Incidence of Cervical Human Papillomavirus and Cervical Intraepithelial Neoplasia in Women with Positive and Negative HIV Status.

Objectives To evaluate the incidence and factors associated with cervical intraepithelial neoplasia (CIN) and cervical infection by human papillomavirus (HPV) among HIV-positive and HIV-negative women. Methods A cohort of 103 HIV positive and 113 HIV negative women were monitored between October 2008 and February 2012, for at least one year. Procedures included cervical cytology, DNA/HPV detection by polymerase chain reaction, colposcopy with biopsy if necessary, followed by an interview for exposure characteristics data. CIN was based on the histopathological results. Results The incidence of CIN was of 8.8 and 4.6 cases/100 women-years in HIV-positive and HIV-negative women, respectively. HIV-positive women presented a hazard ratio (HR) of 2.8 for CIN and developed lesions earlier (0.86 year) than HIV-negative women (2 years) (p = 0.01). The risk of developing CIN decreased with age (HR = 0.9) and marital status (HR = 0.4). HPV patients presented a higher incidence of CIN when compared HIV-positive and HIV-negative women (p = 0.01). The incidence of HPV cervical infection was 18.1 and 11.4 cases/100 women-years in HIV-positive and HIV-negative women, respectively. Those HIV-positive presented earlier HPV infection(p = 0.002). The risk of developing HPV infection decreased with age and was higher among HIV-positive women. HPV 16 was the most common type in HIV-positive women, and also the type most closely associated with CIN in HIV-negative women. Conclusions HIV-positive women had a greater incidence of HPV and CIN, and in a shorter time interval. More rigorous and timely clinical control is required for this group.

Kinetics of hepatitis C virus load and hemodialysis: is there any influence of the reuse of dialysis membrane on HCV viremia?

BACKGROUND: Patients with chronic kidney disease (CKD) on regular hemodialysis are at increased risk of acquiring hepatitis C virus (HCV). Although controversial, a distinct dynamic of the HCV load has been reported in this group - a lower HCV viremia compared to non-uremic patients. The reasons for this remain unclear, but the host immune response related to the hemodialysis procedure and the reuse of dialysis membranes are the most investigated factors. METHODS: We analyzed the kinetics of HCV RNA viremia in 21 hemodialysis patients infected with genotype 1, through a highly sensitive quantitative method (real-time polymerase chain reaction), immediately before and at the end of the first use and the last reuse of the cellulose diacetate dialysis membrane. RESULTS: Initial HCV load did not correlate with demographic or biochemical parameters, but higher HCV viremia was associated with a longer time on hemodialysis (r = 0.44, p = 0.04). Although not significant, HCV RNA decreased in 11/21 (52.3%) patients after the first dialysis session (median 279,000 vs 176,000 IU/ml, p = 0.91). However, a significant increase in HCV RNA viremia was observed in 17/21 (80.9%) patients after the tenth session (median 187,000 vs 342,000 IU/ml, p = 0.009). CONCLUSIONS: Except for the first session of hemodialysis, we did not confirm a decrease in HCV viremia related to the time on hemodialysis or with the reuse of the dialysis membrane. Factors other than the reuse of the dialysis membrane might be involved in the multifaceted kinetics of HCV RNA in CKD patients on hemodialysis.

[Discrepancy of celiac disease presentation in monozygotic twins]. / Discordância de apresentação da doença celíaca em gêmeos monozigóticos.

CONTEXT: The celiac disease is an immune-mediated enteropathy caused by a permanent sensitivity to gluten in genetically susceptible individuals. Despite the genetic characteristic of the disease, studies show discrepancy of 30% in its presentation in monozygotic twins. OBJECTIVE: To present two pairs of monozygotic confirmed by genetic study and discordant for presentation of celiac disease. METHODS: The patients were followed up at the Pediatric Gastroenterology Service - Hospital das Clínicas da Universidade Federal de Minas Gerais, MG, Brazil, since 1990, and were submitted to periodical clinical examinations, intestinal biopsies and serology for IgA and IgG antigliadin antibodies, determined by the ELISA technique, and IgA antiendomysial, determined by indirect immunofluorescence. Genetic study was conducted by the technique of amplification by PCR and later typing loci of microsatellites type of STR (short tandem repeats). RESULTS: In each pair of twins only one has presented celiac disease so far, demonstrating that despite the identical genotype, it was not the single determinant to express the condition. CONCLUSION: Other environmental and genetic factors might contribute to determining the disease.

