Background. The first cases of avian influenza A (H5N1) in humans in Vietnam were detected in early 2004, and Vietnam has reported the second highest number of cases globally. Methods. We obtained ...retrospective clinical data through review of medical records for laboratory confirmed cases of influenza A (H5N1) infection diagnosed in Vietnam from January 2004 through December 2006. Standard data was abstracted regarding clinical and laboratory features, treatment, and outcome. Results. Data were obtained for 67 (72%) of 93 cases diagnosed in Vietnam over the study period. Patients presented to the hospital after a median duration of illness of 6 days with fever (75%), cough (89%), and dyspnea (81%). Diarrhea and mucosal bleeding at presentation were more common in fatal than in nonfatal cases. Common findings were bilateral pulmonary infiltrates on chest radiograph (72%), lymphopenia (73%), and increased serum transaminase levels (aspartate aminotransferase, 69%; alanine aminotransferase, 61%). Twenty-six patients died (case fatality rate, 39%; 95% confidence interval, 27%–51%) and the most reliable predictor of a fatal outcome was the presence of both neutropenia and raised alanine aminotransferase level at admission, which correctly predicted 91% of deaths and 82% of survivals. The risk of death was higher among persons aged ⩽16 years, compared with older persons (P<.001), and the risk of death was higher among patients who did not receive oseltamivir treatment (P=.048). The benefit of oseltamivir treatment remained after controlling for potential confounding by 1 measure of severity (odds ratio, 0.15; 95% confidence interval, 0.026–0.893; P=.034). Conclusion. In cases of infection with Influenza A (H5N1), the presence of both neutropenia and raised serum transaminase levels predicts a poor outcome. Oseltamivir treatment shows benefit, but treatment with corticosteroids is associated with an increased risk of death.
A better description of the extent and structure of genetic diversity in dengue virus (DENV) in endemic settings is central to its eventual control. To this end we determined the complete coding ...region sequence of 187 DENV-2 genomes and 68 E genes from viruses sampled from Vietnamese patients between 1995 and 2009. Strikingly, an episode of genotype replacement was observed, with Asian 1 lineage viruses entirely displacing the previously dominant Asian/American lineage viruses. This genotype replacement event also seems to have occurred within DENV-2 in Thailand and Cambodia, suggestive of a major difference in viral fitness. To determine the cause of this major evolutionary event we compared both the infectivity of the Asian 1 and Asian/American genotypes in mosquitoes and their viraemia levels in humans. Although there was little difference in infectivity in mosquitoes, we observed significantly higher plasma viraemia levels in paediatric patients infected with Asian 1 lineage viruses relative to Asian/American viruses, a phenotype that is predicted to result in a higher probability of human-to-mosquito transmission. These results provide a mechanistic basis to a marked change in the genetic structure of DENV-2 and more broadly underscore that an understanding of DENV evolutionary dynamics can inform the development of vaccines and anti-viral drugs.
As dengue spreads to new geographical regions and the force of infection changes in existing endemic areas, a greater breadth of clinical presentations is being recognised. Clinical experience ...suggests that adults manifest a pattern of complications different from those observed in children, but few reports have described the age-related spectrum of disease in contemporaneous groups of patients recruited at the same geographical location.
Using detailed prospectively collected information from ongoing studies that encompass the full spectrum of hospitalised dengue cases admitted to a single hospital in southern Vietnam, we compared clinical and laboratory features, management, and outcome for 647 adults and 881 children with confirmed dengue. Signs of vascular leakage and shock were more frequent and more severe in children than adults, while bleeding manifestations and organ involvement were more common in adults. Additionally, adults experienced significantly more severe thrombocytopenia. Secondary infection but not serotype was independently associated with greater thrombocytopenia, although with a smaller effect than age-group. The effect of age-group on platelet count was also apparent in the values obtained several weeks after recovery, indicating that healthy adults have intrinsically lower counts compared to children.
