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ABSTRACT Serodiagnosis of strongyloidiasis is usually performed by ELISA for the detection of IgG antibodies due to its high sensitivity and practicality, but its main limitation is a constant source of S. stercoralis antigens. The use of S. venezuelensis as a heterologous source of antigens has facilitated several published studies on the serodiagnosis and epidemiology of human strongyloidiasis. The main objective of this study was to evaluate the diagnostic accuracy of surface cuticle antigens of infective larvae of S. venezuelensis extracted with CTAB detergent (L3-CTAB) in comparison with soluble somatic extracts (L3-SSE) using a panel of sera from immunocompetent and immunocompromised individuals, at three different cut-offs. ROC curve analysis showed that L3-CTAB had an AUC of 0.9926. At the first cut-off value (OD 450 nm = 0.214), sensitivity and specificity were 100% and 90.11%, respectively, with a diagnostic accuracy of 0.93. At a second cut-off value (OD 450 nm = 0.286), sensitivity and specificity were 70% and 100%, respectively, with a diagnostic accuracy of 0.91. However, at an alternative third cut-off value (OD 450 nm = 0.589), sensitivity and specificity were 95% and 97.8%, respectively, with a diagnostic accuracy of 0.97. Using L3-CTAB as an antigenic source, the seropositivity rate in immunocompromised patients was 28.13% (9/32) whereas a seropositivity rate of 34.38% (11/32) was found when L3-SSE was used in ELISA. Therefore, the L3-CTAB is simple and practical to obtain and was found to be highly sensitive and specific.

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ABSTRACT Brazil experienced one of the fastest increasing numbers of coronavirus disease (COVID-19) cases worldwide. The Sao Paulo State (SPS) reported a high incidence, particularly in Sao Paulo municipality. This study aimed to identify clusters of incidence and mortality of hospitalized patients with severe acute respiratory syndrome for COVID-19 in the SPS, in 2020–2021, and describe the origin flow pattern of the cases. Cases and mortality risk area clusters were identified through different analyses (spatial clusters, spatio-temporal clusters, and spatial variation in temporal trends) by weighting areas. Ripley’s K12-function verified the spatial dependence between the cases and infrastructure. There were 517,935 reported cases, with 152,128 cases resulting in death. Of the 470,441 patients hospitalized and residing in the SPS, 357,526 remained in the original municipality, while 112,915 did not. Cases and death clusters were identified in the Sao Paulo metropolitan region (SPMR) and Baixada Santista region in the first study period, and in the SPMR and the Campinas, Sao Jose do Rio Preto, Barretos, and Sorocaba municipalities during the second period. We highlight the priority areas for control and surveillance actions for COVID-19, which could lead to better outcomes in future outbreaks.

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ABSTRACT Amniotic fluid DNA samples were genotyped by multilocus-nested-PCR-RFLP, but only three of 11 markers amplified 113 of 122 (92.6%) samples, resulting in 12 untyped and 101 partial non-archetypal genotypes. The 101 typed samples were subdivided into four groups: G1 with 73 samples (5’and 3’ SAG2 allele I + SAG3 allele III + GRA6 allele III), 53 had parasite load ≤ 102 parasites/mL (43 asymptomatic, 10 mild infections), 17 had load > 102 and ≤ 103 (one mild, 13 moderate and three severe), and three had load > 103 parasites/mL (three severe); G2 with 22 samples (5’and 3’ SAG2 allele I + SAG3 allele III), all parasite load levels ≤ 102 parasites/mL (18 asymptomatic and four mild); G3 with five samples (5’ and 3’ SAG2 allele I + SAG3 allele II), parasite load ≤ 102 parasites/mL (three asymptomatic and two mild); G4 with one sample (5’ and 3’ SAG2 allele II + SAG3 allele II + GRA6 allele I), a parasite load < 102 parasites/mL in an asymptomatic infant. After DNA sequencing, restriction sites confirmed SAG2, SAG3 and GRA6 alleles in 98.7%, 100% and 100% of the cases, respectively, while single nucleotide polymorphisms confirmed 90% of 5’-SAG2 allele I; 98.7% of 3’-SAG2 allele I; 98% of SAG-3 allele III, but only 40% of GRA6 allele III results. For the moment, partial non-archetypal genotypes of parasites did not show any relationship with either parasite load in amniotic fluid samples or clinical outcome of infants at the age of 12 months.

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ABSTRACT Candidemia and other forms of invasive candidiasis (C/IC) are serious conditions, especially for immunosuppressed individuals with prolonged hospitalization in intensive care units (ICU). This study analyzed the incremental cost-effectiveness and budgetary impact (BI) of treatment for IC with anidulafungin compared to amphotericin B lipid complex (ABLC) and amphotericin B deoxycholate (ABD) or conventional amphotericin B (CAB), in the Brazilian Unified Health System (SUS). A decision model was conducted with a time horizon of two weeks from the perspective of SUS. The primary effectiveness endpoints were survival and treatment response rate. All patients were followed up until successful therapy or death. BI analysis was performed based on the measured demand method. A five-year time horizon was adopted based on the number of hospitalizations (per 1,000 hospitalizations). For effectiveness measured in the successful response rate (SRR), anidulafungin dominated the ABLC and ABD formulations. In the results of the analysis with the effectiveness measured according to survival, anidulafungin had a better cost-effectiveness ratio (R$988.26/survival) compared to ABD (R$16,359.50/survival). The BI estimate related to the incorporation of anidulafungin suggests savings of approximately 148 million reais in 5 years when comparing it to ABD. The economic evaluation of anidulafungin and its comparators found it to be cost-effective. The consensus of international scientific societies recommends it as a first-line drug for IC, and its incorporation by SUS would be important.

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ABSTRACT This study aimed to analyze the profile of hospitalizations and factors associated with the deaths of children and adolescents with severe acute respiratory infection (SARI) caused by SARS-CoV-2 nationwide. The study comprised 6,843 children and adolescents hospitalized in 2020 who tested positive for COVID-19, based on data from the Influenza Epidemiological Surveillance Information System. Sociodemographic and clinical profiles, hospitalization frequency, lethality and recovery rates were analyzed. The outcome was recovery or death. The 6,843 children and adolescents comprised 1.9% of SARI hospitalized cases (n = 563,051). Of these, 57.7% developed critical SARI and 90% survived. Comorbidities were present in 40.8%, especially asthma, immunodepression, and neurological and cardiovascular diseases. The main symptoms were fever, cough, dyspnea, respiratory distress, and low oxygen saturation. Among those with critical SARI, 91.4% died. There was a higher frequency of children, especially those under five years of age and of mixed ethnicity. The highest hospitalization frequency occurred in the Southeastern and Northeastern regions, the highest recovery rates in the Southeastern and Southern regions, and the highest lethality rates in the Northern and Northeastern regions. Deaths were associated with ages ranging from 12 to 19 and being under one year of age, living in the Northern and Northeastern regions, progression to critical SARI, and having immunosuppression and cardiovascular disease. In contrast, asthma was associated with lower death rates. The frequency of complications and mortality rates caused by SARS-Cov-2 in the pediatric population are relevant, as well as the severity of the epidemic in the social inequality context and the health services’ frailty.

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ABSTRACT Rare emerging pathogens such as Saprochaete clavata are associated with invasive fungal diseases, high morbidity, mortality, rapidly fatal infections, and outbreaks. However, little is known about S. clavata infections, epidemiology, risk factors, treatment, biofilms, and disease outcomes. The objective of this study was to describe a new case of severe S. clavata infection in a patient diagnosed at a referral children’s hospital in Brazil, including antifungal minimal inhibitory concentration, S. clavata biofilm characterization, and molecular characterization. The S. clavata isolated from an immunocompromised 11-year-old male patient was characterized using MALDI-TOF, Gram staining, scanning electron microscopy (SEM), and next generation sequencing (NGS) of genomic DNA. Biofilm production was also evaluated in parallel with determining minimal inhibitory concentration (MIC) and biofilm sensitivity to antifungal treatment. We observed small to medium, whitish, farinose, dry, filamentous margin colonies, yeast-like cells with bacillary features, and biofilm formation. The MALDI-TOF system yielded a score of ≥ 2,000, while NGS confirmed S. clavata presence at the nucleotide level. The MIC values (in mg L-1) for tested drugs were as follows: fluconazole = 2, voriconazole ≤ 2, caspofungin ≥ 8, micafungin = 2, amphotericin B = 4, flucytosine ≤ 1, and anidulafungin = 1. Amphotericin B can be active against S. clavata biofilm and the fungus can be susceptible to new azoles. These findings were helpful for understanding the development of novel treatments for S. clavata-induced disease, including combined therapy for biofilm-associated infections.

