This study shows a high prevalence of CT infection among young pregnant women in Brazil. We suggest that CT screening should be included as part of antenatal care routine in this group in Brazil.

Background The impact of SARS-CoV-2 in regions endemic for both Dengue and Chikungunya is still not fully understood. Considering that symptoms/clinical features displayed during Dengue, Chikungunya and SARS-CoV-2 acute infections are similar, undiagnosed cases of SARS-CoV-2 in co-endemic areas may be more prevalent than expected. This study was conducted to assess the prevalence of covert cases of SARS-CoV-2 among samples from patients with clinical symptoms compatible with either Dengue or Chikungunya viral infection in the state of Espírito Santo, Brazil. Methods Presence of immunoglobulin G (IgG) antibody specific to SARS-CoV-2 nucleoprotein was detected using a chemiluminescent microparticle immunoassay in samples from 7,370 patients, without previous history of COVID-19 diagnosis, suspected of having either Dengue (n = 1,700) or Chikungunya (n = 7,349) from December 1st, 2019 to June 30th, 2020. Findings Covert cases of SARS-CoV-2 were detected in 210 (2.85%) out of the 7,370 serum samples tested. The earliest undiagnosed missed case of COVID-19 dated back to a sample collected on December 18, 2019, also positive for Dengue Virus. Cross-reactivity with either Dengue virus or other common coronaviruses were not observed. Interpretation Our findings demonstrate that concomitant Dengue or Chikungunya outbreaks may difficult the diagnosis of SARS-CoV-2 infections. To our knowledge, this is the first study to demonstrate, with a robust sample size (n = 7,370) and using highly specific and sensitive chemiluminescent microparticle immunoassay method, that covert SARS-CoV-2 infections are more frequent than previously expected in Dengue and Chikungunya hyperendemic regions. Moreover, our results suggest that SAR-CoV-2 cases were occurring prior to February, 2020, and that these undiagnosed missed cases may have contributed to the fast expansion of SARS-CoV-2 outbreak in Brazil. Data presented here demonstrate that in arboviral endemic regions, SARS-CoV-2 infection must be always considered, regardless of the existence of a previous positive diagnosis for Dengue or Chikungunya.

Patients infected by Leishmania braziliensis develop debilitating skin lesions. The role of inhibitory checkpoint receptors (ICRs) that induce T cell exhaustion during this disease is not known. Transcriptional profiling identified increased expression of ICRs including PD-1, PDL-1, PDL-2, TIM-3, and CTLA-4 in skin lesions of patients that was confirmed by immunohistology where there was increased expression of PD-1, TIM-3, and CTLA-4 in both CD4+ and CD8+ T cell subsets. Moreover, PDL-1/PDL-2 ligands were increased on skin macrophages compared to healthy controls. The proportions PD1+, but not TIM-3 or CTLA-4 expressing T cells in the circulation were positively correlated with those in the lesions of the same patients, suggesting that PD-1 may regulate T cell function equally in both compartments. Blocking PD-1 signaling in circulating T cells enhanced their proliferative capacity and IFN-γ production, but not TNF-α secretion in response to L. braziliensis recall antigen challenge in vitro. While we previously showed a significant correlation between the accumulation of senescent CD8+CD45RA+CD27- T cells in the circulation and skin lesion size in the patients, there was no such correlation between the extent of PD-1 expression by circulating on T cells and the magnitude of skin lesions suggesting that exhausted-like T cells may not contribute to the cutaneous immunopathology. Nevertheless, we identified exhausted-like T cells in both skin lesions and in the blood. Targeting this population by PD-1 blockade may improve T cell function and thus accelerate parasite clearance that would reduce the cutaneous pathology in cutaneous leishmaniasis.

