Clinical features of human influenza A (H5N1) infection in Vietnam: 2004-2006.

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 < or =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.

Risk factors for SARS infection within hospitals in Hanoi, Vietnam.

We investigated a nosocomial infection of severe acute respiratory syndrome (SARS) in Vietnam in 2003 and attempted to identify risk factors for SARS infection. Of the 146 subjects who came into contact with SARS patients at Hospital A, 43 (29.5%) developed SARS, and an additional 16 (11%) were asymptomatic but SARS-coronavirus (CoV) seropositive. The asymptomatic infection rate accounted for 15.5% of the total number of infected patients at Hospital A, which was higher than that of 6.5% observed at Hospital B, to where all patients from Hospital A were eventually transported (P<0.05). At Hospital A, the risk for developing SARS was 12.6 times higher in individuals not using a mask than in those using a mask. The SARS epidemic in Vietnam resulted in numerous secondary infections due to its unknown etiology and delayed recognition at the beginning of the epidemic. The consistent and proper use of a mask was shown to be crucial for constant protection against infection with SARS.

Immunogenicity of a locally produced hepatitis B vaccine with the birth dose stored outside the cold chain in rural Vietnam.

The heat stability of hepatitis B vaccine (HepB vaccine) should enable its storage outside the cold chain (OCC), increasing access to the birth dose in areas lacking refrigeration. We compared the immunogenicity of a locally produced vaccine among infants who received three doses stored within the cold chain (n = 358) or for whom the first dose was stored OCC for up to one month (n = 748). Serum was collected from these infants at age 9-18 months. The vaccine was protective in 80.3% of all infants. There were no differences in the prevalence of a protective level of antibody or antibody titer among groups of infants according to storage strategy. Differences in antibody titer between certain groups of infants could be explained by different vaccination schedules. Where birth dose coverage will be improved, HepB vaccine can be taken OCC for up to one month without affecting its immunogenicity.

Rapid awareness and transmission of severe acute respiratory syndrome in Hanoi French Hospital, Vietnam.

A case-control study was conducted to examine the relationship between severe acute respiratory syndrome (SARS) and the time-dependent precautionary behaviors taken during an outbreak of SARS in Hanoi French Hospital (HFH), Vietnam. Masks (odds ratio [OR] = 0.3; 95% confidence interval [CI]: 0.1, 0.7) and gowns (OR = 0.2; 95% CI: 0.0, 0.8) appeared to prevent SARS transmission. The proportion of doctors and nurses who undertook each measure significantly improved (chi(2) = 9.8551, P = 0.043) after the onset of secondary cases. The impact of individual behaviors on an outbreak was investigated through mathematical approaches. The reproduction number decreased from 4.1 to 0.7 after notification. The basic reproduction number was estimated, and the use of masks alone was shown to be insufficient in containing an epidemic. Intuitive results obtained by means of stochastic individual-based simulations showed that rapid improvements in behavior and isolation would increase the probability of extinction.

Recombinant nucleocapsid protein-based IgG enzyme-linked immunosorbent assay for the serological diagnosis of SARS.

The recombinant nucleocapsid protein (rNP) of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) was expressed in a baculovirus system. The purified SARS-CoV rNP was used as an antigen for detection of SARS-CoV antibodies in IgG enzyme-linked immunosorbent assay (ELISA). The ELISA was evaluated in comparison with neutralizing antibody assay and the authentic SARS-CoV antigen-based IgG ELISA. Two-hundred and seventy-six serum samples were collected from health care workers in a hospital in which a nosocomial SARS outbreak took place and used for evaluation. The SARS-CoV rNP-based IgG ELISA has 92% of sensitivity and specificity compared with the neutralizing antibody assay and 94% sensitivity and specificity compared with the authentic SARS-CoV antigen-based IgG ELISA. The results suggest that the newly developed SARS-CoV rNP-based IgG ELISA is a valuable tool for the diagnosis and seroepidemiological study of SARS. The SARS-CoV rNP-based IgG ELISA has an advantage over the conventional IgG ELISA in that the antigen can be prepared by laboratory workers without the risk of infection.

