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Coinfection
Kinds of Coinfection Selected AbstractsImmune response to leishmania: paradox rather than paradigmFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2007Parul Tripathi Abstract The leishmaniases are a group of diseases caused by protozoan parasites of the genus Leishmania. Various Leishmania species can cause human infection, producing a spectrum of clinical manifestations. It is estimated that 350 million people are at risk, with a global yearly incidence of 1,1.5 million for cutaneous and 500 000 for visceral leishmaniasis (VL). VL is a major cause of morbidity and mortality in East Africa and the Indian subcontinent. Coinfection with HIV enhances the risk of the disease. The only control measure currently available in India is case detection and treatment with antimonial drugs, which are expensive, not always available and cannot be self-administered. Newer drugs like oral miltefosine have not become widely available. Vector and reservoir control is difficult due to the elusive nature of the vector and the diversity of the animal reservoir. A detailed knowledge of immune response to the parasite would help in designing prophylactic and therapeutic strategies against this infection. [source] Hepatitis B and C virus coinfection: A novel model system reveals the absence of direct viral interference,HEPATOLOGY, Issue 1 2009Pantxika Bellecave Coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV) has been associated with severe liver disease and frequent progression to cirrhosis and hepatocellular carcinoma. Clinical evidence suggests reciprocal replicative suppression of the two viruses, or viral interference. However, interactions between HBV and HCV have been difficult to study due to the lack of appropriate model systems. We have established a novel model system to investigate interactions between HBV and HCV. Stable Huh-7 cell lines inducibly replicating HBV were transfected with selectable HCV replicons or infected with cell culture,derived HCV. In this system, both viruses were found to replicate in the same cell without overt interference. Specific inhibition of one virus did not affect the replication and gene expression of the other. Furthermore, cells harboring replicating HBV could be infected with cell culture,derived HCV, arguing against superinfection exclusion. Finally, cells harboring replicating HBV supported efficient production of infectious HCV. Conclusion: HBV and HCV can replicate in the same cell without evidence for direct interference in vitro. Therefore, the viral interference observed in coinfected patients is probably due to indirect mechanisms mediated by innate and/or adaptive host immune responses. These findings provide new insights into the pathogenesis of HBV,HCV coinfection and may contribute to its clinical management in the future. (HEPATOLOGY 2009.) [source] Prospective study on the risk of hepatocellular carcinoma among hepatitis C virus-positive blood donors focusing on demographic factors, alanine aminotransferase level at donation and interaction with hepatitis B virusINTERNATIONAL JOURNAL OF CANCER, Issue 6 2004Hideo Tanaka Abstract The risk for hepatocellular carcinoma (HCC) among asymptomatic hepatitis C virus (HCV) carriers is not well understood. A community-based prospective study was conducted for over 8 years by record linkage to the Osaka Cancer Registry. The subjects were 1,927 individuals who were positive for anti-HCV through screening for second-generation HCV antibody (passive hemagglutination assay: , 212) in voluntary blood donation. The risk factors for HCC and interaction between HCV and hepatitis B virus (HBV) infection were evaluated by including additional blood donors: 2,519 individuals positive for hepatitis B virus surface antigen (HBsAg) alone, 25 positive for both anti-HCV and HBsAg, 150,379 negative for both anti-HCV and HBsAg. The incidence of HCC (/105 person-years) among the HCV-positive individuals increased with age in both genders, ranging from 68 to 1,306 among those aged 45,74 years. In the HCV-positive individuals, the cumulative risk of developing HCC between the ages of 40 and 74 year was 21.6% among males and 8.7% among females. A stepwise increase in risk was noted as the serum alanine aminotransferase level increased or serum cholesterol level at baseline decreased in multivariate Cox proportional hazard analysis. The 9-year cumulative incidence of HCC among individuals positive for HCV alone, those positive for HBsAg alone and those positive for both was 3.0%, 2.0% and 12.0%, respectively. The age-and-sex-adjusted rate ratio was 126, 102 and 572, respectively, when those negative for both were used as a reference. The results demonstrate an increased risk for HCC among asymptomatic HCV-positive individuals in Japan. Coinfection with HBV and HCV carried a superadditive risk for HCC. © 2004 Wiley-Liss, Inc. [source] Coinfection with Campylobacter species: an epidemiological problem?JOURNAL OF APPLIED MICROBIOLOGY, Issue 2 2001J.F. Richardson Aims: To determine the frequency of coinfection with multiple strains in sporadic cases of human Campylobacter infection. Method and Results: During 1999 10 single colonies of Campylobacter were cultured from each of 53 positive faecal samples. Five isolates were taken from nonselective agar after passive filtration of faecal suspensions and five isolates were taken from selective agar plates. All isolates were sero- and phage typed and their antibiotic resistance determined. Pulsed-field gel electrophoresis and flagellin gene typing were performed on selected isolates. One patient was infected with Camp. coli, the remainder with strains of Camp. jejuni. The majority of patients was infected with a single strain of Campylobacter, but from each of four samples, 7·5%, two strains of Camp. jejuni, confirmed by molecular typing, were identified. Conclusions: Coinfection occurs in sporadic cases of