Biophysical and ecological factors are known to shape the distribution of mosquito vectors, yet their interaction across heterogeneous and rapidly transforming landscapes remains insufficiently understood. We assessed the occurrence of Aedes albopictus in relation to environmental and biotic drivers in the Iguazú Department, Misiones Province, Argentina, within the tri-border region shared with Brazil and Paraguay, a key epidemiological corridor for arboviral transmission. Mosquitoes were monitored using adult activity sensors (ovitraps) across 81 sites representing urban, periurban, and wild environments (later divided in pristine and disturbed wild) in eleven sampling sessions between April 2019 and February 2020. Environmental characterization integrated field data and remotely sensed biophysical variables at different spatial scales relevant to vector ecology, which were included in generalized linear mixed models together with the presence of Ae. aegypti as covariate to account for potential interspecific effects, and co-occurrence of both Aedes species was further evaluated using Bayesian analyses. Aedes albopictus showed a strongly stratified spatial pattern, with 30.4-30.6% positive ovitraps in periurban and disturbed wild, in comparison with 14.2% for urban and only 3.9% for pristine wild. Occurrence probability increased with intermediate levels of monthly precipitation and minimum temperature, showed nonlinear responses to vegetation cover, and decreased with impervious surfaces, explaining 67% of the variability. Co-occurrence analyses indicated positive associations in urban and periurban environments, suggesting partial niche overlap under anthropogenic conditions. Our results identify periurban and disturbed wild environments as critical ecological interfaces structuring Ae. albopictus distribution. These findings provide a robust basis for targeted surveillance and highlight the need for coordinated, cross-border vector management strategies in rapidly transforming subtropical regions.

We report a very delayed paradoxical reaction presenting more than 4 years after antibiotic treatment of Buruli ulcer that settled without further antibiotic treatment. Our report aims to alert clinicians to this possibility to avoid misdiagnosis of relapsed infection and unnecessary antibiotic re-treatment which can be associated with toxicity, inconvenience and cost for the patient.

Snakebite envenoming disproportionately affects Indigenous populations in the Brazilian Amazon, where centralized healthcare systems limit timely access to antivenom. The recently implemented SAVING Program has decentralized antivenom delivery to Indigenous primary healthcare facilities, improving access and clinical outcomes. This article examines the ethical considerations encountered and the approaches adopted to address these challenges. Using the WHO/TDR framework for ethics in implementation research as a starting point, we continuously adapted to ethical issues arising during the planning, implementation, and dissemination of the program. The analysis was informed by focus groups and stakeholder discussions involving Indigenous leaders, patients, healthcare professionals, health managers, policymakers, and representatives of Indigenous governance structures. Key themes included community and stakeholder responsiveness, informed consent, balancing risks and benefits, culturally appropriate standards of care, data governance, sustainability, and benefit sharing. Decentralizing antivenom delivery can improve equitable access to lifesaving treatment while strengthening Indigenous health systems. To date, the program has demonstrated the feasibility of building sustainable partnerships with Indigenous communities, enhancing acceptance and equity. The ethical lessons from the SAVING Program may provide practical guidance for implementing health innovations in Indigenous and other historically underserved communities.

The study of snake venom toxicity and evaluation of the neutralisation ability of antivenoms and novel therapeutic agents for envenoming has largely relied on animal tests, especially the analysis of the lethal activity of venoms and its neutralisation. In addition, other animal-based assays are used to assess pathology-specific effects of venoms. Despite their demonstrated value, these assays have several limitations. They involve acute stress and pain in animals, and their validity, vis-à-vis the characteristics of human snakebite envenoming, is limited owing to the nature of the assays. Therefore, urgent innovations are required in this field. Ensuring the implementation of the 3Rs (Replacement, Reduction, and Refinement) is essential when animal studies are required. These include: (a) refinement of the tests (e.g., use of analgesia, reduction of assay duration, and refining of humane endpoints); (b) reduction in the number of animals used by more thorough in vitro assessment of antivenoms prior to in vivo assays, and improved statistical analyses and group sizing; and, most importantly, and (c) replacement of in vivo rodent tests with validated in vitro approaches, such as immunoassays, enzymatic and cell-based assays, the use of invertebrate models, and the implementation of New Approach Methodologies (NAMs), i.e., novel in vitro or in silico techniques that model complex pathophysiological processes of envenoming. A roadmap involving researchers, manufacturers, quality control groups, regulators, and funding agencies is proposed, with the aim of driving significant changes in this field.

