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Biomedical subjects

Joseph Torresi

Publications and source records attributed to Joseph Torresi.

At least 19 recordsLinked to original sources
PubMed2006

Illness in travelers visiting friends and relatives: a review of the GeoSentinel Surveillance Network.

Travelers returning to their country of origin to visit friends and relatives (VFRs) have increased risk of travel-related health problems. We examined GeoSentinel data to compare travel characteristics and illnesses acquired by 3 groups of travelers to low-income countries: VFRs who had originally been immigrants (immigrant VFRs), VFRs who had not originally been immigrants (traveler VFRs), and tourist travelers. Immigrant VFRs were predominantly male, had a higher mean age, and disproportionately required treatment as inpatients. Only 16% of immigrant VFRs sought pretravel medical advice. Proportionately more immigrant VFRs visited sub-Saharan Africa and traveled for >30 days, whereas tourist travelers more often traveled to Asia. Systemic febrile illnesses (including malaria), nondiarrheal intestinal parasitic infections, respiratory syndromes, tuberculosis, and sexually transmitted diseases were more commonly diagnosed among immigrant VFRs, whereas acute diarrhea was comparatively less frequent. Immigrant VFRs and traveler VFRs had different demographic characteristics and types of travel-related illnesses. A greater proportion of immigrant VFRs presented with serious, potentially preventable travel-related illnesses than did tourist travelers.

Adolescent↗
PubMed2006

Co-infection of human parvovirus B19 in Vietnamese patients with hepatitis B virus infection.

BACKGROUND/AIMS: Human parvovirus B19 (B19) has been identified in the serum of hepatitis B virus (HBV) infected patients. However, the effect of B19-infection on the course of HBV-associated liver disease has not previously been investigated. We examined the prevalence of B19-DNA in HBV-infected Vietnamese patients and analysed the association between co-infection and the clinical outcome of HBV-infection. METHODS: Serum samples from 399 HBV-infected patients and 64 healthy individuals were analysed for the presence of B19-DNA by PCR and DNA-sequencing. RESULTS: B19-DNA was detected in 99/463 (21.4%) individuals. The proportion of HBV-infected patients who were also co-infected with B19 was higher than the healthy controls (P<0.001). B19-DNA was detected more frequently in patients with HBV-associated hepatocellular carcinoma compared to patients with acute and chronic HBV, HBV-associated liver cirrhosis and healthy subjects (P<0.006). A positive correlation was also found between B19-DNA loads and both serum HBV-DNA loads and alanine aminotransferase (rho>0.250 and P<0.05). CONCLUSIONS: Our findings demonstrate that B19-infection is frequent in HBV-infected Vietnamese patients. Also, a significant correlation exists between HBV/B19 co-infection and a greater likelihood of progression to more severe hepatitis B-associated liver disease. Further studies are required to determine the role of B19-infection on HBV-associated pathogenesis.

Adult↗
PubMed2006

Impact of the hepatitis B virus genotype and genotype mixtures on the course of liver disease in Vietnam.

Eight genotypes (A-H) of hepatitis B virus (HBV) have been identified. However, the impact of different genotypes on the clinical course of hepatitis B infection remains controversial. We investigated the frequency and clinical outcome of HBV genotypes and genotype mixtures in HBV-infected patients from Vietnam, Europe, and Africa. In addition, we analyzed the effects of genotype mixtures on alterations in in vitro viral replication. In Asian patients, seven genotypes (A-G) were detected, with A, C, and D predominating. In European and African patients, only genotypes A, C, D, and G were identified. Genotype mixtures were more frequently encountered in African than in Asian (P = .01) and European patients (P = .06). In Asian patients, the predominant genotype mixtures included A/C and C/D, compared to C/D in European and A/D in African patients. Genotype A was more frequent in asymptomatic compared with symptomatic patients (P < .0001). Genotype C was more frequent in patients with hepatocellular carcinoma (HCC; P = .02). Genotype mixtures were more frequently encountered in patients with chronic hepatitis in comparison to patients with acute hepatitis B (P = .015), liver cirrhosis (P = .013), and HCC (P = .002). Viral loads in patients infected with genotype mixtures were significantly higher in comparison to patients with a single genotype (P = .019). Genotype mixtures were also associated with increased in vitro HBV replication. In conclusion, infection with mixtures of HBV genotypes is frequent in Asia, Africa, and Europe. Differences in the replication-phenotype of single genotypes compared to genotype-mixtures suggest that co-infection with different HBV-genotypes is associated with altered pathogenesis and clinical outcome.