campylobacteriosis. Significance and Impact of the Study: This study has implications in outbreak investigation when distinct strains have been isolated from epidemiologically related patients and/or the suspected source or vehicle. [source] The impact of human herpesvirus-6 and -7 infection on the outcome of liver transplantationLIVER TRANSPLANTATION, Issue 8 2002Raymund R. Razonable Human herpesvirus (HHV)-6 and -7 are novel members of the ,-herpesvirus family that maintain latency in the human host after primary infection. Reactivation from latency and/or increased degree of viral replication occurs during periods of immune dysfunction. The clinical effect of HHV-6 and HHV-7 reactivation in recipients of liver transplants is now being recognized. Clinical illnesses such as fever, rash, pneumonitis, encephalitis, hepatitis, and myelosuppression have been described in a number of anecdotal reports. Moreover, a growing body of evidence suggests that the more important effect of HHV-6 and HHV-7 reactivation on the outcomes of liver transplantation may be mediated indirectly by their interactions with the other ,-herpesvirus,cytomegalovirus (CMV). Coinfection among these three ,-herpesviruses in clinical syndromes that were classically ascribed to be solely caused by CMV has been shown and has raised substantial interest in the potential role of HHV-6 and HHV-7 as copathogens in the direct and indirect illnesses caused by CMV. This article reviews the current scientific data on the role and the magnitude of impact of HHV-6 and HHV-7 infection on the outcomes of liver transplantation. [source] Multiple human papilloma virus types in cervical infections: competition or synergy?APMIS, Issue 5 2010NINA MEJLHEDE Mejlhede N, Pedersen BV, Frisch M, Fomsgaard A. Multiple human papilloma virus types in cervical infections: competition or synergy? APMIS 2010; 118: 346,52. Coinfection with multiple human papilloma virus (HPV) types is common in cervical HPV infection. To evaluate if infections with different HPV types occur independently, we examined 3558 women above 15 years of age suspected of cervical HPV infection. Among them, 1842 (52%) women were HPV negative and 1716 (48%) were HPV positive as analysed by a PCR-based commercial microarray assay for mucosal types. Of the HPV-positive samples, 824 (48%) had single infections, while 892 (52%) had multiple infections. Observed numbers of concurrent HPV types differed from expected numbers under the assumption of independence between infections by the various HPV types. Significant positive associations were observed for 16 pairs of HPV types in statistical analysis accounting for mass significance. Significant negative associations were also found, i.e. women with HPV-16 infection had 0.4 times the odds of having HPV-51 compared with women not infected with HPV-16. HPV-16 was the only type with odds ratios <1 for all pairwise combinations. While our findings of statistically significant coexistence do not prove biological dependence among HPV types, they do suggest that infections with some HPV types may depend on the existence of certain other HPV types. Any interaction between coexisting HPV types could either decrease or increase the efficacy of current HPV vaccines that offer mainly type-specific protection, depending on whether the types vaccinated against compete with other HPV types or not. [source] Human papillomavirus prevalence and cytopathology correlation in young Ugandan women using a low-cost liquid-based pap preparationDIAGNOSTIC CYTOPATHOLOGY, Issue 8 2010Janis M. Taube M.D. Abstract Screening for HPV-driven cervical dysplasia and neoplasia is a significant public health concern in the developing world. The purpose of this study was to use a manual, low-cost liquid-based Pap preparation to determine HPV prevalence in HIV-positive and HIV-negative young women in Kampala, Uganda and to correlate cervical cytopathology with HPV-DNA genotype. About 196 post-partum women aged 18,30 years underwent rapid HIV testing and pelvic examination. Liquid-based cervical cytology samples were processed using a low-cost manual technique. A DNA collection device was used to collect specimens for HPV genotyping. HIV and HPV prevalence was 18 and 64%, respectively. Overall, 49% of women were infected with a high-risk HPV genotype. The most common high-risk HPV genotypes were 16 (8.2%), 33 (7.7%), 35 (6.6%), 45 (5.1%), and 58 (5.1%). The prevalence of HPV 18 was 3.6%. HIV-positive women had an HPV prevalence of 86% compared to 59% in HIV-negative women (P = 0.003). The prevalence of HPV 16/18 did not differ by HIV status. HIV-positive women were infected with a significantly greater number of HPV genotypes compared to HIV-negative women. By multivariate analysis, the main risk factor for HPV infection was coinfection with HIV. HIV-positive women were four times more likely to have abnormal cytology than HIV-negative women (43% vs. 11.6%, P < 0.001). These data highlight that HIV infection is a strong risk factor for HPV infection and resultant abnormal cervical cytology. Notably, the manual low-cost liquid-based Pap preparation is practical in this setting and offers an alternate method for local studies of HPV vaccine efficacy. Diagn. Cytopathol. 2010;38:555,563. 