Sandra Rocha Gadelha

Molecular epidemiology of human immunodeficiency virus-1 in the state of Ceará, Northeast, Brazil

We analyzed, by env and gag heteroduplex mobility assay, 149 human immunodeficiency virus (HIV-1) positive samples collected in Ceará during the year 2000. The prevalence of subtype B was 81.2% and the prevalence of subtype F and B/F recombinants were both 2.7%. Eight (5.4%) and 12 (8%) out of 149 samples showed indeterminate results in the env and gag analysis respectively. By FokI restriction fragment length polymorphism, 34% of the subtype B samples were identified as the typical Brazilian subtype B. In the present study, we identified HIV-1 subtype F and B/F in Ceará for the first time. Our results contribute to the understanding of HIV in Brazil, and may prove useful for the development of vaccine candidates.

Interleukin-1 beta and interleukin-6 gene polymorphism associations with angiographically assessed coronary artery disease in Brazilians.

The inflammatory process has been considered an important mediator for the development of atherosclerosis. Interleukin-1 beta (IL1B) is a precursor of interleukin-6 (IL6) in the acute phase of inflammatory response and their levels are elevated in patients with coronary artery disease. The aim of the present study was to further investigate the association of IL-1B and IL-6 gene polymorphisms and angiographically assessed coronary artery disease (CAD) in African- and Caucasian-Brazilians. This report analyzed the IL-1B-511C>T and IL-6-174G>C polymorphisms in 667 patients (253 African-Brazilians and 414 Caucasian-Brazilians) who underwent coronary angiography. Patients with a coronary obstructive lesion 50% presented a higher frequency of the IL-1B-511CC genotype (30.4%) compared to lesion-free individuals (16.5%, p=0.032) in African- but not in Caucasian-Brazilians. No significant genotype frequency difference was identified for the IL-6-174G>C polymorphism in either ethnic groups. However, after correction for other CAD risk factors using multivariate logistic regression, both the IL-1B-511CC [Odds ratio (OR)=2.3; p=0.019] and the IL-6-174GG (OR=2.0; p=0.028) genotypes were considered independent CAD risk predictors in African-Brazilians. This report shows that the IL-1B-511C>T and IL-6-174G>C polymorphisms were associated with CAD risk in African-Brazilians and no association was detected among Caucasian-Brazilians.

HTLV-1 in pregnant women from the Southern Bahia, Brazil: a neglected condition despite the high prevalence

BackgroundAs the most frequent pathway of vertical transmission of HTLV-1 is breast-feeding, and considering the higher prevalence in women, it is very important to perform screening examinations for anti-HTLV-1 antibodies as part of routine prenatal care. So far, no studies of HTLV-1 seroprevalence in pregnant women in the Southern region of Bahia, Brazil, have been described.MethodsPregnant women were selected at the two regional reference centers for health care from Southern Bahia. A total of 2766 pregnant women attending the antenatal unit between November 2008 and May 2010 have been analyzed. An extra blood sample was drawn during their routine antenatal testing. A standardized questionnaire was applied and all positive plasma samples were tested by ELISA and were confirmed by Western Blot and PCR. Besides that, positive women were contacted and visited. The family members that were present during the visit were asked to be serologically screened to the virus. A prospective study was also carried out and newborns were followed up to two years for evaluation of vertical transmission.ResultsHTLV prevalence was 1.05% (CI 95%: 0.70-1.50). There was no association of HTLV-1 infection with age, education, income and ethnic differences. The association with marital status was borderline (OR = 7.99; 95% CI 1.07-59.3; p = 0.042). In addition, 43 family members of the HTLV-1 seropositive women have been analyzed and specific reactivity was observed in 32.56%, including two children from previous pregnancy.Conclusion: It is very important to emphasize that the lack of HTLV-1 screening in pregnant women can promote HTLV transmission especially in endemic areas. HTLV screening in this vulnerable population and the promotion of bottle-feeding for children of seropositive mothers could be important cost-effective methods to limit the vertical transmission. Besides that, our data reinforce the need to establish strategies of active surveillance in household and family contacts as important epidemiological surveillance actions for the early detection of virus infection and the prevention of transmission by sexual or and parenteral contact.

