Health policies to control Chagas disease transmission in European countries

Chagas disease (CD) is a highly prevalent parasitic disease in immigrants from Mexico, as well as all of Central and South America. The total number of infected people is estimated between eight and ten million [1], [2], of whom 30%-40% either have, or will, develop cardiopathy, gastrointestinal disease, or both [1]. Cardiac involvement is the main cause of death from this infection through arrhythmias and cardiomyopathy. Nifurtimox and benznidazole are the only available medicines with proven efficacy against Trypanosoma cruzi infection in acute, congenital infection and early chronic infection. Until recently the treatment of chronic disease, particularly of adult patients with indeterminate form, was controversial; but during the past decade there has been a trend to offer treatment to adult patients and those with early cardiomyopathy

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

Towards improving early diagnosis of congenital Chagas disease in an endemic setting.

: Congenital Trypanosoma cruzi transmission is now estimated to account for 22% of new infections, representing a significant public health problem across Latin America and internationally. Treatment during infancy is highly efficacious and well tolerated, but current assays for early detection fail to detect &gt;50% of infected neonates and 9 month follow-up is low. : Women presenting for delivery in two urban hospitals in Santa Cruz department, Bolivia were screened by rapid test. Specimens from infants of infected women were tested by microscopy (micromethod), quantitative PCR (qPCR) and IgM trypomastigote excreted-secreted antigen (TESA)-blots at birth and 1 month, and by IgG serology at 6 and 9 months. : Among 487 infants of 476 seropositive women, congenital T. cruzi infection was detected in 38 infants of 35 mothers (7.8%). In cord blood, qPCR, TESA-blot and micromethod sensitivities/specificities were 68.6%/99.1%, 58.3%/99.1% and 16.7%/100%, respectively. When birth and 1 month results were combined, cumulative sensitivities reached 84.2%, 73.7% and 34.2%, respectively. Low birth weight and/or respiratory distress were reported in 11 (29%) infected infants. Infants with clinical signs had higher parasite loads and were significantly more likely to be detected by micromethod. : The proportion of T. cruzi infected infants with clinical signs has fallen from the 1990s, but symptomatic congenital Chagas disease still represents a significant, albeit increasingly challenging to detect, public health problem. Molecular methods could facilitate earlier diagnosis and circumvent loss to follow-up but remain logistically and economically prohibitive for routine screening in resource-limited settings.<br/

Use of a Chagas Urine Nanoparticle Test (Chunap) to Correlate with Parasitemia Levels in T. cruzi/HIV Co-infected Patients

BackgroundEarly diagnosis of reactivated Chagas disease in HIV patients could be lifesaving. In Latin America, the diagnosis is made by microscopical detection of the T. cruzi parasite in the blood; a diagnostic test that lacks sensitivity. This study evaluates if levels of T. cruzi antigens in urine, determined by Chunap (Chagas urine nanoparticle test), are correlated with parasitemia levels in T. cruzi/HIV co-infected patients.Methodology/Principal FindingsT. cruzi antigens in urine of HIV patients (N = 55: 31 T. cruzi infected and 24 T. cruzi serology negative) were concentrated using hydrogel particles and quantified by Western Blot and a calibration curve. Reactivation of Chagas disease was defined by the observation of parasites in blood by microscopy. Parasitemia levels in patients with serology positive for Chagas disease were classified as follows: High parasitemia or reactivation of Chagas disease (detectable parasitemia by microscopy), moderate parasitemia (undetectable by microscopy but detectable by qPCR), and negative parasitemia (undetectable by microscopy and qPCR). The percentage of positive results detected by Chunap was: 100% (7/7) in cases of reactivation, 91.7% (11/12) in cases of moderate parasitemia, and 41.7% (5/12) in cases of negative parasitemia. Chunap specificity was found to be 91.7%. Linear regression analysis demonstrated a direct relationship between parasitemia levels and urine T. cruzi antigen concentrations (p 105 pg was chosen to determine patients with reactivation of Chagas disease (7/7). Antigenuria levels were 36.08 times (95% CI: 7.28 to 64.88) higher in patients with CD4+ lymphocyte counts below 200/mL (p = 0.016). No significant differences were found in HIV loads and CD8+ lymphocyte counts.ConclusionChunap shows potential for early detection of Chagas reactivation. With appropriate adaptation, this diagnostic test can be used to monitor Chagas disease status in T. cruzi/HIV co-infected patients.Author SummaryReactivation of Chagas disease in people living with HIV is a serious clinical condition that is associated with high mortality. Hence, early diagnosis and treatment can be lifesaving. Although there are not well accepted criteria to identify patients at risk of reactivation, parasitemia levels are usually considered as the best predictor. Microscopy is used in Latin America for detection of parasitemia levels. However, this has low sensitivity, which usually leads to a delay in diagnosis and treatment. Quantitative PCR is used only for research proposes in endemic areas. Antigens in urine (antigenuria) are correlated with parasitemia levels in animal models, as well as in cases of congenital Chagas disease. We believe that antigenuria can also be used for prediction of parasitemia levels in T. cruzi/HIV co-infected patients. In this study, Chunap (Chagas urine nanoparticle test) was used for concentration and quantification of T. cruzi antigens in urine of T. cruzi/HIV co-infected patients. Values of more than 105 pg of T. cruzi antigens in urine were observed only in patients with reactivation of Chagas disease. This study shows that antigenuria levels are highly correlated to levels of parasitemia and can be used as a non-invasive technique for monitoring parasitemia levels in T. cruzi/HIV co-infected patients