Adult↗
PubMed2006

Phylogenetic analysis of human parvovirus B19, indicating two subgroups of genotype 1 in Vietnamese patients.

Recently, three distinct genotypes (1, 2 and 3) of human parvovirus B19 (B19) have been identified. However, the characteristics and distribution of B19 genotypes in Vietnam have not been investigated. Phylogenetic analysis using 49 subgenomic NS1/VP1u regions and two coding NS1-VP1/VP2 regions has been applied to investigate the prevalence of B19 genotypes in Vietnamese patients co-infected with Hepatitis B virus. Genetic analysis of the subgenomic NS1/VP1u region of B19 revealed that two genotypes of B19 were identified in these populations, with predominance of genotype 1 (47/49, 96 %) followed by genotype 2 (2/49, 4 %), but not genotype 3. Further, phylogenetic analysis of subgenomic B19 genomes revealed two major subgroups within genotype 1 (B19-1A and B19-1B) with an estimated nucleotide difference of >5 % between each subgroup, forming different branches. The mean percentage of amino acid variation between subgroup B19-1A and B19-1B was >2 % of the NS1, VP1 and VP2 proteins. Our results indicated that two of the three known genotypes of B19 were present in Vietnamese patients, with genotype 1 predominating, and that this genotype can be classified into at least two subgroups, B19-1A and B19-1B.

Amino Acid Sequence↗
PubMed2004

Malaria in travelers: a review of the GeoSentinel surveillance network.

BACKGROUND: Malaria is a common and important infection in travelers. METHODS: We have examined data reported to the GeoSentinel surveillance network to highlight characteristics of malaria in travelers. RESULTS: A total of 1140 malaria cases were reported (60% of cases were due to Plasmodium falciparum, 24% were due to Plasmodium vivax). Male subjects constituted 69% of the study population. The median duration of travel was 34 days; however, 37% of subjects had a travel duration of < or =4 weeks. The majority of travellers did not have a pretravel encounter with a health care provider. Most cases occurred in travelers (39%) or immigrants/refugees (38%). The most common reasons for travel were to visit friends/relatives (35%) or for tourism (26%). Three-quarters of infections were acquired in sub-Saharan Africa. Severe and/or complicated malaria occurred in 33 cases, with 3 deaths. Compared with others in the GeoSentinel database, patients with malaria had traveled to sub-Saharan Africa more often, were more commonly visiting friends/relatives, had traveled for longer periods, presented sooner after return, were more likely to have a fever at presentation, and were less likely to have had a pretravel encounter. In contrast to immigrants and visitors of friends or relatives, a higher proportion (73%) of the missionary/volunteer group who developed malaria had a pretravel encounter with a health care provider. Travel to sub-Saharan Africa and Oceania was associated with the greatest relative risk of acquiring malaria. CONCLUSIONS: We have used a global database to identify patient and travel characteristics associated with malaria acquisition and characterized differences in patient type, destinations visited, travel duration, and malaria species acquired.

Africa↗
PubMed2004

Severe hepatitis and prolonged hepatitis B virus-specific CD8 T-cell response after selection of hepatitis B virus YMDD variant in an HIV/hepatitis B virus-co-infected patient.

