Diagnosis of helminths depends on worm fecundity and the distribution of parasites within hosts

Author:

Crellen Thomas123ORCID,Haswell Melissa45ORCID,Sithithaworn Paiboon6ORCID,Sayasone Somphou7ORCID,Odermatt Peter89ORCID,Lamberton Poppy H. L.12ORCID,Spencer Simon E. F.10ORCID,Déirdre Hollingsworth T.3ORCID

Affiliation:

1. School of Biodiversity One Health and Veterinary Medicine, Graham Kerr Building, University of Glasgow, 82 Hillhead Street, Glasgow G12 8QQ, UK

2. Wellcome Centre for Integrative Parasitology, Sir Graeme Davies Building, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK

3. Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7LF, UK

4. Office of the Deputy Vice Chancellor, Indigenous Strategy and Services and School of Geosciences, John Woolley Building, University of Sydney, Sydney, New South Wales 2050, Australia

5. School of Public Health and Social Work, Kelvin Grove Campus, Queensland University of Technology, Brisbane City, Queensland 4000, Australia

6. Department of Parasitology, Khon Kaen University, 123 Thanon Mittraphap, Khon Kaen 40002, Thailand

7. Lao Tropical and Public Health Institute, Samsenthai Road, Sisattanak district, Vientiane, Lao PDR

8. Department of Public Health and Epidemiology, Swiss Tropical and Public Health Institute, Kreuzstrasse 2, Allschwil 4123, Switzerland

9. University of Basel, Petersplatz 1, Basel 4001, Switzerland

10. Department of Statistics, University of Warwick, Coventry CV4 7AL, UK

Abstract

Helminth transmission and morbidity are dependent on the number of mature parasites within a host; however, observing adult worms is impossible for many natural infections. An outstanding challenge is therefore relating routine diagnostics, such as faecal egg counts, to the underlying worm burden. This relationship is complicated by density-dependent fecundity (egg output per worm reduces due to crowding at high burdens) and the skewed distribution of parasites (majority of helminths aggregated in a small fraction of hosts). We address these questions for the carcinogenic liver flukeOpisthorchis viverrini, which infects approximately 10 million people across Southeast Asia, by analysing five epidemiological surveys (n= 641) where adult flukes were recovered. Using a mechanistic model, we show that parasite fecundity varies between populations, with surveys from Thailand and Laos demonstrating distinct patterns of egg output and density-dependence. As the probability of observing faecal eggs increases with the number of mature parasites within a host, we quantify diagnostic sensitivity as a function of the worm burden and find that greater than 50% of cases are misdiagnosed as false negative in communities close to elimination. Finally, we demonstrate that the relationship between observed prevalence from routine diagnostics and true prevalence is nonlinear and strongly influenced by parasite aggregation.

Funder

Wellcome Trust

Publisher

The Royal Society

Subject

General Agricultural and Biological Sciences,General Environmental Science,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

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