SummaryBackgroundThe morbidity and socioeconomic effects of onchocerciasis, a parasitic disease that is primarily endemic in sub-Saharan Africa, have motivated large morbidity and transmission control programmes. Annual community-directed ivermectin treatment has substantially reduced prevalence. Elimination requires intensified efforts, including more efficacious treatments. We compared parasitological efficacy and safety of moxidectin and ivermectin.MethodsThis double-blind, parallel group, superiority trial was done in four sites in Ghana, Liberia, and the Democratic Republic of the Congo. We enrolled participants (aged ≥12 years) with at least 10 Onchocerca volvulus microfilariae per mg skin who were not co-infected with Loa loa or lymphatic filariasis microfilaraemic. Participants were randomly allocated, stratified by sex and level of infection, to receive a single oral dose of 8 mg moxidectin or 150 μg/kg ivermectin as overencapsulated oral tablets. The primary efficacy outcome was skin microfilariae density 12 months post treatment. We used a mixed-effects model to test the hypothesis that the primary efficacy outcome in the moxidectin group was 50% or less than that in the ivermectin group. The primary efficacy analysis population were all participants who received the study drug and completed 12-month follow-up (modified intention to treat). This study is registered with ClinicalTrials.gov, number NCT00790998.FindingsBetween April 22, 2009, and Jan 23, 2011, we enrolled and allocated 998 participants to moxidectin and 501 participants to ivermectin. 978 received moxidectin and 494 ivermectin, of which 947 and 480 were included in primary efficacy outcome analyses. At 12 months, skin microfilarial density (microfilariae per mg of skin) was lower in the moxidectin group (adjusted geometric mean 0·6 [95% CI 0·3–1·0]) than in the ivermectin group (4·5 [3·5–5·9]; difference 3·9 [3·2–4·9], p<0·0001; treatment difference 86%). Mazzotti (ie, efficacy-related) reactions occurred in 967 (99%) of 978 moxidectin-treated participants and in 478 (97%) of 494 ivermectin-treated participants, including ocular reactions (moxidectin 113 [12%] participants and ivermectin 47 [10%] participants), laboratory reactions (788 [81%] and 415 [84%]), and clinical reactions (944 [97%] and 446 [90%]). No serious adverse events were considered to be related to treatment.InterpretationSkin microfilarial loads (ie, parasite transmission reservoir) are lower after moxidectin treatment than after ivermectin treatment. Moxidectin would therefore be expected to reduce parasite transmission between treatment rounds more than ivermectin could, thus accelerating progress towards elimination.FundingUNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases.

BackgroundCommunity Directed Treatment with ivermectin is the cornerstone of current efforts to eliminate onchocerciasis. However recent studies suggest there are foci where long-term annual distribution of the drug alone has failed to ensure elimination thresholds are reached. It is important to achieve high levels of compliance in order to obtain elimination targets. An epidemiological and entomological evaluation conducted in the western region of Cameroon in 2011 revealed that two health districts remained with a high prevalence of infection, despite long-term distribution of ivermectin since 1996. This paper explores potential factors that may have contributed to the non-interruption of transmission, focusing on ivermectin treatment compliance and the importance of systematic non-compliance within the population.Methodology/Principal findingsA mixed methods approach was used, including a population-based survey to assess treatment compliance and factors associated and qualitative assessments including focus group discussions and in-depth interviews with key programme stakeholders and drug distributors. Compliance was reported at 71.2% (95%CI: 61.7–79.2%;n = 853/1198). The key factors related to compliance in the most recent round related to either programmatic and delivery issues, primarily absenteeism at the time of the campaign or alternatively individual determinants. An individual’s experience of side effects in the past was strongly associated with non-compliance to ivermectin. Other factors included ethnicity, how long lived in the village and age. There was a high percentage of reported systematic non-compliance at 7.4% (95% CI: 4.3–12.3%; n = 86/1165), higher amongst females. This group may be important in facilitating the sustainment of on-going transmission.Conclusions/SignificanceEfforts to reduce the number of systematic non-compliers and non-compliance in certain groups may be important in ensuring the interruption of transmission in the study area. However, in areas with high pre-control force of transmission, as in these districts, annual distribution with ivermectin, even if sustaining high levels of compliance, may still be inadequate to achieve elimination. Further studies are required to better understand the transmission dynamics and focus of on-going transmission in the study districts.

