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BackgroundEnteric fever, a bacterial infection caused by Salmonella enterica serotypes Typhi and Paratyphi A, frequently presents as a nonlocalizing febrile illness that is difficult to distinguish from other infectious causes of fever. Blood culture is not widely available in endemic settings and, even when available, results can take up to 5 days. We evaluated the diagnostic performance of clinical features, including both reported symptoms and clinical signs, of enteric fever among patients participating in the Surveillance for Enteric Fever in Asia Project (SEAP), a 3-year surveillance study in Bangladesh, Nepal, and Pakistan.MethodsOutpatients presenting with ≥3 consecutive days of reported fever and inpatients with clinically suspected enteric fever from all 6 SEAP study hospitals were eligible to participate. We evaluated the diagnostic performance of select clinical features against blood culture results among outpatients using mixed-effect regression models with a random effect for study site hospital. We also compared the clinical features of S. Typhi to S. Paratyphi A among both outpatients and inpatients.ResultsWe enrolled 20 899 outpatients, of whom 2116 (10.1%) had positive blood cultures for S. Typhi and 297 (1.4%) had positive cultures for S. Paratyphi A. The sensitivity of absence of cough was the highest among all evaluated features, at 65.5% (95% confidence interval [CI], 55.0-74.7), followed by measured fever at presentation at 59.0% (95% CI, 51.6-65.9) and being unable to complete normal activities for 3 or more days at 51.0% (95% CI, 23.8-77.6). A combined case definition of 3 or more consecutive days of reported fever and 1 or more of the following (a) either the absence of cough, (b) fever at presentation, or (c) 3 or more consecutive days of being unable to conduct usual activity--yielded a sensitivity of 94.6% (95% CI, 93.4-95.5) and specificity of 13.6% (95% CI, 9.8-17.5).ConclusionsClinical features do not accurately distinguish blood culture-confirmed enteric fever from other febrile syndromes. Rapid, affordable, and accurate diagnostics are urgently needed, particularly in settings with limited or no blood culture capacity.

BackgroundImplementation of population-based surveys is resource intensive and logistically demanding, especially in areas with rapidly changing demographics and incomplete or no enumeration of the underlying population and their residences. To remove the need for pre-enumeration and to simplify field logistics for the population healthcare utilization survey used for the Surveillance for Enteric Fever in Asia Project in Nepal, we incorporated a geographic information system-based geosurvey and field mapping system into a single-stage cluster sampling approach.MethodsA survey was administered to ascertain healthcare-seeking behavior in individuals with recent suspected enteric fever. Catchment areas were based on residential addresses of enteric fever patients using study facilities; clusters were randomly selected from digitally created grids using available satellite images and all households within clusters were offered enrollment. A tablet-compatible geosurvey and mapping system that allowed for data-syncing and use in areas without cellular data was created using the ArcGIS suite of software.ResultsBetween January 2017 and November 2018, we surveyed 25 521 households in Nepal (16 769 in urban Kathmandu and 8752 in periurban Kavrepalanchok), representing 84 202 individuals. Overall, the survey participation rate was 90.9%, with geographic heterogeneity in participation rates within each catchment area. Areas with higher average household wealth had lower participation rates.ConclusionA geographic information system-based geosurvey and field mapping system allowed creation of a virtual household map at the same time as survey administration, enabling a single-stage cluster sampling method to assess healthcare utilization in Nepal for the Surveillance for Enteric Fever in Asia Project . This system removed the need for pre-enumeration of households in sampling areas, simplified logistics and could be replicated in future community surveys.

BackgroundAntibiotic use prior to seeking care at a hospital may reduce the sensitivity of blood culture for enteric fever, with implications for both clinical care and surveillance. The Surveillance for Enteric Fever in Asia Project (SEAP) is a prospective study of enteric fever incidence in Nepal, Bangladesh, and Pakistan. Nested within SEAP, we evaluated the accuracy of self-reported antibiotic use and investigated the association between antibiotic use and blood culture positivity.MethodsBetween November 2016 and April 2019, we collected urine samples among a subset of SEAP participants to test for antibiotic use prior to the hospital visit using an antibacterial activity assay. All participants were asked about recent antibiotic use and had a blood culture performed. We used mixed-effect logit models to evaluate the effect of antimicrobial use on blood culture positivity, adjusted for markers of disease severity.ResultsWe enrolled 2939 patients with suspected enteric fever. Antibiotics were detected in 39% (1145/2939) of urine samples. The correlation between measured and reported antibiotic use was modest (κ = 0.72). After adjusting for disease severity, patients with antibiotics in their urine were slightly more likely to be blood culture positive for enteric fever; however, the effect was not statistically significant (prevalence ratio, 1.22 [95% confidence interval, .99-1.50]).ConclusionsThe reliability of self-reported prior antibiotic use was modest among individuals presenting with fever to tertiary hospitals. While antibiotics are likely to reduce the sensitivity of blood culture, our findings indicate that there is still considerable value in performing blood culture for individuals reporting antibiotic use.

