Dissertation
Epidemiological methods to evaluate the surveillance and the immunopathology of vector-borne diseases
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Spring 2022
DOI: 10.17077/etd.006383
Abstract
Visceral leishmaniasis (VL), caused by Leishmania infantum and L. donovani, is the most severe form of Leishmaniasis, with an estimated 95% case fatality rate if left untreated. An estimated 50,000 to 90,000 new cases of VL occur worldwide annually, with an estimated 25 – 45% of cases reported to the WHO. Dogs act as reservoir hosts for Leishmania protozoal parasite, retaining transmission in an endemic area regardless of human-specific interventions. Chapters II and III of the present dissertations provide critical data and analyses that will improve our ability to detect, and estimate based on immunological changes, the outcome of VL within this key reservoir host. Chapter III provides valuable insight into the role previously unrecognized tick vectors may have in transmission of Babesiosis, a re-emerging zoonotic tick-borne disease caused by the Babesia spp. parasite.
Like human VL, canines infected with L. infantum can remain relatively healthy for years before developing severe and fatal disease. Therefore, understanding and accurately diagnosing L. infantum infection in dogs is essential for the protection of both human and animal health. We work to establish the accuracy, sensitivity, and specificity of enzyme-linked immunosorbent assays (ELISA), and the immunofluorescence antibody test (IFAT) across the pan-Mediterranean region. We performed a known sample testing “ring” study to compare each location’s Leishmania diagnostic test(s). Using Latent Class Analysis (LCA), we established those European diagnostic veterinary laboratories had highly sensitive and specific diagnostic tests capable of accurately identifying dogs infected with L. infantum. This study found that sensitivity and specificity for the ELISA diagnostics ranged from 94% to 98%, and 95% to 99% respectively. Sensitivity and specificity for the IFAT diagnostics ranged from 86% to 100% and 76% to 98% respectively. The overall agreement of Leishmania serology across the seven laboratories was 76%, with a pair-wise range between 60% and 89%. There was substantial comparative diagnostic precision and accuracy across study site. This study has highlighted the strength of using an objective epidemiologic method to evaluate diagnostic tests in the absence of a gold standard.
Despite promising evidence regarding the interchangeable accuracy of VL detection tests across the Europe and the pan-Mediterranean region, L. infantum infections do not occur in isolation. Our work suggests that dogs that progress to clinical leishmaniosis were frequently co-infected with other infectious diseases. Little is known regarding the immunological mechanisms by which tick-borne disease exposure promotes progression to clinical VL. Understanding the immunological mechanism of disease can help improve our ability to detect and control canine and human VL. We used Bayesian mediation analyses to measure the mediating effects of the protective immune response on VL progression following a tick-borne pathogen exposure. Notably, an increase in time point was significantly (odds ratio: 14.06, 95% credible interval: 2.97 – 76.94) associated with progression of VL in hunting dogs. To our knowledge this is the first-time mediation analysis has been employed to a complex immunologic model.
One of these frequent co-infections, which is emerging in the US, but with limited understanding, is Babesiosis. To better understand transmission of Babesia spp., we evaluated Rhipicephalus sanguineus and Dermacentor variabilis ticks as likely vectors. Establishing which tick species are transmitting Babesia spp. across the US, will allow public health entities to better track the prevalence and spread of Babesiosis. We identified Babesia spp. DNA in both R. sanguineus, Dermacentor variabilis, thus, highlighting an important potential vector for Babesiosis.
In summary, the present work suggests that the ELISA and IFAT performed by the veterinary diagnostic laboratories across Europe have very high concordance across sites. Additionally, this dissertation laid foundational groundwork for the exploration of the complexity of a host immune system as a causal factor regarding why there is progression to severe VL following tick-borne pathogen exposure. Finally, we have established a connection between Rhipicephalus sanguineus and Dermacentor variabilis as potential vectors for Babesiosis.
Details
- Title: Subtitle
- Epidemiological methods to evaluate the surveillance and the immunopathology of vector-borne diseases
- Creators
- Kurayi Mahachi
- Contributors
- Christine Petersen (Advisor)James Torner (Committee Member)Jacob Oleson (Committee Member)Mary Wilson (Committee Member)Noah Butler (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Epidemiology
- Date degree season
- Spring 2022
- Publisher
- University of Iowa
- DOI
- 10.17077/etd.006383
- Number of pages
- xiii, 147 pages
- Copyright
- Copyright 2022 Kurayi Mahachi
- Language
- English
- Description illustrations
- illustrations (chiefly color), maps, tables, graphs
- Description bibliographic
- Includes bibliographical references (pages 114-141).
- Public Abstract (ETD)
- Using complex epidemiological methods, this work provides critical insights to improve our ability to detect and estimate the outcome of Leishmania infections, a disease with 95% mortality rate if left untreated. Additionally, using public health entomology techniques I determine the role of previously unrecognized ticks-vectors in the transmission of Babesiosis, a re-emerging zoonotic tick-borne illness. Finally, by examining the diagnosis, transmission, and immunology of these tick-borne diseases the present work significantly advances our capacity for prevention and treatment.
- Academic Unit
- Epidemiology
- Record Identifier
- 9984270953502771
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