Biology subjects

Monteiro, W. M.

Publications and source records attributed to Monteiro, W. M..

4 recordsLinked to original sources

bioRxiv2025

Navigating parasite antigen genetic diversity in the design of Plasmodium vivax serological exposure markers for malaria

BackgroundPlasmodium vivax poses a major obstacle to malaria elimination because it can lie dormant in the liver for weeks or months before reactivating and causing a relapse of infection. These dormant forms (hypnozoites) cannot be detected using standard diagnostics, but recent P. vivax exposure and by proxy, hypnozoite carriage, can be inferred using antibody-based tests (serological markers). In this study, we examined how genetic variation in P. vivax affects the utility of these antibody markers, and whether redesigned antigens could improve performance. MethodsWe analysed global P. vivax genetic data to assess variation in leading serological markers. Based on this, we produced new antigen versions (haplotypes) that better reflect global sequence diversity, compared to the commonly used reference strain (Sal-1). Antibody responses against these new constructs were then tested using samples from well-characterised cohorts in Brazil and Thailand. Antibody levels were assessed in relation to how recently participants had a qPCR-detectable blood-stage P. vivax infection. We compared the ability of the haplotypes and reference constructs to correctly identify individuals infected within the prior 9-months. FindingsExtensive genetic diversity was identified in two P. vivax antigens, DBPII and MSP5. Several antigens had large numbers of circulating haplotypes globally, with the percentage with similar sequence identity to the reference Sal-1 ranging from 0.4% (MSP5) to 99% (S16). Two antigens exhibited strong differences in immunogenicity by region and construct (RBP2a and DBPII). However, for most proteins (5 out of 8), these differences had little impact on the accuracy of identifying recent exposure. In cases where performance was affected (e.g. RBP2a), this could be overcome by adding multiple antigens into the classification model. InterpretationEven highly diverse antigens can be effective serological exposure markers. Our findings highlight the importance of testing the impact of genetic diversity when designing serological tests and suggest practical strategies, such as using a mix of antigens, to ensure consistent performance across regions.

microbiology↗

bioRxiv2022

The genome of the brackish-water malaria vector Anopheles aquasalis

Anopheles aquasalis is a primary malaria vector in coastal South America that grows in brackish waters of mangroves. Its importance has increased in recent years as it has been established as a model for parasite-vector studies for non-model Plasmodium species, such as P. yoelli. In this study, we present the complete genome of An. aquasalis and offer some insights into evolution and physiology. With a 162Mb and 12,446 coding proteins, the An. aquasalis genome is similar in size and gene content as other neotropical anophelines. 1,038 single-copy orthologs are present in An. aquasalis and all Diptera and it was possible to infer that An. aquasalis diverged from An. darlingi (the main malaria vector in inland South America) nearly 14 million years ago (mya). Ion transport and metabolism proteins is one the major gene families in An. aquasalis with 660 genes. Amongst these genes, important gene families relevant for osmosis control (e.g., aquaporins, vacuolar-ATPases, Na+/K+-ATPases and carbonic anhydrases) were identified in one-to-one orthologs with other anophelines. Evolutionary analysis suggests that all osmotic regulation genes are under strong purifying selection. We also observed low copy number variation in immunity-related genes (for which all classical pathways were described) and insecticide resistance genes. This is the third genome of a neotropical anopheline published so far. The data provided by this study may offer candidate genes for further studies on parasite-vector interactions and for studies on how brackish water anophelines deals with high fluctuation in water salinity. Significance StatementThe brackish water mosquito Anopheles aquasalis is a primary malaria vector in coastal South America. Besides its peculiar ecological features (it is one of the few anopheline mosquitoes that survives high fluctuation of water salinity), An. aquasalis has gained relevance in recent years as a model for parasite-vector studies for non-model Plasmodium parasites. Still, the physiology and genetics of An. aquasalis are poorly understood. Here we present the genome of An. aquasalis with more than 12,000 annotated genes, offering insights in genome evolution, osmoregulation related, immunity, chemosensory and insecticide resistance genes. The data presented here will help to further advance the studies on An. aquasalis genetics and physiology to better understand parasite-vector interactions in non-model organisms.

