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Chagas Disease Drug Discovery in Latin America-A Mini Review of Antiparasitic Agents Explored Between 2010 and 2021.

ABSTRACT: Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi that endangers almost 70 million people worldwide. The only two drugs that are currently approved for its treatment, benznidazole and nifurtimox, have controversial efficacy in adults and restricting safety issues, leaving thousands of patients without a suitable treatment. The neglect of Chagas disease is further illustrated by the lack of a robust and diverse drug discovery and development portfolio of new chemical entities, and it is of paramount importance to build a strong research and development network for antichagasic drugs. Focusing on drug discovery programs led by scientists based in Latin America, the main endemic region for this disease, we discuss herein what has been published in the last decade in terms of identification of new antiparasitic drugs to treat Chagas disease, shining a spotlight on the origin, chemical diversity, level of characterization of hits, and strategies used for optimization of lead compounds. Finally, we identify strengths and weaknesses in these drug discovery campaigns and highlight the importance of multidisciplinary collaboration and knowledge sharing.

SUBMITTER: de Oliveira RG

PROVIDER: S-EPMC8581468 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Chagas Disease Drug Discovery in Latin America-A Mini Review of Antiparasitic Agents Explored Between 2010 and 2021.

de Oliveira Ramon G RG Cruz Luiza R LR Mollo María C MC Dias Luiz C LC Kratz Jadel M JM

Frontiers in chemistry 20211028

Chagas disease is a neglected tropical disease caused by the protozoan parasite <i>Trypanosoma cruzi</i> that endangers almost 70 million people worldwide. The only two drugs that are currently approved for its treatment, benznidazole and nifurtimox, have controversial efficacy in adults and restricting safety issues, leaving thousands of patients without a suitable treatment. The neglect of Chagas disease is further illustrated by the lack of a robust and diverse drug discovery and development ...[more]

PMID: 34778217

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Project description:ObjectiveThere are limited published data about the circulation of influenza B/Victoria and B/Yamagata in Latin America and the Caribbean (LAC) and most countries have a vaccine policy that includes the use of the trivalent influenza vaccine. We analyzed influenza surveillance data to inform decision-making in LAC about prevention strategies, such as the use of the quadrivalent influenza vaccine.MethodsThere are a total of 28 reference laboratories and National Influenza Centers in LAC that conduct influenza virologic surveillance according to global standards, and on a weekly basis upload their surveillance data to the open-access World Health Organization (WHO) platform FluNet. These data include the number of specimens tested for influenza and the number of specimens positive for influenza by type, subtype and lineage, all by the epidemiologic week of specimen collection. We invited these laboratories to provide additional epidemiologic data about the hospitalized influenza B cases. We conducted descriptive analyses of patterns of influenza circulation and characteristics of hospitalized cases. We compared the predominant B lineage each season to the lineage in the vaccine applied, to determine vaccine mismatch. A Chi-square and Wilcoxan statistic were used to assess the statistical significance of differences in proportions and medians at the P<0.05 level.FindingsDuring 2010-2017, the annual number of influenza B cases in LAC was ~4500 to 7000 cases. Since 2011, among the LAC-laboratories reporting influenza B lineage using molecular methods, both B/Victoria and B/Yamagata were detected annually. Among the hospitalized influenza B cases, there were statistically significant differences observed between B/Victoria and B/Yamagata cases when comparing age and the proportion with underlying co-morbid conditions and with history of oseltamivir treatment (P<0.001). The proportion deceased among B/Victoria and B/Yamagata hospitalized cases did not differ significantly. When comparing the predominant influenza B lineage detected, as part of surveillance activities during 63 seasons among 19 countries, to the lineage of the influenza B virus included in the trivalent influenza vaccine used during that season, there was a vaccine mismatch noted during 32% of the seasons analyzed.ConclusionsInfluenza B is important in LAC with both B/Victoria and B/Yamagata circulating annually in all sub regions. During approximately one-third of the seasons, an influenza B vaccine mismatch was identified. Further analyses are needed to better characterize the medical and economic burden of each influenza B lineage, to examine the potential cross-protection of one vaccine lineage against the other circulating virus lineage, and to determine the potential impact and cost-effectiveness of using the quadrivalent vaccine rather than the trivalent influenza vaccine.

