Histoplasmosis in the Muñiz Hospital of Buenos Aires

Some epidemiological and immunological characteristics and the methodology of diagnosis of 44 cases of histoplasmosis (HP); 36 (27 males and 9 women) associated with AIDS (HP+AIDS) and 8 (7 males and 1 female) with other predisposing factors (HP+non AIDS), diagnosed in the Muñiz Hospital (MH) during 1994, were retrospectively studied. The median age (MA) of HP+AIDS patients was 28 years; 25.5 (22-40) in the women and 28.5 (20-42) in the men and 50 (22-58) years in the HP+non AIDS patients. The more frequent risk factors for HIV infection were intravenous drug addiction (55%) and homo/bisexuality (19%). The MA of these groups were 28 (20-39) and 41 (26-42) years, respectively. Tobaccoism was a predisposing factor in 83% of HP+non AIDS patients. The muco-cutaneous lesions scraping and blood-cultures established the initial diagnosis in 53% and 36% of HP+AIDS patients, respectively and the muco-cutaneous lesions biopsies in 75% of HP+non AIDS cases. At time of diagnosis, all HP+AIDS patients had <200 while HP+non AIDS patients had > 200 CD4 + lymphocytes/µl. Seventy two per cent of HP+AIDS patients were born in Buenos Aires (Bs As) city and 62% of HP+non AIDS patients were born in provinces of Argentina other than Bs As. At moment of diagnosis, 87.5% of HP+AIDS and 62.5% of HP+non AIDS patients lived in Bs As city and Bs As outskirts.

Serological, epidemiological and molecular aspects of hepatitis C virus infection in a population from Londrina, PR, Brazil, 2001-2002

Serological, epidemiological and molecular aspects of hepatitis C virus (HCV) infection were evaluated in 183 subjects from Londrina, Paraná, Brazil, and adjacent areas. Serum samples which tested anti-HCV positive by microparticle enzyme immunoassay (MEIA) obtained from eight patients with chronic hepatitis C, 48 blood donors, and 127 patients infected with the human immunodeficiency virus (HIV) were submitted to another enzyme immunoassay (ELISA) and to the polymerase chain reaction (PCR). About 78.7% of samples were also reactive by ELISA, with the greater proportion (70.8%) of discordant results verified among blood donors. A similar finding was observed for HCV-RNA detection by PCR, with 111/165 (67.3%) positive samples, with higher rates among HIV-positive subjects and patients with chronic hepatitis than among blood donors. Sixty-one PCR-positive samples were submitted to HCV genotyping, with 77.1, 21.3 and 1.6% of the samples identified as types 1, 3 and 2, respectively. Finally, analysis of some risk factors associated with HCV infection showed that intravenous drug use was the most common risk factor among HIV/HCV co-infected patients, while blood transfusion was the most important risk factor in the group without HIV infection. The present study contributed to the knowledge regarding risk factors associated with HCV infection and the distribution of HCV genotypes in the population evaluated.

Toxicodependentes Internados numa Enfermaria de Medicina Interna: Relato de uma Experiência

