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ABSTRACT Immunocompromised individuals were considered high-risk for severe disease due to SARS COV-2 infection. This study aimed to describe the safety of two doses of COVID-19 adsorbed inactivated vaccine (CoronaVac; Sinovac/Butantan), followed by additional doses of mRNA BNT162b2 (Pfizer/BioNTech) in immunocompromised (IC) adults, compared to immunocompetent/healthy (H) individuals. This phase 4, multicenter, open label study included solid organ transplant and hematopoietic stem cell transplant recipients, cancer patients and people with inborn errors of immunity with defects in antibody production, rheumatic, end-stage chronic kidney or liver disease, who were enrolled in the IC group. Participants received two doses of CoronaVac and additional doses of mRNA BNT162b2. Adverse reactions (AR) data were collected within seven days after each vaccination. Serious adverse events and of special interest (AESI) were monitored throughout the study. We included 241 immunocompromised and 100 immunocompetent subjects. Arthralgia, fatigue, myalgia, and nausea were more frequent in the IC group after CoronaVac. Following the first additional dose of mRNA BNT162, pain, induration, and tenderness at injection site, fatigue and myalgia were more frequent in the H group. A heart transplant recipient had a graft rejection temporally associated with the second CoronaVac dose, but there was no literature evidence of causal association. Four cases of AESI were considered related to the vaccine: three erythema multiforme after CoronaVac, all in IC participants, and one paresthesia after mRNA, in a H participant. Our findings were comparable to other studies that evaluated the safety of COVID-19 vaccines in different immunocompromised populations. Both vaccines were safe for immunocompromised participants.

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ABSTRACT Rhodococcus equi is an opportunistic soil-borne bacterium that is eliminated in feces of multi-host animals. An increase in multidrug-resistant R. equi isolates has been reported in humans and domestic animals, and it has been hypothesized that the treatment of R. equi in foals could increase the selective pressure on multidrug-resistant isolates and favor human infections by resistant isolates. We investigated the in vitro antimicrobial susceptibility/resistance of 41 R. equi strains from humans, which were isolated from patients with pulmonary signs, using 19 antimicrobials from 10 distinct classes, recommended exclusively to humans, recommended exclusively to domestic animals and used in both. All isolates were subjected to mass spectrometry and identified as R. equi. Among the antimicrobials used exclusively in humans, tigecycline and vancomycin showed 100% efficacy. Amikacin, amoxicillin/clavulanic acid, imipenem, levofloxacin, clarithromycin, rifampin, ciprofloxacin, and gentamicin, used in both humans and animals, revealed high efficacy (97–100%). Conversely, a higher frequency of isolates was resistant to penicillin (87.8%) and trimethoprim/sulfamethoxazole (43.9%), which are used in both humans and animals. Among the antimicrobials used only in animals, isolates were resistant to florfenicol (46.4%), ceftiofur (17.1%), and enrofloxacin (2.5%). Multidrug resistance was observed in 34% of isolates. The identification of drug-resistant R. equi isolated from humans used exclusively in animals is circumstantial evidence of the pathogen transmission from domestic animals to humans. This study contributes to the molecular identification of Rhodococcus species from humans and to the epidemiological vigilance of the multidrug-resistant isolates.

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ABSTRACT Myenteric plexus injury is responsible for the morpho-functional alterations observed in chagasic megaesophagus (CME). The inflammatory response, characterized by elevated synthesis of IFN-γ, TNF-α, and IL-4, contributes to the persistence of parasitism and inflammation. This study assessed the mRNA expression of cytokines, transcription factors, and metalloproteases in subjects with CME. From 2011 to 2017, esophageal samples were collected from 54 subjects with CME (38 advanced and 16 nonadvanced) and eight subjects with idiopathic megaesophagus (IME). The quantitative mRNA expression of TNF-α, IFN-γ, IL-4, IL-10, IL-17, IL-22, IL-23, IL-27, T-bet, ROR-γT, GATA-3, MMP-1, MMP-2, and TIMP-3 genes was analyzed using SYBR Green systems. T-bet expression was significantly higher in the CME group compared to the IME group and the GATA-3 and ROR-γT expression in the CME group, corroborating the higher IFN-γ expression observed in subjects with advanced CME. The increased T-bet and IFN-γ expression in advanced CME reflects the maintenance of a Th1 response in situ and the morpho-functional changes seen in the organ.

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ABSTRACT Trypanosoma cruzi infection involves transmission of metacyclic trypomastigotes through injured skin or mucosa via contaminated feces from insect vectors like Triatoma dimidiata (Latreille, 1811). Currently, there is insufficient information describing the immune response to feces naturally contaminated with metacyclic trypomastigotes. Mice subcutaneously inoculated with tissue-culture derived trypomastigotes (TCT) or T. dimidiata feces containing metacyclic trypomastigotes (MT) or previously multi-exposed (ME) with feces without metacyclic trypomastigotes and then infected with feces containing metacyclic parasites or only T. dimidiata feces (F) was studied from 15 min to three months post-infection. PCR detection of parasite DNA at the inoculation site demonstrated persistence of T. cruzi DNA up to 20 days in MT and TCT but disappeared earlier in the ME test group. A rapid spread of T. cruzi DNA to regional lymph nodes was observed in all experimental groups. A lower amount of amastigote nests in the heart with concomitant intense inflammation was noticed in ME mice in comparison to the MT group. CD4 + T cell subtypes at popliteal lymph nodes shows early Th1 and Th17 responses at seven days in ME mice, whereas Th1, Th17 and Treg predominate in MT mice after three weeks, and feces induces Th1, Th17 and Treg at a later stage. Our study shows that previous exposure to feces prior to infection with T. cruzi helps control parasitism at the inoculation site and in heart tissue, and an early induction of Th1 and Th17 T cell subtypes.

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ABSTRACT Chagas disease (ChD) remains a significant public health concern in the Americas, with challenges to accurately assessing its mortality burden due to under-reporting and misclassification. This study aimed to analyze mortality patterns of two cohorts of individuals with ChD—one comprising asymptomatic individuals with positive serology (REDS) and another with patients showing Chagas cardiomyopathy (SaMi-Trop)—to propose a method for estimating the potential under-registration of Chagas-related deaths and to find the factors influencing the identification of ChD as the underlying cause of death. We carried out a retrospective analysis of mortality data from these cohorts together with data on the Brazilian Mortality Information System. Causes of death were classified according to ICD-10 codes, and an expert review was used to find possible Chagas-related deaths. Logistic regression was used to explore predictors of ChD identification considering demographic and clinical variables. Of 2,488 patients, 381 died, 28.9% attributed to ChD, predominantly chronic ChD with cardiac involvement (B57.2). Using our method, we estimated a 53.8% potential under-registration rate for possible Chagas deaths. Males were negatively associated with Chagas disease identification, with an odds ratio of 0.52 (95%CI 0.24–1.1). No other significant associations were found, and the overall significance of the model was low. Our findings provide a potential measurement of under-registration, indicating that it may be substantial. These results underscore the need for improved identification and accurate reporting on death certificates. Strengthening the quality of mortality data is essential to understand Chagas-related mortality and guide public health strategies to reduce its impact.

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ABSTRACT Tuberculosis (TB) is a treatable disease and one of the leading causes of death worldwide, notably affecting people living with the human immunodeficiency virus. The COVID-2019 pandemic worsened TB outcomes, particularly in high-burden countries such as Brazil. Accurate data on the mortality of hospitalized patients is limited. This study aimed to evaluate clinical and epidemiological characteristics and identify mortality risk factors among all hospitalized patients with TB at a tertiary hospital in Midwest Brazil from 2017 to 2019. The median age of the 154 patients included in the study was 48 years (interquartile range: 38–59 years), and the majority were male (74.68%). The main comorbidities were diabetes mellitus and chronic obstructive pulmonary disease; 44 patients (28.57%) were admitted to the intensive care unit (ICU). The mortality rate was 33.12%, and the leading cause of death was septic shock, followed by respiratory failure due to TB. The main factors associated with death were age (p=0.001), central nervous system TB (p=0.026), reduced consciousness (p<0.001), ICU admission (p<0.001), mechanical ventilation (p<0.001), use of vasoactive drugs (VAD) (p<0.001), and duration of VAD use (p=0.038). A high rate of inpatient deaths was observed, reflecting the severity of TB and the challenges in its clinical management. It is imperative to implement strategies to reduce the mortality rate.

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ABSTRACT We conducted a prospective randomized controlled trial to evaluate the effect of evidence-based nursing care on length of hospital stay, duration of mechanical ventilation, symptom relief, and complication rates among mechanically ventilated children with severe adenovirus pneumonia. A total of 257 children admitted to Hunan Provincial People’s Hospital in Changsha from February 2018 to December 2021 were enrolled. Two patients withdrew from the study, resulting in 124 cases in the conventional care group and 131 cases in the evidence-based care group. Primary outcomes included time to resolution of signs and symptoms, length of hospital stay, complication rates. Secondary outcomes were blood biomarker levels and successful weaning results. The evidence-based care group demonstrated significantly higher overall efficiency than the conventional care group (98.47% vs. 95.97%, p<0.05). Additionally, the evidence-based care group demonstrated quicker resolution of cough, sputum, pulmonary rales, and fever, shorter hospital stays, and reduced need for mechanical ventilation (p < 0.05). The evidence-based care group had a significantly lower complication rate than the conventional care group (9.16% vs. 25.00%, p < 0.05). Post-care blood biomarker analysis showed decreased levels of leukocytes, calcitonin, and C-reactive protein in the evidence-based care group compared to the conventional care group (p<0.05). Evidence-based nursing interventions can improve outcomes for children with adenovirus pneumonia by reducing comorbidities, improving blood gas levels, reducing inflammatory responses, and improving the weaning success rate of mechanically ventilated children with severe adenoviral pneumonia.

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ABSTRACT Tuberculosis (TB) is the most common comorbidity in people living with HIV/AIDS (PLWH), including those under antiretroviral treatment. PLWH are 28 times more likely to develop TB in Brazil, the leading cause of HIV-related deaths globally, with approximately 161,000 reported deaths worldwide in 2023. Early diagnosis of latent tuberculosis infection (LTBI) and prophylactic therapy can reduce TB cases, prevent disease progression, and decrease transmission in high-risk populations. This study assessed the prevalence of LTBI in PLWH using the interferon-gamma release assay (IGRA) and the impact of the 3HP regimen (isoniazid [INH]/rifapentine [RPT]) as prophylactic treatment. Blood samples from 335 PLWH (78% of the 427 in the cohort) were tested for IGRA; 50 PLWH (15%) tested positive and were treated with 3HP. Treatment included 900 mg of INH and 900 mg of RPT in 12 weekly doses according to the Brazilian health guidelines. No specific risk factors, including nadir CD4+T count, age, gender, or antiretroviral therapy (ART), were more frequently observed in the PLWH with LTBI compared to the PLWH without LTBI. All PLWH with LTBI received treatment and no cases of active TB were observed. Our findings highlight the need for wider LTBI screening and treatment among PLWH in the latent phase, emphasizing more stringent approaches for implementing 3HP prophylaxis.

