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Background: Chagas disease, caused by the parasite Trypanosoma cruzi, is a neglected infectious disease that exerts the highest public health burden in the Americas. There are two anti-parasitic drugs approved for its treatment–benznidazole and nifurtimox—but the absence of biomarkers to early assess treatment efficacy hinders patients´ follow-up. Methodology/Principal findings: We conducted a longitudinal, observational study among a cohort of 106 chronically T. cruzi-infected patients in Cochabamba (Bolivia) who completed the recommended treatment of benznidazole. Participants were followed-up for five years, in which we collected clinical and serological data, including yearly electrocardiograms and optical density readouts from two ELISAs (total and recombinant antigens). Descriptive and statistical analyses were performed to understand trends in data, as well as the relationship between clinical symptoms and serological evolution after treatment. Our results showed that both ELISAs documented average declines up to year three and slight inclines for the following two years. The recorded clinical parameters indicated that most patients did not have any significant changes to their cardiac or digestive symptoms after treatment, at least in the timeframe under investigation, while a small percentage demonstrated either a regression or progression in symptoms. Only one participant met the "cure criterion" of a negative serological readout for both ELISAs by the final year. Conclusions/Significance: The study confirms that follow-up of benznidazole-treated T. cruzi-infected patients should be longer than five years to determine, with current tools, if they are cured. In terms of serological evolution, the single use of a total antigen ELISA might be a more reliable measure and suffice to address infection status, at least in the region of Bolivia where the study was done. Additional work is needed to develop a test-of-cure for an early assessment of drugs´ efficacy with the aim of improving case management protocols. Author summary: Chagas disease is a neglected parasitic disease prevalent throughout the Americas, with approximately seven million people infected. The highest infection rates have been identified in Bolivia. There, we followed for five years a cohort of chronically T. cruzi-infected patients attending the Platform for Integral Care of Chagas disease Patients in Cochabamba. With the aim to understand clinical and serological responses after completing treatment with benznidazole, we recorded clinical symptomatology and collected serum samples to run two ELISAs based on total and recombinant antigens in each yearly follow-up visit. Upon analyzing clinical and serological data, we found there were no major changes in the patients´ clinical status while serological reactivity generally declined until the third year of follow-up, particularly with the total antigen test. Remarkably, only one participant met the cure criterion of negative serological reversion for both ELISAs at the final visit. Our findings confirm that, using currently available tools, the appropriate time to address treatment efficacy is longer than five years. Additional studies are needed to find biomarkers for the early assessment of treatment efficacy. [ABSTRACT FROM AUTHOR]

Real-Time PCR (qPCR) testing is recommended as both a diagnostic and outcome measurement of etiological treatment in clinical practice and clinical trials of Chagas disease (CD), but no external quality assurance (EQA) program provides performance assessment of the assays in use. We implemented an EQA system to evaluate the performance of molecular biology laboratories involved in qPCR based follow-up in clinical trials of CD. An EQA program was devised for three clinical trials of CD: the E1224 (NCT01489228), a pro-drug of ravuconazole; the Sampling Study (NCT01678599), that used benznidazole, both conducted in Bolivia; and the CHAGASAZOL (NCT01162967), that tested posaconazole, conducted in Spain. Four proficiency testing panels containing negative controls and seronegative blood samples spiked with 1, 10 and 100 parasite equivalents (par. eq.)/mL of four Trypanosoma cruzi stocks, were sent from the Core Lab in Argentina to the participating laboratories located in Bolivia and Spain. Panels were analyzed simultaneously, blinded to sample allocation, at 4-month intervals. In addition, 302 random blood samples from both trials carried out in Bolivia were sent to Core Lab for retesting analysis. The analysis of proficiency testing panels gave 100% of accordance (within laboratory agreement) and concordance (between laboratory agreement) for all T. cruzi stocks at 100 par. eq./mL; whereas their values ranged from 71 to 100% and from 62 to 100% at 1 and 10 par. eq./mL, respectively, depending on the T. cruzi stock. The results obtained after twelve months of preparation confirmed the stability of blood samples in guanidine-EDTA buffer. No significant differences were found between qPCR results from Bolivian laboratory and Core Lab for retested clinical samples. This EQA program for qPCR analysis of CD patient samples may significantly contribute to ensuring the quality of laboratory data generated in clinical trials and molecular diagnostics laboratories of CD. [ABSTRACT FROM AUTHOR]