2009 Wiley-Liss, Inc. [source] ON THE EVOLUTION OF SEXUAL REPRODUCTION IN HOSTS COEVOLVING WITH MULTIPLE PARASITESEVOLUTION, Issue 6 2010Rafal Mostowy Host,parasite coevolution has been studied extensively in the context of the evolution of sex. Although hosts typically coevolve with several parasites, most studies considered one-host/one-parasite interactions. Here, we study population-genetic models in which hosts interact with two parasites. We find that host/multiple-parasite models differ nontrivially from host/single-parasite models. Selection for sex resulting from interactions with a single parasite is often outweighed by detrimental effects due to the interaction between parasites if coinfection affects the host more severely than expected based on single infections, and/or if double infections are more common than expected based on single infections. The resulting selection against sex is caused by strong linkage-disequilibria of constant sign that arise between host loci interacting with different parasites. In contrast, if coinfection affects hosts less severely than expected and double infections are less common than expected, selection for sex due to interactions with individual parasites can now be reinforced by additional rapid linkage-disequilibrium oscillations with changing sign. Thus, our findings indicate that the presence of an additional parasite can strongly affect the evolution of sex in ways that cannot be predicted from single-parasite models, and that thus host/multiparasite models are an important extension of the Red Queen Hypothesis. [source] MULTIPLE HIV-1 INFECTION OF CELLS AND THE EVOLUTIONARY DYNAMICS OF CYTOTOXIC T LYMPHOCYTE ESCAPE MUTANTSEVOLUTION, Issue 9 2009Dominik Wodarz Cytotoxic T lymphocytes (CTL) are an important branch of the immune system, killing virus-infected cells. Many viruses can mutate so that infected cells are not killed by CTL anymore. This escape can contribute to virus persistence and disease. A prominent example is HIV-1. The evolutionary dynamics of CTL escape mutants in vivo have been studied experimentally and mathematically, assuming that a cell can only be infected with one HIV particle at a time. However, according to data, multiple virus particles frequently infect the same cell, a process called coinfection. Here, we study the evolutionary dynamics of CTL escape mutants in the context of coinfection. A mathematical model suggests that an intermediate strength of the CTL response against the wild-type is most detrimental for an escape mutant, minimizing overall virus load and even leading to its extinction. A weaker or, paradoxically, stronger CTL response against the wild-type both lead to the persistence of the escape mutant and higher virus load. It is hypothesized that an intermediate strength of the CTL response, and thus the suboptimal virus suppression observed in HIV-1 infection, might be adaptive to minimize the impact of existing CTL escape mutants on overall virus load. [source] WITHIN-HOST POPULATION DYNAMICS AND THE EVOLUTION OF MICROPARASITES IN A HETEROGENEOUS HOST POPULATIONEVOLUTION, Issue 2 2002Vitaly V. Ganusov Abstract Why do parasites harm their hosts? The general understanding is that if the transmission rate and virulence of a parasite are linked, then the parasite must harm its host to maximize its transmission. The exact nature of such trade-offs remains largely unclear, but for vertebrate hosts it probably involves interactions between a microparasite and the host immune system. Previous results have suggested that in a homogeneous host population in the absence of super- or coinfection, within-host dynamics lead to selection of the parasite with an intermediate growth rate that is just being controlled by the immune system before it kills the host (Antia et al. 1994). In this paper, we examine how this result changes when heterogeneity is introduced to the host population. We incorporate the simplest form of heterogeneity,random heterogeneity in the parameters describing the size of the initial parasite inoculum, the immune response of the host, and the lethal density at which the parasite kills the host. We find that the general conclusion of the previous model holds: parasites evolve some intermediate growth rate. However, in contrast with the generally accepted view, we find that virulence (measured by the case mortality or the rate of parasite-induced host mortality) increases with heterogeneity. Finally, we link the within-host and between-host dynamics of parasites. We show how the parameters for epidemiological spread of the disease can be estimated from the within-host dynamics, and in doing so examine the way in which trade-offs between these epidemiological parameters arise as a consequence of the interaction of the parasite and the immune response of the host. [source] Microbial interactions and differential protein expression in Staphylococcus aureus ,Candida albicans dual-species biofilmsFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2010Brian M. Peters Abstract The fungal species Candida albicans and the bacterial species Staphylococcus aureus are responsible for a majority of hospital-acquired infections and often coinfect critically ill patients as complicating polymicrobial biofilms. To investigate biofilm structure during polymicrobial growth, dual-species biofilms were imaged with confocal scanning laser microscopy. Analyses revealed a unique biofilm architecture where S. aureus commonly associated with the hyphal elements of C. albicans. This physical interaction may provide staphylococci with an invasion strategy because candidal hyphae can penetrate through epithelial layers. To further understand the molecular mechanisms possibly responsible for previously demonstrated amplified virulence during coinfection, protein expression studies were undertaken. Differential in-gel electrophoresis identified a total of 27 proteins to be significantly differentially produced by these organisms during coculture biofilm growth. Among the upregulated staphylococcal proteins was l -lactate dehydrogenase 1, which confers resistance to host-derived oxidative stressors. Among the downregulated proteins was the global transcriptional repressor of virulence factors, CodY. These findings demonstrate that the hyphae-mediated enhanced pathogenesis of S. aureus may not only be due to physical interactions but can also be attributed to the differential regulation of specific virulence factors induced during polymicrobial growth. Further characterization of the intricate interaction between these pathogens at the molecular level is warranted, as it may aid in the design of novel therapeutic strategies