Emodepside for Trichuris trichiura and Hookworm Infection.

BACKGROUND: Current treatments for soil-transmitted helminth infections in humans have low efficacy against Trichuris trichiura. Emodepside - a drug in veterinary use and under development for the treatment of onchocerciasis in humans - is a leading therapeutic candidate for soil-transmitted helminth infection. METHODS: We conducted two phase 2a, dose-ranging, randomized, controlled trials to evaluate the efficacy and safety of emodepside against T. trichiura and hookworm infections. We randomly assigned, in equal numbers, adults 18 to 45 years of age in whom T. trichiura or hookworm eggs had been detected in stool samples to receive emodepside, at a single oral dose of 5, 10, 15, 20, 25, or 30 mg; albendazole, at a single oral dose of 400 mg; or placebo. The primary outcome was the percentage of participants who were cured of T. trichiura or hookworm infection (the cure rate) with emodepside 14 to 21 days after treatment, determined with the use of the Kato-Katz thick-smear technique. Safety was assessed 3, 24, and 48 hours after the receipt of treatment or placebo. RESULTS: A total of 266 persons were enrolled in the T. trichiura trial and 176 in the hookworm trial. The predicted cure rate against T. trichiura in the 5-mg emodepside group (85% [95% confidence interval {CI}, 69 to 93]; 25 of 30 participants) was higher than the predicted cure rate in the placebo group (10% [95% CI, 3 to 26]; 3 of 31 participants) and the observed cure rate in the albendazole group (17% [95% CI, 6 to 35]; 5 of 30 participants). A dose-dependent relationship was shown in participants with hookworm: the observed cure rate was 32% (95% CI, 13 to 57; 6 of 19 participants) in the 5-mg emodepside group and 95% (95% CI, 74 to 99.9; 18 of 19 participants) in the 30-mg emodepside group; the observed cure rates were 14% (95% CI, 3 to 36; 3 of 21 participants) in the placebo group and 70% (95% CI, 46 to 88; 14 of 20 participants) in the albendazole group. In the emodepside groups, headache, blurred vision, and dizziness were the most commonly reported adverse events 3 and 24 hours after treatment; the incidence of events generally increased in a dose-dependent fashion. Most adverse events were mild in severity and were self-limited; there were few moderate and no serious adverse events. CONCLUSIONS: Emodepside showed activity against T. trichiura and hookworm infections. (Funded by the European Research Council; ClinicalTrials.gov number, NCT05017194.).

Prevalence and Determinants of Undernutrition in Schoolchildren in the Kilombero District, South-Eastern Tanzania.

Childhood undernutrition is a major issue in low- and middle-income countries, affecting the health, well-being, and educational outcomes of schoolchildren. This study aimed to assess the prevalence and associated factors of stunting, wasting, and underweight among schoolchildren in peri-urban areas in the south-eastern part of Tanzania. A cross-sectional study was conducted involving 930 children aged 6-12 years from four primary schools from July to August 2019. The WHO Anthro Survey Analyzer was employed to estimate the prevalence of stunting, wasting, and underweight, while logistic regression analyses examined sociodemographic background, malaria infection, anaemia, anthropometric measures, and dietary diversity score as potential factors. The prevalence of stunting, wasting, underweight, overweight, and obesity was 11.8%, 4.3%, 3.9%, 11.1%, and 2.0%, respectively. Overall, 1.5% of the children had malaria, as determined by rapid diagnostic tests, and 0.4% had severe anaemia. Univariate analysis indicated higher odds of undernutrition among children aged 9-12 compared to their younger peers. Stunting was more common among children with low and medium dietary diversity. Anaemia was found in 11.2% of schoolchildren, and severe anaemia was associated with wasting. Multivariate analysis revealed that age and low dietary diversity were significantly associated with undernutrition. These findings emphasise the need for school-based health and nutrition programmes targeting children beyond the age of 5 to improve their nutritional status and mitigate potential adverse effects on health, cognition, and academic achievement. Regular assessment of the nutritional status of schoolchildren is warranted.

Correlation of Cytokines with Parasitic Infections, Undernutrition and Micronutrient Deficiency among Schoolchildren in Rural Tanzania: A Cross-Sectional Study.

