First Detection of Hepatitis B Virus Subgenotype A5, and Characterization of Occult Infection and Hepatocellular Carcinoma-Related Mutations in Latin American and African Immigrants in Brazil.

This study aims to characterize the molecular profile of the hepatitis B virus (HBV) among socially vulnerable immigrants residing in Brazil to investigate the introduction of uncommon HBV strains into the country. Serum samples from 102 immigrants with positive serology for the HBV core antibody (anti-HBc) were tested for the presence of HBV DNA by PCR assays. Among these, 24 were also positive for the HBV surface antigen (HBsAg). The full or partial genome was sequenced to determine genotype by phylogenetic analysis. Participants were from Haiti (79.4%), Guinea-Bissau (11.8%), Venezuela (7.8%), and Colombia (1%). Of the 21 HBV DNA-positive samples, subgenotypes A1 (52.4%), A5 (28.6%), E (9.5%), F2 (4.8%), and F3 (4.8%) were identified. Among the 78 HBsAg-negative participants, four were positive for HBV DNA, resulting in an occult HBV infection rate of 5.1%. Phylogenetic analysis suggested that most strains were likely introduced to Brazil by migration. Importantly, 80% of A5 sequences had the A1762T/G1764A double mutation, linked to an increased risk of hepatocellular carcinoma development. In conclusion, this study is the first report of HBV subgenotype A5 in Brazil, shedding new light on the diversity of HBV strains circulating in the country. Understanding the genetic diversity of HBV in immigrant communities can lead to better prevention and control strategies, benefiting both immigrants and wider society.

Association of CD133, ALDH1, CD117 and OCT4 expression with prognosis of patients with cervical cancer.

Cancer stem cells (CSC), a small population of neoplastic cells, are associated with worse prognosis. The aim of this study was to evaluate the expression of ALDH1, CD117, CD133 and OCT4; potential markers of CSC; and their associations with the prognosis of women diagnosed with cervical cancer. This retrospective cohort study included 126 women diagnosed with cervical cancer whose biopsies were analyzed by immunohistochemistry. Median values of marked cells were used to define cutoff points for low and high expression. For specific survival, multivariate analyses showed statistical significance for lymph node metastases (HR 8.15; 95% CI 3.00-22.18) and borderline significance for high CD133 expression (p = 0.058). For overall survival, multivariate analyses showed statistical significance for IIA-IVB staging (HR 4.60; 95% CI 1.46-14.56), lymph node metastases (HR 5.13; 95% CI 12.02-13.03) and high CD133 expression (2.67; 95% CI 1.11-6.43). Considering only women with SCC, the same clinicopathological variables were associated with worse specific and overall survival in univariate analyses. However, higher expression of CD 133 (HR 11.10; 95% CI 2.42-50.94 and 6.00; 95% CI 2.02-17.87) and staging IIA-IVB (HR 5.96; 95% CI 1.30-27.34 and HR 12.47; 95% CI 2.45-63.54) respectively impacted negatively specific and overall survival, as multivariate analyses showed. Secondarily, it was observed that ALDH1 expression was associated with adenocarcinoma and CD117 expression with squamous cells carcinoma. Higher expression of CD133 was associated with worse specific and overall survival, indicating that it could have relevance as a clinical marker and therapeutic target.

Seroprevalence of Hantavirus among Manual Cane Cutters and Epidemiological Aspects of HPS in Central Brazil.

Hantavirus pulmonary syndrome (HPS) is a rodent-borne zoonotic disease that is endemic throughout the Americas. Agricultural activities increase exposure to wild rodents, especially for sugarcane cutters. We carried out a survey of the epidemiological aspects of HPS and investigated the prevalence of hantavirus infection in the sugarcane cutter population from different localities in the Brazilian Midwest region. We conducted a retrospective study of all confirmed HPS cases in the state of Goiás reported to the National HPS surveillance system between 2007 and 2017, along with a seroepidemiological study in a population of sugarcane cutters working in Goiás state in 2016, using the anti-hantavirus (Andes) ELISA IgG. A total of 634 serum samples from cane cutters were tested for hantavirus antibodies, with 44 (6.9%) being IgG-reactive according to ELISA. The destination of garbage was the only statistically significant variable (p = 0.03) related to the detection of hantavirus IgG (p < 0.05). We described the epidemiological profile of reported hantavirus cases in Goiás-a highly endemic area for HPS, and where the seroepidemiological study was conducted. Our results increase our knowledge about hantavirus infections in Brazil and highlight the vulnerability of sugarcane cutters to a highly lethal disease that, to date, has no specific treatment or vaccination.

