ORCID Profile
0000-0003-1886-2699
Current Organisation
University of California Davis
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Publisher: Elsevier BV
Date: 07-2022
Publisher: Elsevier BV
Date: 08-2022
Publisher: Cold Spring Harbor Laboratory
Date: 21-10-2021
DOI: 10.1101/2021.10.20.21265277
Abstract: The incidence of enteric fever, an invasive bacterial infection caused by typhoidal Salmonellae , is largely unknown in regions lacking blood culture surveillance. New serologic markers have proven accurate in diagnosing enteric fever, but whether they could be used to reliably estimate population-level incidence is unknown. We collected longitudinal blood s les from blood culture-confirmed enteric fever cases enrolled from surveillance studies in Bangladesh, Nepal, Pakistan, and Ghana and conducted cross-sectional serosurveys in the catchment areas of each surveillance site. We used ELISAs to measure quantitative IgA and IgG antibody responses to Hemolysin E (HlyE) and S . Typhi lipopolysaccharide (LPS). We used Bayesian hierarchical models to fit two-phase power-function decay models to the longitudinal antibody responses among enteric fever cases and used the joint distributions of the peak antibody titers and decay rate to estimate population-level incidence rates from cross-sectional serosurveys. The longitudinal antibody kinetics for all antigen-isotypes were similar across countries and did not vary by clinical severity. The seroincidence of typhoidal Salmonella infection among children years ranged between 58.5 per 100 person-years (95% CI: 42.1 - 81.4) in Dhaka, Bangladesh to 6.6 (95% CI: 4.3-9.9) in Kavrepalanchok, Nepal, and followed the same rank order as clinical incidence estimates. The approach described here has the potential to expand the geographic scope of typhoidal Salmonella surveillance and generate incidence estimates that are comparable across geographic regions and time. This work was supported by the Bill and Melinda Gates Foundation (INV-000572). Previous studies have identified serologic responses to two antigens (Hemolysin E [HlyE] and Salmonella lipopolysaccharide [LPS]) as promising diagnostic markers of acute typhoidal Salmonella infection. We reviewed the evidence for seroepidemiology tools for enteric fever available as of November 01, 2021, by searching the National Library of Medicine article database and medRxiv for preprint publications, published in English, using the terms “enteric fever”, “typhoid fever”, “ Salmonella Typhi”, “ Salmonella Paratyphi”, “typhoidal Salmonella ”, “Hemolysin E”, “ Salmonella lipopolysaccharide”, “seroconversion”, “serosurveillance”, “seroepidemiology”, “seroprevalence” and “seropositivity.” We found no studies using HlyE or LPS as markers to measure the incidence or prevalence of enteric fever in a population. Anti-Vi IgG responses were used as a marker of population seroprevalence in cross-sectional studies conducted in South Africa, Fiji, and Nepal, but were not used to calculate population-based incidence estimates. We developed and validated a method to estimate typhoidal Salmonella incidence in cross-sectional population s les using antibody responses measured from dried blood spots. First, using longitudinal dried blood spots collected from over 1400 blood culture-confirmed cases in four countries, we modeled the longitudinal dynamics of antibody responses for up to two years following infection, accounting for heterogeneity in antibody responses and age-dependence. We found that longitudinal antibody responses were highly consistent across four countries on two continents and did not differ by clinical severity. We then used these antibody kinetic parameters to estimate incidence in population-based s les in six communities across the four countries, where concomitant population-based incidence was measured using blood cultures. Seroincidence estimates were much higher than blood-culture-based case estimates across all six sites, suggestive of a high incidence of asymptomatic or unrecognized infections. Still, the rank order of seroincidence and culture-based incidence rates were the same, with the highest rates in Bangladesh and lowest in Ghana. Many at-risk low- and middle-income countries lack data on typhoid incidence needed to inform and evaluate vaccine introduction. Even in countries where incidence estimates are available, data are typically geographically and temporally sparse due to the resources necessary to initiate and sustain blood culture surveillance. We found that typhoidal Salmonella infection incidence can be estimated from community-based serosurveys using dried blood spots, representing an efficient and scalable approach for generating the typhoid burden data needed to inform typhoid control programs in resource-constrained settings.