Project description:Ecoepidemiological scenarios for Chagas disease transmission are complex, so vector control measures to decrease human-vector contact and prevent infection transmission are difficult to implement in all geographic contexts. This study assessed the geographic abundance patterns of two vector species of Chagas disease: Triatoma maculata (Erichson, 1848) and Rhodnius pallescens (Barber, 1932) in Latin America. We modeled their potential distribution using the maximum entropy algorithm implemented in Maxent and calculated distances to their niche centroid by fitting a minimum-volume ellipsoid. In addition, to determine which method would accurately explain geographic abundance patterns, we compared the correlation between population abundance and the distance to the ecological niche centroid (DNC) and between population abundance and Maxent environmental suitability. The potential distribution estimated for T. maculata showed that environmental suitability covers a large area, from Panama to Northern Brazil. R. pallescens showed a more restricted potential distribution, with environmental suitability covering mostly the coastal zone of Costa Rica and some areas in Nicaragua, Honduras, Belize and the Yucatán Peninsula in Mexico, northern Colombia, Acre, and Rondônia states in Brazil, as well as a small region of the western Brazilian Amazon. We found a negative slope in the relationship between population abundance and the DNC in both species. R. pallecens has a more extensive potential latitudinal range than previously reported, and the distribution model for T. maculata corroborates previous studies. In addition, population abundance increases according to the niche centroid proximity, indicating that population abundance is limited by the set of scenopoetic variables at coarser scales (non-interactive variables) used to determine the ecological niche. These findings might be used by public health agencies in Latin America to implement actions and support programs for disease prevention and vector control, identifying areas in which to expand entomological surveillance and maintain chemical control, in order to decrease human-vector contact.

Project description:BackgroundAs of September 2022, nearly 1.3 billion doses of COVID-19 vaccine products have been administered in Latin America and the Caribbean, where 27% of global COVID-19 deaths have occurred. This study aimed to estimate the effectiveness of COVID-19 vaccines against lab-confirmed COVID-19 related hospitalizations and deaths among adults in Argentina, Brazil, Chile, and Colombia.MethodsUsing a test-negative case control design, we evaluated the effectiveness of a primary vaccination series considering six COVID-19 vaccine products (Sputnik V, mRNA-1273, CoronaVac, ChAdOx1, BNT162b2, Ad26.COV2.S) against lab-confirmed COVID-19 hospitalizations and deaths among 83,708 hospitalized adults from February-December, 2021. Data from hospitalization records, COVID surveillance, and vaccination registries were used. Vaccine effectiveness was estimated using logistic regression ((1-OR) x 100).FindingsThe average age of participants was 56.7 (SD = 17.5), and 45,894 (54.8%) were male. Adjusted VE (aVE) estimates for full vaccination against hospitalization were 82% for mRNA-1273 (95% confidence interval (CI) = -30 to 98%), 76% (71%-81%) for BNT162b2, 65% (61-68%) for ChAdOx1, 57% (10-79%) for Sputnik V, 53% (50-56%) for CoronaVac, and 46% (23-62%) for Ad26.COV2.S. Estimates, particularly for CoronaVac, varied by variant. Decreasing aVE was estimated as age increased, particularly for CoronaVac and ChAdOx1. aVE estimates against death were generally higher, with 100% (CI not estimated) for mRNA-1273, 82% (69-90%) for BNT162b2, 73% (69-77%) for ChAdOx1, 65% (60-67%) for CoronaVac, 38% (-75 to 78%) for Sputnik V, 6% (-58 to 44%) for Ad26.COV2.S.InterpretationPrimary series vaccination with available COVID-19 vaccine products was effective against COVID-19 hospitalization and mortality. Effectiveness varied by product and declined with increasing age.FundingThis study was funded by the Pan-American Health Organization (PAHO, World Health Organization (WHO)). PAHO convened and led the study implementation.

Dataset Information

Chagas Disease Drug Discovery in Latin America-A Mini Review of Antiparasitic Agents Explored Between 2010 and 2021.

Publications

Chagas Disease Drug Discovery in Latin America-A Mini Review of Antiparasitic Agents Explored Between 2010 and 2021.

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