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ABSTRACT Detecting latent tuberculosis infection (LTBI) is important, especially in high-risk populations including healthcare workers (HCWs). QuantiFERON-TB Gold Plus (QFT-Plus) is a new version of the interferon-gamma release assays (IGRAs) to replace the QuantiFERON-TB Gold In-tube (QFT-GIT). However, data on the use of QFT-Plus for LTBI detection in high TB-burden countries are limited. This study was conducted in a TB-endemic setting in Thailand. HCWs were enrolled in the study and underwent both tests during the annual health screening. The testing results were compared and the concordance was determined. Of 102 HCWs, 11 (10.78%) were positive according to both tests, and 15 (14.71%) were positive according to QFT-Plus. The overall agreement between assays was 96.08%, with Cohen’s kappa coefficient (k) at 0.82. All four discordant results occurred with QFT-GIT negative and QFT-Plus positive. The comparison between QFT-GIT and QFT-Plus based on each antigen tube (TB1 or TB2) exhibited similar concordance with 99.02% and 95.10% agreement, respectively. The intra-comparison between TB1 and TB2 of QFT-Plus also showed good concordance at 96.08%. Among this group of HCWs, the LTBI prevalence of any positive results in both tests was low. Overall, the study showed good agreement between QFT-Plus and QFT-GIT (k = 0.82) with a minimal difference, suggesting similar assay performance to that mainly carried out in TB-low incidence countries. The results support the use of QFT-Plus for detecting LTBI in a format similar to QFT-GIT.

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ABSTRACT Vaccination coverage has been dropping in Brazil and other countries. In addition, immune responses after vaccination may not be homogeneous, varying according to sociodemographic and clinical factors. Understanding the determinants of incomplete vaccination and negative antibody test results may contribute to the development of strategies to improve vaccination effectiveness. In this study, we aimed to investigate the frequency of vaccine adherence, factors associated with incomplete vaccination for measles, mumps, rubella (MMR) and hepatitis A, and factors associated with the seronegative test results for measles, mumps and hepatitis A at 2 years of age. This was a population-based cohort that addressed health conditions and mother/infant nutrition in Cruzeiro do Sul city, Brazil. Vaccination data were obtained from official certificates of immunization. The children underwent blood collection at the two-year-old follow-up visit; the samples were analyzed using commercially available kits to measure seropositivity for measles, mumps, and hepatitis A. We used modified Poisson regression models adjusted for covariates to identify factors associated with incomplete vaccination and negative serology after vaccination. Out of the 825 children included in the study, adherence to the vaccine was 90.6% for MMR, 76.7% for the MMRV (MMR + varicella), and 74.9% for the hepatitis A vaccine. For MMR, after the adjustment for covariates, factors associated with incomplete vaccination included: white-skinned mother; paid maternity leave; raising more than one child; lower number of antenatal consultations; and attending childcare. For hepatitis A, the factors included: white-skinned mother and not having a cohabiting partner. The factors with statistically significant association with a negative antibody test result included: receiving Bolsa Familia allowance for measles and mumps; incomplete vaccination for measles; and vitamin A deficiency for mumps. Strategies to improve the efficiency of vaccine programs are urgently needed. These include improvements in communication about vaccine safety and efficacy, and amplification of access to primary care facilities, prioritizing children exposed to the sociodemographic factors identified in this study. Additionally, sociodemographic factors and vitamin A deficiency may impact the immune responses to vaccines, leading to an increased risk of potentially severe and preventable diseases.

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ABSTRACT Brazil is a great source of arbovirus diversity, mainly in the Amazon region. However, other biomes, especially the Atlantic Forest, may also be a hotspot for emerging viruses, including Bunyaviruses (Negarnaviricota: Bunyavirales). For instance, Vale do Ribeira, located in the Southeastern region, has been widely studied for virus surveillance, where Flavivirus, Alphavirus and Bunyaviruses were isolated during the last decades, including Bruconha virus (BRCV), a member of Orthobunyavirus genus Group C, in 1976. Recently, a new isolate of BRCV named Span321532 was obtained from an adult sentinel mouse placed in Iguape city in 2011, and a full-length genome was generated with nucleotide differences ranging between 1.5%, 5.3% and 5% (L, M and S segments, respectively) from the prototype isolated 35 years earlier. In addition, each segment placed BRCV into different clusters, showing the high variety within Bunyavirales. Although no evidence for reassortants was detected, this finding reiterates the need for new surveillance and genomic studies in the area considering the high mutation rates of arbovirus, and also to identify the hosts capable of supporting the continuous circulation of Orthobunyavirus.

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ABSTRACT Dogs are considered to be the main domestic reservoir associated with the transmission of Leishmania (L.) infantum chagasi to humans in endemic areas of visceral leishmaniasis in America. However, little is known about the role of canines as a source of infection in endemic areas of nonulcerated cutaneous leishmaniasis (NUCL). Therefore, the objective of the present study was to investigate the role of dogs as a possible reservoir of the parasite in Southern Honduras. Dogs (n = 107) living with individuals affected by NUCL were clinically examined and biological material was collected for parasitological and immunological diagnosis. Most animals showed a healthy appearance and a few presented slight weight loss (64%), alopecia (7%), onychogryphosis (5%) and skin lesions (1%). The overall seroprevalence of Leishmania infection based on the DDP ® quick test and/or in-house ELISA serological test was 41%. The presence of the parasite’s DNA was confirmed in 94% of the dogs; however, the average parasite load in the buffy coat was low at 6.09 parasites/µL, ranging between 0.221 and 50.2. The skin of seropositive dogs examined by histopathology using paraffin sections stained by hematoxylin and immunohistochemistry did not show cutaneous lesions or parasite amastigotes. Based on the absence of parasites in the skin and the low parasite load detected in the buffy coat, it seems that the dog does not represent a good source of infection for the vector in the endemic area of NUCL transmission in Southern Honduras. Other domestic and/or wild animals should be investigated.

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ABSTRACT Rhodnius prolixus is the most important vector of Trypanosoma cruzi in the northern part of South America. The compound eyes in adults of R. prolixus are involved in the nocturnal flight dispersion from sylvatic environments into human dwellings. During this behavior, the artificial lights play an important role in attracting R. prolixus; however, it is still not clear whether the compound eyes of this species use different visible wavelengths as a cue during active dispersion. We applied electrophysiological (electroretinography or ERG) and behavioral (take-off) experiments in a controlled laboratory setting to determine the spectral sensitivity of the compound eyes and the attraction of R. prolixus adults to discrete visible wavelengths. For the ERG experiments, flashes of 300 ms at wavelengths ranging between 350 and 700 nm at a constant intensity of 3.4 µW/cm2 were tested after adaptation to darkness and to blue and yellow lights. For the behavioral experiments, the adults were exposed to nine visible wavelengths at three different intensities, and their direction of take-off in an experimental arena was established with circular statistics. The ERG results showed peaks of spectral sensitivity at 470–490 nm and 520–550 nm in adults, while behavioral experiments showed attractions to blue, green and red lights, depending on the intensity of the light stimuli. The electrophysiological and behavioral results confirm that R. prolixus adults can detect certain wavelengths in the visible spectrum of light and be attracted to them during take-off.

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ABSTRACT Numerous tests employed to predict cardiac and functional status are expensive and not widely accessible for a considerable number of patients, particularly those diagnosed with Chagas disease (CD) residing in remote and endemic regions. To date, there is no knowledge of studies that have validated instruments that address functionality in an expanded way, including the biopsychosocial factors in patients with CD. This study aims to evaluate the psychometric properties of the World Health Organization Disability Assessment Schedule (WHODAS 2.0), in its 12-item shortened version (WHODAS-12) when applied to patients with CD. This is a cross-sectional study of a prospective cohort that follows individuals with CD (SaMi-Trop). Data collection took place between October 2019 and March 2020. In the interviews, sociodemographic information, life habits, clinical information, and indicators of disability measured by WHODAS-12 were collected. Descriptive analysis, internal consistency and construct validity of the instrument were performed. A total of 628 patients with CD were interviewed, most were women (69.5%), their mean age was of 57 years, and most declared an average self-perception of health (43.4%). The 12 items of WHODAS-12 were distributed into three factors, which together account for 61% of the variance. The Kaiser–Meyer–Olkin (KMO) index was 0.90, indicating adequacy of the sample for factor analysis. The internal consistency of the global scale showed alpha = 0.87. The percentage of incapacity was 16.05%, indicating mild incapacity for the evaluated patients. WHODAS-12 is a valid and reliable measure to assess the disability of the Brazilian population with CD.