The article discusses a symposium entitled "Human African Trypanosomiasis (HAT) in a Spanish traveler returning from Tanzania." Topics discussed include presence of neuropsychiatric disorders in travelers with Trypanosoma brucei rhodesiense (r-HAT), penetration of central nervous system, and erythematous nodules.

Cytoadhesion of Plasmodium falciparum infected erythrocytes to gC1qR has been associated with severe malaria, but the parasite ligand involved is currently unknown. To assess if binding to gC1qR is mediated through the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family, we analyzed by static binding assays and qPCR the cytoadhesion and var gene transcriptional profile of 86 P. falciparum isolates from Mozambican children with severe and uncomplicated malaria, as well as of a P. falciparum 3D7 line selected for binding to gC1qR (Pf3D7gC1qR). Transcript levels of DC8 correlated positively with cytoadhesion to gC1qR (rho = 0.287, P = 0.007), were higher in isolates from children with severe anemia than with uncomplicated malaria, as well as in isolates from Europeans presenting a first episode of malaria (n = 21) than Mozambican adults (n = 25), and were associated with an increased IgG recognition of infected erythrocytes by flow cytometry. Pf3D7gC1qR overexpressed the DC8 type PFD0020c (5.3-fold transcript levels relative to Seryl-tRNA-synthetase gene) compared to the unselected line (0.001-fold). DBLβ12 from PFD0020c bound to gC1qR in ELISA-based binding assays and polyclonal antibodies against this domain were able to inhibit binding to gC1qR of Pf3D7gC1qR and four Mozambican P. falciparum isolates by 50%. Our results show that DC8-type PfEMP1s mediate binding to gC1qR through conserved surface epitopes in DBLβ12 domain which can be inhibited by strain-transcending functional antibodies. This study supports a key role for gC1qR in malaria-associated endovascular pathogenesis and suggests the feasibility of designing interventions against severe malaria targeting this specific interaction. [ABSTRACT FROM AUTHOR]

Chagas disease is a parasitic infection that is prevalent in immigrants from Mexico and Central and South America. It is estimated that 8-10 million people are infected, with a significant percentage developing cardiopathy or gastrointestinal disease. The disease is primarily transmitted through infected bugs, but can also be transmitted through blood transfusion, organ transplantation, and mother-to-child transmission. In Europe, the number of people with Chagas disease is estimated to be between 68,000 and 122,000, but only a small percentage have been diagnosed. Some European countries have implemented measures to control transmission, such as screening blood donations and testing at-risk individuals. However, many countries still lack legislation on the issue. The article discusses the health policies and guidelines in European countries regarding the transmission and control of Chagas disease. It highlights that while the EU directive on solid organ transplantation does not specifically address Chagas disease, three countries (Italy, Spain, and the United Kingdom) have included specific sections on controlling transmission through organ transplantation in their national guidelines. These countries routinely screen transplant donors for Chagas disease, although seropositivity may not be a contraindication for some transplants. Some regions in Spain and Italy have also implemented protocols for screening pregnant women from Chagas-endemic areas and monitoring their newborns for congenital Chagas disease. However, other European countries have not implemented specific legislation or guidelines for Chagas disease. The article recommends changes in health policies and directives to ensure control of Chagas [Extracted from the article]