We describe here a severe flare of hepatitis caused by lamivudine-resistant hepatitis B virus(HBV) in an HIV/HBV co-infected individual.Lamivudine-resistant HBV was detected 6 months before the development of severe hepatitis. Sequencing of the HBV genome isolated from the patients' serum did not identify compensatory mutations in the HBV polymerase that may have restored viral replication. However, a strong HBV-specific CD8 T-cell response was identified and may have resulted in the severe hepatitis.

Adult↗
PubMed2004

Highly reproducible transient transfections for the study of hepatitis B virus replication based on an internal GFP reporter system.

High throughput studies of hepatitis B virus (HBV) replication are limited by the absence of convenient and reliable in vitro systems that can be utilised to examine mutations emerging as a consequence of selective pressures such as drug therapy, immune response and genotypic evolution. We have developed an efficient and reproducible method of transfecting a human hepatoma cell line (Huh7) with a replication competent clone of HBV, which utilises an internal reporter of transfection efficiency. Wild type (WT) and a common lamivudine (LMV) resistant mutant virus characterised by a methionine to isoleucine mutation in the highly conserved YMDD motif of the polymerase gene were used to highlight the utility of this in vitro transfection procedure in studying common HBV mutations. The presence of an internal GFP reporter increased the efficiency of generating highly reproducible results and facilitated multiple forms of analysis from a single transfection accurately.

Antiviral Agents↗
PubMed2004

Neutralising antibody, CTL and dendritic cell responses to hepatitis C virus: a preventative vaccine strategy.

Hepatitis C virus (HCV) accounts for the majority of cases of transfusion acquired hepatitis and hepatitis transmitted by injecting drug use. The patients who do not clear the infection become chronic carriers of HCV and form a reservoir of infection within human populations. Furthermore, these carriers are at serious risk of developing cirrhosis of the liver and hepatocellular carcinoma. The disease is of major concern in developing as well as in developed countries and yet there are no vaccines against HCV, treatment is confined to the use of chemotherapy which is expensive and not always effective. The major obstacle in vaccine development is a limited understanding of the type of immune response that is necessary for viral clearance and the occurrence of various genotypes and quasispecies of HCV. The problems are further compounded by difficulties in growing the virus in vitro and the lack of a suitable and economical animal model.

Antibody Formation↗
PubMed2003

Respiratory tract infections in travelers: a review of the GeoSentinel surveillance network.

Respiratory tract infections are common in travelers, and improving our knowledge of risk factors associated with specific types of respiratory infections should enable implementation of better preventive strategies. Data collected by the GeoSentinel surveillance network were analyzed, and the most significant predictors for developing specific categories of respiratory infections while abroad were age, sex, season of travel, trip duration, and reason for travel. In particular, influenza was associated with travel to the Northern Hemisphere during the period of December through February, travel involving visits to friends or relatives, and trip duration of >30 days. Lower respiratory tract infections were associated with male sex and increasing age. Knowledge of the respiratory tract infections that occur in specific groups of travelers allows for the development of targeted pretravel preventive strategies to high-risk groups.

Adolescent↗
PubMed2003

Immune responses in hepatitis C virus infection: the role of dendritic cells.

Cellular immune responses are critical for the clearance of hepatitis C virus. Persistent infection results from a narrow and weak cellular immune response, in direct contrast to the broad, strong response associated with viral clearance in acute infection. The presence of dendritic cells in the liver facilitates presentation of viral antigens to both CD4+ and CD8+ T cell populations. Exploiting the potent antigen presentation capability of dendritic cells for immunotherapy of chronic hepatitis C is attractive; however, infection or transfection of segments or the entire hepatitis C virus genome appears to impair the allostimulation capacity of dendritic cells. If dendritic cell immunotherapy for hepatitis C virus infection is to become a reality, the mechanism behind the defective allostimulatory capacity needs to be deciphered.

Dendritic Cells↗
PubMed2003

Maturation of dendritic cells with lipopeptides that represent vaccine candidates for hepatitis C virus.