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ABSTRACT Estimates suggest that over 50% of the global population suffer from Helicobacter pylori infections. Nowadays, first-line quadruple therapy is recommended to eradicate the bacteria due to the increasing failures of the standard triple therapy. Thus, antibiotics such as furazolidone have emerged as a new treatment due to their success rate (>90%) in rescue therapies. Nevertheless, furazolidone is not routinely used for treatment of H. pylori in Colombia. Still, some Asian countries commonly prescribe it. This study aimed to determine the susceptibility of H. pylori to furazolidone in isolates from patients with gastroduodenal diseases in Colombia that were extracted from 2019-2022. A descriptive study was carried out with 179 patients with gastroduodenal diseases. Susceptibility was determined by the agar dilution method. The gene oorD from resistant isolates was amplified by polymerase chain reaction, and their PCR products were sequenced. The frequency of H. pylori equaled 23.5% (42/179); the bacterium was isolated in 84 gastric biopsies. Moreover, 1.7% (3/179) of patients had one resistant isolate to furazolidone in at least one of the two gastric biopsies, corresponding to 5.95% (5/84) of the isolates resisting furazolidone. Overall, three new mutations in the oorD gene occurred in one isolate, and two of the mutations in the five isolates had been reported in Iran, Brazil, and China. This research found low in vitro resistance of H. pylori isolates to furazolidone in Colombia. Finally, all five isolates showed mutations in the oorD gene.

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ABSTRACT In Honduras, Leishmania (Leishmania) infantum chagasi, the etiological agent of visceral leishmaniasis (VL), is responsible for non-ulcerated cutaneous leishmaniasis (NUCL). We characterized NUCL and VL Honduran strains to understand intraspecies infectivity. Based on in-vitro assays, we aimed to elucidate certain host-parasite interactions in VL and NUCL isolates through a hamster model. To assess the capacity of these strains to infect peritoneal macrophages, we exposed them to promastigotes from NUCL and VL patients at varying temperatures and time intervals (32, 34, and 36 °C; 24 and 48 h) and infection-index (II) was determined. No significant differences were observed over time for dermotropic strains; however, a higher II was noted at lower temperatures (32 and 34 °C). Interestingly, only the VL strain exhibited a higher II at elevated temperatures (34 and 36 °C) at 48 h. Low levels of oxygen and nitrogen-derived metabolites were detected in both NUCL and VL strains. For in-vivo assays, hamsters were infected subcutaneously (SC) and intraperitoneally (IP) with 107-promastigotes from NUCL and VL patients. After 90 days of infection, parasite-load and histopathological changes were assessed from spleen samples. Regardless of the administration route, no substantial differences were observed in the histopathological features between NUCL and VL strains. In conclusion, lower temperatures may favor parasite infection for NUCL strains, mirroring conditions found in the skin. This contrasts with the VL strain, which demonstrated a superior II at higher temperatures, a condition normally found in the viscera. Our data also indicate that M. auratus is susceptible to Honduran L. (L.) infantum chagasi strains, circumventing the skin barrier by IP or SC injection.

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ABSTRACT Cutaneous leishmaniasis (CL) has substantial epidemiological and clinical differences depending on host characteristics, Leishmania species and geographic areas. CL in Rio de Janeiro State was evaluated. Mandatory notifications of confirmed cases from 2001–2020 were analyzed considering sociodemographic and clinical variables, temporal trends, the Cutaneous Leishmaniasis Composite Indicator (CLCI) for each affected city in relation to the total of affected cities in the state, and each triennium from the beginning to the end of the time series (2001–2003, 2002–2004 until 2018–2020, sequentially). The number of cases decreased over time. High average incidence rates occurred in contiguous cities from the Southernmost to the Northernmost regions of Rio de Janeiro State, following areas where the Atlantic Forest persists. The CLCI showed temporal variations in the intensity of the risk of CL in the affected cities. Rio de Janeiro city was the only one with intense or very intense risk of CL throughout the studied period. The disease predominantly affected people residing in urban areas and in the middle age groups (20–59 years). CL also predominated in males, regardless of age. The mucosal clinical form was also significantly associated with men, with an 80% chance of them being more affected than women. Regarding diagnostic tests, the Leishmanin Skin Test showed higher positivity than the direct parasitological exam and the histopathological exam. No differences regarding cure between sexes were found. This study may guide control actions in areas where they are most needed in Rio de Janeiro State.

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ABSTRACT Early diagnosis plays a pivotal role in breaking the epidemiological chain of Mycobacterium leprae transmission. Currently, diagnosis relies on clinical, dermato-neurological features, and histological/microbiological assessments. This prospective cross-sectional study investigated whether IgA, IgM, and IgG anti-lipid antibodies can be used to improve the diagnostic performance for leprosy-affected patients in a high-burden municipality in Brazil. Serum samples from 91 volunteers, including patients with leprosy (n=62), household contacts (n=21), and endemic controls (n=8) were screened by enzyme-linked immunosorbent assays (ELISA) for IgA, IgM, and total IgG against four lipids—namely, cardiolipin (CL), phosphatidylcholine (PTC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI)—and a glycosphingolipid—sulfatide (SL)—found in the bacterial cell wall. Antibodies against all lipids were detected in the sera of patients with leprosy. Significantly higher levels of IgA anti-CL, anti-PE, and anti-PTC, IgM anti-CL, and total IgG anti-PTC were observed in these patients compared to household contacts and endemic controls (p < 0.0001). ROC curve analyses demonstrated high accuracy in discriminating patients with leprosy from the contacts, with moderate to high sensitivity and specificity, even in paucibacillary patients. Despite the small study population and the absence of patients with other dermatological lesions for differential diagnosis, these findings suggest the potential of anti-lipid antibodies as biomarkers for leprosy detection. This approach offers a promising method to improve early diagnosis in high-burden areas, such as the studied municipality in Brazil.

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ABSTRACT Most SARS-CoV-2 infections are asymptomatic or cause only mild illness, but severe respiratory disease can develop, sometimes requiring oxygen support. Immunopathological damage resulting from an abnormal inflammatory response in patients with severe disease is known to be the main determinant of disease outcome. Studies show that anti-inflammatory therapies work best when used before widespread immunopathological damage has occurred. Similarly, it was thought that intravenous immunoglobulin (IVIG)—holding multiple immunomodulatory effects—would provide clinically favorable results, but recent studies suggest otherwise. Still, the literature shows few studies evaluating the efficacy of IVIG according to the time of administration and there are no studies comparing it with established treatments, such as tocilizumab. In this study, we aimed to evaluate the effects of early administration of tocilizumab and IVIG on clinical outcome in patients with severe COVID-19. Patients with progressive clinical and laboratory deterioration who received tocilizumab or IVIG between 07/2020 and 10/2020 in a public hospital ward were retrospectively evaluated. A total of 74 patients were identified, of whom 29 (39%) received IVIG only and 26 (35%) received tocilizumab only. As a result, patients with severe COVID-19 who received IVIG in early stages of the disease did not have better clinical outcomes regarding mortality, length of hospital stay and ICU admission compared to those who received tocilizumab. Moreover, there is no data to support the use of IVIG in COVID-19 patients with severe disease, as it is associated with more severe side effects and is more expensive than tocilizumab.

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ABSTRACT Early infant immunity to SARS-CoV-2 depends on maternofetal transfer of antibodies. We aimed to analyze the factors modulating the maternofetal transfer of anti-SARS-CoV-2 IgG antibodies following gestational infection during the pandemic in Brazil (April–August 2021). We conducted a retrospective and prospective cohort study involving 509 mother-child dyads tested simultaneously for IgG anti-nucleocapsid antibodies during universal neonatal screening. There were 341 seronegative dyads and 168 seropositive ones. Seropositive neonates were retested two to three months later. We examined the association of neonatal serological status and IgG concentrations with gestational mRNA vaccination, timing of maternal infection, neonatal conditions, and gender. Gestational SARS-CoV-2 infection predicted neonatal IgG seropositivity (OR=3.97; 95%CI=2.69–5.88). Maternal infection in the first, second, or third trimester was associated with progressively greater seropositivity in neonates (34.4%, 51.6%, and 58.2%, respectively; p=0.03). Among seropositive neonates, IgG concentration was higher when mothers reported they had COVID-19 during pregnancy (p=0.04) and tended to be lower in girls (p=0.06). More than half of the seropositive neonates remained seropositive two to three months later (54.1%), which was associated with both maternal and neonatal IgG concentration at birth (p<0.001). Higher neonatal IgG concentrations at birth were associated with the persistence of anti-N IgG antibodies for two to three months in more than half of the seropositive newborns. This study provides an additional understanding of the dynamics of maternofetal antibody transfer.

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ABSTRACT To assess SARS-CoV-2 reinfection incidence in the post-vaccination period, we carried out a prospective cohort study of blood donors from Amazonas and Sao Paulo States, Brazil. Anti-nucleocapsid immunoglobulin (IgG anti-N) tests carried out by blood centers in 2020 were used to identify previous SARS-CoV-2 infections in blood donors and divide them into two groups: prior infection (n=386) and no prior infection (n=111). From March 2021 to January 2022, donors were followed up for six months, during which IgG anti-N and real-time reverse transcription polymerase chain reaction tests were performed every two months to detect SARS-CoV-2 infections. Symptoms and vaccination status were also recorded. Most participants (93.6%) received at least one COVID-19 vaccine dose. Reinfection incidence in the prior infection group equaled 1.39 per 100 person-months (95% CI: 0.90–2.06), in comparison to 2.68 per 100 person-months (95% CI: 1.28–4.93) for new infections in those without prior infection. The incidence risk ratio showed no significant association (0.52, 95% CI: 0.25–1.13). However, prior infection significantly increased the probability of remaining uninfected (Log-rank: p=0.009). Most reinfections (84%) showed no symptoms and occurred post-vaccination during the Delta and Omicron waves. IgG anti-N seroprevalence decreased in the prior infection group (from 35.5% at baseline to 22.5% after six months, p=0.003). Despite no significant incidence risk ratio differences, donors with prior infection had lower infection rates and a higher likelihood of remaining uninfected. Persistent post-vaccination asymptomatic infections emphasize the need for ongoing prevention, genomic surveillance, and booster programs to address emerging variants and protect vulnerable populations.

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ABSTRACT COVID-19, caused by SARS-CoV-2 virus infection, remains a public health concern in many countries. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) is a rapid and cost-effective alternative test for COVID-19 diagnosis. In this study, we developed and evaluated a real-time RT-LAMP (rRT-LAMP) assay coupled with a melting curve analysis to detect SARS-CoV-2. The reaction was carried out in a real-time thermal cycler at 63 °C for 45 min to amplify the region of SARS-CoV-2 orf8; real-time monitoring of amplification was performed by fluorescence detection. The performance was assessed by comparing it to a real-time reverse transcription-polymerase reaction (rRT-PCR) as a reference. The rRT-LAMP could detect as few as 15 copies of SARS-CoV-2 RNA per reaction. Positive results appeared within 30 min, while the melting-temperature analysis could verify the amplification specificity. No positive results from non-SARS-CoV-2 templates and no mis-amplification were observed. The comparative analysis using 262 RNA extracted from nasopharyngeal swab samples revealed the overall accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV) of the rRT-LAMP at 88.55% (95% CI: 77.52–100%), 84.13% (95% CI: 71.56–98.27%), 100% (95% CI: 78.38–100%), 100% (95% CI: 85.06–100%), and 70.87% (95% CI: 55.55–89.11%), respectively. The greatest sensitivity was as high as 98–100% for specimens with threshold rRT-PCR cycle (Ct) values of less than 30 cycles. Overall, this rRT-LAMP showed good performance for the rapid detection of SARS-CoV-2. It is proposed as a potential method for real-time amplification detection, offering increased laboratory capacity for SARS-CoV-2 testing in a cost-effective and timely manner.

