Hepatosplenic involvement of tuberculosis: an uncommon presentation that demands attention in specific scenarios.

Abdominal tuberculosis (TB), a potential differential diagnosis for acute and chronic abdomen, should be considered in specific situations, such as immunosuppressant or biological drug use, HIV, or in patients residing in endemic areas. Although the presence of thoracic tuberculosis may indicate abdominal TB, only 15% of patients with abdominal TB have evidence of pulmonary disease. Involvement of the liver and spleen is a common autopsy finding in patients with disseminated TB. However, the most common pattern is of fine miliary lesions. Hepatic involvement with a macronodular pattern, a rare occurrence, is linked to dissemination through the portal vein. The splenic macronodular form, an extremely rare presentation, can manifest as solitary or multiple nodules, oval or round, with a variable appearance reflecting different stages of the disease, adding to the uniqueness of this case.

When the adrenals alert us to a systemic fungal disease.

We present a patient referred for investigation of adrenal insufficiency, confirmed due to disseminated paracoccidioidomycosis (PCM), with abdominal and central nervous system (CNS) involvement. Establishing the pathogenesis and immunological processes involved in chronic or latent infections by PCM has been challenging. Medical doctors caring for patients with immunodeficiencies should learn about these fungal infections to properly guide travel planning and have this possibility in the diagnostic arsenal when the patient returns from endemic areas. After 13 months of treatment, the patient showed good clinical evolution, and we repeated imaging exams, showing partial improvement of the preview lesions. Diagnosis and treatment can prevent catastrophic events.

Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice.

Zika virus (ZIKV) has the ability to cross placental and brain barriers, causing congenital malformations in neonates and neurological disorders in adults. However, the pathogenic mechanisms of ZIKV-induced neurological complications in adults and congenital malformations are still not fully understood. Gas6 is a soluble TAM receptor ligand able to promote flavivirus internalization and downregulation of immune responses. Here we demonstrate that there is a correlation between ZIKV neurological complications with higher Gas6 levels and the downregulation of genes associated with anti-viral response, as type I IFN due to Socs1 upregulation. Also, Gas6 gamma-carboxylation is essential for ZIKV invasion and replication in monocytes, the main source of this protein, which was inhibited by warfarin. Conversely, Gas6 facilitates ZIKV replication in adult immunocompetent mice and enabled susceptibility to transplacental infection. Our data indicate that ZIKV promotes the upregulation of its ligand Gas6, which contributes to viral infectivity and drives the development of severe adverse outcomes during ZIKV infection.

Specific Biomarkers Associated With Neurological Complications and Congenital Central Nervous System Abnormalities From Zika Virus-Infected Patients in Brazil.

Background: Zika virus (ZIKV) infections have been linked to different levels of clinical outcomes, ranging from mild rash and fever to severe neurological complications and congenital malformations. Methods: We investigated the clinical and immunological response, focusing on the immune mediators profile in 95 acute ZIKV-infected adult patients from Campinas, Brazil. These patients included 6 pregnant women who later delivered during the course of this study. Clinical observations were recorded during hospitalization. Levels of 45 immune mediators were quantified using multiplex microbead-based immunoassays. Results: Whereas 11.6% of patients had neurological complications, 88.4% displayed mild disease of rash and fever. Several immune mediators were specifically higher in ZIKV-infected patients, and levels of interleukin 10, interferon gamma-induced protein 10 (IP-10), and hepatocyte growth factor differentiated between patients with or without neurological complications. Interestingly, higher levels of interleukin 22, monocyte chemoattractant protein 1, TNF-α, and IP-10 were observed in ZIKV-infected pregnant women carrying fetuses with fetal growth-associated malformations. Notably, infants with congenital central nervous system deformities had significantly higher levels of interleukin 18 and IP-10 but lower levels of hepatocyte growth factor than those without such abnormalities born to ZIKV-infected mothers. Conclusions: This study identified several key markers for the control of ZIKV pathogenesis. This will allow a better understanding of the molecular mechanisms of ZIKV infection in patients.