The ability of antigens to elicit immune responses depends upon their initial recognition, uptake, processing and presentation by dendritic cells. This fact has been recognized by many workers and dendritic cells are now regarded as natural 'adjuvants' in the business of vaccine design. One way of persuading dendritic cells to become interested in foreign material is to decorate it with lipid moieties found in bacteria. This approach has been used in the context of synthetic peptide-based immunogens and depending on the nature of the epitopes included, can provide highly immunogenic structures capable of eliciting antibody or cytotoxic T cell responses. In this paper we describe the results of experiments in which the stimulatory effects of peptide-based vaccine candidates on human dendritic cells are examined. Our findings indicate that lipidated structures comprising vaccine target sequences of viral origin coupled to the synthetic lipid groups of bacteria are able to induce the maturation of dendritic cells, as measured by the expression of cell surface MHC class II molecules.

Cell Differentiation↗
PubMed2002

Restoration of replication phenotype of lamivudine-resistant hepatitis B virus mutants by compensatory changes in the "fingers" subdomain of the viral polymerase selected as a consequence of mutations in the overlapping S gene.

The introduction of lamivudine (LMV) for the treatment of chronic hepatitis B infection has been an important advance in the management of this disease. However, the long-term efficacy of LMV may become limited by the emergence of antiviral-resistant hepatitis B virus (HBV) mutants. The two most common LMV-resistant mutants produce changes in the viral polymerase protein (rt) of rtM204I and rtL180M/M204V (previously rtM550I and rtL526M/M550V). A number of studies have demonstrated that these HBV mutants appear to be replication impaired, both in vitro and in vivo. The detection and selection of compensatory mutations in the polymerase protein that restore the replication phenotype of these HBV mutants have been poorly described to date. The effects of mutations in the fingers subdomain of the viral polymerase protein arising as a consequence of vaccine and hepatitis B immune globulin (HBIg) selected changes in the overlapping envelope gene (S), and a determinant of the hepatitis Bs antigen (HBsAg) were analyzed in vitro. The LMV-resistant HBV mutants rtM204I and rtL180M/M204V produced substantially weaker HBV DNA replicative intermediate signals by Southern blot analysis and less total intracellular HBV DNA by real-time PCR compared to wild-type virus. The viral polymerase protein of these mutants produced little detectable radiolabeled HBV DNA in an endogenous polymerase assay. In contrast, the HBV a determinant HBIg/vaccine escape mutants sP120T, sT123N, sG145R, and sD144E/G145R (that produce rtT128N, Q130P, rtW153Q, and rtG153E respectively) yielded as much virus as wild-type HBV while the sM133L (rtY141S) mutant was replication impaired. Two of these mutants, rtT128N and rtW153Q, when introduced into a replication-competent HBV vector containing the rtL180M/M204V polymerase mutation restored the replication phenotype of this LMV-resistant mutant. These viruses produced levels of intracellular HBV DNA as determined by Southern blot and real-time PCR that were comparable to those of wild-type HBV, indicating that the changes in the fingers subdomain were able to compensate for the reduced replication of the LMV-resistant mutations. Since these viruses carry mutations in the a determinant of HBsAg that may potentially decrease the ability of anti-HBs antibody to neutralize these viruses, these HBV mutants also have the potential to behave as vaccine escape mutants.

Cell Line↗
PubMed2002

Reduced antigenicity of the hepatitis B virus HBsAg protein arising as a consequence of sequence changes in the overlapping polymerase gene that are selected by lamivudine therapy.