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ABSTRACT Mosquitoes (Diptera: Culicidae) are arthropods of medical importance because they can carry arboviruses. High-throughput sequencing (HTS) technology and metagenomic approaches conducted in mosquitoes have contributed to the discovery of many insect-specific viruses (ISVs), which have the potential to affect their vector competence. Mosquitoes were collected in urban parks in Sao Paulo city, Brazil and 20 pools with female mosquitoes were subjected to HTS by HiSeq 2500 sequencing system (Illumina). Long viral sequences (1,585-6,701 base pairs) were recovered from two pools of Aedes scapularis. BLASTx analyses revealed they had greater identity with segment L and S of Salarivirus and segment M of Furrundu phlebovirus, which encode, respectively, the RNA-dependent RNA polymerase (RdRd), the nucleocapsid protein, and a polyprotein. Phylogenetic tree of the segment L and S of the Phenuiviridae Family showed our sequences grouped with unverified sequences of Furrundu phlebovirus, an unclassified ISV that belongs to the Hareavirales Order and was first reported in mosquitoes in the Brazilian Pantanal, the largest natural tropical wetland worldwide. We report the second detection of Furrundu phlebovirus in mosquitoes collected in urban parks, showing it could be in mosquitoes from natural places and in green areas in urban cities. We conclude that Furrundu phlebovirus possibly occurs in Aedes scapularis in green areas, in Sao Paulo. Further studies should elucidate the role of this virus in the vector competence of Aedes scapularis and its interaction with different arboviruses.

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ABSTRACT This study aimed to investigate the relationship between inflammatory factors, pathogen distribution, and prognosis in patients with septic shock admitted to the emergency department of internal medicine. A total of 140 patients with septic shock admitted to the emergency department of The Third People’s Hospital of Chengdu, China, from January 2021 to January 2023 were selected for analysis of the distribution of pathogens and infection sites. Patients were divided into death (36 cases) and survival groups (104 cases) based on their condition after 28 days of treatment. A total of 174 pathogenic bacteria strains were cultured, including 124 Gram-negative bacteria (71.26%) and 43 Gram-positive bacteria (24.71%). The main infection sites were the lungs (33.57%) and the abdominal and gastrointestinal tracts (25.00%). The distribution of pathogens and infection sites in the survival and death groups were compared (P > 0.05). The regression equation predicted patient mortality, with the area under the ROC curve of 0.860 (95% CI: 0.792–0.929; P < 0.05), and sensitivity and specificity of 88.90% and 73.10%, respectively. Pathogen distribution in patients with septic shock in the internal medicine emergency department was not related to prognosis; however, inflammatory factors such as CRP and PCT were predictive of outcomes. Along with age, APACHE II score, and SOFA score, they demonstrated significant prognostic value for patient mortality.

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ABSTRACT Visceral leishmaniasis (VL) is a potentially fatal disease, occurring in 76 countries, 12 of which are located in the Americas, with approximately 3,500 new cases annually registered in Brazil. Active visceral leishmaniasis is characterized by an intense inflammatory reaction with a low cell-mediated immune response and a high production of specific and non-specific antibodies. Antibodies are not associated with effective protective mechanisms but have been used widely in diagnostic tests. In this study, we analyzed the immunoglobulin G (IgG) response against crude antigens of Leishmania infantum by using automated western capillary blot in patients with active and clinically cured VL, individuals residing in an endemic area and patients with Chagas disease. The method allowed an accurate analysis of the antibody response. Our results demonstrated that antibody reactivity to L. infantum antigens in the 20–142 kDa range effectively distinguished active VL from clinically cured cases and Chagas disease, although these antigens were not exclusively recognized by patients with active VL. The automated western capillary blot proved to be a useful tool for differentiating patients with active VL from individuals living in endemic areas and those with Chagas disease, highlighting its potential application in serological diagnostics.

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ABSTRACT Guaramiranga, Ceara State, Brazil, a tourist city 105.5 km from the capital Fortaleza, was a pilot site for vaccinating 100% of its 4,002 adult population with the first dose against COVID-19. The city received 3,328 CoronaVac, 1,685 AstraZeneca, and 174 Pfizer–BioNTech doses (5,187 in total). Vaccination with the first dose occurred from January 20, 2021 to April 1, 2022. This study analyzed hospitalized patients’ epidemiological, clinical, and laboratory characteristics and deaths from COVID-19 in Guaramiranga from March 2020 to December 2022. In total, nine cases required hospitalization, seven of which resulted in death. Patients’ median age at death equaled 87 (64-95) years. Only one was male, and five had incomplete vaccination schedules before their hospitalization. Hypertension and diabetes configured the most frequent comorbidities, whereas common symptoms at admission included fever (four cases), cough (four cases), and dyspnea (five cases). Of these nine patients, 4 received anticoagulants and corticosteroids; 6, oxygen supplementation; 2, oseltamivir; and 3, empirical antibiotic for pneumonia. The mean interval between the last vaccine dose and hospitalization totaled 128 days (28–326; SD 137). These findings highlight incomplete vaccination, a prolonged interval since last doses, comorbidities, and advanced age as key factors associated with severe cases and deaths and emphasize the protective role of high vaccination coverage.

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ABSTRACT The Candida genus colonizes the oral mucosa of immunocompetent individuals and healthy people, which is maintained by the innate immune system. However, any disturbance in this relationship, such as immunodepression, can turn this normally harmless yeast into a dangerous pathogen. This study evaluates the prevalence and risk factors for oral candidiasis (OC) among patients hospitalized in the dermatology department of a tertiary public hospital and identifies the Candida species involved. This cross-sectional study involves 240 patients. Oral candidiasis was diagnosed via clinical evaluation and mycological examination, with species confirmed using MALDI-TOF mass spectrometry. The prevalence of Candida species was 32.1%, in which C. albicans was the most common (92.1% of OC cases), followed by Nakaseomyces glabrata, Pichia kudriavzevii, C. tropicalis, and C. parapsilosis. Univariate analysis indicated that aging, use of oral prostheses, need for dental intervention, immunosuppression, and autoimmune diseases increase the risk of candidiasis. Multivariate analysis confirmed that aging, necessity for dental treatment, and immunosuppression were in 80% of OC cases. Given the great prevalence of oral candidiasis in hospitalized patients, dentists need to assess them for oral candidiasis and provide information on oral hygiene and healthy practices. Although C. albicans is the main microorganism responsible for these infections, other species have also been identified, highlighting the need for immediate identification and awareness of risk factors.

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ABSTRACT This study aims to evaluate strategies for diagnosing Chagas disease (CD) using rapid tests and risk questions in an endemic area. This is an analytical cross-sectional study conducted with 751 individuals from two municipalities in an endemic region for CD in the North of Minas Gerais State, Brazil. Participants answered a questionnaire with personal information and the risk criteria for CD infection recommended by the Clinical Protocol and Therapeutic Guidelines for Chagas disease (PCDT). Subsequently, they underwent capillary blood collection for the rapid diagnostic test (RDT). Individuals with a positive RDT result, along with negative controls, underwent venipuncture for serological testing. The mean age of participants was 51.4 (±18.2) years, most were female (n=434/57.8%). In the RDT, 699 (93.1%) individuals tested negative; of these, 109 (15.6%) underwent serology and 4 (3.7%) tested positive. Among the 52 (6.9%) individuals with a positive RDT result, 48 (94.1%) had their result confirmed by the serological tests. RDT result, age, and risk factors—except for blood transfusion before 1992—were statistically associated with positive serology for CD. The RDT demonstrated high sensitivity (0.92; 95% CI: 0.81–0.92) and specificity (0.97; 95%CI: 0.92–0.99).

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ABSTRACT Trypanosoma cruzi can be transmitted by blood transfusion in non-endemic areas, and in endemic areas the risks may be higher. We investigated the seroprevalence of anti-T. cruzi antibodies in 1,500 blood donors from a blood bank in an endemic area where Triatoma dimidiata constitutes the main vector and in 2,800 healthy young subjects. Choosing antigens is crucial in diagnostic tests as it directly influences performance across regions. We screened 1,500 blood donors in parallel for chimeric Trypanosoma cruzi antigens with the ABBOTT PRISM Chagas assay at the State Blood Transfusion Center and with an in-house ELISA assay using local T. cruzi antigenic extracts at a Biomedical Research Center laboratory. Overall, 13 T. cruzi isolates from the Yucatan Peninsula, Mexico, were characterized for their antigenic profiles before being used in an in-house ELISAs. All T. cruzi isolates shared immunodominant antigens among themselves and with South American strains (particularly those below 100 kDa). Seroprevalence of anti-T. cruzi antibodies in blood donors totaled 0.2% (3/1500) in the ABBOTT PRISM Chagas assay and 0.26% (4/1500) in the in-house ELISA. We found low sensitivity (33%; 95%CI 0.01710 to 0.8815), high specificity (99.8%; 95%CI 0.9941 to 0.9995), and a low kappa index (0.2). Seroprevalence in young subjects totaled 0.14 %. We found comparable seroprevalence to blood banks in large Mexican municipalities free of vector transmission. Thus, optimal public immunodominant antigens are needed to cover the broad immune spectrum induced by T. cruzi infection.

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ABSTRACT Leptospirosis, a neglected zoonotic disease of global relevance, particularly affects populations in socio-environmentally vulnerable regions. In tropical countries such as Brazil, the prevalence of leptospirosis increases significantly during floods, increasing human exposure to contaminated environments. This study aims to investigate the spatiotemporal distribution and prevalence of confirmed leptospirosis cases in Espirito Santo State, Brazil, from 2020 to 2024. This ecological study used secondary data from the Espirito Santo State Health Department and population estimates from the Brazilian Institute of Geography and Statistics. Prevalence rates were calculated by municipality. Kernel density estimation was used to assess spatial clustering. A total of 344 confirmed cases were reported during the study period, with the highest prevalence in the Southern and Metropolitan mesoregions. Most cases occurred in urban areas and predominantly affected economically active men aged 20-59 years. These findings highlight the influence of socio-environmental determinants on leptospirosis distribution and reinforce the importance of geospatial tools in finding high-risk areas and supporting targeted public health strategies.

