Safety and immunogenicity of conjugate vaccine for typhoid (Vi-DT): Finding from an observer-blind, active-controlled, randomized, non-inferiority, phase III clinical trial among healthy volunteers.

Typhoid fever is a significant public health concern with most of the sufferers between 15 and 25 y of age in Nepal. We undertook this study to demonstrate Vi polysaccharide conjugated with diphtheria toxoid (Vi-DT) conjugate vaccine which is non-inferior to Typbar typhoid conjugate vaccine, a Vi polysaccharide vaccine conjugated with tetanus toxoid (Vi-TT) with a focus on the adult population from Dhulikhel Hospital which was one of the total four sites in Nepal. In this study, we assigned the eligible participants in 1:1:1:1 ratio by block randomization, and stratified into three age groups (6 months to less than 2 y, 2 y to less than 18 y, and 18 y to 45 y), allotted to Group A, B, C, and D. Group A, B, and C received 25 µg (0.5 mL) of Vi-DT study vaccine and participants in Group D received 25 µg (0.5 mL) Vi-TT vaccine. We descriptively analyzed safety in all the participants receiving one dose of the investigational vaccine. The anti-Vi-IgG seroconversion rate in Vi-DT recipients was 99.71% (97.5% CI 98.04-99.96; 344 of 345 participants) and 99.13% (94.27-99.87; 114 of 115) in Vi-TT recipients which indicates that Vi-DT vaccine is non-inferior to Vi-TT vaccine. In safety aspect, 16.81% of total subject had at least one solicited adverse reaction and 22.61% of the Vi-TT participants experienced at least one solicited adverse reaction with most of them being local adverse reactions. None of the enrolled participants reported serious adverse events. Our study shows that a single dose of the Vi-DT vaccine is immunogenic, safe to administer and non-inferior to the Vi-TT vaccine four weeks after vaccination.

Mean Atd Angle among Type 2 Diabetes Mellitus Patients Visiting a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: An atd angle is one of the dermatoglyphic patterns which is an indication of the degree of distal displacement of the axial triradius on the palm. This is one of the markers of diabetes mellitus that is used as a screening tool in order to reduce the risk of onset and initiate early treatment. The aim of this study is to find the mean atd angle among type 2 diabetes mellitus patients visiting a tertiary care centre. Methods: This descriptive cross-sectional study was done among diabetic patients in a tertiary centre from 9 June 2021 to 5 May 2022. Ethical approval was taken from Institutional Review Committee (Reference number: KUSMS/IRC 40/2021). Both palm prints of study subjects were taken and the atd angle was measured. Convenience sampling was done. Point estimate and 95% confidence interval were calculated. Results: Among 133 palm prints of diabetic patients, the mean atd angle was 42.13±4.73° (male: 41.90±4.75° and female: 42.35±4.70°). The right palms showed mean atd angle of 42.31±4.42° and that of left palms was 41.94±5.04°. Conclusions: The mean atd angle among type 2 diabetes mellitus patients is similar to other studies done in similar settings. Keywords: dermatoglyphic; diabetes mellitus; prevalence.

The epidemiology of typhoid fever in the Dhulikhel area, Nepal: A prospective cohort study.

INTRODUCTION: Typhoid fever (TF) continues to cause considerable morbidity and mortality in Nepal, but only limited epidemiologic data is available about TF outside Kathmandu. METHODS: As part of an interventional trial, we performed a prospective cohort study of bacteremic TF patients in Dhulikhel Hospital between October 2012 and October 2014. Demographic, epidemiological, clinical, and microbiologic data were recorded. RESULTS: 116 bacteremic typhoid patients were included in the study. Most were young, healthy, adults (mean age 27.9±12 years), 41.4% of whom were female. More than 70% of patients were employed in non-manual services or were university students. Salmonella Typhi accounted for 64/115 (55.7%) of all isolates, while Salmonella Paratyphi accounted for 51/115 (44.3%), of which 42 were Paratyphi A and 9 Paratyphi B. A significant proportion of TF cases occurred also during the dry season (48/116, 41.6%). The clinical presentation of Salmonella Typhi and Paratyphi infections was similar, except for a greater proportion of arthralgia in patients with Salmonella Typhi. Most Salmonella Typhi and Paratyphi isolates were resistant to nalidixic acid and susceptible to older antibiotics. One Salmonella Paratyphi isolate was resistant to ceftriaxone. CONCLUSIONS: TF remains common in the Dhulikhel area, even among those with a high level of education. Public health measures aimed at reducing the incidence of TF in the Dhulikhel area are warranted. The relative burden of TF caused by Salmonella Paratyphi is rising; a vaccine with activity against Salmonella Paratyphi is needed. Since Salmonella Paratyphi B was more prevalent in this cohort than in large cohorts of patients from Kathmandu, it is likely that there are significant regional variations in the epidemiology of TF outside Kathmandu.

Open label comparative trial of mono versus dual antibiotic therapy for Typhoid Fever in adults.

BACKGROUND: Emerging resistance to antibiotics renders therapy of Typhoid Fever (TF) increasingly challenging. The current single-drug regimens exhibit prolonged fever clearance time (FCT), imposing a great burden on both patients and health systems, and potentially contributing to the development of antibiotic resistance and the chronic carriage of the pathogens. The aim of our study was to assess the efficacy of combining third-generation cephalosporin therapy with azithromycin on the outcomes of TF in patients living in an endemic region. METHODS: An open-label, comparative trial was conducted at Dhulikhel Hospital, Nepal, between October 2012 and October 2014. Only culture-confirmed TF cases were eligible. Patients were alternately allocated to one of four study arms: hospitalized patients received either intravenous ceftriaxone or a combination of ceftriaxone and oral azithromycin, while outpatients received either oral azithromycin or a combination of oral azithromycin and cefexime. The primary outcome evaluated was FCT and the secondary outcomes included duration of bacteremia. RESULTS: 105 blood culture-confirmed patients, of whom 51 were treated as outpatients, were eligible for the study. Of the 88 patients who met the inclusion criteria for FCT analysis 41 patients received a single-agent regimen, while 47 patients received a combined regimen. Results showed that FCT was significantly shorter for the latter (95 versus 88 hours, respectively, p = 0·004), and this effect was exhibited in both the hospitalized and the outpatient sub-groups. Repeat blood cultures, drawn on day 3, were positive for 8/47 (17%) patients after monotherapy, versus 2/51 (4%) after combination therapy (p = 0·045). No severe complications or fatalities occurred in any of the groups. CONCLUSIONS: Combined therapy of third-generation cephalosporins and azithromycin for TF may surpass monotherapy in terms of FCT and time to elimination of bacteremia. TRIAL REGISTRATION: Trial registration number: NCT02224040.