Medicine (Northwest Academic Centre) - Research Publications
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ItemSevere 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(LIPPINCOTT WILLIAMS & WILKINS, 2004-08-20)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.
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ItemImpact of the hepatitis B virus genotype and genotype mixtures on the course of liver disease in Vietnam(WILEY, 2006-06-01)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.
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ItemHeterochromatin silencing and locus repositioning linked to regulation of virulence genes in Plasmodium faiciparum(CELL PRESS, 2005-04-08)The malaria parasite Plasmodium falciparum undergoes antigenic variation to evade host immune responses through switching expression of variant surface proteins encoded by the var gene family. We demonstrate that both a subtelomeric transgene and var genes are subject to reversible gene silencing. Var gene silencing involves the SIR complex as gene disruption of PfSIR2 results in activation of this gene family. We also demonstrate that perinuclear gene activation involves chromatin alterations and repositioning into a location that may be permissive for transcription. Together, this implies that locus repositioning and heterochromatic silencing play important roles in the epigenetic regulation of virulence genes in P. falciparum.
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ItemMalaria in travelers: A review of the GeoSentinel surveillance network(OXFORD UNIV PRESS INC, 2004-10-15)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.
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ItemBroad analysis reveals a consistent pattern of var gene transcription in Plasmodium falciparum repeatedly selected for a defined adhesion phenotype(WILEY, 2005-05-01)Transcription of the majority of the members of the Plasmodium falciparum var multigene family were analysed in two isolates by a quantitative approach. Both of these isolates had been repeatedly selected for adhesion to chondroitin sulphate A (CSA) and one had also been selected for adhesion to hyaluronic acid (HA). These adhesion phenotypes are expressed by many parasites isolated from placentae and are associated with malaria disease in pregnancy. Increased transcription of the var gene var2csa, or its homologue IT4 var4, was associated with the CSA and HA adhesion phenotypes in all parasites suggesting that it was the dominant, if not the only, var gene that encoded adhesion to CSA in these allogeneic isolates. Some var genes were consistently transcribed at higher levels than others regardless of expressed adhesion phenotypes suggesting a transcriptional hierarchy. Unspliced or partial transcripts were detected for most var genes tested. These atypical var gene transcripts may have implications for the regulation of var gene transcription.
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ItemProspective population-based incidence of Haemophilus influenzae type b meningitis in Thailand(ELSEVIER SCI LTD, 2004-02-25)There are limited prospective data for Haemophilus influenzae type b (Hib) disease in Asia, where some countries are considering vaccine introduction. A prospective population-based study was conducted to measure the incidence of Hib meningitis in children in two northern provinces of Thailand. Children <5 years with symptoms consistent with bacterial meningitis were enrolled in the study if inclusion criteria were met. The study enrolled 598 children with clinical meningitis, 76% of whom received lumbar puncture. The rate of probable bacterial meningitis was 26.6/100,000 children <5 years per year. There were four cases of laboratory confirmed Hib meningitis (rate 3.8/100,000 children <5 years per year). These findings suggest a relatively low incidence of Hib meningitis. However, additional data from studies of pneumonia are needed to define the Hib disease burden in Thailand.
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ItemHepatitis B infection in rural Vietnam and the implications for a National Program of Infant Immunization(AMER SOC TROP MED & HYGIENE, 2003-09-01)To ascertain hepatitis B virus (HBV) infection rates for Vietnam, we surveyed HBV markers in two districts of Thanh Hoa province. We randomly selected 536 infants (9- < or = 18 months old), 228 children (4 to < or = 6 years old), 219 adolescents (14 to < or = 16 years old), and 596 adults (25 to < or = 40 years old). On questioning, none of those surveyed had received vaccine against HBV. Hepatitis B virus surface antigen (HBsAg) and total HBV core antibody (anti-HBc) were measured in all specimens, and HBV e antigen (HBeAg) in those positive for HBsAg, and HBV surface antibody (anti-HBs) were measured in all others. Current infection (HBsAg+) rates were infants = 12.5%, children = 18.4%, adolescents = 20.5%, and adults = 18.8%. Current or previous infection (HBsAg+, anti-HBc+, or anti-HBs+) increased with age (infants = 19.6%, children = 36.4%, adolescents = 55.3%, adults = 79.2%). Rates of HBeAg among those HBsAg+ were infants = 85.1%, children = 88.1%, adolescents = 71.1%, and adults = 30.4%. The epidemiology of HBV in Vietnam resembles that of many southeast Asian nations before introduction of vaccine. Immunization of newborns will have enormous impact on HBV-related morbidity and mortality there.