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ABSTRACT The COVID-19 pandemic continues to highlight the significant impact of pre-existing comorbidities on disease progression and patient outcomes due to the risk factors for severe disease in unvaccinated patients. We evaluated the association between several clinical/laboratory findings and comorbidities in a cohort of unvaccinated patients hospitalized in the intensive care unit in Recife, Pernambuco State, Brazil. We enrolled 36 unvaccinated volunteers, and performed clinical, biochemical, hematological, and microbiological analyses. Cellular immunity, cytokine measurement, and gene expression were also analyzed. Additionally, serum samples were submitted to serological and neutralization assays by using SARS‐CoV‐2 B.1 Lineage, Gamma (P.1), Delta (B.1.617.2-like), and Omicron (BA.1) variants. Hypertension was the most common comorbidity in patients requiring oxygen supplementation, followed by diabetes and metabolic syndrome. Such conditions were linked to increased disease severity, with elevated levels of inflammatory biomarkers (D-dimer, C-reactive protein), neutrophilia, and lymphopenia. Chronic inflammation, which is often seen in diabetes and metabolic syndrome, worsens the inflammatory response triggered by COVID-19, which exacerbates endothelial injury and leads to a hypercoagulable state. Additionally, patients with comorbidities had impaired humoral immunity, and showed reduced seroconversion and neutralizing activity, which hindered their ability to combat the virus effectively. Furthermore, this study revealed that patients with diabetes and metabolic syndrome had an exaggerated Th17-driven immune response, which contributed to severe outcomes and multi-organ failure. These findings underscore the importance of personalized care and targeted interventions for patients with comorbidities, thus highlighting the need for further research on metabolic disorders, immune dysfunction, and COVID-19.

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ABSTRACT Candidemia is a leading cause of bloodstream infection–associated morbidity and mortality, particularly among critically ill patients. Time to detection (TTD) is crucial, but standard blood culture systems often fail to recover yeasts, filamentous fungi, or identify fungi in polymicrobial infections. The BD BACTEC™ Mycosis IC/F bottle was designed to improve fungal detection, yet comparative performance data are limited. This study aimed to compare the detection rate and TTD of BD BACTEC™ Mycosis IC/F with those of standard BD BACTEC™ Plus Aerobic/F and BD BACTEC™ Plus Anaerobic/F bottles using simulated models of fungemia and mixed fungal–bacterial bloodstream infections. This in vitro study included 333 blood culture bottles inoculated with Candida spp., Cryptococcus neoformans, Trichosporon asahii, Fusarium spp., and Aspergillus terreus, as well as bottles simulating coinfections with multidrug-resistant Gram-negative bacteria. All bottles were incubated in the BD BACTEC™ FX system for up to 14 days. BD BACTEC™ Mycosis IC/F achieved 100% detection for Candida spp., outperforming BD BACTEC™ Plus Anaerobic/F (58.5%) and matching BD BACTEC™ Plus Aerobic/F. It showed shorter TTDs for Nakaseomyces glabratus, Candidozyma haemuli, Meyerozyma guilliermondii, and molds. In mixed infections, BD BACTEC™ Mycosis IC/F provided better fungal recovery, especially at low inocula, although recovery was impaired when coinoculated with carbapenemase-producing bacteria. In conclusion, BD BACTEC™ Mycosis IC/F improved fungal detection and recovery compared with standard bottles, including in polymicrobial settings. Its use may enhance diagnostic yield in suspected fungemia, though cost and limited availability may limit widespread adoption.

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ABSTRACT Mycoplasma pneumoniae pneumonia (MPP) is a common pediatric respiratory infection linked to excessive immune-inflammatory responses. This study investigated the role of the Notch ligand DLL4 in the immunopathogenesis of MPP by assessing its expression in peripheral blood mononuclear cells of affected children. A total of 128 children with MPP and 35 controls were recruited. PBMCs were analyzed for the expression of Notch ligands (Jagged1, Jagged2, DLL1, DLL4) using real-time PCR. Lymphocyte subsets were assessed via flow cytometry, and cytokine levels were measured using ELISA. Clinical data were compared between severe and mild MPP cases, and correlations between DLL4 expression and immune indicators were evaluated. DLL4 expression was significantly higher in the MPP and severe MPP groups than in controls (P < 0.01). MPP patients showed lower CD3+ and CD3+CD4+ lymphocyte levels, and higher CD3+CD8+ and CD3-CD19+ levels compared with controls (P < 0.001). Plasma levels of IFN-γ, IL-17, and IL-36α were elevated in MPP patients (P < 0.001), whereas IL-4 and IL-10 levels were reduced (P < 0.01). Severe cases had higher IFN-γ, IL-17, and IL-36α levels than mild cases (P < 0.05). DLL4 expression positively correlated with plasma IFN-γ and IL-17 levels in MPP patients (P < 0.05). Elevated DLL4 expression in MPP patients, particularly in severe cases, suggests its role in enhancing Th1/Th17-mediated immune responses while suppressing Th2 pathways. Such findings implicate the Notch signaling pathway, via DLL4, in the immunopathogenesis of MPP and highlight its potential as a therapeutic target for modulating immune responses in severe MPP.

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ABSTRACT This study examines the prevalence of anti-Leishmania IgG antibodies and Leishmania spp. infections among Brazilian kidney transplant recipients and their living donors before and after transplantation. A total of 48 donor-recipient pairs were recruited from July 14, 2022, to December 18, 2023. ELISA was used to test donors and recipients with a crude antigen of Leishmania major-like (Lm-ELISA), along with recombinant Lb6H (rLb6H-ELISA) and K39 (rK39-ELISA). Additionally, PCR was used to test recipients. Of the 48 donors, 25 (52.1%, 95%CI: 38.3–65.5) tested positive with Lm-ELISA, 4 (8.3%, 95%CI: 2.8–20.1) with rLb6H-ELISA, and 2 (4.2%, 95%CI: 0.4–14.8) with rK39-ELISA. Before transplantation, 31 recipients (64.6%, 95%CI: 50.4–76.6) were positive with Lm-ELISA, 5 (10.4%, 95%CI: 4.1–22.6) with rLb6H-ELISA, 1 (2.1%, 95%CI: <0.01–11.9) with rK39-ELISA, and 2 (4.2%, 95%CI: 0.4–14.8) with PCR. At 365 days post-transplant, 35 recipients underwent serological and molecular testing. Of these, 14 (40.0%, 95%CI: 25.5–56.5) tested positive with Lm-ELISA, 4 (11.4%, 95%CI: 3.9–26.5) with rLb6H-ELISA, 0 (0.0%, 95%CI: 0.0–11.8) with rK39-ELISA, and 2 (5.7%, 95%CI: 0.6–19.6) with PCR. Combining serological and molecular methods showed promising potential for early detection and ongoing monitoring of leishmaniasis in kidney transplant recipients and their donors. These findings highlight the urgent need for regulatory measures to implement Leishmania-specific donor screening and recipient monitoring using PCR and targeted serological tests, as well as close observation of signs and symptoms of leishmaniasis.

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ABSTRACT Invasive fusariosis (IF) is an exceptionally severe disease, particularly affecting patients with prolonged neutropenia. Even with antifungal therapy, mortality rates remain high, emphasizing the need for stringent control over hospital environment and further research to enhance patient outcomes. This study aims to assess the antifungal susceptibility of clinical and environmental Fusarium isolates and their clinical relevance in a cancer hospital. Sixteen environmental and 21 clinical isolates were identified, with the Fusarium solani species complex being the most common. Amphotericin B demonstrated in vitro activity, but most isolates exhibited elevated minimum inhibitory concentrations (MICs) for azoles. A total of 80% of patients had IF, primarily those with hematological malignancies, and the 30-day mortality rate was 43.8%. Isolates with elevated MICs were often managed with combination therapy. In conclusion, elevated azole MICs may lead to increased use of combination therapy in real-world clinical settings. Our findings emphasize the importance of careful interpretation of antifungal susceptibility testing results in IF management.

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ABSTRACT Neotropical Echinococcosis (NE) is an emerging parasitic zoonosis of significant public health concern. The disease is caused by the larval stage (metacestodes) of Echinococcus vogeli and affects humans in tropical forests of Central and South America. While clinical presentation, radiological imaging, and surgical procedures have been investigated, the pathological features of NE remain partially understood. We performed a comparative study of hepatic and mesenteric metacestodes obtained from Brazilian patients in Acre and Amazonas States during surgical procedures, using both light and scanning electron microscopy for detailed analysis. Liver metacestodes showed three characteristic layers: adventitious, laminated, and germinal. In contrast, mesenteric cysts lacked a consistent layer organization, as the adventitious layer was absent, and the laminated layer was the most prominent membrane within the cyst. Compression exerted by the metacestodes led to hepatic and mesenteric hypertension, characterized by passive hyperemia. Other features induced by hypertension included an expanded sinusoidal bed and extensive areas of hemorrhage resulting from vascular rupture and subsequent blood leakage. In conclusion, the development of mesenteric and hepatic cysts follows distinct patterns, and scanning electron microscopy proves to be a valuable investigative tool for evaluating the pathology of Neotropical Echinococcosis.

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ABSTRACT Since 2015, there has been a renewed global commitment to malaria elimination. Understanding the dynamics of the disease in regions with declining cases is essential to prevent reintroduction. This study aims to analyze the epidemiological indicators of malaria in Maranhao, a Brazilian state with a significant decline in cases. This is a descriptive, retrospective, and ecological study, with data from the malaria surveillance system, from 2003 to 2022. Demographic, spatial, temporal, and parasitological variables were analyzed. During this period, 83,517 malaria cases were reported, of which 67.8% were autochthonous, and among these, 83.1% occurred in rural areas. The Annual Parasitic Incidence (API) has recently been considered low risk in most municipalities. The analysis of seasonality was important at the beginning of the series, but with the reduction of cases, it lost relevance. The epidemiological profile has shifted, with an increase in imported cases initially from abroad and more recently from other Brazilian states. There was also a significant reduction in the proportion of P. falciparum, from 17.7% in 2003 to 6.01% in 2022. Most infected individuals were male, predominantly aged 15 to 45 years, of which increased from 59.1% to 70.5%. Although the overall trend is downward, recent changes in the disease profile are concerning, as they could reverse progress and cause a new rise in cases in a state close to elimination. Surveillance must be strengthened and adapted to prevent the reintroduction and resurgence of endemic transmission.

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ABSTRACT This study aims to find evidence of the effectiveness of molecular biology techniques in detecting Plasmodium in Anopheles spp mosquitoes. This systematic review was based on the PRISMA 2020 protocol. It was carried out in five electronic databases (LILACS, PubMed, SciELO, Scopus, and Web of Science, with published studies in health and interdisciplinary areas) in addition to complementary research on Google Scholar. Studies that used molecular biology techniques to detect and evaluate Plasmodium in anopheles (the results of which determined the type of Plasmodium in the samples) were included in this review. In total, 484 recent studies were retrieved from the electronic databases. According to the inclusion/exclusion criteria, only 12 studies met the objectives of this systematic review. Molecular biology was used in mosquitoes to determine parasitic species in all studies. Despite the difficulties and challenges in using molecular biology in mosquitoes, the obtained scientific advances show the accuracy and reliability of the results, contributing to an effective epidemiological response and monitoring of the spread of Plasmodium in endemic areas.

