ABSTRACT Background: Rabies is an anthropozoonosis that greatly impacts public health and is transmitted by infected mammals. Aggression by animals is notifiable and may result in anti-rabies post-exposure prophylaxis (PEP). This study aimed to characterize anti-rabies PEP notifications in São Paulo state, Brazil. Methods: A descriptive study was conducted using data provided by the SINAN between 2013 and 2017. Results: A total of 572,889 aggressions were recorded during the study period, characterized mostly by dogs (83.5%), single wounds (56.9%), superficial wounds (58.6%), and hands/feet (34.6%). Conclusions: Animal observation was the most frequent recommendation, even in cases of attacks from non-domestic animals.

ABSTRACT Background: Brazil has the second largest number of leprosy cases worldwide, and the state of São Paulo has been considered non-endemic since 2006. Methods: We analyzed 16 variable number tandem repeats loci and three single nucleotide polymorphisms loci of Mycobacterium leprae (M. leprae) in 125 clinical isolates from patients in different municipalities in the state. Results: The clustering pattern of M. leprae indicated that the transmission of leprosy persisted in the state and included scenarios of intra-extra-familial transmission in areas with low endemicity. Conclusions: A significantly active circulation of M. leprae was observed. Therefore, surveillance and control measures must be implemented.

ABSTRACT Background: This study aimed to describe the kinetics of Leishmania parasite load determined using kinetoplast DNA (kDNA)-based quantitative polymerase chain reaction (qPCR) in visceral leishmaniasis (VL) patients. Methods: Parasite load in blood was assessed by qPCR at five time points, up to 12 months post-diagnosis. Sixteen patients were followed up. Results: A significant reduction in the parasite load was observed after treatment (P < 0.0001). One patient had an increased parasite load 3 months post-treatment and relapsed clinically at month six. Conclusions: We have described the use of kDNA-based qPCR in the post-treatment follow-up of VL cases.

ABSTRACT Background: Bacterial resistance to extended-spectrum beta-lactamases (ESBL) is present worldwide. Empirical antibiotic therapy is often needed, and the use of fluoroquinolones, such as ciprofloxacin and norfloxacin, is common. This study aimed to analyze the urine cultures from 2,680 outpatients in January 2019, 2020, 2021, and 2022, with bacterial counts above 100,000 CFU/mL in which Escherichia coli was the etiological agent. Methods: We monitored the resistance of ESBL-positive and ESBL-negative strains to ciprofloxacin and norfloxacin and evaluated resistance rates. Results: Significantly higher fluoroquinolone resistance rates were observed among ESBL-positive strains in all years studied. Furthermore, a significant increase in the rate of fluoroquinolone resistance was observed between 2021 and 2022 in ESBL-positive and -negative strains, as well as from 2020 to 2021 among the ESBL-positive strains. Conclusions: The data obtained in the present study showed a tendency towards an increase in fluoroquinolone resistance among ESBL-positive and -negative E. coli strains isolated from urine cultures in Brazil. Since empirical antibiotic therapy with fluoroquinolones is commonly used to treat diverse types of infections, such as community-acquired urinary tract infections, this work highlights the need for continuous monitoring of fluoroquinolone resistance among E. coli strains circulating in the community, which can mitigate the frequency of therapeutic failures and development of widespread multidrug-resistant strains.

ABSTRACT Background: Malaria is a parasitosis conditioned by several factors. This study sought to analyze the spatial distribution of malaria considering environmental, socioeconomic, and political variables in São Félix do Xingu, Pará, Brazil, from 2014 to 2020. Methods: Epidemiological, cartographic, and environmental data were obtained from the Ministry of Health, Brazilian Geographical and Statistical Institute, and National Space Research Institute. Statistical and spatial distribution analyses were performed using chi-squared tests of expected equal proportions and the kernel and bivariate global Moran’s techniques with Bioestat 5.0 and ArcGIS 10.5.1. Results: The highest percentage of cases occurred in adult males with brown skin color, mainly placer miners, with a primary education level, living in rural areas, who were infected with Plasmodium vivax and with parasitemia of two or three crosses as diagnosed by the thick drop/smear test. The disease had a non-homogeneous distribution, with distinct annual parasite indices associated with administrative districts and clusters of cases in locations with deforestation, mining, and pastures close to Conservation Units and Indigenous Lands. Thus, a direct relationship between areas with cases and environmental degradation associated with land use was demonstrated, along with the precarious availability of health services. Pressure on protected areas and epidemiological silence in Indigenous Lands were also noted. Conclusions: Environmental and socioeconomic circuits were identified for development of diseases associated with precarious health services in the municipality. These findings highlight the need to intensify malaria surveillance and contribute to the systematic knowledge of malaria’s epidemiology by considering the complexity of its conditioning factors.