Malnutrition and parasitic infections are often interconnected in a vicious cycle. Malnutrition can lead to changes in immune response, which may affect cytokine concentrations and potentially increase susceptibility to infections. In turn, parasitic infections can exacerbate malnutrition by impairing nutrient absorption. This cross-sectional study aimed to explore this interplay. Schoolchildren aged 6-12 years living in rural Tanzania (n = 120) provided blood, stool and urine samples to determine the relationship between cytokine concentrations (interleukin 4 (IL-4), interferon gamma (IFNγ) and interleukin 17A (IL-17A)), parasitic infections, undernutrition and micronutrient deficiency adjusting for sex, age, inflammatory markers, socioeconomic status and school categories. All schoolchildren had a normal blood cell count. The concentration of IL-4 was significantly higher in schoolchildren diagnosed with stunting, Schistosoma mansoni infection, a high C-reactive protein concentration, nausea, poor housing and increasing age. The concentration of IFNγ was associated with Plasmodium falciparum and Entamoeba histolytica/Entamoeba dispar/Entamoeba moshkovskii infections, vitamin A deficiency, attending the most remote schools and low socioeconomic status. Our study confirms a potential relationship between cytokine concentrations and parasitic infections, malnutrition and low socioeconomic status. A better understanding of long-term effects of parasitic infections and malnutrition on the immune function could help in designing tailored and effective interventions.

Efficacy and safety of moxidectin and albendazole compared with ivermectin and albendazole coadministration in adolescents infected with Trichuris trichiura in Tanzania: an open-label, non-inferiority, randomised, controlled, phase 2/3 trial.

BACKGROUND: Control efforts against soil-transmitted helminths focus on preventive chemotherapy with albendazole and mebendazole, however these drugs yield unsatisfactory results against Trichuris trichiura infections. We aimed to assess the efficacy and safety of moxidectin and albendazole compared with ivermectin and albendazole against T trichiura in adolescents living on Pemba Island, Tanzania. METHODS: This open-label, non-inferiority, randomised, controlled, phase 2/3 trial was done in four secondary schools (Kilindi, Kwale, Ndagoni [Chake Chake District], and Kiuyu [Wete District]) on Pemba Island, Tanzania. Adolescents aged 12-19 years who tested positive for T trichiura in at least two of four Kato-Katz slides with a mean infection intensity of 48 eggs per gram (EPG) of stool or higher were considered for inclusion. Participants were randomly assigned (21:21:2:2:8) to five treatment groups (8 mg moxidectin and 400 mg albendazole [group 1], 200 µg/kg ivermectin and 400 mg albendazole [group 2], 400 mg albendazole [group 3], 200 µg/kg ivermectin [group 4], or 8 mg moxidectin [group 5]) using a computer-generated randomisation code, stratified by baseline T trichiura infection intensity. Study site investigators and participants were not masked to study treatment; however, allocation was concealed to participants. The primary outcome was egg reduction rate (ERR) of T trichiura 14-21 days after treatment in the available case population. Moxidectin and albendazole was considered non-inferior to ivermectin and albendazole (control group) when the lower limit of the two-sided 95% CI of the difference was higher than the non-inferiority margin of -2 percentage points. This study is registered with ClinicalTrials.gov, NCT04700423. FINDINGS: Between March 1 and April 30, 2021, 771 participants were assessed for eligibility. 221 (29%) of 771 participants were ineligible and a further 14 (2%) were excluded. 207 (39%) of 536 participants were randomly assigned to moxidectin and albendazole, 211 (39%) to ivermectin and albendazole, 19 (4%) to albendazole, 19 (4%) to ivermectin, and 80 (15%) to moxidectin. Primary outcome data were available for all 536 participants. The geometric mean ERR of T trichiura after 14-21 days was 96·8% (95% CI 95·8 to 97·6) with moxidectin and albendazole and 99·0% (98·7 to 99·3) with ivermectin and albendazole (difference of -2·2 percentage points [-4·2 to -1·4]). No serious adverse events were reported during the study. The most reported adverse events were headache (160 [34%] of 465), abdominal pain (78 [17%]), itching (44 [9%]), and dizziness (26 [6%]). INTERPRETATION: Our findings show inferiority of moxidectin and albendazole to ivermectin and albendazole against T trichiura. However, given the high efficacy, moxidectin coadministration might complement treatment progammes, particularly in areas in which ivermectin is not available FUNDING: Bill and Melinda Gates Foundation, reference number OPP1153928.

Malnutrition, anemia, micronutrient deficiency and parasitic infections among schoolchildren in rural Tanzania.