Implementation of mass drug administration for lymphatic filariasis (LF) has been delayed in central Africa because of incomplete mapping and coendemic loiasis. We mapped two regions in eastern Democratic Republic of Congo that were suspected to have LF. Night blood samples were collected from 2,724 subjects in 30 villages. Filarial antigenemia rates by card test exceeded 1% in 28 villages (range = 0–14%). Prevalence rates for large sheathed microfilariae (Mf) ranged from 4% to 40%; Mansonella perstans rates ranged from 22% to 98%. Large Mf were exclusively Loa loa by microscopy, and only 1 of 337 samples tested by quantitative polymerase chain reaction (qPCR) was positive for Wuchereria bancrofti DNA. Filarial antigen positivity was strongly associated with high L. loa Mf counts. Periodicity studies revealed atypical patterns, with no significant diurnal periodicity in some individuals. Thus, methods routinely used for LF mapping may not be reliable in areas in central Africa that are highly endemic for loiasis.

Onchocerciasis is a parasitic infection caused by the filarial nematode Onchocerca volvulus and transmitted through the bites of black flies of the genus Similium that breed in rivers and streams. The impact of mass treatment with ivermectin and supplemented by vector control in some countries has changed the global scene of onchocerciasis. There has been reported progress made in elimination of onchocerciasis in central and southern American countries and in some localities in Africa. The target for elimination in the Americas has been set at 2022 while for 12 countries in Africa this is expected in 2030. This review was conducted to examine the current status of onchocerciasis elimination at the global level and report on progress made. Literature searches were made through PubMed, articles in English or English abstracts, reports and any other relevant articles related to the subject. The global burden of onchocerciasis is progressively reducing and is no longer a public health problem in some regions. However, programs are challenged with a range of issues: cross-border transmission, diagnostic tools, Loa loa co-endemicity, limited workforce in entomology and maintaining enthusiasm among community drug distributors. More concerted effort using appropriate tools is required to overcome the challenges.

Abstractobjective To evaluate onchocerciasis control activities in the Democratic Republic of Congo (DRC) in the first 12 years of community-directed treatment with ivermectin (CDTI).methods Data from the National Programme for Onchocerciasis (NPO) provided by the National Onchocerciasis Task Force (NOTF) through the annual reports of the 21 CDTI projects for the years 2001-2012 were reviewed retrospectively. A hypothetical-inputs-process-outputs-outcomes table was constructed.

BackgroundValidation of elimination of trachoma as a public health problem is based on clinical indicators, using the WHO simplified grading system. Chlamydia trachomatis (Ct) infection and anti-Ct antibody responses (anti-Pgp3) have both been evaluated as alternative indicators in settings with varying levels of trachoma. There is a need to evaluate the feasibility of using tests for Ct infection and anti-Pgp3 antibodies at scale in a trachoma-endemic country and to establish the added value of the data generated for understanding transmission dynamics in the peri-elimination setting.Methodology/Principal findingsDried blood spots for serological testing and ocular swabs for Ct infection testing (taken from children aged 1–9 years) were integrated into the pre-validation trachoma surveys conducted in the Northern and Upper West regions of Ghana in 2015 and 2016. Ct infection was detected using the GeneXpert PCR platform and the presence of anti-Pgp3 antibodies was detected using both the ELISA assay and multiplex bead array (MBA). The overall mean cluster-summarised TF prevalence (the clinical indicator) was 0.8% (95% CI: 0.6–1.0) and Ct infection prevalence was 0.04% (95%CI: 0.00–0.12). Anti-Pgp3 seroprevalence using the ELISA was 5.5% (95% CI: 4.8–6.3) compared to 4.3% (95%CI: 3.7–4.9) using the MBA. There was strong evidence from both assays that seropositivity increased with age (p<0.001), although the seroconversion rate was estimated to be very low (between 1.2 to 1.3 yearly events per 100 children).Conclusions/SignificanceInfection and serological data provide useful information to aid in understanding Ct transmission dynamics. Elimination of trachoma as a public health problem does not equate to the absence of ocular Ct infection nor cessation in acquisition of anti-Ct antibodies.