aimed at combating fungal,bacterial polymicrobial infection. [source] Serologic Prevalence of Antibodies to Helicobacter pylori in Internationally Adopted ChildrenHELICOBACTER, Issue 3 2003Laurie C. Miller ABSTRACT Background.Helicobacter pylori (H. pylori) infection has been linked to gastritis, diarrhea, peptic ulcers, failure-to-thrive, anemia, as well as predisposition to gastric malignancies. Because many internationally adopted children have diarrhea, failure-to-thrive, and anemia on arrival to the US, we determined the prevalence of HP antibodies among these children. Methods. Serum samples from 226 unselected children from 18 countries who were evaluated in the International Adoption Clinic at New England Medical Center were tested for antibodies to H. pylori. The results of serologic screening were analyzed in relation to age at adoption, site of residence prior to adoption, weight and height, and the presence or absence of anemia, diarrhea, or intestinal parasites. Results. 31% of internationally adopted children had antibodies to H. pylori. The presence of H. pylori -antibodies was associated with residence in an orphanage (vs. foster care) prior to adoption, older age at adoption, and coinfection with intestinal parasites. No direct effects on height or weight were identified; no associations with diarrhea or anemia were found. Conclusions. Internationally adopted children have a high incidence of exposure to H. pylori, as diagnosed serologically. Residence in an orphanage (compared with foster care), older age at adoption, and coinfection with intestinal parasites were more common among children seropositive for anti- H. pylori antibodies. [source] Hepatitis B and C virus coinfection: A novel model system reveals the absence of direct viral interference,HEPATOLOGY, Issue 1 2009Pantxika Bellecave Coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV) has been associated with severe liver disease and frequent progression to cirrhosis and hepatocellular carcinoma. Clinical evidence suggests reciprocal replicative suppression of the two viruses, or viral interference. However, interactions between HBV and HCV have been difficult to study due to the lack of appropriate model systems. We have established a novel model system to investigate interactions between HBV and HCV. Stable Huh-7 cell lines inducibly replicating HBV were transfected with selectable HCV replicons or infected with cell culture,derived HCV. In this system, both viruses were found to replicate in the same cell without overt interference. Specific inhibition of one virus did not affect the replication and gene expression of the other. Furthermore, cells harboring replicating HBV could be infected with cell culture,derived HCV, arguing against superinfection exclusion. Finally, cells harboring replicating HBV supported efficient production of infectious HCV. Conclusion: HBV and HCV can replicate in the same cell without evidence for direct interference in vitro. Therefore, the viral interference observed in coinfected patients is probably due to indirect mechanisms mediated by innate and/or adaptive host immune responses. These findings provide new insights into the pathogenesis of HBV,HCV coinfection and may contribute to its clinical management in the future. (HEPATOLOGY 2009.) [source] Human leukocyte antigen,associated sequence polymorphisms in hepatitis C virus reveal reproducible immune responses and constraints on viral evolution,HEPATOLOGY, Issue 2 2007Joerg Timm CD8+ T cell responses play a key role in governing the outcome of hepatitis C virus (HCV) infection, and viral evolution enabling escape from these responses may contribute to the inability to resolve infection. To more comprehensively examine the extent of CD8 escape and adaptation of HCV to human leukocyte antigen (HLA) class I restricted immune pressures on a population level, we sequenced all non-structural proteins in a cohort of 70 chronic HCV genotype 1a-infected subjects (28 subjects with HCV monoinfection and 42 with HCV/human immunodeficiency virus [HIV] coinfection). Linking of sequence polymorphisms with HLA allele expression revealed numerous HLA-associated polymorphisms across the HCV proteome. Multiple associations resided within relatively conserved regions, highlighting attractive targets for vaccination. Additional mutations provided evidence of HLA-driven fixation of sequence polymorphisms, suggesting potential loss of some CD8 targets from the population. In a subgroup analysis of mono- and co-infected subjects some associations lost significance partly due to reduced power of the utilized statistics. A phylogenetic analysis of the data revealed the substantial influence of founder effects upon viral evolution and HLA associations, cautioning against simple statistical approaches to examine the influence of host genetics upon sequence evolution of highly variable pathogens. Conclusion: These data provide insight into the frequency and reproducibility of viral escape from CD8+ T cell responses in human HCV infection, and clarify the combined influence of multiple forces shaping the sequence diversity of HCV and other highly variable pathogens. (HEPATOLOGY 2007.) [source] Longitudinal evaluation reveals a complex spectrum of virological profiles in hepatitis B virus/hepatitis C virus,coinfected patients,,HEPATOLOGY, Issue 1 2006Giovanni Raimondo Hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection is often associated with severe forms of liver disease. However, comprehensive studies are lacking, and scant information is available regarding the virological behavior over time in coinfected patients. This study enrolled 133 untreated HBV/HCV-positive patients (male/female = 102/31; median age 51 years [range: 22-83 years]) who were longitudinally followed up for 1 year with bimonthly evaluation of HBV/HCV viremia levels and liver biochemistry. Thirty of these patients had triple infection with hepatitis Delta virus (HDV), while 