Contexto: Nos últimos anos tem-se verificado um aumento da patologia médica associada à toxicodependência, em particular infecciosa, condicionando internamento hospitalar. O próprio internamento, por seu lado, é muitas vezes complicado por problemas directamente associados ao estado de dependência física e psíquica, nomeadamente síndrome de abstinência, comportamento indisciplinado e alta precoce por abandono. Os autores pretenderam caracterizar o impacto desta população numa enfermaria de Medicina Interna durante um ano (1998). Métodos: Foram revistos todos os processos dos doentes internados durante o ano de 1998 numa enfermaria de Medicina Interna. Foram identificados dois grupos: o primeiro constituído por todos os toxicodependentes (definido como doentes com consumo activo de substâncias ilícitas na altura da admissão hospitalar - grupo TD); o segundo pela restante população internada (grupo controlo). Foram identificados para todos os doentes: motivos do internamento, duração do mesmo, e mortalidade; dados demográficos (sexo e idade); todos os episódios infecciosos (na admissão e nosocomiais) e serologias positivas para os vírus da imunodeficiência humana, hepatite B e hepatite C. No grupo TD foram ainda caracterizados os hábitos de consumo e as complicações do mesmo em internamento (em particular síndrome de privação). Resultados: Foram identificados 80 toxicodependentes(5,8% do total de internamentos): 50 homens (7,1 %) e 30 mulheres (4,5%). A idade média no grupo TD foi de 31 anos (no grupo controlo foi de 68,5 anos). Em 70% do grupo TD foi identificada serologia positiva para o VIH e em 48,7% para o VHC (no grupo controlo essa prevalência foi de 2,4% e 1,2%, respectivamente). A mortalidade foi de 11,3% e de 12,7 % respectivamente nos grupos TD e controlo, sendo a demora média de 18,7 e de 16,0 dias. Foram identificados 46 casos de tuberculose (18,8% em doentes TD e 2,4 % nos restantes), 293 de pneumonia (28,7% e 21%) e 54 casos de infecção dos tecidos moles (27,5% e 1,5% respectivamente). Só foram identificados 4 casos de endocardite (2 em cada grupo) e 6 de hepatite aguda (todos no grupo TD). No grupo TD verificaram-se 33 casos de síndrome de privação (41,3%). 16 das altas (20%) foram precoces; destes doentes, 4 tinham diagnóstico de tuberculose. Desta população 10 doentes (12,5%) eram sem abrigo (9 homens, 1 mulher) e 66 (82,5%) eram consumidores de drogas endovenosas. Conclusões: No ano de 1998 os doentes toxicodependentes constituíram uma percentagem significativa da população internada, tendo tido demora média e mortalidade semelhantes às da restante população, embora fossem significativamente mais jovens. A maioria foi internada por patologia infecciosa, sendo de assinalar a alta prevalência de tuberculose e de infecção pelo VIH e VHC. É igualmente relevante o elevado número de altas precoces nesta população, algumas das quais de doentes com patologia potencialmente contagiosa.

Serological markers and risk factors for hepatitis B and C viruses in patients infected with human immunodeficiency virus

Both hepatitis B and hepatitis C viruses (HBV and HCV) infection are common in HIV-infected individuals as a result of shared risk factors for acquisition. A serological study for HBV and HCV was performed in 251 HIV-positive individuals from Medellín, Colombia. A qualitative RT-PCR for HCV was done in 90 patients with CD4+ T-cell count < 150 per mm³. Serological markers for HBV infection were present in 97 (38.6%) patients. Thirty six of them (37.1%) had isolated anti-HBc. A multivariate analysis indicated that the following risk factors were significantly associated with the presence of these markers: age (OR = 1.05, 95% CI: 1.01-1.08), pediculosis pubis (OR = 1.83, 95% CI: 1.01-3.33), men who have sex with men and women (OR = 3.23, 95% CI: 1.46-7.13) and men who have sex only with men (OR = 3.73, 95% CI: 1.58-8.78). The same analysis restricted to women showed syphilis as the only significant risk factor. Thus, HBV infection was considerably associated with high risk sexual behavior. HCV was present in only two (0.8%) of HIV patients. Both of them were positive by RT-PCR and anti-HCV. This low frequency of HIV/HCV coinfection was probably due to the uncommon intravenous drug abuse in this population. The frequent finding of isolated anti-HBc warrants molecular approaches to rule out the presence of cryptic HBV infection.

Sexual transmission of hepatitis C

It is generally agreed that the hepatitis C virus (HCV) can be efficiently transmitted parenterally, although data on viral transmission by sexual or non-sexual intrafamilial contact are conflicting. Since data collection began in 1989, the first study dealt with the risk of sexual transmission among multiple sex partners. Other investigations followed, emphasizing that risk increases in specific groups such as patients co-infected with HIV and HBV, sex workers, homosexuals, illicit drug users and patients attended at sexually transmittable disease clinics. The question arises as to what might be the risk for monogamous heterosexuals in the general population, in which one of the partners has HCV? The literature provides overall rates that vary from zero to 27%; however, most studies affirm that the chances of sexual transmission are low or almost null, with rates for this mode fluctuating from zero to 3%. Intrafamilial transmission is strongly considered but inconclusive, since when mentioning transmission between sex partners within the same household, specific situations also should be considered, such as the sharing of personal hygiene items, like razorblades, toothbrushes, nail clippers and manicure pliers, which are important risk factors in HCV transmission. In this review, we discuss the hypotheses of sexual and/or intrafamilial transmission.

