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ABSTRACT Leptospirosis is a zoonotic infection with a global distribution, though it has a greater impact on marginalized rural agricultural and urban communities in developing countries. Kidney injury, which can lead to severe and lethal infections, is the most frequent complication associated with leptospirosis. Novel biomarkers are being studied as tools for assessing kidney injury in different pathological processes to improve early detection. This review aimed to gather information on the use of novel kidney biomarkers for human leptospirosis. A search of the literature was carried out in September 2021 using the parameters “((kidney) OR (renal) OR (chronic kidney disease) OR (acute kidney injury)) AND ((biomarker) OR (marker)) AND ((Leptospira) OR (leptospirosis))”. The review identified 11 original studies that evaluated the performance of 15 kidney biomarkers related to leptospirosis. Assessment of the evidence for biomarker utility was limited because of the small number of studies and sample sizes. Although some biomarkers were associated with kidney disease, no specific biomarker appeared to be ready for clinical practice, and more research in this field is necessary.

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ABSTRACT Timely and accurate diagnosis is one of the strategies for managing visceral leishmaniasis (VL). Given the specificities of this infection, which affects different vulnerable populations, the local assessment of the accuracy of the available diagnostic test is a requirement for the good use of resources. In Brazil, performance data are required for test registration with the National Regulatory Agency (ANVISA), but there are no minimum requirements established for performance evaluation. Here, we compared the accuracy reported in the manufacturer’s instructions of commercially available VL-diagnostic tests in Brazil, and the accuracies reported in the scientific literature which were obtained after test commercialization. The tests were identified via the electronic database of ANVISA, and their accuracy was obtained from the manufacturer’s instructions. A literature search for test accuracy was performed using two databases. A total of 28 VL diagnostic tests were identified through the ANVISA database. However, only 13 presented performance data in the manufacturer’s instructions, with five immunoenzymatic tests, three indirect immunofluorescence tests, one chemiluminescence test, and four rapid tests. For most tests, the manufacturers did not provide the relevant information, such as sample size, reference standards, and study site. The literature review identified accuracy data for only 61.5% of diagnostic tests registered in Brazil. These observations confirmed that there are significant flaws in the process of registering health technologies and highlighted one of the reasons for the insufficient control of policies, namely, the use of potentially inaccurate and inappropriate diagnostic tools for a given scenario.

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ABSTRACT There is a consensus that the antifungal repertoire for the treatment of cryptococcal infections is limited. Standard treatment involves the administration of an antifungal drug derived from natural sources (i.e., amphotericin B) and two other drugs developed synthetically (i.e., flucytosine and fluconazole). Despite treatment, the mortality rates associated with fungal cryptococcosis are high. Amphotericin B and flucytosine are toxic, require intravenous administration, and are usually unavailable in low-income countries because of their high cost. However, fluconazole is cost-effective, widely available, and harmless with regard to its side effects. However, fluconazole is a fungistatic agent that has contributed considerably to the increase in fungal resistance and frequent relapses in patients with cryptococcal meningitis. Therefore, there is an unquestionable need to identify new alternatives or adjuvants to conventional drugs for the treatment of cryptococcosis. A potential antifungal agent should be able to kill cryptococci and “bypass” the virulence mechanism of the yeast. Furthermore, it should have fungicidal action, low toxicity, high selectivity, easily penetrate the central nervous system, and widely available. In this review, we describe cryptococcosis, its conventional therapy, and failures arising from the use of drugs traditionally considered to be the reference standard. Additionally, we present the approaches used for the discovery of new drugs to counteract cryptococcosis, ranging from the conventional screening of natural products to the inclusion of structural modifications to optimize anticryptococcal activity, as well as drug repositioning and combined therapies.

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ABSTRACT Venomous fish are commonly found in Brazilian waters. The most important marine venomous fish species are stingrays (Dasyatidae, Gimnuridae, Myliobatidae, and Rhinopteridae families), catfish (Ariidae family), scorpionfish and lionfish (both Scorpaenidae family), and toadfish (Batrachoididae family). Meanwhile, Potamotrygonidae stingrays and Pimelodidae catfish are the most important venomous freshwater fish. The mechanisms of envenomation vary and involve various venomous apparatuses and glands. Despite not being highly developed, these venomous apparatuses in fish appear rudimentary, using structures such as fins and rays to inoculate toxins and rarely presenting with specialized structures. Toxins are produced by glandular tissue made up of proteinaceous cells, lacking true glands, and are positioned along the inoculation structures. However, systemic manifestations are rare. No antivenom serum has been developed for any species of American venomous fish. Brazilian venomous fish and their venoms have only recently attracted attention, leading to new studies not only addressing clinical issues in humans, but also exploring the discovery of new active substances with immense pharmacological potential.

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ABSTRACT While there are conflicting data concerning interleukin (IL)-17 levels in the serum of patients with leprosy compared with those in healthy controls, higher levels have been more evident in the tuberculoid clinical form of leprosy and type 1 reactions. This review aimed to highlight the role of Th17 cells and their cytokines in leprosy. Cytokines such as IL-1β and IL-23 induce Th17, while transforming growth factor beta and IL-10 inhibit Th17, indicating that the balance between Th17 and regulatory T cells is crucial for leprosy polarization. However, more comprehensive paired studies are required to better elucidate the role of Th17 cells in leprosy.

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ABSTRACT The increase in inflammatory markers associated with persistent chronic fibrosing myocarditis, a characteristic of chronic Chagas disease, can result in a reduction in inspiratory muscle strength (IMS) in Chagas cardiomyopathy (CC). However, literature in this field is still scarce. This review aimed to map and summarize the evidence regarding IMS in patients with CC. The inclusion criteria included reports with adult participants with a CC diagnosis, with or without heart failure (HF). The core concept examined was the maximum inspiratory pressure evaluated in the untrained and trained groups in the pre-training period. The context was open, including but not limited to hospitals and health centers. Two authors independently identified eligible studies and extracted the data. Descriptive synthesis was used as the primary strategy for analyzing the results. Nine studies (five clinical trials, three cross-sectional, and one cohort) were included. The CC classification differed among the studies, with no mention of HF in five and no CC staging specification in six. IMS was assessed using a manovacuometer, and only six studies analyzed and interpreted the data concerning the predicted values. The CC population with HF appeared to have impaired IMS. All studies involved only Brazilian volunteers. In conclusion, randomized clinical trials evaluating IMS and the effects of inspiratory muscle training need to be conducted to better understand the prevalence and risk of inspiratory muscle weakness in the CC population, as well as the effects of training. Such studies should be conducted at different stages of CC in different populations and countries.

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ABSTRACT Molecular methods have been responsible for a notable increase in the detection of Leishmaniinae infections in wild animals. Determining their infectiousness is of paramount importance in evaluating their epidemiological significance. One of the most efficient ways of determining infectiousness for vector borne diseases is xenodiagnosis with the appropriate vector. However, this is logistically very difficult to accomplish in the field, and an ideal solution is to find a molecular surrogate for xenodiagnosis. In this review we discuss different approaches to the problem by focusing on the infectiousness of Leishmania (Viannia) braziliensis in rodents under laboratory and field conditions. Comparisons with similar studies for other Leishmania species emphasizes that there are pivotal differences in the infectiousness and the importance of asymptomatic infections in different hosts. Potentially the most promising surrogate is the real time quantitative PCR (qPCR). However, its success depends on choosing a tissue that relates to the vector’s feeding location and the parasite’s tissue tropism. This requires detailed knowledge of the infection of each species in its wild hosts. We conclude that for L. (V.) braziliensis infections in wild rodents the tissue of choice for a molecular xenodiagnostic test, based on the qPCR is blood, providing that a significant number of samples must be examined.