ABSTRACT Background: Cases of coronavirus disease 2019 (COVID-19) requiring hospitalization continue to appear in vulnerable populations, highlighting the importance of novel treatments. The hyperinflammatory response underlies the severity of the disease, and targeting this pathway may be useful. Herein, we tested whether immunomodulation focusing on interleukin (IL)-6, IL-17, and IL-2, could improve the clinical outcomes of patients admitted with COVID-19. Methods: This multicenter, open-label, prospective, randomized controlled trial was conducted in Brazil. Sixty hospitalized patients with moderate-to-critical COVID-19 received in addition to standard of care (SOC): IL-17 inhibitor (ixekizumab 80 mg SC/week) 1 dose every 4 weeks; low-dose IL-2 (1.5 million IU per day) for 7 days or until discharge; or indirect IL-6 inhibitor (colchicine) orally (0.5 mg) every 8 hours for 3 days, followed by 4 weeks at 0.5 mg 2x/day; or SOC alone. The primary outcome was accessed in the “per protocol” population as the proportion of patients with clinical improvement, defined as a decrease greater or equal to two points on the World Health Organization’s (WHO) seven-category ordinal scale by day 28. Results: All treatments were safe, and the efficacy outcomes did not differ significantly from those of SOC. Interestingly, in the colchicine group, all participants had an improvement of greater or equal to two points on the WHO seven-category ordinal scale and no deaths or patient deterioration were observed. Conclusions: Ixekizumab, colchicine, and IL-2 were demonstrated to be safe but ineffective for COVID-19 treatment. These results must be interpreted cautiously because of the limited sample size.

ABSTRACT Background: To analyze the temporal evolution of research on Neglected Tropical Diseases (NTDs) published by the Journal of the Brazilian Society of Tropical Medicine (JBSTM). Methods: We performed an analysis of the scientific production in JBSTM on NTDs using an advanced search, which included authors’ descriptors, title, and abstract, and by combining specific terms for each NTDs from 1991 to 2021. Data related to authors, countries of origin, institutions, and descriptors, were evaluated and analyzed over time. Bibliographic networks were constructed using VOSviewer 1.6.16. Results: The JBSTM published 4,268 scientific papers during this period. Of these 1,849 (43.3%) were related to NTDs. The number of publications on NTDs increased by approximately 2.4-fold, from 352 (total 724) during 1991-2000 to 841 (total 2,128) during 2011-2021, despite the proportional reduction (48.6% versus 39.5%). The most common singular NTDs subject of publications included Chagas disease (31.4%; 581/1,849), leishmaniasis (25.5%, 411/1,849), dengue (9.4%, 174/1,849), schistosomiasis (9.0%; 166/1,849), and leprosy (6.5%, 120/1,849), with authorship mostly from Brazil’s South and Southeast regions. Conclusions: Despite the proportional reduction in publications, JBSTM remains an important vehicle for disseminating research on NTDs during this period. There is a need to strengthen the research and subsequent publications on specific NTDs. Institutions working and publishing on NTDs in the country were concentrated in the South and Southeast regions, requiring additional investments in institutions in other regions of the country.

ABSTRACT Background: The World Health Organization recommends a market-ready, urine-based point-of-care diagnostic test for circulating cathodic antigens (CCA) to determine the prevalence of S. mansoni. This study evaluated the performance of the URINE CCA (SCHISTO) ECO TESTE® (POC-ECO), which is currently available in Brazil. Methods: Residents from eight sites with different prevalence estimates provided one urine sample for POC-ECO and one stool sample for Kato-Katz (KK) and Helmintex® (HTX) testing as an egg-detecting reference for infection status. Results: None of the study sites had significantly higher POC-ECO accuracy than KK. Conclusions: POC-ECO is not currently recommended in Brazilian schistosomiasis elimination programs.