Comparison of HPV genotyping by type-specific PCR and sequencing.

Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide and there is a strong link between certain high-risk viral types and cervical carcinogenesis. Although there are several typing methods, it is still unclear which test is the best. This study compared the effectiveness of type-specific PCR (TS-PCR) and sequencing, with a focus on their clinical application. A total of 260 cervical samples from HPV-positive patients were tested for types 6, 11, 16, 18, 31, 33 and 35 using TS-PCR and sequencing. The genotype was identified in 36% of cases by TS-PCR and in 75% by sequencing. Sequencing was four times more likely to identify the viral type in positive samples than TS-PCR (p = 0.00). Despite being more effective for virus genotyping, sequencing was unable to identify viral types in multiple infections. Combining both techniques resulted in highly sensitive detection (87% of cases), showing that they are complementary methods. HPV genotyping is an important step in HPV management, helping to identify patients with a higher risk of developing cervical cancer and contributing to the development of type-specific vaccines.

Comparison of HPV genotyping by type-specific PCR and sequencing

Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide and there is a strong link between certain high-risk viral types and cervical carcinogenesis. Although there are several typing methods, it is still unclear which test is the best. This study compared the effectiveness of type-specific PCR (TS-PCR) and sequencing, with a focus on their clinical application. A total of 260 cervical samples from HPV-positive patients were tested for types 6, 11, 16, 18, 31, 33 and 35 using TS-PCR and sequencing. The genotype was identified in 36 percent of cases by TS-PCR and in 75 percent by sequencing. Sequencing was four times more likely to identify the viral type in positive samples than TS-PCR (p = 0.00). Despite being more effective for virus genotyping, sequencing was unable to identify viral types in multiple infections. Combining both techniques resulted in highly sensitive detection (87 percent of cases), showing that they are complementary methods. HPV genotyping is an important step in HPV management, helping to identify patients with a higher risk of developing cervical cancer and contributing to the development of type-specific vaccines.

Coinfecção HIV-HPV: prevalência e multiplicidade de genótipos do HPV no colo uterino / Co-infection of HIV-HPV: prevalence and multiplicity of HPV genotypes in the cervix uterine

Indivíduos que praticam atividade sexual desprotegida têm risco combinado de se infectarem pelo HIV e HPV porque esses vírus têm forma de aquisição comum. Dados atuais sugerem que a exposição à infecção pelo HIV pode aumentar a prevalência do HPV, provavelmente pela fraca resposta do sistema imune. O desenvolvimento de métodos baseados em reação em cadeia da polimerase (PCR), que são mais sensíveis e capazes de detectar tipos específicos de HPV simultaneamente, tem permitido a investigação sistemática de infecções múltiplas. Foram pesquisados no MEDLINE (Pubmed) e LILACS os artigos relacionados ao tema, publicados entre 2004 e 2008, e selecionados artigos relevantes na literatura sobre prevalência e multiplicidade do HPV em pacientes infectadas pelo HIV. Mulheres infectadas por HIV têm mais prevalência de HPV, de múltiplos tipos de HPV, e prevalência mais elevada de subtipos oncogênicos que mulheres não infectadas pelo HIV. O HPV-16 tem sido o genótipo mais prevalente, e a infecção múltipla pelo HPV é comumente detectada quando se emprega a PCR. A prevalência de HPV na cérvice uterina de mulheres portadoras do HIV é alta, variando de 52 a 87 por cento. A infecção por múltiplos genótipos é o padrão predominante de infecção pelo HPV nesse grupo de pacientes (41 a 52 porcento).

Individuals that practice umprotected sexual activity have the risk to be infected by both HIV and HPV because these viruses have similar form of acquisition. Current data suggest that the exposition to the infection by HIV can increase the prevalence of the HPV, probably because of the weak reply of the immune system. The development of methods based on polymerase chain reaction (PCR), which are more sensible and capable of detect specific types of HPV simultaneously, has allowed the systematic study of multiple infections. Articles related to the subject published between 2004 and 2008 hab been searched in MEDLINE (Pubmed) and LILACS and relevant articles in literature on prevalence and multiplicity of the HPV in patients infected by HIV were chosen. Women infected by HIV have mores prevalence of HPV, multiple types of HPV and higher prevalence of oncogenic subtypes than women who are not infected by HIV. The HPV-16 has been the most prevalent genotype and the multiple infection by HPV is usually detected when the PCR is used. The prevalence of HPV in the uterine cervix of HIV women is high, varying from 52 to 87 percent. The infection with multiple genotypes is the predominant standard of infection by HPV in this group of patients (41 a 52 percent).