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ABSTRACT Chagas disease (CD) remains one of the most significant endemic diseases in Latin America. Approximately 30% of individuals with CD develop the cardiac form, the main determinant of morbidity and mortality, which is characterized by typical electrocardiogram (ECG) changes caused by chronic chagasic cardiopathy (CCC). This review accentuates to how crucial it is for research teams and reference centers that treat patients with CD to standardize ECG in CCC. This was a non-systematic review of the literature. ECG is the most widely used examination in the diagnosis and evaluation of CCC, and it is also employed in epidemiological surveys, risk stratification for cardiovascular events and death, and monitoring the clinical progression of the disease. Carlos Chagas and Eurico Villela published the first work addressing CCC in 1922. Other works followed, including the study by Evandro Chagas' which was the first to perform ECG in CD, culminating in Francisco Laranja's seminal work in 1956. Since the 1980s, standardizations and ECG reading codes for CD have been established. This standardization aimed to code complex arrhythmias and characteristic ventricular conduction disorders and standardize ECG readings for clinical and epidemiological studies in CD. Nearly all existing electrocardiographic abnormalities can be found in CD, with a predominance of abnormalities in the formation and conduction of cardiac stimuli. The complex and heterogeneous substrate of CD with varied electrocardiographic manifestations poses a significant challenge when comparing studies involving patients with CCC, emphasizing the need for ECG standardization in CD.

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ABSTRACT Enterobius vermicularis, an intestinal helminth, is transmitted through the ingestion of eggs found in food, water, dust, or other fomites, including infected individuals. This review aimed to examine the frequency and distribution of E. vermicularis infections in Brazil between 1991 and 2022. The conducted bibliographic survey revealed that the frequency of E. vermicularis infections in Brazil ranged from 0.1 to 26.1%, depending on factors such as population ethnicity, individual age group, geographic area, time frame, and diagnostic method. However, these findings were based on a limited number of publications, suggesting that the actual prevalence rates of E. vermicularis infection may still be unknown and potentially underestimated.

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ABSTRACT Chikungunya fever (CHIK) is a neglected tropical disease associated with chronic arthritis. CHIK is usually a self-limiting condition; however, extra-articular manifestations present as atypical illness in a minority of patients. These atypical features may mimic other conditions and potentially distract physicians from the true diagnosis. This review analyzes the evidence of many unusual extra-articular manifestations reported in cases of CHIK. Depending on the affected system, these unusual manifestations include encephalitis, myocarditis, acute interstitial nephritis, cutaneous manifestations, acute anterior uveitis, abdominal pain, and depression. In addition, coinfections and comorbidities may cause atypical illness and obscure the diagnosis. Further studies are required to clarify the pathophysiology and natural history of CHIK, as it remains a burdening condition. Exploring its atypical symptoms may be the missing scientific piece of this puzzle.

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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.

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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.

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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.

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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).

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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.

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ABSTRACT Background: Chagas disease (CD) treatment is commonly associated with a high incidence of adverse effects. It is crucial to study and update these adverse effects to improve the existing knowledge of which drugs to use and to clarify the information presented to patients. Methods: We analyzed the adverse effects of benznidazole in two cohorts of patients: a large retrospective study and a small prospective study. Results: This large retrospective study described the most and least common adverse effects in our area and characterized our Chagas disease population. This prospective study, along with a close follow-up of the treatment, detected more adverse effects and enhanced the patients’ perception of the disease and treatment. Conclusions: This information is important for preventing non-medical-related withdrawals and for removing baseless fears. Better knowledge of patients could help us provide better care.

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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.

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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.

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ABSTRACT Background: The rate of tuberculosis (TB) infection among the prison population (PP) in Brazil is 28 times higher than that in the general population, and prison environment favors the spread of TB. Objective: To describe TB transmission dynamics and drug resistance profiles in PP using whole-genome sequencing (WGS). Methods: This was a retrospective study of Mycobacterium tuberculosis cultivated from people incarcerated in 55 prisons between 2016 and 2019; only one isolate per prisoner was included. Information about movement from one prison to another was tracked. Clinical information was collected, and WGS was performed on isolates obtained at the time of TB diagnosis. Results: Among 134 prisoners included in the study, we detected 16 clusters with a total of 58 (43%) cases of M. tuberculosis. Clusters ranged from two to seven isolates with five or fewer single nucleotide polymorphism (SNP) differences, suggesting a recent transmission. Six (4.4%) isolates were resistant to at least one anti-TB drug. Two of these clustered together and showed resistance to rifampicin, isoniazid, and fluoroquinolones, with 100% concordance between WGS and phenotypic drug-susceptibility testing. Prisoners with clustered isolates had a high amount of movement between prisons (two to eight moves) during the study period. Conclusions: WGS demonstrated the recent transmission of TB within prisons in Brazil. The high movement among prisoners seems to be related to the transmission of the same M. tuberculosis strain within the prison system. Screening for TB before and after the movement of prisoners using rapid molecular tests could play a role in reducing transmission.

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ABSTRACT Background: Chagas disease (CD) is caused by Trypanosoma cruzi and transmitted by triatomines. Historical information from the 20th century demonstrates T. cruzi records in the metropolitan region of Salvador (MRS), the third largest urban agglomeration in the Brazilian Northeast and the eighth largest in Brazil, an area with intense migratory activity from CD-endemic regions. Therefore, this study aimed to evaluate CD indicators (prevalence and mortality) in the MRS. Methods: A mixed ecological and descriptive study was conducted using secondary data. We analyzed data from 2008 to 2015: deaths due to CD, self-reported cases of CD, and blood donors that were non-negative for T. cruzi infection. Results: São Francisco do Conde was one of the municipalities with the highest mortality rates due to CD. The seroprevalence rates varied by year and municipality; those with the highest values were 2008: Vera Cruz, 2009: Mata de São João, 2010: Dias D'Ávila, 2011 and 2015: São Francisco do Conde, 2012: São Sebastião do Passé, and 2013 and 2014: Pojuca. Spatial correlations between the municipalities were not detected. Conclusions: We conclude that CD is present in the MRS. The indicators analyzed in the MRS are below-state-level data. Given the importance of indicator analysis for the surveillance and control of CD at the state and national levels, it is important to strengthen the surveillance program at the municipal level, including the regions classified as low risk for T. cruzi vector transmission.

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ABSTRACT Background: This study aimed to assess the immunoglobulin G (IgG) antibody response rate in emergency department (ED) healthcare workers (HCWs) and potential adverse effects after CoronaVac vaccination. Methods: All included HCWs were grouped based on the previous history of coronavirus disease 2019 (COVID-19) and the number of vaccinations. Furthermore, the IgG antibody response was evaluated based on the sex and smoking status of HCWs. Those with a cut-off index of ≥1.00 after vaccination with CoronaVac were considered to have had COVID-19 and had an adequate humoral response. Results: Among 224 ED HCWs, 18% experienced the adverse effects of CoronaVac vaccine, the most prevalent being pain in the injection site. The IgG antibody response rate was 20% after the first dose of vaccine, while the response rate increased to 90% after the second dose. Female HCWs had higher IgG response rates compared with male HCWs (53.8 [15.9-147.0] vs 31.2 [4.5-124.0]). Non-smokers had higher IgG response rate compared with smokers (49.0 [11.5-160.5] vs 23.1 [7.4-98.5]). Conclusion: A single dose of CoronaVac does not produce a sufficient antibody response; hence, two doses are recommended. Men have a lower IgG response compared with women. Smokers had a lower IgG response rate compared with non-smokers. Therefore, it may be necessary to carefully assess the humoral responses of men and smokers when implementing a community vaccination program.