Correlation between polymorphisms at interleukin-6 but not at interleukin-10 promoter and the risk of human T lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis in Brazilian individuals

HTLV‐1 is the etiologic agent of ATL and HAM/TSP. The majority of HTLV‐1‐infected individuals remain asymptomatic, indicating that the infection alone is not sufficient to cause the diseases. It has been reported that cytokine gene polymorphisms, including polymorphisms at IL‐6 and IL‐10 gene, might be important. We analyzed SNP in the promoter region of the IL‐6: −174, −572, −597, and −634 positions, and IL‐10: −592 position to evaluate the role of these polymorphisms in the HAM/TSP pathogenesis in 133 HTLV‐1 infected individuals and in 100 healthy individuals from Salvador, Bahia, Brazil. The −634C allele frequencies were higher among HAM/TSP patients (21.2%) than among oligosymptomatic (6.5%; P = 0.038) and asymptomatic (9.5%; P = 0.025) subjects. Similarly, the −174G allele frequencies were higher in HAM/TSP patients than in oligosymptomatic patients (P = 0.02). Moreover, the −634GC/−174GG genotype combination was identified at a higher frequency (38.5%) in the HAM/TSP patients than in subjects with other clinical status (8.7%; P = 0.016 for oligosymptomatic and 15.5%, P = 0.012 for asymptomatic patients). However, the multivariate logistic regression including the genotypes of the three studied loci showed that only −634 C IL‐6 carriers remain as significant and independent TSP/HAM predictor (odds ratio [OR] = 5.31; 95% [CI] = 1.60–17.56; P = 0.006). We suggest that −634 G C in IL‐6 could contribute to HAM/TSP development and that identification of the collective influence of several cytokine polymorphisms, their prevalence, and their interaction could help to better understand this disease. J. Med. Virol. 80:2141–2146, 2008.

Ethnic differences in the distribution of interleukin-6 polymorphisms among three brazilian ethnic groups

Polymorphisms in the interleukin-6 promoter region have been associated with diseases. In this study we investigated the -634G/C and -174G/C IL-6 promoter polymorphisms in three Brazilian ethnic groups. We verified that the allele frequencies of the two polymorphisms and haplotype frequencies varied significantly between the populations.

The use of saliva as a practical and feasible alternative to urine in large-scale screening for congenital cytomegalovirus infection increasesinclusion and detection rates

INTRODUCTION Although urine is considered the gold-standard material for the detection of congenital cytomegalovirus (CMV) infection, it can be difficult to obtain in newborns. The aim of this study was to compare the efficiency of detection of congenital CMV infection in saliva and urine samples. METHODS One thousand newborns were included in the study. Congenital cytomegalovirus deoxyribonucleic acid (DNA) was detected by polymerase chain reaction (PCR). RESULTS Saliva samples were obtained from all the newborns, whereas urine collection was successful in only 333 cases. There was no statistically significant difference between the use of saliva alone or saliva and urine collected simultaneously for the detection of CMV infection. CONCLUSIONS Saliva samples can be used in large-scale neonatal screening for CMV infection.

Polymorphisms at GLUT1 Gene Are Not Associated With the Development of TSP/HAM in Brazilian HTLV-1 Infected Individuals and the Discovery of a New Polymorphism at GLUT1 Gene

The development of HTLV‐1 associated clinical manifestations, such as TSP/HAM and ATLL, occur in 2–4% of the infected population and it is still unclear why this infection remains asymptomatic in most infected carriers. Recently, it has been demonstrated that HTLV uses the Glucose transporter type 1 (GLUT1) to infect T‐CD4+ lymphocytes and that single nucleotide polymorphisms (SNP) in the GLUT1 gene are associated with diabetic nephropathy in patients with diabetes mellitus in different populations. These polymorphisms could contribute to a higher GLUT1 protein expression on cellular membrane, facilitating the entry of HTLV and its transmission cell by cell. This could result in a higher provirus load and consequently in the development of TSP/HAM. To evaluate the role of GLUT1 gene polymorphisms in the development of TSP/HAM in HTLV‐1 infected individuals, the g.22999G > T, g.15339T > C and c.‐2841A > T sites were analyzed by PCR/RFLP or sequencing in 244 infected individuals and 102 normal controls. The proviral load of the HTLV‐1 infected patients was also analyzed using Real Time Quantitative PCR. Genotypic and allelic frequencies of the three sites did not differ significantly between controls and HTLV‐1 infected individuals. There was no difference in genotypic and allelic distributions among patients as to the presence or absence of HTLV‐1 associated clinic manifestations. As regards the quantification of the provirus load, we observed a significant reduction in the asymptomatic individuals compared with the oligosymptomatic and TSP/HAM individuals. These results suggest that g.22999G > T, g.15339T > C, and c.‐2841A > T SNP do not contribute to HTLV‐1 infection nor to the genetic susceptibility of TSP/HAM in Brazilian HTLV‐1 infected individuals. J. Med. Virol. 81:552–557, 2009.

