BackgroundIn South Asia, data on enteric fever are sparse outside of urban areas. We characterized enteric fever diagnosis patterns and the burden of culture-confirmed cases in peri-urban and rural Nepal.MethodsWe used national reports to estimate enteric fever diagnosis rates over 20 years (1994–2014) and conducted a prospective study of patients presenting with a >72-hour history of fever to 4 peri-urban and rural healthcare facilities (during August 2013–June 2016). We compared clinical characteristics of patients with culture-confirmed Salmonella Typhi or Paratyphi infection to those of patients without enteric fever. We used generalized additive models with logistic link functions to evaluate associations of age and population density with culture positivity.ResultsNational rates of enteric fever diagnosis were high, reaching 18.8 cases per 1000 during 2009–2014. We enrolled 4309 participants with acute febrile illness. Among those with a provisional clinical diagnosis, 55% (1334 of 2412) received a diagnosis of enteric fever; however, only 4.1% of these had culture-confirmed typhoidal Salmonella infection. Culture positivity was highest among young adults and was strongly associated with higher population density (P < .001).ConclusionsEnteric fever diagnosis rates were very high throughout Nepal, but in rural settings, few patients had culture-confirmed disease. Expanded surveillance may inform local enteric fever treatment and prevention strategies.

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Background. There is a need for a reliable, simple diagnostic assay for typhoid fever. Available commercial serologic assays for typhoid fever have limited sensitivity and specificity. Using high-throughput immunoscreening technologies, we previously identified several immunoreactive Salmonella Typhi antigens that seem promising for possible inclusion in a new diagnostic assay: hemolysin E (HlyE), cytolethal distending toxin, S. Typhi lipopolysaccharide (LPS), and S. Typhi membrane preparation.Methods. We assessed plasma antibody responses (immunoglobulin [Ig] M, IgA, and IgG) to these antigens by means of enzyme-linked immunosorbent assay in patients with suspected enteric fever, controls with other febrile illnesses, and healthy controls in Dhaka, Bangladesh and performed Tubex and Typhidot tests, the Widal assay, and the typhoid/paratyphoid test (TPTest) in each patient. Using machine learning methods, we identified a parsimonious serology signature to distinguish acute typhoid cases from controls and then validated our findings in an independent test cohort from Nepal of patients with culture-confirmed S. Typhi and controls with other bacteremic illnesses.Results. We demonstrated that the use of 2 antigens (HlyE and LPS) with 1 antibody isotype (IgA) could distinguish typhoid from other invasive bacterial infections (area under the receiver operating characteristic curve [AUC], 0.95; sensitivity, 90%, specificity, 92%). Use of a single antigen (HlyE) and isotype (IgA) had an AUC of 0.93. Conclusion.Our results suggest that development of a diagnostic assay for acute typhoid fever focused on detecting IgA responses against HlyE, with or without LPS, is warranted.

Introduction We have previously determined the prevalence of human papillomavirus (HPV) infection among women in rural Nepal. In the current study, we also wanted to examine the prevalence of and risk factors for other sexually transmitted infections (STIs) in the same population. Methods Population-based study of nonpregnant women ≥ 15 years who were married or had a history of marriage in the past, residing in five rural villages in Nepal. Data on sociodemographic characteristics, reproductive history, and genitourinary symptoms were collected, and a gynecological examination was conducted. Cervical samples were analyzed by real-time PCR for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis and HPV, and a serum sample was analyzed for syphilis, hepatitis B virus (HBV) and HIV infection by serology. Results Of 2416 eligible women, 62% participated. Trichomoniasis, Chlamydia trachomatis infection, HPV and HBV infection, and syphilis were detected in 5.4%, 0.8%, 14.3%, 0.3%, and 0.2% of the women. None had gonorrhea or HIV infection. Of those with genitourinary symptoms, 6.3% had a curable STI. Vaginal discharge classified as abnormal by gynecological examination, but not self-reported discharge, was significantly associated with laboratory diagnosis of a curable STI. Risk factors for trichomoniasis were reproductive age and high cast/ethnicity. Due to low prevalence, risk factors for other STIs could not be disclosed. Conclusion We observed high prevalence of HPV infection followed by trichomoniasis, while other STIs were rare among women in rural Nepal. There was no association between genitourinary symptoms and laboratory-confirmed STIs.

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Background Characterizing healthcare-seeking patterns for acute febrile illness is critical for generating population-based enteric fever incidence estimates from facility-based surveillance data. Methods We used a hybrid model in the Surveillance for Enteric Fever in Asia Project (SEAP) to assess incidence of enteric fever at 6 study hospitals in 3 countries. We recruited individuals presenting to the hospitals and obtained blood cultures to evaluate for enteric fever. For this analysis, we undertook cluster random household surveys in Dhaka, Bangladesh (2 sites); Karachi, Pakistan; Kathmandu, Nepal; and Kavrepalanchok, Nepal between January 2017 and February 2019, to ascertain care-seeking behavior for individuals with 1) fever for ≥3 consecutive days within the past 8 weeks; or 2) fever resulting in hospitalization within the past year. We also collected data about disease severity and household demographics and assets. We used mixed-effect multivariable logistic regression models to identify determinants of healthcare seeking at study hospitals and determinants of culture-confirmed enteric fever. Results We enrolled 31 841 households (53 926 children) in Bangladesh, 25 510 households (84 196 children and adults) in Nepal, and 21 310 households (108 031 children and adults) in Pakistan. Children &lt;5 years were most likely to be taken to the study hospitals for febrile illness at all sites. Household wealth was positively correlated with healthcare seeking in 4 of 5 study sites, and at least one marker of disease severity was positively associated with healthcare seeking in 3 of 5 catchment areas. Wealth and disease severity were variably predictive of blood culture-confirmed enteric fever. Conclusions Age, household wealth, and disease severity are important determinants of healthcare seeking for acute febrile illness and enteric fever risk in these communities, and should be incorporated into estimation models for enteric fever incidence.

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