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ABSTRACT Background: This cross-sectional study compared the general impact of cutaneous leishmaniasis (CL) and patient satisfaction with treatment and health services as perceived by those undergoing different therapeutic regimens in an endemic region in South-Eastern Brazil. We also investigated the factors associated with both outcomes (general impact and satisfaction). Methods: We included 84 patients with CL treated between 2018 and 2019 with intravenous meglumine antimoniate, liposomal amphotericin B, or intralesional meglumine antimoniate therapy. Data were collected through interviews that assessed sociodemographic characteristics, comorbidity status, access and use of health services for CL diagnosis and treatment, and the items of the Cutaneous Leishmaniasis Impact Questionnaire (CLIQ). The CLIQ is a psychometric questionnaire previously validated to assess the general impact of CL on patient satisfaction with treatment and health services. Multivariate logistic regression analysis was used to identify the factors associated with high CL impact and low patient satisfaction. Results: The general impact of CL and patient satisfaction with treatment and health services were not significantly associated with the therapeutic regimen. High CL impact was associated with low family income (odds ratio [OR]:3.3; 95% confidence interval [CI]:1.0-10.3), occurrence of complications/adverse effects during treatment (OR:7.7; 95%CI:2.4-25.6), and additional costs during diagnosis and/or treatment (OR:12.1; 95% CI:2.8-52.4). Low satisfaction was associated with high disease impact (OR: 9.5; 95% CI:2.7-33.9), occurrence of complications/adverse effects (OR:4.2; 95% CI:1.3-13.0), and high family income (OR:7.1; 95%CI:1.7-28.2). Conclusions: Our data support public health policies aimed at reducing the impact of CL and its treatment as well as the use of therapy with fewer adverse effects.

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ABSTRACT Background: Leprosy is a neglected chronic infection caused by Mycobacterium leprae, that is curable. The magnitude of the disease and severity of the debilitation it causes renders leprosy a public health problem. This study aimed to analyze the endemic profile of leprosy in the Murrupula district and evaluate the socioeconomic, clinical, and serological profiles of leprosy contacts. Methods: A cross-sectional study of patients with leprosy diagnosed between 2013 and 2017 and their household and community contacts was conducted in Murrupula District, Nampula Province, Mozambique. Interviews, simplified dermatoneurological examinations, Mycobacterium leprae flow (ML Flow) tests, and Mitsuda tests were performed. Results: Most of the leprosy cases were multibacillary. The patients had some degree of physical disability. ML Flow positivity was more common in household contacts of the patients diagnosed with leprosy and in community individuals who spontaneously presented for testing. In total, 17 patients were diagnosed with leprosy. Conclusions: This study revealed an active chain of transmission, hidden prevalence, and operational deficiencies in leprosy surveillance and care. The results suggest that the implementation of a public health policy for leprosy prevention and control in Nampula Province is necessary. In future, the possibility of expanding the policy to the entire country should be considered.

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ABSTRACT Background: The long-term effects of schistosomiasis on the glomerulus may contribute to the development of chronic kidney disease. This study aimed to investigate baseline Schistosoma mansoni-Circulating Anodic Antigen (CAA) levels and their association with kidney biomarkers related to podocyte injury and inflammation in long-term follow-up after praziquantel (PZQ) treatment. Methods: Schistosoma infection was diagnosed by detecting CAA in urine using a quantitative assay based on lateral flow using luminescent up-converting phosphor reporter particles. A cutoff threshold of 0.1 pg/mL CAA was used to diagnose Schistosoma infection (baseline) in a low-prevalence area in Ceará, Northeast, Brazil. Two groups were included: CAA-positive and CAA-negative individuals, both of which received a single dose of PZQ at baseline. Urinary samples from 55 individuals were evaluated before (baseline) and at 1, 2, and 3 years after PZQ treatment. At all time points, kidney biomarkers were quantified in urine and adjusted for urinary creatinine levels. Results: CAA-positive patients had increased baseline albuminuria and proteinuria and showed greater associations between kidney biomarkers. CAA levels correlated only with Vascular Endothelial Growth Factor (VEGF) (podocyte injury) levels. Increasing trends were observed for malondialdehyde (oxidative stress), monocyte chemoattractant protein-1 (inflammation marker), and VEGF. In the follow-up analysis, no relevant differences were observed in kidney biomarkers between the groups and different periods. Conclusions: S. mansoni-infected individuals presented subclinical signs of glomerular damage that may reflect podocyte injury. However, no causal effect on long-term renal function was observed after PZQ treatment.

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ABSTRACT Background: Scorpions are a leading cause of envenomation in Brazil. The species Tityus serrulatus is associated with the most severe cases, especially in children. Despite not being endemic to the state of Santa Catarina, such occurrences have increased more than 500% in the state recently. Therefore, this study aimed to analyze the occurrence of envenomation by T. serrulatus, attended by the Center for Toxicological Information and Assistance of Santa Catarina. Methods: This was a retrospective and descriptive study of the occurrence of T. serrulatus, identified by the agency, from 2014 to 2021 in Santa Catarina, using data obtained by the BI-DATATOX system. Results: A total of 112 occurrences were classified as envenomation. Of these cases, 48.2% were recorded in the Itajaí Valley region and 33% in Greater Florianópolis. Men were involved in 59.8% of these, and the most common age group was 20-39 years (39.3%). Most envenomation occurred in urban areas (89.3%) under non-occupational circumstances (83%). Stings were more frequent on the hands (50.9%). Care was sought within 1 h after the event in 75.9% of the cases, and 94.6% were classified as mild. Conclusions: Occurrence of envenomation involving T. serrulatus in Santa Catarina increased significantly during the study period. Most cases occurred in urbanized areas, which suggests that they might have been transported from other states, and it must be considered that, in the urban environment, scorpions find a large supply of food and shelter and a reduced number of specific predators, allied to parthenogenesis.

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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.

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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.

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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.

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ABSTRACT Background: SARS-CoV-2 virus originated in Wuhan (China) in December (2019) and quickly spread worldwide. Antigen tests are rapid diagnostic tests (RDT) that produce results in 15-30 min and are an important tool for the scale-up of COVID-19 testing. COVID-19 diagnostic tests are authorized for self-testing at home in some countries, including Brazil. Widespread COVID-19 diagnostic testing is required to guide public health policies and control the speed of transmission and economic recovery. Methods: Patients with suspected COVID-19 were recruited at the Hospital da Baleia (Belo Horizonte, Brazil). The SARS-CoV-2 antigen-detecting rapid diagnostic tests were evaluated from June 2020 to June 2021 using saliva, nasal, and nasopharyngeal swab samples from 609 patients. Patient samples were simultaneously tested using a molecular assay (RT-qPCR). Sensitivity, specificity, accuracy, and positive and negative predictive values were determined using the statistical program, MedCalc, and GraphPad Prism 8.0. Results: The antigen-detecting rapid diagnostic tests displayed 98% specificity, 60% sensitivity, 96% positive predictive value, and moderate concordance with RT-qPCR. Substantial agreement was found between the two methods for patients tested < 7 days of symptom onset. Conclusions: Our findings support the use of Ag-RDT as a valuable and safe diagnostic method. Ag-RDT was also demonstrated to be an important triage tool for suspected COVID-19 patients in emergencies. Overall, Ag-RDT is an effective strategy for reducing the spread of SARS-CoV-2 and contributing to COVID-19 control.