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ABSTRACT We report a rare case of disseminated Cryptococcus gattii species complex (CGSC) infection in a 51-year-old immunocompetent man who initially had extensive ulcerated skin nodules, an uncommon cutaneous manifestation of cryptococcosis. Positron emission tomography/computed tomography (PET/CT) revealed hypermetabolic lesions in the skin and lungs, while brain magnetic resonance imaging (MRI) demonstrated multiple cryptococcomas with mass effect. The diagnosis was confirmed by skin and lung biopsies and a positive serum cryptococcal antigen test. Induction therapy with lipid complex amphotericin B, flucytosine, and corticosteroids was initiated. This case highlights the importance of recognizing atypical cutaneous lesions as potential indicators of disseminated CGSC infection in immunocompetent individuals, and underscores the need for early antifungal management.

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ABSTRACT Panstrongylus megistus is the most important autochthonous vector of Trypanosom cruzi, the etiological agent of Chagas disease, in the midwest region of the Minas Gerais State, Brazil. This study investigates the vectorial roles of Triatoma infestans and P. megistus in Chagas disease in this geographical area during the late 1970s. A retrospective analysis of entomological and serological surveys from 1975–1983 was conducted, comparing the presence of T. infestans and P. megistus with the seroprevalence of T. cruzi infection in the human population within the Divinopolis Regional Health Superintendency. Panstrongylus megistus was recorded in all surveyed municipalities (52/52), whereas T. infestans co-occurrence with P. megistus was recorded in only 19.2% (10/52) of them. In the 41 municipalities where only P. megistus was found and relevant data were available, the mean seroprevalence of human T. cruzi infection was 17.8% ranging from 1.0% to 41.9%. In the municipalities where T. infestans occurred, the mean seroprevalence was higher, at 25.8%, ranging from 9.8% to 40.8%. Among the municipalities where only P. megistus was present, 19.5% had a low, 29.3% an intermediate, and 51.2% a high seroprevalence of human T. cruzi infection. In the ten municipalities where both T. infestans and P. megitus were found, 80% showed high seroprevalence, whereas only one municipality each showed low or intermediate levels. The findings highlight the significant role of P. megistus in T. cruzi transmission, even in the absence of T. infestans. The wide distribution of P. megistus increased the risk of transmission. P. megistus was the main household vector in the region in the 1970s. Nowadays, continuous surveillance remains essential for monitoring triatomine infestations and evaluating the current risk of T. cruzi transmission.

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ABSTRACT Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma, which may lead to liver transplantation. Co-infection with HIV may accelerate liver disease and impact treatment response. Monitoring liver fibrosis involves non-invasive methods such as transient hepatic elastography (THE), AST to Platelet Ratio Index (APRI), and Fibrosis-4 (FIB-4). This study compared changes in THE, APRI, and FIB-4 among patients with HCV alone and those with HIV-HCV co-infection before and after direct-acting antiviral (DAA) therapy. We conducted a retrospective cohort study using medical records from patients treated at a reference clinic in Sao Paulo, Brazil, between January 2015 and February 2019. Fibrosis assessments (THE, APRI, FIB-4) were performed pre-treatment and six months post-treatment. APRI and FIB-4 were also evaluated at 12 months. Among 148 participants, 105 (70%) had HCV mono-infection and 43 (30%) had HIV-HCV co-infection. Genotype 1 was most prevalent (86%). At six months post-treatment, greater reductions in THE, APRI, and FIB-4 were observed in the HCV mono-infection group. Pre-treatment THE values positively correlated with subsequent reductions. However, multivariable analysis showed no significant differences between groups in THE reductions, and no significant group differences in APRI or FIB-4 at six and 12 months. DAA treatment led to fibrosis regression in most participants. HIV co-infection did not significantly alter fibrosis outcomes following successful HCV treatment.

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ABSTRACT Urinary tract infections (UTI) lie among the most common bacterial infections worldwide. Since their manifestations can range from laboratory findings (asymptomatic bacteriuria) to septic shock, using appropriate antimicrobial agents is crucial to avoid complications and the misuse of antibiotics. This study aims to review scientific publications and the main guidelines to treat complicated UTI. A literature review was carried out in September 2022 on the LILACS, MEDLINE via PubMed, and SciELO databases. Descriptors, keywords, and MeSH terms were used to develop search strategies. Full documentation meeting the following criteria was included: management of patients with a diagnosis of complicated UTI; guidelines, recommendations, consensus articles, expert opinion articles (with recommendations), and meta-analyses including data from randomized controlled trials; and articles published from 2001 to 2022. Articles published in languages other than English, Spanish, French, and Portuguese and those unrelated to complicated UTI were excluded. After applying the eligibility criteria, 28 studies were included in this review. Fluoroquinolones are the most frequently recommended option for complicated cystitis and pyelonephritis. Guideline recommendations for recurrent UTI include antibiotic prophylaxis and treatment. Guidelines developed to propose treatment strategies for the pediatric population typically stratify cases according to their infection site (upper or lower),and the presence of fever. Guidelines propose different approaches, likely related to local antibiotic resistance and varying clinical manifestations. In this context, antimicrobial stewardship practices are essential to promote the adequate use of antibiotics for complicated UTI and to avoid antimicrobial resistance.

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ABSTRACT This study reports the first documented case of COVID-19-associated pulmonary aspergillosis (CAPA) caused by Aspergillus welwitschiae in the Americas, which occurred in a rural area of Sao Paulo State, Brazil. The case involves a 52-year-old woman with COVID-19, hypertension, and dyslipidemia, who was admitted following severe respiratory deterioration. Imaging tests revealed extensive pulmonary involvement, including nodular and cavitary lesions indicative of CAPA. Bronchoalveolar lavage (BAL) analysis identified Aspergillus spp. using morphological and molecular techniques, and sequencing of the benA gene confirmed the isolate as A. welwitschiae, closely related to the reference strain CBS 139.54. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry further validated this identification. Traditionally recognized as a plant pathogen, A. welwitschiae has recently been implicated in human diseases, such as otomycosis, and is increasingly detected in respiratory samples. However, its association with CAPA remains underreported globally, particularly in the Americas. This case highlights the critical importance of accurate fungal diagnosis, as overlapping morphological features among Aspergillus species can hinder clinical management. The identification of A. welwitschiae in this context raises concerns about its potential as an emerging pathogen in agricultural regions, where environmental exposure may drive its epidemiological relevance. Given the growing recognition of A. welwitschiae as a CAPA agent, this report underscores its importance in the epidemiology of the disease and its potential role in regions with high agricultural activity. Accurate identification is essential for guiding targeted interventions and addressing the public health risks posed by this emerging fungal threat toCOVID-19 patients.

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ABSTRACT Hospital-associated infections (HAIs) pose significant risks in clinical settings, and sterile supply centers management plays a crucial role in infection control. This systematic review and meta-analysis aimed to evaluate the impact of supply center management on the incidence of HAIs and adverse events. The systematic review encompassed studies that compared supply center management protocols with standard care. The PRISMA guidelines were followed to search seven databases for relevant studies. The meta-analysis calculated pooled odds ratios (OR) for HAIs and adverse events, and heterogeneity was assessed using Tau2, Chi-squared, and I2 statistics. Eight studies were included in the final analysis, each assessing intervention efficacy. The results revealed a significant reduction in HAIs (pooled OR=0.3; 95%CI [0.19; 0.49]). Adverse events were also significantly reduced (pooled OR=0.15; 95%CI [0.09; 0.25]). Heterogeneity was low for both HAIs (Tau2=0.00; I2=0%) and adverse events (Tau2=0.04; I2=19%), which indicated a consistent effect across the studies. Sterile supply center management significantly reduced the incidence of HAIs and adverse events. This suggests these interventions are effective in improving clinical outcomes and could be a vital component of infection control strategies in healthcare facilities.

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ABSTRACT This review explores the landscape of prevalent zoonotic diseases in Sao Paulo State, Brazil, focusing on the role of bats as reservoirs and the application of molecular biology in the diagnosis. The zoonoses covered include visceral and cutaneous leishmaniasis, Chagas disease, toxoplasmosis, bartonellosis, Q fever, Brazilian spotted fever, and leptospirosis. Molecular techniques can improve public health responses by accurately identifying pathogens and tracking their transmission dynamics in populations, thus enhancing early detection, characterization of strains, and monitoring of disease outbreaks. By elucidating the epidemiology and molecular aspects of zoonoses associated with bats in Sao Paulo State, we highlight the importance of integrated surveillance systems and multidisciplinary approaches to effectively manage and prevent these diseases.

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ABSTRACT Chlamydia trachomatis infection has been implicated as a potential risk factor for ovarian cancer (OC), but evidence remains inconclusive. This study aims to assess the association between C. trachomatis infection and OC risk using a systematic review and meta-analysis. A comprehensive literature search was conducted in PubMed, Embase, Scopus, Web of Science, and SciELO from their inception to October 2024. Observational studies examining the association between C. trachomatis infection and OC risk were included. Pooled odds ratios (ORs) were calculated using random-effects models. Subgroup and sensitivity analyses were performed based on diagnostic methods and control group types, and publication bias was assessed using Egger's test. Out of 3,288 records, 11 studies involving 4,518 participants were included. The overall meta-analysis revealed a non-significant association between C. trachomatis infection and OC risk (OR = 1.30, 95% CI = 0.99–1.70). However, sensitivity analysis excluding two studies demonstrated a significant association (OR = 1.37, 95% CI = 1.16–1.61). Subgroup analysis showed that PCR-diagnosed C. trachomatis infection was significantly associated with an increased risk (OR = 6.64, 95% CI = 1.62–25.71), while serology-based studies yielded non-significant results. Heterogeneity was high (I² = 70.83%), and publication bias was detected (Egger's test p = 0.015). These findings highlight the role of infection chronicity in OC pathogenesis and suggest that diagnostic methodology significantly impacts observed associations. Future research should employ longitudinal designs with serial molecular testing to establish temporality and evaluate whether targeted Chlamydia screening or treatment interventions could mitigate OC risk in high-prevalence populations.

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ABSTRACT Candidemia poses a significant challenge for hospitalized neonates with an increase in morbidity and mortality. However, candidemia caused by Candida haemulonii in newborns is rare but fatal. We report such a case in China and performed a literature review. A neonate with a gestational age of 31+6 weeks and a birth weight of 1,420g was diagnosed with C. haemulonii candidemia. The infectious agent was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and sequencing of the internal transcribed spacer region. The in vitro antifungal susceptibility testing indicated high minimal inhibitory concentrations for fluconazole (>128 µg/mL), voriconazole (>8 μg/mL), and amphotericin B (>4 µg/mL). Fortunately, the newborn was successfully treated with fluconazole. After a literature review of C. haemulonii candidemia, we found that the risk factors of the candidemia might involve premature, low birth weight, invasive therapeutic devices, broad-spectrum antimicrobial agents, and parenteral nutrition infusion. This study will broaden our knowledge on neonatal candidemia caused by C. haemulonii.