ABSTRACT Background: To analyze the epidemiology, surveillance, and control strategies for trachoma in the state of Ceará, northeast Brazil, from 2007 to 2021. Methods: This ecological study was based on secondary data from the Information System on Notifiable Diseases of the Secretary of Health of the state of Ceará. Data from school and home surveys for trachoma detection obtained during the study period were analyzed, the percentage of positivity was estimated, and sociodemographic and clinico-epidemiological factors were investigated. Results: The coverage of trachoma surveillance and control actions in Ceará municipalities increased from 12.5% in 2007 to 55.9% in 2019, but with an average restriction of 8.0% during the COVID-19 pandemic. The estimated trachoma positivity (mean overall positivity) was less than 5.0% (2.76%, 95% CI 1.2-5.2), with a higher proportion of cases in the 5-9-year age group (45.0%, 95% CI 44.6-45.4), in females (53.2%, 95% CI 52.8-53.6), and rural areas (52.6%, 95% CI 52.2-53.0). Positivity above 10.0% was observed in the Litoral Leste/Jaguaribe and Sertão Central regions, with a higher occurrence of the follicular inflammatory clinical form (98.1%, 95% CI 98.0-98.2). Conclusions: Trachoma remains in the state of Ceará and is likely underreported. Despite recent advances, the fragility of health surveillance activities compromises the recognition of the actual magnitude and distribution of trachoma in the state. Accurate information is fundamental for planning, monitoring, and evaluating surveillance and disease control.

ABSTRACT Background: The spread of carbapenemase- and extended-spectrum β-lactamase (ESBL)-producing gram-negative bacilli (GNB) represent a global public health threat that limits therapeutic options for hospitalized patients. This study aimed to evaluate the in-vitro susceptibility of β-lactam-resistant GNB to ceftazidime-avibactam (C/A) and ceftolozane-tazobactam (C/T), and investigate the molecular determinants of resistance. Methods: Overall, 101 clinical isolates of Enterobacterales and Pseudomonas aeruginosa collected from a general hospital in Brazil were analyzed. Susceptibility to the antimicrobial agents was evaluated using an automated method, and the minimum inhibitory concentrations (MIC50/90) of C/A and C/T were determined using Etest®. The β-lactamase-encoding genes were investigated using polymerase chain reaction. Results: High susceptibility to C/A and C/T was observed among ESBL-producing Enterobacterales (100% and 97.3% for CLSI and 83.8% for BRCAST, respectively) and carbapenem-resistant P. aeruginosa (92.3% and 87.2%, respectively). Carbapenemase-producing Klebsiella pneumoniae exhibited high resistance to C/T (80%- CLSI or 100%- BRCAST) but high susceptibility to C/A (93.4%). All carbapenem-resistant K. pneumoniae isolates were susceptible to C/A, whereas only one isolate was susceptible to C/T. Both antimicrobials were inactive against metallo-β-lactamase-producing K. pneumoniae isolates. Resistance genes were concomitantly identified in 44 (44.9%) isolates, with bla CTX-M and bla SHV being the most common. Conclusions: C/A and C/T were active against microorganisms with β-lactam-resistant phenotypes, except when resistance was mediated by metallo-β-lactamases. Most C/A- and C/T-resistant isolates concomitantly carried two or more β-lactamase-encoding genes (62.5% and 77.4%, respectively).

ABSTRACT Background: Brazil has one of the highest numbers of COVID-19 cases and deaths. Rio Grande do Sul (RS) in southern Brazil is one of the leading states in terms of case numbers. As part of the national public health network, the State Central Laboratory (LACEN-RS) changed its routine in 2020 to focus on the diagnosis of COVID-19. This study evaluated the laboratory surveillance of COVID-19 suspected cases analyzed at the LACEN-RS in 2020. Methods: Viral detection was performed using RT-qPCR in samples from patients with respiratory infection who met the study criteria. Viral RNA was isolated using commercial manual kits or automated extractors, and SARS-CoV-2 RT-qPCR was performed using the Bio-Manguinhos/Rio de Janeiro, IBMP/Paraná, or Allplex 2019-nCoV assay. In total, 360 representative SARS-CoV-2 samples were sequenced using the Illumina platform. Results: In total, 31,197 of 107,578 (positivity rate = 29%) tested positive for SARS-CoV-2. The number of RT-qPCR tests performed per month followed the COVID-19 epidemic curve observed for the state, with peaks in July-August and December. Females accounted for 63% of the samples, whereas the positivity rate was higher among males (33.1% males vs. 26.5% females). The positivity rate was higher in adults aged 50-79 years compared to the overall positivity rate. The majority of cases were observed in the capital, Porto Alegre, and the metropolitan region. Ten distinct lineages were identified, with B.1.1.28, B.1.1.33, and P.2 being the most frequent. Conclusions: Here, we describe laboratory surveillance of COVID-19 to identify priorities for epidemiological surveillance actions in RS.