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ABSTRACT Background: Ocular toxoplasmosis is the leading cause of infectious posterior uveitis worldwide, accounting for 30-50% of all cases in immunocompetent patients. Conventional treatment is associated with adverse effects and does not prevent recurrence. Intravitreal drug administration can improve disease outcomes and reduce side effects. Herein, we conducted a systematic review and meta-analysis on the efficacy of intravitreal injections for treating ocular toxoplasmosis. Methods: The systematic search was conducted using PubMed, SciELO, and Google Scholar with the descriptors “ocular toxoplasmosis” AND “intravitreal”. We analyzed studies that met the inclusion criteria, i.e., experimental cases in patients treated intravitreally for ocular toxoplasmosis. Considering the systematic review, we focused on the number of intravitreal injections, the therapeutic drug class, and the presence of preexisting conditions. To assess the efficacy of intravitreal injections, a meta-analysis was performed using visual acuity, side effects, disease recurrence, and inflammatory responses as variables. Results: Intravitreal injection-induced side effects were rarely observed (0.49% [0.00, 1.51%] ). The use of antiparasitic and anti-inflammatory drugs afforded improved visual acuity (99.81% [98.60, 100.00%]) and marked effectiveness in treating ocular toxoplasmosis. Conclusions: Intravitreal injections may facilitate the successful treatment of ocular toxoplasmosis. However, clinicians should carefully evaluate the presence of preexisting conditions for ocular toxoplasmosis or previous diseases, as these can impact the decision to administer intravitreal injections.

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ABSTRACT Background: We investigated the time to death and factors associated with deaths from dengue and chikungunya during the first epidemic after the introduction of the chikungunya virus in Northeastern Brazil. Methods: This retrospective cohort study was conducted in Pernambuco between 2015 and 2018. Logistic regression was used to identify independent risk factors. The probability of survival among individuals with different arbovirus infections was estimated and the survival curves were compared using log-rank tests. Results: The lethality coefficients for dengue and chikungunya viruses were 0.08% and 0.35%, respectively. The chance of death due to chikungunya infection increased progressively from the age of 40 years. At 40-49 years, the odds ratio was 13.83 (95%CI, 1.80-106.41). At 50-59 years and 60 years or older, the odds ratio was 27.63 (95%CI, 3.70-206.48); and 78.72 (95%CI, 10.93-566.90), respectively. The probability of death associated with dengue virus infection increased from the age of 50 years. Among patients aged 50-59 years and 60 years or older, the odds ratio was 4.30 (95%CI, 1.80-10.30) and 8.97 (95%CI, 4.00-20.0), respectively. Independent factors associated death were headache and age of 50 years or older for dengue; and headache, nausea, back pain, intense arthralgia, age 0-9 years or 40 years and older, and male sex for chikungunya. The ratio between mortality rates revealed that the time to death from dengue was 2.1 times faster than that from chikungunya (95%CI, 1.57-2.72). Conclusions: The time to death was shorter in patients with dengue than in those with chikungunya disease. This study reinforces the need for faster and more effective decision-making in public health services to enhance patient outcomes and minimize mortality.

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ABSTRACT Background: Safety and efficacy concerns regarding coronavirus disease 2019 (COVID-19) vaccines are common among the public and have a negative impact on their uptake. We aimed to report the adverse effects currently associated with the vaccine in Pakistan to build confidence among the population for its adoption. Methods: A cross-sectional study was conducted in five districts of the Punjab province of Pakistan between January and March 2022. The participants were recruited using convenience sampling. All data were analyzed using SPSS 22. Results: We recruited 1622 people with the majority aged between 25-45 years. Of these, 51% were female, including 27 pregnant women and 42 lactating mothers. Most participants had received the Sinopharm (62.6%) or Sinovac (17.8%) vaccines. The incidences of at least one side effect after the first (N = 1622), second (N = 1484), and booster doses (N = 219) of the COVID-19 vaccine were 16.5%, 20.1%, and 32%, respectively. Inflammation/erythema at the injection site, pain at the injection site, fever, and bone/muscle pain were common side effects of vaccination. No significant differences were observed in the adverse effect scores between all demographic variables except for pregnancy (P = 0.012) after the initial dose. No significant association was observed between any variable and the side effect scores of the second and booster doses of the vaccine. Conclusions: Our study showed a 16-32% prevalence of self-reported side effects after the first, second, and booster COVID-19 vaccinations. Most adverse effects were mild and transient, indicating the safety of different COVID-19 vaccines.

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ABSTRACT Background: The number of tuberculosis (TB) cases in prisons is higher than that in the general population and has been reported as the most common cause of death in prisons. This study evaluated the delay in the diagnosis and treatment of TB in Brazilian prisons. Methods: A retrospective cohort study was conducted between 2007 and 2015 using data from the five largest male prisons in Mato Grosso do Sul, Brazil. TB case data was collected from the National Database of Notifiable Diseases (SINAN), GAL-LACEN, and prison medical records. The following variables were recorded: prison, year of diagnosis, age, race, education, HIV status, smoking status, comorbidities, number of symptoms, percentage of cures, delay in diagnosis, patient delay, provider delay, laboratory delay, and delay in treatment. Descriptive statistics were used for the variables of interest. Results: A total of 362 pulmonary TB cases were identified. The average time between the first symptom and reporting of data was 94 days. The mean time between symptom onset and laboratory diagnosis was 91 days. The average time from symptom onset to first consultation was 80 days. The time between diagnosis and treatment initiation was 5 days. Conclusions: Delays were significant between reporting of the first symptoms and diagnosis and significantly smaller from the time between notification and start of treatment. Control strategies should be implemented to diagnose cases through active screening, to avoid delays in diagnosis and treatment, and to reduce TB transmission.

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ABSTRACT Background: Heterologous COVID-19 booster vaccination is an alternative strategy to homologous vaccination, especially in developing countries, due to shortages, delays, or unequal distribution of COVID-19 vaccines. We compared cohorts vaccinated with different vaccine combinations to investigate whether a heterologous booster dose of mRNA-based BNT162b2 vaccine boosts the immune response in individuals primed with the CoronaVac vaccine. Methods: Anti-RBD IgG is generally measured 4 weeks after primary immunization and 4 weeks after booster vaccination. Data on anti-receptor-binding domain (anti-RBD) IgG antibody titers and clinical characteristics were provided by infection control units. Results: The highest median anti-RBD IgG antibody titers (14589 AU/mL) after primary immunization was observed in the group vaccinated with two doses of BNT162b2 vaccine. Antibody titers were lower 4 months or more after the second CoronaVac vaccine dose in CoronaVac recipients with or without previous COVID-19. In the homologous COVID-19 booster vaccine group (primed with two doses of CoronaVac 4 weeks apart and a single booster dose of CoronaVac) the median anti-RBD titers decreased from 1025 to 242 AU/mL before the booster dose. In the heterologous group (primed with two doses of CoronaVac 4 weeks apart and a single booster dose of BNT162b2), the median anti-RBD titer increased to 31624 AU/mL, a 132-fold increase, 16 days after the booster dose. Conclusions: After the second dose of CoronaVac, protective neutralizing antibody levels decrease over time, and a booster dose is required. Heterologous COVID-19 booster vaccination with BNT162b2 is effective at boosting neutralizing antibody levels.

