Genetic Diversity and Population Structure of Canarium tramdenum Dai and Yakovl. in Northern Vietnam

Canarium tramdenum occurs naturally in subtropical and tropical regions of Indochina and China. The wood is used for making high quality furniture and the fruit and leaves are used in traditional medicine. However, a lack of information on genetic diversity and population structure has handicapped the genetic conservation and domestication of this high-value species. This study evaluated genetic variation within and among four C. tramdenum populations. Sixty individuals were collected from four natural populations in Vietnam in the provinces of Ninhbinh, Bacgiang, Nghean, and Backan. Genetic diversity and genetic structure were determined using 20 ISSR markers. A total of 192 DNA fragments with sizes ranging from 110 bp to 3,000 bp were detected, of which 154 segments (80.2%) were polymorphic and 38 segments (19.8%) were monomorphic. The ISSR data indicated a moderate degree of genetic diversity for the species (h = 0.252). The four populations were separated into three genetic clusters with low levels of genetic distance between them. AMOVA result showed that most (78%) of the genetic variation was within the populations. The moderate to high genetic diversity of C. tramdenum and the low genetic differentiation among populations suggested that all existing natural populations in the particular regions needed to be preserved to protect the genetic diversity of this species

Temporal fluctuation of multidrug resistant salmonella typhi haplotypes in the mekong river delta region of Vietnam.

BACKGROUND: typhoid fever remains a public health problem in Vietnam, with a significant burden in the Mekong River delta region. Typhoid fever is caused by the bacterial pathogen Salmonella enterica serovar Typhi (S. Typhi), which is frequently multidrug resistant with reduced susceptibility to fluoroquinolone-based drugs, the first choice for the treatment of typhoid fever. We used a GoldenGate (Illumina) assay to type 1,500 single nucleotide polymorphisms (SNPs) and analyse the genetic variation of S. Typhi isolated from 267 typhoid fever patients in the Mekong delta region participating in a randomized trial conducted between 2004 and 2005. PRINCIPAL FINDINGS: the population of S. Typhi circulating during the study was highly clonal, with 91% of isolates belonging to a single clonal complex of the S. Typhi H58 haplogroup. The patterns of disease were consistent with the presence of an endemic haplotype H58-C and a localised outbreak of S. Typhi haplotype H58-E2 in 2004. H58-E2-associated typhoid fever cases exhibited evidence of significant geo-spatial clustering along the Sông H u branch of the Mekong River. Multidrug resistance was common in the established clone H58-C but not in the outbreak clone H58-E2, however all H58 S. Typhi were nalidixic acid resistant and carried a Ser83Phe amino acid substitution in the gyrA gene. SIGNIFICANCE: the H58 haplogroup dominates S. Typhi populations in other endemic areas, but the population described here was more homogeneous than previously examined populations, and the dominant clonal complex (H58-C, -E1, -E2) observed in this study has not been detected outside Vietnam. IncHI1 plasmid-bearing S. Typhi H58-C was endemic during the study period whilst H58-E2, which rarely carried the plasmid, was only transient, suggesting a selective advantage for the plasmid. These data add insight into the outbreak dynamics and local molecular epidemiology of S. Typhi in southern Vietnam

A Multi-Center Randomised Controlled Trial of Gatifloxacin versus Azithromycin for the Treatment of Uncomplicated Typhoid Fever in Children and Adults in Vietnam

