Materiały źródłowe

• #1 Increased mortality attributed to Chagas disease: a systematic review and meta-analysis | Parasites & Vectors | Full Text

  https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-016-1315-x

  The clinical outcomes associated with Chagas disease remain poorly understood. […] The results indicate a statistically significant excess of mortality due to Chagas disease that is shared among both symptomatic and asymptomatic populations. […] Although Chagas disease was first described more than a century ago, the course of the disease and its clinical outcomes are still not well understood. […] Based on early cohort studies, an estimated 20-30 % of infected individuals would eventually develop heart disease, with an associated increased mortality. […] A better understanding of the magnitude of morbidity and mortality associated with Chagas disease is imperative for appropriately measuring burden of disease and evaluating the cost effectiveness of strategies to prevent and control T. cruzi infection and its clinical sequelae.

• #2 Cardiac Abnormalities in a Predictive Mouse Model of Chagas Disease

  https://www.mdpi.com/2076-0817/12/11/1364

  Chagas disease (CD) is caused by the insect-transmitted protozoan parasite Trypanosoma cruzi and has a major impact on public health throughout Latin America, where six to seven million people are infected. […] Approximately 30% of infected individuals will develop chronic Chagas cardiomyopathy (CCC), although the condition can take many years or decades to become symptomatic. This can give rise to a wide spectrum of manifestations, ranging from minor myocardial involvement to left ventricular systolic dysfunction, dilated cardiomyopathy (myofiber hypertrophy and interstitial fibrosis), arrhythmias, thromboembolic events, and terminal cardiac failure, including sudden death. […] Electrocardiography (ECG) has played a key role in CD patient evaluation and management. It represents a low-cost diagnostic method and can be predictive of CCC outcomes.

• #3 Increased mortality attributed to Chagas disease: a systematic review and meta-analysis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4728795/

  The clinical outcomes associated with Chagas disease remain poorly understood. […] The results indicate a statistically significant excess of mortality due to Chagas disease that is shared among both symptomatic and asymptomatic populations. […] The overall excess mortality, estimated as a relative risk ratio, was equal to 1.74 (95 % CI 1.49-2.03), which was robust to both publication bias (RR=1.42, 95 % CI 1.19-1.70) and highest quality studies (RR=2.07, 95 % CI 1.54-2.78). […] Interestingly, this (statistically significant) magnitude of excess mortality appeared to affect equally patients with mild, moderate or severe symptoms (relative to their baseline, background mortality). […] Our study provides a strong evidence base to help inform the understanding of Chagas-associated mortality rates by researchers and practitioners in the field of Chagas disease.

• #4 Increased mortality attributed to Chagas disease: a systematic review and meta-analysis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4728795/

  The systematic review and meta-analysis conducted in this study identified a consistent body of evidence indicating that Chagas disease is associated with statistically significant excess mortality. The relative risk was 1.74 (95 % CI 1.49-2.03) and the attributable risk percent was 42.5 %. This excess mortality affected all Chagas disease patients regardless of their clinical presentation. Annual mortality rates increased with clinical severity.

• #5 Increased mortality attributed to Chagas disease: a systematic review and meta-analysis | Parasites & Vectors | Full Text

  https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-016-1315-x

  The overall excess mortality, estimated as a relative risk ratio, was equal to 1.74 (95 % CI 1.492.03), which was robust to both publication bias (RR=1.42, 95 % CI 1.191.70) and highest quality studies (RR=2.07, 95 % CI 1.542.78). […] Interestingly, this (statistically significant) magnitude of excess mortality appeared to affect equally patients with mild, moderate or severe symptoms (relative to their baseline, background mortality). […] Our study indicates that much of the heterogeneity in the mortality rates quoted and used in the literature stems from a lack of agreement on clearly-defined disease stages. […] The systematic review and meta-analysis conducted in this study identified a consistent body of evidence indicating that Chagas disease is associated with statistically significant excess mortality.

• #6 Chagas Disease (American Trypanosomiasis): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/214581-overview

  Chagas disease, also known as American trypanosomiasis, is caused by infection with the protozoan parasite Trypanosoma cruzi. […] T cruzi infection is life-long. A minority of persons with long-standing T cruzi infection develop the serious cardiac and gastrointestinal problems that characterize chronic symptomatic Chagas disease. […] The heart is the most commonly affected organ in persons with chronic Chagas disease. […] The pathogenesis of cardiac and gastrointestinal lesions of chronic Chagas disease was a focus of debate for decades. […] The lifetime risk for the development of such symptoms in chronically infected persons is only 10-30%. […] Most of the estimated 12,000 deaths attributable to Chagas disease are due to chronic heart disease or, less frequently, megadisease or meningoencephalitis.