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ABSTRACT Background: Autophagy can inhibit the survival of intracellular microorganisms including Mycobacterium tuberculosis (Mtb), and the PI3K/AKT/mTOR pathway plays a crucial role. This study investigated the association between PI3K/AKT/mTOR pathway autophagy-related gene polymorphisms and pulmonary tuberculosis (PTB) susceptibility. Methods: KEGG pathway and gene ontology (GO) databases were searched for genes belonging to the PI3K/AKT/mTOR and autophagy pathways. Thirty SNPs in nine genes were identified and tested for their associations with tuberculosis in 130 patients with PTB and 271 controls. We constructed genetic risk scores (GRSs) and divided the participants into 3 subgroups based on their GRSs:0-5, 6-10, and 11-16. Results: This analysis revealed that the AKT1 (rs12432802), RPTOR (rs11654508, rs12602885, rs2090204, rs2589144, and rs2672897), and TSC2 (rs2074969) polymorphisms were significantly associated with PTB risk. A decreasing trend was observed (P trend 0.020), in which a lower GRS was associated with a higher risk of PTB ([6-10] vs. [0-5]: OR (95%CI) 0.590 (0.374-0.931); [11-16] vs. [0-5]: OR (95%CI) 0.381 (0.160-0.906)). Conclusions: Polymorphisms in AKT1, RPTOR, and TSC2 may influence susceptibility to PTB.

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ABSTRACT Background: This study examined the relationship between levels of the chemokines CXCL9, CXCL10, CXCL11, and CXCR3 and mortality in patients with COVID-19.. Methods: A total of 71 patients hospitalized with COVID-19 and 35 health workers with no symptoms and negative SARS-CoV-2 PCR results were included in the study. CXCL9, CXCL10, CXCL11, and CXCR3 levels were measured in blood samples using enzyme-linked immunosorbent assays. Participants were divided into three groups: healthy individuals, patients with mild to moderate pneumonia, and patients with severe pneumonia. Patients were also divided into sub-groups according to the outcome: dead and survived. Results: Serum CXCL9, CXCL10, CXCL11, and CXCR3 levels were significantly higher in patients with severe COVID-19 than in those with non-severe COVID-19; were higher in both patient groups than in the control group; and were higher in patients who died than in those who survived. Lymphocyte counts, and fibrinogen and PaO2/FiO2 levels were significantly lower in patients with severe COVID-19 than in those with moderate disease. Patients with COVID-19 also had elevated neutrophil/lymphocyte ratios, neutrophil counts, and lactate dehydrogenase, C-reactive protein, D-dimer, and ferritin levels. Conclusions: This study confirmed that CXCL9, CXCL10, CXCL11, and CXCR3 levels are associated with disease severity in patients with COVID-19. These laboratory parameters can help to estimate disease severity and predict outcomes, and are useful in clinical decision-making.

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ABSTRACT Background: Complications of leprosy neuritis are considered serious and apparent, with the potential to disable and/or limit individuals. These complications affect not only a patient’s physical functioning, but also their family and social lives, while directly impacting the ability to work and/or maintain financial independence, subsequently interfering with their overall quality of life. The present review, therefore, aimed to analyze the effectiveness of neurolysis as an alternative treatment for the complications associated with leprosy neuritis. Methods: The present review was performed based on the Joanna Briggs Institute methodology, in an effort to answer the following research question: what is the effectiveness of neurolysis as a treatment for leprosy neuritis complications? This research question was defined using the patient-intervention-outcome (PIO) framework, where leprosy represents ‘P’, neurolysis for ‘I’, and neuropathic pain/motor function/sensorial function/physical disability/quality of life for ‘O’. Randomized and non-randomized clinical trials and prospective observational cohort studies were included in the present review, with no time or date restrictions. Results: The present review included 1 randomized clinical trial and 10 prospective studies, published between 1976 and 2020. All of the outcomes showed improvement, with relief from neuropathic pain being the primary finding. Conclusions: The evidence obtained in the present review suggested that neurolysis is an effective alternative for the treatment of physical disabilities, the recovery of sensory and motor function, the restoration of quality of life, and neuropathic pain relief.

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ABSTRACT Background: The 2019 coronavirus (COVID-19) has precipitated a significant public health crisis. Our study aimed to evaluate the prevalence and risk factors associated with adverse reactions to the inactivated CoronaVac vaccine. Methods: The study involved voluntary health workers who received CoronaVac vaccine. We documented the sociodemographic information of 2,019 participants who volunteered for our study. Of these, 1,964 and 1,702 participants were interviewed by phone 1 month after the first and second dose, respectively, during which they were queried about any adverse reactions. Results: Within the first week after the first dose, adverse reactions were observed in 856 (43.3%) participants, with 133 (6.7%) experiencing them during the second week, and 96 (4.9%) people at the end of the first month. For the second dose, 276 individuals (16.2%) reported adverse reactions. The prevalence of both local and systemic adverse events ranged from 9.5-11.2% overall. Fatigue was the most common adverse reaction overall, while pain at the injection site was the most frequent local adverse reaction. Conclusions: The evaluation of both systemic and local side effects revealed no significant adverse reactions to the inactivated CoronaVac vaccine (Sinovac Life Sciences, Beijing, China). Our study found that the incidence of systemic and local adverse responses to the CoronaVac vaccination was lower than the rates reported in studies involving the recombinant adenovirus type-5, BNT162b1, and ChAdOx1nCoV-19 COVID-19 vaccines, all of which underwent the World Health Organization LULUC/PQ evaluation process.

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ABSTRACT Background: Brazil ranks first in the number of snakebites in South America. A detailed analysis of these cases is required to improve the public health planning. In this study, we retrospectively examined the clinical and epidemiological profiles of snakebites in Maranhão between January 2009 and December 2019. Methods: Data were obtained from the compulsory notification forms provided by the Health Department of Maranhão. Results: A total of 17,658 cases were recorded during the study period. Most of the bites were from snakes belonging to the genus Bothrops. Medical care was mostly within three hours after the bite. Most cases were classified as mild and most victims recovered; however, 139 deaths were recorded. Most bites occurred among people aged 20-39 years, mainly among rural workers. The most frequent local clinical manifestations were pain, edema, and ecchymosis. The most common systemic clinical manifestations include neuroparalysis, vagal syndrome, and myolysis. Most snakebites occurred between January and March. The municipalities with the highest number of notifications were Buriticupu (936 cases), Arame (705 cases), and Grajaú (627 cases). Conclusions: The clinical profile of snakebites in Maranhão is similar to that observed in other states of Northeast Brazil. However, we found that some systemic manifestations are not compatible with the etiology of snakebites, which leads us to believe that the problem could be the lack of knowledge of the health professionals at the site of envenomation, who may not be ready for attendance, and an important lack of health centers with snake antivenom to treat snakebites.

