, 3.67, and 11.87 in subjects with initial Ov-MFD of 1-7, 8-70, 71-200, and >200 microfilariae per skin snip, respectively. This study further demonstrates reproducibility in the Bradford Hill’s criteria for causality.

A high epilepsy prevalence has been reported in several onchocerciasis-endemic villages along the Mbam and Sanaga river valleys in Cameroon, including Bilomo and Kelleng. We sought to determine the prevalence of epilepsy in these two villages following more than 13 years of community-directed treatment with ivermectin (CDTI). Door-to-door surveys were performed on the entire resident population in the villages in August 2017 and January 2018. Epilepsy was diagnosed using a 2-step approach: administration of a standardized 5-item questionnaire followed by confirmation by a neurologist. Previously published diagnostic criteria for onchocerciasis-associated epilepsy (OAE) were used. Ov16 serology was done for children aged 7–10 years to assess onchocerciasis transmission. Findings were compared with previous data from these two villages. A total of 1525 individuals (1321 in Bilomo and 204 in Kelleng) in 233 households were surveyed in both villages. The crude prevalence of epilepsy was 4.6% in Bilomo (2017) and 7.8% in Kelleng (2018), including 12 (15.6% of cases) persons with epilepsy (PWE) with nodding seizures. The age and sex-standardized prevalence in Kelleng decreased from 13.5% in 2004 to 9.3% in 2018 (P < 0.001). The median age of PWE shifted from 17 (IQR: 12–22) years to 24 (IQR: 20–30) years in Bilomo (P < 0.001); and slightly from 24 (IQR: 14–34) years to 28 (IQR: 21.25–36.75) years in Kelleng (P = 0.112). Furthermore, 47.6% of all tested children between 7 and 10 years had Ov16 antibodies. There is a decrease in epilepsy prevalence after 13 years and more of CDTI in both villages. The age-shift observed in PWE suggests that ivermectin may prevent OAE in younger residents. Ov16 seropositivity in children indicates ongoing onchocerciasis transmission possibly due to suboptimal control measures. Our findings support the existence of OAE in Cameroon and highlight the need to strengthen onchocerciasis elimination programs.

Since the mid-2000s, the immunochromatographic card test (ICT), a point-of-care test for detecting Wuchereria bancrofti circulating filarial antigens (CFAs), has been the backbone for mapping and monitoring lymphatic filariasis (LF) worldwide. Recently, there have been instances in which CFA positivity has been associated with Loa loa microfilaremia. Here, we examined the association, at both the community and individual levels, between L. loa and CFA using additional diagnostic tools (quantitative polymerase chain reaction [qPCR], Og4C3 enzyme-linked immunosorbent assay, and IgG4 antibodies to Wb123 assays) to demonstrate the relationship between L. loa microfilaremia and ICT positivity. In May 2013, peripheral blood was collected during the day from 1,812 individuals living in southern Cameroon. ICT tests were done on the spot, and positive individuals were resampled at night. Results of qPCR and Wb123 assays concurred proving the absence of W. bancrofti infection. Og4C3 assays indicate a quantitative relationship between the level of L. loa microfilaremia and that of CFA. This was confirmed by epidemiological analyses, which reveal a strong association between L. loa microfilaremia and ICT positivity, with 50% of ICT reacting to L. loa when its microfilarial density exceeds 30,000 microfilariae/mL. At the community level, the proportion of positive ICT would exceed 2% when the prevalence of L. loa microfilaremia in the total population is above 20%. This has significant implications in terms of mapping and control of LF caused by W. bancrofti in Loa-endemic areas. Cross-reactivity of ICT with L. loa has to be considered in the context of both individual and community diagnostics.

Ivermectin is known to cause severe encephalopathies in subjects infected with loiasis, an endemic parasite in Sub-Saharan Africa (SSA). In addition, case reports have described ivermectin-related serious adverse drug reactions (sADRs) such as toxidermias, hepatic and renal disorders. The aim of this study was to identify suspected sADRs reported after ivermectin administration in VigiBase, the World Health Organization’s global individual case safety reports database and analyze their frequency relative to the frequency of these events after other antinematodal drugs reported in SSA and other areas of the world (ROW). All antinematodal-related sADRs were extracted from VigiBase. Disproportionality analyses were conducted to investigate nervous, cutaneous, psychiatric, respiratory, renal, hepatic and cardiac suspected sADRs reported after ivermectin and benzimidazole drug administration across the world, in SSA and RoW. 2041 post-ivermectin or post-benzimidazole suspected sADRs were identified including 667 after ivermectin exposure (208 in SSA and 459 in the RoW). We found an increased reporting for toxidermias, encephalopathies, confusional disorders after ivermectin compared to benzimidazole drug administration. Encephalopathies were not only reported from SSA but also from the RoW (adjusted reporting odds ratios [aROR] 6.30, 95% confidence interval: 2.68–14.8), highlighting the fact these types of sADR occur outside loiasis endemic regions. We described for the first time suspected sADRs associated with ivermectin exposure according to geographical origin. While our results do not put in question ivermectin’s excellent safety profile, they show that as for all drugs, appropriate pharmacovigilance for adverse reactions is indicated. Ivermectin is a drug used worldwide for various indications: onchocerciasis, lymphatic filariasis, strongyloidiasis, human sarcoptic scabies, acarodermatitis and rosacea. In the early 1990s, it was discovered that ivermectin could induce severe encephalopathies in some patients with high parasite loads of Loa loa, a filarial nematode. This objective of this pharmacovigilance study is to summarize serious neurological and non-neurological post-ivermectin adverse drug reactions reported in the World Health Organization database called VigiBase. This study shows that reported serious adverse drug reactions associated with ivermectin are fairly consistent with those mentioned in the official product information of ivermectin but also provides some new signals. Serious post-ivermectin encephalopathies can also occur outside of Loa loa endemic regions but the understanding of the mechanism by which it occurs requires further studies. A new signal concerning two serious toxidermias (DRESS syndrome and acute generalized exanthematous pustulosis) is also described. A lack of reporting of adverse drug reactions is noticeable in some Sub-Saharan African countries, and actions are needed to increase the reporting rates of these adverse effects in these countries.

Loiasis (Loa loa filariasis) is considered a benign disease and is currently not included in the WHO’s list of Neglected Tropical Diseases, despite mounting evidence suggesting significant disease burden in endemic areas. We conducted a retrospective cohort study to assess the mortality associated with L. loa microfilaremia in southwestern Republic of Congo. The cohort included 3329 individuals from 53 villages screened for loiasis in 2004. We compared mortality rates in 2021 for individuals initially diagnosed as with or without L. loa microfilariae 17 years earlier. Data were analysed at the community level to calculate crude mortality rates. Survival models were used to estimate the effect of L. loa microfilaremia on mortality in the population. At baseline, prevalence of microfilaremia was 16.2%. During 17.62 years of cohort follow-up, 751 deaths were recorded, representing a crude mortality rate of 15.36 (95% Confidence interval [CI], 14.28-16.50) per 1000 person-years. Median survival time were 58.5 years (95% CI, 49.7-67.3) and 39.2 (95% CI, 32.6-45.8), for amicrofilaremic and microfilaremic indiviudals, respectively. A significant reduction in life expectancy was associated with L. loa microfilaremia, confirming previous observations from Cameroon. This adds to the evidence that loiasis is not a benign disease and deserves to be included in the WHO’s list of Neglected Tropical Diseases.