Background Individuals with high microfilarial densities (MFD) of Loa loa are at risk of developing serious adverse events (SAEs) after ivermectin treatment. Pretreatment with drugs progressively reducing Loa MFD below the risk threshold might help prevent these SAEs. We assessed the safety and efficacy of levamisole for this purpose. Methods A double-blind, randomized, placebo-controlled, MFD-ascending trial was conducted in the Republic of the Congo. Participants were treated in 3 cohorts defined by pretreatment MFD and levamisole dose (Cohort 1: 1.0 kg and 1.5 mg/kg, Cohorts 2 and 3: 2.5 mg/kg). Safety outcomes were occurrence of SAE and AE frequency during the first week. The efficacy outcomes were MFD reduction from baseline and proportions of individuals with at least 40% and 80% MFD reduction at day 2 (D2), D7 and D30. Results The two lowest doses (1.0 mg/kg and 1.5 mg/kg) caused no SAE but were ineffective. Compared to placebo, 2.5 mg/kg levamisole caused more mild AEs (10/85 vs. 3/85, P = .018), a higher median reduction from baseline to D2 (-12.9% vs. + 15.5%, P < .001), D7 (-4.9% vs. +18.7%, P < .001) and D30 (-0.5% vs. +13.5%, P = .036) and a higher percentage of participants with >40% MFD reduction at D2 (17.5% vs. 1.2%, P < .001), D7 (11.8% vs. 6.3%, P = .269) and D30 (18.5% vs. 9.6%, P = .107). Conclusions A single 2.5 mg/kg levamisole dose induces a promising transient reduction in Loa loa MFD and should encourage testing different regimens.

Background 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. Methods 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. Results 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. Conclusion 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.

Background Individuals with high Loa loa microfilarial densities are at risk of developing severe encephalopathy after administration of antiparasitic drugs. Apart from this finding, loiasis is considered benign with no effect on brain function. However, recent epidemiological data suggest an increased mortality and morbidity in L. loa infected individuals, underscoring the importance of studies on the possible neurological morbidity associated with loiasis. Methodology Using MoCA tests and neurological ultrasounds, we conducted a cross-sectional study to assess cognitive alteration in a population living in a rural area endemic for loiasis in the Republic of Congo. Fifty individuals with high microfilarial densities (MFD) were matched on sex, age and residency with 50 individuals with low MFD and 50 amicrofilaremic subjects. Analyses focused on individuals with MoCA scores indicating an altered cognition (i.e. < 23/30) and on the total MoCA score according to Loa loa MFD, sociodemographic characteristics and neurological ultrasound results. Principal findings MoCA scores were very low in the studied population (mean of 15.6/30). Individuals with more than 15,000 microfilariae per milliliter of blood (mean predicted score:14.0/30) are more than twenty times more likely to have an altered cognition, compared to individuals with no microfilaremia (mean predicted score: 16.3/30). Years of schooling were strongly associated with better MoCA results. Extracranial and intracranial atheroma were not associated with L. loa MFD. Conclusion/significance Loaisis microfilaremia is probably involved in cognitive impairment, especially when the MFD are high. These results highlight the urgent need to better understand loaisis-induced morbidity. Further studies investigating neurological morbidity of loiasis are needed.