There are clear distinctions between adults and children in the pattern of complications seen in association with dengue infection, and these depend partly on intrinsic age-dependent physiological differences. Knowledge of such differences is important to inform research on disease pathogenesis, as well as to encourage development of management guidelines that are appropriate to the age-groups at risk.
Acute encephalitis is an important and severe disease in children in Vietnam. However, little is known about the etiology while such knowledge is essential for optimal prevention and treatment. To ...identify viral causes of encephalitis, in 2004 we conducted a one-year descriptive study at Children's Hospital Number One, a referral hospital for children in southern Vietnam including Ho Chi Minh City.
Children less than 16 years of age presenting with acute encephalitis of presumed viral etiology were enrolled. Diagnostic efforts included viral culture, serology and real time (RT)-PCRs. A confirmed or probable viral causative agent was established in 41% of 194 enrolled patients. The most commonly diagnosed causative agent was Japanese encephalitis virus (n = 50, 26%), followed by enteroviruses (n = 18, 9.3%), dengue virus (n = 9, 4.6%), herpes simplex virus (n = 1), cytomegalovirus (n = 1) and influenza A virus (n = 1). Fifty-seven (29%) children died acutely. Fatal outcome was independently associated with patient age and Glasgow Coma Scale (GCS) on admission.
Acute encephalitis in children in southern Vietnam is associated with high mortality. Although the etiology remains unknown in a majority of the patients, the result from the present study may be useful for future design of treatment and prevention strategies of the disease. The recognition of GCS and age as predictive factors may be helpful for clinicians in managing the patient.
The pathogenesis of dengue in infants is poorly understood. We postulated that dengue severity in infants would be positively associated with markers of viral burden and that maternally derived, ...neutralizing anti-dengue antibody would have decayed before the age at which infants with dengue presented to the hospital. In 75 Vietnamese infants with primary dengue, we found significant heterogeneity in viremia and NS1 antigenemia at hospital presentation, and these factors were independent of disease grade or continuous measures of disease severity. Neutralizing antibody titers, predicted in each infant at the time of their illness, suggested that the majority of infants (65%) experienced dengue hemorrhagic fever when the maternally derived neutralizing antibody titer had declined to <1:20. Collectively, these data have important implications for dengue vaccine research because they suggest that viral burden may not solely explain severe dengue in infants and that neutralizing antibody is a reasonable but not absolute marker of protective immunity in infants.
Avian influenza A (H5N1) infection in humans Beigel, John H; Farrar, Jeremy; Han, Aye Maung ...
New England journal of medicine/The New England journal of medicine,
09/2005, Letnik:
353, Številka:
13
Journal Article
The factors that govern the development of tuberculosis disease are incompletely understood. We hypothesized that some strains of Mycobacterium tuberculosis (M. tuberculosis) are more capable of ...causing disseminated disease than others and may be associated with polymorphisms in host genes responsible for the innate immune response to infection. We compared the host and bacterial genotype in 187 Vietnamese adults with tuberculous meningitis (TBM) and 237 Vietnamese adults with uncomplicated pulmonary tuberculosis. The host genotype of tuberculosis cases was also compared with the genotype of 392 cord blood controls from the same population. Isolates of M. tuberculosis were genotyped by large sequence polymorphisms. The hosts were defined by polymorphisms in genes encoding Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) and Toll-like receptor-2 (TLR-2). We found a significant protective association between the Euro-American lineage of M. tuberculosis and pulmonary rather than meningeal tuberculosis (Odds ratio (OR) for causing TBM 0.395, 95% confidence intervals (C.I.) 0.193-0.806, P = 0.009), suggesting these strains are less capable of extra-pulmonary dissemination than others in the study population. We also found that individuals with the C allele of TLR-2 T597C allele were more likely to have tuberculosis caused by the East-Asian/Beijing genotype (OR = 1.57 95% C.I. 1.15-2.15) than other individuals. The study provides evidence that M. tuberculosis genotype influences clinical disease phenotype and demonstrates, for the first time, a significant interaction between host and bacterial genotypes and the development of tuberculosis.