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ABSTRACT Advances in deforestation and climate change directly cause changes in habits and the distribution of Culicidae across the globe, especially mosquitoes of medical importance and the main vectors of arboviruses. The viral metagenomics technique can be an important tool in characterizing viral diversity in mosquitoes. Thus, this study aimed to identify evidence of the effectiveness of the viral metagenomics technique in detecting arboviruses in mosquitoes. This is a systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 protocol. The research was carried out using five electronic databases: LILACS, PubMed, SciELO, Scopus, and Web of Science, and included studies published in health and interdisciplinary fields, as well as complementary research on Google Scholar. Studies that used the viral metagenomics approach for the genomic evaluation of arboviruses found in mosquito samples were included; the results demonstrated the presence of viral diversity and the identification of the genome of probable pathogenic viruses. The protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO) platform under the number CRD42024484713. Thus, 249 studies were identified via searches on electronic databases. According to the inclusion/exclusion criteria, only 23 studies met the objectives for the systematic review. In all studies, genomic sequencing was applied to detect viruses, mainly those related to insect-specific viruses (ISV) and arboviruses known to infect humans and animals, belonging to various viral families. Despite the challenges reagrdingthe absence of reference sequences in genomic databases, the effectiveness of the metagenomics technique in characterizing the mosquito virome is clear from the studies, which broadens the understanding of viral diversity.

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ABSTRACT Loss to follow-up (LTFU) among people living with HIV (PLHIV) is a concerning reality in various healthcare services and can occur at any stage of HIV care. LTFU can lead to a decline in overall health and quality of life for PLHIV; moreover, antiretroviral therapy (ART) interruption increase the risk of HIV sexual transmission. This systematic review investigated factors related to LTFU among PLHIV. The review included sources from PubMed, Cochrane Library, Embase, and others. We included observational studies published in English, Spanish, or Portuguese, from January 1, 2004, to December 31, 2024. We identified 36 studies from 20 countries in North and South America, Europe, Asia, and Africa. The studies included 69,789 PLHIV, of whom 22% were classified as LTFU. The time frame used to define LTFU varied across studies, ranging from 14 to 365 days. The most frequently reported factors associated with LTFU were younger age, low educational level, financial instability, illicit drug use, stigma, absence of family and social support, and ART side effects. Other relevant factors included long commuting time to healthcare facilities, long waiting time at health units, and issues with provider-patient relationships. Multiple factors may contribute to LTFU among PLHIV in complex and context-dependent ways. To address this issue, healthcare services must develop a comprehensive understanding of the communities they assist, recognizing distinct subgroups and their specific needs. Public health policies should be implemented to promote continuous care for PLHIV, including early diagnosis, multidisciplinary assessment, and social support.

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ABSTRACT Brucellosis is a zoonotic disease caused by Brucella species In pregnant women, this disease may lead to adverse obstetric outcomes, such as abortion, preterm delivery, intrauterine fetal death (IUFD), and congenital brucellosis. However, only a few studies have reported IUFD due to Brucella. In our case, one woman residing in Guangxi Province, China—a non-endemic region—developed symptoms 11 months after exposure. The disease manifested during her pregnancy—Brucella melitensis was identified via blood culture and confirmed by MALDI-TOF mass spectrometry. Despite receiving antibiotic treatment for brucellosis, she subsequently experienced IUFD. Additionally, we reviewed cases of IUFD secondary to brucellosis in the literature published until December 2024. Only three cases from the literature were enrolled in this study, which demonstrates that Brucella-related IUFD can occur in non-endemic zones, underscoring the need for increased clinical awareness.

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ABSTRACT Catheter-associated urinary tract infections (CAUTIs) are a prevalent and preventable healthcare-associated infection that significantly impacts healthcare systems, contributing to increased patient morbidity, length of stay, and costs. This systematic review aims to evaluate the effectiveness of various interventions in reducing CAUTI incidence in healthcare settings. Following the PRISMA guidelines, we conducted a thorough literature search across multiple databases—Web of Science, Scopus, PubMed, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Google Scholar—up to August 8, 2024. Eligible studies included randomized controlled trials, case-control studies, and experimental designs that met inclusion criteria, namely CAUTIs prevention among hospitalized adult patients. After screening 9,476 titles and abstracts, we reviewed 163 texts in full. Of these, 12 studies were included in this review. Results showed that antiseptic solutions like chlorhexidine, specialized catheters (e.g., BIP Foley and silver alloy-coated types) and educational sessions all significantly reduced CAUTI rates, with some interventions achieving reductions as high as 94%. Reminder systems promoting timely catheter removal and amikacin bladder washing also showed notable effectiveness. Adverse effects were minimal. This review underscores the importance of evidence-based CAUTI prevention strategies and the need for consistent implementation across healthcare facilities. Enhanced catheter maintenance practices and judicious catheter use can significantly reduce CAUTI rates, thereby improving patient outcomes and reducing healthcare-associated costs. Future research should continue exploring diverse, context-specific interventions to address barriers to CAUTI prevention.

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ABSTRACT For decades, research and development toward malaria vaccine has prioritized infections caused by Plasmodium falciparum, since it is the species responsible for the most severe cases of malaria, which results in a comparatively smaller number of studies devoted to Plasmodium vivax. This disparity is due to complexities inherent in the biology of P. vivax, including the formation of hypnozoites in the pre-erythrocytic phase, difficulties in establishing robust in vitro culture systems, and the absence of fully representative experimental models. Among the antigens investigated for vaccine formulations, the Plasmodium vivax circumsporozoite surface protein (PvCSP) stands out for its immunogenic potential and the partial protection observed in preclinical studies. However, clinical trials with PvCSP-based vaccines have not yet demonstrated a consistent protective response. This review aims to show a historical overview of the studies that have evaluated the potential of vaccines based on the PvCSP protein, as well as to explore the innovative approaches that have been investigated in the last decade to overcome the challenges and advance the development of an effective vaccine against malaria caused by P. vivax.

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ABSTRACT Leprosy remains a significant public health challenge, with approximately 182,815 new cases annually. This review synthesizes current knowledge on pathogenesis, diagnosis, and treatment, emphasizing recent advances. We discuss the immunological spectrum, ranging from Th1-dominant tuberculoid forms to Th2/regulatory-dominant lepromatous forms, and highlight the roles of B-lymphocyte, inflammasome activation, and Schwann cell antigen presentation in granuloma formation and neural damage. Leprosy reactions—type 1 and 2—arise from distinct immunopathological mechanisms triggered by various factors, with emerging evidence pointing to the involvement of Th17 and regulatory B cells. Diagnostic advances include molecular techniques, nerve ultrasonography, monofilament testing, and serological assays that complement traditional approaches. Treatment is based on multidrug therapy, with country-specific adaptations such as Brazil’s PQT-U, although challenges with adherence and resistance persist. Alternative regimens may include minocycline, clarithromycin, and fluoroquinolones, with bedaquiline showing promising results. Prophylactic strategies include BCG vaccination and the debated use of single-dose rifampicin for contacts. Management of reactional states employs corticosteroids, thalidomide, with biologics and JAK inhibitors reserved for refractory cases. Genetic and epigenetic factors, including TLR polymorphisms and HLA variants, influence susceptibility and outcomes. Despite recent progress, delayed detection, stigma, and inadequate follow-up remain barriers. Comprehensive approaches integrating early diagnosis, active case finding, chemoprophylaxis, stigma reduction, and rehabilitation are essential. The elimination of leprosy requires sustained commitment, improved resource access, and ongoing research into host-pathogen interactions. This review offers clinicians and researchers an updated understanding to support global control strategies.

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ABSTRACT Immune thrombocytopenia (ITP) is an autoimmune hematological condition characterized by a markedly isolated decrease in platelets without any apparent associated clinical conditions, resulting in bleeding and bruising of the skin, mucous membranes, and major organs. It is often triggered by preceding illness or several immune stimulants such as immunizations, infections, allergic reactions, among others. While uncommon, arthropod bites can trigger acute ITP. Four cases have been reported due to bee stings and insect bites, as well as a case of ITP following honeybee-venom therapy. Here, we report a case of acute ITP possibly triggered by multiple tick bites.

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ABSTRACT Myiasis, a condition stemming from the parasitic infestation of Diptera fly larvae, constitutes a complication for cancer patients, particularly those with malignant skin wounds. The factors that contribute to myiasis include old age, inadequate hygiene, poor living conditions, vascular disease, and diabetes. Cases of myiasis in neoplastic wounds in the head and neck region are rare and guidelines or recommendations regarding the best treatment approach remain lacking. Herein, we describe a case of myiasis that developed into an extensive squamous cell carcinoma of the lip in an older male adult due to the delay in oncological treatment stemming from the COVID-19 pandemic. Patients with oral squamous cell carcinoma, especially those residing in rural areas, face a notable risk of developing oral myiasis. Therefore, it is imperative that patients and caregivers adopt strict preventive measures to avoid fly infestations in wounds. Maintaining optimal hygiene (including meticulous cleaning with antiseptic solutions before daily dressing changes) is essential to prevent myiasis. Adequate wound coverage is crucial, especially during warmer seasons.

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ABSTRACT Although ketamine is an FDA-approved drug, its mechanism of action is not fully understood. Currently, there is an increase in its recreational use, causing irreparable social and physical damage. We report the case of a musician who developed sepsis due to gas necrosis in his arm after using veterinary ketamine purchased via the internet. Despite the amputation recommendation, it was possible to save the arm and preserve motor and sensory function. The scientific community, as well as the police and the government, must ponder the prescription, efficacy and safety of ketamine for medical treatments.

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ABSTRACT Leeches are segmental worms commonly found in fresh water in tropical regions. They can enter the human body via the consumption of contaminated water or through the mouth and nose during washing, generally affecting the upper airway and digestive tract. During the blood-sucking process, the leech releases the anticoagulant enzyme “hirudin” from the wound site into the host’s circulation together with an anesthetic to prevent the host from feeling its attachment. Leech endoparasitism is a very rare cause of epistaxis. We report a case of a living leech lodged in the posterior nasal floor in a patient that presented to the emergency department with unilateral epistaxis and a difficult diagnosis.

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ABSTRACT Nocardia keratitis is a rare cause of microbial keratitis, primarily affecting patients in tropical and subtropical regions. Its diagnostic challenge arises from this keratitis uncommon presentation, which often mimics other infectious keratitis types, leading to delays in appropriate treatment. This case report aims to elucidate the complexities of diagnosing and managing Nocardia keratitis of a 41-year-old male who had a chronic, progressively worsening wreath-pattern corneal infiltrate and hypopyon following ocular trauma. Initial empirical treatments were ineffective. Diagnostic confirmation via corneal scraping culture enabled targeted antimicrobial therapy. Subconjunctival amikacin and topical tobramycin led to gradual improvement, though complications such as corneal scarring and neovascularization remained, indicating potential need for surgical intervention. This case emphasizes the importance of high clinical suspicion and precise laboratory diagnostics in managing rare cases of Nocardia keratitis. Establishing standardized treatment guidelines for rare ocular infections could improve clinical outcomes.

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ABSTRACT Urogenital tuberculosis (UGT) constitutes a significant extrapulmonary form of tuberculosis, often presenting non-specific symptoms and a prolonged indolent course that leads to delayed diagnosis and treatment, which can result in severe and irreversible complications such as urinary strictures, renal failure, and infertility. This report describes a case of a 38-year-old man with a five-month history of low back pain, hematuria, dysuria, and altered urinary frequency. Initial treatment for a presumed urinary tract infection failed, and subsequent diagnostic investigations showed stones, nodules, and cysts in his left kidney. A positive tuberculin skin test confirmed the diagnosis of UGT and identification of Mycobacterium tuberculosis in urine samples. The patient underwent standard six-month antituberculosis therapy and subsequent retreatment due to persistent symptoms. Despite significant symptom amelioration, irreversible urological sequelae, including infundibular stenosis, polyuria, and nocturia, remained. This case underscores the importance of early suspicion, accurate diagnosis, and timely treatment of UGT to minimize long-term complications. It also highlights the potential need for extended treatment length in complex cases to improve outcomes and reduce sequelae, warranting further research in this area.