Prevalence, Risk Factors and Vaccine Response against Hepatitis B in People Aged 50 Years or Older.

Universal immunization against hepatitis B has contributed to reducing incidence of the disease, but older individuals remain susceptible to acquiring the hepatitis B virus worldwide. Thus, this study aimed to investigate the epidemiology of HBV infection in individuals aged 50 years and over in central Brazil and to evaluate the immunogenicity of the monovalent vaccine against hepatitis B in this age group using two vaccine regimens. METHOD: Initially, a cross-sectional and analytical study was carried out to investigate the epidemiology of hepatitis B. Then, individuals without proof of vaccination for hepatitis B were recruited for a phase IV randomized and controlled clinical trial using two vaccine regimens: Intervention Regimen (IR) (three doses of 40 µg at months 0, 1 and 6) vs. Comparison Regimen (CR) (three doses of 20 µg at months 0, 1 and 6). RESULTS: The overall prevalence of exposure to HBV was 16.6% (95% CI: 14.0%-9.5%). In the clinical trial, statistical differences in protective titers were observed (p = 0.007; IR 96% vs. CR 86%) and the geometric mean of anti-HBs titers was higher in individuals who received the IR (518.2 mIU/mL vs. 260.2 mIU/mL). In addition, the proportion of high responders was higher among those who received the IR (65.3%). CONCLUSION: reinforced doses should be used in individuals aged 50 years or older to overcome the lower efficacy of the vaccine against hepatitis B.

Risk perception and vulnerabilities for HIV/AIDS among transgender women in Brazil: mixed methods approach.

Transgender women (TW) are a key population in the dynamics of human immunodeficiency virus (HIV) dissemination, although little is known about their perceptions of HIV risk. In this embedded, nested, mixed-methods study, we assessed factors associated with condomless sexual intercourse among TW and explored their risk perceptions and vulnerabilities regarding HIV exposure. The first phase involved a cross-sectional study, followed by qualitative interviews. Condomless sexual intercourse during their last sexual encounter was reported by 37.3% of participants, and 16.1% previously tested positive for HIV. Age older than 21 years, single status, and being a sex worker were protective factors for condomless intercourse. Otherwise, TW who reported a past sexual partner with a known sexually transmitted infection and those aware of post-exposure prophylaxis had a greater risk of condomless sexual intercourse (p < 0.05) during their most recent encounter. The qualitative interviews revealed that, despite TW being aware of their risk of contracting HIV, their vulnerabilities overlapped their risk perception, making them trivialize or ignore the risk. This study will help to understand the HIV dynamics among TW and contribute to further health research, education, policymaking, and planning associated with specific health strategies to promote the sexual health of TW.

Detection of Human papillomavirus and the role of p16INK4a in colorectal carcinomas.

INTRODUCTION: Human papillomavirus (HPV) infection is associated with the development of anogenital and head and neck cancers. In recent years a potential role of HPV in colorectal cancer (CRC) has been suggested. OBJECTIVE: To investigate the presence of HPV in colorectal carcinomas and to study the role of p16INK4a as a marker of transcriptionally active HPV infection. In addition, to investigate the correlation between these findings and the CRC prognostic factors. METHODS: Case control study with 92 cases of colorectal cancers, 75 controls of normal tissue adjacent to the tumor, and 30 controls of precursor lesions, including polyps and colorectal adenomas. Paraffinized samples were used, HPV detection and genotyping were performed by PCR and reverse hybridization by using the INNO LIPA kit, with SPF10 plus primers. The expression of the p16INK4a protein was investigated using immunohistochemistry. Data analysis was performed using descriptive, univariate statistics and survival curves were calculated by using the Kaplan Meier and log-rank method. RESULTS: HPV was detected in 13% of the cases and the most prevalent genotype was HPV 16. HPV DNA was not detected in either control groups. The high expression of p16INK4a was observed in 30% of the cases, but it was not associated to the presence of HPV. The overall survival was 53.3% and was influenced by prognostic factors such as later stage, lymph node and distant metastasis. CONCLUSIONS: Based on these results, HPV is unlikely to be involved in colorectal carcinogenesis and p16INK4a expression is not a relevant marker of transcriptionally active HPV infection in CRC.

