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Abstract Background Worldwide, several efforts have been made to develop, distribute and administer safe and effective vaccines to reduce morbidity and mortality and control the Covid-19 pandemic. This study aimed to analyze the effect of vaccination against Covid-19, one year after its introduction in Brazil. Methods An ecological study that analyzed the general effect of vaccination against Covid-19 on disease morbidity and mortality indicators among the Brazilian population aged 18 years or older per epidemiological week (EW), comparing the pre and postvaccination period. Morbidity and mortality indicators were calculated from secondary databases (hospitalization rate, severity, case fatality rate and mortality) and vaccination coverage by age groups (18 to 59 years and 60 years or older). Morbimortality trends were estimated using the JoinPoint model and their association with vaccine coverage using the Poisson model. Results The average weekly percentage change (AWPC) of morbidity and mortality indicators reduced after the introduction of Covid-19 vaccination: hospitalization rate (from 15.3% to -6.0%), severity (from 0.4% to -0.2%), case fatality rate (from 0.3% to -0.2%) and mortality (from 20.5% to -4.3%). The following indicators were inversely associated with the increase in vaccine coverage against Covid-19: hospitalization (IRR: 0.974), mortality (IRR: 0.975) and lethality for people aged 60 years or older (IRR: 0.997). Conclusions In spite of the three epidemic waves and the circulation of variants of concern, the general effect of vaccination against Covid-19 in reducing the trend of morbidity and mortality from the disease in Brazil was demonstrated. These findings contribute to a better understanding of the mass vaccination program against Covid-19 and may inform future public health policies.

Abstract Background Aquatic matrices impacted by sewage may shelter carbapenem-resistant (CR) Gram-negative bacilli (GNB) harboring resistance genes of public health concern. In this study, sewage treatment plants (STPs) servicing well-defined catchment areas were surveyed for the presence of CR-GNB bearing carbapenemase genes (bla KPC or bla NDM). Results A total of 325 CR-GNB were recovered from raw (RS) and treated (TS) sewage samples as well as from water body spots upstream (UW) and downstream (DW) from STPs. Klebsiella-Enterobacter (KE) group amounted to 116 isolates (35.7%). CR-KE isolates were recovered from TS, DW (35.7%) and RS samples (44.2%) (p = 0.001); but not from UW samples. KE isolates represented 65.8% of all bla KPC or bla NDM positive strains. The frequency of bla KPC-or-NDM strains was positively associated with the occurrence of district hospitals located near STPs, as well as with the number of hospitalizations and of sewer connections serviced by the STPs. bla KPC-or-NDM strains were recovered from ST samples in 7 out of 14 STPs, including four tertiary-level STPs; and from 6 out of 13 DW spots whose RS samples also had bla KPC-or-NDM strains. Conclusions Clinically relevant GNB bearing bla KPC-or-NDM resist sewage treatments and spread into environmental aquatic matrices mainly from STPs impacted by hospital activities.

Abstract Background Vector-borne diseases, especially arboviruses transmitted by Aedes sp. mosquitos, should be a health policy priority in Brazil. Despite this urgency, there are significant limitations in the traditional surveillance system, mainly in vulnerable areas. This study aimed to investigate the circulation of dengue (DENV), Zika (ZIKV), and chikungunya viruses (CHIKV) by laboratory syndromic surveillance (LSS) in a slum area of the Federal District of Brazil, comparing the results with traditional surveillance data. Methods LSS for acute febrile and/or exanthematous symptoms was developed at a health unit of Cidade Estrutural, in order to identify the circulation of arboviruses transmitted by Aedes sp. mosquitos. Between June 2019 and March 2020, 131 valid participants were identified and sera tested by reverse transcription polymerase chain reaction (RT-PCR) for DENV (by serotype), ZIKV, and CHIKV acute infection and by immunoglobulin M enzyme-inked immunosorbent assay (ELISA-IgM) for DENV and CHIKV 15–21 days after symptom onset, when the participant reported no respiratory signs (cough and/or coryza). The results obtained were compared with traditional surveillance data for the study area and period. Results At least three DENV-1 (2.3%), four DENV-2 (3%), and one CHIKV (0.7%) cases were confirmed in the laboratory, showing evidence of hyperendemicity even though LSS had not reached the historic peak dengue fever months in the Federal District (April–May). When the results obtained here were compared with traditional surveillance, a significant discrepancy was observed, including underreporting of CHIKV infection. Conclusions In addition to the risks posed to the study population, the area investigated with its respective socio-environmental profile may be a potential site for spread of the virus, given the cosmopolitan presence of Aedes sp. and human mobility in the Federal District. It is also suggested that traditional epidemiological surveillance may be reporting acute viral infections other than DENV as dengue fever, while underreporting other arboviruses transmitted by Aedes sp. mosquitos in the Federal District. Graphical Abstract