Probable transfusion-transmitted Zika virus in Brazil.

BACKGROUND: Zika virus (ZIKV) is an emerging arthropod-borne flavivirus transmitted by Aedes mosquitoes. Recent commentaries regarding ZIKV routes of transmission describe a potential transmission by transfusion. Herein, we report a probable case of transfusion-transmitted ZIKV infection through a platelet transfusion that was detected from postdonation information. CASE REPORT: A blood donor made a voluntary telephone report to the blood donor facility 3 days after donation and informed the facility of a febrile illness (fever, malaise, and headaches). Due to the ongoing dengue epidemic, the initial clinical investigation included dengue among other possible diagnoses. The serology and molecular laboratory results excluded dengue infection. However, stored samples from the donation were positive for ZIKV on reverse transcription-polymerase chain reaction (RT-PCR) analysis. A retrospective investigation demonstrated that the platelet concentrate, which was part of a pool, had been transfused after a liver transplantation. A physician had evaluated the patient 4 days after surgery. Laboratory investigation showed enzyme-linked immunosorbent assay results that were negative for dengue immunoglobulin M antibodies; however, the results were positive for hemagglutination inhibition antibodies against flavivirus. ZIKV RT-PCR and virus isolation analyses in cell cultures from recipient serum were both positive. The sequencing confirmed ZIKV in the donor and patient samples. Ten partial nucleotide sequences from the ZIKV strain that were detected in the donor were aligned and compared with the ZIKV genome detected in the recipient, revealing a 99.8% homology between the two strains. CONCLUSIONS: This is a case of probable transmission of ZIKV through blood transfusion. The patient had been transfused with the blood product from an infected donor, most likely in the incubation period after ZIKV infection but prior to clinical disease onset. This report emphasizes the importance of postdonation information and recipient investigations during outbreaks of potentially blood-borne infections.

Potential role of CC chemokine receptor 6 in prediction of late-onset cytomegalovirus infection following solid organ transplant.

CCR6 is a chemokine receptor involved in homing memory T cells, particularly Th17 cells, to sites of mucosal inflammation. Despite the critical role of memory T cells in long-term protective immunity against cytomegalovirus (CMV), a virus that reactivates at multiple mucosal sites, the ability of CCR6 or other Th17 marker expression to predict CMV reactivation following transplantation is not clear. Using 11-color flow cytometry, in this prospective single-center pilot study, we measured the expression of CCR6 and other markers of T-cell function in peripheral blood samples obtained from 21 SOT recipients at the time of discontinuation of anti-CMV prophylaxis. CMV viremia was monitored on a monthly basis after discontinuation of prophylaxis. Eleven patients (52%) developed CMV viremia during the six-month follow-up period. Late-onset CMV infection was preceded by an immune phenotype characterized by increased CCR6 expression on bulk CD4(+) T cells and a reduced number of circulating CMV IE-1-specific Th1 (CD4(+) IFN-γ(+)) cells. Among the markers evaluated, CCR6 was the best single predictor of late-onset CMV infection. Our results suggest that CCR6 expression at the time of discontinuation of antiviral prophylaxis might be a useful predictor of late-onset CMV reactivation and provide the basis for future larger prospective studies.

Simkania negevensis and acute cellular rejection in lung transplant recipients.

Simkania negevensis infection has been hypothesized to play a role in lung transplant rejection. The incidence of S. negevensis infection and its association with acute cellular rejection (ACR) were determined in a prospective cohort study of 78 lung transplant recipients (LTRs) in Toronto, Canada, and Pittsburgh, USA, from July 2007 to January 2010. Simkania negevensis testing was detected by quantitative polymerase chain reaction (PCR) on bronchoalveolar lavage fluid. The relationship between S. negevensis and ACR was examined using Cox proportional hazards models and generalized linear and latent mixed models. Cumulative incidence estimates for time-to-ACR in S. negevensis PCR-positive vs. PCR-negative LTRs were 52.7% vs. 31.1% at six months and 68.9% vs. 44.6% at one yr, respectively. Although not statistically significant, there was a trend toward a higher risk of ACR among S. negevensis PCR-positive vs. PCR-negative LTRs in all statistical models.