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ABSTRACT Background: Women living with human immunodeficiency virus (HIV) (WLWH) are more likely to be infected with the oncogenic human papillomavirus (HPV). We assessed the prevalence of high-risk (HR) (16/18/31/33/35/39/45/51/52/56/58/59/68/73/82), probable high-risk (pHR) (26/53/66), and low-risk (LR) (6/11/40/42/43/44/54/61/70) HPV types and their associated risk factors. Methods: This cross-sectional study of WLWH aged 18-64 years included one laboratory and eight HIV-specialty healthcare facilities in the pilot network. Descriptive statistics were used to assess sociodemographic and behavioral characteristics. Adjusted analyses were conducted to evaluate risk factors associated with HR and/or pHR HPV infection in WLWH. Results: From May/2021 to May/2022, 1,914 (92.5%) WLWH participated in the pilot study and had valid HPV-DNA results of self-collected vaginal samples. The median age of the participants was 45 years, 60.1% had ≥ 9 years of schooling, 80.5% were ≤ 18 years at first sexual intercourse, and 51.7% had > 4 sexual partners throughout life. The prevalence of any HPV type, HR HPV, pHR HPV, and LR HPV was 65.8%, 49.6%, 16.7%, and 40.0%, respectively. Age was inversely associated with pHR and/or HR-HPV (p < 0.001), and education level was inversely associated with HR-HPV (p = 0.003) types. Any HR or pHR was associated with being single (p = 0.029) and exchanging sex for drugs (p = 0.037). Conclusions: The prevalence of HPV, especially HR HPV, among WLWH is high in Brazil, highlighting the need for HPV screening in this population. Self-collection of vaginal samples is an important strategy for increasing testing access.

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ABSTRACT Background: Multidrug-resistant tuberculosis (MDR-TB) is a serious global public health concern associated with social vulnerability. In Brazil, the Unified Health System (SUS, Portuguese) provides free diagnosis and treatment for MDR-TB; however, other expenses may still be incurred for patients and their families which, according to the World Health Organization (WHO), can be catastrophic when these costs surpass 20.0% of the annual household income. This study aimed to assess the extent of catastrophic costs related to the diagnostic and therapeutic aspects of MDR-TB among patients receiving care at an outpatient clinic in Rio de Janeiro. Methods: This prospective study used convenience sampling from July 2019 to June 2021. Data regarding direct and indirect costs were collected using a standardized questionnaire endorsed by the WHO. To analyze any impoverishment occurred from MDR-TB, a threshold established by the Brazilian Institute of Geography and Statistics for 2019 and 2020 of US$ 79,562 and US$ 94,5273, respectively, was applied. Descriptive statistics were used for data analysis, including mean; standard deviation; variation coefficient; median; and maximum, minimum, and interquartile ranges. Results: A total of 65 patients were interviewed. Among the participants, 73.8% experienced catastrophic costs, with indirect costs exerting the most significant impact (median: US$ 3,825.9), in contrast to direct costs (median: US$ 542.7). When comparing the periods before and after diagnosis, the prevalence of poverty increased from 12.0% to 28.0%. Conclusions: Despite the support from the SUS in Brazil, diagnostic and therapeutic cascades incur additional costs, exacerbating social vulnerability among patients with MDR-TB.

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ABSTRACT Background: Chagas disease (ChD) is a neglected tropical disease that is caused by the protozoan parasite Trypanosoma cruzi and can negatively impact quality of life (QoL). This study aimed to assess and compare QoL between individuals with and without ChD. Methods: This cross-sectional study was performed within a concurrent cohort study (REDS). The participants were derived from two blood donation centers: São Paulo capital and Montes Claros, Minas Gerais, Brazil. Participants with ChD were identified in blood donations by serological diagnosis between 2008 and 2010, and those without ChD were donors with negative serology identified during the same period. QoL was assessed using the World Health Organization Quality of Life-BREF questionnaire. Logistic regression was used to compare sociodemographic and clinical characteristics between the groups, and mean, standard deviation, and beta regression were used to compare QoL. Results: In total, 611 individuals participated in the study (328 with ChD and 283 without ChD). Participants with ChD had lower QoL in the physical (p=0.02) and psychological (p<0.01) domains than did individuals without CD. Conclusions: Individuals with ChD had worse QoL perceptions. These results provide a comprehensive understanding of the impact of ChD on individuals' QoL, while also highlighting potential opportunities for improving the care and treatment of those affected.

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ABSTRACT Background: Gonorrhea is not a notifiable disease in Brazil, and the national health information system does not collect data on reported cases or infection prevalence. Methods: We compiled published data on gonorrhea prevalence in Brazil from cross-sectional surveys and clinical trials between 2000 and 2020. The study entry criteria included a sample size of 50 or more, and Neisseria gonorrhoeae infection detected in urine, urethral, anal, or cervicovaginal specimens using either Nucleic Acid Amplification Test or culture. Gonorrhea prevalence trends between 2000 and 2020 were generated using Spectrum-STI, a statistical trend-fitting model. Results: Forty-five studies with 59 gonorrhea prevalence data points were identified. Fifty data points were for women and represented 21,815 individuals, eight for men encompassing a total of 4,587 individuals, and one for transgender people comprising 345 individuals. The Spectrum-STI estimate for the prevalence of urogenital infection with gonorrhea in women 15-49 in 2020 was 0.63% (95% confidence interval (CI): 0.13-2.23) and was lower than the 1.05% estimated value for 2000 (95% CI: 0.36-2.79). The corresponding figures for men were 0.70% (95% CI: 0.16-2.44) and 1.14% (95% CI: 0.34-3.15). Anal prevalence estimates could not be generated because of insufficient data (three data points). Conclusions: These results suggest that the overall prevalence of genitourinary gonococcal infections in Brazil is less than 1%. Data on gonorrhea prevalence in men and in populations at increased STI vulnerability are limited.

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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.

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ABSTRACT Background: Mucormycosis is a severe invasive fungal disease. During the coronavirus disease 2019 (COVID-19) pandemic, outbreaks have been reported worldwide, but epidemiological studies are still scarce in Brazil. Methods: We conducted a time-series cohort hospitalization study (2010-2021) in southeastern Brazil. Results: There were 311 cases (85 during the pandemic), with significant (P < 0.05) involvement of patients older than 40 years (84%), white patients (78%), rhinocerebral site (63%), and São Paulo State residents (84%). Conclusions: Mucormycosis hospitalizations were highly prevalent. Further studies are needed to assess the burden of COVID-19 on mucormycosis in Brazil.

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ABSTRACT Background: We evaluated the association between polymorphisms in the tumor necrosis factor alpha (TNF-α) (-G308A) gene and upper gastrointestinal bleeding (UGIB) in schistosomiasis. Methods: This was a transverse study involving 294 Brazilian patients infected with Schistosoma mansoni. Results: The homozygous A/A genotype in TNF-α (-G308A) showed a risk association (prevalence ratio = 1.90, p = 0.008) with UGIB. There was no statistically significant difference in serum TNF-α levels between the clinical groups. Conclusions: The polymorphic TNF-α (-G308A) can be a risk factor for UGIB, in addition to being a potentially predictive factor for the severity of UGIB in schistosomiasis.

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ABSTRACT Background: Mansonia mosquitoes transmit arboviruses to humans. This study describes the karyotypes and C-banding of Mansonia humeralis, Mansonia titillans, Mansonia pseudotitillans, and Mansonia indubitans. Methods: From the 202 larvae, the brain ganglia were dissected (n=120) for the preparation of slides. Twenty slides with well-distended chromosomes for each species (10 for karyotyping and 10 for C-banding) were selected for further study. Results: The haploid genome and the average lengths of the chromosomal arms differed in relation to the centromere between species, and intraspecific differences also occurred in the distribution of the C-bands. Conclusions: These results are useful for better understanding of the chromosomal variability of Mansonia mosquitoes.