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ABSTRACT Psoas muscle abscess is an insidious disease, with varied clinical manifestations and a challenging diagnosis. This pathology has been more frequently identified due to the increased availability of high-quality radiological imaging, such as computed tomography. In Brazil, Mycobacterium tuberculosis is the most common secondary etiologic agent of psoas abscess. We report the case of a 28-year-old immunocompetent man diagnosed with disseminated tuberculosis, affecting the lungs, lumbar spine, and psoas muscle, leading to permanent locomotion sequelae. This case is very relevant for osteoarticular complaints, as low back pain and limping were the initial symptoms. Diagnosis was confirmed by ultrasound-guided percutaneous drainage of the psoas muscle abscess and detection of the M. tuberculosis complex via Xpert MTB/RIF. A 12-month treatment with antitubercular drugs was effective.

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ABSTRACT Coinfection with leptospirosis and other infectious agents pose major challenges in medical practice, often due to difficulties in isolating these agents, symptoms overlap, and lack of specific investigation protocols in areas with emerging and re-emerging diseases. Consequently, knowledge regarding these coinfections and their impact on clinical outcomes are limited. A previously healthy 33-year-old woman, with no history of chronic or malignance diseases, was admitted with febrile icteric illness, pulmonary hemorrhage, acute kidney injury, thrombocytopenia, and shock. Leptospirosis, COVID-19, human rhinovirus, and dengue in the acute phase were clinically and pathologically diagnosed. Multiple coinfections can rapidly lead to multiple organ and system failure, often resulting in a fatal outcome.

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ABSTRACT Sporotrichosis, a neglected zoonotic fungal infection, is becoming increasingly prevalent in Brazil, with cats being the primary source of human transmission. This report details the first documented case of zoonotic human sporotrichosis in Mato Grosso State, a non-endemic area; the infection was acquired from an animal in an endemic area. The patient developed a subcutaneous ulcerative lesion following contact with a cat from Minas Gerais State, a known disease hotspot. Initially misdiagnosed, the infection was later confirmed as Sporothrix brasiliensis after fungal culture and molecular analysis. The patient was successfully treated with itraconazole. This case highlights the importance of considering sporotrichosis in the differential diagnosis, even in non-endemic areas, due to the risk of zoonotic transmission. It also emphasizes the need for a One Health approach to improve surveillance, diagnostic accuracy, and management of emerging fungal diseases in endemic and expanding areas.

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ABSTRACT Mycobacterium marinum is a nontuberculous mycobacterium and an opportunistic pathogen which infects humans. Here, we report a case of an 87-year-old female who had extensive verrucous skin lesions on her upper limbs for 18 months. The patient was diagnosed with Mycobacterium marinum infection by pathology and quantitative polymerase chain reaction (qPCR) assay of skin tissue. After five months of oral rifampicin and clarithromycin, the skin lesions regressed completely.

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ABSTRACT Gastrointestinal mucormycosis (GIM) and leptospirosis are two severe diseases associated with high morbidity and mortality rates. The coexistence of these two conditions has not yet been reported in the literature. This study presents a case involving this rare association. A 49-year-old man from Sao Paulo, Brazil, was hospitalized with acute abdominal pain, low blood pressure, and jaundice. He had a history of contact with floodwater and ingestion of contaminated water, was hospitalized with acute abdominal pain, low blood pressure, and jaundice. Upon ICU admission, he developed jaundice, acute renal failure requiring hemodialysis, and alveolar hemorrhage necessitating intubation. Leptospirosis was confirmed by serological tests and treated with ceftriaxone for 14 days. Two weeks later, he developed severe enterorrhagia, requiring a massive transfusion and a total colectomy with terminal ileostomy. Histopathology revealed necrotizing granulomatous inflammation with hyphae indicative of mucormycosis. He was treated with amphotericin B for 7 weeks, followed by posaconazole. Abdominal CT scans over the next five months showed complete clinical and radiological improvement. The association between mucormycosis and leptospirosis has not been previously documented, highlighting the diagnostic challenges and the critical importance of early detection. Successful management in this case required timely surgical intervention combined with prolonged antifungal therapy.

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ABSTRACT Rickettsia species are Gram-negative, pleomorphic coccobacilli that are obligate intracellular pathogens transmitted by arthropod vectors such as ticks. Among them, Rickettsia conorii, the causative agent of Mediterranean spotted fever (MSF), is endemic in many Mediterranean countries, including Turkey. This case series describes three patients from Balıkesir, Turkey, who developed high-grade fever, generalized maculopapular rash involving the palms and feet soles, arthralgia, and necrotic eschars (tache noire) at the tick bite sites. All cases occurred during summer and had documented exposure to Rhipicephalus sanguineus. Laboratory evaluations ruled out other tick-borne diseases, while real-time PCR performed on skin biopsy samples confirmed Rickettsia spp. Subsequent DNA sequencing of the gltA and ompA gene regions enabled species identification. Additionally, serological tests showed a significant rise in IgM and IgG antibody titers reacting with Rickettsia conorii antigen by indirect immunofluorescence assay. All patients were treated with doxycycline and recovered without complications. This case series highlights the importance of considering rickettsial infections in the differential diagnosis of febrile patients with rash and recent tick exposure, especially in endemic regions during warm seasons.

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ABSTRACT Paracoccidioidomycosis (PCM) configures a deep mycosis caused by Paracoccidioides spp., a neglected tropical disease. We describe a fatal case of PCM that manifested itself as osteomyelitis with thrombosis in the iliac artery in a man with frequent contact with an endemic region in Sao Paulo, Brazil. A 67-year-old man living in an endemic area presented with osteomyelitis of the femur and iliac artery thrombosis on admission to the hospital. Computed tomography of the chest showed multiple cavitated pulmonary nodules. The patient rapidly progressed to irreversible respiratory failure. The autopsy showed disseminated PCM and iliac artery thrombosis. Laboratory investigation confirmed P. brasiliensis infection with a strain identified in Sao Paulo as P. brasiliensis complex by phylogenetic analysis. Atypical PCM remains a diagnostic challenge. Increased awareness of the sites of infection and its clinical presentations will improve patient management.

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ABSTRACT Currently, at least 22 species of Bartonella are known to cause diseases in humans, with Bartonella henselae being the main one. Among the clinical manifestations associated with bartonellosis, cutaneous vasculitis is rare, but it can be severe. We report the case of a 9-year-old child who presented with cervical lymphadenopathy, arthritis, epididymitis, and cutaneous vasculitis as clinical manifestations of systemic bartonellosis, with positive detection of B. henselae in blood and skin fragment using species-specific conventional polymerase chain reaction (PCR) techniques. Vasculitis caused by Bartonella spp. occurs due to the endothelial tropism of the bacteria and can mimic systemic vasculitis with positive anti-neutrophil cytoplasmic antibodies (ANCA). Furthermore, we found just one previous report about epididymitis related to B. henselae infection, and arthritis is also considered an unusual manifestation of the infection. This case emphasizes the need to consider bartonellosis among differential diagnoses when faced with presentations of purpura, cutaneous vasculitis, arthritis, or epididymitis.

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ABSTRACT A 52-year-old female patient suffering from chronic suppurative otitis media had a bacterial strain isolated from her ear swab specimens, which could not be identified using conventional methods, but it was eventually identified as Kerstersia gyiorum via whole genome sequencing (WGS). Antimicrobial drug susceptibility testing was conducted on the isolated strain and the results demonstrated its susceptibility to a range of antimicrobial drugs, including ofloxacin, ceftriaxone, and other agents. However, resistance to chloramphenicol was observed. The patient was treated with ofloxacin, ceftriaxone, and dexamethasone, resulting in an improvement in symptoms. This report describes the first documented case of Kerstersia gyiorum causing chronic suppurative otitis media in China. WGS provided definitive species identification in which conventional methods failed, demonstrating its critical role in diagnosing atypical pathogens.

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ABSTRACT Behçet’s disease (BD) is a chronic and multisystem disorder characterized by recurrent oral and genital ulcers, along with ocular, cutaneous, vascular, gastrointestinal, and neurologic manifestations. The etiology is thought to involve an autoimmune response triggered by infectious or environmental factors in genetically predisposed individuals. Mycobacterium tuberculosis has been proposed as a potential trigger for BD, although this association remains rarely reported. We show a compelling case of a patient with BD diagnostic criteria who subsequently developed mediastinal tuberculous lymphadenitis, which was initially suspected as disease activity. This case underscores the importance of considering tuberculosis in BD patients with new or worsening symptoms despite appropriate therapy.

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ABSTRACT Chikungunya virus (CHIKV) is globally distributed and transmitted by Aedes mosquitoes, with a mortality rate of 0.8/1,000 cases. The heart is the second most affected organ, with the osteoarticular system being the first. Cardiac involvement ranges from acute symptoms like myocarditis and exacerbation of pre-existing conditions to long-term complications such as dilated cardiomyopathy. While a direct association between CHIKV and acute myocardial infarction (AMI) is rare, systemic inflammation associated with chronic post-Chikungunya arthritis may destabilize atherosclerotic plaques, increasing AMI risk. This case report describes an AMI with non-obstructive coronary arteries in a previously healthy 24-year-old male infected with CHIKV. He presented low back pain, nausea, sweating, dyspnea, progressive leg edema, fever, and polyarticular pain in the knees and ankles. He was in critical condition upon admission, with decreased consciousness and hemodynamic instability, requiring transfer to the intensive care unit. He died 24 h later. Autopsy revealed a significantly enlarged heart, no visible atherosclerosis in the coronary arteries, and an extensive infarction in the interventricular septum. Histology showed coagulation necrosis, alveolar hemorrhage, and hepatic congestion. RT-PCR for CHIKV was detected in the lungs and heart tissues, while tests for other infectious diseases were negative. Studies highlight the role of mitochondrial antiviral signaling protein (MAVS) in protecting cardiac tissue from chronic CHIKV-related effects. Impaired MAVS signaling may enable continued viral replication, leading to myocarditis and vascular inflammation. Co-infection with dengue fever further increases the risk of cardiac complications. Postmortem analysis is essential to confirm CHIKV-related cardiac deaths and improve understanding and management of severe manifestations.

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ABSTRACT A 62-year-old Brazilian woman with type 2 diabetes mellitus developed necrosis in her right arm following a single wasp sting. Severe reactions such as hers are typically associated with multiple stings and often manifest as anaphylactic shock rather than necrosis.

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ABSTRACT Sarocladium spp. are filamentous fungi commonly associated with plant diseases and only rarely cause hyalohyphomycosis in humans. Immunosuppressed patients are at risk for this infection, which typically presents with skin and subcutaneous lesions that may eventually disseminate to internal organs. This study reports a case of a man in intensive care following SARS-CoV-2 infection. During hospitalization, he developed neutropenia, persistent fever, and a cavitary lung lesion. Sarocladium spp. was isolated from blood cultures, and the patient was treated with voriconazole, leading to a successful cure. To our knowledge, this is the first reported case of Sarocladium implicatum infection in a COVID-19 patient, underscoring the importance of monitoring opportunistic fungal infections in immunocompromised individuals, particularly during epidemics and pandemics.