Influence of human t-cell lymphotropic virus type 1 (HTLV-1) Infection on laboratory parameters of patients with chronic hepatitis C virus

Hepatitis C virus (HCV) and human T-cell lymphotropic virus type 1 (HTLV-1) share routes of transmission and some individuals have dual infection. Although some studies point to a worse prognosis of hepatitis C virus in patients co-infected with HTLV-1, the interaction between these two infections is poorly understood. This study evaluated the influence of HTLV-1 infection on laboratory parameters in chronic HCV patients. Twelve HTLV-1/HCV-coinfected patients were compared to 23 patients infected only with HCV, in regard to demographic data, risk factors for viral acquisition, HCV genotype, presence of cirrhosis, T CD4+ and CD8+ cell counts and liver function tests. There was no difference in regard to age, gender, alcohol consumption, smoking habits, HCV genotype or presence of cirrhosis between the groups. Intravenous drug use was the most common risk factor among individuals co-infected with HTLV-1. These patients showed higher TCD8+ counts (p = 0.0159) and significantly lower median values of AST and ALT (p = 0.0437 and 0.0159, respectively). In conclusion, we have shown that HCV/HTLV-1 co-infected patients differs in laboratorial parameters involving both liver and immunological patterns. The meaning of these interactions in the natural history of these infections is a matter that deserves further studies.

Diversidade genética e resistência natural ao Maraviroc em estirpes do vírus da imunodeficiência humana Tipo 1 (HIV-1) em circulação em utilizadores de drogas por via endovenosa na Grande Lisboa

RESUMO: O maraviroc (MVC) é o único anti-retroviral antagonista do co-receptor CCR5 licenciado e interage com as ansas transmembranares de CCR5, induzindo uma alteração da sua conformação e impedindo a interacção com gp120. O MVC é activo apenas contra estirpes R5 de HIV-1, sendo utilizado em terapia de recurso. Neste trabalho, foi estudada a diversidade genética da região C2V3C3 do gene env de estirpes de HIV-1 de oxicodependentes por via endovenosa da Grande Lisboa, pesquisando-se também a presença de polimorfismos genéticos naturais. Foram utilizadas 52 amostras de plasma e para 35 destas foi amplificado por RT-nested PCR um produto de 565 pb. A análise filogenética revelou a seguinte distribuição de genótipos: 23 B (incluindo, provavelmente, 2 CRF14_BG), 8 A, 3 G e 1 F1. Após tradução, e por comparação com a sequência consenso B, verificou-se uma elevada frequência de polimorfismos genéticos, sendo encontradas algumas “assinaturas de aminoácidos” relativas aos subtipos não-B. Realizou-se ainda uma pesquisa de locais de N-glicosilação e a previsão da utilização de co-receptores (abordagem genotípica), com recurso às regras 11/25 e da carga líquida da ansa V3 e aos programas PSSM e geno2pheno[coreceptor]. Observou-se uma conservação genérica do número de locais de N-glicosilação e foram identificadas 5 sequências com tropismo X4 ou duplo. Por fim, com base na literatura, realizou-se uma pesquisa de polimorfismos genéticos associados a resistência ao MVC presentes na ansa V3. Foi observado um número elevado destas mutações. A presença dos padrões 11S+26V e 20F+25D+26V, num total de 3 sequências, é relevante, visto estes estarem inequivocamente associados à resistência in vivo ao MVC. Apesar de não estar ainda definido um perfil de resistência para o MVC, a presença das mutações encontradas, em indivíduos sem contacto prévio com o fármaco, trará implicações relevantes na sua gestão clínica, considerando a introdução do MVC na terapia de recurso.---------- ABSTRACT: Maraviroc (MVC) is the only CCR5 inhibitor licensed today. This drug interacts with the transmembrane helices of CCR5 co-receptor, inducing a conformation change of its extracellular loops and preventing the interaction with gp120. MVC is only active against R5 strains of HIV-1 and is currently used in salvage therapy. The genetic diversity of the env C2V3C3 region of HIV-1 strains from injecting drug users in the Greater Lisbon was studied, along with the presence of natural genetic polymorphisms. 52 plasma samples were used and the amplification by RT-nested PCR of a 565 bp-product was possible in 35 of them. The phylogenetic analysis revealed 23 sequences classified as subtype B (probably including 2 CRF14_BG), 8 A, 3 G and 1 F1. After translation, the presence of natural genetic polymorphisms was studied by comparison to a subtype B consensus. A high frequency of genetic polymorphisms was observed and significant “amino acid signatures” were found in association with non-B subtypes. A full characterization of the N-glycosylation sites was also performed and a coreceptor prediction (genotypic approach) was accomplished using the 11/25 and the V3 net charge rules and the programs PSSM and geno2pheno[coreceptor]. The number of N-glycosylation sites was generically preserved. Five sequences were defined as X4 or dual-tropic. Based on published data, a search for genetic polymorphisms, present in V3loop, associated to MVC resistance was finally undertaken. Several of such mutations were observed, being particularly interesting the presence of the patterns 11S+26V and 20F+25D+26V, in a total of 3 sequences, since these patterns have unequivocally been associated with MVC resistance in vivo. Although a resistance profile for MVC is not yet defined, the presence of these mutations in MVC-naïve populations may have significant impact in their clinical management in the future, especially considering the introduction of this drug in salvage therapy.