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ABSTRACT Mycetoma is a neglected tropical disease (NTD) declared by the World Health Organization (WHO) in 2016. It is characterized by the progressive growth of nodules and granulomatous lesions on the legs, arms, and trunk. It is potentially disfiguring and causes disability or amputations in working-age people from marginalized areas. The causative agents can be fungi (eumycetoma) or actinobacteria (actinomycetoma), the latter being the most common in America and Asia. Nocardia brasiliensis is the most important causal agent of actinomycetoma in the Americas. Taxonomic problems have been reported when identifying this species, so this study aimed to detect the 16S rRNA gene variations in N. brasiliensis strains using an in silico enzymatic restriction technique. The study included strains from clinical cases of actinomycetoma in Mexico, isolated from humans and previously identified as N. brasiliensis by traditional methods. The strains were characterized microscopically and macroscopically, then subjected to DNA extraction and amplification of the 16S rRNA gene by PCR. The amplification products were sequenced, and consensus sequences were constructed and used for genetic identification and in silico restriction enzyme analysis with the New England BioLabs® NEBcutter program. All study strains were molecularly identified as N. brasiliensis; however, in silico restriction analysis detected a diversity in the restriction patterns that were finally grouped and subclassified into 7 ribotypes. This finding confirms the existence of subgroups within N. brasiliensis. The results support the need to consider N. brasiliensis as a complex species.

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ABSTRACT This study aimed to analyze the spatial pattern of natural infection index (NII) for triatomines and the risk of Chagas disease transmission in an endemic area of Northeastern Brazil. An ecological study was conducted, based on 184 municipalities in five mesoregions. The NII for triatomines was evaluated in the Pernambuco State, Brazil, from 2016 to 2018. Spatial autocorrelations were evaluated using Global Moran Index (I) and Local Moran Index (II) and were considered positive when I > 0 and p < 0.05, respectively. In total, 7,302 triatomines belonging to seven different species were detected. Triatoma brasiliensis had the highest frequency (53%; n = 3,844), followed by Triatoma pseudomaculata (25%; n = 1,828) and Panstrongylus lutzi (18.5%; n=1,366). The overall NII was 12%, and the higher NII values were P. lutzi (21%) and Panstrongylus megistus (18%). In the mesoregions of Zona da Mata, Agreste, Sertao, and Sertao do Sao Francisco, 93% of triatomines were detected indoors. The global spatial autocorrelation of I to NII was positive (0.2; p = 0.01), and II values calculated using BoxMap, MoranMap, Lisa Cluster Map were statistically significant for natural infections. With regard to the risk areas for the presence of triatomines, Zone 2 (the Agreste and Sertao regions) presented a relative risk of 3.65 compared to other areas in the state. Our study shows the potential areas of vector transmission of Chagas disease. In this study, the application of different methods of spatial analysis made it possible to locate these areas, which would not have been identified by only applying epidemiological indicators.

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ABSTRACT Children have an increased likelihood of becoming carriers of the chronic hepatitis B virus. A total of 1,381 children and adolescents were assessed in five municipalities of Maranhao State, Brazil, for detection of anti-HBc, HBsAg and anti-HBs serologic markers and sociodemographic and behavioral features. Among those who were HBsAg negative and anti-HBc negative, the proportion of anti-HBs positives was calculated after the individuals had completed the vaccination schedule. The robust variance of the Poisson’s regression model was used in order to have adjusted tables and calculate the prevalence ratio. Multivariate analysis was performed to identify the factors associated with the prevalence of anti-HBc with or without HBsAg and the vaccine response. It was observed that 163 children were anti-HBc positive and nine individuals were HBsAg positive. The factors associated with the infection were: municipality of residence (residing in Morros municipality or Humberto de Campos municipality), residence in a rural area, aged between 13 and 15 years old, and illicit drug use. The percentage of individuals who were anti-HBc negative and received all three doses of the vaccine was 48.5%. Among these, only 276 (38.9%) had antibodies at protective concentrations. In an adjusted analysis, Morros municipality presented an increased positivity of vaccine response (p < 0.001), and the age ranging between 6 and 10 years old presented a reduced frequency of response. This study reveals a high prevalence of current and past HBV infection within the targeted age group which, in addition to the low vaccination coverage and serological responses, raises concerns about the management of prevention measures, especially the quality of vaccination in these locations.

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ABSTRACT The aim of this study was to estimate the rate of Mother-to-child Transmission (MTCT) of HIV to neonates in a reference university hospital in Sao Luis city, the capital of Maranhao State (MA), evaluating MTCT-associated factors. A retrospective cohort study based on data from the Notifiable Diseases Data System (SINAN) was carried out and included all HIV-exposed neonates notified from 2013 to 2017 by the university hospital. The study population comprised 725 HIV-exposed neonates, of whom 672 neonates were exposed and uninfected, and 53 were exposed and infected. The estimated rate of MTCT in the period of 2013 to 2017 was 7.3%. Most pregnant women were ≥ 20 years old (86.9%), reported ≥ 8 years of schooling (53.2%), reported full-time or independent paid work (46.9%) and were residents in other cities of the state (61.7%). Regarding healthcare, 86.3% received prenatal care, 74.6% received Antiretroviral Therapy (ART) as prophylaxis during pregnancy, 81.8% received ART prophylaxis during childbirth and 78.1% underwent cesarean section. Among the neonates, 92.8% received ART prophylaxis and 94.3% were not breastfed. Despite these variables, the 7.3% MTCT rate found in this study makes it clear that the interventions recommended by the Ministry of Health were not fully adopted.

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ABSTRACT Triatoma rubrovaria has been captured in some areas of Rio Grande do Sul State (RS), Brazil, as this species can be found in the Pampa biome. Its distribution across this biome should be described in detail to verify the potential of this vector to transmit Trypanosoma cruzi. This study aimed to investigate the occurrence of T. rubrovaria in the Pampa biome and transitional areas of RS. The collected information resulted from the analysis of secondary data provided by the Centro Estadual de Vigilancia em Saude (CEVS – State’s Center of Health Surveillance). The following aspects were taken into consideration: the year in which the insect was captured, the city, the number of specimens captured, invasion or domiciliation, the notification in the household, surroundings or both, and T. cruzi infection. The data comprised the period from 2009 to 2020, in 109 cities located in the Pampa biome and 98 located in transitional areas. The Pampa biome exhibited 85% of the occurrences of T. rubrovaria, while 1.2% of specimens were T. cruzi-like positive. Both the first and second biennia concentrated 64.6% of captures. Alegrete city, Cangucu city and Piratini city were the locations in the Pampa where the largest numbers of specimens were found. Regarding the transitional areas, Roque Gonzales city, Santiago city and Santana da Boa Vista city exhibited the largest numbers. Most insects were adults, which were found in households. Even though positivity for T. cruzi-like was low, the species still has epidemiological importance in the region.

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ABSTRACT Sporotrichosis is the most frequent subcutaneous mycosis in Latin America. It is caused by species of the genus Sporothrix. Infection in humans occurs through the entry of the fungus into the skin. Zoonotic outbreaks involving cats in the transmission of the disease have been frequently reported. The lymphocutaneous form is the most commonly observed and the upper limbs are the most affected sites. We report a case of a 64-year-old healthy female patient with a lymphocutaneous form with rapid progression of lesions, which was refractory to initial treatment with itraconazole. Treatment with liposomal amphotericin B was performed with a satisfactory resolution, but aesthetic and functional sequelae in the left upper limb were installed.

