BackgroundBolivia has the highest prevalence of Chagas disease (CD) in the world (6.1%), with more than 607,186 people with Trypanosoma cruzi infection, most of them adults. In Bolivia CD has been declared a national priority. In 2009, the Chagas National Program (ChNP) had neither a protocol nor a clear directive for diagnosis and treatment of adults. Although programs had been implemented for congenital transmission and for acute cases, adults remained uncovered. Moreover, health professionals were not aware of treatment recommendations aimed at this population, and research on CD was limited; it was difficult to increase awareness of the disease, understand the challenges it presented, and adapt strategies to cope with it. Simultaneously, migratory flows that led Bolivian patients with CD to Spain and other European countries forced medical staff to look for solutions to an emerging problem.InterventionIn this context, thanks to a Spanish international cooperation collaboration, the Bolivian platform for the comprehensive care of adults with CD was created in 2009. Based on the establishment of a vertical care system under the umbrella of ChNP general guidelines, six centres specialized in CD management were established in different epidemiological contexts. A common database, standardized clinical forms, a and a protocolized attention to adults patients, together with training activities for health professionals were essential for the model success. With the collaboration and knowledge transfer activities between endemic and non-endemic countries, the platform aims to provide care, train health professionals, and create the basis for a future expansion to the National Health System of a proven model of care for adults with CD.ResultsFrom 2010 to 2015, a total of 26,227 patients were attended by the Platform, 69% (18,316) were diagnosed with T. cruzi, 8,567 initiated anti-parasitic treatment, more than 1,616 health professionals were trained, and more than ten research projects developed. The project helped to increase the number of adults with CD diagnosed and treated, produce evidence-based clinical practice guidelines, and bring about changes in policy that will increase access to comprehensive care among adults with CD. The ChNP is now studying the Platform’s health care model to adapt and implement it nationwide.ConclusionsThis strategy provides a solution to unmet demands in the care of patients with CD, improving access to diagnosis and treatment. Further scaling up of diagnosis and treatment will be based on the expansion of the model of care to the NHS structures. Its sustainability will be ensured as it will build on existing local resources in Bolivia. Still human trained resources are scarce and the high staff turnover in Bolivia is a limitation of the model. Nevertheless, in a preliminary two-years-experience of scaling up this model, this limitations have been locally solved together with the health local authorities.

Chagas disease (CD) and tuberculosis (TB) are important health problems in Bolivia. Current treatments for both infections require a long period of time, and adverse drug reactions (ADRs) are frequent. This study aims to strengthen the Bolivian pharmacovigilance system, focusing on CD and TB. A situation analysis of pharmacovigilance in the Department of Cochabamba was performed. The use of a new local case report form (CRF) was implemented, together with the CRF established by the Unidad de Medicamentos y Tecnología en Salud (UNIMED), in several healthcare centers. Training and follow-up on drug safety monitoring and ADR reporting was provided to all health professionals involved in CD and TB treatment. A comparative analysis of the reported ADRs using the CRF provided by UNI-MED, the new CRF proposal, and medical records, was also performed. Our results showed that out of all patients starting treatment for CD, 37.9% suffered ADRs according to the medical records, and 25.3% of them were classified as moderate/severe (MS). Only 47.4% of MS ADRs were reported to UNIMED. Regarding TB treatment, 9.9% of all patients suffered ADRs, 44% of them were classified as MS, and 75% of MS ADRs were reported to UNI-MED. These findings show that the reinforcement of the Bolivian pharmacovigilance system is an ambitious project that should involve a long-term perspective and the engagement of national health workers and other stakeholders at all levels. Continuity and perseverance are essential to achieve a solid ADR reporting system, improving patient safety, drug efficacy and adherence to treatment.

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.

BackgroundTuberculosis (TB) is the most common opportunistic infection and the leading cause of death in HIV-positive people worldwide. Diagnosing TB is difficult, and is more challenging in resource-scarce settings where culture-based diagnostic methods rely on poorly sensitive smear microscopy by Ziehl-Neelsen stain (ZN).MethodsWe performed a cross-sectional study examining the diagnostic utility of Microscopic Observation Drug Susceptibility liquid culture (MODS) versus traditional Ziehl-Neelsen staining (ZN) and Lowenstein Jensen culture (LJ) of pulmonary tuberculosis (TB) and multidrug-resistant tuberculosis (MDRTB) in HIV-infected patients in Bolivia. For sputum scarce individuals we assessed the value of the string test and induced sputum for TB diagnosis. The presence of Mycobacterium tuberculosis (Mtb) in the sputum of 107 HIV-positive patients was evaluated by ZN, LJ, and MODS. Gastric secretion samples obtained by the string test were evaluated by MODS in 102 patients.ResultsThe TB-HIV co-infection rate of HIV patients with respiratory symptoms by sputum sample was 45 % (48/107); 46/48 (96 %) were positive by MODS, 38/48 (79 %) by LJ, and 30/48 (63 %) by ZN. The rate of MDRTB was 9 % (4/48). Median time to positive culture was 10 days by MODS versus 34 days by LJ (p < 0.0001). In smear-negative patients, MODS detected TB in 17/18 patients, compared to 11/18 by LJ (94.4 % vs 61.0 %, p = 0.03 %). In patients unable to produce a sputum sample without induction, the string test cultured by MODS yielded Mtb in of 9/11 (82 %) TB positive patients compared to 11/11 (100 %) with induced sputum. Of the 10 patients unable to produce a sputum sample, 4 were TB-positive by string test.ConclusionMODS was faster and had a higher Mtb detection yield compared to LJ, with a greater difference in yield between the two in smear-negative patients. The string test is a valuable diagnostic technique for HIV sputum-scarce or sputum-absent patients, and should be considered as an alternative test to induced sputum to obtain sample for Mtb in resource-limited settings. Nine percent of our TB+ patients had MDRTB, which reinforces the need for rapid detection with direct drug susceptibility testing in HIV patients in Bolivia.

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.

2 Introduction: Chagas disease (CD) and Tuberculosis (TB) are important health problems in 3 Bolivia. Current treatments for both infections require a long period of time, and unwanted 4 drug-related adverse events (ADRs) are frequent. 5 Purpose: This study aims to strengthen the Bolivian Pharmacovigilance system, focusing on CD 6 and TB. 7 Methods: A situational diagnosis of Pharmacovigilance in the Department of Cochabamba was 8 performed. The use of a new Local Case Report Form (CRF) was implemented, together with 9 the CRF established by the Unidad de Medicamentos y Tecnología en Salud (UNIMED), in 10 several health care centers. Training and follow-up on drug safety monitoring and ADR 11 reporting was provided to all health professionals involved in CD and TB treatment. A 12 comparative analysis of the reported ADRs using the CRF provided by UNIMED, the new CRF 13 proposal, and medical records, was performed. 14 Results: Out of the total patients starting treatment for CD, 35,35% suffered ADR according to 15 the information collected in the medical records, and 25% of them were classified as 16 moderate/severe (MS) types. Only 51,43% of MS ADRs were reported to UNIMED. Regarding 17 TB treatment, 9,89% of the total patients suffered ADR, 44% of them were classified as MS, 18 and 75% of MS ADRs were reported to UNIMED. 19 Conclusions: The reinforcement of the Bolivian Pharmacovigilance system is an ambitious 20 project that should take a long-term perspective and the engagement of national health 21 workers and other stake holders at all levels. Continuity and perseverance are essential to 2 22 achieve a solid ADR reporting system, improving patient safety, drug efficacy and adherence to 23 treatment. 24

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.