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.

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.

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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).

Background Schistosomiasis, caused by Schistosoma mansoni, is of great significance to public health in sub-Saharan Africa. In the Democratic Republic of Congo (DRC), information on the burden of S. mansoni infection is scarce, which hinders the implementation of adequate control measures. We assessed the geographical distribution of S. mansoni infection across Ituri province in north-eastern DRC and determined the prevailing risk factors. Methods / Principal Findings Two province-wide community-based studies were conducted. First, in 2016, a geographical distribution study was carried out in 46 randomly selected villages, covering 12 of the 36 health districts across Ituri. Second, in 2017, an in-depth study was conducted in 12 purposively-selected villages, across six health districts. In each study village, households were randomly selected and members, aged one year and older and present on the survey day, were enrolled. In 2016, one stool sample was collected per participant, while in 2017, several samples were collected per participant. S. mansoni eggs were detected using the Kato-Katz technique. The 2017 study also incorporated a point-of-care circulating cathodic S. mansoni antigen (POC-CCA) urine test. Household and individual questionnaires were used to collect data on demographic, socioeconomic, environmental, behavioural and knowledge risk factors. The 2016 study included 2,131 participants, 40.0% of whom had S. mansoni infections. Infection prevalence in the villages ranged from 0 to 90.2%. The 2017 study included 707 participants, of whom 73.1% tested positive for S. mansoni. Infection prevalence ranged from 52.8 to 95.0 % across the health districts visited. In general, infection prevalence increased from north to south and from west to east. Exposure to the waters of Lake Albert and the village altitude above sea level were associated with the distribution. Both men and women had the same infection risk (odds ratio [OR] 1.2, 95% confidence interval [CI] 0.82-1.76). Infection prevalence and intensity peaked in the age groups between 10 and 29 years. Preschool children were highly infected (62.3%). Key risk factors were poor housing structure (OR 2.1, 95% CI 1.02-4.35), close proximity to water bodies (OR 1.72, 95% CI 1.1-2.49), long-term residence in a community (OR 1.41, 95% CI 1.11-1.79), lack of latrine in the household (OR 2.00, 95% CI 1.11-3.60), and swimming (OR 2.53, 95% CI 1.20-5.32) and washing (OR 1.75, 95% CI 1.10-2.78) in local water bodies. A family history of schistosomiasis (OR 0.52, 95%, 95% CI 0.29-0.94) and knowledge of praziquantel treatment (OR 0.33, 95% CI 0.16-0.69) were protective risk factors, while prevention knowledge (OR 2.35, 95% CI 1.36-4.08) was associated with increased infection risk. Conclusions/Significance: Our results confirm high endemicity of S. mansoni in Ituri province, DRC. Both the prevalence and intensity of infection, and its relationship with the prevailing socioeconomic, environmental, and behavioural risk factors indicate intense exposure and alarming transmission levels. The study findings warrant control interventions that pay particular attention to high-risk communities and population groups, including preschool children.

Background Reducing morbidity is the main target of schistosomiasis control efforts, yet only rarely do control programmes assess morbidity linked to Schistosoma sp. infection. In the Democratic Republic of Congo (DRC), and particularly in north-eastern Ituri Province, little is known about morbidity associated with Schistosoma mansoni infection. For this reason, we aimed to assess intestinal and hepatosplenic morbidity associated with S. mansoni infection in Ituri Province. Methods/Principal findings In 2017, we conducted a cross-sectional study in 13 villages in Ituri Province, DRC. S. mansoni infection was assessed with a Kato-Katz stool test (2 smears) and a point-of-care circulating cathodic antigen (POC-CCA) urine test. A questionnaire was used to obtain demographic data and information about experienced intestinal morbidity. Each participant underwent an abdominal ultrasonography examination to diagnose hepatosplenic morbidity. Of the 586 study participants, 76.6% tested positive for S. mansoni. Intestinal morbidity reported in the two preceding weeks was very frequent, and included abdominal pain (52.7%), diarrhoea (23.4%) and blood in the stool (21.5%). Hepatosplenic morbidity consisted of abnormal liver parenchyma patterns (42.8%), hepatomegaly (26.5%) and splenomegaly (25.3%). Liver pathology (adjusted odds ratio [aOR] 1.20, 95% confidence interval [CI] 1.06–1.37, p = 0.005) was positively and significantly associated with S. mansoni infection. Hepatomegaly (aOR 1.52, 95% CI 0.99–2.32, p = 0.053) and splenomegaly (aOR 1.12, 95% CI 0.73–1.72, p = 0.619) were positively but not significantly associated with S. mansoni infection at the individual level. At the village level, S. mansoni prevalence was positively associated with the prevalence of hepatomegaly and splenomegaly. High-intensity S. mansoni infections were associated with diarrhoea, blood in the stool, hepatomegaly, splenomegaly, and liver parenchyma (C, D, E and F pathology patterns). Four study participants were diagnosed with ascites and five reported hematemesis. Conclusions/Significance Our study documents a high burden of intestinal and hepatosplenic morbidity associated with S. mansoni infection status in Ituri Province. The findings call for targeted interventions to address both S. mansoni infection and related morbidity.