• #7

  https://www.who.int/news-room/fact-sheets/detail/chagas-disease-(american-trypanosomiasis)

  Chagas disease is curable if antiparasitic treatment is initiated early, in the acute phase. In chronic infection, the treatment and follow up can potentially prevent or curb disease progression and prevent transmission, for instance, during pregnancy and birth. […] Without early diagnosis and treatment, up to a third of people with chronic infection develop cardiac alterations and 1 in 10 develop digestive, neurological or mixed alterations which may require specific treatment. […] During the chronic phase, the parasites are hidden mainly in the heart and digestive muscles. One to three decades after infection, up to a third of patients suffer from cardiac disorders and up to 1 in 10 suffer from digestive (typically enlargement of the oesophagus or colon), neurological or mixed alterations. In later years these patients may experience the damage to the nervous system and muscles of the heart and digestive system, leading to cardiac arrhythmias, progressive heart failure, and sudden death, among other clinical manifestations and complications.

• #8 Chagas Disease (American Trypanosomiasis): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/214581-overview

  In persons with chronic chagasic heart disease, mortality primarily is due to the rhythm disturbances and congestive heart failure that result from the chronic inflammatory cardiomyopathy driven by the persistent presence of parasites in heart tissue. […] Predictors of mortality in chronic Chagas disease: a systematic review of observational studies. […] Incidence and Predictors of Progression to Chagas Cardiomyopathy: Long-Term Follow-Up of Trypanosoma cruzi-Seropositive Individuals. […] Systematic Review and Meta-Analysis of Clinical Outcome After Implantable Cardioverter-Defibrillator Therapy in Patients With Chagas Heart Disease.

• #9 Evolution of anti-Trypanosoma cruzi antibody production in patients with chronic Chagas disease: Correlation between antibody titers and development of cardiac disease severity | PLOS Neglected Tropical Diseases

  https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0005796

  In fact, the cardiac form can lead to death due to disease progression. Seeking for biomarkers of cardiomyopathy progression has become important to understand the cardiac progression and to predict or even prevent the disease worsening and to improve the quality of life of affected individuals. […] We found an inverse correlation between anti-T. cruzi IgG1 titers and cardiac disease severity in patients with progressive disease. These data suggest that anti-T. cruzi IgG1 levels could be considered a suitable candidate tool for early identification of cardiac disease progression. […] Our data suggest a lack of correlation between IgA production and severity or progression of cardiac disease. […] Therefore, in this study, patients with higher titers of anti-T. cruzi IgG1, even many years before the decline in cardiac function, tend to have disease progression through a decrease in cardiac function as LVEF worsens.

• #10 Evolution of anti-Trypanosoma cruzi antibody production in patients with chronic Chagas disease: Correlation between antibody titers and development of cardiac disease severity | PLOS Neglected Tropical Diseases

  https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0005796

  Chagas disease is one of the most important endemic infections in Latin America affecting around 67 million people. About 30-50% of patients develop the cardiac form of the disease, which can lead to severe cardiac dysfunction and death. […] In this observational study, the production of anti-Trypanosoma cruzi antibodies through a retrospective longitudinal follow-up in chronic Chagas disease patients cohort and its correlation with disease progression and heart commitment was evaluated. […] Strong inverse correlation ( = -0.6375, p = 0.0005) between anti-T. cruzi IgG1 titers and left ventricular ejection fraction (LVEF) in chronic Chagas cardiomyopathy (CCC) patients were observed after disease progression. […] Taken together, these results indicate that the levels of anti-T. cruzi IgG1 could be considered to seek for promising biomarkers to predict the severity of chronic Chagas disease cardiomyopathy.

• #11 Cardiac Abnormalities in a Predictive Mouse Model of Chagas Disease

  https://www.mdpi.com/2076-0817/12/11/1364

  Overall, individuals with CD have a 40% prevalence of ECG abnormalities, and conditions such as right bundle branch block (RBBB) can be up to 15 times higher than in seronegative individuals. […] The mechanisms that drive these cardiac abnormalities in CD patients have been the subject of multiple studies focused on the central question of whether parasite persistence is required to cause those changes. […] Elucidating the underlying mechanisms responsible for myocardial dysfunction in CD has major implications for diagnosis, risk stratification, and clinical management. This highlights the need for improved predictive models to aid research on disease pathogenesis and therapies that might reverse or block the resulting pathology. […] The particular susceptibility of the heart to progressive chronic disease could result from its low regenerative capacity and the crucial role of neurological homeostasis.