In co-endemic regions, mixed Plasmodium vivax (Pv) and Plasmodium falciparum (Pf) infections are commonly reported. How mixed species infections compare to single species infections in terms of parasite densities and transmission to mosquitoes is poorly understood. Parasitemia, gametocytemia, and mosquito infectivity were evaluated among Pv mono-infections (n = 284), Pf mono-infections (n = 150), and mixed-Pv-Pf infections (n = 77) recruited at four Ethiopian health facilities. Parasitemia and gametocytemia were quantified in patient blood samples by qPCR. Mosquito infectivity was assessed using direct membrane feeding assays (DMFA), with Plasmodium species confirmation by quantitative PCR. Pf gametocyte prevalence was lower in mixed-infections (64.5%, 49/76) compared with mono-infections (91.8%, 135/147). Gametocyte density among positive carriers was also lower in mixed-infections (p < 0.001). Pv gametocyte prevalence was similar in mono- and mixed-infections despite lower asexual parasite density in mixed infections (p < 0.001). Statistically significant positive correlations between asexual parasitemia and gametocytemia were observed in mono-infections (p < 0.001), but not in mixed-species infections (p = 0.120 for Pv; and p = 0.570 for Pf). The overall proportion of infectious feeds to mosquitoes was high across infection types. Among mixed Pv-Pf parasite carriers, 56.3% (27/48) transmitted both species, often with both species being transmitted to individual mosquitoes. Species-specific gametocyte density remained associated with mosquito infection rates, and these associations were not altered by concurrent infection with the other species. Thus, mixed-species infections were associated with altered asexual and gametocyte densities, notably reduced gametocyte biomass, while mosquito infectivity was not reduced. Because mixed infections are often undetected, they represent a hidden risk for sustaining malaria transmission.

Chagas disease (CD) remains a persistent public health challenge in endemic areas of Brazil, where access to diagnosis, clinical staging, and etiological treatment is often limited. Tremedal and Novo Horizonte, municipalities in the state of Bahia, continue to report chronic cases despite advances in vector control. This study provides a retrospective assessment of CD detection and clinical management in these municipalities prior to the full implementation of the Oxente Chagas Bahia Project. We analyzed individuals tested for CD serology between 2019 and 2023 using data from the Laboratory Environment Manager (GAL) system and electronic primary care records (e-SUS). Sociodemographic characteristics, seropositivity, turnaround time for serological testing, and clinical manifestations were evaluated. A total of 472 individuals underwent serological testing. Testing volume increased markedly in Tremedal over time, whereas Novo Horizonte initiated screening only in 2023. Fourteen individuals (3.0%) tested positive for anti-Trypanosoma cruzi antibodies, all from Tremedal; 13 were included in the clinical analysis. The median age of confirmed cases was 52 years, and 61.5% were female. Among the 13 confirmed cases, the indeterminate form predominated (61.5%), followed by the cardiac and mixed forms (15.4% each) and the digestive form (7.7%) Electrocardiographic conduction abnormalities predominated among individuals with cardiac involvement, while severe digestive manifestations, including megacolon and megaesophagus, were documented in three individuals. Median turnaround time for serological results was longer in Tremedal than in Novo Horizonte. Documentation of etiological treatment with benznidazole was limited, with treatment records identified for only two of the thirteen confirmed cases in the available medical records. These findings highlight the ongoing burden of chronic CD, substantial gaps in screening and treatment, and the need to strengthen diagnostic access and guideline-based management. This study establishes a critical pre-intervention baseline for evaluating the impact of the Oxente Chagas Bahia Project in endemic municipalities.