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ABSTRACT Dengue fever is an acute, systemic, and debilitating febrile illness that poses a significant global public health threat. Vaccination is important in combating the virus in highly prevalent countries, as it reduces the risk of symptomatic infection, hospitalizations, morbidity, and mortality. We report a unique case of atypical dengue fever in a previously healthy 42-year-old Brazilian woman. She developed dengue without the characteristic fever or elevated inflammatory markers 15 days after her initial TAK-003 (Q-denga) vaccine dose, setting her case apart from typical manifestations. ’Whether the mildness of the case was due to the vaccine’s protective effect or if it was caused by the vaccine virus itself, as genetic sequencing of DENV-2 was not possible, is unclear. In regions where the vaccine is being introduced, atypical cases, particularly those without fever, require thorough investigation, so dengue can be excluded.

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ABSTRACT Secondary syphilis can compromise many organs and is widely known for manifesting with classic signs, such as a rash that involves palms and soles along with mucosal lesions. The absence of these manifestations, along with false negative serological tests, as seen with the prozone phenomenon, poses a difficult challenge for the clinician. When skin lesions are visible, a biopsy for pathological description and immunohistochemistry for Treponema pallidum may help aid in the confirmation and certainty of the diagnosis. Here, we report a case of secondary syphilis with atypical manifestations.

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ABSTRACT Adverse reactions to antituberculosis drugs can lead to treatment abandonment, prolonging the burden of the disease. The role of sex in pyrazinamide exposure and uric acid metabolism raises questions about its influence on the rates of arthralgia and hyperuricemia in patients with tuberculosis. Given the limited evidence in the literature regarding sex-related differences in adverse reaction rates, this study compares serum levels of pyrazinamide and uric acid, as well as the rates of hyperuricemia and arthralgia, between male and female patients with pulmonary tuberculosis. Uric acid levels were measured using the spectrophotometric uricase method, and serum pyrazinamide levels were determined by high-performance liquid chromatography. A total of 88 patients were enrolled in the study. The mean weight, pyrazinamide dosage, and median uric acid levels were similar between sexes. However, the proportion of males with hyperuricemia was higher than that of females. Pyrazinamide maximum concentrations ranged from 10 to 98 µg/mL and were higher in females than in males. The overall rate of arthralgia was 25%, occurring primarily in male patients with hyperuricemia. Serum pyrazinamide levels were higher in patients with arthralgia compared to those without it. No significant correlations were found between drug levels and uric acid in either sex. In conclusion, sex influences pyrazinamide exposure and arthralgia and hyperuricemia rates. Close monitoring of uric acid levels may help improve adherence to tuberculosis therapy.

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ABSTRACT The recent Oropouche fever outbreak in Sergipe State, Northeastern Brazil, represents a significant expansion of the disease beyond the Amazon. This shift in transmission patterns highlights the urgent need to adapt public health strategies and strengthen surveillance efforts to better understand and manage the spread of the Oropouche virus across diverse ecological and climatic settings.

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ABSTRACT The identification of Leishmania species is crucial for eco-epidemiological purposes and may be useful for clinical management. Notably, archived smear slides can be valuable in this scenario. ITS-1 PCR followed by sequencing was used to identify Leishmania species from archived lesion smears of patients with suspected cutaneous leishmaniasis in Santarem city, Para State, Brazil. A total of 44 microscopically positive lesion smears were analyzed, of which 34 yielded positive PCR results. Of these, 22 were subjected to Sanger sequencing and 15 were successfully sequenced, revealing five Leishmania species. This study demonstrates the applicability of molecular testing on archived samples. ITS-1 sequencing effectively differentiated between species, revealing significant diversity of Leishmania in the Brazilian Amazon.

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ABSTRACT Evidence suggests a risk of maternal transmission of chikungunya virus (CHIKV) during the first and third trimesters, potentially leading to miscarriage or neurological consequences for the fetus. This study aimed to conduct a serological survey for CHIKV among women with high-risk pregnancies and analyze neonatal variables and placental tissue alterations. From March 2016 to April 2021, serological, histological, and molecular tests for CHIKV were performed. Blood samples were analyzed for anti-CHIKV IgG and IgM antibodies, and placental tissue was examined for CHIKV RNA and histological changes. Among pregnant patients, 1.33% (7/526) had reactive IgG, and 0.38% (2/526) had IgM/IgG-type antibodies during delivery. Although placental histology of CHIKV disease showed alterations, no viral genetic material was identified in the analyzed tissues. Therefore, further research is needed, including the use of complementary diagnostic techniques, to better understand the impact of this relatively new disease among high-risk pregnant women and newborns.

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ABSTRACT Pregnant and postpartum women are considered at increased risk for severe COVID-19. However, information about disease progression and management in this population is scarce. This study aims to describe sociodemographic, clinical, and radiological characteristics of pregnant and postpartum women admitted to intensive care due to severe COVID-19, emphasizing respiratory outcomes. This is a retrospective, descriptive cohort study evaluating consecutive admissions of pregnant and postpartum women to an infectious diseases intensive care unit due to confirmed or suspected COVID-19, from May 2020 to June 2022. Numerical variables were described by median and interquartile range (IQR), and categorical variables, by frequency and percentage. Missing data were excluded from the analysis. A total of 101 admissions were recorded (85 pregnant and 16 postpartum women), with most patients in their second or third trimester. Forty-seven women (46.5%) required invasive mechanical ventilation (IMV), most of whom (62.1%) showed at least 50% of lung involvement on CT scans and requiring neuromuscular blocking agents (89.1%). Lethality was 15.8% in the cohort and 34.0% among women who required IMV. Pregnant and postpartum women are at risk of developing severe COVID-19, with high mortality and need for IMV and neuromuscular blocking. They should be prioritized in public health policies addressing COVID-19.

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ABSTRACT Multidrug-resistant (MDR) Klebsiella pneumoniae, particularly the lineages resistant to carbapenems and aminoglycosides, is an escalating global public health threat across human, animal, and environmental reservoirs. We examined phenotypic and genetic features of MDR K. pneumoniae isolates. A total of 70 K. pneumoniae strains were collected from clinical (n=55), environmental (n=7), and animal (n=8) sources. To better understand the evolutionary relationship between these isolates, a phylogenetic analysis was performed alongside 35 publicly available K. pneumoniae genomes from NCBI and Pathogenwatch. Whole-genome sequencing (WGS) revealed that 43 isolates carried the blaKPC gene, including blaKPC-2 and blaKPC-3 variants, with different susceptibility profiles to aminoglycosides. Among all isolates, 84% (n = 59/70) were resistant to amikacin and 53% (n = 37/70) were resistant to gentamicin. Aminoglycoside resistance was primarily associated with aminoglycoside-modifying enzymes, including aph(3’)-Ia (52%), aac(3)-IIa/aadA2 (49%), and aac(6’)-Ib-cr (37%). Additionally, 16S rRNA methyltransferases rmtB and rmtG were detected in 14% of isolates and were associated with high-level amikacin MICs. Overall, 81% of strains were non-susceptible to at least one aminoglycoside, underscoring the clinical importance of these determinants. Phylogenetic analysis based on WGS data showed two main clusters (A and B), and the multilocus sequence type ST11 predominated among Brazilian isolates. Our findings showed a heterogeneous distribution of sequence type profiles across the two clusters and a close relationship between K. pneumoniae strains from human, animal, and environmental sources, highlighting the need for integrated One Health surveillance.

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ABSTRACT Despite its 100% lethality and approximately 59,000 human deaths every year, rabies still lacks an effective treatment. Numerous trials have aimed to impair the life cycle of Lyssavirus rabies (RABV), the primary worldwide lyssavirus causing rabies, but with limited success. Treatments targeting host factors and attempting to mitigate the damage caused by RABV have also been unsatisfactory. This article describes the effects of intracerebral transfection of anti-RABV recombinant monoclonal nanobodies as antivirals against rabies in vivo, in a post-exposure protocol. Mice were intranasally inoculated with the RABV CVS strain and, 72 h later, were injected via the intracerebral route with two different anti-RABV llama-derived VHH nanobodies complexed with a transfection agent. One of the VHHs was able to reduce the viral load in mice, but no significant effect on survival was detected. Though not completely effective, nanobody therapy could be attempted in association with other antivirals to improve therapies against rabies.

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ABSTRACT Blood transfusion is a major way of Trypanosoma cruzi transmission, a neglected parasite infection that produces Chagas disease (CD). CD has high morbidity and is potentially fatal in the chronic phase due to the parasite’s ability to invade the myocardium, colon, and esophagus. CD prevalence focuses on Latin America; however, its presence in non-endemic areas has been increasing in the last decade, particularly in North America and Europe, due to high migration rates of infected people. This study established the CD seroprevalence in a blood bank located in Mexico City. A total of 851 donor samples were analyzed by ELISAn and Western blotn (ELISA and WB using native antigens obtained from Mexican strains). Positive samples were analyzed by a commercial ELISA kit, named Chagatest (non-native antigens). Average donor age was 36.5 years, and most were men. Seroprevalence by ELISAn and WBn was 3.9% (33/851); whereas by Chagatest only six samples (0.7%) were reactive. Mexico City is not considered an endemic CD area; however, the high mobility of infected people increases the transmission risk in all receptor areas, particularly in blood banks, as seen in this study. Our findings showed a difference between native and non-native serological tests, and the need to maximize the identification of infected people to curb CD spread.

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ABSTRACT Paracoccidioidomycosis (PCM) is a neglected fungal disease with a rising incidence in Brazil, including increasing hospitalizations in previously non-endemic regions outside the Amazon. This study analyzed the spatiotemporal patterns of acute PCM hospitalizations and their relationship with deforestation. We carried out a retrospective ecological analysis of all PCM-related hospitalizations that were registered in the Brazilian Hospital Information System from 2014 to 2023. Acute and subacute cases were defined using ICD-10 codes (B40.0, B40.7, B40.8, B40.9, B41.0, B41.7, B41.8, and B41.9), whereas chronic forms were excluded. Rates were calculated with census population data and stabilized by Spatial Empirical Bayes smoothing. Space-time cube analysis was applied to detect clusters, which were then compared with deforestation alerts from the DETER-B satellite monitoring system. This study found 4,232 acute PCM hospitalizations, predominantly in men (80%), with a median age of 49 years. Cases were reported in 1,292 municipalities (23%), of which 78% were outside the Amazon. This study also found four significant hotspot clusters, including a newly emergent area in the Cerrado region along the Tocantins–Goias border near Brasilia. Hotspot municipalities showed the largest deforested areas (1,178 km2) when compared to coldspots (24 km2), suggesting a strong spatial association. The spatiotemporal dynamics of acute PCM indicate expansion into deforested areas of the Cerrado, highlighting the role of environmental disruption in shaping disease risk. Mitigating PCM spread in Brazil urgently requires strengthened surveillance and integrated health–environmental policies.