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Ho Chi Minh City, Vietnam

Nguyen N.T.,The Hospital for Tropical Diseases
PLoS neglected tropical diseases | Year: 2010

BACKGROUND: Plasmid mediated antimicrobial resistance in the Enterobacteriaceae is a global problem. The rise of CTX-M class extended spectrum beta lactamases (ESBLs) has been well documented in industrialized countries. Vietnam is representative of a typical transitional middle income country where the spectrum of infectious diseases combined with the spread of drug resistance is shifting and bringing new healthcare challenges. METHODOLOGY: We collected hospital admission data from the pediatric population attending the hospital for tropical diseases in Ho Chi Minh City with Shigella infections. Organisms were cultured from all enrolled patients and subjected to antimicrobial susceptibility testing. Those that were ESBL positive were subjected to further investigation. These investigations included PCR amplification for common ESBL genes, plasmid investigation, conjugation, microarray hybridization and DNA sequencing of a bla(CTX-M) encoding plasmid. PRINCIPAL FINDINGS: We show that two different bla(CTX-M) genes are circulating in this bacterial population in this location. Sequence of one of the ESBL plasmids shows that rather than the gene being integrated into a preexisting MDR plasmid, the bla(CTX-M) gene is located on relatively simple conjugative plasmid. The sequenced plasmid (pEG356) carried the bla(CTX-M-24) gene on an ISEcp1 element and demonstrated considerable sequence homology with other IncFI plasmids. SIGNIFICANCE: The rapid dissemination, spread of antimicrobial resistance and changing population of Shigella spp. concurrent with economic growth are pertinent to many other countries undergoing similar development. Third generation cephalosporins are commonly used empiric antibiotics in Ho Chi Minh City. We recommend that these agents should not be considered for therapy of dysentery in this setting.

Daniel E.,University of Pennsylvania | Rao P.S.S.,Mission Research | Ffytche T.J.,The Hospital for Tropical Diseases | Courtright P.,Tumaini University Makumira
Indian Journal of Leprosy | Year: 2010

The prevalence and incidence of ocular hypotony (IOP<7 mm Hg) and hypotension (IOP<10 mm Hg) and factors associated with them were determined in a Leprosy Referral Centre at Tamilnadu, India. Applanation intraocular pressures were measured every six months in a cohort of newly diagnosed multibacillary (MB) leprosy patients who were followed-up during the two year period of multidrug therapy (MDT) and for five years thereafter. Transient hypotony was present in two patients at the time of diagnosis, in 3 patients during MDT and in 9 patients after MDT with a cumulative prevalence of 4.65%. Transient ocular hypotension was present in 24 patients (8%) at disease diagnosis. 25 patients developed hypotension during MDT that was associated with trichiasis (HR 8.83 95% CI 2.06,37.78 p=0.003) and flare or/and cells (HR 4.60 95% Cl 1.08, 19.64 p=0.039). 29 patients developed ocular hypotension after MDT that was associated with punctate keratitis and uveal involvement. In general, MB leprosy patients with hypotension had a mean IOP of 12.60 mm Hg which differed significantly (p<0.0001) from the mean IOP of 14.9 mm Hg in those who did not have hypotension. Transient hypotension and hypotony in MB leprosy patients are associated with signs of intraocular inflammation. © Hind Kusht Nivaran Sangh, New Delhi.

Tran T.H.,University of Oxford | Nguyen T.D.,The Hospital for Tropical Diseases | Nguyen T.T.,The Hospital for Tropical Diseases | Ninh T.T.V.,University of Oxford | And 22 more authors.
PLoS ONE | Year: 2010