Drug use among female sex workers in Hanoi, Vietnam.

AIMS: To describe the drug use practices among female sex workers (FSWs) in Hanoi and to identify factors associated with their drug injecting. DESIGN, SETTING AND PARTICIPANTS: A two-stage cluster survey of 400 FSWs was conducted from June to September, 2002. Participating FSWs were both establishment- (160) and street-based (240), who were practising in seven urban and one suburban districts of Hanoi. MEASUREMENTS: Subjects were interviewed face to face using a structured questionnaire. FINDINGS: Among the middle-class FSWs, 27% used drugs, of whom 79% injected. Among low-class FSWs, 46% used drugs and 85% injected. Among drug-using FSWs, 86% had started using drugs within the past 6 years. Among drug-injecting FSWs, 81% had started injecting within the past 4 years. Cleaning of injecting equipment was not common among those who shared. Having drug-injecting 'love mates', drug-using clients, longer residence in Hanoi, more clients and not currently cohabiting were found to be independently associated with drug injecting among FSWs. CONCLUSIONS: The high prevalence of injecting drug use among FSWs makes them susceptible to HIV infection, and is a threat to their clients. There is a strong relationship between drug-using FSWs and male drug-using clients and non-client partners. Intervention to prevent drug use initiation among non-drug-using FSWs and harm reduction among drug-using FSWs are urgently needed.

Association of human leukocyte antigen class II alleles with severe acute respiratory syndrome in the Vietnamese population.

Excessive immune response is believed to play a role in the development of severe acute respiratory syndrome (SARS). Inhomogeneous spread of SARS led one to think of an Asian genetic predisposition and contribution of human leukocyte antigen (HLA) to the disease susceptibility. However, past case-control studies showed inconsistent results. In Viet Nam, of 62 patients with SARS, 44 participated in the present study together with 103 individuals who had contact with SARS patients and 50 without contact history. HLA-DRB1*12 was more frequently shown in SARS patients than in controls (corrected p = 0.042). HLA-DRB1*1202, the predominant allele in the Vietnamese population showed the strongest association with SARS in a dominant model (corrected p = 0.0065 and 0.0052, depending on the controls to be compared). Our results and accumulated data on HLA in the Asian populations would help in the understanding of associations with emerging infectious diseases.

Risk factors for human infection with avian influenza A H5N1, Vietnam, 2004.

To evaluate risk factors for human infection with influenza A subtype H5N1, we performed a matched case-control study in Vietnam. We enrolled 28 case-patients who had laboratory-confirmed H5N1 infection during 2004 and 106 age-, sex-, and location-matched control-respondents. Data were analyzed by matched-pair analysis and multivariate conditional logistic regression. Factors that were independently associated with H5N1 infection were preparing sick or dead poultry for consumption < or =7 days before illness onset (matched odds ratio [OR] 8.99, 95% confidence interval [CI] 0.98-81.99, p = 0.05), having sick or dead poultry in the household < or =7 days before illness onset (matched OR 4.94, 95% CI 1.21-20.20, p = 0.03), and lack of an indoor water source (matched OR 6.46, 95% CI 1.20-34.81, p = 0.03). Factors not significantly associated with infection were raising healthy poultry, preparing healthy poultry for consumption, and exposure to persons with an acute respiratory illness.

HIV infection and risk characteristics among female sex workers in Hanoi, Vietnam.