103 patients were HDV-negative. In the HDV-negative group, active infection with both HBV and HCV was revealed in 24 cases, inactive infection by both viruses was seen in 15 cases, active HBV/inactive HCV was seen in 15 cases, and inactive HBV/active HCV was seen in 49 cases. However, 32 subjects (31%) presented dynamic virological profiles characterized by fluctuation of HBV and/or HCV viremia levels that at different time points were over or under the cutoff limits. Consequently, a correct diagnosis could be performed in these subjects only by serially repeating the virological tests 1 year apart. Similarly, 15 of the 30 HDV-positive subjects showed active HBV and/or HCV infection, with fluctuating virological patterns in 8 cases. In conclusion, this study showed that the virological patterns in HBV/HCV coinfection are widely divergent and have dynamic profiles. A careful longitudinal evaluation of the viremia levels of both viruses is essential for making a correct diagnosis and tailoring the appropriate therapeutic schedule in coinfected patients. (HEPATOLOGY 2005.) [source] Hepatitis C virus load and survival among injection drug users in the United States,HEPATOLOGY, Issue 6 2005Michie Hisada Persons chronically infected with hepatitis C virus (HCV), some of whom may be coinfected with HIV and human T-lymphotropic virus type II (HTLV-II), are at high risk for end-stage liver disease (ESLD). We evaluated whether ESLD death was associated with premorbid HCV RNA level or specific HCV protein antibodies among persons with or without HIV/HTLV-II coinfection in a cohort of 6,570 injection drug users who enrolled in 9 US cities between 1987 and 1991. We compared 84 ESLD descendents and 305 randomly selected cohort participants with detectable HCV RNA, stratified by sex, race, HIV, and HTLV-II strata. Relative hazard (RH) of ESLD death was derived from the proportional hazard model. Risk of ESLD death was unrelated to the intensity of antibodies against the HCV c-22(p), c-33(p), c-100(p), and NS5 proteins, individually or combined, but it increased with HCV RNA level (RHadj= 2.26 per log10 IU/mL, 95% CI: 1.45-5.92). The association between HCV RNA level and ESLD death remained significant after adjustment for alcohol consumption (RHadj= 2.57 per log10 IU/mL, 95% CI: 1.50-8.10). Deaths from AIDS (n = 45) and other causes (n = 43) were unrelated to HCV RNA (RHadj= 1.14 and 1.29 per log10 IU/mL, respectively). HIV infection was not associated with ESLD risk in multivariate analyses adjusted for HCV RNA. Men had an increased risk of ESLD death in unadjusted analyses (RH = 1.92, 95% CI: 1.15-3.56) but not in multivariate analysis (RHadj= 0.98, 95% CI: 0.48-2.88). Non-black patients were at increased risk for ESLD death (RHadj= 2.76, 95% CI: 1.49-10.09). In conclusion, HCV RNA level is a predictor of ESLD death among persons with chronic HCV infection. (HEPATOLOGY 2005.) [source] Sexual activity as a risk factor for hepatitis CHEPATOLOGY, Issue S1 2002M.P.H., Norah A. Terrault M.D. The accumulated evidence indicates that hepatitis C virus (HCV) can be transmitted by sexual contact but much less efficiently than other sexually transmitted viruses, including hepatitis B virus and human immunodeficiency virus (HIV). However, because sex is such a common behavior and the reservoir of HCV-infected individuals is sizable, sexual transmission of HCV likely contributes to the total burden of infection in the United States. Risk of HCV transmission by sexual contact differs by the type of sexual relationship. Persons in long-term monogamous partnerships are at lower risk of HCV acquisition (0% to 0.6% per year) than persons with multiple partners or those at risk for sexually transmitted diseases (0.4% to 1.8% per year). This difference may reflect differences in sexual risk behaviors or differences in rates of exposure to nonsexual sources of HCV, such as injection drug use or shared razors and toothbrushes. In seroprevalence studies in monogamous, heterosexual partners of HCV-infected, HIV-negative persons, the frequency of antibody-positive and genotype-concordant couples is 2.8% to 11% in Southeast Asia, 0% to 6.3% in Northern Europe, and 2.7% in the United States. Among individuals at risk for sexually transmitted diseases (STDs), the median seroprevalence of antibody to HCV (anti-HCV) is 4% (range, 1.6% to 25.5%). HIV coinfection appears to increase the rate of HCV transmission by sexual contact. Current recommendations about sexual practices are different for persons with chronic HCV infection who are in steady monogamous partnerships versus those with multiple partners or who are in short-term sexual relationships. (HEPATOLOGY 2002;36:S99,S105). [source] Mitochondrial toxicity in HIV-HCV coinfection: It depends on the choice of antiretroviral drugs?HEPATOLOGY, Issue 2 2002Raffaele Bruno M.D. No abstract is available for this article. [source] Chronic ethanol increases adeno-associated viral transgene expression in rat liver via oxidant and NF,B-dependent mechanismsHEPATOLOGY, Issue 5 2000Michael D. Wheeler Recombinant adeno-associated virus (rAAV) transduction is limited in vivo, yet can be enhanced by hydroxyurea, ultraviolet-irradiation, or adenovirus coinfection, possibly via mechanisms involving stress in the host cell. Because chronic ethanol induces oxidative stress, it was hypothesized that chronic ethanol would increase rAAV transduction in vivo. To test this hypothesis, rAAV encoding ,-galactosidase was given to Wistar rats that later received either ethanol diet or high-fat control diet via an enteral-feeding protocol for 3 weeks. Expression and activity of ,-galactosidase in the liver were increased nearly 5-fold by ethanol. The increase in transgene expression was inhibited by antioxidant diphenylene iodonium (DPI), which is consistent with the hypothesis that ethanol causes an increase in rAAV transduction via oxidative stress. Ethanol increased DNA synthesis only slightly; however, it