BACKGROUND: Drug resistant typhoid fever is a major clinical problem globally. Many of the first line antibiotics, including the older generation fluoroquinolones, ciprofloxacin and ofloxacin, are failing. OBJECTIVES: We performed a randomised controlled trial to compare the efficacy and safety of gatifloxacin (10 mg/kg/day) versus azithromycin (20 mg/kg/day) as a once daily oral dose for 7 days for the treatment of uncomplicated typhoid fever in children and adults in Vietnam. METHODS: An open-label multi-centre randomised trial with pre-specified per protocol analysis and intention to treat analysis was conducted. The primary outcome was fever clearance time, the secondary outcome was overall treatment failure (clinical or microbiological failure, development of typhoid fever-related complications, relapse or faecal carriage of S. typhi). PRINCIPAL FINDINGS: We enrolled 358 children and adults with suspected typhoid fever. There was no death in the study. 287 patients had blood culture confirmed typhoid fever, 145 patients received gatifloxacin and 142 patients received azithromycin. The median FCT was 106 hours in both treatment arms (95% Confidence Interval [CI]; 94-118 hours for gatifloxacin versus 88-112 hours for azithromycin), (logrank test p = 0.984, HR [95% CI] = 1.0 [0.80-1.26]). Overall treatment failure occurred in 13/145 (9%) patients in the gatifloxacin group and 13/140 (9.3%) patients in the azithromycin group, (logrank test p = 0.854, HR [95% CI] = 0.93 [0.43-2.0]). 96% (254/263) of the Salmonella enterica serovar Typhi isolates were resistant to nalidixic acid and 58% (153/263) were multidrug resistant. CONCLUSIONS: Both antibiotics showed an excellent efficacy and safety profile. Both gatifloxacin and azithromycin can be recommended for the treatment of typhoid fever particularly in regions with high rates of multidrug and nalidixic acid resistance. The cost of a 7-day treatment course of gatifloxacin is approximately one third of the cost of azithromycin in Vietnam. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN67946944

Clinically and microbiologically derived azithromycin susceptibility breakpoints for Salmonella enterica serovars Typhi and Paratyphi A.

Azithromycin is an effective treatment for uncomplicated infections with Salmonella enterica serovar Typhi and serovar Paratyphi A (enteric fever), but there are no clinically validated MIC and disk zone size interpretative guidelines. We studied individual patient data from three randomized controlled trials (RCTs) of antimicrobial treatment in enteric fever in Vietnam, with azithromycin used in one treatment arm, to determine the relationship between azithromycin treatment response and the azithromycin MIC of the infecting isolate. We additionally compared the azithromycin MIC and the disk susceptibility zone sizes of 1,640 S. Typhi and S. Paratyphi A clinical isolates collected from seven Asian countries. In the RCTs, 214 patients who were treated with azithromycin at a dose of 10 to 20 mg/ml for 5 to 7 days were analyzed. Treatment was successful in 195 of 214 (91%) patients, with no significant difference in response (cure rate, fever clearance time) with MICs ranging from 4 to 16 μg/ml. The proportion of Asian enteric fever isolates with an MIC of ≤ 16 μg/ml was 1,452/1,460 (99.5%; 95% confidence interval [CI], 98.9 to 99.7) for S. Typhi and 207/240 (86.3%; 95% CI, 81.2 to 90.3) (P 16 μg/ml and to determine MIC and disk breakpoints for S. Paratyphi A

Outbreak of central nervous system infections among children in Thai Binh, Viet Nam

International audienceFrom July to October 2020, 99 cases of central nervous system (CNS) infections were identified in Thai Binh Pediatric Hospital, Viet Nam, representing a five-fold increase compared to the baseline incidence during the previous five years. Clinical data were retrospectively collected. Cerebrospinal fluid specimens (CSF) were secondarily tested for pathogens using viral culture and PCR assays. Patient median age was 5 years (0-12 years); 58.6% were male. Of these children, 83.8% had CSF white blood culture (WBC) counts of ≥ 10 cells/µL, including 58 of 99 (58.6%) with a WBC count ≥ 100 cells/µL. Overall, 72 (72.7%) patients had confirmed infections with a pathogen identified in the CSF, the majority of which (66) were enterovirus. Sequencing results suggested that the rise of incidence observed in 2020 was due to Echovirus 4 (n = 45), Echovirus 30 (n = 8), and Echovirus 6 (n = 1) circulation. A confirmed CNS infection was significantly associated with older age (≥5 years, OR = 3.64, p = 0.03) and with an increased WBC count in the CSF (OR = 6.38, p-value = 0.01 for WBCs from 10 to <100 and OR = 7.90, p-value = 0.002 for WBCs ≥100). Ninety-seven (97) of 99 (98.0%) children received empiric antimicrobial treatment, and 35 (35.3%) were treated with multiple antibiotics. Eighty-four (84) patients (84.9%) were discharged home, and 11 (11.1%) were transferred to the National Hospital because their condition had worsened. No deaths were recorded. Point-of-care tests, including real-time PCR assays to identify common pathogens, should be implemented for more accurate diagnosis and more appropriate antibiotic use

Transcriptional response in the peripheral blood of patients infected with Salmonella enterica serovar Typhi