Toward Improving Early Diagnosis of Congenital Chagas Disease in an Endemic Setting.

BACKGROUND: Congenital Trypanosoma cruzi transmission is now estimated to account for 22% of new infections, representing a significant public health problem across Latin America and internationally. Treatment during infancy is highly efficacious and well tolerated, but current assays for early detection fail to detect >50% of infected neonates, and 9-month follow-up is low. METHODS: Women who presented for delivery at 2 urban hospitals in Santa Cruz Department, Bolivia, were screened by rapid test. Specimens from infants of infected women were tested by microscopy (micromethod), quantitative PCR (qPCR), and immunoglobulin (Ig)M trypomastigote excreted-secreted antigen (TESA)-blots at birth and 1 month and by IgG serology at 6 and 9 months. RESULTS: Among 487 infants of 476 seropositive women, congenital T. cruzi infection was detected in 38 infants of 35 mothers (7.8%). In cord blood, qPCR, TESA-blot, and micromethod sensitivities/specificities were 68.6%/99.1%, 58.3%/99.1%, and 16.7%/100%, respectively. When birth and 1-month results were combined, cumulative sensitivities reached 84.2%, 73.7%, and 34.2%, respectively. Low birthweight and/or respiratory distress were reported in 11 (29%) infected infants. Infants with clinical signs had higher parasite loads and were significantly more likely to be detected by micromethod. CONCLUSIONS: The proportion of T. cruzi-infected infants with clinical signs has fallen since the 1990s, but symptomatic congenital Chagas disease still represents a significant, albeit challenging to detect, public health problem. Molecular methods could facilitate earlier diagnosis and circumvent loss to follow-up but remain logistically and economically prohibitive for routine screening in resource-limited settings

Severity of Chagasic Cardiomyopathy Is Associated With Response to a Novel Rapid Diagnostic Test for Trypanosoma cruzi TcII/V/VI.