Isolation and drug susceptibility of Candida parapsilosis sensu lato and other species of C. parapsilosis complex from patients with blood stream infections and proposal of a novel LAMP identification method for the species.

Candida parapsilosis complex (CPC) is the third Candida species isolated in blood cultures of patients from our Hospital, following C. albicans and C. tropicalis. From 2006 to 2010, the median annual distribution of CPC was 8 cases/year. Records of 36 patients were reviewed. CPC were 31 (86.1%) C. parapsilosis; 4 (11.1%) C. orthopsilosis; and 1 (2.8%) C. metapsilosis. Clinical characteristics were central venous catheter, 34 (94.4%); parental nutrition, 25 (70%); surgery, 27 (57.9%); prior bacteremia, 20 (51.3%); malignancy, 18 (50%). General mortality was 47.2%. Death was higher in immunosuppressed patients (17 vs. 11; p = 0.003). Three out four (75%) patients with C. orthopsilosis and 14 out 31 (45.2%) with C. parapsilosis died (p = 0.558). Thirty-nine individual isolates were tested for susceptibility to seven antifungal drugs, with MICs values showing susceptibility to all of them. Two isolates, one C. orthopsilosis and one C. parapsilosis, had fluconazole MIC = 4 µg/mL. Differentiation among CPC has implication in caring for patients with invasive candidiasis since there are differences in virulence, pathogenicity and drug susceptibility. A method targeting the topoisomerase II gene based on loop-mediated isothermal amplification (LAMP) was developed. LAMP emerges as a promising tool for the identification of fungal species due to the high sensitivity and specificity. LAMP can be performed at the point-of-care, being no necessary the use of expensive equipment. In our study, the method was successful comparing to the DNA sequencing and proved to be a reliable and fast assay to distinguish the three species of CPC.

Six-year experience with GM test in hematological patients in a public Brazilian tertiary hospital.

Invasive fungal infection (IFI) is frequent in patients with hematologic malignancies or submitted hematopoietic stem cell transplantation (HSCT). OBJECTIVES: To evaluate the role of the GM (galactomannan) test in prescribing therapeutic antifungals; to determine invasive aspergillosis (IA) frequency, the factors associated with positive GM test, and the in-hospital mortality. METHODS: We conducted a retrospective observational study including patients aged 18 or over with hematological malignancy or submitted to HSCT. GM test was measured twice weekly. The hypothesis of IFI was considered in patients with neutropenia and persistent fever despite broad-spectrum antibiotics. RESULTS: A total of 496 patients were evaluated; the mean of GM tests performed per patient was 4.2 (+3.1), and 86 (17.3 %) had positive results. IFI was diagnosed in 166 (33.5 %) and IA in 22 (24.6 %) patients. Positive GM test was more frequent in patients with IFI (72.2 % and 25.1 %; OR 8.1; 95 % CI 4.8 - 13.8), and was associated with therapeutic antifungals prescription (52, 9 % and 20.5 %; OR 4.3, 95CI% 2.0 - 9.4), as well as lung abnormalities on HRCT (45.3% vs. 21.5 %; OR 3.0, 95 %CI 1.4 - 6.5). Mortality was 31.6 %. In the multivariate analysis, the variables associated with mortality were the hypothesis of IFI (OR 6.35; 95 % CI 3.63-11.12.0), lung abnormalities on HRCT (57.9 % and 26.9 %; OR 2 0.6; 95 % CI 1.5 - 4.4), and positive GM test (57.9 % and 26.9 %; OR 2.7 95 % CI 1.6 - 4.5). CONCLUSIONS: Positive GM test was associated with lung abnormalities on HRCT and with the introduction of therapeutic antifungals. If adequate anti-mold prophylaxis is available, the GM test should not be used as screening, but to investigate IFI in high-risk patients. The diagnosis of IFI, positive GM test and lung abnormalities on HRCT were predictors of hospital mortality in patients with hematological malignancies or undergoing HSCT.

