Analysis of inpatient data on dengue fever, malaria and leishmaniasis in Ecuador: A cross-sectional national study, 2015-2022.

Background: Despite concerted efforts in South America, these diseases continue to pose a significant burden of morbidity and mortality in endemic regions. This study aimed to analyse hospital data and investigate the hospitalisation rates of dengue fever, leishmaniasis, and malaria in Ecuador between 2015 and 2022. Methods: Open-access databases from the National Institute of Statistics and Censuses of Ecuador between 2015 and 2022 were analysed. Data were filtered using specific terms for each disease (ICD-10), and descriptive statistics of geographical distributions were calculated using Microsoft Excel, Stata 14.2, and Rstudio. Results: Dengue had the highest burden, with 31,616 reported cases, followed by malaria (1,316) and leishmaniasis (283). From 2015 to 2022, the highest hospitalisation rate per 105 inhabitants for dengue was observed in Sucumbios province (697.2), for malaria in Pastaza province (108.4), and for leishmaniasis in Morona Santiago province (18.8). The data's trend analysis revealed a slight increase in dengue and mild downward trends in hospitalisation for malaria and leishmaniasis. Conclusions: The results suggest that vector-borne disease control has failed in Ecuador. Unfortunately, there was no significant trend towards a decrease in dengue, malaria, and leishmaniasis in Ecuador during the years studied. This study highlights the need to optimise sustainable vector control programs and emphasises continuous monitoring of disease incidence and control measures.

Phage therapy: resurrecting a historical solution for the contemporary challenge of rising antibiotic resistance in Latin America.

INTRODUCTION: Antimicrobial resistance in Latin America is a growing concern in both human and non-human animal populations. The economic burden that is likely to be imposed through increased resistance will cause further strains on public health systems and the population at large. AREAS COVERED: We propose the rapid adoption and implementation of phage therapy as a necessary addition to the medical arsenal to help mitigate antimicrobial resistance, with an emphasis on considering the potential benefits that highly biodiverse countries such as Ecuador may have on phage discovery. However, programs may count on limited government support and/or facilitation, which could slow progress. EXPERT OPINION: We highlight the need for educational campaigns to be implemented in parallel with the development of phage therapy programs, particularly to implement these novel treatments in rural and indigenous communities.

Pulmonary Inflammatory Response in Lethal COVID-19 Reveals Potential Therapeutic Targets and Drugs in Phases III/IV Clinical Trials.

Background: It is imperative to identify drugs that allow treating symptoms of severe COVID-19. Respiratory failure is the main cause of death in severe COVID-19 patients, and the host inflammatory response at the lungs remains poorly understood. Methods: Therefore, we retrieved data from post-mortem lungs from COVID-19 patients and performed in-depth in silico analyses of single-nucleus RNA sequencing data, inflammatory protein interactome network, and shortest pathways to physiological phenotypes to reveal potential therapeutic targets and drugs in advanced-stage COVID-19 clinical trials. Results: Herein, we analyzed transcriptomics data of 719 inflammatory response genes across 19 cell types (116,313 nuclei) from lung autopsies. The functional enrichment analysis of the 233 significantly expressed genes showed that the most relevant biological annotations were inflammatory response, innate immune response, cytokine production, interferon production, macrophage activation, blood coagulation, NLRP3 inflammasome complex, and the TLR, JAK-STAT, NF-κB, TNF, oncostatin M signaling pathways. Subsequently, we identified 34 essential inflammatory proteins with both high-confidence protein interactions and shortest pathways to inflammation, cell death, glycolysis, and angiogenesis. Conclusion: We propose three small molecules (baricitinib, eritoran, and montelukast) that can be considered for treating severe COVID-19 symptoms after being thoroughly evaluated in COVID-19 clinical trials.

In silico Analyses of Immune System Protein Interactome Network, Single-Cell RNA Sequencing of Human Tissues, and Artificial Neural Networks Reveal Potential Therapeutic Targets for Drug Repurposing Against COVID-19.

Background: There is pressing urgency to identify therapeutic targets and drugs that allow treating COVID-19 patients effectively. Methods: We performed in silico analyses of immune system protein interactome network, single-cell RNA sequencing of human tissues, and artificial neural networks to reveal potential therapeutic targets for drug repurposing against COVID-19. Results: We screened 1,584 high-confidence immune system proteins in ACE2 and TMPRSS2 co-expressing cells, finding 25 potential therapeutic targets significantly overexpressed in nasal goblet secretory cells, lung type II pneumocytes, and ileal absorptive enterocytes of patients with several immunopathologies. Then, we performed fully connected deep neural networks to find the best multitask classification model to predict the activity of 10,672 drugs, obtaining several approved drugs, compounds under investigation, and experimental compounds with the highest area under the receiver operating characteristics. Conclusion: After being effectively analyzed in clinical trials, these drugs can be considered for treatment of severe COVID-19 patients. Scripts can be downloaded at https://github.com/muntisa/immuno-drug-repurposing-COVID-19.