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ABSTRACT The incidence and clinical characteristics of NTM diseases in Brazil remain relatively unknown. The present study describes the diagnosis of NTM isolates, the clinical presentation and treatment outcomes. We analyzed NTM isolates in patients of a tertiary hospital in the Southeast region of Brazil, from January 2008 to July 2019. The ATS/IDSA criteria for diagnosis and treatment of these patients was applied. Mycobacterium kansasii were identified in 13/113 (11.5%) patients. In 59/113 (52.2%) patients who met the ATS criteria for disease, 29/59 (49.1%) received treatment, and 22/29 (75.8%) were cured. The major species identified was M. kansasii. The most frequent symptoms among the treated patients were dyspnea and cough, and the proportion of cured patients was high.

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ABSTRACT PreS/S gene mutations could impact virus secretion, infection and immune evasion. However, the relationship between PreS/S mutations and intrauterine transmission has not yet been clarified. Thus, we aimed to explore the associations between PreS/S gene mutations of HBV isolated from mothers and intrauterine transmission. We analyzed the mutations of PreS/S regions of the HBV genome in mothers with HBV DNA levels ≥ 106 IU/mL whose neonates experienced HBV intrauterine transmission (transmission group, GT) and those whose neonates did not experience intrauterine transmission (control group, GC) analyzed using clone-based sequencing. In total, 206 sequences were successfully amplified, including 98 sequences (from 21 mothers) from GT and 108 sequences (from 20 mothers) from GC of genotype C for mutational analysis. Among the 1203 nucleotides of PreS/S regions, there were 219 (18.20%) base substitutions, of which 103 (47.03%) base mutations caused amino acid changes. F80S, A90V and I68T were mutation hotspots. Mothers in GT had a higher mutation rate of A90V in the PreS1 gene than mothers in GC. The A90V mutation increased the risk of HBV intrauterine transmission after adjusting the maternal age and the mode of delivery (OR = 6.23, 95% CI: 1.18–32.97). Moreover, the area under the ROC curve (AUC) for intrauterine transmission due to A90V and a combination of A90V with the mode of delivery were 0.723 (95% CI: 0.575 to 0.891, P = 0.011) and 0.848 (95% CI: 0.723 to 0.972, P < 0.001), respectively. Mothers with the A90V mutation in the PreS1 gene may be a potential risk factor for HBV intrauterine transmission.

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ABSTRACT This study aimed to assess the factors associated with mucosal leishmaniasis (ML) within the scope of tegumentary leishmaniasis (TL) cases reported in Brazil. Surveillance data were assessed, and comparisons were made between ML and cutaneous leishmaniasis (CL) cases. Additionally, ML incidence rates for municipalities were depicted through a geographic information system. From 2007 to 2017, 235,489 TL cases were reported, of which 235,232 were classified as follows: 14,204 (6%) were ML cases and 221,028 (94%) were CL cases. Multivariate analysis showed that the proportion of ML cases reached 16.8% among individuals >75 years (adjusted OR = 2.77; 95% CI = 2.41-3.19; p < 0.001), and ML was also more frequent among males (aOR = 1.28; 95% CI = 1.20-1.38; p < 0.001), HIV-positive patients (aOR = 2.15; 95% CI = 1.80-2.56; p < 0.001), patients residing in urban areas (aOR = 1.52; 95% CI = 1.43-1.62; p < 0.001), and imported cases (with respect to county) when compared to autochthonous cases (aOR = 1.84; 95% CI = 1.71-1.98; p < 0.001). A lower proportion of positive results in direct parasitological examinations was observed in ML cases (32.6% vs. 60.8%; p < 0.001). The leishmanin skin test results were more often positive in ML cases (41.7% vs. 25.9%; p < 0.001). In ML, compatible changes in histopathology were more frequent (14.6% vs. 3.9%; p < 0.001). A greater proportion of ML cases were treated with amphotericin B (6.9% vs. 0.9%; p < 0.001). The case-fatality rate was higher in ML (0.6% vs. 0.1%; p < 0.001). A higher incidence of ML was observed in a geographical band extending across the Amazon region from the southern Para State to the Acre State. ML exhibited varying frequencies within specific populations. The definition of predictable factors predisposing Leishmania-infected subjects to develop ML is important for defining strategies to mitigate the mucosal damage caused by leishmaniasis.

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ABSTRACT Chagas disease (CD) is a neglected disease caused by the protozoan Trypanosoma cruzi. It has high morbidity and mortality rates and mainly affects socially vulnerable populations. This is a cross-sectional study, with retrospective and prospective data collection. Using questionnaires applied to environmental surveillance coordinators, we characterized the status of CD surveillance activities in municipalities endemic for the disease in Northern Minas Gerais State (MG) and Jequitinhonha Valley (Vale do Jequitinhonha). Moreover, we spatialized the vulnerability index for chronic CD in the study area. The population consisted of 22 environmental surveillance coordinators, active in 2020, from Northern MG and Jequitinhonha Valley, 21 municipalities included in the SaMi-Trop research project, and Montes Claros municipality. After applying the questionnaires to the coordinators, a descriptive analysis of the variables was performed. To characterize the active municipalities, the explanatory variables collected in the questionnaire were compared with the dichotomous variable. Bivariate descriptive analysis was performed. Finally, geoprocessing techniques were used to spatialize the data and prepare maps. Regarding the team of endemic combat agents (ECA), 90.9% reported the lack of a specific team for CD vector control actions. Of the 22 municipalities participating in this study, nine were active (41.1%). Only 25% (n=2) of active municipalities (9% of the municipalities studied) met the target of visiting 50% of households per year. Finally, 81.1% of the coordinators stated that in their municipality, they developed actions linked to primary health care (PHC). The implementation of CD surveillance activities weakened in the endemic region. Few municipalities have a surveillance team, with low regularity of active surveillance and noncompliance with the program’s goal. The results suggest insufficient recording of activities in the information system, considering that there are municipalities that report performing the activities, but no production record was observed in the system.

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ABSTRACT Health care workers (HCW) are the frontline workforce for COVID-19 patient care and, consequently, are exposed to SARS-CoV-2 infection due to close contact to infected patients. Here, we evaluate the prevalence of SARS-CoV-2 infection among HCW from an infectious disease hospital, reference center for COVID-19 care in the metropolitan area of Sao Paulo city, Brazil. Among 2,204 HCW, 1,417 (64.29%) were subjected to detection of anti-SARS-CoV-2 antibodies by chemiluminescent immunoassay. Out of the total, 271 (19.12%) presented anti-SARS-CoV-2 antibodies. Prevalence varied according to HCW categories. The highest prevalence was observed in workers from outsourced companies, cooks and kitchen assistants, hospital cleaning workers, and maintenance workers. On the other hand, resident physicians and HCW from the institution itself presented lower prevalence (nurses, nursing assistants, physicians, laboratory technicians). Social and environmental factors are important determinants, associated with exposure in the hospital environment, which can determine the greater or lesser risk of infection by pathogens that spread rapidly by air.

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ABSTRACT Cycle threshold (Ct) values in COVID-19 reverse-transcription polymerase chain reaction (RT-PCR) tests estimate the viral load in biological samples. Studies have investigated variables associated with SARS-CoV-2 viral load, aiming to identify factors associated with higher transmissibility. Using the results from tests performed between May/2020-July/2022 obtained from the database of a referent hospital in Sao Paulo, Brazil, we investigated associations between Ct values and patient’s age, gender, sample collection setting and pandemic period according to the predominant SARS-CoV-2 variant locally. We also examined variations in Ct values, COVID-19 incidence, mortality, and vaccination coverage over time. The study sample included 42,741 tests. Gender was not significantly associated with Ct values. Age, sample collection setting and the pandemic period were significantly associated with Ct values even after adjustment to the multivariable model. Results showed lower Ct values in older groups, during the Gamma and Delta periods, and in samples collected in emergency units; and higher Ct values in children under 10 years old, home-based tests, during the Omicron period. We found evidence of a linear trend in the association between age and Ct values, with Ct values decreasing as age increases. We found no clear temporal associations between Ct values and local indicators of COVID-19 incidence, mortality, or vaccination between February/2020-November/2022. Our findings suggest that SARS-CoV-2 Ct values, a proxy for viral load and transmissibility, can be influenced by demographic and epidemiological variables.