Background: Trypanosoma cruzi causes Chagas disease in the Americas. The outcome of infection ranges from lifelong asymptomatic status to severe disease. Relationship between T. cruzi lineage (TcI-TcVI) infection history and prognosis is not understood. We previously described peptide-based lineage-specific enzyme-linked immunosorbent assay (ELISA) with trypomastigote small surface antigen (TSSA). Methods: A novel rapid diagnostic test (RDT; Chagas Sero K-SeT) that incorporates a peptide that corresponds to the TSSA II/V/VI common epitope was developed and validated by comparison with ELISA. Patients from Bolivia and Peru, including individuals with varying cardiac pathology, and matched mothers and neonates, were then tested using Chagas Sero K-SeT. Results: Chagas Sero K-SeT and ELISA results, with a Bolivian subset of cardiac patients, mothers, and neonates, were in accord. In adult chronic infections (n = 121), comparison of severity class A (no evidence of Chagas cardiomyopathy) with class B (electrocardiogram suggestive of Chagas cardiomyopathy) and class C/D (decreased left ventricular ejection fraction; moderate/severe Chagas cardiomyopathy) revealed a statistically significant increase in Chagas Sero K-SeT reactivity with increasing severity (χ2 for trend, 7.39; P = .007). In Peru, Chagas Sero K-SeT detected the sporadic TcII/V/VI infections. Conclusions: We developed a low cost RDT that can replace ELISA for identification of TSSA II/V/VI immunoglobulin G. Most importantly, we show that response to this RDT is associated with severity of Chagas cardiomyopathy and thus may have prognostic value. Repeated challenge with T. cruzi infection may both exacerbate disease progression and boost the immune response to the TSSApep-II/V/VI epitope

Epidemiology of congenital Chagas disease 6 years after implementation of a public health surveillance system, Catalonia, 2010 to 2015

Background: Chagas disease is endemic in Latin America and affects 8 million people worldwide. In 2010, Catalonia introduced systematic public health surveillance to detect and treat congenital Chagas disease. Aim: The objective was to evaluate the health outcomes of the congenital Chagas disease screening programme during the first 6 years (2010–2015) after its introduction in Catalonia. Methods: In a surveillance system, we screened pregnant women and newborns and other children of positive mothers, and treated Chagas-positive newborns and children. Diagnosis was confirmed for pregnant women and children with two positive serological tests and for newborns with microhaematocrit and/or PCR at birth or serology at age 9 months. Results: From 2010 to 2015, the estimated screening coverage rate increased from 68.4% to 88.6%. In this period, 33,469 pregnant women were tested for Trypanosoma cruzi and 937 positive cases were diagnosed. The overall prevalence was 2.8 cases per 100 pregnancies per year (15.8 in Bolivian women). We followed 82.8% of newborns until serological testing at age 9–12 months and 28 were diagnosed with Chagas disease (congenital transmission rate: 4.17%). Of 518 siblings, 178 (34.3%) were tested and 14 (7.8%) were positive for T. cruzi. Having other children with Chagas disease and the heart clinical form of Chagas disease were maternal risk factors associated with congenital T. cruzi infection (p<0.05). Conclusion: The increased screening coverage rate indicates consolidation of the programme in Catalonia. The rate of Chagas disease congenital transmission in Catalonia is in accordance with the range in non-endemic countries

Use of a rapid test on umbilical cord blood to screen for Trypanosoma cruzi infection in pregnant women in Argentina, Bolivia, Honduras, and Mexico

Fil: Sosa-Estani, Sergio. ANLIS Dr.C.G.Malbrán. Centro Nacional de Diagnóstico e Investigación en Endemo-Epidemias; Argentina.Fil: Gamboa-León, Miriam Rubi. Universidad Autónoma de Yucatán. Laboratorio de Parasitología; México.Fil: Del Cid-Lemus, Jaime. Intibucá. Región Sanitaria No. 10; Honduras.Fil: Althabe, Fernando. Instituto de Efectividad Clínica y Sanitaria; Argentina.Fil: Alger, Jackeline. Instituto de Enfermedades Infecciosas y Parasitología Antonio Vidal; Honduras.Fil: Almendares, Olivia. Tulane University. School of Public Health and Tropical Medicine; Estados Unidos.Fil: Cafferata, María L. Hospital de Clínicas. Unidad de Investigación Clínica y Epidemiológica Montevideo; Uruguay.Fil: Chippaux, Jean-Philippe. L'Institut de recherche pour le développement (IRD); Bolivia.Fil: Dumonteil, Eric. Universidad Autónoma de Yucatán. Laboratorio de Parasitología; México.Fil: Gibbons, Luz. Instituto de Efectividad Clínica y Sanitaria; Argentina.Fil: Schneider, Dominique. L'Institut de recherche pour le développement (IRD); Bolivia.Fil: Belizán, José M. Instituto de Efectividad Clínica y Sanitaria; Argentina.Fil: Buekens, Pierre. Tulane University. School of Public Health and Tropical Medicine; Estados Unidos.Fil: Padilla-Raygoza, Nicolás. Universidad de Guanajuato; México.Fil: Perinatal Chagas Disease Working Group; Estados Unidos.We conducted a cross-sectional study of Chagas disease in five endemic areas in Argentina, Bolivia, Honduras, and México to estimate the prevalence of Trypanosoma cruzi–specific antibodies in pregnant women, and to assess the use of a rapid test (Chagas Stat-Pak) to screen for T. cruzi infection at the time of delivery. The prevalence of antibodies to T. cruzi measured by enzyme-linked immunosorbent assay (ELISA) in maternal blood was 5.5% (a range of 0.8–28.8% among the countries) in 2,495 women enrolled. Compared with ELISA in maternal blood samples, the Chagas Stat-Pak rapid test sensitivity and specificity in umbilical cord blood were 94.6% and 99.0%, respectively. These results show the ability for a rapid determination of the presence of T. cruzi–specific antibodies in umbilical cord blood as a pragmatic strategy to screen for infection in pregnant women

