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.

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.

Collateral Impact of Community-Directed Treatment with Ivermectin (CDTI) for Onchocerciasis on Parasitological Indicators of Loa loa Infection.

Ivermectin (IVM) is a broad spectrum endectocide whose initial indication was onchocerciasis. Although loiasis is not among its indications, IVM also exhibits antiparasitic activity against Loa loa. IVM-based preventive chemotherapies (PCs), so-called community-directed treatment with ivermectin (CDTI), have led to the interruption of transmission of onchocerciasis in some foci. A cross-sectional study was conducted in the Yabassi Health District where CDTI have been implemented since 20 years to fight onchocerciasis. All volunteers aged ≥ 5 years underwent daytime calibrated thick blood smears to search for L. loa microfilariae (mf). The prevalence of loiasis was 3.7% (95% CI: 2.2-6.2), significantly lower than its baseline prevalence (12.4%; 95% CI: 10.1-15.2; Chi-Square = 21.4; df = 1; p < 0.0001). Similarly, the microfilarial density was significantly low (mean = 1.8 mf/mL; SD = 13.6; max = 73,600) compared to baseline microfilarial density (mean = 839.3 mf/mL; SD = 6447.1; max = 130,840; Wilcoxon W = 179,904.5; p < 0.0001). This study revealed that the endemicity level of loiasis was significantly low compared to its baseline value, indicating a significant impact of IVM-based PC on this filarial disease. However, transmission is still ongoing, and heavily infected individuals are still found in communities, supporting why some individuals are still experiencing severe adverse events despite > 2 decades of CDTI in this Health District.

Prevalence and intensity of Loa loa infection over twenty-three years in three communities of the Mbalmayo health district (Central Cameroon).

BACKGROUND: Loiasis is a vector-borne parasitic disease due to Loa loa and transmitted to humans by tabanids of the genus Chrysops. Loiasis has been historically considered as the second or third most common reason for medical consultation after malaria, and a recent study has reported an excess mortality associated with the infection. However, the clinical impact of this filarial disease is yet to be elucidated, and it is still considered a benign disease eliciting very little attention. As a consequence of post-treatment severe adverse events occurring in individuals harboring very high Loa microfilarial loads, ivermectin is not recommended in onchocerciasis hypo-endemic areas that are co-endemic for loiasis. Without treatment, it is likely that the transmission of the disease and the morbidity associated with the infection will increase over time. This study aimed at investigating the long-term trends in prevalence and intensity of Loa loa infection in an area where no mass anti-filarial treatment has ever been distributed. METHODS: A cross-sectional survey was conducted in three communities of the Mbalmayo health district (Central Cameroon). All volunteers, males and females aged five years and above, underwent daytime calibrated thick blood smears (CTBS) to search for L. loa microfilariae (mf). A structured questionnaire was administered to assess the history of both loiasis related clinical signs and migration of enrollees. RESULTS: The prevalence of loiasis was 27.3% (95% CI: 22.3-32.9) in the three surveyed communities, with a mean mf density of 1922.7 (sd: 6623.2) mf/mL. Loa loa infection rate was higher amongst females than in males (p = 0.0001) and was positively associated with age of (OR = 1.018; p = 0.007). The intensity of infection was higher among males than in females (p < 0.0001), and displayed a convex in form trends with age groups. The follow up over 23 years revealed that both the rate and intensity of infection were similar to baseline. CONCLUSIONS: The prevalence and intensity of Loa loa infection 23 years on is stable over time, indicating that this filarial disease might be noncumulative as regarded till now.

First evidence of lymphatic filariasis transmission interruption in Cameroon: Progress towards elimination.

BACKGROUND: Lymphatic filariasis (LF) is among the 10 neglected tropical diseases targeted for control or elimination by 2020. For LF elimination, the World Health Organization (WHO) has proposed a comprehensive strategy including (i) interruption of LF transmission through large-scale annual treatment (or mass drug administration (MDA)) of all eligible individuals in endemic areas, and (ii) alleviation of LF-associated suffering through morbidity management and disability prevention. In Cameroon, once-yearly mass administration of ivermectin and albendazole has been implemented since 2008. The aim of this study was to assess progress towards the elimination goal, looking specifically at the impact of six rounds of MDA on LF transmission in northern Cameroon. METHODOLOGY: The study was conducted in the North and Far North Regions of Cameroon. Five health districts that successfully completed six rounds of MDA (defined as achieving a treatment coverage ≥ 65% each year) and reported no positive results for Wuchereria bancrofti microfilariaemia during routine surveys following the fifth MDA were grouped into three evaluation units (EU) according to WHO criteria. LF transmission was assessed through a community-based transmission assessment survey (TAS) using an immunochromatographic test (ICT) for the detection of circulating filarial antigen (CFA) in children aged 5-8 years old. PRINCIPAL FINDINGS: A total of 5292 children (male/female ratio 1.04) aged 5-8 years old were examined in 97 communities. Positive CFA results were observed in 2, 8 and 11 cases, with a CFA prevalence of 0.13% (95% CI: 0.04-0.46) in EU#1, 0.57% (95% CI: 0.32-1.02) in EU#2, and 0.45% (95% CI: 0.23-0.89) in EU#3. CONCLUSION/SIGNIFICANCE: The positive CFA cases were below WHO defined critical cut-off thresholds for stopping treatment and suggest that transmission can no longer be sustained. Post-MDA surveillance activities should be organized to evaluate whether recrudescence can occur.

Mapping of Bancroftian Filariasis in Cameroon: Prospects for Elimination.

BACKGROUND: Lymphatic filariasis (LF) is one of the most debilitating neglected tropical diseases (NTDs). It still presents as an important public health problem in many countries in the tropics. In Cameroon, where many NTDs are endemic, only scant data describing the situation regarding LF epidemiology was available. The aim of this study was to describe the current situation regarding LF infection in Cameroon, and to map this infection and accurately delineate areas where mass drug administration (MDA) was required. METHODOLOGY: The endemicity status and distribution of LF was assessed in eight of the ten Regions of Cameroon by a rapid-format card test for detection of W. bancrofti antigen (immunochromatographic test, ICT). The baseline data required to monitor the effectiveness of MDA was collected by assessing microfilariaemia in nocturnal calibrated thick blood smears in sentinel sites selected in the health districts where ICT positivity rate was ≥ 1%. PRINCIPAL FINDINGS: Among the 120 health districts visited in the eight Regions during ICT survey, 106 (88.3%) were found to be endemic for LF (i.e. had ICT positivity rate ≥ 1%), with infection rate from 1.0% (95% CI: 0.2-5.5) to 20.0% (95% CI: 10-30). The overall infection rate during the night blood survey was 0.11% (95% CI: 0.08-0.16) in 11 health districts out of the 106 surveyed; the arithmetic mean for microfilaria density was 1.19 mf/ml (95% CI: 0.13-2.26) for the total population examined. CONCLUSION/SIGNIFICANCE: ICT card test results showed that LF was endemic in all the Regions and in about 90% of the health districts surveyed. All of these health districts qualified for MDA (i.e. ICT positivity rate ≥ 1%). Microfilariaemia data collected as part of this study provided the national program with baseline data (sentinel sites) necessary to measure the impact of MDA on the endemicity level and transmission of LF important for the 2020 deadline for global elimination.