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ABSTRACT Paracoccidioidomycosis (PCM) is a systemic fungal infection caused by Paracoccidioides spp. It can occur as an acute/subacute form (A/SAF), a chronic form (CF) and rarely as a mixed form combining the features of the two aforementioned forms in an immunocompromised patient. Here, we report a 56-year-old male patient with CF-PCM who presented with atypical manifestations, including the development of an initial esophageal ulcer, followed by central nervous system (CNS) lesions and cervical and abdominal lymphatic involvement concomitant with severe SARS-CoV-2 infection. He was HIV-negative and had no other signs of previous immunodeficiency. Biopsy of the ulcer confirmed its mycotic etiology. He was hospitalized for treatment of COVID-19 and required supplemental oxygen in the intensive unit. The patient recovered without the need for invasive ventilatory support. Investigation of the extent of disease during hospitalization revealed severe lymphatic involvement typical of A/SAF, although the patient`s long history of high-risk exposure to PCM, and lung involvement typical of the CF. Esophageal involvement is rare in non-immunosuppressed PCM patients. CNS involvement is also rare. We suggest that the immunological imbalance caused by the severe COVID-19 infection may have contributed to the patient developing atypical severe CF, which resembles the PCM mixed form of immunosuppressed patients. Severe COVID-19 infection is known to impair the cell-mediated immune response, including the antiviral response, through T-lymphopenia, decreased NK cell counts and T-cell exhaustion. We hypothesize that these alterations would also impair antifungal defenses. Our case highlights the potential influence of COVID-19 on the course of PCM. Fortunately, the patient was timely treated for both diseases, evolving favorably.

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ABSTRACT Direct-acting antivirals are the gold-standard treatment for chronic HCV infections, but few studies have investigated their use on kidney and liver transplant recipients. We conducted a real-world study to evaluate the rates of sustained virological response with direct-acting antivirals in kidney and liver transplant recipients. Moreover, it also aimed to evaluate direct-acting antivirals (DAAs) interference with immunosuppressant levels and to describe the frequency of adverse events. As part of this retrospective observational cohort, we included adult patients that had undergone a kidney transplant (KT) or liver transplant (LT) at our center, had a chronic HCV infection, and were treated with DAAs from June 2016 to December 2021. A total of 165 patients were included in the analysis, divided in 108 KT and 57 LT recipients. HCV genotype 1 was more frequent in KT (58.4%), and genotype 3 was more prevalent in LT (57.9%) patients. Sustained virological response was achieved in 89.6% of patients. Adverse effects were reported by 36% of patients. There were significant interactions with immunosuppressants requiring dose adjustments. A total of three episodes of rejection were reported in KT recipients. In conclusion, DAA treatment resulted in high rates of SVR and was well tolerated in both kidney and liver transplant patients. Adverse events were frequent but not severe in most patients, with low treatment drop-out rates. Interactions with immunosuppressants need monitoring since dose adjustments may be required. Reporting real-life experiences is important to help build evidence for patient management in non-controlled environments.

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ABSTRACT Toxoplasmosis is an infection of vast worldwide distribution whose etiologic agent is Toxoplasma gondii. This disease can cause problems ranging from mild symptoms to serious conditions, such as encephalitis, miscarriage and blindness. Therefore, it is of utmost importance to perform a diagnosis with reproducible techniques in order to obtain a good prognosis. The aim of this review was to analyze the efficiency of toxoplasmosis diagnostic techniques based on sensitivity and specificity results. Five research platforms in English language were used (Eric, Elsevier, Google Scholar, PubMed and SciELO), which contained data on the diagnosis of toxoplasmosis. The search and selection were performed for studies published prior to June 2021. The search resulted in the inclusion of 13 articles published from 2005 to 2020. The data revealed the use of different samples in the standardization of techniques such as serum, total blood, colostrum and amniotic fluid. The flow cytometry, lateral flow immunoassay and qPCR techniques showed 100% sensitivity, whereas the ELISA, western blotting, qPCR and RE-LAMP techniques achieved 100% specificity. Significantly, the qPCR and LAMP techniques were more accurate when the likelihood ratio was assessed. The meta-analysis identified that ISAGA and western blotting have low sensitivity values and LIASON, ELFA and ELISA, using a silica bioconjugate, also have low specificity values. It was noted that a wide range of methods have high values of sensitivity and specificity. Therefore, the choice of the method will be based on the conditions and its financial viability.

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ABSTRACT Acid-fast bacteria can be implicated in skin and soft tissue infections. Diagnostic identification can be challenging or not feasible by routine laboratory techniques, especially if there is no access to the Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) technology. Here, we present two cases of skin and soft tissue infections caused by two different acid-fast bacteria, Nocardia brasiliensis and Mycobacterium marinum. They both grew on Löwenstein–Jensen medium, Sabouraud agar medium and blood agar medium. Both bacteria appeared acid-fast by Ziehl–Neelsen stain and Gram-positive by Gram stain. The identification was performed by MALDI-TOF MS and gene analysis. N. brasiliensis and nontuberculous mycobacterium M. marinum represent rare pathogens that cause severe skin and soft tissue infections. Failure to identify the causative agent and subsequent inappropriate or inadequate treatment may lead to severe complications or even disseminated disease, especially in immunocompromised individuals.

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ABSTRACT This review aims to provide current information about Q fever, elucidating the etiological, epidemiological, pathogenic, clinical, diagnostic, therapeutic, and prophylactic aspects of the disease for the medical community. We discuss the main forms of presentation of the agent, its ability to persist in the body, the infinite possibilities of susceptible hosts, the main known forms of transmission, its importance in populations at occupational risk, and the role of arthropods in the natural history of the disease. Focusing on Brazil, we present the cases already described and studies developed since its first report, and how there is still much to unravel. We are aware of the possibilities of the persistence of the agent and the development of severe clinical pictures and the specific treatments currently instituted. We also wish to raise awareness about the future, the new genotypes that are emerging, the need to study the effects of vaccines, and the impact of Q fever on the population. Q fever is a poorly understood disease in Latin America, and recent studies, especially in Brazil, have revealed the importance of developing new studies.

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ABSTRACT Pediatric tetanus is a rare and forgotten disease in countries with high childhood tetanus toxoid vaccination rates. Therefore, the clinical manifestations, treatment and management of this potentially life-threatening disease are not well known. With a literature review and discussion of tetanus management in pediatric patients, we describe a clinical course of a rare and fatal but vaccine-preventable disease, the generalized tetanus, in an adolescent who was successfully treated.

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ABSTRACT One of the main challenges in the clinical management of dengue is the early identification of cases that could progress to severe forms of the disease. A biomarker that may enable this identification is the presence of genetic polymorphisms in genes associated with immune responses. The objective of this study was to perform a systematic review of the Latin American literature on these genes. An electronic literature search was carried out in PubMed, Scopus, Lilacs, and the Virtual Health Library, and reference lists of systematic reviews in the area. Case-control studies conducted in Latin American countries examining at least one form of genetic polymorphism related to immune responses against severe dengue were included. In total, 424 articles were identified and 26 were included in this systematic review. Of the 26 selected articles, 16 reported polymorphisms associated with the risk of developing severe dengue (Risk); Similarly, 16 articles reported polymorphisms associated with a decreased risk of severe dengue (Protective). The final analysis revealed that multiple polymorphisms in immune system genes were early markers of the progression of dengue in Latin Americans and found that polymorphisms of the TNF-alpha gene may have a critical role in dengue pathogenesis.

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ABSTRACT Schistosomiasis is a major health problem that affects over 200 million people worldwide. There are few reports of Schistosoma mansoni found in liver transplants as well as scarce information about the course of the disease and the long-term effects on the graft. Herein, we report two cases of schistosomiasis in liver transplant recipients who presented abnormal serum liver enzymes, with evidence of gradual improvement after antiparasitic treatment. Furthermore, we discuss the possible role of screening the parasite infection in potential liver transplant recipients from endemic areas.

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ABSTRACT The use of herbal tea with Artemisia annua by travelers and traditional communities in Africa has increased in recent years as a supposed form of malaria prophylaxis, although its use is not recommended due to lack of efficacy. The risk of severe malaria complications that can lead to death is real regarding said behavior, and awareness needs to be raised. We report a case of severe Plasmodium falciparum malaria imported in the Amazon rainforest by a traveler returning from Cameroon who treated himself with Artemisia annua herbal tea.

