Resumo em Inglês:

Abstract Background The heterogeneity in detection rates of Human immunodeficiency virus, (HIV), Human T lymphotropic virus (HTLV) and Hepatitis B and C infections among pregnant women and the continuous exposure to risk factors limits the adoption of preventive and control actions. Objective To evaluate the HIV, HTLV, Hepatitis B and C seroprevalence rates, and associated risk factors in parturient women in Salvador, Brazil. Methods This was a cross-sectional study in 2099 parturient women attended in two public maternity hospitals in Salvador, Brazil. One blood sample was drawn for serological screening and socio-demographic, obstetric and clinical data were collected. Results HIV seroprevalence rate was 1.5% (of which 0.6% were new cases); seroprevalence rates for HTLV, HBV, and HCV were 0.4%, 0.4%, and 0.1%, respectively. Univariate analysis showed a significant association between socio-demographic and behavioral factors with retroviral infections, while viral hepatitis was mainly associated with parenteral exposure. In a multivariate analysis, multiple sexual partners (OR 3.3; 95% CI: 1.1–9.2), history of sexual/domestic violence (OR 2.8; 95% CI: 1.1–6.9), syphilis co-infection (OR 2.6; 95% CI: 1.0–6.9), use of alcohol or drugs (OR 2.5; 95% CI: 1.2–5.5), and low schooling level (OR 2.3; 95% CI: 1.1–4.9) were independent risk factors for HIV infection. History of stillbirth and low birth weight infants was significantly associated with HTLV positive status, showing a negative impact on gestation. Conclusions The seroprevalence rates for HIV, HCV, HBV, and HTLV were similar to that found in previous studies in other Brazilian regions. The high individual, socioeconomic, and social vulnerability detected in seropositive parturient women indicates the need to improve coverage and effectiveveness of STDs control with prevention, detection and monitoring strategies, focusing in pregnant women exposed to high biopsychosocial risk.

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Abstract Introduction Life expectancy of people living with human immunodeficiency (PLHIV) has increased mainly due to the accessibility and effectiveness of antiretroviral therapy (ART). However, adverse effects from long-term use of antiretrovirals, and the physiological changes associated with aging, may compromise the quality of life of PLHIV, in addition to causing new demands on the healthcare system. Objectives Estimate the frequency of osteoporosis and osteopenia in patients on prolonged ART and to verify their associated factors. Methods A cross-sectional study was conducted in Belo Horizonte, Minas Gerais, Brazil, from August 2017 to June 2018, in a sample of PLHIV (age≥18 years) who started ART between 2001 and 2005. Data were collected through face-to-face interviews, physical evaluation, laboratory tests, and Dual-Energy X-Ray Absorptiometry Screening (DEXA). The outcome of interest was presence of bone alteration, defined as presence of osteopenia or osteoporosis in DEXA. The association between the explanatory variables and the event was assessed through odds ratio (OR) estimate, with 95% confidence interval (CI). Multiple logistic regression was performed to evaluate factors independently associated with bone alteration. Results Among 92 participants, 47.8% presented bone alteration (19.6% osteoporosis and 28.2% osteopenia). The variables that remained in the final logistic regression model were age ≥ 50 years (OR: 12.53; 95% CI: 4.37–35.90) and current alcohol use (OR: 2.63; 95% CI: 0.94–7.37). Conclusions This study showed a high frequency of bone changes, especially in PLHIV older than 50 years. This information is useful to stimulate the screening and timely intervention of this comorbidity of PLHIV on prolonged use of ART in order to prevent or minimize complications and new demands on the healthcare system.

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Abstract The frequencies of the Human leukocyte antigen (HLA) alleles in the Puyanawa indigenous reserve population and their association with the NDO-LID and ELISA PGL-1 rapid serological test was assessed. This was a cross-sectional study with an epidemiological clinical design conducted in two indigenous communities in the state of Acre, Brazil. Blood was collected in a tube with EDTA to identify HLA alleles and perform serological tests. DNA was obtained using the salting out procedure. The LabType™ technique (One-Lambda-USA) was used for HLA class I (loci A*, B* and C*) and II (loci DRB1*, DQA1* and DQB1*) typing. Allele frequency was obtained by direct count, and the chi-square test was used to assess the association with the NDO-LID and PGL-1 tests. The most frequent alleles in the two communities were: HLA-A*02:01, HLA-B*40:02, HLA-DRB1*16:02, HLA-DQA1*05:05 and HLA-DQB1*03:01. The allele HLA-C*04:01 was the most common in the Barão community, and the allele HLA-C*07:01 in Ipiranga. Among individuals who presented seropositivity to the NDO-LID test, the association with alleles HLA-A*02 (43.18% vs 24.8%, p = 0.03, OR = 2.35) and HLA-B*53 (6.83% vs 0.0%, p = 0.03, OR = 8.95) was observed in the Barão community. HLA-B*15 was associated with non-seroconversion to the NDO-LID test in Ipiranga. In both communities, HLA-B*40 and HLA-C*03 were associated with positive serological response to ELISA PGL-1. The HLA class I and II alleles most frequently found in this study have already been described among Terena indigenous groups, and HLA class I contributes to seroconversion to NDO-LID and PGL-1 tests in inhabitants of the Barão and Ipiranga communities.