BackgroundTyphoid fever is endemic in the urban Kathmandu Valley of Nepal; however, there have been no population-based studies of typhoid outside of this community in the past 3 decades. Whether typhoid immunization should be prioritized in periurban and rural communities has been unclear.MethodsWe performed population-based surveillance for enteric fever in 1 urban catchment (Kathmandu) and 1 periurban and rural catchment (Kavrepalanchok) as part of the Surveillance for Enteric Fever in Asia Project (SEAP). We recruited individuals presenting to outpatient and emergency departments at 2 study hospitals with suspected enteric fever and performed blood cultures. Additionally, we conducted a household survey in each catchment area to characterize care seeking for febrile illness. We evaluated spatial heterogeneity in febrile illness, care seeking, and enteric fever incidence.ResultsBetween September 2016 and September 2019, we enrolled 5736 participants with suspected enteric fever at 2 study hospitals. Among these, 304 (5.3%) were culture positive for Salmonella Typhi (249 [81.9%]) or Paratyphi A (55 [18.1%]). Adjusted typhoid incidence in Kathmandu was 484 per 100 000 person-years and in Kavrepalanchok was 615 per 100 000 person-years. While all geographic areas for which estimates could be made had incidence >200 per 100 000 person-years, we observed spatial heterogeneity with up to 10-fold variation in incidence between communities.ConclusionsIn urban, periurban, and rural communities in and around Kathmandu, we measured a high but heterogenous incidence of typhoid. These findings provide some support for the introduction of conjugate vaccines in Nepal, including outside urban areas, alongside other measures to prevent enteric fever.

BackgroundCharacterizing healthcare-seeking patterns for acute febrile illness is critical for generating population-based enteric fever incidence estimates from facility-based surveillance data.MethodsWe 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.ResultsWe 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

Building on previous multicountry surveillance studies of typhoid and others salmonelloses such as the Diseases of the Most Impoverished program and the Typhoid Surveillance in Africa Project, several ongoing blood culture surveillance studies are generating important data about incidence, severity, transmission, and clinical features of invasive Salmonella infections in sub-Saharan Africa and South Asia. These studies are also characterizing drug resistance patterns in their respective study sites. Each study answers a different set of research questions and employs slightly different methodologies, and the geographies under surveillance differ in size, population density, physician practices, access to healthcare facilities, and access to microbiologically safe water and improved sanitation. These differences in part reflect the heterogeneity of the epidemiology of invasive salmonellosis globally, and thus enable generation of data that are useful to policymakers in decision-making for the introduction of typhoid conjugate vaccines (TCVs). Moreover, each study is evaluating the large-scale deployment of TCVs, and may ultimately be used to assess post-introduction vaccine impact. The data generated by these studies will also be used to refine global disease burden estimates. It is important to ensure that lessons learned from these studies not only inform vaccination policy, but also are incorporated into sustainable, low-cost, integrated vaccine-preventable disease surveillance systems.

Oral cholera vaccination (OCV) campaigns are increasingly used to prevent cholera outbreaks; however, little is known about their cost-effectiveness in refugee camps. We conducted a cost-effectiveness analysis of a pre-emptive OCV campaign in the Maela refugee camp in Thailand, where outbreaks occurred with an annual incidence rate (IR) of up to 10.7 cases per 1000. Data were collected via health sector records and interviews and household interviews. In the base-case scenario comparing the OCV campaign with no campaign, we estimated the campaign effect on the cholera IR and case fatality rate (CFR: 0.09%) from a static cohort model and calculated incremental cost-effectiveness ratios for the outcomes of death, disability-adjusted life-years (DALYs), and cases averted. In sensitivity analyses, we varied the CFR and IR. The household economic cost of illness was USD 21, and the health sector economic cost of illness was USD 51 per case. The OCV campaign economic cost was USD 289,561, 42% attributable to vaccine costs and 58% to service delivery costs. In our base case, the incremental cost was USD 1.9 million per death averted, USD 1745 per case averted, and USD 69,892 per DALY averted. Sensitivity analyses that increased the CFR to 0.35% or the IR to 10.4 cases per 1000 resulted in a cost per DALY of USD 15,666. The low multi-year average CFR and incidence of the cholera outbreaks in the Maela camp were key factors associated with the high cost per DALY averted. However, the sensitivity analyses indicated higher cost-effectiveness in a setting with a higher CFR or cholera incidence, indicating when to consider campaign use to reduce the outbreak risk. [ABSTRACT FROM AUTHOR]