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ABSTRACT Streptococcus constellatus is a gram-positive coccus member of the Streptococcus anginosus group (SAG). It can be found in the oral flora, and may cause abscess more commonly in the gastrointestinal tract, lungs, and heart. Brain abscesses are severe neurological infections with high mortality rates. Streptococcus species other than S. pneumoniae are rare causes of brain abscesses. This case report highlights a severe case of extra and intracranial abscesses due to S. constellatus in an immunocompetent host

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ABSTRACT Chagas disease (CD) is a neglected tropical disease caused by Trypanosoma cruzi and is genetically classified in six discrete typing units (DTUs). The isolates reported in Mexico are generally associated with DTU I. We presented a case of a prolonged cutaneous lesion in a Mexican man, caused by DTU II in coinfection with Bacillus velezensis and Corynebacterium sp. The patient assessment included a complete clinical history, physical exam, laboratory tests, and a skin biopsy. In the facial tissues, intracellular parasites were revealed. The PCR tests were positive for T. cruzi in tissue and blood samples. DNA satellite sequencing was correlated with the DTU II. The initial serological tests reported negative results. However, four months later, two serological tests reported positive results. These exams were performed in different health centers. Mexico is considered an endemic area for CD; nevertheless, this is just the second cutaneous case associated with a DTU different from DTU-I noted in this country. From an ecological point of view, this fact suggests a geographical expansion of DTU II and an association with atypical skin manifestations. Further studies should be conducted to understand this exciting association between DTU-II and prolonged cutaneous expression in humans.

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ABSTRACT Since SARS-CoV-2 disease (COVID-19) has been labeled as a pandemic, it took the spotlight in the differential diagnosis for patients presenting with acute respiratory and systemic symptoms. Leptospirosis is one of the most common zoonoses in the world, yet it is mainly a disease of differential diagnosis for places that do not have it as an endemic. Due to the high burden of COVID-19 on the healthcare field, patients suffering from other infections may have been inadvertently neglected. COVID-19 infection can mimic other infectious diseases and can confuse physicians in their search for a confirmatory diagnosis. Nonetheless, it is very crucial to broaden the differential diagnosis and keep diseases like leptospirosis within the differential diagnosis despite its rarity, especially in patients presenting with unexplained systemic infectious symptoms. This is a unique case of a patient who presented with dyspnea, jaundice and change in urine color who was suspected to be COVID-19 positive. After a detailed investigation, the patient was diagnosed with leptospirosis instead of COVID-19 and was treated with plasmapheresis and antibiotics accordingly.

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ABSTRACT We report a case of COVID-19-associated meningoencephalitis with a fatal outcome in a male patient with concomitant influenza A, who had been hospitalized at the beginning of 2022, in the Northeastern region of Brazil. He died due to cardiopulmonary arrest after developing status epilepticus on the third day of hospitalization. The SARS-CoV-2 RNA was detected in cerebrospinal fluid and Influenza A was detected in the nasopharyngeal swab. Meningoencephalitis due to COVID-19 is a rare manifestation and physicians must be aware of this complication, mainly during the pandemic. In viral co-circulation situations, the possibility of respiratory coinfections should be remembered.

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ABSTRACT The treatment of infections caused by carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strains is difficult due to the limited antimicrobial options and high mortality. There are many reports on intracranial infections caused by CR-Kp, but only a few on brain abscesses caused by CR-Kp. Here, we present a case of brain abscess caused by CR-Kp successfully treated with combined antibiotics. A 26-year-old male patient was admitted to our hospital due to high fever and headache. His past medical history includes a surgical intervention due to an acute subdural hematoma, performed at an external healthcare center. After the current diagnosis of cerebral abscess, he underwent two surgeries. During the procedure, multiple cerebral abscesses were drained and capsulotomies were performed under ultrasound guidance. The combination of meropenem and vancomycin was started. The contents of the abscesses were sent to the microbiology and pathology laboratory. On the 3 rd day of treatment, the medical team was informed that CR-Kp grew in an abscess culture. The patient’s treatment was changed to meropenem + colistin + tigecycline. The patient developed electrolyte disturbances during the follow-up and this was considered an adverse effect of colistin. On the 41 st day of treatment, colistin was discontinued, fosfomycin was added, and meropenem and tigecycline were maintained. Treatment was discontinued on the 68 th day, when the patient was discharged. The general condition of the patient, who has been followed up for two years, is satisfactory. The treatment of CR-Kp infections should be individualized, and the pharmacokinetics and pharmacodynamics of antibiotics should be considered in each case.

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ABSTRACT Oral myiasis is a rare parasitic disease that requires immediate treatment once diagnosed. However, no standard treatment protocol can be found in the literature. Through a clinical-surgical report, we present the case of an 82-year-old man with lesions extending through the vestibule and alveolar ridge of the maxilla on both sides, in addition to occupying a large part of the palate, with a considerable number of larvae. The patient was initially treated with a single dose of systemic ivermectin (6 mg orally) and topical application of a tampon soaked in ether. The larvae were then surgically removed and debridement of the wound was performed. A crushed tablet of ivermectin 6 mg was applied topically for 2 days, the remaining larvae were again mechanically removed, and the patient received intravenous antimicrobial therapy. Treatment with systemic and topical ivermectin combined with antibiotic therapy and debridement proved to be effective in treating oral myiasis.

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ABSTRACT AIDS-related disseminated histoplasmosis (DH) can cause septic shock and multiorgan dysfunction with mortality rates of up to 80%. A 41-year-old male presented with fever, fatigue, weight loss, disseminated skin lesions, low urine output, and mental confusion. Three weeks before admission, the patient was diagnosed with HIV infection, but antiretroviral therapy (ART) was not initiated. On day 1 of admission, sepsis with multiorgan dysfunction (acute renal failure, metabolic acidosis, hepatic failure, and coagulopathy) was identified. A chest computed tomography showed unspecific findings. Yeasts suggestive of Histoplasma spp. were observed in a routine peripheral blood smear. On day 2, the patient was transferred to the ICU, where his clinical condition progressed with reduced level of consciousness, hyperferritinemia, and refractory septic shock, requiring high doses of vasopressors, corticosteroids, mechanical ventilation, and hemodialysis. Amphotericin B deoxycholate was initiated. On day 3, yeasts suggestive of Histoplasma spp. were observed in the bone marrow. On day 10, ART was initiated. On day 28, samples of peripheral blood and bone marrow cultures revealed Histoplasma spp. The patient stayed in the ICU for 32 days, completing three weeks of intravenous antifungal therapy. After progressive clinical and laboratory improvement, the patient was discharged from the hospital on oral itraconazole, trimethoprim-sulfamethoxazole, and ART. This case highlights the inclusion of DH in the differential diagnosis of patients with advanced HIV disease, septic shock and multiorgan dysfunction but without respiratory failure. In addition, it provides early in-hospital diagnosis and treatment and comprehensive management in the ICU as determining factors for a good outcome.

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ABSTRACT Visceral leishmaniasis (VL) is a chronic vector-borne zoonotic disease caused by trypanosomatids, considered endemic in 98 countries, mainly associated with poverty. About 50,000–90,000 cases of VL occur annually worldwide, and Brazil has the second largest number of cases in the world. The clinical picture of VL is fever, hepatosplenomegaly, and pancytopenia, progressing to death in 90% of cases due to secondary infections and multi-organ failure, if left untreated. We describe the case of a 25-year-old female who lived in the metropolitan area of Sao Paulo, who had recently taken touristic trips to several rural areas in Southeastern Brazil and was diagnosed post-mortem. During the hospitalization in a hospital reference for the treatment of COVID-19, the patient developed acute respiratory failure, with chest radiographic changes, and died due to refractory shock. The ultrasound-guided minimally invasive autopsy diagnosed VL (macrophages containing amastigote forms of Leishmania in the spleen, liver and bone marrow), as well as pneumonia and bloodstream infection by gram-negative bacilli.

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ABSTRACT In this study, we report the presence of a female Amblyomma americanum tick attached to a former resident of the East Coast of the United States who moved to Mexico city. The amplification and sequencing of gene fragments of the 16S-rDNA and cytochrome c oxidase subunit 1 corroborated the identification of the species of the tick. Additionally, the presence of DNA of Rickettsia amblyommatis was confirmed. This work is the first report of an exotic tick of the genus Amblyomma in a traveler from the US to Mexico and represents the second record of an imported tick attached to humans in Mexico.