Publisher: Oxford University Press (OUP)
Date: 11-2020
DOI: 10.1093/CID/CIAA1310
Abstract: Implementation 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 s ling approach. A survey was administered to ascertain healthcare-seeking behavior in in iduals 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. Between 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 in iduals. 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. A 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 s ling 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 s ling areas, simplified logistics and could be replicated in future community surveys.
Publisher: Oxford University Press (OUP)
Date: 11-2020
DOI: 10.1093/CID/CIAA1321
Abstract: Characterizing healthcare-seeking patterns for acute febrile illness is critical for generating population-based enteric fever incidence estimates from facility-based surveillance data. 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 in iduals 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 in iduals 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. 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 & 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. 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.
Publisher: Oxford University Press (OUP)
Date: 29-07-2020
DOI: 10.1093/CID/CIAA367
Abstract: 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.
Publisher: Cold Spring Harbor Laboratory
Date: 10-11-2022
DOI: 10.1101/2022.11.07.22282017
Abstract: Scrub typhus is an acute febrile illness caused by the bacterium Orientia tsutsugamushi . Characterizing the population-level burden of scrub typhus is challenging due to the lack of accessible and accurate diagnostics. In this study, we present a novel approach that utilizes information on antibody dynamics after infection to generate population-level scrub typhus seroincidence estimates from cross-sectional serosurveys. We use data from three cohorts of scrub typhus patients enrolled in Chiang Rai, Thailand, and Vellore, India, and representative population data from two serosurveys in and around the Kathmandu valley, Nepal, and Vellore, India. The s les were tested for IgM and IgG responses to Orientia tsutsugamushi -derived recombinant 56-kDa antigen using commercial ELISA kits. We used Bayesian hierarchical models to fit two-phase models to the antibody responses from scrub typhus cases and used the joint distributions of the peak antibody titers and decay rates to estimate population-level incidence rates in the cross-sectional serosurveys. We compared this new method to a traditional cut-off-based approach for estimating seroincidence. Median IgG antibodies persisted above OD 1.7 for 22 months, while IgM displayed longer persistence than expected, with 50% of participants having an OD for 5 months. We estimated an overall seroincidence of 18 per 1000 person-years (95% CI: 16-21) in India and 4 per 1000 person-years (95% CI: 3-6) in Nepal. Among 18 to 29-year-olds, the seroincidence was 8 per 1000 person-years (95% CI 4 -16) in India and 9 per 1000 person-years (95% CI: 6-14) in Nepal. In both India and Nepal, seroincidence was higher in urban and periurban settings compared to rural areas. Compared to our method, seroincidence estimates derived from age-dependent IgG-seroprevalence without accounting for antibody decay underestimated the disease burden by 50%. By incorporating antibody dynamics, the approach described here provides more accurate age-specific infection risk estimates, emphasizing the importance of considering both IgG and IgM decay patterns in scrub typhus seroepidemiology. The sero-surveillance approach developed in this study efficiently generates population-level scrub typhus seroincidence estimates from cross-sectional serosurveys. This methodology offers a valuable new tool for informing targeted prevention and control strategies, ultimately contributing to a more effective response to scrub typhus in endemic regions worldwide.
Publisher: Cold Spring Harbor Laboratory
Date: 16-02-2023
DOI: 10.1101/2023.02.13.23285881
Abstract: Trachoma, caused by ocular Chlamydia trachomatis infection, is targeted for global elimination as a public health problem by 2030. To provide evidence for use of antibodies to monitor C. trachomatis transmission, we collated IgG responses to Pgp3 antigen, PCR positivity, and clinical observations from 19,811 children aged 1– 9 years in 14 populations. We demonstrate that age-seroprevalence curves consistently shift along a gradient of transmission intensity: rising steeply in populations with high levels of infection and active trachoma and becoming flat in populations near elimination. Seroprevalence (range: 0–54%) and seroconversion rates (range: 0–15 per 100 person-years) correlate with PCR prevalence (r: 0.87, 95% CI: 0.57, 0.97). A seroprevalence threshold of 13.5% (seroconversion rate 2.75 per 100 person-years) identifies clusters with any PCR-identified infection at high sensitivity ( %) and moderate specificity (69-75%). Antibody responses in young children provide a robust, generalizable approach to monitor population progress toward and beyond trachoma elimination.
No related grants have been discovered for Kristen Aiemjoy.