BackgroundVaccination has been increasingly promoted to help control epidemic and endemic typhoid fever in high-incidence areas. Despite growing recognition that typhoid incidence in some areas of sub-Saharan Africa is similar to high-incidence areas of Asia, no large-scale typhoid vaccination campaigns have been conducted there. We performed an economic evaluation of a hypothetical one-time, fixed-post typhoid vaccination campaign in Kasese, a rural district in Uganda where a large, multi-year outbreak of typhoid fever has been reported.MethodsWe used medical cost and epidemiological data retrieved on-site and campaign costs from previous fixed-post vaccination campaigns in Kasese to account for costs from a public sector health care delivery perspective. We calculated program costs and averted disability-adjusted life years (DALYs) and medical costs as a result of vaccination, to calculate the cost of the intervention per DALY and case averted.ResultsOver the 3 years of projected vaccine efficacy, a one-time vaccination campaign was estimated to avert 1768 (90%CI: 684-4431) typhoid fever cases per year and a total of 3868 (90%CI: 1353-9807) DALYs over the duration of the immunity conferred by the vaccine. The cost of the intervention per DALY averted was US$ 484 (90%CI: 18-1292) and per case averted US$ 341 (90%CI: 13-883).ConclusionWe estimated the vaccination campaign in this setting to be highly cost-effective, according to WHO's cost-effective guidelines. Results may be applicable to other African settings with similar high disease incidence estimates.

As of 2015, [approximately equal to] 3.2 million internally displaced persons (IDPs) were dispersed throughout Iraq due to increased activity by an armed antigovernment group and subsequent counter-insurgency operations by [...]

Since October 2010, Haiti has endured one of the largest cholera epidemics ever recorded in a single country, accounting for 54% of all cholera cases and 41% of all cholera [...]

Background Cholera remains a public health threat for low- and middle-income countries, particularly in Asia and Africa. Shanchol™, an inactivated oral cholera vaccine (OCV) is currently in use globally. OCV and oral poliovirus vaccines (OPV) could be administered concomitantly, but the immunogenicity and safety of coadministration among children aged 1–3 years is unknown. Methods We undertook an open-label, randomized, controlled, inequality trial in Dhaka city, Bangladesh. Healthy children aged 1–3 years were randomly assigned to 1 of 3 groups: bivalent OPV (bOPV)-alone, OCV-alone, or combined bOPV + OCV and received vaccines on the day of enrollment and 28 days later. Blood samples were collected on the day of enrollment, day 28, and day 56. Serum poliovirus neutralizing antibodies and vibriocidal antibodies against Vibrio cholerae O1 were assessed using microneutralization assays. Results A total of 579 children aged 1‒3 years were recruited, 193 children per group. More than 90% of the children completed visits at day 56. Few adverse events following immunization were recorded and were equivalent among study arms. On day 28, 60% (90% confidence interval: 53%–67%) and 54% (46%–61%) of participants with co-administration of bOPV + OCV responded to polioviruses type 1 and 3, respectively, compared to 55% (47%–62%) and 46% (38%–53%) in the bOPV-only group. Additionally, >50% of participants showed a ≥4-fold increase in vibriocidal antibody titer responses on day 28, comparable to the responses observed in OCV-only arm. Conclusions Co-administration of bOPV and OCV is safe and effective in children aged 1–3 years and can be cost-beneficial. Clinical Trial Registration ClinicalTrials.gov (NCT03581734). [ABSTRACT FROM AUTHOR]

After an absence of over a century, cholera was reported in Haiti on October 22, 2010, in the Artibonite River valley (1). This happened within 9 months of the January [...]