Background: The emergence of drug resistant typhoid fever is a major public health problem, especially in Asia. An oral single dose typhoid vaccine would have major advantages. M01ZH09 is a live oral single dose candidate typhoid vaccine containing Salmonella enterica serovar Typhi (Ty2 aroC- ssaV-) ZH9 with two independently attenuating deletions. Studies in healthy adults demonstrated immunogenicity and an acceptable safety profile. Objectives: We conducted a randomised placebo controlled, single-blind trial to evaluate the safety and immunogenicity of M01ZH09 in healthy Vietnamese children aged 5 to 14 years. Methods: Subjects were randomly assigned to receive either a nominal dose of 5×109 CFU of M01ZH09 or placebo and were followed up for 28 days. The primary safety outcome was the proportion of subjects with any adverse event attributed to M01ZH09. The primary immunogenicity endpoint was the proportion of subjects who showed a positive immune response to M01ZH09 in the Salmonella Typhi lipopolysaccharide (LPS) specific serum IgA and IgG ELISA. Principal Findings: One hundred and fifty-one children were enrolled, 101 subjects received M01ZH09 and 50 subjects received placebo. An intention to treat analysis was conducted. There were no serious adverse events and no bacteraemias. In the M01ZH09 group, 26 (26%; 95% CI, 18-5%) of 101 subjects experienced adverse events compared to 11 (22%; 95% CI, 12-36%) of 50 subjects in the placebo group (odds ratio (OR) [95%CI] = 1.23 [0.550-2.747]; p = 0.691). Faecal shedding of S. Typhi (Ty2 aroC- ssaV-) ZH9 was detected in 51 (51%; 95% CI, 41-61%) of 100 M01ZH09 subjects. No shedding was detected beyond day 3. A positive immune response, defined as 70% increase (1.7 fold change) in LPS specific serum IgG (day 14 or 28) and/or 50% increase (1.5 fold change) in LPS specific serum IgA (day 7 or 14) from baseline was detected in 98 (97%; 95% CI, 92-99%) of 101 M01ZH09 recipients and 8 (16%; 95% CI, 7-29%) of 50 placebo recipients. Twenty-eight (100%; 95% CI, 88-100%) of 28 vaccine recipients who were evaluated in the LPS specific IgA ELISPOT assay showed a positive response compared to none of the 14 placebo recipients tested. Conclusions: This was the first phase II trial of a novel oral candidate typhoid vaccine in children in an endemic country. M01ZH09 had an appropriate safety profile and was immunogenic in children. © 2010 Hien et al.

Nga T.V.T.,University of Oxford | Parry C.M.,Mahidol University | Le T.,University of Hawaii at Manoa | Lan N.P.H.,The Hospital for Tropical Diseases | And 11 more authors.
Transactions of the Royal Society of Tropical Medicine and Hygiene | Year: 2012

The etiological spectrum of bloodstream infections is variable between industrialized and developing countries and even within a defined location over time. We investigated trends in bloodstream infections at an infectious disease hospital in Ho Chi Minh City, Vietnam, from 1994-2008. Amongst 66. 111 blood cultures performed, a clinically relevant pathogen was isolated in 7645 episodes (positivity rate; 116/1000 cultures). Salmonella Typhi was the predominant pathogen until 2002; however, a considerable annual decline in the proportion of S. Typhi was observed (OR 0.6993, 95% CI [0.6885, 0.7103], p. < 0.0001). Conversely, there was a significant increase in the proportions of non-typhoidal Salmonella (NTS), Cryptococcus neoformans and Penicillium marneffei, concurrent with increasing HIV prevalence. These data document a substantial longitudinal shift in bloodstream infection etiology in southern Vietnam. We propose such changes are related to increasing economic prosperity and HIV prevalence, and this pattern marks a substantial change in the epidemiology of invasive salmonellosis in Southeast Asia. © 2011 Royal Society of Tropical Medicine and Hygiene.

Parry C.M.,University of Oxford | Parry C.M.,Mahidol University | Vinh H.,The Hospital for Tropical Diseases | Chinh N.T.,The Hospital for Tropical Diseases | And 5 more authors.
PLoS Neglected Tropical Diseases | Year: 2011

Background: Infection with Salmonella enterica serovar Typhi (S. Typhi) with reduced susceptibility to fluoroquinolones has been associated with fluoroquinolone treatment failure. We studied the relationship between ofloxacin treatment response and the ofloxacin minimum inhibitory concentration (MIC) of the infecting isolate. Individual patient data from seven randomised controlled trials of antimicrobial treatment in enteric fever conducted in Vietnam in which ofloxacin was used in at least one of the treatment arms was studied. Data from 540 patients randomised to ofloxacin treatment was analysed to identify an MIC of the infecting organism associated with treatment failure. Principal Findings: The proportion of patients failing ofloxacin treatment was significantly higher in patients infected with S. Typhi isolates with an MIC≥0.25 μg/mL compared with those infections with an MIC of ≤0.125 μg/mL (p<0.001). Treatment success was 96% when the ofloxacin MIC was ≤0.125 μg/mL, 73% when the MIC was between 0.25 and 0.50 μg/mL and 53% when the MIC was 1.00 μg/mL. This was despite a longer duration of treatment at a higher dosage in patients infected with isolates with an MIC≥0.25 μg/mL compared with those infections with an MIC of ≤0.125 μg/mL. Significance: There is a clear relationship between ofloxacin susceptibility and clinical outcome in ofloxacin treated patients with enteric fever. An ofloxacin MIC of ≥0.25 μg/mL, or the presence of nalidixic acid resistance, can be used to define S. Typhi infections in which the response to ofloxacin may be impaired. © 2011 Parry et al.

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