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

Studying the Nonlinear Optical Properties of Fluoride Laser Host Materials in the Ultraviolet Wavelength Region

Fluoride host materials doped with trivalent cerium ions have previously been demonstrated as successful laser materials in the ultraviolet wavelength region. However, the nonlinear optical properties of the fluoride hosts in this wavelength region have not been investigated yet, although nonlinearity could result in undesirable effects such as self-focusing and pulse distortion when these fluoride materials are used as gain media in high-power, ultrashort pulse laser oscillator and amplifier systems. In this work, the nonlinear refractive index of lithium calcium aluminum fluoride (LiCaAlF6), lithium strontium aluminum fluoride (LiSrAlF6), lanthanum fluoride (LaF3), and yttrium lithium fluoride (YLiF4) fluoride host materials are determined using the Kramers–Krönig relation model in the ultraviolet wavelength region. Self-focusing conditions, particularly at the peak laser emission wavelength of these materials, are further analyzed. Results show that LiCaAlF6 has the smallest nonlinear refractive index and self-focusing, making it an ideal host material under the conditions of ultrashort pulse and ultrahigh-power laser generation

Studying the Nonlinear Optical Properties of Fluoride Laser Host Materials in the Ultraviolet Wavelength Region

Fluoride host materials doped with trivalent cerium ions have previously been demonstrated as successful laser materials in the ultraviolet wavelength region. However, the nonlinear optical properties of the fluoride hosts in this wavelength region have not been investigated yet, although nonlinearity could result in undesirable effects such as self-focusing and pulse distortion when these fluoride materials are used as gain media in high-power, ultrashort pulse laser oscillator and amplifier systems. In this work, the nonlinear refractive index of lithium calcium aluminum fluoride (LiCaAlF6), lithium strontium aluminum fluoride (LiSrAlF6), lanthanum fluoride (LaF3), and yttrium lithium fluoride (YLiF4) fluoride host materials are determined using the Kramers–Krönig relation model in the ultraviolet wavelength region. Self-focusing conditions, particularly at the peak laser emission wavelength of these materials, are further analyzed. Results show that LiCaAlF6 has the smallest nonlinear refractive index and self-focusing, making it an ideal host material under the conditions of ultrashort pulse and ultrahigh-power laser generation

The clinical features and genomic epidemiology of carbapenem-resistant Acinetobacter baumannii infections at a tertiary hospital in Vietnam

ABSTRACT: Objectives: To characterise the clinical features of Acinetobacter baumannii infections and investigate the phylogenetic structure and transmission dynamics of A. baumannii in Vietnam. Methods: Between 2019 and 2020, a surveillance of A. baumannii (AB) infections was conducted at a tertiary hospital in Ho Chi Minh City, Vietnam. Risk factors for in-hospital mortality were analysed using logistic regressions. Whole-genome sequence data were used to characterise genomic species, sequence types (STs), antimicrobial resistance genes, surface antigens, and phylogenetic relatedness of AB isolates. Results: Eighty-four patients with AB infections were enrolled in the study, 96% of whom were hospital-acquired. Half of the AB isolates were identified from ICU-admitted patients, while the remaining isolates were from non-ICU patients. The overall in-hospital mortality was 56%, with associated risk factors including advanced age, ICU stay, exposure to mechanical ventilation/central venous catheterization, pneumonia as source of AB infection, prior use of linezolid/aminoglycosides, and AB treatment with colistin-based therapy. Nearly 91% of isolates were carbapenem-resistant; 92% were multidrug-resistant; and 6% were colistin-resistant. ST2, ST571, and ST16 were the three dominant carbapenem-resistant A. baumannii (CRAB) genotypes, exhibiting distinct AMR gene profiles. Phylogenetic analysis of CRAB ST2 isolates together with previously published ST2 collection provided evidence of intra- and inter-hospital transmission of this clone. Conclusions: Our study highlights a high prevalence of carbapenem resistance and multidrug resistance in A. baumannii and elucidates the spread of CRAB within and between hospitals. Strengthening infection control measures and routine genomic surveillance are crucial to reducing the spread of CRAB and detecting novel pan-drug-resistant variants in a timely fashion

Influenza virus infection history shapes antibody responses to influenza vaccination.

Studies of successive vaccination suggest that immunological memory against past influenza viruses may limit responses to vaccines containing current strains. The impact of memory induced by prior infection is rarely considered and is difficult to ascertain, because infections are often subclinical. This study investigated influenza vaccination among adults from the Ha Nam cohort (Vietnam), who were purposefully selected to include 72 with and 28 without documented influenza A(H3N2) infection during the preceding 9 years (Australian New Zealand Clinical Trials Registry 12621000110886). The primary outcome was the effect of prior influenza A(H3N2) infection on hemagglutinin-inhibiting antibody responses induced by a locally available influenza vaccine administered in November 2016. Baseline and postvaccination sera were titrated against 40 influenza A(H3N2) strains spanning 1968-2018. At each time point (baseline, day 14 and day 280), geometric mean antibody titers against 2008-2018 strains were higher among participants with recent infection (34 (29-40), 187 (154-227) and 86 (72-103)) than among participants without recent infection (19 (17-22), 91 (64-130) and 38 (30-49)). On days 14 and 280, mean titer rises against 2014-2018 strains were 6.1-fold (5.0- to 7.4-fold) and 2.6-fold (2.2- to 3.1-fold) for participants with recent infection versus 4.8-fold (3.5- to 6.7-fold) and 1.9-fold (1.5- to 2.3-fold) for those without. One of 72 vaccinees with recent infection versus 4 of 28 without developed symptomatic A(H3N2) infection in the season after vaccination (P = 0.021). The range of A(H3N2) viruses recognized by vaccine-induced antibodies was associated with the prior infection strain. These results suggest that recall of immunological memory induced by prior infection enhances antibody responses to inactivated influenza vaccine and is important to attain protective antibody titers

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

Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis

Background: It is uncertain whether all adults with bacterial meningitis benefit from treatment with adjunctive dexamethasone. Methods: We conducted a randomized, double-blind, placebo-controlled trial of dexamethasone in 435 patients over the age of 14 years who had suspected bacterial meningitis. The goal was to determine whether dexamethasone reduced the risk of death at 1 month and the risk of death or disability at 6 months. Results: A total of 217 patients were assigned to the dexamethasone group, and 218 to the placebo group. Bacterial meningitis was confirmed in 300 patients (69.0%), probable meningitis was diagnosed in 123 patients (28.3%), and an alternative diagnosis was made in 12 patients (2.8%). An intention-to-treat analysis of all the patients showed that dexamethasone was not associated with a significant reduction in the risk of death at 1 month (relative risk, 0.79; 95% confidence interval [CI], 0.45 to 1.39) or the risk of death or disability at 6 months (odds ratio, 0.74; 95% CI, 0.47 to 1.17). In patients with confirmed bacterial meningitis, however, there was a significant reduction in the risk of death at 1 month (relative risk, 0.43; 95% CI, 0.20 to 0.94) and in the risk of death or disability at 6 months (odds ratio, 0.56; 95% CI, 0.32 to 0.98). These effects were not found in patients with probable bacterial meningitis. Results of multivariate analysis indicated that dexamethasone treatment for patients with probable bacterial meningitis was significantly associated with an increased risk of death at 1 month, an observation that may be explained by cases of tuberculous meningitis in the treatment group. Conclusions: Dexamethasone does not improve the outcome in all adolescents and adults with suspected bacterial meningitis; a beneficial effect appears to be confined to patients with microbiologically proven disease, including those who have received prior treatment with antibiotics. (Current Controlled Trials number, ISRCTN42986828.)