increased the nuclear transcription factor ,B (NF,B) 4-fold, a phenomenon also sensitive to DPI. Moreover, a 6-fold increase in rAAV transgene expression was observed in an acute ischemia-reperfusion model of oxidative stress. Transgene expression was transiently increased 24 hours after ischemia-reperfusion 3 days and 3 weeks after rAAV infection. Further, adenoviral expression of superoxide dismutase or I,B, superrepressor inhibited rAAV transgene expression caused by ischemia-reperfusion. Therefore, it is concluded that ethanol increases rAAV transgene expression via mechanisms dependent on oxidative stress, and NF,B likely through enhancement of cytomegaloviral (CMV) promoter elements. Alcoholic liver disease is an attractive target for gene therapy because consumption of ethanol could theoretically increase expression of therapeutic genes (e.g., superoxide dismutase). Moreover, this study has important implications for rAAV gene therapy and potential enhancement and regulation of transgene expression in liver. [source] Hepatitis C virus infection among HIV-1 infected individuals from northern MexicoHEPATOLOGY RESEARCH, Issue 5 2007Ana M. Rivas-Estilla Aims:, The prevalence of hepatitis C virus (HCV) infection, risk factors and HCV genotypes in 140 HIV-1 infected individuals from northern Mexico was determined. Methods:, Hepatitis C infection was confirmed by the detection of anti-HCV antibodies and HCV-RNA in sera, and genotyping was performed by the InnoLiPA-HCV genotype assay. Results:, Seventeen (12.1%) out of 140 HIV-infected individuals were found to be HCV-positive. Coinfected individuals were more likely to be male (87%). The most frequent genotype was 1a (41%), followed by 1b (29.4%), 2a/c (17.6%), 2b (5.9%) and 3 (5.9%). Serum transaminase concentrations (AST and ALT) were higher in coinfected patients. Among the risk factors for coinfection: sexual transmission was the most frequently observed (men who have sex with men (MSM); 64.7% and bisexual behavior; 64.7%) followed by intravenous drug users (IVDU) (53%). There was no association of the HCV genotypes with the age and risk factors for HIV-1 and HCV infection observed in the studied patients. Conclusion:, The results suggest that the prevalence of HIV-1/HCV coinfection in Mexico is lower than in other American countries. [source] Cocirculation of and coinfections with hepatitis A virus subgenotypes IIIA and IB in patients from Pune, western IndiaHEPATOLOGY RESEARCH, Issue 2 2007Shobha Chitambar Aim:, During the 1990s, a changing pattern of epidemiology of hepatitis A was reported in different populations of India. The present study was undertaken to investigate the molecular epidemiology of hepatitis A virus (HAV) strains over a period of 10 years. Methods:, Stool/serum samples were collected from hepatitis A patients clinically presenting acute viral hepatitis and hepatic encephalopathy. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to detect HAV-RNA. HAV genomes were examined by sequencing PCR products of VP1/2A junction (168 bp) and RNA polymerase (116 bp) regions. Results:, Subgenotype IIIA and IB were detected in 74.2% and 9.7% of specimens, respectively, while 16.1% of patients had mixed infections. Sewage samples also showed presence of both IIIA (9/10) and IB (1/10) subgenotypes. RNA polymerase region showed two clusters constituting 51.6% and 19.4% strains closer to Nor21 and HM175 strains, respectively, in clinical specimens. Three isolates appeared as discordant subgenotypes in VP1/2A and RNA polymerase regions. Conclusion:, The data revealed cocirculation of and coinfection with subgenotypes IIIA and IB, with predominance of IIIA and genetic heterogeneity of HAV strains in western India. [source] Prevalence of coinfection with human immunodeficiency virus and hepatitis C virus in JapanHEPATOLOGY RESEARCH, Issue 1 2007Kazuhiko Koike People with human immunodeficiency virus (HIV) infection are frequently infected with hepatitis C virus (HCV), because of the common transmission routes. Since the dissemination of hyperactive antiretrovirus therapy (HAART), the morbidity and mortality associated with HIV infection have declined. However, the reduction in mortality due to opportunistic infection has made HCV-associated liver diseases the leading cause of mortality in Western countries. A similar situation is assumed in Japan, but the status of coinfection with HIV and HCV is unclear. We conducted a nationwide survey to determine the prevalence of coinfection with HIV and HCV by distributing a questionnaire to the hospitals in the HIV/AIDS Network of Japan. Among 4877 patients reported to be HIV-positive, 935 (19.2%) were also positive for the anti-HCV antibody. Most (84.1%) of the patients coinfected with HIV and HCV were recipients of blood products. These data, for the first time, show the current status of coinfection with HIV and HCV in Japan. A detailed analysis of the progression and severity of liver diseases in the coinfected patients is expected. [source] HIV and the body: a review of multidisciplinary managementHIV MEDICINE, Issue 2010J Rockstroh Abstract The increase in the life expectancy achieved following the introduction of more effective antiretroviral therapy (ART) in recent years now means that the HIV-infected population are for the first time being exposed to the age-related diseases that affect the general population. Nevertheless, the prevalence of these diseases (which include cardiovascular disease, dyslipidaemia, glucose intolerance and diabetes) is higher, and their onset earlier in the HIV population, probably due to the complex interplay between HIV infection, coinfection with hepatitis B and C, and ART. As a result, HIV physicians are now required to adopt a new approach to the management of HIV, which involves screening and regular monitoring of all HIV-infected individuals for the presence of comorbidities and prompt referral to other clinical specialties when required. If this challenge