Visual analysis of DNA microarray data for accurate molecular identification of non-albicans Candida isolates from patients with candidemia episodes.

The performance of a visual slide-based DNA microarray for the identification of non-albicans Candida spp. was evaluated. Among 167 isolates that had previously been identified by Vitek 2, the agreement between DNA microarray and sequencing results was 97.6%. This DNA microarray platform showed excellent performance.

Is the incidence of candidemia caused by Candida glabrata increasing in Brazil? Five-year surveillance of Candida bloodstream infection in a university reference hospital in southeast Brazil.

From 2006 to 2010, a retrospective study was conducted in a university referral tertiary care hospital to study the frequency and distribution of Candida species in different medical specialties. The use of mechanical ventilation, central venous catheter, and urinary catheter were recorded per 1,000 patient-days and the use of antifungals was calculated using defined daily dose (DDD). A total of 313 episodes were identified and the overall incidence was 0.54 (0.41-0.71) episodes per 1,000 patient-days. Candida albicans caused 44% of the overall episodes, followed by C. tropicalis (21.7%), C. parapsilosis (14.4%), C. glabrata (11.2%), and C. krusei (3.5%). The incidence of C. glabrata significantly increased from 2006-2010 (range: 4.8-23.5%) (P = 0.024). Candida glabrata was associated with malignancies (P = 0.004) and C. krusei with hematologic malignancies (P < 0.0001). The use of antifungals was higher in the hematology/bone marrow transplant units and represented 40% of all fluconazole prescription in the hospital. There was no correlation with the use of fluconazole and the increasing ratio of C. glabrata (r = 0.60). The use of invasive devices was significantly higher in the intensive care units (ICUs) than the medical and surgical emergencies units (P < 0.001). In contrast, the emergencies had higher incidence of candidemia (2-2.1 episodes/1,000 patient-days) than the ICUs (1.6 episodes 1,000 patient-days). Candida glabrata candidemia showed a significant increase in contrast to the current national literature where C. parapsilosis remained the most important non-C. albicans Candida species in Brazilian hospitals. Our findings suggested that the increasing incidence of C. glabrata was not associated with use of fluconazole and other risk factors might play an important role.

Low seroconversion after one dose of AS03-adjuvanted H1N1 pandemic influenza vaccine in solid-organ transplant recipients.

BACKGROUND: Immunocompromised individuals are more susceptible to complications produced by influenza infection. As a result, solid-organ transplant (SOT) recipients were targeted as a priority group to receive AS03-adjuvanted H1N1 influenza vaccine during 2009. OBJECTIVE: To evaluate seroconversion after one dose of adjuvanted pandemic influenza H1N1 (pH1N1) vaccine in SOT recipients. METHODS: Adult SOT recipients were enrolled to receive one 3.75 µg dose of adjuvanted pH1N1 vaccine. Serological status was tested using a hemagglutination inhibition assay before and two and four weeks postvaccination. RESULTS: The five SOT recipients (one liver, two kidney and two lung transplants) had a median age of 50 years (range 36 to 53 years), and three were male, who were a median time of three years (range two months to 15 years) post-transplant. All patients were on a double or triple immunosuppressive regimen. The prevaccination pH1N1 titre was 1:10 in four patients and 1:40 in one patient. Seroprotection was observed only in one patient, with a rise in titre from 1:40 at baseline to 1:320 at both two and four weeks after vaccination. This lung transplant recipient had documented previous infection with pH1N1. CONCLUSION: Results of the present small study call into question whether one dose of adjuvanted pH1N1 vaccine can provide seroprotection in SOT recipients.

