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

<div><p>Background</p><p>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.</p><p>Methods</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusions</p><p>Combined therapy of third-generation cephalosporins and azithromycin for TF may surpass monotherapy in terms of FCT and time to elimination of bacteremia.</p><p>Trial registration</p><p>Trial registration number: <a href="https://clinicaltrials.gov/ct2/show/NCT02224040" target="_blank">NCT02224040</a>.</p></div

Nepal Pioneer Worksite Intervention Study to lower cardio-metabolic risk factors: design and protocol

Abstract Background To increase cardiovascular disease prevention efforts, worksite interventions can promote healthy food choices, facilitate health education, increase physical activity and provide social support. This pioneer study will measure the effectiveness of a cafeteria and a behavioral intervention on cardio-metabolic risk in a worksite in Nepal. Methods The Nepal Pioneer Worksite Intervention Study is a two-step intervention study conducted in Dhulikhel Hospital in eastern Nepal. In the first step, we will assess the effectiveness of a 6-month cafeteria intervention on cardio-metabolic risk using a pre-post design. In the second step, we will conduct a 6-month, open-masked, two-arm randomized trial by allocating half of the participants to an individual behavioral intervention based on the ‘diabetes prevention program’ for the prevention of cardio-metabolic risk. We will recruit 366 full time employees with elevated blood pressure, fasting blood sugar, or glycosylated haemoglobin (HbA1c). At baseline, we will measure their demographic variables, lifestyle factors, anthropometry, fasting blood sugar, HbA1c,and lipid profiles. We will measure cardio-metabolic outcomes at 6 months, 12 months, and 18 months. At 12 months, we will compare the proportion of participants who have attained two or more cardio-metabolic risk factor reduction goals (HbA1c decrease ≥0.5%; systolic blood pressure decrease ≥5 mmHg; or triglycerides decrease ≥10 mg/dL) during the cafeteria intervention period and the control period using generalized estimating equations. At 18 months, we will compare the proportion from the ‘cafeteria only arm’ to the ‘cafeteria and behavior arm’ for the same outcome using a chi-square test. Discussion This pioneer study will estimate the effect of environmental-level changes on lowering cardio-metabolic risks; and added benefit of an individual-level dietary intervention. If the study demonstrates a significant effect, a scaled up approach could produce an important reduction in cardiovascular disease burden through environmental and individual level prevention programs in Nepal and similar worksites worldwide. Trial registration The trial was retrospectively registered on clincaltrials.gov (Identification Member: NCT03447340; Date of Registration: February 27, 2018)

Patient characteristics upon enrollment.

<p>Patient characteristics upon enrollment.</p

Open label comparative trial of mono versus dual antibiotic therapy for Typhoid Fever in adults - Fig 2

<p><b>Kaplan-Meir curve of fever clearance time (FCT) in dual antibiotic therapy versus monotherapy</b>. A. Time to defervescence for the outpatient study arms; B. Time to defervescence for the inpatient study arms; C. Time to defervescence for the two study arms receiving monotherapy versus the two study arms receiving dual therapy. Dashed lines represent monotherapy, continuous lines represents dual therapy.</p

Study flow diagram of patients with blood cultures positive for <i>S</i>. Typhi and <i>S</i>. Paratyphi.

<p>Study flow diagram of patients with blood cultures positive for <i>S</i>. Typhi and <i>S</i>. Paratyphi.</p