BackgroundMassangam health district (HD), in the West Region of Cameroon, has received ivermectin mass drug administration (MDA) for 20 years, however there is evidence of continued high transmission of Onchocerca volvulus. In order to better understand the transmission dynamics in the HD and inform intervention strategies there is a need to delineate the boundaries of the suspected area of high transmission within the wider transmission zone.Methodology/Principal findingsParasitological and entomological surveys were conducted to map out the breeding sites of Simulium damnosum and evaluate the prevalence of onchocerciasis in neighbouring communities, including Makouopsap sentinel community. Potential rapids were prospected for identification of S. damnosum larvae and black flies collected to determine infectivity rates. Adults were assessed for the presence of O. volvulus microfilariae through a skin snip biopsy and examined for the presence of nodules. Anti Ov-16 antibodies were tested for in children. Four perennial breeding sites were identified on the Rivers Mbam and Nja. Large number of flies were collected along the River Mbam, especially in the rainy season, with up to 955 flies per day, suggesting this river is a perennial source of black flies. A total of 0.8% of parous flies were infective across the study area. Parasitological studies provided evidence of high rates of infection in the sentinel community and three neighbouring communities, with 37.1% of adults microfilariae positive in Makouopsap. High Ov-16 seropositivity in children also provided evidence of recent on-going transmission. In comparison, communities sampled further away from the sentinel community and neighbouring breeding sites were much closer to reaching onchocerciasis elimination targets.Conclusions/SignificanceThis study provides evidence of a particular geographic area of high transmission in an approximate 12 km range around the sentinel community of Makouopsap and the neighbouring breeding sites on the River Nja. To eliminate onchocerciasis by 2025, there is a need to explore alternative intervention strategies in this area of high transmission.

Background Our study in CDTI-naïve areas in Nord Kivu and Ituri (Democratic Republic of the Congo, DRC), Lofa County (Liberia) and Nkwanta district (Ghana) showed that a single 8 mg moxidectin dose reduced skin microfilariae density (microfilariae/mg skin, SmfD) better and for longer than a single 150μg/kg ivermectin dose. We now analysed efficacy by study area and pre-treatment SmfD (intensity of infection, IoI). Methodology/Principal findings Four and three IoI categories were defined for across-study and by-study area analyses, respectively. We used a general linear model to analyse SmfD 1, 6, 12 and 18 months post-treatment, a logistic model to determine the odds of undetectable SmfD from month 1 to month 6 (UD1-6), month 12 (UD1-12) and month 18 (UD1-18), and descriptive statistics to quantitate inter-interindividual response differences. Twelve months post-treatment, treatment differences (difference in adjusted geometric mean SmfD after moxidectin and ivermectin in percentage of the adjusted geometric mean SmfD after ivermectin treatment) were 92.9%, 90.1%, 86.8% and 84.5% in Nord Kivu, Ituri, Lofa and Nkwanta, and 74.1%, 84.2%, 90.0% and 95.4% for participants with SmfD 10–20, ≥20-<50, ≥50-<80, ≥80, respectively. Ivermectin’s efficacy was lower in Ituri and Nkwanta than Nord Kivu and Lofa (p≤0.002) and moxidectin’s efficacy lower in Nkwanta than Nord Kivu, Ituri and Lofa (p<0.006). Odds ratios for UD1-6, UD1-12 or UD1-18 after moxidectin versus ivermectin treatment exceeded 7.0. Suboptimal response (SmfD 12 months post-treatment >40% of pre-treatment SmfD) occurred in 0%, 0.3%, 1.6% and 3.9% of moxidectin and 12.1%, 23.7%, 10.8% and 28.0% of ivermectin treated participants in Nord Kivu, Ituri, Lofa and Nkwanta, respectively. Conclusions/Significance The benefit of moxidectin vs ivermectin treatment increased with pre-treatment IoI. The possibility that parasite populations in different areas have different drug susceptibility without prior ivermectin selection pressure needs to be considered and further investigated. Clinical Trial Registration Registered on 14 November 2008 in Clinicaltrials.gov (ID: NCT00790998).