ABSTRACT Background: Egg collection traps have been studied to assist in the integrated control of arbovirus vectors. Many enhancements have been made over the years. Methods: This study evaluated the use of a hydrated superabsorbent polymer (SAP) in the egg collection of Aedes aegypti and Aedes albopictus in ovitraps. An experiment was conducted in the laboratory to determine the minimum concentration of the product to be used in traps in the field to prevent the development of larvae into adults. In the field, the use of polymers has been evaluated using a traditional model of ovitraps. The positive ovitrap index and mean number of eggs per trap indicator were calculated. Results: In the laboratory, the larvae did not successfully develop to the adult stage, even at the lowest SAP concentration. In the field, the results showed that ovitraps with SAP proved to be effective for egg collection from both species. It was possible to identify sites with the highest concentration of species and expose the ovitraps for a longer period without larval development. Conclusions: There is a need for studies on the adequacy of this technology for control programs. However, the results showed that ovitraps with hydrogel were potentiated to capture eggs, configuring themselves as another tool for vector control.

ABSTRACT Introduction: Immunogenicity has emerged as a challenge in the development of vaccines against coronavirus disease of 2019 (COVID-19). Immunogenicity is a determinant of the efficacy and safety of vaccines. This systematic review and associated meta-analysis summarized and characterized the immunogenicity of COVID-19 vaccines in randomized controlled trials (RCTs). Methods: Relevant RCTs were systematically sourced from different medical databases in August 2021. The risk ratios and mean differences with 95% confidence intervals were calculated. Results: Of 2,310 papers, 16 RCTs were eligible for review. These RCTs involved a total of 26,698 participants (15,292 males and 11,231 females). The pooled results showed a significant difference in the geometric mean titer between the vaccinated and control groups in favor of the vaccine group after 1 and 2 months of follow-up, for the young age group (18 - < 55y), and with different doses (P < 0.001). The difference in the older age group (>55y) was insignificant (P = 0.24). The seroconversion rate of spike neutralizing antibodies favored the vaccine groups 1 or 2 months after vaccination (P < 0.001). The seroconversion rate of the vaccine group was significantly different (P < 0.001) from that of the control group. Conclusions: Vaccination elicits immunogenicity in the follow-up period for all age groups and at low and large doses. Therefore, people should be encouraged to receive vaccines currently being offered. A boost dose has been asserted for the elderly.

ABSTRACT Background: Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis. In Brazil, TB is a public health problem, and the treatment dropout rate contributes to it. Methods: This systematic review investigated the factors associated with TB treatment dropout in Brazil using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. The databases used were Bireme, Scopus, PubMed, Medline, Pan-American Health Organization (PAHO), and Latin-American and Caribbean Literature on Health Sciences (LILACS). The search was conducted on May 16, 2021. Nine articles were reviewed, and all were published within the last 5 years in English, Spanish, or Portuguese. Results: The sample sizes in the studies ranged from 148 to 77,212 individuals, and the studies enrolled only adult patients (aged 18-59 years) in Brazil. Evidence suggests that the significant risk factors associated with TB treatment dropout are male sex, black race/ethnicity, age between 19 and 49 years, human immunodeficiency virus (HIV) co-infection, low education (<8 years), use of alcohol and illicit drugs, and unsupervised treatment. This study’s limitations were the small number of articles published on this topic with stronger study designs, use of secondary data sources in most articles, and a moderate to high risk of bias in most papers. Conclusions: There was a significant association between abandonment of TB treatment and HIV/acquired immunodeficiency syndrome co-infection; socioeconomic factors (low education and homelessness); use of alcohol, tobacco, and illicit drugs; and failure to use directly observed treatment. These results can guide more efficient measures to prevent dropout.