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Background Chagas disease (CD) has significant global health impact, but safe, effective treatments remain elusive. The nitroimidazole fexinidazole is a potential treatment. Methods This double-blind, randomized, placebo-controlled, dose-finding, proof-of-concept study was conducted in Bolivia. Adults with serologically confirmed chronic indeterminate CD and positive PCR were randomly assigned to 1 of 6 fexinidazole regimens (1200 or 1800 mg/day for 2, 4, or 8 weeks) or placebo. Target recruitment was 20 patients/arm. The primary endpoint was sustained parasitological clearance by serial negative qPCR from end of treatment (EOT) until 6 months follow-up in the intention-to-treat (ITT) population. Follow-up was extended to 12 months. Results Enrollment was interrupted after 4/47 patients presented with transient asymptomatic grade 3 and 4 neutropenia. Treatment of ongoing patients was stopped in all patients administered >2 weeks. A total of 40 patients received treatment with fexinidazole from 3 days to 8 weeks. Delayed-onset neutropenia (n = 8) and increased liver enzymes (n = 8) were found in fexinidazole patients vs none in the placebo arm. In the ITT analysis, sustained parasitological clearance from EOT to 12 months follow-up varied between 66.7% (1200 mg–2 week) and 100.0% (1800 mg–2 week). Rapid, sustained clearance of parasitemia was observed in all treated patients with available data, but not in any patients in the placebo group, at 12 months (P =.0056). Further exploratory exposure-response analysis suggested low dosages of fexinidazole may be safe and effective. Conclusions Further evaluation is needed to establish fexinidazole's minimum effective dosage and risk–benefit relationship. Results suggest potential for effective treatment regimens <10 days. Clinical Trials Registration NCT02498782. [ABSTRACT FROM AUTHOR]

Background: Most people with chronic Chagas disease do not receive specific care and therefore are undiagnosed and do not receive accurate treatment. This manuscript discusses and evaluates a collaborative strategy to improve access to healthcare for patients with Chagas in Bolivia, a country with the highest prevalence of Chagas in the world. Methods: With the aim of reinforcing the Chagas National Programme, the Bolivian Chagas Platform was born in 2009. The first stage of the project was to implement a vertical pilot program in order to introduce and consolidate a consensual protocol-based healthcare, working in seven centers (Chagas Platform Centers). From 2015 on the model was extended to 52 primary healthcare centers, through decentralized, horizontal scaling-up. To evaluate the strategy, we have used the WHO ExpandNet program. Results: The strategy has significantly increased the number of patients cared for, with 181,397 people at risk of having T. cruzi infection tested and 57,871 (31·9%) new diagnostics performed. In those with treatment criteria, 79·2% completed the treatment. The program has also trained a significant number of health personnel through the specific Chagas guidelines (67% of healthcare workers in the intervention area). Conclusions: After being recognized by the Chagas National Programme as a healthcare model aligned with national laws and priorities, the Bolivian platform of Chagas as an innovation, includes attributes that they have made it possible to expand the strategy at the national level and could also be adapted in other countries. Author summary: The Bolivian Chagas Platform was born in 2009 to promote comprehensive care for Chagas disease (CD), a neglected tropical disease that affects more than a million people in Bolivia. A two-phase strategy was designed to introduce protocol-based healthcare in Bolivia through prevention, case-management, healthcare professionals training, and community activities. From an initial seven centers in the vertical phase (Chagas Platform centers), 52 healthcare primary healthcare centers adopted CD protocolized care in a second phase (Chagas Healthcare Network) through decentralized, horizontal scaling-up. 181,397 people at risk of having T. cruzi infection were tested (15%), 57,871 (31.9%) tested positive, and 18,582 (32.1%) were treated. Sixty-seven percent of healthcare workers were trained. Adequate domestic financial and human resources were ensured at the end of the scaling-up. Translational research and training activities improved evidence-based decision-making in clinical management. The Bolivian Chagas Platform as innovation, included attributes that enabled scaling-up at national and international level. [ABSTRACT FROM AUTHOR]