The prevalence of hepatitis B virus vaccine escape mutants has increased as a consequence of the introduction of global vaccination programs. Furthermore and as a consequence of the organization of the genome of hepatitis B virus (HBV) into overlapping reading frames, the selection of polymerase mutants during long-term lamivudine therapy can select viruses with changes in the overlapping S gene coding for the hepatitis B small antigen (HBsAg). We have investigated the role of lamivudine in selecting HBV mutants with antigenically altered HBsAg protein using pooled human vaccine sera in enzyme immunosorbent assays and radioimmunoassays. HBsAg proteins containing the vaccine escape mutations G145R and D144E/G145R demonstrated markedly reduced binding to anti-HBs antibody. HBsAg mutants including E164D, W196S, I195M, M198I, and E164D/I195M (corresponding to the polymerase protein changes of V519L, M550I, L526M/M550V V553I, and V519L/L526M/M550V) selected during lamivudine treatment also demonstrated reduced binding to anti-HBs antibody. These findings raise the possibility of lamivudine-resistant mutants arising that possess antigenically distinct HBsAg proteins.

DNA-Directed DNA Polymerase↗
PubMed2002

The virological and clinical significance of mutations in the overlapping envelope and polymerase genes of hepatitis B virus.

The potential for hepatitis B virus (HBV) to alter its genome is considerable. This occurs because the virus utilizes a reverse transcription step in replicating the viral genome. Like human immunodeficiency virus, the reverse transcriptase of HBV is error prone and as a consequence of specific selection pressures within a host a population of viral quasispecies emerges. HBV mutants with survival advantages over the wild type virus appear within the selective in vivo environment. Some of these viruses include HBV vaccine escape and anti-viral resistant mutants that have changes in the envelope (S) and polymerase genes, respectively. In addition, the genome of HBV is organised in to overlapping reading frames. The S gene is completely overlapped by the polymerase gene. As a consequence, mutations in the S gene may produce changes in the overlapping polymerase gene. Similarly, mutations in the polymerase gene may produce changes in the S gene. The virological and clinical significance of such overlapping mutations is unclear. However, we have shown that certain mutations in either the S or polymerase gene produce functionally significant changes in the respective overlapping gene. Treatment of chronic hepatitis B carriers with long-term lamivudine (LMV) results in the selection of HBV mutants that are resistant to this nucleoside analogue. The polymerase mutations associated with LMV resistance produce changes in the overlapping S gene and in its envelope protein (hepatitis B small antigen, HBsAg) that results in a reduced antigenicity of the HBsAg protein. The selection of vaccine escape mutants by HBV vaccination or hepatitis B immune globulin is associated with changes in the S gene that are accompanied by mutations in the fingers sub-domain of the polymerase protein. When combined with polymerase mutations that are associated with resistance to LMV the changes within the fingers sub-domain of the viral enzyme behave as compensatory mutations that are able to restore the replication of LMV resistant HBV. The ability to change a viral protein by mutations in an overlapping but unrelated viral gene may produce HBV mutants with altered antigenicity and/or replication and a natural history that may be distinctly different to wild type HBV.

DNA-Directed DNA Polymerase↗
PubMed2002

Selection of hepatitis B virus polymerase mutants with enhanced replication by lamivudine treatment after liver transplantation.

BACKGROUND & AIMS: Lamivudine has become a main therapeutic option for treating hepatitis B virus (HBV) infection. Although drug resistance develops, the clinical course after selection of antiviral-resistant HBV mutants seems to be benign. However, we observed a severe clinical course of hepatitis B infection in several liver transplant recipients after the emergence of lamivudine resistance. This was associated with high viral load in the blood. METHODS: In this report, we characterize the molecular mechanisms underlying drug-dependent enhanced replication of particular lamivudine-resistant HBV mutants selected in these patients, which were associated with sudden onset of liver failure. RESULTS: The clinical course was characterized by a sudden rise in serum bilirubin, prothrombin time, and transaminase. HBV sequence analysis of these patients revealed both mutations in the "a-determinant" of the envelope and the YMDD (tyrosine, methionine, aspartate, aspartate) motif (domain C) of the polymerase protein. Transfection experiments with replication competent vectors indicated that the "a-determinant" changes were not associated with resistance, whereas mutations in the YMDD motif conferred resistance to lamivudine. More importantly, combinations of mutations in the "a-determinant" and the YMDD motif in patients with a severe hepatitis were not only resistant to lamivudine treatment, but showed enhanced replication in vitro in the presence of lamivudine. This observation was confirmed in separate laboratories. CONCLUSIONS: Severe and fatal hepatitis B infection can occur during lamivudine therapy and may be associated with certain HBV mutants selected during sequential nucleoside and HBIg treatment. The lamivudine-enhanced replication shown by these mutants suggests that continuation of therapy with lamivudine could be deleterious in some patients.