to patient management is to be overcome, it is clear that educating physicians in the diagnosis and treatment of age-associated comorbidities is essential, either through ongoing programmes such as the HIV and the Body initiative, an overarching independent medical education programme established in 2007 and overseen by an independent Steering Committee, organized and funded by Gilead, and/or through internal training. To assist in this process, this article provides an overview of common comorbidities affecting HIV-infected persons and provides practical guidance on their management. [source] British HIV Association guidelines for the management of coinfection with HIV-1 and hepatitis B or C virus 2010HIV MEDICINE, Issue 1 2010G Brook First page of article [source] Ankle,branch index and HIV: the role of antiretroviralsHIV MEDICINE, Issue 1 2009J Olalla Objective To study the relationship between antiretroviral (ARV) treatment and abnormal ankle,branch index (ABI) and to compare the risk factors for altered ABI. Methods Patients coming to the office from April 2007 until July 2007 were offered the chance to take part in the study. ABI was obtained by the standard technique. Those ,0.9 or ,1.3 were considered altered ABI. Clinical reports were reviewed to examine traditional vascular risk factors, coinfection with hepatitis C virus and/or hepatitis B virus, tobacco use, highly active antiretroviral therapy use and its components and length of use of each ARV drug. Results ABI was measured in 147 patients, 82.3% males. Thirty-three patients (22.45%) had an altered ABI, and it was related to CD4 cell nadir, dyslipidaemia and protease inhibitor (PI) use. When logistic regression was carried out, only dyslipidaemia (OR 2.68, CI 95%: 1.06,6.91) and PI use (OR 2.79, CI 95%: 1.15,6.54) remained in the model. Conclusions Altered ABI is associated with PI use independently of dyslipidaemia. Probably, it marks patients with high vascular risk not identified with traditional scales. [source] Hepatitis B or hepatitis C coinfection in HIV-infected pregnant women in EuropeHIV MEDICINE, Issue 7 2008M Landes Objectives The aim of the study was to investigate the prevalence of and risk factors for hepatitis C or B virus (HCV or HBV) coinfection among HIV-infected pregnant women, and to investigate their immunological and virological characteristics and antiretroviral therapy use. Methods Information on HBV surface antigen (HBsAg) positivity and HCV antibody (anti-HCV) was collected retrospectively from the antenatal records of HIV-infected women enrolled in the European Collaborative Study and linked to prospectively collected data. Results Of 1050 women, 4.9% [95% confidence interval (CI) 3.6,6.3] were HBsAg positive and 12.3% (95% CI 10.4,14.4) had anti-HCV antibody. Women with an injecting drug use(r) (IDU) history had the highest HCV-seropositivity prevalence (28%; 95% CI 22.8,35.7). Risk factors for HCV seropositivity included IDU history [adjusted odds ratio (AOR) 2.92; 95% CI 1.86,4.58], age (for ,35 years vs. <25 years, AOR 3.45; 95% CI 1.66,7.20) and HBsAg carriage (AOR 5.80; 95% CI 2.78,12.1). HBsAg positivity was associated with African origin (AOR 2.74; 95% CI 1.20,6.26) and HCV seropositivity (AOR 6.44; 95% CI 3.08,13.5). Highly active antiretroviral therapy (HAART) use was less likely in HIV/HCV-seropositive than in HIV-monoinfected women (AOR 0.34; 95% CI 0.20,0.58). HCV seropositivity was associated with a higher adjusted HIV RNA level (+0.28log10 HIV-1 RNA copies/mL vs. HIV-monoinfected women; P=0.03). HIV/HCV-seropositive women were twice as likely to have detectable HIV in the third trimester/delivery as HIV-monoinfected women (AOR 1.95; P=0.049). Conclusions Although HCV serostatus impacted on HAART use, the association between HCV seropositivity and uncontrolled HIV viraemia in late pregnancy was independent of HAART. [source] Hepatitis B virus and HIV coinfection: relationship of different serological patterns to survival and liver diseaseHIV MEDICINE, Issue 5 2007MK Osborn Objectives Eighty per cent of HIV-positive patients show evidence of past or current infection with hepatitis B virus (HBV). The impact of chronic HBV infection or the presence of isolated HBV core antibody on survival in the era of highly active antiretroviral therapy (HAART) has not been well studied. Methods This retrospective analysis included patients from the HIV Atlanta Veterans Affairs Cohort Study (HAVACS). This cohort comprises 2818 HIV-positive patients followed since 1982. For this analysis, 1685 patients with available HBV serologies were included, based on laboratory records available since 1992. Adjusted survival analyses were performed for patients showing any of four serological patterns for HBV: (1) surface antigen positive (chronic HBV infection), (2) isolated core antibody, (3) surface antibody with or without core antibody (resolved/vaccinated) and (4) no HBV markers (negative group). Risk factors for liver disease were identified. Results A trend was seen for a lower survival rate from AIDS to death in the chronic HBV infection group compared with the negative group [hazard ratio (HR) 1.43; P=0.118]. The only independent predictor of lower survival rate was hepatitis C virus positivity (HR 1.62; P=0.008). Protective factors were use of HAART (HR 0.40; P=0.0003), use of lamivudine (HR 0.36; P<0.0001) and use of tenofovir (HR 0.23; P<0.0001). Survival from HIV diagnosis to death was not different among the HBV groups. Isolated core antibody patients did not have a lower survival rate compared with those with resolved HBV infection. Patients with chronic HBV infection were 3.5 times more likely to have liver disease than those with no HBV infection (P<0.02). Conclusions There is a trend towards a lower survival rate in patients with HIV and chronic HBV infection, but the difference did not reach statistical significance. The presence of isolated core antibody was not associated with a lower survival