HISTORIQUE: Les personnes immunocompromises sont plus vulnérables aux complications de l'infection par l'influenza. Par conséquent, les receveurs d'une transplantation d'organe plein (TOP) faisaient partie des groupes prioritaires appelés à recevoir le vaccin contre la grippe pandémique H1N1 contenant l'adjuvant AS03 en 2009. OBJECTIF: Évaluer la séroconversion après une dose du vaccin contre la grippe pandémique H1N1 contenant l'adjuvant (pH1N1) chez les receveurs d'une TOP. MÉTHODOLOGIE: Les receveurs d'une TOP d'âge adulte ont été retenus afin de recevoir une dose de 3,75 µg du vaccin pH1N1 contenant l'adjuvant. Les chercheurs ont vérifié leur statut sérologique au moyen de la réaction d'inhibition de l'hémagglutination avant la vaccination, puis deux et quatre semaines plus tard. RÉSULTATS: Les cinq receveurs d'une TOP (un foie, deux reins et deux poumons) avaient un âge médian de 50 ans (plage de 36 à 53 ans), trois étaient de sexe masculin et avaient subi leur transplantation depuis une médiane de trois ans (plage de deux mois à 15 ans). Tous les patients étaient sous bithérapie ou trithérapie immunosuppressive. Le titrage du pH1N1 avant la vaccination était de 1:10 chez quatre patients et de 1:40 chez un patient. Les chercheurs ont observé une séroprotection chez seulement un patient, son titre étant passé de 1:40 avant le vaccin à 1:320 tant deux que quatre semaines après la vaccination. Ce receveur d'une transplantation de poumon avait eu une infection par la pH1N1 attestée. CONCLUSION: Les résultats de la présente petite étude mettaient en doute la capacité d'une dose du vaccin pH1N1 contenant l'adjuvant à assurer une séroprotection chez les receveurs d'une TOP.

Cohort study of hospitalized patients with COVID-19 at Brazilian tertiary-care hospital: Occurrence of adverse events and mortality.

INTRODUCTION: Patients hospitalized with COVID-19 are often submitted to invasive procedures and they are at risk for hospital-associated adverse events. OBJECTIVES: To evaluate the epidemiological and clinical aspects of patients hospitalized with COVID-19; the occurrence of adverse events and the risk factors for mortality. METHOD: Cohort study that included adult patients hospitalized with a diagnosis of SARSCoV-2 infection, at the tertiary University Hospital of UNICAMP from March 2020 to March 2021. Patients were identified through the hospital epidemiological surveillance system and followed until discharge or death. Descriptive, comparative, and logistic regression analysis was performed. RESULTS: 650 adult patients were included. The main adverse events identified were nosocomial infections (31.5%), renal failure (33.8%), thromboembolic and vascular events (12.6%). Mortality was higher among those with bloodstream infections (30.2% vs. 8.6%; p < 0.0001), ventilator-associated pneumonia (VAP, 52.5% vs. 12.3%; p < 0.0001), catheter associated urinary infection (27.3% vs. 7.2%; p < 0.0001); thromboembolic and vascular events (23.0% vs. 9.9%; p < 0.0001) and renal failure (81.3% vs. 20.9%; p < 0.0001). Klebsiella pneumoniae (15.6%), Pseudomonas aeruginosa (14.4%), Enterococcus faecalis (8.6%) were the most isolated bacteria. Logistic regression analysis identified age, (RR = 1.03; 95% CI 1.02 to 1.05); ICU admission (RR = 3.06; 95% CI 1.59 to 5.87), vasoactive drug use (RR = 3.1; 95% CI 1.79 to 4.82); renal failure (RR = 7.76; 95% CI 4.54 to 13.26); and VAP (RR = 2.2; 95% CI 1.23 to 3.96), independently associated with mortality. CONCLUSION: adverse events have an important impact on the evolution of patients with COVID-19, reinforcing the need for optimized prevention and control measures as an essential part of care for these patients.

