An outbreak of multidrug resistant typhoid fever in Bangalore

Six hundred and eighty five blood cultures from children clinically diagnosed as enteric fever yielded 176 salmonella strains showing isolation success rate of 25.7%,S. typhi were 164 (93.2%),S. paratyphi A 5 (2.8%),S. choleraesuis 4 (2.3%) andS. typhimurium 3 (1.7%). Antibiogram of 164 isolates ofS. typhi showed triple drug resistance (TDR) in 156 strains (95.1%) to chloramphenicol, ampicillin and cotrimoxazole, and sensitivity of 90.2% and 95.1% to norfloxacin and ciprofloxacin respectively. Minimum inhibitory concentrations (MIC) of chloramphenicol were between 360 mcg and 640 mcg per ml. Phage types of 38 strains of TDRS. typhi were predominantly E1 and 0 with prevalences of 47.4% and 36.8% respectively in this region. All children with S.typhi isolates sensitive to quinolones inVitro responded well to these drugs with almost no relapse and hence, the newer generation of quinolones could be considered as the first choice in the primary treatment of enteric fever.     

A randomized comparison of oral chloramphenicol versus ofloxacin in the treatment of uncomplicated typhoid fever in Laos

We conducted a randomized open trial of oral chloramphenicol (50mg/kg/day in four divided doses for 14 days) versus ofloxacin (15 mg/kg/day in two divided doses for 3 days) in 50 adults with culture-confirmed uncomplicated typhoid fever in Vientiane, Laos. Patients had been ill for a median (range) of 8 (2-30) days. All Salmonella enterica serotype typhi isolates were nalidixic acid-sensitive, four (8%) were chloramphenicol-resistant and three (6%) were multidrug-resistant. Median (range) fever clearance times were 90 (24-224) hours in the chloramphenicol group and 54 (6-93) hours in the ofloxacin group (P<0.001). One patient in the chloramphenicol group developed an ileal perforation. Three days ofloxacin was more effective than 14 days chloramphenicol for the in-patient treatment of typhoid fever, irrespective of antibiotic susceptibility, and was of similar cost.     

A simple validated prediction rule to diagnose typhoid fever in Turkey

The goal of this study was to develop a simple prediction rule for the diagnosis of typhoid fever. A model for the prediction of patients with typhoid fever at hospital admission was derived and validated by assigning weighted point values to independent predictive factors associated with a diagnosis of typhoid fever at hospital admission. Patient demographic, clinical and laboratory variables were used to compare patients with blood culture-confirmed typhoid fever with patients with fever of unknown origin. The model was derived and validated in two separate cohorts of patients from Dicle University Hospital in Diyarbakir, Turkey. A total of 371 patients were enrolled. A diagnostic index score was created using seven independent predictive factors associated with typhoid fever at hospital admission: age <30 years, abdominal distention, confusion, leukopenia, relative bradycardia, positive Widal test and a typhoid tongue. A clinical prediction rule helped to differentiate patients with typhoid fever.     

伤寒患者血清TNF,IL—2,sIL—2R水平的研究

为了解肿瘤坏死因子（ＴＮＦ）、白细胞介素２（ＩＬ－２）和可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）在伤寒发病中的作用，以双抗体夹心法检测２７例伤寒患者及１６例正常人血清ＴＮＦ、ＩＬ－２和ｓＩＬ－２Ｒ水平。结果发现，伤寒患者血清ＴＮＦ水平和ｓＩＬ－２Ｒ水平均明显高于正常人水平（Ｐ＜０．０１）。而血清ＩＬ－２水平显著低于正常对照（Ｐ＜０．０１）。对１５例伤寒患者各病期血清ＴＮＦ、ＩＬ－２和ｓＩＬ－２Ｒ水平动态观察发现伤寒患者血清ＴＮＦ、ｓＩＬ－２Ｒ水平动态变化与患者体温、病期、病情变化具有密切关系。伴肝功能损伤和有诸如消化道出血、肺炎、急性肾衰等并发症及复发性伤寒的患者其血清ＴＮＦ、ｓＩＬ－２Ｒ水平明显高于无肝功能损伤及无并发症的患者。结果提示，临床检测伤寒患者血清ＴＮＦ、ｓＩＬ－２Ｒ除可协助诊断外，对于患者病情、病期、预后的判断及治疗效果的观察均具有重要意义，因此可作为临床观察伤寒病情及判断预后的监测指标。血清ＩＬ－２检测对于伤寒的诊断有一定帮助，但作为判断临床病情、病期及预后的指标意义不大     

Immunogenicity,safety and reactogenicity of a Phase II trial of Vi-DT typhoid conjugate vaccine in healthy Filipino infants and toddlers: A preliminary report

