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

ABSTRACT: 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.

SUBMITTER: Petersiel N

PROVIDER: S-EPMC6160059 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Petersiel Neta N Shresta Sudeep S Tamrakar Rajendra R Koju Rajendra R Madhup Surendra S Shresta Ashish A Bedi Trs T Zmora Niv N Paran Yael Y Schwartz Eli E Neuberger Ami A

PloS one 20180927 9

<h4>Introduction</h4>Typhoid fever (TF) continues to cause considerable morbidity and mortality in Nepal, but only limited epidemiologic data is available about TF outside Kathmandu.<h4>Methods</h4>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.<h4>Results</h4>116 bacteremic typhoid patients were included ...[more]

PMID: 30261024

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Project description:BackgroundTyphoid fever remains a significant public health problem in developing countries. In October 2011, a typhoid fever epidemic was declared in Harare, Zimbabwe - the fourth enteric infection epidemic since 2008. To orient control activities, we described the epidemiology and spatiotemporal clustering of the epidemic in Dzivaresekwa and Kuwadzana, the two most affected suburbs of Harare.MethodsA typhoid fever case-patient register was analysed to describe the epidemic. To explore clustering, we constructed a dataset comprising GPS coordinates of case-patient residences and randomly sampled residential locations (spatial controls). The scale and significance of clustering was explored with Ripley K functions. Cluster locations were determined by a random labelling technique and confirmed using Kulldorff's spatial scan statistic.Principal findingsWe analysed data from 2570 confirmed and suspected case-patients, and found significant spatiotemporal clustering of typhoid fever in two non-overlapping areas, which appeared to be linked to environmental sources. Peak relative risk was more than six times greater than in areas lying outside the cluster ranges. Clusters were identified in similar geographical ranges by both random labelling and Kulldorff's spatial scan statistic. The spatial scale at which typhoid fever clustered was highly localised, with significant clustering at distances up to 4.5 km and peak levels at approximately 3.5 km. The epicentre of infection transmission shifted from one cluster to the other during the course of the epidemic.ConclusionsThis study demonstrated highly localised clustering of typhoid fever during an epidemic in an urban African setting, and highlights the importance of spatiotemporal analysis for making timely decisions about targetting prevention and control activities and reinforcing treatment during epidemics. This approach should be integrated into existing surveillance systems to facilitate early detection of epidemics and identify their spatial range.

Project description:BackgroundPrecise enteric fever disease burden data are needed to inform prevention and control measures, including the use of newly available typhoid vaccines. We established the Surveillance for Enteric Fever in Asia Project (SEAP) to inform these strategies.MethodsFrom September, 2016, to September, 2019, we conducted prospective clinical surveillance for Salmonella enterica serotype Typhi (S Typhi) and Paratyphi (S Paratyphi) A, B, and C at health facilities in predetermined catchment areas in Dhaka, Bangladesh; Kathmandu and Kavrepalanchok, Nepal; and Karachi, Pakistan. Patients eligible for inclusion were outpatients with 3 or more consecutive days of fever in the last 7 days; inpatients with suspected or confirmed enteric fever; patients with blood culture-confirmed enteric fever from the hospital laboratories not captured by inpatient or outpatient enrolment and cases from the laboratory network; and patients with non-traumatic ileal perforation under surgical care. We used a hybrid surveillance model, pairing facility-based blood culture surveillance with community surveys of health-care use. Blood cultures were performed for enrolled patients. We calculated overall and age-specific typhoid and paratyphoid incidence estimates for each study site. Adjusted estimates accounted for the sensitivity of blood culture, the proportion of eligible individuals who consented and provided blood, the probability of care-seeking at a study facility, and the influence of wealth and education on care-seeking. We additionally calculated incidence of hospitalisation due to typhoid and paratyphoid.FindingsA total of 34 747 patients were enrolled across 23 facilitates (six tertiary hospitals, surgical wards of two additional hospitals, and 15 laboratory network sites) during the study period. Of the 34 303 blood cultures performed on enrolled patients, 8705 (26%) were positive for typhoidal Salmonella. Adjusted incidence rates of enteric fever considered patients in the six tertiary hospitals. Adjusted incidence of S Typhi, expressed per 100 000 person-years, was 913 (95% CI 765-1095) in Dhaka. In Nepal, the adjusted typhoid incidence rates were 330 (230-480) in Kathmandu and 268 (202-362) in Kavrepalanchok. In Pakistan, the adjusted incidence rates per hospital site were 176 (144-216) and 103 (85-126). The adjusted incidence rates of paratyphoid (of which all included cases were due to S Paratyphi A) were 128 (107-154) in Bangladesh, 46 (34-62) and 81 (56-118) in the Nepal sites, and 23 (19-29) and 1 (1-1) in the Pakistan sites. Adjusted incidence of hospitalisation was high across sites, and overall, 2804 (32%) of 8705 patients with blood culture-confirmed enteric fever were hospitalised.InterpretationAcross diverse communities in three south Asian countries, adjusted incidence exceeded the threshold for "high burden" of enteric fever (100 per 100 000 person-years). Incidence was highest among children, although age patterns differed across sites. The substantial disease burden identified highlights the need for control measures, including improvements to water and sanitation infrastructure and the implementation of typhoid vaccines.FundingBill & Melinda Gates Foundation.