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Abstract Background Despite the emergence of more effective therapies, hepatitis C virus (HCV) infection remains a serious public health problem at the global level. Currently, this virus is classified into seven genotypes and 67 subgenotypes, which in turn are distributed heterogeneously in Brazil and worldwide. Studies have shown that this genetic divergence results in differences in the progression of chronic disease associated with HCV infection and its treatment. Objective The aim of this study was to report the frequency of HCV genotypes in the state of Pará, Northern Brazil, and to assess the association between genotype and different clinical and laboratory characteristics, as well as risk factors for infection. Method Data from 85 medical records of untreated patients who had chronic hepatitis C infection were analyzed; the patients were evaluated at two hospitals in Belem, Pará, Brazil. Results Circulation of genotypes 1 and 3 was detected, with a higher prevalence of genotype 1 (75.3%) than genotype 3 (24.7%). In addition, there was a predominance of subgenotype 1b (60.34%) compared to 1a (20.69%) and 3a (18.97%). Reuse of needles and/or glass syringes was significantly associated with infection by HCV genotype 1 than genotype 3; however, the small number of patients infected with genotype 3 may have biased the results. No associations between genotype and the evaluated clinical and laboratory characteristics were observed. Conclusion This study reinforces the differences in the distribution of HCV genotypes in Brazil and showed no association between HCV genotype and progression of chronic hepatitis C in the studied group.

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Abstract Multi-drug resistant Gram-negative bacilli (GNB) have been reported as cause of serious hospital-acquired infections worldwide. The aim of this study was to investigate the in vitro activity of ceftolozane-tazobactam compared to other agents against GNB isolated from patients admitted to Brazilian medical centers between the years 2016 and 2017. Presence of β-lactamase encoding genes was also evaluated. Methods Antimicrobial susceptibility testing of GNB isolated from intra-abdominal (IAI), respiratory (RTI), and urinary tract infections (UTI) was performed according to ISO 227-1 guidelines and interpreted following CLSI and BrCAST/EUCAST guidelines. Qualifying Enterobacteriaceae isolates were screened for the presence of β-lactamase genes by PCR followed by DNA sequencing. Results 1748 GNB collected from UTI (45.2%), IAI (25.7%) and RTI (29.1%) were evaluated. Ceftolozane-tazobactam remained highly active (94.7%) against E. coli isolates. Among K. pneumoniae, susceptibility rates were 85.9% and 85.4% for amikacin and colistin, whereas ceftolozane-tazobactam (44.1% susceptible) and carbapenems (55.2-62.2% susceptible) showed poor activity due to bla KPC-2. Against E. cloacae amikacin, imipenem, and meropenem retained good activity (>90%). Ceftolozane-tazobactam was the most potent β-lactam agent tested against P. aeruginosa (90.9% susceptible), including ceftazidime and imipenem resistant isolates. β-lactamase encoding genes testing was carried out in 433 isolates. bla CTX-M variants were predominant in E. coli, P. mirabilis and E. cloacae. Among the K. pneumoniae molecularly tested, most carried bla KPC (68.5%), with all harboring bla KPC-2, except two isolates carrying bla KPC-3 or bla KPC-30. ESBL encoding genes, mainly CTX-M family, were frequently detected in K. pneumoniae, plasmid-mediated AmpC were rare. A variety of PDC encoding genes were detected in P. aeruginosa isolates with five isolates harboring MBL and one KPC encoding genes. Conclusion Ceftolozane-tazobactam was very active against E. coli, P. mirabilis and P. aeruginosa isolates and could constitute an excellent therapeutic option including for those isolates resistant to extended-spectrum cephalosporins and carbapenems but not producers of carbapenemases.