Health policies to control Chagas disease transmission in European countries

Chagas disease (CD) is a highly prevalent parasitic disease in immigrants from Mexico, as well as all of Central and South America. The total number of infected people is estimated between eight and ten million [1], [2], of whom 30%-40% either have, or will, develop cardiopathy, gastrointestinal disease, or both [1]. Cardiac involvement is the main cause of death from this infection through arrhythmias and cardiomyopathy. Nifurtimox and benznidazole are the only available medicines with proven efficacy against Trypanosoma cruzi infection in acute, congenital infection and early chronic infection. Until recently the treatment of chronic disease, particularly of adult patients with indeterminate form, was controversial; but during the past decade there has been a trend to offer treatment to adult patients and those with early cardiomyopathy

Use of a Novel Chagas Urine Nanoparticle Test (Chunap) for Diagnosis of Congenital Chagas Disease

<div><p>Background</p><p>Detection of congenital <i>T. cruzi</i> transmission is considered one of the pillars of control programs of Chagas disease. Congenital transmission accounts for 25% of new infections with an estimated 15,000 infected infants per year. Current programs to detect congenital Chagas disease in Latin America utilize microscopy early in life and serology after 6 months. These programs suffer from low sensitivity by microscopy and high loss to follow-up later in infancy. We developed a Chagas urine nanoparticle test (Chunap) to concentrate, preserve and detect <i>T. cruzi</i> antigens in urine for early, non-invasive diagnosis of congenital Chagas disease.</p><p>Methodology/Principal Findings</p><p>This is a proof-of-concept study of Chunap for the early diagnosis of congenital Chagas disease. Poly N-isopropylacrylamide nano-particles functionalized with trypan blue were synthesized by precipitation polymerization and characterized with photon correlation spectroscopy. We evaluated the ability of the nanoparticles to capture, concentrate and preserve <i>T. cruzi</i> antigens. Urine samples from congenitally infected and uninfected infants were then concentrated using these nanoparticles. The antigens were eluted and detected by Western Blot using a monoclonal antibody against <i>T. cruzi</i> lipophosphoglycan. The nanoparticles concentrate <i>T. cruzi</i> antigens by 100 fold (western blot detection limit decreased from 50 ng/ml to 0.5 ng/ml). The sensitivity of Chunap in a single specimen at one month of age was 91.3% (21/23, 95% CI: 71.92%–98.68%), comparable to PCR in two specimens at 0 and 1 month (91.3%) and significantly higher than microscopy in two specimens (34.8%, 95% CI: 16.42%–57.26%). Chunap specificity was 96.5% (71/74 endemic, 12/12 non-endemic specimens). Particle-sequestered <i>T. cruzi</i> antigens were protected from trypsin digestion.</p><p>Conclusion/Significance</p><p>Chunap has the potential to be developed into a simple and sensitive test for the early diagnosis of congenital Chagas disease.</p></div