Background Regulatory T cells (Tregs) play a critical role during Mycobacterium tuberculosis (Mtb) infection, modulating host responses while neutralizing excessive inflammation. However, their impact on regulating host protective immunity is not completely understood. Here, we demonstrate that Treg cells abrogate the in vitro microbicidal activity against Mtb. Methods We evaluated the in vitro microbicidal activity of peripheral blood mononuclear cells (PBMCs) from patients with active tuberculosis (TB), individuals with latent tuberculosis infection (LTBI, TST+/IGRA+) and healthy control (HC, TST-/IGRA-) volunteers. PBMCs, depleted or not of CD4+CD25+ T-cells, were analyzed to determine frequency and influence on microbicidal activity during in vitro Mtb infection with four clinical isolates (S1, S5, R3, and R6) and one reference strain (H37Rv). Results The frequency of CD4+CD25highFoxP3+ cells were significantly higher in Mtb infected whole blood cultures from both TB patients and LTBI individuals when compared to HC. Data from CD4+CD25+ T-cells depletion demonstrate that increase of CD4+CD25highFoxP3+ is associated with an impairment of Th-1 responses and a diminished in vitro microbicidal activity of LTBI and TB groups. Conclusions Tregs restrict host anti-mycobacterial immunity during active disease and latent infection and thereby may contribute to both disease progression and pathogen persistence.

An increased number of regulatory T (Treg) cells has been reported in patients with HTLV-1 and Strongyloides stercoralis co-infection, suggesting the contribution of these cells to worm survival. As Strongyloides infections have been found to be highly prevalent in chronic alcoholics, we investigated the effect of abusive ethanol ingestion on the induction of Treg cells in alcoholic patients with Strongyloides infection. Treg cells were assessed by flow cytometry in the peripheral blood of 12 healthy non-alcoholic (control) and 14 alcoholic patients (alcoholic) without Strongyloides infection and five non-alcoholics (controlSs) and five chronic alcoholics (alcoholSs) with Strongyloides infection. The results showed significantly higher frequencies of Treg cells in the alcoholic, controlSs and alcoholSs group patients than in the control group patients. However, the frequencies of Treg cells did not differ between the alcoholSs and controlSs groups. In conclusion, our results demonstrate that ethanol consumption induced an increase in the number of circulating Treg cells in chronic alcoholics in this study but was unable to potentiate the induction of these cells in alcoholics with Strongyloides infection.

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Methods Analyses of positivity trends were conducted using available data for opportunistic asymptomatic tests (screens) from the NCSP national dataset for 2005 to 2010 from areas that implemented screening throughout this time period. Age, sex, ethnicity, sexual behaviour, regional and venue of screen weights for the English population of 15e24-year-olds were derived (from national sources where available) and applied to the dataset. Results From 2005 to 2010 there was an increase in screens among men. There were no major changes in characteristics known to be associated with infection (year of age, sexual behavioural variables). Available data on sexual behavioural variables and ethnicity decreased over time. There were some changes in venue use over time. Weighting for 5-year age group, sex, <2 sexual partners in past 12 months, ethnicity and region lowered positivity in each year but slightly increased the decline in positivity from an average decline of 13% per year (from 11% in 2005 to 6% in 2010) to an average of 14% per year (from 10% to 4%). Additional standardisation by screening venue did not reduce the overall observed decline in positivity during this period. Differences in positivity between venues remained, but were slightly reduced, after weighting for differences in known characteristics of screened clients. Conclusions The observed decline in positivity over time among screens was not accounted for by weighting for known characteristics of those screened or changes in testing venues. Together with the consistency of declining positivity in all sub-categories this suggests that a true decline in population prevalence may have occurred. Further analyses of the potential effects of data limitations and using regression techniques with additional variables (eg, deprivation) are in progress to better understand the relationship between screen positivity and population prevalence at different levels of screening uptake in England. Background National notifiable disease data indicate that 99 of every 100 000 persons in the USA were infected with gonorrhoea in 2009, the lowest recorded gonorrhoea rate in US history. However, the extent to which declining case reports signify a reduction in prevalence is unknown. In order to better understand national gonorrhoea trends, we examined prevalence over time among men and women entering the National Job Training Program (NJTP). Methods Gonorrhoea prevalence was estimated among 16e24-yearold men and women entering the NJTP in 48 states and the District of Columbia from 2004e2009. To approximate gonorrhoea screening, only data from the 105 (85% of all 123) centers that performed gonorrhoea testing on at least 50% of the population were included. Conditional logistic regression was used to assess the probability of testing positive for gonorrhoea over time, adjusted for variables associated with gonorrhoea risk. Gonorrhoea prevalence among black women decreased from 3.6% in 2004 to 2.5% in 2009 and was 2e4 times higher than prevalence among white women during th...