Estimating typhoid incidence from community-based serosurveys: a multicohort study

Aiemjoy, Kristen; Seidman, Jessica C.; Saha, Senjuti; Munira, Sira Jam; Sajib, Mohammad Saiful Islam; Sium, Syed Muktadir Al; Sarkar, Anik; Alam, Nusrat; Zahan, Farha Nusrat; Kabir, Md Shakiul; Tamrakar, Dipesh; Vaidya, Krista; Shrestha, Rajeev; Shakya, Jivan; Katuwal, Nishan; Shrestha, Sony; Yousafzai, Mohammad Tahir; Iqbal, Junaid; Dehraj, Irum F; Ladak, Yasmin; Maria, Noshi; Adnan, Mehreen; Pervaiz, Sadaf; Carter, Alice S.; Longley, Ashley T; Fraser, Clare; Ryan, Edward T.; Nodoushani, Ariana; Fasano, Alessio; Leonard, Maureen M.; Kenyon, Victoria; Bogoch, Isaac I.; Jeon, Hyon Jin; Haselbeck, Andrea; Park, Se Eun; Zellweger, Raphaël M.; Marks, Florian; Owusu‐Dabo, Ellis; Adu‐Sarkodie, Yaw; Owusu, Michael; Teunis, Peter; Luby, Stephen P.; Garrett, Denise O; Qamar, Farah Naz; Saha, Samir K.; Charles, Richelle C.; Andrews, Jason R

doi:10.1016/s2666-5247(22)00114-8

Cited by 26 publications

(30 citation statements)

References 35 publications

(56 reference statements)

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“…We expect seroincidence to be higher than clinical incidence because it captures subclinical infections and is independent of a person's ability to access and afford healthcare, including diagnostic tests. Indeed, the enteric fever seroincidence rate for Juba is on the same scale of magnitude as recent estimates using the same approach in Nepal, Pakistan, Bangladesh, and Ghana (12).…”

Section: Discussionsupporting

confidence: 55%

“…Finally, we used longitudinal antibody kinetics estimates from enteric fever cases in Bangladesh, Pakistan, Nepal, and Ghana. We did not observe major differences in the kinetics of antibody responses across countries (12), but the decay rate among enteric fever cases in Juba may be different because of the high force of infection and differences in exposure to other infections.…”

Section: Discussioncontrasting

confidence: 55%

“…IQR, interquartile range. in(12) and a control population from 3 United States groups: 48 children 1-5 years of age who had first degree relatives with celiac disease, enrolled nationally; 31 healthy controls, children and young adults 2-18 years of age, enrolled at Massachusetts General Hospital (17); and a population-based sample of 205 children and adults 3-50 years of age participating in a SARS-CoV serosurvey in California, USA. The dashed blue line across all panels represents the mean +3 SD of HlyE IgA and IgG values observed in the pediatric control population.…”

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confidence: 99%

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Seroincidence of Enteric Fever, Juba, South Sudan

Aiemjoy¹,

Rumunu²,

Hassen³

et al. 2022

Emerg. Infect. Dis.

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E nteric fever, caused by Salmonella enterica serovars Typhi and Paratyphi, causes substantial illness and death globally (1). However, estimating the population-level burden of infection is challenging. Blood culture, the standard for both diagnosis and surveillance, requires microbiological laboratory facilities that are not available in many low-and-middle-income countries. Challenges in accessing blood culture, along with an estimated diagnostics sensitivity of only 60% (2), contribute to chronic underdetection (3).Juba, the capital of South Sudan, experiences a high burden of enteric infections such as cholera and hepatitis E virus (4,5). Enteric fever is a frequently diagnosed etiology of acute fever, but few laboratories have blood culture capacity for confirmation. Consequentially, the population-level burden of enteric fever is unknown.Hemolysin E (HlyE), a pore-forming toxin, is a sensitive and specific serologic marker for diagnosing typhoidal Salmonella (6-10) and is not associated with typhoid carriage (11). New serologic and analytic tools enable measurement of population-level enteric fever incidence from cross-sectional serosurveys using HlyE IgG and IgA (12). We applied those tools to generate population-level enteric fever seroincidence estimates in Juba. The StudyWe used dried blood spots (DBS) collected for a SARS-CoV-2 serosurvey in Juba, South Sudan, enrolled during August 7-September 20, 2020; enrollment and sampling methods are described elsewhere (13). In brief, 2-stage cluster sampling was used to randomly select households from predefined enumeration units from 6 administrative divisions within and surrounding Juba; all persons >1 year of age and residing for >1 week within the sampled household were eligible to participate. Capillary blood was collected onto Whatman 903 Protein Saver cards (Sigma-Aldrich, https:// www.sigmaaldrich.com), air dried, and transported at ambient temperature to Massachusetts General Hospital (Boston, MA, USA), where they were stored at 4°C. We tested all banked samples collected from participants <25 years of age and a random sample of participants >25 years of age. Younger participants were prioritized because they matched the age distribution of typhoid case data used for the seroincidence estimation ( 12). The study protocol was approved by ethical review boards with the South Sudan Ministry of Health and Massachusetts General Hospital.We used kinetic ELISAs to quantify HlyE IgA and IgG levels in eluted DBS as described (7,11). To estimate seroincidence, we used the antibody dynamics from a longitudinal cohort of 1,420 blood culture-confirmed enteric fever cases (12). In brief, we created a likelihood function for observed crosssectional population antibody response data based on antibody dynamics after blood-culture confirmed infection. We generated joint incidence estimates by