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Abstract Two types of Epstein Barr virus (EBV1/EBV2) have been shown to infect humans. Although their genomes are similar, the regions containing the EBNA genes differ. This study aimed to characterize the EBV genotypes of infectious mononucleosis (IM) cases in the metropolitan region of Belém, Brazil, from 2005 to 2016. A total of 8295 suspected cases with symptoms/signs of IM were investigated by infectious disease physicians at Evandro Chagas Institute, Health Care Service, from January 2005 to December 2016. Out of the total, 1645 (19.8%) samples had positive results for EBV by enzyme immunoassay and 251 (15.3%) were submitted to polymerase chain reaction (PCR) technique, using the EBNA3C region, in order to determine the type of EBV. Biochemical testing involving aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase were also performed. EBV type was identified by PCR in 30.3% (76/251) of individuals; of those, 71.1% (54/76) were classified as EBV1, 17.1% (13/76) as EBV2, and 11.8% (9/76) as EBV1+EBV2. The main symptoms/signs observed with EBV1 infection were cervical lymphadenopathy (64.8%, 35/54), fever (63%, 34/54), headache (20.4%, 11/54), arthralgia (20.4%, 11/54), and exanthema (18.5%, 10/54). EBV2 infection was detected in all but two age groups, with an average age of 24 years. The most common signs/symptoms of EBV2 were fever (76.9%, 10/13), average duration of 18 days, and lymphadenopathy (69.2%, 9/13). In contrast, EBV1+EBV2 coinfections were more frequent in those aged five years or less (20.0%, 2/10). The symptoms of EBV1+EBV2 coinfection included fever (66.7%, 6/9), and cervical lymphadenopathy and headache (33.3%, 3/9) each. The mean values of hepatic enzymes according to type of EBV was significantly different (p<0.05) in those EBV1 infected over 14 years of age. Thus, this pioneering study, using molecular methods, identified the EBV genotypes in 30.3% of the samples, with circulation of EBV1, EBV2, and EBV1+EBV2 co-infection in cases of infectious mononucleosis in the northern region of Brazil.

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Abstract Objective To evaluate the clinical and epidemiological profile of bacterial meningitis and meningococcal disease in pediatric patients admitted to a Brazilian Secondary Public Hospital. Methods A descriptive observational study was conducted. Microbiologically proven bacterial meningitis or meningococcal disease diagnosed from 2008 to 2018 were included. Results A total of 90 patients were diagnosed with proven bacterial meningitis. There were 64 confirmed cases of meningococcal disease. The prevalence was higher in boys (n=38), median age 30 months (1–185). The main clinical manifestations were: meningococcal meningitis (n=27), meningococcemia without meningitis (n=14), association of meningococcemia with meningitis (n=13), and fever without a known source in infants (n=7).Admissions to intensive care unit were necessary for 45 patients. Three deaths were notified. Serogroup C was the most prevalent (n=32) followed by serogroup B (n=12).Pneumococcal meningitis was identified in 21 cases; out of the total, 10 were younger than two years. The identified serotypes were: 18C, 6B, 15A, 28, 7F, 12F, 15C, 19A and 14. Pneumococcal conjugate 10-valent vaccine covered four of the nine identified serotypes.Haemophilus influenzae meningitis serotype IIa was identified in three patients, median age 4 months (4–7). All of them needed intensive care. No deaths were notified. Conclusion Morbidity and mortality rates from bacterial meningitis and meningococcal disease remain high, requiring hospitalization and leading to sequelae. Our study observed a reduced incidence of bacterial disease over the last decade, possibly reflecting the impact of vaccination.

Resumo em Inglês:

Abstract Objectives Differential diagnosis of COVID-19 includes a broad range of conditions. Prioritizing containment efforts, protective personal equipment and testing can be challenging. Our aim was to develop a tool to identify patients with higher probability of COVID-19 diagnosis at admission. Methods This cross-sectional study analyzed data from 100 patients admitted with suspected COVID-19. Predictive models of COVID-19 diagnosis were performed based on radiology, clinical and laboratory findings; bootstrapping was performed in order to account for overfitting. Results A total of 29% of patients tested positive for SARS-CoV-2. Variables associated with COVID-19 diagnosis in multivariate analysis were leukocyte count ≤7.7 × 103 mm–3, LDH >273 U/L, and chest radiographic abnormality. A predictive score was built for COVID-19 diagnosis, with an area under ROC curve of 0.847 (95% CI 0.77–0.92), 96% sensitivity and 73.5% specificity. After bootstrapping, the corrected AUC for this model was 0.827 (95% CI 0.75–0.90). Conclusions Considering unavailability of RT-PCR at some centers, as well as its questionable early sensitivity, other tools might be used in order to identify patients who should be prioritized for testing, re-testing and admission to isolated wards. We propose a predictive score that can be easily applied in clinical practice. This score is yet to be validated in larger populations.