Populational genetic data for 15 STR markers in the Brazilian population of Minas Gerais.

Fifteen short tandem repeats (STR) markers were analyzed (TPOX, D2S1338, D3S1358, FGA, D5S818, CSF1PO, D7S820, D8S1179, TH01, vWA, D13S317, D16S539, D18S51, D19S433, and D21S11) in unrelated individuals undergoing paternity studies from Minas Gerais state, Brazil. Allele frequencies and statistical parameters for the 15 loci were calculated.

[High prevalence of genotype 1 in individuals with hepatitis C in Belo Horizonte, MG]. / Alta prevalência do genótipo 1 em portadores de hepatite C crônica em Belo Horizonte, MG.

The hepatitis C virus is characterized by significant genetic heterogeneity. It is currently classified into six main genotypes and several subtypes. Determining the genotype of the virus is important in clinical practice for guiding the treatment for individuals with chronic hepatitis C. The prevalence of different genotypes and subtypes of the hepatitis C virus has not been fully studied in some regions of Brazil. In this study, 788 samples from patients with chronic hepatitis C who were attended at the Viral Hepatitis Reference Centers in Belo Horizonte were analyzed between 2002 and 2006. The genotyping of the virus was performed by direct sequencing of the 5 UTR region. Additionally, phylogenetic analysis was performed, including all of the genotypic variants obtained. High prevalence of genotype 1 (78.4%; 1b [40.4%], 1a [37.5%] and 1a/b [0.5%]) was observed, followed by genotypes 3a (17.9%) and 2b (3.1%). Three samples were identified as genotype 2a/c (0.4%) and two as genotype 4 (0.2%). The phylogenetic analysis showed the expected segregation of the sequences obtained, with regard to the reference sequences for genotypes 1, 2, 3 and 4, except for two samples of genotype 1a. The high prevalence of genotype 1 (78.4%) found in this population from Belo Horizonte was similar to previous reports from other cities such as Rio de Janeiro, but it was higher than what has been described in São Paulo and in the south of the country. The presence of rare atypical sequences from the 5 UTR region suggests that variants in the hepatitis C virus exist in this population.

Alta prevalência do genótipo 1 em portadores de hepatite C crônica em Belo Horizonte, MG / High prevalence of genotype 1 in individuals with hepatitis C in Belo Horizonte, MG

O vírus da hepatite C é caracterizado pela significativa heterogeneidade genética e é atualmente classificado em seis genótipos principais e diversos subtipos. A determinação do genótipo do vírus tem importância na prática clínica para orientar o tratamento dos pacientes portadores de hepatite C crônica. A prevalência dos diferentes genótipos e subtipos do vírus da hepatite C não tem sido amplamente estudada em algumas regiões do Brasil. Neste estudo foram analisadas 788 amostras de pacientes portadores de hepatite C crônica atendidos nos Centros de Referência em Hepatites Virais de Belo Horizonte, entre 2002 e 2006. A genotipagem do vírus foi realizada por seqüenciamento direto da região 5’ UTR. Adicionalmente, foi realizada análise filogenética incluindo todas as variantes genotípicas obtidas. Observou-se alta prevalência do genótipo 1 (78,4 por cento; 1b [40,4 por cento], 1a [37,5 por cento] e 1a/b [0,5 por cento]), seguida pelo genótipo 3a (17,9 por cento) e pelo 2b (3,1 por cento). Foram identificadas três amostras (0,4 por cento) com o genótipo 2a/c e duas amostras (0,2 por cento) com o genótipo 4. A análise filogenética mostrou a segregação esperada das seqüências obtidas junto às seqüências de referência para os genótipos 1, 2, 3 e 4, exceto em duas amostras do genótipo 1a. A alta prevalência do genótipo 1 (78,4 por cento), encontrada na população de Belo Horizonte é semelhante à previamente descrita em outras cidades, como Rio de Janeiro, mas superior à encontrada em São Paulo e no Sul do país. A presença de raras seqüências atípicas da região 5’UTR sugere a presença de variantes do vírus da hepatite C nesta população.