Clinical outcomes of aspergillosis among paediatric and adult inpatients: A multicentre study in a Brazilian metropolitan area.

BACKGROUND: Invasive Aspergillosis (IA) is a disease of significant clinical relevance, especially among immunosuppressed patients, and is associated with high mortality rates. In this study, we evaluated the epidemiological features and clinical outcomes in children and adults with IA. METHODS: This was an observational, multicentre, prospective surveillance study of inpatients with IA at two different hospitals in Campinas, Brazil, between 2018 and 2021. RESULTS: A total of 44 patients were identified (54.5% males), with a median age of 42 years (interquartile range (IQR):19.25-59 years, varying between 1 and 89 years). The following baseline conditions were identified: 61.4% were oncohaematological patients and 20.5% were solid organ transplant recipients. Among oncohaematological patients, 77.8% exhibited severe or persistent neutropenia. The median time between the onset of neutropenia and the diagnosis of fungal infection was 20 days (IQR: 10.5-26 days; range, 0-68 days). The interval between neutropenia onset and fungal infection was longer in paediatric than in general hospital (average, 29 vs. 13.4 days; median 26 vs 11 days; p=0.010). After the diagnosis of IA, the survival rates were 44.2% and 30.0% at 180 and 360 days, respectively. Survival was greater in patients aged ≤ 21 years (p = 0.040; log-rank test). They observed no difference in IA mortality related to COVID-19 pandemic. CONCLUSION: High mortality associated with IA was observed in both hospitals. Individuals over the age of 21 have a lower survival rate than younger patients.

Oximetry at admission as a predictor of tomographic and functional impairment after 3-6 months in hospitalized patients with COVID-19.

OBJECTIVE: To investigate characteristics that may be associated with radiologic and functional findings following discharge in patients with severe coronavirus disease 2019 (COVID-19). METHODS: This single-center, prospective, observational cohort study comprised patients aged >18 years who were hospitalized with COVID-19 pneumonia, between May and October 2020. After 3 to 6 months of discharge, patients were clinically evaluated and underwent spirometry, a 6-minute walk test (6MWT), and chest computed tomography (CT). Statistical analysis was performed using association and correlation tests. RESULTS: A total of 134 patients were included (25/114 [22%] were admitted with severe hypoxemia). On the follow-up chest CT, 29/92 (32%) had no abnormalities, regardless of the severity of the initial involvement, and the mean 6MWT distance was 447 m. Patients with desaturation on admission had an increased risk of remaining CT abnormalities: patients with SpO2 between 88 and 92% had a 4.0-fold risk, and those with SpO2 < 88% had a 6.2-fold risk. The group with SpO2 < 88% also walked shorter distances than patients with SpO2 between 88 and 92%. CONCLUSION: Initial hypoxemia was found to be a good predictor of persistent radiological abnormalities in follow-up and was associated with low performance in 6MWT.

Clinical outcomes and molecular characterization of drug-resistant tuberculosis in pre- and extensively drug-resistant disease based on line probe assays.

Multidrug-resistant tuberculosis (MDR-TB) represents a significant impact in transmission, outcome, and health costs. The World Health Organization recommends implementation of rapid diagnostic methods for multidrug-resistance detection. This study was performed to evaluate the frequency of pre- and extensively drug resistant tuberculosis (pre-XDR-TB and XDR-TB) among MDR-TB patients, the pattern of resistance mutations for fluoroquinolones and the clinical outcome. Adult patients followed at a Brazilian regional reference center for TB, from January 2013 to June 2019 were included. Stored Mycobacterium tuberculosis (Mtb) cultures were recovered, the DNA was extracted, and the susceptibility test was performed using the line probe assay for second line antimycobacterial drugs, Genotype MTBDRsl version 2.0 (Hain Lifescience, CmbH, Germany). Among 33 MDR-TB included patients, we diagnosed XDR-TB or pre-XDR in five (15%) cases. Of these, mutations related to fluoroquinolones resistance were observed in four Mtb isolates, including one who had no phenotypic resistance profile. In two other patients with phenotypic resistance to ofloxacin, genotypic resistance was not found. Case fatality rate was 60% in pre/XDR-TB group, compared to 3.6% in the remaining of patients. This study observed few cases of pre-XDR and XDR-TB among a MDR-TB cohort. Phenotypic and genotypic assays presented good agreement. Clinical outcome was more favorable for patients with susceptibility to fluoroquinolones and injectable drugs.