Abstract Background Treatment outcomes were evaluated of a cohort of new pulmonary tuberculosis (TB) cases that were rifampicin resistant, multidrug-resistant, or extensively resistant during 2013 and 2014 in Brazil. The objective of this study is to identify factors associated with unfavorable treatment outcomes for drug-resistant TB cases. Methods The Brazilian Special Tuberculosis Treatment Information System (SITE-TB) was the main data source. The independent variables were classified into four blocks (block I: individual characteristics; block II: clinical characteristics and proposed treatment; block III: treatment follow-up characteristics; and block IV: TB history). The category of successful therapeutic outcome was compared with lost to follow-up, failure, and death. Considering the multiple outcomes as the dependent variable, the odds ratios (OR) and its respective 95% confidence interval (95% CI) were estimated by multinomial logistic regression. Results After applying the exclusion criteria, 980 (98.8%) individuals were included in the study. Of these, 621 (63.4%) had successful treatment, 163 (16.6%) lost to follow-up, 76 (7.8%) failed, and 120 (12.2%) died. Important factors associated with lost to follow-up in the final model included use of illicit drugs (OR = 2.5 95% CI: 1.57–3.82). Outcome failure was associated with having disease in both lungs (OR = 2.0; 95% CI: 1.09–3.62) and using more than one or not using injectable medication (OR = 2.8; 95% CI: 1.05–7.69). Major factors for the death outcome were at least 60 years old (OR = 3.4; 95% CI: 1.90–6.03) and HIV positive (OR = 2.7; 95% CI: 1.45–4.83). Conclusions The factors associated with unfavorable treatment outcomes were different. Some of these factors are specific to each outcome, which reflects the complexity of providing care to these individuals.

Abstract Background Recently developed immunosuppressive drugs, especially TNF antagonists, may enhance the risk of granulomatous infections, including leprosy. We aimed to evaluate the leprosy detection rate in patients under immunosuppression due to rheumatological, dermatological and gastroenterological diseases. Methods We performed a systematic review of the literature by searching the PubMed, EMBASE, LILACS, Web of Science and Scielo databases through 2018. No date or language restrictions were applied. We included all articles that reported the occurrence of leprosy in patients under medication-induced immunosuppression. Results The search strategy resulted in 15,103 articles; finally, 20 articles were included, with 4 reporting longitudinal designs. The detection rate of leprosy ranged from 0.13 to 116.18 per 100,000 patients/year in the USA and Brazil, respectively. In the meta-analysis, the detection rate of cases of leprosy per 100,000 immunosuppressed patients with rheumatic diseases was 84 (detection rate = 0.00084; 95% CI = 0.0000–0.00266; I 2 = 0%, p = 0.55). Conclusion Our analysis showed that leprosy was relatively frequently detected in medication-induced immunosuppressed patients suffering from rheumatological diseases, and further studies are needed. The lack of an active search for leprosy in the included articles precluded more precise conclusions. Trial registration This review is registered in PROSPERO with the registry number CRD42018116275 .