We used microarrays and transcriptional profiling of peripheral blood to investigate the host response of 29 individuals who contracted typhoid fever in the Mekong Delta region of Vietnam. Samples were taken over a nine month period encompassing acute disease, convalescence, and recovery. We found that typhoid fever induced a distinct and highly reproducible signature in the peripheral blood that changed during treatment and convalescence, returning in the majority of cases to the “normal” profile as measured in healthy uninfected controls. Unexpectedly, there was a strong, distinct signature of convalescence present at day 9 after infection that remained virtually unchanged one month after acute infection and in some cases persisted as long as nine months despite a complete clinical recovery in all patients. Patients who retain the convalescent signature may be genetically or temporarily incapable of developing an effective immune response and may be more susceptible to reinfection, relapse, or the establishment of a carrier state

Aetiologies of central nervous system infection in Viet Nam: a prospective provincial hospital-based descriptive surveillance study.

Infectious diseases of the central nervous system (CNS) remain common and life-threatening, especially in developing countries. Knowledge of the aetiological agents responsible for these infections is essential to guide empiric therapy and develop a rational public health policy. To date most data has come from patients admitted to tertiary referral hospitals in Asia and there is limited aetiological data at the provincial hospital level where most patients are seen.We conducted a prospective Provincial Hospital-based descriptive surveillance study in adults and children at thirteen hospitals in central and southern Viet Nam between August 2007-April 2010. The pathogens of CNS infection were confirmed in CSF and blood samples by using classical microbiology, molecular diagnostics and serology.We recruited 1241 patients with clinically suspected infection of the CNS. An aetiological agent was identified in 640/1241 (52%) of the patients. The most common pathogens were Streptococcus suis serotype 2 in patients older than 14 years of age (147/617, 24%) and Japanese encephalitis virus in patients less than 14 years old (142/624, 23%). Mycobacterium tuberculosis was confirmed in 34/617 (6%) adult patients and 11/624 (2%) paediatric patients. The acute case fatality rate (CFR) during hospital admission was 73/617 (12%) in adults and to 42/624 (7%) in children.Zoonotic bacterial and viral pathogens are the most common causes of CNS infection in adults and children in Viet Nam

Temporal Fluctuation of Multidrug Resistant <em>Salmonella</em> Typhi Haplotypes in the Mekong River Delta Region of Vietnam

<div><h3>Background</h3><p>Typhoid fever remains a public health problem in Vietnam, with a significant burden in the Mekong River delta region. Typhoid fever is caused by the bacterial pathogen <em>Salmonella enterica</em> serovar Typhi (<em>S</em>. Typhi), which is frequently multidrug resistant with reduced susceptibility to fluoroquinolone-based drugs, the first choice for the treatment of typhoid fever. We used a GoldenGate (Illumina) assay to type 1,500 single nucleotide polymorphisms (SNPs) and analyse the genetic variation of <em>S</em>. Typhi isolated from 267 typhoid fever patients in the Mekong delta region participating in a randomized trial conducted between 2004 and 2005.</p><h3>Principal Findings</h3><p>The population of <em>S</em>. Typhi circulating during the study was highly clonal, with 91% of isolates belonging to a single clonal complex of the <em>S</em>. Typhi H58 haplogroup. The patterns of disease were consistent with the presence of an endemic haplotype H58-C and a localised outbreak of <em>S</em>. Typhi haplotype H58-E2 in 2004. H58-E2-associated typhoid fever cases exhibited evidence of significant geo-spatial clustering along the Sông H u branch of the Mekong River. Multidrug resistance was common in the established clone H58-C but not in the outbreak clone H58-E2, however all H58 <em>S</em>. Typhi were nalidixic acid resistant and carried a Ser83Phe amino acid substitution in the <em>gyrA</em> gene.</p><h3>Significance</h3><p>The H58 haplogroup dominates <em>S</em>. Typhi populations in other endemic areas, but the population described here was more homogeneous than previously examined populations, and the dominant clonal complex (H58-C, -E1, -E2) observed in this study has not been detected outside Vietnam. IncHI1 plasmid-bearing <em>S</em>. Typhi H58-C was endemic during the study period whilst H58-E2, which rarely carried the plasmid, was only transient, suggesting a selective advantage for the plasmid. These data add insight into the outbreak dynamics and local molecular epidemiology of <em>S</em>. Typhi in southern Vietnam.</p></div