Albendazole (ALB), a benzimidazole antiparasitic, is widely used in mass drug administration (MDA) campaigns against lymphatic filariasis (LF). It is rapidly metabolized to its active form, albendazole sulfoxide (ALB-OX), which exhibits considerable interindividual variability (IIV) in pharmacokinetics (PK). This variation may affect ALB efficacy in MDA programs. We developed a population pharmacokinetic (PopPK) model characterizing ALB and ALB-OX exposure and identifying demographic and clinical covariates contributing to IIV in patients with LF and healthy individuals. Plasma concentration-time data were pooled from three clinical studies involving ALB co-administered with ivermectin and diethylcarbamazine. Nonlinear mixed-effects modeling was conducted using Phoenix NLME. Covariate effects (e.g., sex, age, infection status) were assessed, and model validation employed visual predictive checks and bootstrapping. Simulations explored covariate impact on exposure. A joint two-compartment model with transit absorption for ALB and pre-systemic ALB-OX formation best described the data. Sex significantly influenced ALB-OX clearance and volume of distribution, with males exhibiting higher clearance and lower exposure. Body weight, age, and LF infection status did not significantly affect PK parameters. Simulations confirmed 33% lower ALB-OX levels in males compared to females following a 400 mg oral ALB dose. This is the first PopPK model of ALB and ALB-OX in LF-endemic populations. It highlights sex as a key covariate explaining IIV in ALB-OX exposure, with implications for optimized dosing in MDA programs. Further studies incorporating pharmacogenetics and pediatric data are warranted.This study is registered with ClinicalTrials.gov as NCT04410406, NCT02845713, and NCT03664063.

Dirofilaria repens is a zoonotic parasite expanding across Europe due to climate change. We hypothesised that in this process, the Carpathian Basin has a facilitating effect. Using 426 georeferenced European cases, the probability of infection occurrence was determined in relation to climatic factors, surface water availability, regional social deprivation, and stray dog population density. To analyse the potential impacts of ecological and social factors (deprivation and stray dog population density), the MaxEnt algorithm, and spatial Empirical Bayes smoothing and bivariate local indicators of spatial association (BiLISA) index calculation were employed, respectively. MaxEnt analysis revealed that the mean warmest month temperature (MWMT; 22.8-25.1°C), winter mean minimum temperature (>-2.1°C), and summer precipitation (28.6-231 mm) have the strongest impact on the probability of the parasite's occurrence in Europe. Social factors have significance in the eastern Balkans and the Carpathian Basin, but not in Western Europe. The Carpathian Basin appears to be a hotspot, similar to Mediterranean coastal areas. Furthermore, the Danube Valley acts as an ecological corridor for subtropical vector-borne parasites. Our findings confirm that summer warmth is the primary ecological driver of the parasite's range expansion, which is facilitated by the Carpathian Basin due to climatic and socioeconomic conditions.

This issue of Public Health Action includes a series of articles on 'Research leadership in India', a Structured Operational Research and Training Initiative (SORT IT), led by TDR, as a model for strengthening operational research capacity within health systems globally. Conducted in 19 institutions in India, it transforms frontline health challenges into research that informs policy and practice. The 11 articles in this issue address public health challenges while enhancing self-reliance and people-centered health approaches as drivers for universal health coverage and equity. By placing individuals, communities and frontline realities at the center of research, the series reaffirms that meaningful and lasting health system transformation begins with listening, learning, and leading from within.

Lymphatic filariasis, caused by Brugia malayi, leads to chronic lymphatic dysfunction and lymphedema. The molecular mechanisms underlying interactions between filarial worms and their hosts remain poorly understood. Using untargeted metabolomics, we identify previously unknown acetylcholine analogs synthesized from leucine and isoleucine that are secreted by Brugia adult males. In the mammalian host, these metabolites selectively activate host M2 muscarinic acetylcholine receptors, alter lymphatic endothelial cell integrity, and trigger constriction of lymphatic vessels. These metabolites added to cultures also reduce microfilarial production in B. malayi and egg-laying in Caenorhabditis elegans, implying a role in regulating nematode reproduction. Their production is potently inhibited by ethacrynic acid, an existing FDA-approved drug. Our findings reveal a previously unexplored role for filarial-derived cholinergic signaling in parasite reproduction that impacts host lymphatic homeostasis. This work offers insights into the biochemical adaptations that function in the worm life cycle and reveals potential metabolic vulnerabilities in filarial worms.

We took advantage of rhinoceros translocations and entomological studies in the 1990s to elucidate some aspects of the biology of Stephanofilaria in Kenya, which remains largely undocumented. Blood samples from 88 black and 27 white rhinos were screened for microfilariae during routine haematology. Microfilariae matching S. dinniki were found in three individual black rhinos on single occasions and were not found in white rhinos; the parasite was not transmissible to tsetse or laboratory mice. Thousands of proboscides of 19 species of Stomoxyinae and other Diptera were dissected from Nairobi National Park and Solio Ranch to detect larval forms of filarial nematodes. Stephanofilaria was found in seven Stomoxys species at low prevalence (< 2%, mean of nine per fly), with a few similar parasites found in two Haematobosca species. Larval filaria were measured for basic landmarks and were described through light microscopy. This information now provides a foundation for more detailed studies of the life cycle of this parasite.