Molecular and epidemiological aspects of hepatitis C virus infection among crack cocaine users.

The aim is to investigate the prevalence, risk factors, and hepatitis C virus (HCV) genotypes/subtypes among crack users in-treatment in Central Brazil. A cross-sectional survey in which 600 in-treatment crack users were interviewed and tested for anti-HCV Ab by enzyme-linked immunosorbent assay was conducted between August 2012 and April 2013. Anti-HCV-positive samples were also submitted for HCV RNA detection by polymerase chain reaction. Positive HCV RNA samples were genotyped by direct sequencing analysis of the NS5B region of the viral genome, followed by phylogenetic analysis. Of the total, 3.7% (95.0% CI, 2.4%-5.6%) were anti-HCV positive. Age over 40 years and history of injecting drugs were risk factors for HCV, while snorting cocaine was a protector variable. HCV RNA was detected in 14 of 22 anti-HCV-positive samples, and the genotypes 1 (n = 10) and 3 (n = 2), subtypes 1a (n = 7), 1b (n = 3), and 3a (n = 2) were identified. The HCV prevalence found among crack users is almost threefold that observed in the general population in Brazil supporting that this population is at higher risk for HCV. The findings of cocaine insufflation as a protective behavior for HCV infection in this population should be explored.

Epidemiology of HIV, syphilis, and hepatitis B and C among manual cane cutters in low-income regions of Brazil.

BACKGROUND: In recent decades the epidemic of asymptomatic sexually transmitted infections has extended deep into Brazil, including small towns and rural areas. The purpose of this study was to investigate the epidemiology of HIV, syphilis, and hepatitis B (HBV) and hepatitis C viruses (HCV), and to evaluate immunization coverage against hepatitis B in a group of rural workers in Brazil. METHODS: In 2016, a cross-sectional study was conducted with 937 manual sugarcane cutters of the Midwest and Northeast Regions of Brazil. All individuals were interviewed and screened for HIV, syphilis, HBV and HCV. Correlating factors with lifetime HBV infection were investigated using logistic regression. Positive Predictive Values, Negative Predictive Values, sensitivity and specificity were also calculated relative to vaccination against Hepatitis B, comparing anti-HBs titers to vaccination reports. RESULTS: Most reported previous hospitalization (55%), occupational injuries (54%), sharing of personal items (45.8%), alcohol consumption (77.2%), multiple sexual partners in previous 12 months (39.8%), and no condom use during sexual intercourse in last 12 months (46.5%). Only 0.2% reported using injection drugs. Anti-HIV-1 was detected in three individuals (0.3%). Serological markers of lifetime syphilis (treponemal test) were detected in 2.5% (95% CI: 1.6-3.6) of participants, and active syphilis (treponemal test and VDRL) present in 1.2%. No samples were positive for anti-HCV. The prevalence of lifetime HBV infection (current or past infection) was 15.9%, and 0.7% (95% CI 0.4 to 1.5) were HBsAg-positive. Previous hospitalization (OR 1.53, CI 1.05-2.24, p < 0.01) and multiple sexual partners in the last 12 months (OR 1.80, CI 1.25-2.60, p < 0.01) were predictors for lifetime HBV infection. Although 46.7% (95% CI 43.4-49.9) of individuals reported having been vaccinated against hepatitis B, only 20.6% (95% CI 18.1-23.3) showed serological evidence of previous hepatitis B vaccination (positive for anti-HBs alone). CONCLUSIONS: The high prevalence of syphilis and HBV compared to the general population and the high frequency of risk behaviors show the potential for sexual and parenteral dissemination of these agents in this rural population. In addition, the low frequency of hepatitis B vaccinated individuals suggests a need for improved vaccination services.

