Results and evaluation of the expansion of a model of comprehensive care for Chagas disease within the National Health System: The Bolivian Chagas network.

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.

Serological reactivity against T. cruzi-derived antigens: Evaluation of their suitability for the assessment of response to treatment in chronic Chagas disease.

Chagas disease, caused by the protozoan Trypanosoma cruzi, affects more than 6 million people worldwide. Following a mostly asymptomatic acute phase, the disease progresses to a long-lasting chronic phase throughout which life-threatening disorders to the heart and/or gastrointestinal tract will manifest in about 30% of those chronically infected. During the chronic phase, the parasitemia is low and intermittent, while a high level of anti-T. cruzi antibodies persist for years. These two features hamper post-chemotherapeutic follow-up of patients with the tools available. The lack of biomarkers for timely assessment of therapeutic response discourages a greater use of the two available anti-parasitic drugs, and complicates the evaluation of new drugs in clinical trials. Herein, we investigated in a blinded case-control study the serological reactivity over time of a group of parasite-derived antigens to potentially address follow up of T. cruzi chronically infected subjects after treatment. We tested PFR2, KMP11, HSP70, 3973, F29 and the InfYnity multiplexed antigenic array, by means of serological assays on a multi-national retrospective collection of samples. Some of the antigens exhibited promising results, underscoring the need for further studies to determine their potential role as treatment response biomarkers.

Multi-criteria decision analysis approach for strategy scale-up with application to Chagas disease management in Bolivia.

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.

Cost-effectiveness of different strategies for screening and treatment of Strongyloides stercoralis in migrants from endemic countries to the European Union.

BACKGROUND: The best strategy for controlling morbidity due to imported strongyloidiasis in migrants is unclear. We evaluate the cost-effectiveness of six possible interventions. METHODS: We developed a stochastic Markov chain model. The target population was adult migrants from endemic countries to the European Union; the time horizon, a lifetime and the perspective, that of the health system. Average and incremental cost-effectiveness ratios (ACER and ICER) were calculated as 2016 EUR/life-year gained (LYG). Health interventions compared were: base case (no programme), primary care-based presumptive treatment (PCPresTr), primary care-based serological screening and treatment (PCSerTr), hospital-based presumptive treatment (HospPresTr), hospital-based serological screening and treatment (HospSerTr), hospital-based presumptive treatment of immunosuppressed (HospPresTrim) and hospital-based serological screening and treatment of the immunosuppressed (HospSerTrim). The willingness to pay threshold (WTP) was €32 126.95/LYG. RESULTS: The base case model yielded a loss of 2 486 708.24 life-years and cost EUR 3 238 393. Other interventions showed the following: PCPresTr: 2 488 095.47 life-years (Δ1 387.23LYG), cost: EUR 8 194 563; ACER: EUR 3573/LYG; PCSerTr: 2 488 085.8 life-years (Δ1377.57LYG), cost: EUR 207 679 077, ACER: EUR 148 407/LYG; HospPresTr: 2 488 046.17 life-years (Δ1337.92LYG), cost: EUR 14 559 575; ACER: EUR 8462/LYG; HospSerTr: 2 488 024.33 life-years (Δ1316.08LYG); cost: EUR 207 734 073; ACER: EUR 155 382/LYG; HospPresTrim: 2 488 093.93 life-years, cost: EUR 1 105 483; ACER: EUR -1539/LYG (cost savings); HospSerTrim: 2 488 073.8 life-years (Δ1365.55LYG), cost: EUR 4 274 239; ACER: EUR 759/LYG. One-way and probabilistic sensitivity analyses were undertaken; HospPresTrim remained below WTP for all parameters' ranges and iterations. CONCLUSION: Presumptively treating all immunosuppressed migrants from areas with endemic Strongyloides would generate cost savings to the health system.

Purification of Glycosylphosphatidylinositol-Anchored Mucins from Trypanosoma cruzi Trypomastigotes and Synthesis of α-Gal-Containing Neoglycoproteins: Application as Biomarkers for Reliable Diagnosis and Early Assessment of Chemotherapeutic Outcomes of Chagas Disease.

Chagas disease (ChD), caused by the protozoan parasite Trypanosoma cruzi, affects millions of people worldwide. Chemotherapy is restricted to two drugs, which are partially effective and may cause severe side effects, leading to cessation of treatment in a significant number of patients. Currently, there are no biomarkers to assess therapeutic efficacy of these drugs in the chronic stage. Moreover, no preventive or therapeutic vaccines are available. In this chapter, we describe the purification of Trypanosoma cruzi trypomastigote-derived glycosylphosphatidylinositol (GPI)-anchored mucins (tGPI-mucins) for their use as antigens for the reliable primary or confirmatory diagnosis and as prognostic biomarkers for early assessment of cure following ChD chemotherapy. We also describe, as an example, the synthesis of a potential tGPI-mucin-derived α-Gal-terminating glycan and its coupling to a carrier protein for use as diagnostic and prognostic biomarker in ChD.

Cost-effectiveness of Chagas disease screening in Latin American migrants at primary health-care centres in Europe: a Markov model analysis.