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Section: Discussionsupporting

confidence: 55%

Section: Discussioncontrasting

confidence: 55%

mentioning

confidence: 99%

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Seroincidence of Enteric Fever, Juba, South Sudan

Aiemjoy¹,

Rumunu²,

Hassen³

et al. 2022

Emerg. Infect. Dis.

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“…New approaches to serological surveillance using novel serological markers of infection and/or carriage (such as HlyE and CdtB) are being validated in multiple sites where blood culture surveillance is also ongoing and appear promising [10 ▪▪ ,11]. Approaches to validating standardized methods for detection of S .…”

Section: Improved Diagnostics For Surveillancementioning

confidence: 99%

Typhoid fever control in the 21st century: where are we now?

Carey

McCann

Gibani

2022

Current Opinion in Infectious Diseases

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Purpose of reviewMomentum for achieving widespread control of typhoid fever has been growing over the past decade. Typhoid conjugate vaccines represent a potentially effective tool to reduce the burden of disease in the foreseeable future and new data have recently emerged to better frame their use-case.Recent findingsWe describe how antibiotic resistance continues to pose a major challenge in the treatment of typhoid fever, as exemplified by the emergence of azithromycin resistance and the spread of Salmonella Typhi strains resistant to third-generation cephalosporins. We review efficacy and effectiveness data for TCVs, which have been shown to have high-level efficacy (≥80%) against typhoid fever in diverse field settings. Data from randomized controlled trials and observational studies of TCVs are reviewed herein. Finally, we review data from multicountry blood culture surveillance studies that have provided granular insights into typhoid fever epidemiology. These data are becoming increasingly important as countries decide how best to introduce TCVs into routine immunization schedules and determine the optimal delivery strategy.SummaryContinued advocacy is needed to address the ongoing challenge of typhoid fever to improve child health and tackle the rising challenge of antimicrobial resistance.

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“…In Thailand, hospitalized patients >15 years old with acute fever duration <2 weeks were recruited from a fever surveillance study in Prachanukhao Hospital in Chiang Rai, Thailand (10,11). Nepal (periurban and rural) (12). Within catchment areas, we randomly selected geographically defined grid clusters and enumerated all households in each cluster.…”

Section: Study Populations and Enrollmentmentioning

confidence: 99%

Estimating the seroincidence of scrub typhus using antibody dynamics following infection

Aiemjoy

Kutawal

Vaidya

et al. 2022

Preprint

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Introduction: 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. We describe a new approach using information about seroresponse after infection to generate population-level scrub typhus seroincidence estimates. Methods: We use data from two clinical studies 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 samples 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. Results: Among 18 to 29-year-olds, the seroincidence of scrub typhus was 886 (95% CI 432-1817) per 100,000 person-years in India and 945 (95% CI: 616-1449) per 100,000 in Nepal. Seroincidence rose with age, reaching a rate of 3231 (95% CI: 2630-3969) per 100,000 among 50 to 89-year-olds in Vellore, India. The seroincidence rates estimated using a cutoff were half the rates we estimated using antibody dynamics. Conclusion: The approach described here can be deployed prospectively, coupled with existing serosurveys, or leverage banked samples to rapidly characterize scrub typhus burden and generate scrub typhus seroincidence estimates that are comparable across populations, regions, and time.

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Estimating typhoid incidence from community-based serosurveys: a multicohort study

Cited by 26 publications

References 35 publications

Seroincidence of Enteric Fever, Juba, South Sudan

Seroincidence of Enteric Fever, Juba, South Sudan

Typhoid fever control in the 21st century: where are we now?

Estimating the seroincidence of scrub typhus using antibody dynamics following infection

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