Background Chagas disease is endemic throughout most of Bolivia, with prevalence rates of 25% observed in some geographic areas located mainly in the sub-Andean region. Methods Community-based entomological surveillance was carried out in the sub-Andean departments of Cochabamba (municipalities of Cochabamba, Punata and Sacaba), Tarija (municipality of Tarija) and Chuquisaca (municipality of Sucre). The surveillance parameters evaluated were: (i) the proportion of cards with the presence of triatomines; (ii) the distribution of positive cards by area; and (iii) the proportion of cards with the presence of infected triatomines. Results Of the cards returned, in 852 (3.1%) there was a mention of the presence of triatomines. The species Triatoma infestans, Triatoma sordida and Triatoma guasayana were identified in 812 (95.3%), 39 (4.6%) and 1 (0.1%), respectively. The median monthly positivity rate of the cards during 2011-2018 was higher in Punata (9.1%; IQR=3.2–15.4%). The median monthly rate was highest in 2012 (2.7%; IQR=0–5.6%). Fifty positive cards (5.8%) presented insects that were positive for trypanosomatids, mainly in Cochabamba and Punata. Conclusions The report of triatomines foci by inhabitants represents an effective surveillance system coordinated by a network of specialized and multidisciplinary health centers. These strategies, which should be included in the health policies of endemic countries, enable extending and deepening the dialogue among technicians, communities and their local authorities. [ABSTRACT FROM AUTHOR]

Objective: Design and build a strategy construction and evaluation software system to help stakeholders to develop viable strategies to expand (and adapt) the Chagas Platform healthcare model through the primary healthcare system in Bolivia. Methods: The software was built based on a ranking of medical Interventions and Actions (needed to support Interventions' implementation) needed for comprehensive management of Chagas Disease in Bolivia. The ranking was performed using a Multi Criteria Decision Analysis (MCDA) methodology adapted to the WHO's building blocks framework. Data regarding the criteria and the rankings was obtained through surveys and interviews with health care professionals working on Chagas disease. The Analytical Hierarchy Process was used to construct the decision criteria weights. Data Envelopment Analysis was used to identify the Interventions that lay on the efficiency frontier of outcomes and the complexity of associated Actions. These techniques were combined with integer programing tools using the open-source software R to build a decision-making tool to assess the outcomes and complexity of any combination of Interventions and Actions. This model and tool were applied to data concerning the care of Chagas disease in Bolivia collected through surveys of experts. The tool works by loading the data from each specific context. Results: The initial set of Interventions and Actions recommended after analysis of the survey data was further refined through face-to-face interviews with field experts in Bolivia, resulting in a strategy of 18 Interventions and 15 Actions. Within the WHO model the Leadership and Governance building block came up as the one needing more support with Actions such as the inclusion of Chagas into Annual Municipal Operational Plans by appointing local and provincial coordinators. Conclusion: This project established the suitability of the model for constructing healthcare strategies. The model could be developed further resulting in a decision-making tool for program managers in a wide range of healthcare related issues, including neglected and/ or prevalent diseases. The tool has the potential to be used at different stages of decision making by diverse stakeholders in order to coordinate activities needed to address a health problem. Author summary: This manuscript presents a strategy construction tool to generate viable strategies to expand the Chagas platforms for healthcare pilot through the primary healthcare system in Bolivia. Relevance of this work resides in the need for performing a rational planification to address Neglected Diseases in low- and middle-income countries, by prioritizing Interventions and Actions. After gathering and loading the data from each specific context and problem, policy makers can use the tool for construction or evaluation of strategies using the WHO Building Block model. The main comparative advantage is that the model does not only include the identification and evaluation of Interventions for the comprehensive care of Chagas, but also includes the necessary activities in the health system to support the large-scale implementation of them. The tool has the potential to be used at different stages of decision making to coordinate activities to address a health problem. The tool could be adapted for its use in other neglected and/ or prevalent diseases or in other locations. [ABSTRACT FROM AUTHOR]