Project description:BACKGROUND:Domestic violence is one of the most common forms of violence against women. Domestic violence during pregnancy is associated with adverse perinatal and maternal outcomes. We aimed to assess whether domestic violence was associated with mode of delivery, low birthweight and preterm birth in two sites in Nepal. METHODS:In this prospective cohort study we consecutively recruited 2004 pregnant women during antenatal care at two hospitals between June 2015 and September 2016. The Abuse Assessment Screen (modified) was used to assess fear and violence. Having ever experienced either fear or violence was defined as any domestic violence. Obstetric outcomes were obtained from hospital records for 1381 (69%) women, selecting singleton pregnancies only. Mode of delivery was assessed as birth by cesarean section or not. A birthweight of less than 2500?g was defined as low birthweight and preterm birth as birth before completion of 37?weeks gestation. Descriptive and multiple logistic regression analyses were performed to assess associations. RESULTS:Twenty percent of the women reported any domestic violence. Among all 1381 women, 37.6% gave birth by cesarean section. Of those women who delivered by cesarean section, 84.7% had an emergency cesarean section. Less than 10% of the babies were born prematurely and 13.5% were born with low birthweight. We found no significant association between exposure to any domestic violence during pregnancy and risk of a low birthweight baby or birth by cesarean section. However, having experienced both violence and fear was significantly associated with giving birth to a preterm infant [aOR 2.33 (95% CI;1.10-4.73)]. CONCLUSIONS:Domestic violence is common in Nepal. This is a potential risk factor for severe morbidity and mortality in newborns. We found that the risk of having a preterm baby was higher for pregnant women who experienced both fear and violence. This should be recognized by the health sector. In this study, no significant differences were found in the rate of cesarean section nor low birthweight for women who had experienced any domestic violence compared to those who did not.

Project description:Patient Selection: Three hospitals were involved in the study: Dong Thap Provincial and An Giang Provincial hospitals, both located in the Mekong Delta Region of Vietnam where most of the Typhoid patients were admitted, and the Hospital for Tropical Diseases, Ho Chi Minh City, where the malarial patients were admitted. Infection status of each patient was determined by blood culture for the Typhoid patients and by microscopic examination of stained thick and thin peripheral-blood slides for the patients suspected of having Malaria. Patients with blood cultures positive for S. Typhi or S. enterica serovar Paratyphi A (S. Paratyphi A) (samples designated ST) or peripheral blood smears positive for Plasmodium falciparum or Plasmodium vivax (samples designated PF) were consented and enrolled in the study. A total of 28 S. Typhi positive patients and one S. Paratyphi A positive patient were enrolled in the first phase of the study and a further 9 S. Typhi and one S. Paratyphi A positive patient were enrolled in the second phase. Nine patients with Malaria caused by P. falciparum and one caused by P. vivax were enrolled. Sixteen uninfected healthy individuals (samples designated HC) were also enrolled in the study (one sample each). The Typhoid patients were randomly chosen to receive either Azithromycin or Gatifloxicin (20mg/kg/day for 7 days) antibiotics. Uncomplicated malaria patients were treated for 3 days with Artekin (dihydroartemisinin with piperaquine phosphate). Venous blood (2.5ml) was collected for total RNA extraction into PaxGene RNA collection tubes (Qiagen) at various times. The first sample (T1) was taken immediately on admission or entry into the study, then samples were collected, 3 (T3), 6-9 (T9 for Typhoid, T7 for Malaria), and 28-45 (T28) days following entry into the study and an average of 9 months (T9M) later. The PaxGene tubes were stored at 4degC until RNA was extracted as per the manufacturers instructions. Purified RNA was shipped on dry ice to Stanford University, CA for use in Microarray analyses. Microarrays: Experimental and reference samples (Human Universal RNA reference {Stratagene}) were amplified using the MessageAmp II aRNA Kit (Ambion) as per the manufacturer's instructions. Four micrograms amplified RNA was labeled through indirect incorporation of Cy5 (experimental) and Cy3 (reference) dyes (protocols can be found at http://cmgm.stanford.edu/pbrown/protocols/index.html). The labeled probes were then mixed and hybridized to Stanford Human cDNA arrays with 42 K features. Arrays were scanned using a Genepix 4000A laser scanner and data extracted with Genepix Pro Software version 5.1 (Axon Instruments). The data were then uploaded into the Stanford Microarray Database (SMD). A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Compound Based Treatment: Drugs used for treatment Disease State: Malaria, Typhoid or Healthy Controls Keywords: disease_state_design

Dataset Information

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

Publications

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

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