The origin of HTLV-1 in the South Bahia by phylogenetic, mitochondrial DNA and β-globin analysis

In order to clarify the HTLV introduction and dispersion in the south of Bahia, we analyzed 29 samples from HTLV-1 seropositive women. Before the blood collection, all of them answered a standardized questionnaire. The DNA was extracted by QIAgen Kit. It was performed a nested-PCR to the LTR region of the HTLV. The sequences were submitted to the LASP HTLV-1 Automated Subtyping Tool. The phylogenetic analyses were generated using the neighbor-joining e maxima-verossimilhanca methods. The evolutionary model of Tamura-Nei with gamma distribution was selected as the best adaptive model by software Modeltest 3.7. The likelihood ratio was used to calculate the statistical support for the branches in trees. Bayesian tree were constructed to verify the posterior probability statistical parameter. To evaluate genetic ancestry of the population, it was analyzed mtDNA ancestry markers and β-globina haplotypes. From the total, 21 samples were successfully amplified and sequenced and they were classified as HTLV-1 aA (bootstrap support of 100%). The phylogeny analysis showed multiple introductions of the virus in Brazil. In addition, for the first time, Mozambique sequences were grouped with Brazilian and South Africa sequences, supporting the hypothesis that Africans infected with the virus have been brought from the southern regions of Africa. In relation to the genetic ancestry, the African ethnicity was predominantly found by mtDNA markers. In addition, the type benin was detected by β-globin analyses. These data corroborate to clarify the introduction and dispersion of this virus in Brazil, especially in the Bahia.

Are lipid disorders involved in the predominance of human T-lymphotropic virus-1 infections in women?

INTRODUCTION The human T-lymphotropic virus-1 (HTLV-1) is associated with chronic inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic inflammatory disease. Disturbances in lipid metabolism are involved in inflammatory and demyelinating diseases. METHODS Plasma levels of triglycerides, total cholesterol, and fractions of HTLV-1-infected individuals of both sexes with different clinical progressions were determined. RESULTS Elevated levels of triglyceride and very low-density lipoproteins (VLDL) were exclusively detected in HTLV-1-infected women from asymptomatic and HAM/TSP groups compared with uninfected individuals (p = 0.02). CONCLUSIONS Elevated triglyceride and VLDL levels in HTLV-1-infected women may be related to the predominance of HAM/TSP in women.

Interfamilial transmission of HTLV-1 in the South of Bahia, Brazil

The objective of this study was to investigate the prevalence of HTLV in the south of Bahia and to verify the interfamilial transmission of this virus. Initially, blood was collected from pregnant women in hospitals in southern Bahia.The HTLV-1 status was analyzed by ELISA and confirmed by Western Blot and PCR. The HTLV positive women were contacted and visited. In this opportunity, it was explained the results and collected samples from family members. They signed a consent informed and it was applied questionnaire. A total of 2766 pregnant women were analyzed. The prevalence was 1.05% (n=29) (CI95%:0,70-1,50). Besides, it was possible to follow 18 mothers (16 positives and 2 indeterminates) for 2 years. During the following, it was collected samples from 34 family members, including: partners (n=8), mothers (n=7), father (n=1), sisters (n=2), brothers (n=4), sons (n=5), daughters (n=4), others (n=3). Specific reactivity was observed in 11/34 (32,35%) individuals, of which two samples were from children (1 son and 1 daughter - 2,3 and 8 years old, respectively). The others members were: 3 mothers, 1 father, 3 partners, 2 sisters. In one case, we had three generation HTLV-1 positive: grandmother, mother and daughter. These results are very relevant because: (1) so far no studies of HTLV-1 seroprevalence in pregnant/puerperal women from the South region of Bahia had been described, (2) previous studies in areas endemic for the HTLV in Brazil found: 0.84% - Salvador, Bahia and 1.1% in Belo Horizonte, Minas Gerais, (3) evidence of important interfamilial transmission in this area.