The hepatitis C virus is characterized by significant genetic heterogeneity. It is currently classified into six main genotypes and several subtypes. Determining the genotype of the virus is important in clinical practice for guiding the treatment for individuals with chronic hepatitis C. The prevalence of different genotypes and subtypes of the hepatitis C virus has not been fully studied in some regions of Brazil. In this study, 788 samples from patients with chronic hepatitis C who were attended at the Viral Hepatitis Reference Centers in Belo Horizonte were analyzed between 2002 and 2006. The genotyping of the virus was performed by direct sequencing of the 5’ UTR region. Additionally, phylogenetic analysis was performed, including all of the genotypic variants obtained. High prevalence of genotype 1 (78.4 percent; 1b [40.4 percent], 1a [37.5 percent] and 1a/b [0.5 percent]) was observed, followed by genotypes 3a (17.9 percent) and 2b (3.1 percent). Three samples were identified as genotype 2a/c (0.4 percent) and two as genotype 4 (0.2 percent). The phylogenetic analysis showed the expected segregation of the sequences obtained, with regard to the reference sequences for genotypes 1, 2, 3 and 4, except for two samples of genotype 1a. The high prevalence of genotype 1 (78.4 percent) found in this population from Belo Horizonte was similar to previous reports from other cities such as Rio de Janeiro, but it was higher than what has been described in São Paulo and in the south of the country. The presence of rare atypical sequences from the 5’ UTR region suggests that variants in the hepatitis C virus exist in this population.

Associação entre a contagem de linfócitos T CD4+ e a gravidade da neoplasia intra-epitelial cervical diagnosticada pela histopatologia em mulheres infectadas pelo HIV / Association between CD4+ T-cell count and intraepithelial cervical neoplasia diagnosed by histopathology in HIV-infected women

OBJETIVO: avaliar a associação entre a contagem de linfócitos T CD4+ e a gravidade da neoplasia intra-epitelial cervical em pacientes HIV positivas. MÉTODOS: estudo transversal no qual foram incluídas 87 pacientes infectadas pelo HIV, confirmado por testes sorológicos prévios. Todas eram portadoras do HPV cervical, diagnosticado por meio da reação em cadeia da polimerase. Foram realizados anamnese, exame físico e colposcopia de todas em pacientes. A biópsia do colo uterino foi realizada quando indicada pelo exame colposcópico. Os resultados histopatológicos foram classificados com neoplasia intra-epitelial de baixo grau (NIC I) ou de alto grau (NIC II e II). A associação entre a contagem de linfócitos T CD4+ e a gravidade da lesão foi verificada por meio da comparação de médias utilizando a análise da variância (ANOVA). RESULTADOS: entre as 60 pacientes biopsiadas foram encontrados 24 casos (40,0 por cento) com NIC I, oito (13,3 por cento) NIC II, três (5 por cento) NIC III, 14 (23,3 por cento) pacientes somente com cervicite crônica e 11 (18,3 por cento) apresentando efeito citopático produzido pelo HPV, mas sem perda da polaridade celular. Isso equivale a 35 mulheres com lesão intra-epitelial de baixo grau (NIC I + HPV) (58,3 por cento) e 11 (18,3 por cento) com lesão intra-epitelial de alto grau (NIC II + NIC III). A associação entre a média da contagem de linfócitos T CD4+ e a gravidade da lesão intra-epitelial cervical não foi significativa (p=0,901). CONCLUSÕES: não houve associação entre a contagem de linfócitos T CD4+ e a gravidade da lesão intra-epitelial do colo uterino, diagnosticada pelo exame histopatológico.

PURPOSE: to evaluate association between CD4+ cell count and cervical intraepithelial lesion severity in HIV-infected women. METHODS: cross-sectional study of 87 HIV-infected patients which were confirmed by previous serologic examinations. All had cervical HPV diagnosed by polymerase chain reaction (PCR). All patients underwent anamnesis, physical examinations and colposcopy. Cervix biopsy was performed when indicated by colposcopical examination. Histopathological results followed Richart's classification, adapted by Wright, and CD4+ cell count and cervical intraepithelial lesion severity association was analysed by comparison of means using analysis using analysis of variance (ANOVA). RESULTS: among 60 biopsied women 24 were found (40.0 percent) with CIN I, eight (13.3 percent) with CIN II, three (5 percent) with CIN III, 14 (23.3 percent) with chronic cervicitis and 11 with cytopathic effect of HPV, without cell polarity loss. This corresponds to 35 (58.3 percent) women with intraepithelial lesion of low grade (CIN I + HPV) and 11 (18.3 percent) with intraepithelial lesion of high grade (CIN II + CIN III). There was no significant association between CD4+ cell count mean and cervical intraepithelial lesion severity (p=0.901). CONCLUSIONS: there was no association between CD4+ cell count and cervical intraepithelial lesion severity diagnosed by histopathological examination.