African swine fever virus is the etiological agent of African swine fever, a transmissible severe hemorrhagic disease that affects pigs, causing massive economic losses. There is neither a treatment nor a vaccine available, and the only method to control its spread is by extensive culling of pigs. So far, classical vaccine development approaches have not yielded sufficiently good results in terms of concomitant safety and efficacy. Nowadays, thanks to advances in genomic and proteomic techniques, a reverse vaccinology strategy can be explored to design alternative vaccine formulations. In this study, ASFV protein sequences were analyzed using an in-house pipeline based on publicly available immunoinformatic tools to identify epitopes of interest for a prospective vaccine ensemble. These included experimentally validated sequences from the Immune Epitope Database, as well as de novo predicted sequences. Experimentally validated and predicted epitopes were prioritized following a series of criteria that included evolutionary conservation, presence in the virulent and currently circulating variant Georgia 2007/1, and lack of identity to either the pig proteome or putative proteins from pig gut microbiota. Following this strategy, 29 B-cell, 14 CD4⁺ T-cell and 6 CD8⁺ T-cell epitopes were selected, which represent a starting point to investigating the protective capacity of ASFV epitope-based vaccines.

Chagas disease, caused by parasite Trypanosoma cruzi, is the most important neglected tropical disease in the Americas. Two drugs are available for treatment, but access to them is challenging, in part due to complex diagnostic algorithms. These are stage-dependent, involve multiple tests and are ill-adapted to the reality of vast areas where the disease is endemic. Molecular and serologic tools are used to detect acute and chronic infections, with the performance of the latter showing geographic differences. Breakthroughs in the development of new diagnostic tools include the validation of a loop-mediated isothermal amplification assay for acute infections (T. cruzi-LAMP), and the regional validation of several rapid diagnostic tests (RDTs) for chronic infection, which simplify testing in resource-limited settings. The literature search was carried out in the MEDLINE database until NaN Invalid Date NaN. This review outlines existing algorithms, and proposes new ones focused on point-of-care testing. Integrating point-of-care testing into existing diagnostic algorithms in certain endemic areas will increase the access to timely diagnosis and treatment. However, additional research is needed to validate the use of these techniques across a wider geography, and to better understand the cost-effectiveness of their large-scale implementation.

Malaria and Chagas disease, caused by Plasmodium spp. and Trypanosoma cruzi parasites, remain important global health problems. Available treatments for those diseases present several limitations, such as lack of efficacy, toxic side effects, and drug resistance. Thus, new drugs are urgently needed. The discovery of new drugs may be benefited by considering the significant biological differences between hosts and parasites. One of the most striking differences is found in the purine metabolism, because most of the parasites are incapable of de novo purine biosynthesis. Herein, we have analyzed the in vitro anti-P. falciparum and anti-T. cruzi activity of a collection of 81 purine derivatives and pyrimidine analogs. We firstly used a primary screening at three fixed concentrations (100, 10, and 1 µM) and progressed those compounds that kept the growth of the parasites < 30% at 100 µM to dose–response assays. Then, we performed two different cytotoxicity assays on Vero cells and human HepG2 cells. Finally, compounds specifically active against T. cruzi were tested against intracellular amastigote forms. Purines 33 (IC₅₀ = 19.19 µM) and 76 (IC₅₀ = 18.27 µM) were the most potent against P. falciparum. On the other hand, 6D (IC₅₀ = 3.78 µM) and 34 (IC₅₀ = 4.24 µM) were identified as hit purines against T. cruzi amastigotes. Moreover, an in silico docking study revealed that P. falciparum and T. cruzi hypoxanthine guanine phosphoribosyltransferase enzymes could be the potential targets of those compounds. Our study identified two novel, purine-based chemotypes that could be further optimized to generate potent and diversified anti-parasitic drugs against both parasites.

Chagas disease is a devastating neglected disease caused by the parasite Trypanosoma cruzi, which affects millions of people worldwide. The two anti-parasitic drugs available, nifurtimox and benznidazole, have a good efficacy against the acute stage of the infection. But this is short, usually asymptomatic and often goes undiagnosed. Access to treatment is mostly achieved during the chronic stage, when the cardiac and/or digestive life-threatening symptoms manifest. Then, the efficacy of both drugs is diminished, and their long administration regimens involve frequently associated adverse effects that compromise treatment compliance. Therefore, the discovery of safer and more effective drugs is an urgent need. Despite its advantages over lately used phenotypic screening, target-based identification of new anti-parasitic molecules has been hampered by incomplete annotation and lack of structures of the parasite protein space. Presently, the AlphaFold Protein Structure Database is home to 19,036 protein models from T. cruzi, which could hold the key to not only describe new therapeutic approaches, but also shed light on molecular mechanisms of action for known compounds. In this proof-of-concept study, we screened the AlphaFold T. cruzi set of predicted protein models to find prospective targets for a pre-selected list of compounds with known anti-trypanosomal activity using docking-based inverse virtual screening. The best receptors (targets) for the most promising ligands were analyzed in detail to address molecular interactions and potential drugs’ mode of action. The results provide insight into the mechanisms of action of the compounds and their targets, and pave the way for new strategies to finding novel compounds or optimize already existing ones.

Heterakis is a genus of parasitic nematodes, the majority of which are found in ground-feeding birds and only rarely in mammals. The best-known species is Heterakis spumosa, a parasite associated with the cosmopolitan invasive rodent Rattus rattus of Asiatic origin. Heterakis dahomensis was described in 1911 as a parasite of the Gambian giant rat (Cricetomys gambianus) from Benin (Africa), subsequently synonymized to H. spumosa by Hall (1916). The study of helminths in African rodents is scarce and patchy. Since the original description of H. dahomensis, there have been only a few reports from Africa of species belonging to the genus Heterakis and the validity of this species has never in fact been confirmed or rejected. In the present study individual Heterakis spp. were collected from C. gambianus from Senegal. The morphological data taken point to differences between Heterakis dahomensis and H. spumosa, specifically in the number of tail papillae in males and in the vulva cuticular processes of females. In addition, molecular data revealed differences between these taxa and so H. dahomensis should be considered as a valid species. Moreover, recent changes in the systematics of the genus Cricetomys mean that it is now necessary to study the morphology and genetics of the Heterakis specimens collected from Cricetomys spp. (previously assigned to C. gambianus) in order to determine their taxonomic status as either H. dahomensis o H. spumosa.

Snakebite envenomation is a neglected tropical disease that causes over 100,000 deaths each year. The only effective treatment consists of antivenoms derived from animal sera, but these have been deemed with highly variable potency and are usually inaccessible and too costly for victims. The production of antivenoms by venom-independent techniques, such as the immunization with multi-epitope constructs, could circumvent those drawbacks. Herein, we present a knowledge-based pipeline to prioritize potential epitopes of therapeutic relevance from toxins of medically important snakes in West Sub-Saharan Africa. It is mainly based on sequence conservation and protein structural features. The ultimately selected 41 epitopes originate from 11 out of 16 snake species considered of highest medical importance in the region and 3 out of 10 of those considered as secondary medical importance. Echis ocellatus, responsible for the highest casualties in the area, would be covered by 12 different epitopes. Remarkably, this pipeline is versatile and customizable for the analysis of snake venom sequences from any other region of the world.