Corrección a: Nifurtimox versus benznidazol o placebo para la infección asintomática por Trypanosoma cruzi (Equivalencia de intervenciones habituales para tripanosomiasis - EQUITY): protocolo de estudio para un ensayo controlado aleatorio (vol 20, 431, 2019)

Background: Either benznidazole (BZN) or nifurtimox (NFX) is recommended as equivalent to treat Trypanosoma cruzi infection. Nonetheless, supportive data from randomised trials is limited to individuals treated with BZN in southern cone countries of Latin America. Methods: The goal of this randomised, concealed, blind, parallel-group trial is to inform the trypanocidal efficacy and safety of NFX and its equivalence to BZN among individuals with T. cruzi positive serology (TC+). Eligible individuals are TC+, 20–65 years old, with no apparent symptoms/signs or uncontrolled risk factors for cardiomyopathy and at negligible risk of re-infection. Consenting individuals (adherent to a 10-day placebo run-in phase) receive a 120-day BID blinded treatment with NFX, BZN or matching placebo (2:2:1 ratio). The four active medication arms include (1) a randomly allocated sequence of 60-day, conventional-dose (60CD) regimes (BZN 300 mg/day or NFX 480 mg/day, ratio 1:1), followed or preceded by a 60-day placebo treatment, or (2) 120-day half-dose (120HD) regimes (BZN 150 mg/day or NFX 240 mg/day, ratio 1:1). The primary efficacy outcome is the proportion of participants testing positive at least once for up to three polymerase chain reaction (PCR) assays (1 + PCR) 12–18 months after randomisation. A composite safety outcome includes moderate to severe adverse reactions, consistent blood marker abnormalities or treatment abandons. The trial outside Colombia (expected to recruit at least 60% of participants) is pragmatic; it may be open-label and not include all treatment groups, but it must adhere to the randomisation and data administration system and guarantee a blinded efficacy outcome evaluation. Our main comparisons include NFX groups with placebo (for superiority), NFX versus BZN groups and 60CD versus 120HD groups (for non-inferiority) and testing for the agent-dose and group-region interactions. Assuming a 1 + PCR ? 75% in the placebo group, up to 25% among BZN-treated and an absolute difference of up to ? 25% with NFX to claim its trypanocidal effect, 60–80 participants per group (at least 300 from Colombia) are needed to test our hypotheses (80–90% power; one-sided alpha level 1%)

Marburg virus disease outbreaks, mathematical models, and disease parameters: a systematic review

The 2023 Marburg virus disease outbreaks in Equatorial Guinea and Tanzania highlighted the importance of better understanding this lethal pathogen. We did a systematic review (PROSPERO CRD42023393345) of peer-reviewed articles reporting historical outbreaks, modelling studies, and epidemiological parameters focused on Marburg virus disease. We searched PubMed and Web of Science from database inception to March 31, 2023. Two reviewers evaluated all titles and abstracts with consensus-based decision making. To ensure agreement, 13 (31%) of 42 studies were double-extracted and a custom-designed quality assessment questionnaire was used for risk of bias assessment. We present detailed information on 478 reported cases and 385 deaths from Marburg virus disease. Analysis of historical outbreaks and seroprevalence estimates suggests the possibility of undetected Marburg virus disease outbreaks, asymptomatic transmission, or cross-reactivity with other pathogens, or a combination of these. Only one study presented a mathematical model of Marburg virus transmission. We estimate an unadjusted, pooled total random effect case fatality ratio of 61·9% (95% CI 38·8–80·6; I2=93%). We identify epidemiological parameters relating to transmission and natural history, for which there are few estimates. This systematic review and the accompanying database provide a comprehensive overview of Marburg virus disease epidemiology and identify key knowledge gaps, contributing crucial information for mathematical models to support future Marburg virus disease epidemic responses

Modelling the epidemiology and healthcare burden of chagas disease in colombia

Chagas disease remains as a major cause of heart disease burden in Latin American countries. Although in the last three decades most endemic countries have implemented various control strategies, the impact of such interventions has not been rigorously quantified, and questions remain as how to address old and new challenges as countries progress towards the 2020 goals proposed by the World Health Organization (WHO). These goals are aimed to achieve interruption of domiciliary transmission in all endemic countries and to have all infected/ill patients under care. However, estimates on the current status of domiciliary transmission and on the burden of disease in those countries remains poorly understood and even ambiguous. Since the majority of Trypanosoma cruzi infections remain in asymptomatic state for decades before showing the heart/digestive complications, most infected people continue unaware of their condition. Therefore, access to early diagnosis and treatment are yet very precarious and the surveillance health systems are not really capturing the changing epidemiology of the disease. Given the nature of the multi-pronged interventions required to Chagas disease control, obtaining disease estimates is crucial to understand how the health system is responding to such demand and how to better plan interventions. Taking Colombia as a case study, in this PhD thesis I am presenting a methodological and analytical approach to understand five key issues relevant for planning interventions for Chagas disease in endemic countries: historical exposure to Force-of-Infection, disease progression, disease burden, costs and access to early diagnosis and treatment. The methods, results and limitations of this approach and its components are presented and discussed.Open Acces

Corrección a: Nifurtimox versus benznidazol o placebo para la infección asintomática por Trypanosoma cruzi (Equivalencia de intervenciones habituales para tripanosomiasis - EQUITY): protocolo de estudio para un ensayo controlado aleatorio (vol 20, 431, 2019)

Background: Either benznidazole (BZN) or nifurtimox (NFX) is recommended as equivalent to treat Trypanosoma cruzi infection. Nonetheless, supportive data from randomised trials is limited to individuals treated with BZN in southern cone countries of Latin America. Methods: The goal of this randomised, concealed, blind, parallel-group trial is to inform the trypanocidal efficacy and safety of NFX and its equivalence to BZN among individuals with T. cruzi positive serology (TC+). Eligible individuals are TC+, 20–65 years old, with no apparent symptoms/signs or uncontrolled risk factors for cardiomyopathy and at negligible risk of re-infection. Consenting individuals (adherent to a 10-day placebo run-in phase) receive a 120-day BID blinded treatment with NFX, BZN or matching placebo (2:2:1 ratio). The four active medication arms include (1) a randomly allocated sequence of 60-day, conventional-dose (60CD) regimes (BZN 300 mg/day or NFX 480 mg/day, ratio 1:1), followed or preceded by a 60-day placebo treatment, or (2) 120-day half-dose (120HD) regimes (BZN 150 mg/day or NFX 240 mg/day, ratio 1:1). The primary efficacy outcome is the proportion of participants testing positive at least once for up to three polymerase chain reaction (PCR) assays (1 + PCR) 12–18 months after randomisation. A composite safety outcome includes moderate to severe adverse reactions, consistent blood marker abnormalities or treatment abandons. The trial outside Colombia (expected to recruit at least 60% of participants) is pragmatic; it may be open-label and not include all treatment groups, but it must adhere to the randomisation and data administration system and guarantee a blinded efficacy outcome evaluation. Our main comparisons include NFX groups with placebo (for superiority), NFX versus BZN groups and 60CD versus 120HD groups (for non-inferiority) and testing for the agent-dose and group-region interactions. Assuming a 1 + PCR ? 75% in the placebo group, up to 25% among BZN-treated and an absolute difference of up to ? 25% with NFX to claim its trypanocidal effect, 60–80 participants per group (at least 300 from Colombia) are needed to test our hypotheses (80–90% power; one-sided alpha level 1%)