genomics↗

bioRxiv2018

Development and validation of serological markers for detecting recent exposure to Plasmodium vivax infection

In order to accelerate towards malaria elimination, improved targeting of limited resources is essential. A major gap in our elimination toolkit for Plasmodium vivax malaria is the identification of individuals carrying arrested liver stages, called hypnozoites. These clinically silent but frequently relapsing hypnozoites are key to P. vivax persistence. Whilst hypnozoites cannot be directly detected, individuals who have had recent exposure to P. vivax and have not been treated are likely to harbor these parasites. By measuring IgG antibody responses to over 300 P. vivax proteins, a panel of serological markers capable of detecting exposure to P. vivax infections in the prior 9-month period was identified and validated. Using antibody responses to 8 P. vivax proteins, 80% sensitivity and specificity for detecting recent infections were achieved in three independent studies conducted in Thailand, Brazil and the Solomon Islands. As these individuals have a high likelihood of harboring hypnozoites, the suite of these 8 antibody responses can serve as biomarkers for the identification of individuals who should be targeted for treatment with liver-stage drugs such as primaquine and tafenoquine in mass drug administration programs aimed at controlling and eliminating P. vivax malaria.\n\nOne Sentence SummaryThe manuscript describes identification and validation of a novel panel of P. vivax proteins that can be used to detect recent exposure to P. vivax infections within the prior 9 months.

microbiology↗

bioRxiv2018

Stepping into a dangerous quagmire: environmental determinants of human-lancehead pit vipers (Bothrops genus) contact resulting in injuries, Brazilian Amazon

Despite significant and successful efforts in Brazil regarding snakebites in the areas of research, antivenom manufacture and quality control, training of health professionals in the diagnosis and clinical management of bites, little is known about determinants of snakebites incidence in order to further plan interventions to reduce the impact of this medical condition. Understanding the complexity of ecological interactions in a geographical region is important for prediction, prevention and control measures of snakebites. The aim of this investigation is to describe spatial distribution and identify environmental determinants of human- lancehead pit vipers (Bothrops genus) contact resulting in injuries, in the Brazilian Amazon. Aggregated data by municipality was used to analyze the spatial distribution of Bothrops bites cases and its relationship with geographic and environmental factors. Eight geo-environmental factors were included in the analysis as independent variables: (1) tree canopy loss increase; (2) area with vegetation cover; (3) area covered by water bodies; (4) altitude; (5) precipitation; (6) air relative humidity; (7) soil moisture; and (8) air temperature. Human- lancehead pit vipers (Bothrops genus) contact resulting in envenomings in the Amazon region is more incident in lowlands [-0.0006827 (IC95%: -0.0007705; - 0.0005949), p<0.0001], with high preserved original vegetation cover [0.0065439 (IC95%: 0.0070757; 0.0060121), p<0.0001], with heaviest rainfall [0.0000976 (IC95%: 0.0000925; 0.0001026), p<0.0001] and higher air relative humidity [- 0.0081773 (IC95%: -0.0107681; -0.0055865), p<0.0001]. This association is interpreted as the result of the higher forest productivity and abundance of pit vipers in such landscapes.\n\nAuthor summaryDespite successful efforts in Brazil regarding snakebites in the areas of research, antivenom manufacture and quality control and training of health professionals, little is known about determinants of snakebites incidence in order to further plan interventions to reduce the impact of this medical condition. Understanding the complexity of ecological interactions in a geographical region is important for prediction, prevention and control measures of snakebites. The aim of this study is to describe spatial distribution and identify environmental determinants of human- lancehead pit vipers (Bothrops genus) contact resulting in injuries, in the Brazilian Amazon. An increase in the forest productivity with a higher availability of some types of prey, such as frogs and amphibians, anurans and lizards, was suggested as a cause for the higher snake abundance in the rainy season. Probably due to the higher forest productivity and abundance of pit vipers in such landscapes, human-lancehead pit vipers contact resulting in envenomings in the Amazon region is more incident in lowlands, with high preserved original vegetation cover, with heaviest rainfall and higher air relative humidity.

animal behavior and cognition↗