BACKGROUND: Malnutrition, anemia, micronutrient deficiency and parasitic infections continue to impact the nutritional status and health of children in lower-income countries. However, not enough data concerning this issue is available. The aim of this study was to assess the distribution of nutritional indicators, anemia and micronutrient deficiency and their underlying risk factors among schoolchildren in south-eastern Tanzania. METHODOLOGY/PRINCIPAL FINDINGS: This cross-sectional study enrolled primary schoolchildren aged 6-12 years from Kikwawila and Kiberege wards, Tanzania. In total, 471 schoolchildren underwent a physical examination and provided blood, stool and urine samples for an assessment of the levels of different micronutrients, nutritional and anemia status, and parasitic infection status. We employed bivariate and multivariate logistic regression to determine the association between nutritional statuses, anemia, micronutrient deficiency and parasitic infections. We found that 23.90%, 12.60% and 16.20% of schoolchildren were stunted, underweight and wasted, respectively. About 14.0% of schoolchildren were found to be anemic. Children diagnosed with Plasmodium falciparum infection were more likely to have low levels of ferritin (aOR: 10.40, 95% CI: 2.88-40.53) and elevated levels of serum soluble transferrin receptor (aOR: 3.59, 95% CI: 1.27-11.23), respectively. Vitamin A (34.71%) and vitamin B12 (8.79%) were the most prevalent micronutrients found to be deficient in diagnosed children. Finally, we found that schoolchildren attending the most rural schools were five times more likely to be diagnosed with at least one micronutrient deficiency (aOR: 5.04, 95% CI: 2.38-11.44). CONCLUSIONS/SIGNIFICANCE: Malnutrition, anemia and micronutrient deficiency still pose a significant health burden among schoolchildren living in rural Tanzania. To effectively tackle this burden, health interventions such as deworming, micronutrient supplementation, vector control, health education and access to clean water and improved sanitation should be strengthened and made sustainable.

A cross-sectional survey on parasitic infections in schoolchildren in a rural Tanzanian community.

Infectious diseases remain the leading cause of death in children in low- and middle-income countries. Infection with helminths and intestinal protozoa cause considerable morbidity. The aim of this study was to assess the health status of schoolchildren in nine villages of the Kilombero district in Tanzania. We conducted a cross-sectional survey and subjected 427 children aged 6-12 years to standardized diagnostic tests. We found that 15% of children were infected with Entamoeba histolytica/Entamoeba dispar/Entamoeba moshkovskii, 12% with Schistosoma mansoni, and 5% with Plasmodium falciparum. The most common soil-transmitted helminth species was Trichuris trichiura (7%). Strongyloides stercoralis, Schistosoma haematobium, Giardia intestinalis and lymphatic filariasis were rare. Having a latrine inside the house was associated with a lower odds of parasite infections (odds ratio (OR) 0.51, 95% confidence interval (CI) 0.27-0.96, p = 0.04). Children from households with goats were at higher odds of E. histolytica/E. dispar/E. moshkovskii infection (OR 3.03, 95%%CI 1.29-7.10, p = 0.01).When compared to a cross-sectional survey conducted in the same district in the 1980s, there seems to have been a substantial reduction in the prevalence and intensity of parasitic infections, except for T. trichiura, which showed a similar prevalence. Our data suggest that the general development, coupled with infectious disease control programmes improved children's health markedly. However, continued efforts to control parasitic diseases, including new approaches of drug combinations, stronger intersectoral collaboration, rigorous surveillance and public health responses tailored to the local settings are needed to move from control to elimination.

Efficacy and safety of moxidectin and albendazole compared to ivermectin and albendazole co-administration in adolescents infected with Trichuris trichiura: a randomized controlled trial protocol.

Background: Infections with soil-transmitted helminths (STHs) predominantly affect impoverished populations in tropical environments. The periodic administration of single dose benzimidazoles (i.e., albendazole, mebendazole) to at-risk individuals in endemic regions is at the center of STH control strategies. Given the low efficacy of these drugs against trichuriasis, investigation of drug combinations including moxidectin and ivermectin has recently been initiated, yet the identification of the best treatment option requires more research. We present the protocol for a trial investigating the efficacy and safety of co-administered moxidectin and albendazole compared to co-administered ivermectin and albendazole against Trichuris trichiura. Methods: We will conduct a randomized controlled trial enrolling 540 T. trichiura-infected adolescents aged 12-19 years on Pemba Island (Tanzania). The trial will be open-label with blinded outcome assessors. The primary objective is to demonstrate non-inferiority of orally co-administered single-dose moxidectin (8 mg)/albendazole (400 mg) compared to orally co-administered single-dose ivermectin (200 µg/kg)/albendazole (400 mg) in terms of egg reduction rates (ERRs) against T. trichiura infections assessed by Kato-Katz at 14-21 days post-treatment. Secondary objectives include the assessment of the drug combinations' superiority compared to their respective monotherapies, of the cure rates (CRs) against T. trichiura, and the safety and tolerability of all treatments, as well as CRs and ERRs against concomitant STH infections ( Ascaris lumbricoides and hookworm). Potential effects of the treatment regimens on follow-up prevalences of STH at 5-6 weeks and 3 months post-treatment and pharmacokinetic/  pharmacodynamic parameters will also be assessed. Conclusions: Results from this trial will help to inform decision- and policymakers on which anthelminthic combination therapy might improve existing deworming programs and provide a valuable adjunct tool for interrupting STH transmission. Clinicaltrials.gov registration: NCT04700423 (07/01/2021).