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ABSTRACT Background: Sporotrichosis, a cosmopolitan mycosis caused by dimorphic fungi of the Sporothrix complex, affects humans and animals. This study aimed to develop new molecular markers for Sporothrix genome detection in biological samples using PCR. Methods: A specific region of DNA sequences from the Sporothrix genus, publicly available in GenBank, was chosen for primer design. After testing the in silico specificity of these primers, in vitro specificity was evaluated using the PCR technique. Results: Three specific primers with 100% specificity for the Sporothrix genus were generated. Conclusions: PCR using the designed primers can be used to develop molecular diagnostics for sporotrichosis.

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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.

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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.

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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.

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ABSTRACT Background: Triatomines infest atypical public spaces in the Western Amazon. Methods: Frequent visitors to these spaces captured the insects in the state of Acre, Brazil (Rio Branco and Cruzeiro do Sul). Results: Six insects were found in a penitentiary, a church, a school, a university, a hospital, and a health center. Five of the insects were adults (three positive for Trypanosoma cruzi) and one was a nymph. Conclusions: This is the first report of triatomine occurrence in schools or churches. These data are important for implementing surveillance strategies and alerting individuals about possible changes in Chagas disease transmission dynamics.

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ABSTRACT Background: Malaria is one of the leading causes of morbidity worldwide, and patient adherence to prescribed antimalarials is essential for effective treatment. Methods: This cross-sectional study, with in-depth telephone interviews, analyzed participants’ perceptions of short message service (SMS) in adherence to treatment. Results: Five thematic categories emerged: decreased forgetfulness, the novelty of the tool, easy-to-understand language, the impact of SMS messages during treatment, and suggestions for improvement and complaints. Conclusions: SMS could assist patients in adhering to prescribed antimalarials.

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ABSTRACT Background: We report the presence of Triatoma longipennis for the first time in two localities in Hidalgo, Mexico. Methods: This study was conducted at Tecozautla municipality, Hidalgo. Collection was performed in April 2022. Results: We collected eight triatomines from Guadalupe: two fourth-instar nymphs, three fifth-instar nymphs, one female, and two males. In San Miguel Caltepantla, a female was collected inside a dwelling. One sample tested positive for Trypanosoma cruzi. Conclusions: These findings suggest the need to investigate the dynamics of this species with respect to the inhabitants of the study area.

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ABSTRACT Background: Snakebite is a neglected global health problem with high morbidity. We describe compartment syndrome (CS) cases related to snakebites by Bothrops spp. Methods: The medical records of patients admitted with snakebites envenomation were reviewed. Results: Of 47 patients with Bothrops spp. envenomation (4 male; mean age: 42 years), 7 (15%) developed CS. The mean time to antivenom administration was 9.5 hours. The time to fasciotomy was variable. Seven patients developed infection and four had acute kidney injury. Conclusions: The incidence of CS is higher than that reported previously. This may be due to the clinical severity and long delay before administering antivenom.

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ABSTRACT Background: Triatominae are vectors of the protozoan Trypanosoma cruzi, the causative agent of Chagas disease. This study aims to report an infestation on Triatominae colonies by a beetle, previously identified as a pest. Methods: The management of these colonies should be improved to maximize their usefulness, and factors that may cause harm to them should be avoided as much as possible. Results: This is the first report on a coleopteran infestation on living Triatominae colonies worldwide. Conclusions: The present record provides an important warning to researchers who maintain insectaries in general, especially those who rear triatomines, to carry protective measures against such invasions.

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ABSTRACT Background: We aimed to evaluate the costs of GenoType® MTBDRplus and MTBDRsl incurred during the diagnosis of first- and second-line drug-resistant tuberculosis (TB) in São Paulo, Brazil. Methods: Mean and activity-based costs of GenoType® were calculated in a referral laboratory for TB in Brazil. Results: The mean cost value and activity-based cost of GenoType® MTBDRplus were USD 19.78 and USD 35.80 and those of MTBDRsl were USD 54.25 and USD 41.85, respectively. Conclusions: The cost of GenoType® MTBDRplus was reduced owing to the high number of examinations performed and work optimization.

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ABSTRACT Background: Leptospirosis represents a One Health issue, affecting humans and animals. This study investigated pathogenic leptospires in small wild rodents in São Paulo, Brazil. Methods: Kidney samples from 164 rodents underwent qPCR testing, targeting pathogenic Leptospira spp. Results: Thirty-five animals (21.34%) tested positive, including five rodent species: Akodon montensis (2/21; 9.5%), Necromys lasiurus (1/4; 25%), Oligoryzomys nigripes (24/92; 26.1%), Oligoryzomys flavescens (5/26; 19.2%), and Sooretamys angouya (3/14; 21.4%). Botucatu municipality exhibited the highest prevalence, with 42.5% (20/47) of the animals testing positive. Conclusions: The presence of Leptospira spp. in wild rodents suggests they may be chronic carriers, contaminating the environment.

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ABSTRACT Background: An external quality assessment on the identification of triatomines within the laboratory network in the state of Rondônia. Methods: Seven laboratories participated in this evaluation. Each was provided with support materials and nine insects from the Hemiptera order for identification. Results: All samples were accurately identified at the species level. However, correct sex identification was achieved for only 79% of the samples. The most significant challenges were encountered in determining the sex of predators, phytophagous species, Rhodnius robustus, and Rhodnius pictipes. Conclusions: The identified shortcomings can inform enhancements in vector control programs for Chagas disease.

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ABSTRACT Introduction: Chikungunya chronic joint disease causes debilitating arthralgia, significantly impacting the quality of life of affected individuals. Methods: In this study, patients underwent clinical follow-ups, joint biopsies, and pre-biopsy and 24 months post-biopsy serum dosage of cytokines. Results: All participants were female and had pain in 12 joints on average, with 41.17% exhibiting moderate disease activity. Histopathological analysis revealed collagen deposition. Indirect immunofluorescence detected the CHIKV glycoprotein E1 antigen, and an increase in cytokines. Conclusions: Persistent inflammation and ineffective antiviral immune responses leading to antigen persistence may contribute to chronic CHIKV arthritis.

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ABSTRACT Introduction: By July 2023, Brazil had administered approximately 540 million COVID-19 vaccine doses. This study aimed to quantify wasted doses resulting from dead space in vaccine supplies. Methods: The vaccine supply was initially weighed, filled with distilled water, and expelled to simulate administration. Weighing it again after the application determined the dead space volume. Descriptive analyses calculated the waste rate/wasted dose count. Results: The estimated total number of wasted vaccine doses using supplies with the lowest dead space was 62,097,338. Conclusions: Syringe dead space is a crucial factor in dose wastage, directly influencing the number of wasted doses.

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ABSTRACT Background: Bloodstream infections (BSI) are a global health issue, leading to high mortality and morbidity among hospitalized patients. Methods: A retrospective, observational and descriptive study was conducted by reviewing blood culture records collected from patients with suspected BSI, between January 2017 and December 2019. Results: The most frequent antimicrobial resistant (AMR) pathogens were methicillin-resistantStaphylococcus aureus(MRSA) (40%), methicillin-resistantS. epidermidis (MRSE) (9.5%), and extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (35.3%). Conclusions: Our findings underscore the importance of continued vigilance and advocate for the rational use of antimicrobial agents.

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ABSTRACT Background: Here, Leishmania presence in sand flies from Três Lagoas, Mato Grosso do Sul, Brazil, after visceral leishmaniasis (VL) was investigated. Methods: In April 2022, two light traps were deployed within and around the residence for two days post-VL case report. Results: A total of 120 Lutzomyia longipalpis were collected. Suprapyloric flagellates were found in a female sand fly with eggs and residual blood during midgut dissection. Sequencing of ITS1 and cytb fragments confirmed Leishmania infantum DNA and identified Homo sapiens as the blood source, respectively. Conclusions: This study emphasizes the importance of monitoring sand flies in VL endemic areas.

