The α-Gal antigen [Galα(1,3)Galβ(1,4)GlcNAcα] is an immunodominant epitope displayed by infective trypomastigote forms of Trypanosoma cruzi, the causative agent of Chagas disease. A virus-like particle displaying a high density of α-Gal was found to be a superior reagent for the ELISA-based serological diagnosis of Chagas disease and the assessment of treatment effectiveness. A panel of sera from patients chronically infected with T. cruzi, both untreated and benznidazole-treated, was compared with sera from patients with leishmaniasis and from healthy donors. The nanoparticle-α-Gal construct allowed for perfect discrimination between Chagas patients and the others, avoiding false negative and false positive results obtained with current state-of-the-art reagents. As previously reported with purified α-Gal-containing glycosylphosphatidylinositol-anchored mucins, the current study also showed concentrations of anti-α-Gal IgG to decrease substantially in patients receiving treatment with benznidazole, suggesting that the semiquantitative assessment of serum levels of this highly abundant type of antibody can report on disease status in individual patients.

BackgroundControl strategies adopted by the Brazilian Visceral Leishmaniasis Surveillance and Control Programme (VLSCP) include identifying and culling seropositive infected dogs, early diagnosis and treatment of human cases, chemical control of the vector and population awareness. This study evaluated the effectiveness of the VLSCP on the prevalence and incidence rates of Leishmania infantum in children residing in areas under different VLSCP intervention times.MethodsA quasi-experimental epidemiological study with a panel (two cross-sectional) and a concurrent cohort was performed in three areas of Belo Horizonte, southeast Brazil. The first cross-sectional study (I) was carried out with 1875 children, 478 of which were enrolled in the cohort study. In the second cross-sectional study (II), 413 additional children were included, totalizing 891 children. Laboratory diagnosis was performed by ELISA-rK39. Analyses included multilevel logistic and Poisson regression models.ResultsThe incidence rates of L. infantum infection were: 14.4% in the area where VLSCP intervention was initiated in 2006 (AI2006); 21.1% in the area where intervention was initiated in 2008 (AI2008); and 11.6% in the area where intervention was initiated in 2010 (AI2010 - control area). A follow-up period of 24 months showed that the persons-time incidence rates in AI2006, AI2008, and AI2010 were: 6.2/100, 10/100, and 5.6/100 persons/24 months, respectively. The final prevalence rates of infection (cross-sectional II - in 2012), compared to the initial rates (cross-sectional I - in 2010), increased 83.7% in AI2006, 74.1% in AI2008, and decreased 5% in AI2010. Analysis of the effectiveness revealed that children residing in AI2008 are more likely to be infected (OR = 1.84; 95% CI: 1.06-3.23) and present a higher risk of infection (IRR = 1.76; 95% CI: 1.05-2.95) compared to those in AI2010. No statistically significant differences were observed in asymptomatic infection (OR and IRR) in AI2006 compared to AI2010.ConclusionsThe VLSCP was not effective at controlling L. infantum infection in areas where interventions had respectively been carried out for six and four years. However, it is unclear what the consequences in terms of human infection and diseases would be in the absence of the VLSCP. Efforts to improve the effectiveness of control measures remain a necessary priority.Electronic supplementary materialThe online version of this article (10.1186/s13071-018-3166-0) contains supplementary material, which is available to authorized users.

a b s t r a c tObjectives: We aimed to detect Leishmania DNA carriage in nasal mucosa of individuals with cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis. Methods: A cross-sectional study was performed in all individuals with CL without nasal lesions (n ¼ 153) attended within 2 years in an endemic area of L. (Viannia) braziliensis in Bahia (Brazil). An otorhinolaryngologist assessed the clinical status of the nasal mucosa by anterior rhinoscopy and endoscopic examinations. Swab samples were collected for parasite DNA detection by PCR from all individuals before standard treatment for leishmaniasis. A second evaluation 3 months after treatment was performed to assess clinical outcomes. Results: Parasite DNA was detected in 7.8% (12/153) of clinically healthy nasal mucosa of individuals with CL. Interestingly, DNA was more frequently identified in individuals with more skin lesions (median 1.5, interquartile range (IQR) 1e3.5 versus 1.0, IQR 1e1.5; p 0.044), or larger injuries (median 2.7, IQR 2e3.8 versus 1.6, IQR 1e2.5; p 0.013). Additionally, the disease of those individuals with positive PCR evolved more frequently to unusual forms of leishmaniasis (recidiva cutis and disseminated) (45.5% (5/11) versus 11.5% (14/122); p 0.009), and required more cycles of treatment to reach clinical cure (median 2, IQR 1e4 versus 1, IQR 1e2; p 0.05). Conclusion: These findings suggest an early parasite tropism to nasal mucosa in L. (Viannia) braziliensis infection and a clinical phenotype of CL cases associated with parasite DNA in nasal mucosa. Future studies should evaluate whether PCR of nasal swab samples could serve as a prognostic tool for individuals at risk of mucocutaneous leishmaniasis. A. Can ario, Clin Microbiol Infect 2019;25:515.e5 e515.e7