ORIGIN AND PREVALENCE OF HUMAN T-LYMPHOTROPIC VIRUS TYPE 1 (HTLV-1) AND TYPE 2 (HTLV-2) AMONG INDIGENOUS POPULATIONS IN THE AMERICAS

Human T-lymphotropic virus type 1 (HTLV-1) is found in indigenous peoples of the Pacific Islands and the Americas, whereas type 2 (HTLV-2) is widely distributed among the indigenous peoples of the Americas, where it appears to be more prevalent than HTLV-1, and in some tribes of Central Africa. HTLV-2 is considered ancestral in the Americas and is transmitted to the general population and injection drug users from the indigenous population. In the Americas, HTLV-1 has more than one origin, being brought by immigrants in the Paleolithic period through the Bering Strait, through slave trade during the colonial period, and through Japanese immigration from the early 20th century, whereas HTLV-2 was only brought by immigrants through the Bering Strait. The endemicity of HTLV-2 among the indigenous people of Brazil makes the Brazilian Amazon the largest endemic area in the world for its occurrence. A review of HTLV-1 in all Brazilian tribes supports the African origin of HTLV-1 in Brazil. The risk of hyperendemicity in these epidemiologically closed populations and transmission to other populations reinforces the importance of public health interventions for HTLV control, including the recognition of the infection among reportable diseases and events.

Detection of HTLV-IIa in blood donors in an urban area of the Amazon Region of Brazil (Belém, PA)

The human lymphotropic viruses type I (HTLV-I) and type II (HTLV-II) are members of a group of mammalian retroviruses with similar biological properties, and blood transfusion is an important route of transmission. HTLV-I is endemic in a number of different geographical areas and is associated with several clinical disorders. HTLV-II is endemic in several Indian groups of the Americas and intravenous drug abusers in North and South America, Europe and Southeast Asia. During the year of 1995, all blood donors tested positive to HTLV-I/II in the State Blood Bank (HEMOPA), were directed to a physician and to the Virus Laboratory at the Universidade Federal do Pará for counselling and laboratory diagnosis confirmation. Thirty-five sera were tested by an enzyme immune assay, and a Western blot that discriminates HTLV-I and HTLV-II infection. Two HTLV-II positive samples were submitted to PCR analysis of pX and env genomic region, and confirmed to be of subtype IIa. This is the first detection in Belém of the presence of HTLV-IIa infection among blood donors. This result emphasizes that HTLV-II is also present in urban areas of the Amazon region of Brazil and highlights the need to include screening tests that are capable to detect antibodies for both types of HTLV.