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ABSTRACT Background: Systematic data on the occurrence of tungiasis are scarce. Methods: We analyzed data on tungiasis in humans and animals from all municipalities of Ceará State, Northeast Brazil, using a rapid assessment questionnaire. Results: Among the 184 municipalities, 181 (98.3%) reported tungiasis in the past (before 2021) or currently, 120 (65.2%) reported current occurrence, 155 (84.2%) reported severe cases in the past or currently, 47 (25.5 %) reported severe cases currently, and 132 (71.7%) reported tungiasis in animals. Conclusions: Tungiasis is a significant public health concern in Ceará. A One Health approach is required to reduce the disease burden in humans and animals.

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ABSTRACT Differential diagnosis of coronavirus disease 2019 (COVID-19) from other febrile diseases is one of several challenges imposed by the pandemic. We present a case of severe malaria and COVID-19 coinfection in a non-malaria-endemic region. A 44-year-old female with malaise, fever, hypotension, jaundice, and enlarged liver and spleen was admitted to the intensive care unit. Reverse transcription-quantitative PCR results for severe acute respiratory syndrome coronavirus 2 were positive. Rapid tests, microscopy, and quantitative PCR were positive for Plasmodium vivax. Cytokine storm profiles were identified. We could not determine whether the severe vivax malaria in our patient was triggered by COVID-19 coinfection.

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ABSTRACT Paracoccidioidomycosis (PCM) is a systemic fungal infection caused by Paracoccidioides species. Chylothorax is a rare complication of PCM. A 16-year-old adolescent presented daily fever, lymphadenomegaly, sweating, weight loss, ventilatory-dependent pain, and dysphagia, which confirmed PCM. During treatment, the patient developed chylothorax and chylous ascites. Chronic inflammatory and fibrotic lymphadenopathy may obstruct lymphatic vessels, resulting in the extravasation of lymph into the abdomen or pleural cavities. Chylothorax is one of several complications of PCM and can lead to respiratory insufficiency, even in patients undergoing antifungal therapy.

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ABSTRACT The Cogan’s sign is indicative of myasthenia gravis. This is the first report of neurological signs in a patient with post-COVID-19 vaccine-associated myasthenia gravis in Brazil. In this case, a previously healthy 68-year-old woman presented with proximal limb weakness, left ptosis, and diplopia 1 month after receiving her fourth dose of the COVID-19 vaccine. Neurological examination revealed the presence of Cogan’s sign, and she recovered rapidly after treatment. To our knowledge, this is the first reported case of myasthenia gravis associated with the COVID-19 vaccine in Brazil.

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ABSTRACT Erythema multiforme (EM), an immune-mediated skin condition, can occur after infection or following the use of medications. In this study, we describe a patient who developed EM after nirmatrelvir/ritonavir administration. An 81-year-old woman presented with fever and dyspnea. Laboratory investigations showed positive coronavirus disease (COVID-19) based on polymerase chain reaction assay, and she received a 5-day regimen of nirmatrelvir/ritonavir. We observed development of EM after this treatment and initiated prednisone (1 mg/kg) therapy, which led to rapid improvement. Our study is the first to report EM in a patient with COVID-19, who received nirmatrelvir/ritonavir and showed a favorable response.

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ABSTRACT Congenital and gestational syphilis are increasingly prevalent multisystemic infections in Brazil. This study aimed to present a case series of three children diagnosed with congenital syphilis even though their mother had unreactive treponemal tests. The VDRL (Venereal Disease Research Laboratory) titers of a 22-year-old mother with three pregnancies decreased after treatment. The mother did not have a reactive treponemal test, but all the three children were diagnosed with early congenital syphilis. This case series highlights the difficulty in diagnosing gestational and congenital syphilis in Brazil.

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ABSTRACT Extrapulmonary tuberculosis associated with immune thrombocytopenia (ITP) is extremely rare. A likely association between ITP and pulmonary and lymph node tuberculosis was reported in a 29-year-old male patient. His platelet count decreased to 4,000/µL. Chest tomography revealed mediastinal adenomegaly, lymph node clusters in the aorta, and consolidation in the left upper lung lobe. Immunoglobulin and methylprednisolone were administered intravenously. The histopathology of the left upper lung lobe confirmed tuberculosis. The rifampicin/isoniazid/pyrazinamide/ethambutol regimen was initiated, and the corticosteroids were tapered off. This case suggests an association of tuberculosis with ITP, since the platelet count effectively normalized after tuberculosis treatment.

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ABSTRACT Shewanella algae are gram-negative bacteria commonly found in aquatic environments. Infections caused by this agent are rarely documented; however, they are increasingly reported, mainly in countries with warm to temperate climates. Herein, we present a case of a 46-year-old immunocompetent woman with acute cellulitis and S. algae bacteremia (the first isolation culture performed at our hospital). To better understand the epidemiology, clinical outcomes, and treatment possibilities for S. algae bacteremia, we searched literature for similar cases; however, we did not find any cases of infections caused by this microorganism reported in Portugal or the Azores.

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ABSTRACT Mycetoma is a neglected tropical disease caused by fungi (eumycetoma) or bacteria (actinomycetoma), with high morbidity. Gordonia spp. are gram-positive bacteria that have previously been reported to cause mycetoma. Here, we report a case of Gordonia soli (initially misidentified as Nocardia spp.) as the etiological agent of actinomycetoma in a 64-year-old patient. After a literature search in the Cochrane Library, LILACS, SciELO, MEDLINE, PubMed, and PubMed Central databases, we concluded that this is the first case report of mycetoma caused by Gordonia soli. The current case highlights the importance of microbiological diagnosis of mycetoma and the challenges in its management.

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ABSTRACT We report the first pediatric case of a Jaguajir agamemnon scorpion sting. This case occurred in the state of Paraná and is the first record of this species in southern Brazil. The patient was admitted within 15 min, with pain, local edema, erythema, whole-body pruritus, and tongue paresthesia within the first two hours, which disappeared thereafter. The patient’s condition was considered mild, with a positive outcome, and she recovered completely.

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ABSTRACT Herein, we report two cases of severe mpox in patients with advanced acquired immunodeficiency syndrome from Brazil who developed atypical lesions and prolonged illness, one of whom had a fatal outcome. Both patients experienced serious complications involving the perianal and genital regions and prolonged disease with persistent viremia.

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ABSTRACT Visceral Leishmaniasis (VL) is a potentially fatal disease and may be associated with primary or acquired immunodeficiencies. There are few reports, in the literature, of inborn errors of immunity. Here, we report two cases of VL as a marker of inborn errors of immunity, namely, GATA2 and RAB27A deficiency. Our data suggest that VL patients should be screened for primary immunodeficiency, particularly in cases of VL relapse.

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ABSTRACT Crotalic envenomation is responsible for approximately 8%-13% of ophidism cases in Brazil, yet it is associated with the highest mortality among snakes. We describe the case of a patient bitten by a rattlesnake who developed ventilatory muscle paralysis within hours after envenomation. While diaphragmatic paralysis is a rare late neurotoxic event following crotalic envenomation, in this case, paralysis occurred early but was rapidly reversed after antivenom administration. This report discusses potential contributing factors based on a comprehensive literature review.