Human T-cell leukemia virus type 1 infection among Japanese immigrants and their descendants living in Southeast Brazil: A call for preventive and control responses.

Human T-cell leukemia virus type 1 (HTLV-1) has worldwide distribution and is considered endemic in southwestern Japan. HTLV-1 infection has been associated with adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) besides other diseases. This cross-sectional study aimed to investigate the prevalence, risk factors and molecular characterization of HTLV-1, among the world's largest population of Japanese immigrants and their descendants outside of Japan, in São Paulo, Southeast Brazil, as well as to analyze the phylogenetic relationship among isolates of HTLV-1. From July to December 2017, 2,139 individuals from five Japanese associations were interviewed and submitted to blood collection. All serum samples were first tested for the presence of anti-HTLV-1/2 antibodies by ELISA and then peripheral blood from individuals with positive serological results were analyzed for the presence of HTLV-1 5'LTR proviral DNA. Partial sequencing of the 5'LTR region of HTLV-1 proviral DNA was performed by Sanger. The prevalence of HTLV-1 infection was 5.1% (CI 95%: 4.2-6.0). In the multiple logistic regression model, HTLV-1 infection was associated with age ≥ 45 years, female sex, being first and second-generation Japanese immigrants, and having sexual partners with history of blood transfusion. The phylogenetic analysis revealed that all HTLV-1 were classified as Cosmopolitan (1a) subtype. Of them, 47.8% were classified as Transcontinental (A) subgroup and 52.2% as belonging to the Japanese (B) subgroup. Although most HTLV-1-infected patients were asymptomatic (97.3%), blurred vision was associated with HTLV-1 infection. The high prevalence of HTLV-1 infection found in this studied population and especially the intra- and interfamily HTLV-1 transmission presents an urgent call for preventive and control responses of this infection in Brazil.

Changing pattern of chronic hepatitis C in renal transplant patients over 20 years.

BACKGROUND: The prevalence and clinical epidemiological profile of hepatitis C virus (HCV) infection have changed over time. AIM: This study aimed to evaluate these changes in renal transplant recipients (RTx) comparing two different decades. MATERIALS AND METHODS: RTx with HCV referred to RTx from 1993 to 2003 (A) and from 2004 to 2014 (B) were studied retrospectively. The demographic and clinical characteristics and different outcomes were compared between groups A and B. Variables that were statistically different were tested for inclusion in a multivariate Cox proportional hazard model predicting patient survival within the group. RESULTS: Among 11 715 RTx, the prevalence of HCV was 7% in A and 4.9% in B. In the more recent period (B), the mean age was older (46.2 vs. 39.5 years), with more males (72 vs. 60.7%), larger number of deceased donors (74 vs. 55%), higher percentage of previous RTx (27 vs. 13.7%), less frequent history of blood transfusion (81 vs. 89.4%), lower prevalence of hepatitis B virus coinfection (4.7 vs. 21.4%), and higher percentage of cirrhotic patients (13 vs. 5%). Patients of group B more frequently underwent treatment of HCV (29 vs. 9%), less frequently used azathioprine (38.6 vs. 60.7%) and cyclosporine (11.8 vs. 74.7%), and more frequently used tacrolimus (91 vs. 27.3%). In the outcomes, graft loss showed no difference between periods; however, decompensation was more frequent (P = 0.007) and patients' survival was lower in the more recent period (P = 0.032) compared with the earlier one. CONCLUSION: The profile of RTx with HCV has changed over the last 20 years. Despite a decrease in the prevalence of HCV, new clinical challenges have emerged, such as more advanced age and a higher prevalence of cirrhosis.

HTLV-1 intrafamilial transmission among Japanese immigrants in Brazil.

Human T-lymphotropic virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The aim of this study was to investigate the intrafamilial transmission of HTLV-1 among Japanese immigrants and their descendants living in a non-endemic area of central Brazil. Six families were investigated. Thirty-seven relatives of the six index cases were tested by ELISA for the presence of anti-HTLV antibodies, and the positive cases were confirmed by Western blot. HTLV-1 isolates were genotyped by partial nucleotide sequencing (5' LTR) of the proviral DNA. All individuals, including index cases and relatives, were asymptomatic. In five families, at least one relative was infected with HTLV-1. In all, eight (22%) relatives (one mother, four wives, one brother, and two brothers-in-law) were infected. However, none of the 22 individuals under 55 years of age was infected. In each family, the HTLV-1 sequences from the relatives were identical or almost identical to that of the index case, except in one case. Pedigrees of the families, together with socio-demographic data of the HTLV-1 infected individuals, strongly suggested the occurrence of both vertical and sexual transmission, with breastfeeding as an important risk factor. Whether and why the virus transmission is less effective among younger generations deserves to be further investigated.