Background. Dengue is the most common arboviral infection of humans. There are currently no specific treatments for dengue. Balapiravir is a prodrug of a nucleoside analogue (called R1479) and an ...inhibitor of hepatitis C virus replication in vivo. Methods. We conducted in vitro experiments to determine the potency of balapiravir against dengue viruses and then an exploratory, dose-escalating, randomized placebo-controlled trial in adult male patients with dengue with <48 hours of fever. Results. The clinical and laboratory adverse event profile in patients receiving balapiravir at doses of 1500 mg (n = 10) or 3000 mg (n = 22) orally for 5 days was similar to that of patients receiving placebo (n = 32), indicating balapiravir was well tolerated. However, twice daily assessment of viremia and daily assessment of NS1 antigenemia indicated balapiravir did not measurably alter the kinetics of these virological markers, nor did it reduce the fever clearance time. The kinetics of plasma cytokine concentrations and the whole blood transcriptional profile were also not attenuated by balapiravir treatment. Conclusions. Although this trial, the first of its kind in dengue, does not support balapiravir as a candidate drug, it does establish a framework for antiviral treatment trials in dengue and provides the field with a clinically evaluated benchmark molecule. Clinical Trials Registration. NCT01096576.
The pathogenesis of dengue shock syndrome (DSS, grade 3 and 4) is not yet completely understood. Several factors are reportedly associated with DSS, a more severe form of dengue infection that ...reportedly causes 50 times higher mortality compared to that of dengue patients without DSS. However, the results from these reports remain inconclusive. To better understand the epidemiology, clinical manifestation, and pathogenesis of DSS for development of new therapy, we systematically reviewed and performed a meta-analysis of relevant studies that reported factors in both DSS and dengue hemorrhagic fever (DHF, grade 1 and 2) patients.
PubMed, EMBASE, Scopus, Google Scholar, Dengue Bulletin, Cochrane Library, Virtual Health Library, and a manual search of reference lists of articles published before September 2010 were used to retrieve relevant studies. A meta-analysis using fixed- or random-effects models was used to calculate pooled odds ratios (OR) or event rate with corresponding 95% confidence intervals. Assessment of heterogeneity and publication bias, meta-regression analysis, subgroup analysis, sensitivity analysis, and analysis of factor-specific relationships were further performed. There were 198 studies constituting 203 data sets that met our eligibility criteria. Our meta-regression analysis showed a sustained reduction of DSS/dengue hemorrhagic fever (DHF) ratio over a period of 40 years in Southeast Asia, especially in Thailand. The meta-analysis revealed that age, female sex, neurological signs, nausea/vomiting, abdominal pain, gastrointestinal bleeding, hemoconcentration, ascites, pleural effusion, hypoalbuminemia, hypoproteinemia, hepatomegaly, levels of alanine transaminase and aspartate transaminase, thrombocytopenia, prothrombin time, activated partial thromboplastin time, fibrinogen level, primary/secondary infection, and dengue virus serotype-2 were significantly associated with DSS when pooling all original relevant studies.
The results improve our knowledge of the pathogenesis of DSS by identifying the association between the epidemiology, clinical signs, and biomarkers involved in DSS.
Influenza A (H5N1) virus with an amino acid substitution in neuraminidase conferring high-level resistance to oseltamivir was isolated from two of eight Vietnamese patients during oseltamivir ...treatment. Both patients died of influenza A (H5N1) virus infection, despite early initiation of treatment in one patient. Surviving patients had rapid declines in the viral load to undetectable levels during treatment. These observations suggest that resistance can emerge during the currently recommended regimen of oseltamivir therapy and may be associated with clinical deterioration and that the strategy for the treatment of influenza A (H5N1) virus infection should include additional antiviral agents.
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