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ABSTRACT The pancreatic form of tuberculosis (TB) is rare and its diagnosis is challenging, since it manifests itself with non-specific symptoms and non-pathognomonic radiological findings, mimicking a neoplasia of the pancreas. Here, we report the case of a patient who had previously undergone liver transplantation and sought care for abdominal pain, weight loss, anorexia, hematochezia and postprandial fullness. Following an exploratory laparotomy and nucleic acid amplification testing on a pancreatic sample that had been collected, the patient was diagnosed with pancreatic TB. The patient received anti-tubercular pharmacological therapy and required percutaneous biliary drainage. Awareness of the possibility of a pancreatic TB diagnosis is important for clinicians. This attention should be even greater in patients who have undergone transplants, who are immunodeficient or who are from endemic areas.

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ABSTRACT Histoplasmosis is a systemic mycosis prevalent in the Americas. Humans become infected via the respiratory route by inhaling aerosols from soil contaminated with bird and bat excretions. Acute pulmonary histoplasmosis is usually asymptomatic and is more often a self-limiting illness. We report a series of seven acute pulmonary cases in adults during an outbreak in Nova Friburgo city, Rio de Janeiro State, Brazil, in a group of volunteers who were cleaning an old, abandoned house without using personal protective equipment. The patients had a favorable evolution after suitable treatment, but all required hospitalization.

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ABSTRACT Leptospirosis is one of the most common zoonotic bacterial infections worldwide. It is an infection that usually affects people with low socioeconomic status, with morbidity and mortality risk. The clinical course of the disease may range from mild, featuring nonspecific clinical signs and symptoms, to severe, resulting in death. The respective studies conducted in Turkey indicate that leptospirosis seropositivity in animals and humans is higher in coastal and rural areas. Turkey’s Eastern Black Sea Region has a humid climate with heavy rainfalls and a large population of mice and other rodents. However, a Leptospira interrogans serovar Bratislava case is yet to be reported in this region. This article reports the case of a 38-year-old patient who presented fever and acute renal failure and was diagnosed with Leptospira interrogans serovar Bratislava after hospitalization.

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ABSTRACT The precise pathogenesis of COVID-19-related multisystem inflammatory syndrome remains largely elusive, despite its rarity. The syndrome symptoms often overlap with those of other infections, posing challenges for prompt diagnosis. A male patient, 34 years old, was admitted with suspicion of severe dengue, rapidly progressing to multiple organ dysfunction. Dengue tests resulted negative, and he passed away after four days. This case occurred approximately four weeks after the initial onset of COVID-19 and met all diagnostic criteria as defined by the Centers for Disease Control and Prevention. This report presents the first documented case of fatal multisystem inflammatory syndrome in adult (MIS-A) in Brazil. Recognizing the significance of suspecting this syndrome and promptly initiating treatment at an early stage are essential for minimizing damage and mortality.

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ABSTRACT Rhinocerebral and pulmonary mucormycosis are the main manifestations of mucormycosis; however, disseminated pulmonary associated with renal mucormycosis is rarely reported. In this paper, we report a rare fatal case of disseminated pulmonary and renal mucormycosis caused by Rhizopus microsporus in a 50-year-old man with poorly controlled hypertension, type 2 diabetes, and prolonged use of corticosteroids for the treatment of his reiterative gouty arthritis. In this patient, the use of corticosteroids and poorly controlled diabetes were considered underlying risk factor for his disseminated mucormycosis, along with acute renal dysfunction, suggesting the need for clinical suspicion of disseminated pulmonary and renal mucormycosis in hospitalized patients with poorly controlled diabetes and immunocompromised host.

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ABSTRACT Naganishia albida (Cryptococcus albidus) is considered saprophytic fungi, and is rarely reported as a human pathogen. Cutaneous infections caused by non-neoformans cryptococcus are rare. We describe a case of an immunocompetent older male with cutaneous cryptococcosis caused by Naganishia albida following skin trauma, and conduct a literature review in PubMed, Lilacs, and Embase. Only six previous similar reports were found. The seven cases (including ours) were widely distributed geographically (Brazil, the US, the UK, Hungary, South Korea, and Iran), all males, and their ages varied, ranging from 14 to 86 years. Four individuals had underlying skin diseases (Sezary Syndrome, psoriasis, and skin rash without etiology) plus potentially immunosuppressive underlying conditions (diabetes mellitus, kidney transplantation, and the use of etanercept, adalimumab, and methylprednisolone). Cutaneous presentation was polymorphic, with lesions characterized as warts, ulcers, plaques, and even macules. Two patients presented disseminated disease. Serum cryptococcal antigen was negative in six patients, and diagnosis was made by fungal culture in all. There is a lack of data on optimal antifungal treatment and outcomes.

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ABSTRACT Tuberculosis (TB) is one of the leading causes of death by infectious diseases worldwide. Multidrug-resistant tuberculosis is a growing problem, especially in countries with high TB prevalence. Although the lungs are the organs most frequently affected by this disease, Mycobacterium tuberculosis can harm any organ, including the urogenital tract, causing extrapulmonary tuberculosis, which leads to a challenging diagnosis and consequent treatment delays. In this article, we present a case of orchiepididymitis caused by multidrug-resistant TB (MDR-TB) with a significantly delayed diagnosis, the proposed treatment according to the resistance profile, and the clinical outcomes.

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ABSTRACT The genus Bartonella encompasses 38 validated species of Gram-negative, facultative intracellular bacteria that colonize the endothelial cells and erythrocytes of a wide spectrum of mammals. To date, 12 Bartonella species have been recorded infecting humans, causing diseases of long historical characterization, such as cat scratch fever and trench fever, and emerging bartonellosis that mainly affect animal health professionals. For this reason, this study aimed to report a documented case of Bartonella bovis infecting a veterinarian from Mexico by the amplification, sequencing and phylogenetic reconstruction of the citrate synthase (gltA) and the RNA polymerase beta-subunit (rpoB) genes, and to report the natural course of this infection. To our knowledge, this work is the first to report the transmission of B. bovis via needlestick transmission to animal health workers in Latin America.

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ABSTRACT New viruses of the Picornavirales order have been discovered with the increase in the number of sequences obtained by high-throughput sequencing, as well as human stool-associated RNA virus (husavirus [HuV]), found in human stool samples. However, there is much to be clarified about HuV. Its cellular host, evolutionary history, and other biological characteristics are still unknown. Therefore, samples collected from human beings and environmental samples in a watershed in Southern Brazil were processed for the metagenomic library. Upon metagenomic analysis, we identified a HuV (husavirus LMM_67754 OP019707) genome with 8,846 bp, which was reported for the first time in Southern Brazil. The new genome presents only 37% of nucleotide identity with Brazilian strains and more than 90% with genomes from China, Vietnam, Venezuela, and the Netherlands. The HuV phylogeny presents significant differences among genomes, probably because multiple introductions of the virus may have occurred. Many questions still need to be answered about HuV. Therefore, more sequences and studies on this virus are necessary to improve the comprehension of the unknown origin of Picornavirales.

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ABSTRACT This study describes the laboratory investigation of two acute Chagas disease outbreaks that occurred in the riverside communities of Marimarituba and Cachoeira do Arua, in the Santarem municipality, Para State, located in the Northern region of Brazil, and occurred in March 2016 and August 2017, respectively. The generation of data regarding the diversity of Trypanosoma cruzi parasites circulating in the Amazon region is key for understanding the emergence and expansion of Chagas disease. This study aimed to identify T. cruzi Discrete Typing Units (DTUs) involved in two outbreaks of acute Chagas disease (ACD) directly from the patient’s biological sample. Nested and multiplex PCR targeting the 24Sα (rRNA) and mini-exon genes, respectively, were used to identify T. cruzi DTU in blood samples from patients diagnosed with ACD. The samples with positive cPCR were submitted for analysis for T. cruzi DTUs, which included 13 samples from the patients with ACD by oral transmission and two samples collected from two newborns of two women with ACD, from Marimarituba and Cachoeira do Arua. The samples were classified as T. cruzi TcIV, from Marimarituba’s outbreak, and T. cruzi TcI, from Cachoeira do Arua’s outbreak. The molecular identification of T. cruzi may increase understanding of the role of this parasite in Chagas disease’s emergence within the Amazon region, contributing to the improvement of the management of this important, but also neglected, disease.