Prevalence of HIV-1/2, HTLV-I/II, hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum and Trypanosoma cruzi among prison inmates at Manhuaçu, Minas Gerais State, Brazil

The purpose of this study was to determine the seroprevalence of human immunodeficiency virus (HIV-1/2), human T-cell lymphotropic virus (HTLV-I/II), hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum and Trypanosoma cruzi among 63 male prisoners in Manhuaçu, Minas Gerais, Brazil and to compare this with data from eligible blood donors. The positive results were as follows: 11/63 (17.5%) for HBV, 5/63 (7.4%) for syphilis, 4/63 (6.3%) for HCV, 3/63 (4.8%) for Chagas' disease, 2/63 (3.2%) for HIV-1/2 and 1/63 (1.6%) for HTLV-I/II. The seroprevalence in prisoners was higher than among blood donors, mainly for antibodies to HIV-1/2, HCV and HBV. This is probably due to low social economic level, illiteracy, higher proportion with a prior history of intravenous drug use and/or unsafe sexual behavior. Therefore, these prisoners constitute a high risk group and routine screening and counseling are recommended.

Molecular epidemiology of HIV-1 in Rio Grande, RS, Brazil

We conducted a molecular epidemiological study to investigate HIV-1 strains in Rio Grande, southern Brazil, searching for an association with transmission mode and risk behavior. Patients (185) identified at an AIDS treatment reference Hospital, from 1994 to 1997, were included; from which 107 blood samples were obtained. Nested PCR was realized once for each sample; for amplified samples (69) HIV subtypes were classified using the heteroduplex mobility assay. Subtypes identified were B (75%), C (22%) and F (3%). All infections with C were diagnosed after 1994. Comparing patients with B and C, no differences were detected regarding demographic, clinical and laboratory characteristics; survival analysis did not reveal differences in HIV to AIDS evolution. A higher proportion of injecting drug users, IDU (not significant, p<.07) was found among those with C. This suggests that C may have been introduced in this area through IDU, and is being spread, probably by their sexual partners, to persons with other risk practices.

Distribution of hepatitis C virus genotypes among different exposure categories in the State of Pará, Brazilian Amazon

INTRODUCTION: Epidemiological studies concerning HCV genotypic distribution in the Brazilian Amazon are scarce. Thus, this study determined the patterns of distribution of HCV genotypes among different exposure categories in the State of Pará, Brazilian Amazon. METHODS: A cross-sectional study was conducted on 312 HCV-infected individuals belonging to different categories of exposure, who were attended at the HEMOPA, CENPREN and a private hemodialysis clinic in Belém. They were tested for HCV antibodies using an immunoenzymatic test, RNA-HCV, using real-time PCR and HCV genotyping through phylogenetic analysis of the 5' UTR. The population groups were epidemiologically characterized according to data collected in a brief interview or medical consultation. RESULTS: Genotype 1 predominated in all the different categories of HCV exposure. HCV genotypic distribution among blood donors comprised genotypes 1 (94%) and 3 (6%). All patients with chronic hematologic diseases had HCV genotype 1. The genotypic distribution in illicit-drug users comprised genotypes 1 (59.6%) and 3 (40.4%). In patients under hemodialysis, genotypes 1 (90.1%), 2 (3.3%), and 3 (6.6%) were detected. Finally, the frequency of genotypes 1 and 3 was significantly different between the groups: BD and DU, PUH and DU, PUH and PCHD and PCHD and DU. CONCLUSIONS: The genotypic frequency and distribution of HCV in different categories of exposure in the State of Pará showed a predominance of genotype 1, regardless of the possible risk of infection.