Harmine (HM), a bioactive alkaloid, exhibits remarkable antiparasitic potency. Nevertheless, its translational potential is substantially constrained by neurotoxicity, necessitating the development of safer analogs. H-2-168, a rationally designed derivative synthesized via targeted structural modifications of the HM core, has emerged as a leading candidate for further therapeutic exploration due to its favorable pharmacological profile. To optimize its pharmacokinetic properties and enhance treatment efficacy, this study reports the fabrication of H-2-168-loaded poly (lactic - co - glycolic acid) (PLGA) nanoparticles (H8-PLGA-NPs). Results demonstrated that H8-PLGA-NPs exhibited uniform spherical morphology with an average diameter of 198 nm (PDI = 0.15) and a high drug encapsulation efficiency of 88.6%. Following 30-day oral administration (100 mg/kg/day), H8-PLGA-NPs demonstrated significantly enhanced anthelmintic efficacy and tissue regenerative capacity compared to free H-2-168, while effectively ameliorating inflammatory responses and hepatic fibrosis progression. Notably, systemic toxicity was substantially reduced, particularly hepatotoxicity and cytotoxicity. This study substantiates that PLGA-based nanocarriers markedly improve the therapeutic outcomes of H-2-168 against cystic echinococcosis (CE) through optimized drug encapsulation and delivery efficiency, thereby proposing a promising therapeutic strategy for CE management. Nevertheless, comprehensive investigations into the long-term biosafety profiles of these nanoparticles and optimal dosing regimens warrant further exploration.

During an investigation of animals as reservoirs for the filarial parasite Brugia malayi, three molecularly undescribed filarial species were co-detected. Individual microfilariae (Mf) were isolated and analyzed from blood samples of crab-eating macaques (Macaca fascicularis) from Belitung, Indonesia, and from pet dogs and cats in Sabah, Malaysia. Among 163 macaques, 33 (20.2%) were positive for large Mf (mean length 498.9 µm) similar to Dirofilaria ('Belitung I'). One macaque was infected with small Mf (mean length 150.4 µm) ('Belitung II'), with a high density of 17,150 Mf/mL. In two cats co-infected with B. malayi, Mf of a Dirofilaria species ('Sabah') with an average length of 299.1 µm were detected. Morphometric analysis of Mf showed distinct differences between these three species and other Mf described in the area. Whole genome amplification and genome sequencing of 24 individual Mf enabled phylogenetic analysis of mitochondrial genomes, and analysis of specific mitochondrial and nuclear barcode regions. The three Mf groups formed distinct clusters and could not be identified by comparison with available reference sequences. Cluster 'Belitung I' from macaques formed a sister group to other characterized Dirofilaria. Cluster 'Belitung II' included bird filariae and primate filariae of the genus Mansonella as close relatives. The cluster 'Sabah' formed a monophyletic group with the zoonotic species Dirofilaria asiatica and Dirofilaria sp. 'Thailand'. DNA of Wolbachia endobacteria was detected in Mf of 'Belitung I' and 'Sabah', but not in 'Belitung II'. These findings highlight the limited understanding of filarial diversity in macaques and cats in Asia and underscore the need for a more comprehensive approach that combines morphological and molecular data to identify and assess the pathogenicity and zoonotic potential of these parasites.

Mosquito-borne diseases pose a growing global health threat, largely driven by the human-mediated introduction of vector species beyond their native regions. Although only a few mosquito species have historically established populations outside their native ranges, the number of such invasions has increased rapidly in recent decades. Once established, these non-native invasive mosquitoes are difficult to control, emphasizing the need for proactive identification before introduction occurs. Here, we present a framework to predict invasion potential for 184 mosquito species of medical importance based on their ecological, life-history, and macroecological traits. We compiled a comprehensive dataset of 26 traits characterizing each species and used random forest models to relate these traits to the probabilities of introduction into non-native regions (before and after 1950, marking the onset of widespread trade globalization) and establishment following introduction. Models achieved moderate to good predictive performance (AUC = 0.78-0.85) and revealed that species native to Asia and Australia, adapted to human-made breeding sites, and associated with high-precipitation and thermally extreme environments were consistently more likely to be introduced or establish in non-native regions. Among species with no known invasion history, we identified 24 with high predicted introduction probabilities, of which 17 also showed high establishment probabilities. These results demonstrate that invasion potential can be inferred from species traits and provide a quantitative basis for proactive surveillance and prioritization of species most likely to be introduced in the future.