Background Controlling morbidity is the main target of schistosomiasis control. Yet, only rarely do we assess morbidity linked to Schistosoma sp. infection. In the Democratic Republic of Congo (DRC), and particularly in the northeastern Ituri province, morbidity associated with Schistosoma mansoni infection is unknown. For this reason, we aimed to assess intestinal and hepatosplenic morbidity associated with S. mansoni infection in Ituri province. Methods / Principal Findings In 2017, we conducted a cross sectional study in 13 villages in Ituri province, DRC. S. mansoni infection was assessed with a Kato-Katz stool test (2 smears) and a point-ofcare circulating cathodic antigen (POC CCA) test in urine. A questionnaire was used to obtain demographic data and information about experienced intestinal morbidity. Each participant underwent an abdominal ultrasonography examination to diagnose hepatosplenic morbidity. Of the 586 study participants, 76.6% tested positive for S. mansoni . Intestinal morbidity, such as abdominal pain (52.7%), diarrhoea (23.4%) and blood in the stool (21.5%) in the previous two weeks, was very frequent, as was hepatosplenic morbidity, such as splenomegaly (60.1%), hepatomegaly (23.2%) and abnormal liver parenchyma pattern (52.6%). Hepatomegaly (adjusted odds ratio [aOR] 2.04, 95% confidence interval [CI] 1.27 to 3.26, P =0.003) and splenomegaly (aOR 1.69, 95% CI 1.17 to 2.45, P =0.005) were positively associated with S. mansoni infection at the individual level. At the village level, S. mansoni prevalence was positively associated with the prevalence of hepatomegaly and splenomegaly. Higher S. mansoni infection intensities were associated with diarrhoea, blood in the stool, hepatomegaly, splenomegaly and with liver parenchyma, pathology pattern D-E. Four study participants were diagnosed with ascites and five reported hematemesis. Conclusions/Significance : Our study documents a high burden of intestinal and hepatosplenic morbidity associated with S. mansoni infection status in Ituri province. The results call for targeted interventions to address both S. mansoni infection and related morbidity.

Schistosomiasis is a neglected invasive worm disease with a huge disease burden in developing countries, particularly in children, and is seen increasingly in non-endemic regions through transfer by travellers, expatriates, and refugees. Undetected and untreated infections may be responsible for the persistence of transmission. Rapid and accurate diagnosis is the key to treatment and control. So far, parasitological detection methods remain the cornerstone of Schistosoma infection diagnosis in endemic regions, but conventional tests have limited sensitivity, in particular in low-grade infection. Recent advances contribute to improved detection in clinical and field settings. The recent progress in micro- and nanotechnologies opens a road by enabling the design of new miniaturized point-of-care devices and analytical platforms, which can be used for the rapid detection of these infections. This review starts with an overview of currently available laboratory tests and their performance and then discusses emerging rapid and micro/nanotechnologies-based tools. The epidemiological and clinical setting of testing is then discussed as an important determinant for the selection of the best analytical strategy in patients suspected to suffer from Schistosoma infection. Finally, it discusses the potential role of advanced technologies in the setting near to disease eradication is examined.