rate. [source] Long-term survival of HIV-infected patients treated with highly active antiretroviral therapy in Serbia and MontenegroHIV MEDICINE, Issue 2 2007DO Jevtovi Background Highly active antiretroviral therapy (HAART) has dramatically changed the prognosis of HIV disease, even in terminally ill patients. Although these patients may survive many years after the diagnosis of AIDS if treated with HAART, some still die during treatment. Methods A retrospective study in a cohort of 481 HIV-infected patients treated with HAART between January 1998 and December 2005 was conducted to compare subgroups of long-term survivors (LTSs) and patients who died during treatment. Results A total of 48 patients survived for more than 72 months (mean 83.8±standard deviation 5.6 months). Thirty patients died during treatment (mean 35.3±25.0 months), of whom nine died from non-AIDS-related causes, 18 died from AIDS-related causes, and three died as a result of HAART toxicity. Although LTSs were significantly (P=0.015) younger at HAART initiation, age below 40 years was not a predictor of long-term survival. The subgroups did not differ in the proportion of clinical AIDS cases at HAART initiation, in the prevalence of hepatitic C virus (HCV) coinfection, or in pretreatment and end-of-follow-up CD4 cell counts. In contrast, the viral load achieved during treatment was lower in the survivors (P=0.03), as was the prevalence of hepatitis B virus (HBV) coinfection (P=0.03). Usage of either protease inhibitor (PI)-containing regimens [odds ratio (OR) 9.0, 95% confidence interval (CI) 2.2,35.98, P<0.001] or all three drug classes simultaneously (OR 7.4, 95% CI 2.2,25.1, P<0.001) was associated with long-term survival. Drug holidays incorporated in structured treatment interruption (STI) were also associated with a good prognosis (OR 14.9, 95% CI 2.9,75.6, P<0.001). Conclusions Long-term survival was associated with PI-based HAART regimens and lower viraemia, but not with the immunological status either at baseline or at the end of follow up. STI when CD4 counts reach 350 cells/,L, along with undetectable viraemia, was a strong predictor of long-term survival. [source] Safety of nevirapine in pregnancyHIV MEDICINE, Issue 1 2007U Natarajan Background Nevirapine has been widely used in pregnancy for its efficacy, low pill burden, bioavailability and rapid transplacental transfer. Concern about nevirapine toxicity during pregnancy has emerged over recent years. Objectives The aims of the study were to document the frequency of cutaneous and hepatic toxicity secondary to nevirapine use during pregnancy and to compare rates in women starting nevirapine during the current pregnancy with those in women who had commenced nevirapine prior to the current pregnancy. Design This was a retrospective, comparative, five-centre study carried out in London, UK, in 1997,2003. Methods All HIV-1-infected women who received nevirapine as part of combination antiretroviral therapy (ART) during pregnancy were included in the study. Data on demographics, HIV infection risk, Centers for Disease Control and Prevention (CDC) status, surrogate markers at initiation of therapy, other medications hepatitis B and C virus coinfection and clinical data relating to potential toxicity were collated and analysed. Results Fifteen of 235 eligible women (6.4%) developed rash and eight (3.4%) developed hepatotoxicity, including four with coexistent rash, giving a combined incidence of 19 potential cases of nevirapine toxicity during pregnancy (8.1%). Alternative causes of rash/hepatotoxicity were suspected in seven cases and only 10 mothers (5.8%) discontinued nevirapine. Of the 170 women who commenced nevirapine during this pregnancy, 13 (7.6%) developed rash and eight (4.7%) hepatotoxicity, a combined incidence of 10%. Only two of 65 women with nevirapine exposure prior to this pregnancy developed rash (3.1%). Conclusions Nevirapine-containing ART was well tolerated in this cohort of pregnant women. Although pregnancy did not appear to increase the risk of nevirapine-associated toxicity compared to published adult data, CD4 count may be less predictive of toxicity in pregnancy. [source] Validation of a simple model for predicting liver fibrosis in HIV/hepatitis C virus-coinfected patientsHIV MEDICINE, Issue 6 2005H Al-Mohri Objectives Recently, several models incorporating laboratory measurements have been validated for use as surrogate markers for liver fibrosis in hepatitis C virus (HCV) mono-infection, the simplest of these being the aspartate aminotransferase (AST) to platelet ratio index (APRI). We evaluated how well the APRI predicts significant hepatic fibrosis in patients with HIV/HCV coinfection. Methods Forty-six HIV/HCV-coinfected patients who underwent liver biopsy and had concomitant laboratory measurements (±3 months) were included in the study. Significant fibrosis was defined as F2,F4 using Batt and Ludwig scoring (=3 Ishak). APRI=[(AST/upper limit of normal)/platelet count (109/L)] × 100. We used sas proc logistic (SAS Institute, Cary, NC) to calculate the area under the receiver operating curve (ROC) (AUC). Sensitivities, specificities, positive predictive value (PPV) and negative predictive value (NPV) were compared using cut-offs previously identified in the literature. Results Thirty-three of 46 patients (72%) had significant fibrosis on biopsy. For significant fibrosis, the area under the ROC for the APRI was 0.847±0.057. APRI scores >1.5 (the higher cut-off) were 100% specific and 52% sensitive; PPV was 100% and NPV 45%. Scores <0.5 (the lower cut-off) were 82% sensitive and 46% specific in ruling out significant fibrosis (PPV 79%; NPV 50%). Conclusions A simple model incorporating readily available laboratory data is highly predictive of significant fibrosis in HIV/HCV coinfection and could serve as a biopsy-sparing measure, thus making treatment more accessible for this population. [source] | ||||||||||||||||||||||||||||||||||