Efficacy and safety of moxidectin compared with ivermectin against Strongyloides stercoralis infection in adults in Laos and Cambodia: a randomised, double-blind, non-inferiority, phase 2b/3 trial.

BACKGROUND: Infection with the soil-transmitted helminth Strongyloides stercoralis affects up to 600 million people globally, most of whom live in rural areas with poor sanitation. If untreated, infection leads to long-lasting morbidity and might even be life-threatening. Moxidectin might be a promising alternative to ivermectin, the only currently recommended single-dose treatment. We aimed to assess whether moxidectin is non-inferior in terms of efficacy and safety compared with ivermectin. METHODS: In this randomised, double-blind, parallel-group, non-inferiority, phase 2b/3 trial in communities in Laos and Cambodia, adults aged 18-65 years were screened for the presence of S stercoralis larvae in their stool via sextuplicate quantitative Baermann assays. Using computer-generated group allocation (block randomisation stratified by infection intensity), parasitologically (two or more positive Baermann assays) and clinically eligible participants were randomly assigned (1:1) to receive single oral doses of either moxidectin (8 mg) and ivermectin-matched placebo, or ivermectin (200 µg/kg bodyweight) and moxidectin-matched placebo. The primary endpoint was cure rate assessed at 14-21 days after treatment, using the available-case population analysed according to intention-to-treat principles. Moxidectin was considered non-inferior to ivermectin if the lower limit of the two-sided 95% CI of the difference was greater than the non-inferiority margin of -10 percentage points. Safety endpoints were assessed before treatment, and at 2-3 h, 24 h, and 14-21 days after treatment. This trial is registered at ClinicalTrials.gov, NCT04056325 and NCT04848688. FINDINGS: Between Dec 6, 2020, and May 21, 2022, 4291 participants were screened, 726 of whom were enrolled and randomly assigned to moxidectin (n=363) or ivermectin (n=363). For the participants with primary outcome data, we observed a cure rate of 93·6% (95% CI 90·5 to 96·0; 324 of 346 participants) in the moxidectin group and 95·7% (93·0 to 97·6; 335 of 350 participants) in the ivermectin group, resulting in a between-group difference of -2·1 percentage points (95% CI -5·5 to 1·3). The most common adverse events were abdominal pain (32 [9%] of 363 with moxidectin vs 34 [9%] of 363 with ivermectin) and headache (25 [7%] vs 30 [8%]), which were predominantly mild and transient. INTERPRETATION: Moxidectin was non-inferior to ivermectin in terms of efficacy in the treatment of strongyloidiasis. Additionally, both drugs had a similar safety profile. The fixed dose and lower cost of moxidectin compared with ivermectin make it a valuable alternative for people with strongyloidiasis. FUNDING: Swiss National Science Foundation.

Dynamics and consequences of nutrition-related microbial dysbiosis in early life: study protocol of the VITERBI GUT project.

Introduction: Early life under- and overnutrition (jointly termed malnutrition) is increasingly recognized as an important risk factor for adult obesity and metabolic syndrome, a diet-related cluster of conditions including high blood sugar, fat and cholesterol. Nevertheless, the exact factors linking early life malnutrition with metabolic syndrome remain poorly characterized. We hypothesize that the microbiota plays a crucial role in this trajectory and that the pathophysiological mechanisms underlying under- and overnutrition are, to some extent, shared. We further hypothesize that a "dysbiotic seed microbiota" is transmitted to children during the birth process, altering the children's microbiota composition and metabolic health. The overall objective of this project is to understand the precise causes and biological mechanisms linking prenatal or early life under- or overnutrition with the predisposition to develop overnutrition and/or metabolic disease in later life, as well as to investigate the possibility of a dysbiotic seed microbiota inheritance in the context of maternal malnutrition. Methods/design: VITERBI GUT is a prospective birth cohort allowing to study the link between early life malnutrition, the microbiota and metabolic health. VITERBI GUT will include 100 undernourished, 100 normally nourished and 100 overnourished pregnant women living in Vientiane, Lao People's Democratic Republic (PDR). Women will be recruited during their third trimester of pregnancy and followed with their child until its second birthday. Anthropometric, clinical, metabolic and nutritional data are collected from both the mother and the child. The microbiota composition of maternal and child's fecal and oral samples as well as maternal vaginal and breast milk samples will be determined using amplicon and shotgun metagenomic sequencing. Epigenetic modifications and lipid profiles will be assessed in the child's blood at 2 years of age. We will investigate for possible associations between metabolic health, epigenetics, and microbial changes. Discussion: We expect the VITERBI GUT project to contribute to the emerging literature linking the early life microbiota, epigenetic changes and growth/metabolic health. We also expect this project to give new (molecular) insights into the mechanisms linking malnutrition-induced early life dysbiosis and metabolic health in later life, opening new avenues for microbiota-engineering using microbiota-targeted interventions.

Assessment of cognitive function among adults aged ≥ 60 years using the Revised Hasegawa Dementia Scale: cross-sectional study, Lao People's Democratic Republic.

BACKGROUND: Rapid population ageing remains an important concern for health, social and economics systems; thus, a broader assessment of cognitive decline among adults aged ≥ 60 years is essential. It is important to regularly collect reliable data through validated and affordable methods from people living in different areas and in different circumstances to better understand the significance of this health problem. This study aimed to identify the prevalence of cognitive impairment and the related risk factors by reassessing the scoring of the Revised Hasegawa Dementia Scale among older adults in the Lao People's Democratic Republic. METHODS: A community-based cross-sectional investigation was conducted in rural and urban settings in six districts of three provinces in the country from January to July 2020. In total, 2206 individuals aged 60-98 years (1110 men and 1096 women) were interviewed in person using a pretested Lao version of the Revised Hasegawa Dementia Scale and the WHO STEPwise approach to noncommunicable disease (NCD) risk factor surveillance (the STEPS survey tool). The adjusted odds ratios (AORs) and 95% confidence intervals (95% CIs) were estimated using a logistic model. RESULTS: The study found that 49.3% (1088/2206) of respondents (39.7% [441/1110] of men and 59.0% [647/1096] of women) had scores associated with some level of cognitive impairment. In addition to age, the following factors were significantly associated with cognitive impairment: having no formal education (AOR = 9.5; 95% CI: 5.4 to 16.8, relative to those with a university education), living in the northern region of the country (AOR = 1.4; 95% CI: 1.1 to 1.9, relative to living in the central region), living in a rural area (AOR = 1.5; 95% CI: 1.2 to 1.8), needing assistance with self-care (AOR = 1.8; 95% CI: 1.2 to 2.7) and being underweight (AOR = 1.5; 95% CI: 1.1 to 2.2). Factors associated with no cognitive impairment among older adults include engaging in moderate-intensity physical activity lasting for 10 minutes and up to 1 hour (AOR = 0.6; 95% CI: 0.5 to 0.8) and for > 1 hour (AOR = 0.6; 95% CI: 0.4 to 0.8). CONCLUSIONS: Using the Lao version of the Revised Hasegawa Dementia Scale, this study found that more than half of adults aged ≥ 60 years had cognitive impairment, and this impairment was associated with several risk factors. The limitations of this study may include possible overdetection due to the cutoff point for the assessment of cognitive decline used in the Revised Hasegawa Dementia Scale, given that the participants were not familiar with the instrument. However, the study results can be used to help inform health policy in the Lao People's Democratic Republic regarding the urgent need for a routine data collection system and for providing an environment that addresses and reduces the identified risk factors for cognitive decline to mitigate their impact.