HTLV-1 and -2 in a first-time blood donor population in Northeastern Brazil: Prevalence, molecular characterization, and evidence of intrafamilial transmission.

Independent epidemiology for respective human T-cell lymphotropic virus (HTLV) types 1 and 2 is little known in blood donors in Brazil, where screening for HTLV-1/2 is mandatory at blood banks, but no testing to confirm/differentiate these viruses. Therefore, this study aims to assess the prevalence of HTLV-1 and -2 in a first-time blood donor population in Northeastern Brazil and to carry out molecular characterization of respective isolates. A cross-sectional study was conducted at the State Blood Bank in Piauí. Samples were screened for anti-HTLV-1/2 by enzyme immunoassay, and reactive samples were confirmed using a line immunoassay and polymerase chain reaction (PCR). Of 37 306 blood donors, 47 were anti-HTLV-1/2 reactive by enzyme immunoassay. After confirmed by line immunoassay, 22 were positive for HTLV-1 (0.59 per 1000; 95% CI: 0.38-0.87), 14 were positive for HTLV-2 (0.37 per 1000; 95% CI: 0.21-0.61), 1 was indeterminate, and the remaining donors were negative. The HTLV-1 infection was also confirmed by PCR in all anti-HTLV-1-positive samples, and sequencing classified these isolates as belonging to the Transcontinental (A) subgroup of the Cosmopolitan (1a) subtype. Of 14 anti-HTLV-2-positive samples, 11 were also PCR positive, which belonged to subtype a (HTLV-2a/c). In addition, 38 family members of 5 HTLV-1- and 3 HTLV-2-infected donors were analyzed. Familial transmission of HTLV-1 and -2 was evidenced in 3 families. In conclusion, in Northeastern Brazil, where HTLV-1 and -2 are endemic, counseling blood donor candidates and their families might play a key role in limiting the spread of these viruses.

Gender differences in patterns of drug use and sexual risky behaviour among crack cocaine users in Central Brazil.

BACKGROUND: The aim of this study was to compare sociodemographic characteristics, patterns of drug use, and risky sexual behaviour among female and male users of crack cocaine. METHODS: Between 2012 and 2013, we conducted a cross-sectional study of 919 crack cocaine users (783 men and 136 women) in Central Brazil using face-to-face interviews. Blood samples were collected to test for syphilis. The Chi-Square Automatic Interaction Detector (CHAID) was used to explore the differences between genders. We implemented two models: the first model included previous incarceration and variables related to patterns of drug use, and the second model included variables related to sexual risky behaviours and syphilis exposure. RESULTS: Women consumed more crack cocaine than men on a regular basis; however, poly-drug use was more common among men. More women than men reported exchanging sex for money and/or drugs and inconsistent condom use during sexual intercourse; women also reported more sexual partners. In addition, the frequency of sexual violence was higher for women than men. A higher proportion of women than men were positive for syphilis (27.2% vs. 9.2%; p < 0.001). The CHAID decision tree analysis identified seven variables that differentiated the genders: previous incarceration, marijuana use, daily crack cocaine consumption, age at first illicit drug use, sexual violence, exchange of sex for money and/or drugs, and syphilis exposure. CONCLUSION: Our findings demonstrate a difference in patterns of crack cocaine consumption and sexual risky behaviours between genders, thus indicating a need for gender-specific interventions in this population.

Association between the human papillomavirus, bacterial vaginosis and cervicitis and the detection of abnormalities in cervical smears from teenage girls and young women.