Liver fibrosis progression in HIV/hepatitis C virus coinfected patients with normal aminotransferases levels

INTRODUCTION: Approximately 30% of hepatitis C virus (HCV) monoinfected patients present persistently normal alanine aminotransferase (ALT) levels. Most of these patients have a slow progression of liver fibrosis. Studies have demonstrated the rate of liver fibrosis progression in hepatitis C virus-human immunodeficiency virus (HCV-HIV) coinfected patients is faster than in patients infected only by HCV. Few studies have evaluated the histological features of chronic hepatitis C in HIV-infected patients with normal ALT levels. METHODS: HCV-HIV coinfected patients (HCV-RNA and anti-HIV positive) with known time of HCV infection (intravenous drugs users) were selected. Patients with hepatitis B surface antigen (HBsAg) positive or hepatitis C treatment before liver biopsy were excluded. Patients were considered to have a normal ALT levels if they had at least 3 normal determinations in the previous 6 months prior to liver biopsy. All patients were submitted to liver biopsy and METAVIR scale was used. RESULTS: Of 50 studied patients 40 (80%) were males. All patients were treated with antiretroviral therapy. The ALT levels were normal in 13 (26%) patients. HCV-HIV co-infected patients with normal ALT levels had presented means of the liver fibrosis stages (0.77±0.44 versus 1.86±1.38; p<0.001) periportal inflammatory activity (0.62±0.77 versus 2.24±1.35; p<0.001) and liver fibrosis progression rate (0.058±0.043 fibrosis unit/year versus 0.118±0.102 fibrosis unit/year) significantly lower as compared to those with elevated ALT. CONCLUSIONS: HCV-HIV coinfected patients with persistently normal ALTs showed slower progression of liver fibrosis. In these patients the development of liver cirrhosis is improbable.

Clinical and epidemiological features of AIDS/tuberculosis comorbidity

Considering the relevance of AIDS/tuberculosis comorbidity worldwide, especially in Brazil, this study was developed to describe the clinical and epidemiological features of the comorbid cases identified from 1989 to 1997 by the epidemiology service of the Hospital das Clínicas of the Universidade de São Paulo. METHODS: Databases containing information on all identified AIDS/tuberculosis cases cared for at the hospital were used to gather information on comorbid cases. RESULTS: During the period, 559 patients were identified as presenting with AIDS/tuberculosis comorbidity. Risk behavior for AIDS was primarily heterosexual contact (38.9%), followed by intravenous drug use (29.3%) and homosexual/bisexual contact (23.2%). Regarding clinical features, there were higher rates of extrapulmonary tuberculosis when compared to tuberculosis without comorbidity. There was an increase in reporting of AIDS by ambulatory units during the period. Epidemiologically, there was a decrease in the male/female ratio, a predominance in the 20 to 39 year-old age group, and a majority of individuals who had less than 8 years of schooling and had low professional qualifications. CONCLUSIONS: High rates of AIDS/tuberculosis cases at our hospital indicate the need for better attention towards early detection of tuberculosis, especially in its extrapulmonary form. Since the population that attends this hospital tends to be of a lower socioeconomic status, better management of AIDS and tuberculosis is required to increase the rates of treatment adherence and thus lower the social costs.

Transmission and progression to disease of Mycobacterium tuberculosis phylogenetic lineages in The Netherlands

The aim of this study was to determine if mycobacterial lineages affect infection risk, clustering, and disease progression among Mycobacterium tuberculosis cases in The Netherlands. Multivariate negative binomial regression models adjusted for patient-related factors and stratified by patient ethnicity were used to determine the association between phylogenetic lineages and infectivity (mean number of positive contacts around each patient) and clustering (as defined by number of secondary cases within 2 years after diagnosis of an index case sharing the same fingerprint) indices. An estimate of progression to disease by each risk factor was calculated as a bootstrapped risk ratio of the clustering index by the infectivity index. Compared to the Euro-American reference, Mycobacterium africanum showed significantly lower infectivity and clustering indices in the foreign-born population, while Mycobacterium bovis showed significantly lower infectivity and clustering indices in the native population. Significantly lower infectivity was also observed for the East African Indian lineage in the foreign-born population. Smear positivity was a significant risk factor for increased infectivity and increased clustering. Estimates of progression to disease were significantly associated with age, sputum-smear status, and behavioral risk factors, such as alcohol and intravenous drug abuse, but not with phylogenetic lineages. In conclusion, we found evidence of a bacteriological factor influencing indicators of a strain's transmissibility, namely, a decreased ability to infect and a lower clustering index in ancient phylogenetic lineages compared to their modern counterparts. Confirmation of these findings via follow-up studies using tuberculin skin test conversion data should have important implications on M. tuberculosis control efforts.