• #12 Cardiac Abnormalities in a Predictive Mouse Model of Chagas Disease

  https://www.mdpi.com/2076-0817/12/11/1364

  In humans, ECG abnormalities are prevalent in T. cruzi-infected individuals, the most common being ventricular (RBBB and LAFB), often progressing to bifascicular blocks. […] Thus, the development of CCC is extremely heterogeneous in both timing and severity, presumably a consequence of diverse host and parasite genetics, complex behavioural and lifestyle issues, and environmental factors. […] The ability of these models to capture the spectrum of human disease pathology is critical for translation. As described here, the C3H/HeN:JR host:parasite combination displays many of the diverse features of T. cruzi-induced pathology observed in humans and therefore represents a valuable predictive model for experimental research on this debilitating disease.

• #13

  https://www.who.int/news-room/fact-sheets/detail/chagas-disease-(american-trypanosomiasis)

  Adults with infection, especially those with no symptoms, should be offered treatment because antiparasitic medicines can also prevent or curb disease progression. […] Additionally, life-lasting follow up and specific treatment for cardiac, digestive or neurological manifestations are usually required. […] The medical care cost of patients with chronic cardiac, digestive, neurologic or mixed forms of the disease has been calculated to be 80% higher than the cost of spraying residual insecticide to control vectors and prevent infection.

• #14 Linear and Machine Learning modelling for spatiotemporal disease predictions: Force-of-Infection of Chagas disease | PLOS Neglected Tropical Diseases

  https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0010594

  Chagas disease is a long-lasting disease with a prolonged asymptomatic period. Cumulative indices of infection such as prevalence do not shed light on the current epidemiological situation, as they integrate infection over long periods. Instead, metrics such as the Force-of-Infection (FoI) provide information about the rate at which susceptible people become infected and permit sharper inference about temporal changes in infection rates. FoI is estimated by fitting (catalytic) models to available age-stratified serological (ground-truth) data. Predictive FoI modelling frameworks are then used to understand spatial and temporal trends indicative of heterogeneity in transmission and changes effected by control interventions. Ideally, these frameworks should be able to propagate uncertainty and handle spatiotemporal issues.

• #15 Linear and Machine Learning modelling for spatiotemporal disease predictions: Force-of-Infection of Chagas disease | PLOS Neglected Tropical Diseases

  https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0010594

  The choice of FoI predictive models will depend on the objectives of the analysis. ML methods will help characterise the mean behaviour of the estimates, while LM will provide insight into the uncertainty surrounding such estimates. Our approach can be extended to the modelling of FoI patterns in other Chagas disease-endemic countries and to other infectious diseases for which serosurveys are regularly conducted for surveillance. […] Metrics such as the per susceptible rate of infection acquisition (Force-of-Infection) are crucial to understand the current epidemiological situation and the impact of control interventions for long-lasting diseases in which the infection event might have occurred many years previously, such as Chagas disease. […] All methods, when fitted on the median FoI alone (MedFoI approach), were unable to capture the uncertainty in the response variable (the FoI observations generated by fitting the catalytic model to the age-stratified serosurveys), leading to overconfident predictions (with high predictive R2 values but smaller % of overlap values). This highlights an important issue not fully addressed in the literature, as most publications using FoI data to infer spatiotemporal patterns of infectious disease incidence tend to use the central FoI estimates alone to fit predictive models (i.e. using what we labelled here as the MedFoI approach).

• #16 Linear and Machine Learning modelling for spatiotemporal disease predictions: Force-of-Infection of Chagas disease | PLOS Neglected Tropical Diseases

  https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0010594

  Indeed, quantifying and communicating uncertainty in FoI appropriately is critical when the results of predictive models are used to inform stakeholders and public health programme managers on the level of certitude associated with exposure risk or number of cases. Thus areas/populations for which exposure has been certainly high or low can be differentiated from those with exposure levels or number of cases that necessitate further investigation due to highly uncertain estimation. […] While the final ML models showed no evidence of residual spatial correlation, the spatial extrapolation shown should be interpreted with caution, as the (ground-truth) serosurveys available had only been conducted in a relatively small number of municipalities and tended to be aggregated in the same area. […] These features render the ML models more flexible, more readily updatable, and thus easier and simpler to be extended to other Chagas disease-endemic countries, and potentially to other infectious diseases, including neglected tropical diseases, for which serological surveys are regularly conducted as surveillance tools to assess epidemiological situation, incidence, and impact of control interventions across spatial and temporal scales.

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