BACKGROUND: Human papillomavirus (HPV) infection, bacterial vaginosis (BV), and cervicitis may play a role in the presence of cytological abnormalities in female adolescents and young women. This study aimed to estimate the prevalence of HPV, BV and cervicitis in female adolescents and young women and evaluate whether these conditions are associated with a finding of cytological abnormalities in cervical smears. METHODS: Cervical smears were screened using the conventional method and HPV-DNA detection was performed by PGMY-PCR. BV was defined as ≥20% clue cells in cervical smears. Cervicitis was assessed by counting leukocytes in five non-adjacent microscopic fields at 1000× magnification. Odds ratios and 95% confidence intervals were calculated. RESULTS: The study analyzed 251 samples, with cytological abnormalities being found in 9.5% (24/251). Atypical squamous cells of undetermined significance (50.0%) and low-grade squamous intraepithelial lesions (29.1%) were the most common findings. HPV, BV and cervicitis were found in 44.2% (111/251), 41.0% (103/251) and 83.2% (209/251) of cases, respectively. Of the variables investigated, BV and an abnormal cytological diagnosis were independently associated with HPV positivity. Cytological abnormalities were significantly associated with a finding of HPV and BV in the same woman, and also with a simultaneous finding of HPV, BV and cervicitis; however, the independent association of these combined variables did not remain significant in the multivariate analysis. CONCLUSIONS: BV and cytological abnormalities were independently associated with HPV infection in female adolescents and young women.

Association of HPV infection and Chlamydia trachomatis seropositivity in cases of cervical neoplasia in Midwest Brazil.

High-risk human papillomavirus (HPV) is considered the main etiological agent for cervical neoplasia. However, the presence of a single type HPV infection alone is unlikely to be sufficient to cause cervical cancer. There is epidemiologic evidence suggesting that HPV and Chlamydia trachomatis play a central role in the etiology of cervical intraepithelial neoplasia and subsequent cervical cancer. To evaluate the HPV prevalence and the seropositivity for C. trachomatis in women referred to the colposcopy clinic due to an abnormal cervical smear and to examine the effect of this association on the severity of cervical neoplasia. Following enrollment, 131 patients underwent colposcopy and biopsies when necessary. HPV DNA was detected by the polymerase chain reaction (PCR) and genotyping was performed by reverse line-blot hybridization assay. C. trachomatis seropositivity was tested by ELISA for the detection of IgG antibodies. The prevalence of HPV infection was 86.3%. Seropositivity for C. trachomatis was 26%. Thirty-one women (27.4%) were positive for C. trachomatis antibodies and HPV-DNA. The most prevalent HPV type in C. trachomatis-seropositive women were HPV 16 (51.6%) and this HPV type was present mainly in neoplasia cases. Positivity for HPV, particularly HPV types 16 and 18, and C. trachomatis seropositivity was significantly associated with a diagnosis of high grade neoplasia. Borderline significance was observed after adjustment for HPV. C. trachomatis seropositivity is associated with high grade neoplasia in women infected with HPV, mainly when the types 16 and 18 were involved.

Association between HPV types and species groups and cervical neoplasia from a high-risk area for cervical cancer, Goiânia, Brazil.

This study was designed to evaluate the effect of single or multiple-human papillomavirus (HPV) infection and phylogenetic groups on the prevalence and severity of cervical intraepithelial neoplasia (CIN) in women undergoing colposcopy after an abnormal cervical smear. Colposcopy was performed in 198 cases and biopsy was performed in 193 patients. All specimens were tested for 27 HPV genotypes using the Roche polymerase chain reaction reverse line blot assay. The overall prevalence of HPV infection in women with an abnormal cervical smear was 86% (171 of 198). The prevalence of HPV 16 in high-grade CIN (2/3) was 52% (40 of 76), being detected in 88.8% of cases (8 of 9) of invasive carcinoma. The prevalence of HPV types 31 and 35 in high-grade CIN was 10.5% (8 of 76) and 6.6% (5 of 76), respectively. Single or multiple-type infection involving HPV 16 were significantly associated with a diagnosis of high-grade neoplasia (≥ CIN 2) [odds ratio (OR) 6.49; 95% confidence interval (CI): 1.88-23.44 and OR: 3.65; 95% CI: 1.13-12.15] even after adjustment for HPV-DNA. A statistically significant association was also found between HPV 16 and the other HPV types belonging to species α 9 and a diagnosis of high-grade neoplasia (OR: 7.62; 95% CI: 1.28-51.58); however, no association was found between HPV 16 and the other HPV types belonging to species α 7. HPV 16 is the most important predictor of high-grade cervical neoplasia. Multiple-type infections are predictors of high-grade cervical neoplasia when type 16 is present.