The prevalence of HIV/sexually transmitted diseases (STDs) was determined, the risk characteristics examined, and factors associated with HIV infection identified among noninstitutionalized female sex workers (FSWs), using a cross-sectional survey with 2-stage cluster sampling. Four hundred FSWs were interviewed face to face using a structured questionnaire and tested for HIV, syphilis, Chlamydia infection, and gonorrhea. HIV seroprevalence was 12%, syphilis 17% (using the treponemal pallidum hemagglutination assay), Chlamydia infection 3.8% (using polymerase chain reaction [PCR]), and gonorrhea 6.3% (PCR). Lower-class FSWs averaged 2 clients per day, and middle-class FSWs about 1.2. Median duration in sex work was 2.3 years. Consistent condom use was 63% with irregular clients, 41% with regular clients, and only 4.8% with "love mates." Fifty-five percent had had sex with a drug user(s). Thirty-eight percent used drugs, of whom 83% injected. Factors associated with HIV included being young, having a low level of education, longer residence in Hanoi, being a lower-class FSW, having higher income compared with peers, perception of self being at low risk for HIV, poor knowledge of HIV, and sharing injecting equipment. Intervention strategies should include reduction of both stigmatization and sharing of drug paraphernalia, promotion of nonstigmatizing voluntary testing and counseling, and aggressive marketing and promotion of condoms.

Identification of an alternative 5'-untranslated exon and new polymorphisms of angiotensin-converting enzyme 2 gene: lack of association with SARS in the Vietnamese population.

We analyzed genetic variations of angiotensin-converting enzyme 2 (ACE2), considering that it might influence patients' susceptibility to severe acute respiratory syndrome-associated coronavirus (SARS-CoV) or development of SARS as a functional receptor. By cloning of the full-length cDNA of the ACE2 gene in the lung, where replication occurs on SARS-CoV, it was shown that there are different splicing sites. All exons including the new alternative exon, exon-intron boundaries, and the corresponding 5'-flanking region of the gene were investigated and 19 single nucleotide polymorphisms (SNPs) were found. Out of these, 13 SNPs including one non-synonymous substitution and three 3'-UTR polymorphisms were newly identified. A case control study involving 44 SARS cases, 16 anti-SARS-CoV antibody-positive contacts, 87 antibody-negative contacts, and 50 non-contacts in Vietnam, failed to obtain any evidence that the ACE2 gene polymorphisms are involved in the disease process in the population. Nevertheless, identification of new 5'-untranslated exon and new SNPs is considered helpful in investigating regulation of ACE2 gene expression in the future.

Polymorphisms of interferon-inducible genes OAS-1 and MxA associated with SARS in the Vietnamese population.

We hypothesized that host antiviral genes induced by type I interferons might affect the natural course of severe acute respiratory syndrome (SARS). We analyzed single nucleotide polymorphisms (SNPs) of 2',5'-oligoadenylate synthetase 1 (OAS-1), myxovirus resistance-A (MxA), and double-stranded RNA-dependent protein kinase in 44 Vietnamese SARS patients with 103 controls. The G-allele of non-synonymous A/G SNP in exon 3 of OAS-1 gene showed association with SARS (p=0.0090). The G-allele in exon 3 of OAS-1 and the one in exon 6 were in strong linkage disequilibrium and both of them were associated with SARS infection. The GG genotype and G-allele of G/T SNP at position -88 in the MxA gene promoter were found more frequently in hypoxemic group than in non-hypoxemic group of SARS (p=0.0195). Our findings suggest that polymorphisms of two IFN-inducible genes OAS-1 and MxA might affect susceptibility to the disease and progression of SARS at each level.

ACE1 polymorphism and progression of SARS.

We have hypothesized that genetic predisposition influences the progression of SARS. Angiotensin converting enzyme (ACE1) insertion/deletion (I/D) polymorphism was previously reported to show association with the adult respiratory distress syndrome, which is also thought to play a key role in damaging the lung tissues in SARS cases. This time, the polymorphism was genotyped in 44 Vietnamese SARS cases, with 103 healthy controls who had had a contact with the SARS patients and 50 controls without any contact history. SARS cases were divided into either non-hypoxemic or hypoxemic groups. Despite the small sample size, the frequency of the D allele was significantly higher in the hypoxemic group than in the non-hypoxemic group (p=0.013), whereas there was no significant difference between the SARS cases and controls, irrespective of a contact history. ACE1 might be one of the candidate genes that influence the progression of pneumonia in SARS.