COVID-19 and invasive fungal coinfections: A case series at a Brazilian referral hospital.

BACKGROUND: COVID-19 co-infections have been described with different pathogens, including filamentous and yeast fungi. METHODOLOGY: A retrospective case series study conducted from February to December 2020, at a Brazilian university hospital. Data were collected from two hospital surveillance systems: Invasive fungal infection (IFI) surveillance (Mycosis Resistance Program - MIRE) and COVID-19 surveillance. Data from both surveillance systems were cross-checked to identify individuals diagnosed with SARS-CoV-2 (by positive polymerase chain reaction (PCR)) and IFI during hospital stays within the study period. RESULTS: During the study period, 716 inpatients with COVID-19 and 55 cases of IFI were identified. Fungal co-infection with SARS-CoV-2 was observed in eight (1%) patients: three cases of aspergillosis; four candidemia and one cryptococcosis. The median age of patients was 66 years (IQR 58-71 years; range of 28-77 years) and 62.5% were men. Diagnosis of IFI occurred a median of 11.5 days (IQR 4.5-23 days) after admission and 11 days (IQR 6.5-16 days) after a positive PCR result for SARS-CoV-2. In 75% of cases, IFI was diagnosed in the intensive care unit (ICU). Cases of aspergillosis emerged earlier than those of candidemia: an average of 8.6 and 28.6 days after a positive PCR for SARS-CoV-2, respectively. All the patients with both infections ultimately died. CONCLUSION: A low rate of COVID-19 co-infection with IFI was observed, with high mortality. Most cases were diagnosed in ICU patients. Aspergillosis diagnosis is highly complex in this context and requires different criteria.

A novel association of acquired ADAMTS13 inhibitor and acute dengue virus infection.

BACKGROUND: Dengue is a mosquito-borne viral disease with an increasing incidence worldwide. Thrombocytopenia is a common finding in dengue virus (DV) infection; however, the underlying mechanisms remain unknown. CASE REPORT: Here we provide the first evidence of a case of antibody formation against ADAMTS13 (ADAMTS13 inhibitor) in the course of a severe acute DV infection resulting in thrombotic microangiopathy (TMA). The patient presented with classical dengue symptoms (positive epidemiology, high fever, myalgia, predominantly in the lower limbs and lumbar region for 1 week) and, after 11 days of initial symptoms, developed TMA. Clinical and laboratorial investigation of dengue and TMA was performed. RESULTS: The patient presented with ADAMTS13 inhibitor (IgG) during the acute phase of the disease, without anti-platelet antibodies detectable. Dengue infection had laboratorial confirmation. There were excellent clinical and laboratory responses to 11 serial plasma exchanges. Anti-ADAMTS13 inhibitor disappeared after remission of TMA and dengue resolution. No recurrence of TMA symptoms was observed after 2-year follow-up. CONCLUSIONS: Although the real incidence of dengue-related TMA is unknown, this case provides the basis for future epidemiologic studies on acquired ADAMTS13 deficiency in DV infection. The prompt clinical recognition of this complication and early installment of specific therapy with plasma exchange are likely to improve the outcome of severe cases of dengue.

Susceptibility of Mycobacterium tuberculosis to first-line antimycobacterial agents in a Brazilian hospital: assessing the utility of the tetrazolium (MTT) microplate assay.