BackgroundTyphoid fever remains an important public health problem in developing countries and is endemic in many parts of Asia and Africa where the incidence of disease typically peaks in school-aged children. Age restrictions and other limitations of existing oral live-attenuated typhoid and parenteral Vi polysaccharide vaccines have triggered the development of Vi conjugate vaccines with improved immunological properties, use in younger age range, and longer durability of protection. We present the safety, reactogenicity, and immunogenicity data from a Phase II study after a single dose of Vi polysaccharide conjugated to diphtheria toxoid (Vi-DT) conducted in 6–23-month old Filipino children.MethodsThis is a randomized, observer-blinded Phase II study to assess the immunogenicity, safety and reactogenicity of Vi-DT compared to placebo, conducted in Muntinlupa City, The Philippines. Participants aged 6–23 months were enrolled and randomized to Vi-DT (25 µg) or placebo (0.9% sodium chloride) and evaluated for immunogenicity and overall safety 28 days post vaccination.ResultsA total of 285 participants were enrolled and age-stratified: 6 to < 9 months, 9–12 months, and 13–23 months. Seventy-six (76) participants received Vi-DT and 19 received placebo per each strata. All participants seroconverted after a single dose of Vi-DT versus 7% of placebo recipients. Anti-Vi IgG GMT was 444.38 [95% CI (400.28; 493.34)] after a single dose of Vi-DT; there was no change in GMT after placebo administration, 0.41 [95% CI (0.33; 0.51), p < 0.0001]. A similar pattern of immunogenicity was reported across all age strata. The vaccine reported to be safe and well tolerated.ConclusionsVi-DT vaccine was immunogenic, safe, and well tolerated in children aged 6–23 months.ClinicalTrials.gov registration number: NCT03527355.     

Development of a synthetic Vi polysaccharide vaccine for typhoid fever

Typhoid fever remains a serious public health problem with a high impact on toddlers and young children. Vaccines against the Vi capsular polysaccharide are efficacious against typhoid fever demonstrating that antibodies against Vi confer protection. The currently licensed Vi typhoid vaccines have however limited efficacy and are manufactured by a complex process from wild-type bacteria. Due to these inherent issues with the current vaccines, an alternative vaccine based on an O-acetylated high molecular weight (HMW) polygalacturonic acid (GelSite-OAc™) was generated. The HMW polygalacturonic acid shares the same backbone as the Vi polysaccharide of Salmonella Typhi. The GelSite-OAc™ has a high molecular weight (>1 × 10⁶ Da) and a high degree of O-acetylation (DOAc) (>5 μmole/mg), both exceeding the potency specifications of the current Vi vaccine. Studies in Balb/c mice demonstrated that GelSite-OAc™ was highly immunogenic, inducing a strong antigen-specific antibody response in a DOAc- and dose-dependent manner which was comparable to or higher than those induced by the licensed Vi vaccine. Importantly, the GelSite-OAc™ was shown to be fully protective in mice against lethal challenge with Salmonella Typhi. Furthermore, the GelSite-OAc™ demonstrated a boosting effect or memory response, exhibiting a >2-fold increase in antibody levels upon the second immunization with either GelSite-OAc™ or the Vi vaccine. This novel boosting effect is unique among polysaccharide antigens and potentially makes GelSite-OAc™ effective in people under 2 years old. Together these results suggest that the GelSite-OAc™ could be a highly effective vaccine against Salmonella Typhi.     

Comparative frequency of specified adverse events following Vero cell culture-derived Japanese encephalitis and Vi capsular polysaccharide typhoid vaccines in U.S. military personnel,July 2011–August 2019

Vero cell culture-derived Japanese encephalitis (JE) vaccine (JE-VC; Ixiaro) was approved in the United States in 2009. The previous JE vaccine, an inactivated mouse brain-derived vaccine, had been associated with rare, but serious, allergic and neurologic adverse events (AE). Studies and AE surveillance have supported JE-VC’s safety, but one evaluation among military personnel found elevated hypersensitivity and neurologic AE rates. However, co-administration of multiple vaccines to some personnel might have affected results. We retrospectively compared rates of hypersensitivity and neurologic AEs within 28 days following vaccination of military personnel with JE-VC or parenteral Vi capsular polysaccharide typhoid vaccine administered without other vaccines from July 1, 2011, through August 31, 2019. Rates of most events were similar between the vaccines. Only delayed hypersensitivity reactions occurred more frequently following JE-VC (rate ratio: 4.2, 95 % CI 1.2–15.3; p = 0.03), but rates were low for both vaccines. These results support JE-VC’s safety.     

Effect of Plasmodium and Salmonella co-infection in a murine model

The present study was designed to evaluate the effect of Plasmodium and Salmonella co-infection in LACA mice. The parasitaemic level, bacterial load, histological alterations and levels of oxidants/antioxidant activity were measured. Co-infected mice had a high parasitaemic level, increased bacterial load, and died earlier than Plasmodium-infected mice. Histologically, co-infected mice had more architectural damage in the liver, spleen, kidney, and brain than the control groups. The level of lipid peroxidation was significantly increased and the activities of antioxidative enzymes (superoxide dismutase and catalase) were decreased in all organs of co-infected mice compared to the control groups, indicating depression of the antioxidant defense system. The present study demonstrates more severe histological and biochemical alterations in co-infected mice, highlighting the importance of early diagnosis for selection of appropriate treatments and reducing the likelihood of further complications.     

Science and society: vaccines and public health

Most public health research is devoted to the measurement of disease burdens and of the costs and effectiveness of control measures. The history of immunization provides many colourful examples of various ways in which such measurements are made, of how they have influenced policies, and of the importance of public perception of the magnitudes of the various burdens, benefits and risks. Improving the public's ability to evaluate evidence is itself an important aspect of public health.