Age- and exposure-dependent immune responses during a malaria episode may be key to understanding the role of these factors in the acquisition of immunity to malaria. Plasma/serum samples collected from naïve Mozambican children (n = 48), European adults (naïve travelers, n = 22; expatriates with few prior malaria exposures, n = 15) and Mozambican adults with long-life malaria exposure (n = 99) during and after a malaria episode were analyzed for IgG against merozoite proteins by Luminex and against infected erythrocytes by flow cytometry. Cytokines and chemokines were analyzed in plasmas/sera by suspension array technology. No differences were detected between children and adults with a primary infection, with the exception of higher IgG levels against 3D7 MSP-142 (P = 0.030) and a P. falciparum isolate (P = 0.002), as well as higher IL-12 (P = 0.020) in children compared to other groups. Compared to malaria-exposed adults, children, travelers and expatriates had higher concentrations of IFN-γ (P≤0.0090), IL-2 (P≤0.0379) and IL-8 (P≤0.0233). Children also had higher IL-12 (P = 0.0001), IL-4 (P = 0.003), IL-1β (P = 0.024) and TNF (P = 0.006) levels compared to malaria-exposed adults. Although IL-12 was elevated in children, overall the data do not support a role of age in immune responses to a first malaria episode. A TH1/pro-inflammatory response was the hallmark of non-immune subjects. [ABSTRACT FROM AUTHOR]

Background/Aims: The epidemiology of Chagas disease, until recently confined to areas of continental Latin America, has undergone considerable changes in recent decades due to migration to other parts of the world, including Spain. We studied the prevalence of Chagas disease in Latin American patients treated at a health center in Barcelona and evaluated its clinical phase. We make some recommendations for screening for the disease. Methodology/Principal Findings: We performed an observational, cross-sectional prevalence study by means of an immunochromatographic test screening of all continental Latin American patients over the age of 14 years visiting the health centre from October 2007 to October 2009. The diagnosis was confirmed by serological methods: conventional in-house ELISA (cELISA), a commercial kit (rELISA) and ELISA using T cruzi lysate (Ortho-Clinical Diagnostics) (oELISA). Of 766 patients studied, 22 were diagnosed with T. cruzi infection, showing a prevalence of 2.87% (95% CI, 1.6–4.12%). Of the infected patients, 45.45% men and 54.55% women, 21 were from Bolivia, showing a prevalence in the Bolivian subgroup (n = 127) of 16.53% (95% CI, 9.6–23.39%). All the infected patients were in a chronic phase of Chagas disease: 81% with the indeterminate form, 9.5% with the cardiac form and 9.5% with the cardiodigestive form. All patients infected with T. cruzi had heard of Chagas disease in their country of origin, 82% knew someone affected, and 77% had a significant history of living in adobe houses in rural areas. Conclusions: We found a high prevalence of T. cruzi infection in immigrants from Bolivia. Detection of T. cruzi–infected persons by screening programs in non-endemic countries would control non-vectorial transmission and would benefit the persons affected, public health and national health systems. Author Summary: Chagas disease is a parasitic infection caused by the protozoan Trypanosoma cruzi, and is becoming an emerging health problem in non-endemic areas because of growing population movements. The clinical manifestations of chronic T. cruzi infection include the latent form (the indeterminate chronic form), the cardiac form, the digestive or cardiodigestive form, and sudden death. Therefore, many diagnoses of Chagas disease are based on epidemiological suspicion rather than on clinical signs and symptoms. This study showed that the prevalence of Chagas disease in Latin American patients attending at a health center in Barcelona is 2,87% and the highest prevalence was found among Bolivian patients (16,53%). All the infected patients were in a chronic phase of Chagas disease. Detection of T. cruzi–infected persons by screening programs in non-endemic countries would control non-vectorial transmission and would benefit the persons affected, public health and national health systems. The data obtained in this study and the experiences described elsewhere suggest that it is advisable to perform Chagas disease screening in non-endemic countries on all patients from continental Latin America who: (1)have a suggestive epidemiologic history, (2)are pregnant, (3)are immunosuppressed, (4)have symptoms suggestive of Chagas disease, or (5)request screening. [ABSTRACT FROM AUTHOR]