We conducted a cross-sectional, hospital-based study between January 2006-March 2008 to estimate the resistance of Mycobacterium tuberculosis to first-line drugs in patients with tuberculosis at a Brazilian hospital. We evaluated the performance of the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] (MTT) microplate assay compared with the Bactec-MGIT 960 system for mycobacteria testing. The prevalence of resistance in M. tuberculosis was 6.7%. Multidrug-resistance [resistance to rifampicin (RMP) and isoniazid (INH)], INH-resistance and streptomycin (SM)-resistance accounted for 1%, 3.8% and 3.8% of all resistance, respectively, and all isolates were susceptible to ethambutol (EM). The resistance was primary in four cases and acquired in three cases and previous treatment was associated with resistance (p = 0.0129). Among the 119 M. tuberculosis isolates, complete concordance of the results for INH and EM was observed between the MTT microplate and Bactec-MGIT 960TM methods. The observed agreement for RMP was 99% (sensitivity: 90%) and 95.8% for SM (sensitivity 90.9%), lower than those for other drugs. The MTT colourimetric method is an accurate, simple and low-cost alternative in settings with limited resources.

Cost-Effectiveness Analysis of Influenza A (H1N1) Chemoprophylaxis in Brazil.

Background: Oseltamivir and zanamivir are recommended for treating and preventing influenza A (H1N1) worldwide. In Brazil, this official recommendation lacks an economic evaluation. Our objective was to assess the efficiency of influenza A chemoprophylaxis in the Brazilian context. Methods: We assessed the cost-effectiveness of oseltamivir and zanamivir for prophylaxis of influenza for high risk population, compared to no prophylaxis, in the perspective of Brazilian public health system. Quality-adjusted life years (QALY) and effectiveness data were based on literature review and costs in Brazilian real (BRL) were estimated from official sources and micro-costing of 2016's H1N1 admissions at a university hospital. We used a decision-tree model considering prophylaxis and no prophylaxis and the probabilities of H1N1, ambulatory care, admission to hospital, intensive care, patient discharge, and death. Adherence and adverse events from prophylaxis were included. Incremental cost-effectiveness ratio was converted to 2016 United States dollar (USD). Uncertainty was assessed with univariated and probabilistic sensitivity analysis. Results: Adherence to prophylaxis was 0.70 [95% confidence interval (CI) 0.54; 0.83]; adverse events, 0.09 (95% CI 0.02; 0.18); relative risk of H1N1 infection in chemoprophylaxis, 0.43 (95% CI 0.33; 0.57); incidence of H1N1, 0.14 (95% CI 0.11; 0.16); ambulatory care, 0.67 (95% CI 0.58; 0.75); hospital admission, 0.43 (CI 95% 0.39; 0.42); hospital mortality, 0.14 (CI 95% 0.12; 0.15); intensive care unit admission, 0.23 (95% CI 0.20; 0.27); and intensive care mortality, 0.40 (95% CI 0.29; 0.52). QALY in H1N1 state was 0.50 (95% CI 0.46; 0.53); in H1N1 inpatients, 0.23 (95% CI 0.18; 0.28); healthy, 0.885 (95% CI 0.879; 0.891); death, 0. Adverse events estimated to affect QALY in -0.185 (95% CI -0.290; -0.050). Cost for chemoprophylaxis was BRL 39.42 [standard deviation (SD) 17.94]; ambulatory care, BRL 12.47 (SD 5.21); hospital admission, BRL 5,727.59 (SD 7,758.28); intensive care admission, BRL 19,217.25 (SD 7,917.33); and adverse events, BRL 292.05 (SD 724.95). Incremental cost-effectiveness ratio was BRL -4,080.63 (USD -1,263.74)/QALY and -982.39 (USD -304.24)/H1N1 prevented. Results were robust to sensitivity analysis. Conclusion: Chemoprophylaxis of influenza A (H1N1) is cost-saving in Brazilian health system context.