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ABSTRACT Immune exhaustion and senescence are scarcely studied in HIV-pediatric patients. We studied the circulatory CD8 T cells activation/exhaustion and senescent phenotype of children and adolescents vertically infected with HIV or uninfected controls based on the expression of human leukocyte antigen (HLA-DR), CD38, T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), programmed death 1 (PD-1) and CD57 by flow cytometry, during approximately one year. Eleven HIV-infected (HI) and nine HIV-uninfected (HU) children/adolescents who received two doses or one dose of meningococcal C conjugate vaccine (MenC), respectively, were involved in this study. Blood samples were collected before the immunization (T0), 1–2 months after the first dose (T1), and 1–2 months after the second dose (T2), which was administered approximately one year after the first one. HI patients not receiving combined antiretroviral therapy (cART) showed a higher frequency of CD8 T cells TIGIT+, PD-1+ or CD57+, as well as a higher frequency of CD8 T cells co-expressing CD38/HLA-DR/TIGIT or CD38/HLA-DR/PD-1 when compared to HI treated or HU individuals, at all times that they were assessed. CD8 T cells co-expressing CD38/DR/TIGIT were inversely correlated with the CD4/CD8 ratio but positively associated with viral load. The co-expression of CD38/DR/TIGIT or CD38/DR/PD-1 on CD8 T cells was also inversely associated with the CD4 T cells expressing co-stimulatory molecules CD127/CD28. The results showed a higher expression of exhaustion/senescence markers on CD8 T cells of untreated HI children/adolescents and its correlations with viral load.

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ABSTRACT Aedes (Stegomyia) albopictus (Skuse, 1854) was reported in Brazil for the first time in 1986 and has shown marked expansion throughout the Brazilian territory. During a routine activity to control dengue fever conducted by the Division of Entomology of the Municipal Health Department in Rio Branco city, adults and immatures of Culicidae were collected in a peri-urban area. The identified Culicidae forms indicated that they belonged to the species Ae. albopictus. This is the first official record of the presence of Ae. albopictus in the Acre State, confirming its current presence in all Brazilian states.

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ABSTRACT The measles, mumps and rubella (MMR) vaccine is usually recommended from 24 months after a hematopoietic stem cell transplant (HSCT). Some authors have demonstrated that the MMR vaccination can be safe from 12 months post-HSCT in non-immunosuppressed patients, as recommended by the Brazilian National Immunization Program/Ministry of Health, since 2006. The objectives of this study were to evaluate when patients received MMR vaccine after an HSCT in our care service and if there were reports of any side effects. We retrospectively reviewed the records of HSCT recipients who received at least one MMR dose in our care service, a quaternary teaching hospital in Sao Paulo city, Brazil, from 2017 to 2021. We identified 82 patients: 75.6% (90.1% in the autologous group and 45.1% in the allogeneic group) were vaccinated before 23 months post-transplantation. None reported side effects following the vaccination. Our data support that the MMR vaccination is safe from 12 to 23 months after HSCT.

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ABSTRACT Two triatomine genera (Panstrongylus and Triatoma) have essentially been recorded in Rio Grande do Sul State, Brazil. Panstrongylus megistus should be highlighted since this species is one of the main vectors of Trypanosoma cruzi in Brazil, due to its wide geographical distribution and the high susceptibility to this protozoan. This study aimed to present not only the occurrence and distribution of P. megistus in the Porto Alegre city’s metropolitan area (PAMA), Rio Grande do Sul State, Brazil, but also the rates of T. cruzi infection, from 2009 to 2020. The PAMA, which comprises 34 cities and 4.4 million habitants, extends across the transition area in two biomes – Pampa and Mata Atlantica – found in the state. Results showed that P. megistus was recorded in 76.5% of cities (i.e., 26 out of 34), mainly in Porto Alegre city, where the vector was found in 11 out of the 12 years that were monitored. Three hundred and nineteen specimens were captured. Two hundred and sixty-seven specimens (83.7%) were located intradomicile (p < 0.0001), while 52.3% positivity for T. cruzi was found. Thus, P. megistus is important in the PAMA, because it invades and colonizes the households. Moreover, the high rates of T. cruzi infection have drawn attention.

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ABSTRACT Dengue is a global and growing health threat, especially in Southeast Asia, West Pacific and South America. Infection by the dengue virus (DENV) results in dengue fever, which can evolve to severe forms. Cytokines, especially interferons, are involved in the immunopathogenesis of dengue fever, and so may influence the disease outcomes. The aim of this study was to investigate the association between severe forms of dengue and two single nucleotide polymorphisms (SNPs) in the interferon-gamma gene (IFNG): A256G (rs2069716) and A325G (rs2069727). We included 274 patients infected with DENV serotype 3: 119 cases of dengue without warning signs (DWoWS), and 155 with warning signs (DWWS) or severe dengue (SD). DNA was extracted, and genotyped with Illumina Genotyping Kit or real time PCR (TaqMan probes). We estimated the adjusted Odds Ratios (OR) by multivariate logistic regression models. When comparing with the ancestral AA/AA diplotype (A256G/A325G), we found a protective association of the AA/AG against DWWS/SD among patients with secondary dengue (OR 0.51; 95% IC 0.24-1.10, p = 0.085), adjusting for age and sex. The variant genotype at locus A325G of the IFNG, in combination with the ancestral genotype at locus A256G, can protect against severe clinical forms of secondary dengue in Brazilian DENV3-infected patients.

Resumo em Inglês:

ABSTRACT Aedes albopictus is considered a potential vector of arboviruses in Colombia. Females and males naturally infected with dengue, Zika and chikungunya viruses have already been found in this country. We document the first record of Ae. albopictus in the Cordoba department, in North of Colombia. The finding was carried out during Ae. aegypti collection activities in the Ayapel, Montelibano, Planeta Rica, Pueblo Nuevo and Puerto Libertador municipalities. The entomological material was collected in water containers such as cement water tanks, tanks, bottles, tires, abandoned toilets, and plastic lids with natural water located in the intradomicile, peridomicile, and extra-domicile spaces of the homes. We collected 658 Ae. albopictus samples in the larva and pupa stages, and once these reached adulthood, we determined that 389 were female and 269 were male. This is the first record of the presence of Ae. albopictus in the Cordoba department.

Resumo em Inglês:

ABSTRACT Leishmania infantum is a protozoan that causes visceral leishmaniasis (VL) in the Americas and some regions of Europe. The disease is mainly characterized by hepatosplenomegaly and fever, and can be fatal. Factors related to the host and parasite can contribute to the transmission of Leishmania and the clinical outcome. The intraspecific genetic variability of L. infantum strains may be one of these factors. In this study, we evaluated the genetic variability of L. infantum obtained from bone marrow smear slides from patients in the Sao Paulo State, Brazil. For this, the minicircle of the kDNA hypervariable region was used as target by Sanger sequencing. By analyzing the similarity of the nucleotides and the maximum likelihood tree (Fasttree), we observed a high similarity (98%) among samples. Moreover, we identified four different profiles of L. infantum. In conclusion, L. infantum strains from Sao Paulo State, Brazil, showed low diversity measured by minicircle of the kDNA hypervariable region.

Resumo em Inglês:

ABSTRACT Isoniazid is a key component of tuberculosis treatment. Adequate exposure is a determinant for therapeutic success; however, considerable inter- and intraindividual variations in drug plasma levels can lead to unfavorable outcomes. While some predictors of isoniazid levels are well-known, others, such as sex, yield controversial results, requiring further investigation to optimize exposure. This study investigates whether the sex of patients influences the dose administered and the concentrations of isoniazid in plasma. Levels of isoniazid were associated with the N-acetyltransferase 2 phenotypes. A total of 76 male and 58 female patients were included. Isoniazid was measured by high-performance liquid chromatography, and N-acetyltransferase 2 phenotypes were assessed using molecular techniques. The results show that the dose administered, expressed in mg/kg, was higher in females, but the plasma levels were similar between both sexes. Among patients, 46.2%, 38.8%, and 15% were slow, intermediate, and fast acetylators, respectively. As expected, isoniazid levels were associated with the acetylation phenotypes, with higher concentrations in the slow acetylators. Thus, sex-related difference in isoniazid levels is due to the body weight of patients, and the optimized dose regimen based on patient weight and acetylator phenotypes can improve the treatment outcomes.