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Abstract The aim of this study was to compare the trajectory of serogroups causing Invasive Meningococcal Disease (IMD) in the Santa Catarina (SC) state with those of whole Brazil. A retrospective analysis of all IMD cases reported from January 2007 to December 2019 was carried out. During the study period, 26,058 IMD cases were registered in Brazil and 644 and in SC state alone. Overall, Brazil showed progressive reduction in cases since 2010, when the meningococcal C conjugate vaccine was introducted on National Immunization Program, while SC showed an increase in total cases since 2013, particularly from serogroups W and C. Serogroups distribution was significantly different between Brazil and SC. The emergence of serogroup W highlights the improved meningococcal surveillance through increased accuracy in identification methods in SC state. This finding is important for discussing recommendations of quadrivalent (ACWY) conjugate vaccines in different geographical areas of Brazil.

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Abstract Rifampicin is a key component of treatment for tuberculosis and its efficacy is determined by the blood levels attained after therapeutic doses. However, there is a high variability of rifampicin blood levels that is related to both the patient and the formulation used. To date, the effect of diabetes mellitus on the plasma levels of rifampicin was low exploited, which could be relevant either by the significant increase of the comorbidity worldwide as by the probable influence of diabetes on the rifampicin exposure. The study aims to evaluate whether diabetes mellitus contribute to the variation of the maximum concentration of rifampicin in patients with tuberculosis treated with a daily dose of 10 mg/kg. Rifampicin and glycated hemoglobin were measured by high-performance liquid chromatography, and blood glucose by spectrophotometry. A total of 62 male patients were included in the study, and 26 presented diabetes mellitus. Rifampicin plasma levels in 2-h plasma samples collected at day 61 ranged from 3 µg/mL to 14.2 µg/mL. Drugs levels were similar between diabetic and non-diabetic patients and were not correlated with blood glucose and glycated hemoglobin. Moreover, a high percentage of patients in both groups presented low levels of rifampicin.

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Abstract Purpose The aim of this study was to compare pharmacokinetic characteristics between intermittent infusion and continuous infusion of vancomycin for critically ill patients admitted to intensive care units. Methods Intermittent therapy was administered for 60 minutes and prescribed as a loading dose of 30 mg/kg and continued with 15 mg/kg q12 h. Continuous infusion was prescribed as a loading dose of 30 mg/kg followed by 30 mg/kg on constant infusion pump. Blood samples from vancomycin intermittent infusion group were collected 1 h before third dose, 1 h, 8 h and 24 h after third dose infusion. Blood samples from vancomycin continuous infusion group were collected 1 h after loading dose, 12 h, 24 h, 36 h, and 48 h after continuous infusion initiation. Results Median serum concentration of continuous infusion group at 24-hour was 23.59 µg/mL [14.52–28.97], while of intermittent infusion group at 23-hour was 12.30 µg/mL [7.27–18.12] and on 25-hour was 17.58 µg/mL [12.5–22.5]. Medians AUC24–48h were 357.2 mg.h/L and 530.2 mg.h/L for intermittent infusion and continuous infusion groups, respectively (p = 0.559). Conclusion Vancomycin CI reached steady state earlier, which guaranteed therapeutic levels from the first day and made it possible to manage therapeutic drug monitoring faster.

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Abstract COVID-19 public health responses such as social distancing and community containment measures protocols are critical to preventing and containing the spread of coronavirus. Brazil accounts for almost half of Latin American HIV cases and Rio de Janeiro is the city with the second largest number of AIDS. Clinical appointments and pharmacy antiretroviral refills may be impaired due to restricted traffic and possible lockdowns, preventing people living with HIV and those using PrEP from accessing needed antiretrovirals. We hereby describe the telemedicine procedures implemented in a large PrEP delivery service in Rio de janeiro in the context of the COVID-19 pandemic. At the initial teleconsultation, individuals undergoe HIV rapid testing and are assessed by phone for PrEP related procedures. Individuals receive a digital prescription to retrieve a 120-day PrEP supply plus two HIV self-test kits. Subsequent follow-up teleconsultations will be performed remotely by phone call, including instructions for the HIV self-test performance, which results are to be sent using a digital picture. Participants will attend the service only for PrEP refill. The use of telemedicine procedures is being effective to avoid PrEP shortage and reduce the time PrEP users spend at the service during the COVID-19 pandemic and social distancing recommendations.

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Abstract The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can cause mild, moderate or severe disease (COVID-19). In severe disease, there is hyperinflammation causing severe symptoms. Severe COVID-19 is an immunological phenomenon, rather than a direct viral damage disease. Therapies for COVID-19 are all investigational therapies. In case of severe disease, treatment with a calcineurin inhibitor could be promising. In this article we explain the mechanisms of calcineurin inhibitor treatment for COVID-19, based on experiences seen in solid organ transplant recipients who suffered from COVID-19.