Immunological imbalance between IFN-³ and IL-10 levels in the sera of patients with the cardiac form of Chagas disease

The immune response is crucial for protection against disease; however, immunological imbalances can lead to heart and digestive tract lesions in chagasic patients. Several studies have evaluated the cellular and humoral immune responses in chagasic patients in an attempt to correlate immunological findings with clinical forms of Chagas disease. Moreover, immunoglobulins and cytokines are important for parasitic control and are involved in lesion genesis. Here, cytokine and IgG isotype production were studied, using total epimastigote antigen on sera of chagasic patients with indeterminate (IND, n = 27) and cardiac (CARD, n = 16) forms of the disease. Samples from normal, uninfected individuals (NI, n = 30) were use as controls. The results showed that sera from both IND and CARD patients contained higher levels of Trypanosoma cruzi-specific IgG1 (IgG1) antibodies than sera from NI. No difference in IgG2 production levels was observed between NI, IND and CARD patients, nor was a difference in IL-10 and IFN-³ production detected in the sera of IND, CARD and NI patients. However, IND patients displayed a positive correlation between IL-10 and IFN-³ levels in serum, while CARD patients showed no such correlation, indicating an uncontrolled inflammatory response in CARD patients. These findings support the hypothesis that a lack of efficient regulation between IFN-³ and IL-10 productions in CARD patients may lead to cardiac immunopathology.CNP

Myeloid Sirtuin 2 expression does not impact long-term Mycobacterium tuberculosis control

Sirtuins (Sirts) regulate several cellular mechanisms through deacetylation of several transcription factors and enzymes. Recently, Sirt2 was shown to prevent the development of inflammatory processes and its expression favors acute Listeria monocytogenes infection. The impact of this molecule in the context of chronic infections remains unknown. We found that specific Sirt2 deletion in the myeloid lineage transiently increased Mycobacterium tuberculosis load in the lungs and liver of conditional mice. Sirt2 did not affect long-term infection since no significant differences were observed in the bacterial burden at days 60 and 120 post-infection. The initial increase in M. tuberculosis growth was not due to differences in inflammatory cell infiltrates in the lung, myeloid or CD4+ T cells. The transcription levels of IFN-?, IL-17, TNF, IL-6 and NOS2 were also not affected in the lungs by Sirt2-myeloid specific deletion. Overall, our results demonstrate that Sirt2 expression has a transitory effect in M. tuberculosis infection. Thus, modulation of Sirt2 activity in vivo is not expected to affect chronic infection with M. tuberculosis.Fundação para a Ciência e Tecnologia, Portugal and cofunded by Programa Operacional Regional do Norte (ON.2–O Novo Norte), Quadro de Referência Estratégico Nacional (QREN), through the Fundo Europeu de Desenvolvimento Regional (FEDER). Project grants: PTDC/SAU-MII/101977/2008 (to AGC) and PTDC/BIA-BCM/102776/2008 (to MS). LMT was supported by FCT Grant SFRH/BPD/77399/20

Towards the elimination of dog-mediated rabies: development and application of an evidence-based management tool

Abstract: Background: International organizations advocate for the elimination of dog-mediated rabies, but there is only limited guidance on interpreting surveillance data for managing elimination programmes. With the regional programme in Latin America approaching elimination of dog-mediated rabies, we aimed to develop a tool to evaluate the programme’s performance and generate locally-tailored rabies control programme management guidance to overcome remaining obstacles. Methods: We developed and validated a robust algorithm to classify progress towards rabies elimination within sub-national administrative units, which we applied to surveillance data from Brazil and Mexico. The method combines criteria that are easy to understand, including logistic regression analysis of case detection time series, assessment of rabies virus variants, and of incursion risk. Subjecting the algorithm to robustness testing, we further employed simulated data sub-sampled at differing levels of case detection to assess the algorithm’s performance and sensitivity to surveillance quality. Results: Our tool demonstrated clear epidemiological transitions in Mexico and Brazil: most states progressed rapidly towards elimination, but a few regressed due to incursions and control lapses. In 2015, dog-mediated rabies continued to circulate in the poorest states, with foci remaining in only 1 of 32 states in Mexico, and 2 of 27 in Brazil, posing incursion risks to the wider region. The classification tool was robust in determining epidemiological status irrespective of most levels of surveillance quality. In endemic settings, surveillance would need to detect less than 2.5% of all circulating cases to result in misclassification, whereas in settings where incursions become the main source of cases the threshold detection level for correct classification should not be less than 5%. Conclusion: Our tool provides guidance on how to progress effectively towards elimination targets and tailor strategies to local epidemiological situations, while revealing insights into rabies dynamics. Post-campaign assessments of dog vaccination coverage in endemic states, and enhanced surveillance to verify and maintain freedom in states threatened by incursions were identified as priorities to catalyze progress towards elimination. Our finding suggests genomic surveillance should become increasingly valuable during the endgame for discriminating circulating variants and pinpointing sources of incursions