Abstract Background Although it is known that Zika virus (ZIKV) infection during pregnancy may lead to microcephaly in the fetus, the prognostic factors associated with this tragic disorder remain unclear. We conducted a systematic review and meta-analysis to assess the prognostic factors associated with the incidence of microcephaly in congenital ZIKV infection. Methods We conducted a comprehensive search in Ovid MEDLINE, Ovid MEDLINE (R) Epub ahead of print, Embase, Embase Classic, Web of Science, CINAHL, Cochrane CENTRAL, LILACS, and various thesis databases to identify human studies reporting microcephaly associated with congenital ZIKV infection. We requested primary data from the authors of the included studies to calculate summary estimates and conduct the meta-analysis of the most prevalent factors. Results We screened 4106 titles and abstracts, and identified 12 studies for inclusion in the systematic review. The assessment of ZIKV infection and the definition of microcephaly varied among studies. A total of 6154 newborns/fetuses were enrolled; of those, 1120 (18.20%) had a diagnostic of ZIKV infection, of which 509 (45.45%) were diagnosed with microcephaly. Nine studies addressed the link between congenital ZIKV infection and neurological findings in newborns/fetuses. Half of the studies provided primary data. Three out of 11 factors of interest seem to be prognostic factors of microcephaly: infant’s sex – males compared to females: Relative Risk (RR) 1.30, 95% Confidence Interval (95% CI) 1.14 to 1.49; the stage of pregnancy when infection occurred – infection in the first trimester of pregnancy compared to infection at other stages of pregnancy: RR 1.41, 95% CI 1.09 to 1.82; and asymptomatic infection compared to symptomatic infection during pregnancy: RR 0.68; 95% CI 0.60 to 0.77. Conclusion Our findings support the female-biased resistance hypothesis and reinforce the risk associated with the stage of pregnancy when ZIKV infection occurs. Continued surveillance of ZIKV infection during pregnancy is needed to identify additional factors that could contribute to developing microcephaly in affected fetuses. Protocol registration This systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration no. CRD 42018088075 .

Abstract Background The identification of Trypanosoma cruzi and blood-meal sources in synanthropic triatomines is important to assess the potential risk of Chagas disease transmission. We identified T. cruzi infection and blood-meal sources of triatomines caught in and around houses in the state of Bahia, northeastern Brazil, and mapped the occurrence of infected triatomines that fed on humans and domestic animals. Methods Triatominae bugs were manually captured by trained agents from the Epidemiologic Surveillance team of Bahia State Health Service between 2013 and 2014. We applied conventional PCR to detect T. cruzi and blood-meal sources (dog, cat, human and bird) in a randomized sample of triatomines. We mapped triatomine distribution and analyzed vector hotspots with kernel density spatial analysis. Results In total, 5906 triatomines comprising 15 species were collected from 127 out of 417 municipalities in Bahia. The molecular analyses of 695 triatomines revealed a ~10% T. cruzi infection rate, which was highest in the T. brasiliensis species complex. Most bugs were found to have fed on birds (74.2%), and other blood-meal sources included dogs (6%), cats (0.6%) and humans (1%). Trypanosoma cruzi-infected triatomines that fed on humans were detected inside houses. Spatial analysis showed a wide distribution of T. cruzi-infected triatomines throughout Bahia; triatomines that fed on dogs, humans, and cats were observed mainly in the northeast region. Conclusions Synanthropic triatomines have a wide distribution and maintain the potential risk of T. cruzi transmission to humans and domestic animals in Bahia. Ten species were recorded inside houses, mainly Triatoma sordida, T. pseudomaculata, and the T. brasiliensis species complex. Molecular and spatial analysis are useful to reveal T. cruzi infection and blood-meal sources in synanthropic triatomines, identifying areas with ongoing threat for parasite transmission and improving entomological surveillance strategies.

Abstract Background Zika infection during pregnancy (ZIKVP) is known to be associated with adverse outcomes. Studies on this matter involve both rare outcomes and rare exposures and methodological choices are not straightforward. Cohort studies will surely offer more robust evidences, but their efficiency must be enhanced. We aim to contribute to the debate on sample selection strategies in cohort studies to assess outcomes associated with ZKVP. Main body of the abstract A study can be statistically more efficient than another if its estimates are more accurate (precise and valid), even if the studies involve the same number of subjects. Sample size and specific design strategies can enhance or impair the statistical efficiency of a study, depending on how the subjects are distributed in subgroups pertinent to the analysis. In most ZIKVP cohort studies to date there is an a priori identification of the source population (pregnant women, regardless of their exposure status) which is then sampled or included in its entirety (census). Subsequently, the group of pregnant women is classified according to exposure (presence or absence of ZIKVP), respecting the exposed:unexposed ratio in the source population. We propose that the sample selection be done from the a priori identification of groups of pregnant women exposed and unexposed to ZIKVP. This method will allow for an oversampling (even 100%) of the pregnant women with ZKVP and a optimized sampling from the general population of pregnant women unexposed to ZIKVP, saving resources in the unexposed group and improving the expected number of incident cases (outcomes) overall. Conclusion We hope that this proposal will broaden the methodological debate on the improvement of statistical power and protocol harmonization of cohort studies that aim to evaluate the association between Zika infection during pregnancy and outcomes for the offspring, as well as those with similar objectives.