To evaluate the distribution of asymptomatic infection by Leishmania infantum in a metropolis in Brazil with different relative risks (RRs) for disease and risk factors associated with the infection, an ecological study was conducted using a Bayesian approach to estimate the RR of human visceral leishmaniasis (HVL) based on cases between 2008 and 2011. The areas were categorized and selected according to disease incidence: low (area-1), medium (area-2) and high (area-3). Cross-sectional study enrolling 935 children was used to estimate the prevalence of infection by L. infantum. Volunteers from these three areas were tested for L. infantum infection by ELISA (rK39 and soluble antigens). Infection prevalence rates were estimated and compared with the RR of disease. Multilevel logistic regression model evaluated the relationship between infection and the analysed variables. The RR of HVL was distributed heterogeneously in the municipality. The infection prevalence rates were: 34·9% in area-1; 29·3% in area-2; and 33·6% in area-3, with no significant differences between these areas. The variables 'Presence of backyards in the neighbourhood' and 'Younger children' were associated with L. infantum infection. We conclude that infection by L. infantum affects a significant proportion of the infant population regardless of the RR of disease.

Chagas disease, caused by the parasite Trypanosoma cruzi, is considered endemic in more than 20 countries but lacks both an approved vaccine and limited treatment for its chronic stage. Chronic infection is most harmful to human health because of long-term parasitic infection of the heart. Here we show that immunization with a virus-like particle vaccine displaying a high density of the immunogenic α-Gal trisaccharide (Qβ-αGal) induced several beneficial effects concerning acute and chronic T. cruzi infection in α1,3-galactosyltransferase knockout mice. Approximately 60% of these animals were protected from initial infection with high parasite loads. Vaccinated animals also produced high anti-αGal IgG antibody titers, improved IFN-γ and IL-12 cytokine production, and controlled parasitemia in the acute phase at 8 days post-infection (dpi) for the Y strain and 22 dpi for the Colombian strain. In the chronic stage of infection (36 and 190 dpi, respectively), all of the vaccinated group survived, showing significantly decreased heart inflammation and clearance of amastigote nests from the heart tissue.

The leading animal model of experimental Chagas disease, the mouse, plays a significant role in studies for vaccine development, diagnosis, and human therapies. Humans, along with Old World primates, alone among mammals, cannot make the terminal carbohydrate linkage of the α-Gal trisaccharide. It has been established that the anti-α-Gal immune response is likely to be a critical factor for protection against Trypanosoma cruzi (T. cruzi) infection in humans. However, the mice customarily employed for the study of T. cruzi infection naturally express the α-Gal epitope and therefore do not produce anti-α-Gal antibodies. Here, we used the C57BL/6 α-1,3-galactosyltransferase knockout (α-GalT-KO) mouse, which does not express the α-Gal epitope as a model for experimental Chagas disease. We found the anti-α-Gal IgG antibody response to an increase in α-GalT-KO mice infected with Arequipa and Colombiana strains of T. cruzi, leading to fewer parasite nests, lower parasitemia, and an increase of INF-γ, TNF-α, and IL-12 cytokines in the heart of α-GalT-KO mice compared with α-GalT-WT mice on days 60 and 120 postinfection. We therefore agree that the C57BL/6 α-GalT-KO mouse represents a useful model for initial testing of therapeutic and immunological approaches against different strains of T. cruzi.

In areas endemic for Leishmania infantum, an asymptomatic infection may be an indicator of the extent of transmission. The main goal of this study was to evaluate the applicability of measuring circulating immunological biomarkers as an alternative strategy to characterize and monitor L. infantum asymptomatic infections in combination with serological methods. To this end, 179 children from a region endemic for visceral leishmaniasis (VL), aged 1–10 years old, selected from a cross-sectional study, were identified as asymptomatic (n = 81) or uninfected (n = 98) by qPCR and/or serological tests (ELISA using L. infantum soluble antigen and rK39), and, together with serum samples of children diagnosed with VL (n = 43), were subjected to avidity tests and cytokine levels measurement. Avidity rates (AR) ranging from 41 to 70% were found in 29 children (66%) from the asymptomatic group. On the other hand, high AR (above 70%) were observed in 27 children (64%) from the VL group. Logistic Regression and Classification and Regression Tree (CART) analyses demonstrated that lower AR and IFN-γ production associated with higher IL-17A levels were hallmarks in asymptomatic L. infantum infections. Therefore, this study proposes an association of immunological biomarkers that can be used as a complementary strategy for the characterization and monitoring of asymptomatic VL infections in children living in endemic areas.