Prevalence of naturally occurring protease inhibitor resistance-associated variants in hemodialysis and renal transplant patients with hepatitis C virus infection.

Background NS3 protease inhibitors (PIs) were the first direct antiviral agents used for the treatment of hepatitis C virus. The combination of second-wave PIs with other direct antiviral agents enabled the use of interferon-free regimens for chronic kidney disease patients on dialysis and renal transplant (RTx) recipients, populations in which the use of interferon and ribavirin is limited. However, the occurrence of PI resistance-associated variants (RAVs), both baseline and induced by therapy, has resulted in the failure of many treatment strategies. Methods The aim of this study was to estimate the prevalence of PI RAVs and of the Q80K polymorphism in chronic kidney disease patients on hemodialysis and RTx recipients. Direct sequencing of the NS3 protease was performed in 67 patients (32 hemodialysis and 35 RTx).Results RAVs to PIs were detected in 18% of the patients: V55A (9%), V36L (1.5%), T54S (1.5%), S122N (1.5%), I170L (1.5%), and M175L (1.5%). Only 1.5% of the patients carried the Q80K polymorphism. The frequency of these mutations was more than two times higher in patients infected with GT1a (25%) than GT1b (9.7%) (P=0.1). The mutations were detected in 20% of treatment-naive patients and in 15.6% of peginterferon/ribavirin-experienced patients (P=0.64). Furthermore, no mutation that would confer high resistance to PIs was detected.Conclusion The Q80K polymorphism was rare in the population studied. The occurrence of RAVs was common, with predominance in GT1a. However, the variants observed were those associated with a low level of resistance to PIs, facilitating the use of these drugs in this special group of patients.

High prevalence of HTLV-1 infection among Japanese immigrants in non-endemic area of Brazil.

BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1) has worldwide distribution and is considered endemic in many world regions, including southwestern Japan and Brazil. Japanese immigrants and their descendants have a high risk of acquiring this infection due to intense population exchange between Brazil and Japan. OBJECTIVE: This cross-sectional study aimed to estimate the prevalence of HTLV, analyze the main risk factors associated with this infection, identify the main circulating types and subtypes of HTLV in Japanese immigrants and descendants living in Campo Grande-MS (Middle-West Brazil), as well as analyze the phylogenetic relationship among isolates of HTLV. STUDY DESIGN: A total of 219 individuals were interviewed and submitted to blood collection. All collected blood samples were submitted for detection of anti-HTLV-1/2 using the immunoassay ELISA and confirmed by immunoblot method. The proviral DNA of the 14 samples HTLV- 1 positive were genotyped by nucleotide sequencing. RESULTS: The overall prevalence of HTLV-1 was 6.8% (IC 95%: 3,5-10,2). Descriptive analysis of behavioral risk factors showed statistical association between HTLV-1 and age greater than or equal to 45 years. The proviral DNA of HTLV-1 was detected in all HTLV-1 positive samples. Of these, 14 were sequenced and classified as Cosmopolitan subtype, and 50% (7/14) belonged to subgroup A (transcontinental) and 50% (7/14) to the subgroup B (Japanese). CONCLUSION: The high prevalence of HTLV-1 found evidence of the importance of early diagnosis and counseling of individuals infected with HTLV-1 for the control and prevention of the spread of this infection among Japanese immigrants and their descendants in Central Brazil.

Obstetric, clinical, and perinatal implications of H1N1 viral infection during pregnancy.

OBJECTIVE: To determine perinatal outcome and epidemiologic, clinical, and obstetric characteristics among pregnant women infected with the H1N1 virus admitted to a Brazilian university hospital. METHODS: A cross-sectional study was conducted of pregnant women infected with H1N1 who were admitted to the University Hospital at the School of Medicine, Federal University of Mato Grosso do Sul, Campo Grande, Brazil, during the 2009 pandemic. Data were obtained via a questionnaire, which was administered during the hospital evaluation of patients' medical records. RESULTS: Thirty-one patients were included in the study. Antiviral therapy was initiated within 48 hours of the onset of symptoms in 64.5% of cases. Infection with the H1N1 virus was associated with severe clinical complications in 22.6% of patients and adverse perinatal outcomes in 41.9% of cases. The rate of maternal and perinatal mortality was 9.7%. There was a statistically significant association between late treatment with oseltamivir and increase in systemic complications in pregnancy (odds ratio 22.80 [95% confidence interval, 2.20-235.65]; P=0.007). CONCLUSION: Early treatment with oseltamivir may prevent serious complications associated with H1N1 infection in pregnant women but it does not affect perinatal outcome.