Amino Acid Sequence↗
PubMedDate not supplied

Illness in returned travelers and immigrants/refugees: the 6-year experience of two Australian infectious diseases units.

BACKGROUND: Data comparing returned travelers and immigrants/refugees managed in a hospital setting is lacking. METHODS: We prospectively collected data on 1,106 patients with an illness likely acquired overseas who presented to two hospital-based Australian infectious diseases units over a 6-year period. RESULTS: Eighty-three percent of patients were travelers and 17% immigrants/refugees. In travelers, malaria (19%), gastroenteritis/diarrhea (15%), and upper respiratory tract infection (URTI) (7%) were the most common diagnoses. When compared with immigrants/refugees, travelers were significantly more likely to be diagnosed with gastroenteritis/diarrhea [odds ratio (OR) 8], malaria (OR 7), pneumonia (OR 6), URTI (OR 3), skin infection, dengue fever, typhoid/paratyphoid fever, influenza, and rickettsial disease. They were significantly less likely to be diagnosed with leprosy (OR 0.03), chronic hepatitis (OR 0.04), tuberculosis (OR 0.05), schistosomiasis (OR 0.3), and helminthic infection (OR 0.3). In addition, travelers were more likely to present within 1 month of entry into Australia (OR 96), and have fever (OR 8), skin (OR 6), gastrointestinal (OR 5), or neurological symptoms (OR 5) but were less likely to be asymptomatic (OR 0.1) or have anaemia (OR 0.4) or eosinophilia (OR 0.3). Diseases in travelers were more likely to have been acquired via a vector (OR 13) or food and water (OR 4), and less likely to have been acquired via the respiratory (OR 0.2) or skin (OR 0.6) routes. We also found that travel destination and classification of traveler can significantly influence the likelihood of a specific diagnosis in travelers. Six percent of travelers developed a potentially vaccine-preventable disease, with failure to vaccinate occurring in 31% of these cases in the pretravel medical consultation. CONCLUSIONS: There are important differences in the spectrum of illness, clinical features, and mode of disease transmission between returned travelers and immigrants/refugees presenting to hospital-based Australian infectious diseases units with an illness acquired overseas.

Adolescent↗
PubMedDate not supplied

Dengue Fever in travelers returning from southeast Asia.

BACKGROUND: Dengue fever is an important illness facing travelers from nonendemic to endemic countries. METHODS: We reviewed 696 consecutive returned travelers managed at an Australian tertiary-care hospital for an illness acquired overseas. Patients with dengue fever were compared to those with a dengue-like illness, malaria, typhoid fever and rickettsial infections. RESULTS: In total, 19 cases of dengue fever and 20 cases of dengue-like illness were diagnosed, with 85% of cases acquired in Asia. The most common presenting features of dengue were fever (100%), myalgia (79%), rash (74%), headache (68%), nausea (37%), and diarrhea (37%). Compared to those with malaria, typhoid fever and rickettsial infections, patients with dengue were significantly more likely to have myalgia and a temperature <39 degrees C. Compared to all other illnesses in our returned travelers, dengue fever was 18 times more likely if fever and leukopenia were present, 71 times if fever and rash were present, and 230 times if fever, rash and leukopenia were present. All patients with dengue recovered completely. CONCLUSIONS: Dengue fever is an important health problem for travelers not only to Southeast Asia but to all endemic countries. The prevalence appears to be increasing in travelers, and health care professionals need to be familiar with its presentation in travelers. The clinical presenting features provide important guides to establishing the diagnosis.

Adolescent↗