BACKGROUND: Chagas disease is currently prevalent in European countries hosting large communities from Latin America. Whether asymptomatic individuals at risk of Chagas disease living in Europe should be screened and treated accordingly is unclear. We performed an economic evaluation of systematic Chagas disease screening of the Latin American population attending primary care centres in Europe. METHODS: We constructed a decision tree model that compared the test option (screening of asymptomatic individuals, treatment, and follow-up of positive cases) with the no-test option (screening, treating, and follow-up of symptomatic individuals). The decision tree included a Markov model with five states, related to the chronic stage of the disease: indeterminate, cardiomyopathy, gastrointestinal, response to treatment, and death. The model started with a target population of 100 000 individuals, of which 4·2% (95% CI 2·2-6·8) were estimated to be infected by Trypanosoma cruzi. The primary outcome was the incremental cost-effectiveness ratio (ICER) between test and no-test options. Deterministic and probabilistic analyses (Monte Carlo simulations) were performed. FINDINGS: In the deterministic analysis, total costs referred to 100 000 individuals in the test and no-test option were €30 903 406 and €6 597 403 respectively, with a difference of €24 306 003. The respective number of quality-adjusted life-years (QALYs) gained in the test and no-test option were 61 820·82 and 57 354·42. The ICER was €5442. In the probabilistic analysis, total costs for the test and no-test option were €32 163 649 (95% CI 31 263 705-33 063 593) and €6 904 764 (6 703 258-7 106 270), respectively. The respective number of QALYs gained was 64 634·35 (95% CI 62 809·6-66 459·1) and 59 875·73 (58 191·18-61 560·28). The difference in QALYs gained between the test and no test options was 4758·62 (95% CI 4618·42-4898·82). The incremental cost-effectiveness ratio (ICER) was €6840·75 (95% CI 2545-2759) per QALY gained for a treatment efficacy of 20% and €4243 per QALY gained for treatment efficacy of 50%. Even with a reduction in Chagas disease prevalence to 0·05% and with large variations in all the parameters, the test option would still be more cost-effective than the no-test option (less than €30000 per QALY). INTERPRETATION: Screening for Chagas disease in asymptomatic Latin American adults living in Europe is a cost-effective strategy. Findings of our model provide an important element to support the implementation of T cruzi screening programmes at primary health centres in European countries hosting Latin American migrants. FUNDING: European Commission 7th Framework Program.

Economic evaluation of Chagas disease screening of pregnant Latin American women and of their infants in a non endemic area.

Migration is a channel through which Chagas disease is imported, and vertical transmission is a channel through which the disease is spread in non-endemic countries. This study presents the economic evaluation of Chagas disease screening in pregnant women from Latin America and in their newborns in a non endemic area such as Spain. The economic impact of Chagas disease screening is tested through two decision models, one for the newborn and one for the mother, against the alternative hypothesis of no screening for either the newborn or the mother. Results show that the option "no test" is dominated by the option "test". The cost effectiveness ratio in the "newborn model" was 22€/QALYs gained in the case of screening and 125€/QALYs gained in the case of no screening. The cost effectiveness ratio in the "mother model" was 96€/QALYs gained in the case of screening and 1675€/QALYs gained in the case of no screening. Probabilistic sensitivity analysis highlighted the reduction of uncertainty in the screening option. Threshold analysis assessed that even with a drop in Chagas prevalence from 3.4% to 0.9%, a drop in the probability of vertical transmission from 7.3% to 2.24% and with an increase of screening costs up to €37.5, "test" option would still be preferred to "no test". The current study proved Chagas screening of all Latin American women giving birth in Spain and of their infants to be the best strategy compared to the non-screening option and provides useful information for health policy makers in their decision making process.

Vaccination strategies against hepatitis A in travelers older than 40 years: an economic evaluation.

BACKGROUND: In recent years, the number of travelers aged >40 years who acquire hepatitis A while traveling has increased. Therefore, there is a need to review hepatitis A vaccination protocols in travelers. The aims of the study were to assess immunity levels to hepatitis A virus (HAV) in international travelers >40 years and to determine the least costly immunization strategy. METHODS: A serological examination of HAV antibodies in 427 international travelers aged >40 years traveling endemic zones was carried out. The prevalence of antibodies in each age group was assessed. The costs of two preventive strategies, direct vaccination of all subjects (independent of the immune status) or screening and subsequent vaccination of susceptible subjects were compared. The critical value of prevalence (CVP) (the value at which the costs for the two strategies are equal) was calculated. RESULTS: Total prevalence of HAV antibodies was 78.9% [95% confidence interval (CI): 74.8-82.5] and was 80.0% (95% CI: 73.8-85.2) in men and 77.9% (95% CI: 71.9-83.2) in women. There was a positive association with age. In the 40 to 49, 50 to 59, 60 to 69, and 70 to 95 years age groups, the prevalence rates were 62.6 (95% CI: 53.8-71.5), 76.8 (95% CI: 70.0-82.7), 91.7 (95% CI: 85.2-95.6), and 97.5% (95% CI: 87.4-99.6), respectively. The CVP was 58.4% using two doses of vaccine. CONCLUSIONS: The CVP was lower than the prevalence rate found in our international travelers. Therefore, we recommend systematic screening for HAV antibodies before selective vaccination of international travelers aged >40 years traveling to hepatitis A endemic zones.