Estimating the Seroincidence of Scrub Typhus using Antibody Dynamics after Infection

Kristen Aiemjoy Department of Public Health Sciences, University of California Davis School of Medicine, Davis, California;
Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;

Search for other papers by Kristen Aiemjoy in
Current site
Google Scholar
PubMed
Close
,
Nishan Katuwal Dhulikhel Hospital, Kathmandu University Hospital, Dhulikhel, Nepal;

Search for other papers by Nishan Katuwal in
Current site
Google Scholar
PubMed
Close
,
Krista Vaidya Department of Public Health Sciences, University of California Davis School of Medicine, Davis, California;

Search for other papers by Krista Vaidya in
Current site
Google Scholar
PubMed
Close
,
Sony Shrestha Dhulikhel Hospital, Kathmandu University Hospital, Dhulikhel, Nepal;

Search for other papers by Sony Shrestha in
Current site
Google Scholar
PubMed
Close
,
Melina Thapa Dhulikhel Hospital, Kathmandu University Hospital, Dhulikhel, Nepal;

Search for other papers by Melina Thapa in
Current site
Google Scholar
PubMed
Close
,
Peter Teunis Center for Global Safe Water, Sanitation and Hygiene, Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia;

Search for other papers by Peter Teunis in
Current site
Google Scholar
PubMed
Close
,
Isaac I. Bogoch Department of Medicine, University of Toronto, Toronto, Ontario, Canada;

Search for other papers by Isaac I. Bogoch in
Current site
Google Scholar
PubMed
Close
,
Paul Trowbridge Michigan State University College of Human Medicine, Grand Rapids, Michigan;

Search for other papers by Paul Trowbridge in
Current site
Google Scholar
PubMed
Close
,
Stuart D. Blacksell Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;
Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom;

Search for other papers by Stuart D. Blacksell in
Current site
Google Scholar
PubMed
Close
,
Daniel H. Paris Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;
Department of Medicine, Swiss Tropical and Public Health Institute, Basel, Switzerland;
Department of Clinical Research, University of Basel, Switzerland;

Search for other papers by Daniel H. Paris in
Current site
Google Scholar
PubMed
Close
,
Tri Wangrangsimakul Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;

Search for other papers by Tri Wangrangsimakul in
Current site
Google Scholar
PubMed
Close
,
George M. Varghese Department of Infectious Diseases, Christian Medical College, Vellore, India;

Search for other papers by George M. Varghese in
Current site
Google Scholar
PubMed
Close
,
Richard J. Maude Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;
Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom;
The Open University, Milton Keynes, United Kingdom;
School of Public Health, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong;

Search for other papers by Richard J. Maude in
Current site
Google Scholar
PubMed
Close
,
Dipesh Tamrakar Dhulikhel Hospital, Kathmandu University Hospital, Dhulikhel, Nepal;

Search for other papers by Dipesh Tamrakar in
Current site
Google Scholar
PubMed
Close
, and
Jason R. Andrews Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, California

Search for other papers by Jason R. Andrews in
Current site
Google Scholar
PubMed
Close
Restricted access

Scrub typhus, a vector-borne bacterial infection, is an important but neglected disease globally. Accurately characterizing the burden is challenging because of nonspecific symptoms and limited diagnostics. Prior seroepidemiology studies have struggled to find consensus cutoffs that permit comparisons of estimates across contexts and time. In this study, we present a novel approach that does not require a cutoff and instead uses information about antibody kinetics after infection to estimate seroincidence. We use data from three cohorts of scrub typhus patients in Chiang Rai, Thailand, and Vellore, India, to characterize antibody kinetics after infection and two population serosurveys in the Kathmandu Valley, Nepal, and Tamil Nadu, India, to estimate seroincidence. The samples were tested for IgM and IgG responses to Orientia tsutsugamushi-derived recombinant 56-kDa antigen using commercial enzyme-linked immunosorbent assay kits. We used Bayesian hierarchical models to characterize antibody responses after scrub typhus infection and used the joint distributions of the peak antibody titers and decay rates to estimate population-level incidence rates in the cross-sectional serosurveys. Median responses persisted above an optical density (OD) of 1.8 for 23.6 months for IgG and an OD of 1 for 4.5 months for IgM. Among 18- to 29-year-olds, the seroincidence was 10 per 1,000 person-years (95% CI, 5–19) in Tamil Nadu, India, and 14 per 1,000 person-years (95% CI: 10–20) in the Kathmandu Valley, Nepal. When seroincidence was calculated with antibody decay ignored, the disease burden was underestimated by more than 50%. The approach can be deployed prospectively, coupled with existing serosurveys, or leverage banked samples to efficiently generate scrub typhus seroincidence estimates.

    • Supplemental Materials (PDF 768.61 KB)

Author Notes

Financial support: This work was supported by grants from the National Institutes of Health Fogarty International Center (FIC) (grant number K01 TW012177), the National Institute of Allergy and Infectious Diseases (NIAID) (grant number R21 1AI176416) to K. Aiemjoy, a Stanford University Global Health Seed Grant to K. Aiemjoy and J. R. Andrews, and the Wellcome Trust (grant number 220211) to S. Blacksell. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Disclosures: Institutional Review Boards in India (Christian Medical College, Vellore), Thailand (Chiang Rai Hospital, the Faculty of Tropical Medicine, Mahidol University, and the Thai Ministry of Public Health), the United States (Stanford University Institutional Review Board), and Nepal (Nepal Health Research Council Ethical Review Board) approved the study forms and protocols. Formal consent was obtained from all participants.

Authors’ addresses: Kristen Aiemjoy, Division of Epidemiology, Department of Public Health Sciences, University of California Davis School of Medicine, Davis, CA, and Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. E-mail: kaiemjoy@ucdavis.edu. Nishan Katuwal, Sony Shrestha, Melina Thapa, and Dipesh Tamrakar, Dhulikhel Hospital, Kathmandu University Hospital, Dhulikhel, Nepal, E-mails: nishankatuwal07@gmail.com, me.sonyshrestha11@gmail.com, melinathapa033@gmail.com, and dipesht@kusms.edu.np. Krista Vaidya, Department of Public Health Sciences, University of California Davis School of Medicine, Davis, CA, E-mail: kvaidya@ucdavis.edu. Peter Teunis, Center for Global Safe Water, Sanitation and Hygiene, Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, E-mail: p.teunis@emory.edu. Isaac I. Bogoch, Department of Medicine, University of Toronto, Toronto, Ontario, Canada, E-mail: isaac.bogoch@uhn.ca. Paul Trowbridge, Michigan State University College of Human Medicine, Grand Rapids, MI, E-mail: ptrowb@hotmail.com. Stuart D. Blacksell and Tri Wangrangsimakul, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, E-mails: stuart@tropmedres.ac and tri@tropmedres.ac. Daniel H. Paris, Department of Medicine, Swiss Tropical and Public Health Institute, Basel, Switzerland, Department of Clinical Research, University of Basel, Switzerland, E-mail: daniel.paris@swisstph.ch. George M. Varghese, Department of Infectious Diseases, Christian Medical College, Vellore, India, E-mail: georgemvarghese@hotmail.com. Richard J. Maude, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom, The Open University, Milton Keynes, United Kingdom, and School of Public Health, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, E-mail: richard@tropmedres.ac. Jason R. Andrews, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA, E-mail: jandr@stanford.edu.

Address correspondence to Kristen Aiemjoy, Division of Epidemiology, Department of Public Health Sciences, University of California Davis School of Medicine, Davis, CA 94305. E-mail: kaiemjoy@ucdavis.edu
Save