Understanding human exposure to viral haemorrhagic fevers in Uganda: occupational, behavioural, and ecological factors

Kugler, Marina (2026) Understanding human exposure to viral haemorrhagic fevers in Uganda: occupational, behavioural, and ecological factors. PhD thesis, University of Glasgow.

Abstract

Introduction:
Uganda experiences frequent outbreaks of viral haemorrhagic fever viruses (VHFVs), placing healthcare workers (HCWs) and local communities at risk of exposure. Among these, Crimean Congo haemorrhagic fever virus (CCHFV) is a tick-borne zoonotic pathogen that can cause severe haemorrhagic disease with high fatality rates among hospitalised cases. Despite a rise in reported infections over the past decade, the true burden of CCHFV remains underestimated due to mild or misdiagnosed presentations. Understanding the complex interplay of occupational, behavioural, and ecological risk factors is essential for identifying high-risk populations and guiding effective interventions. Previous research has highlighted the importance of geographic variability in exposure risk, yet socioecological determinants remain poorly understood. This thesis aims to address these gaps and increase the knowledge around VHFVs with a focus on CCHFV.

Methods:
The body of work is based on three cohort studies designed to investigate exposure to CCHFV and other VHFVs in Uganda. Firstly, a case-control study was conducted among 639 HCWs and 714 age- and sex-matched community members, to understand occupational risk for VHFV exposure. The study sites comprised hospitals in Gulu, Arua and Kasese districts of Uganda. Serum was tested for Ebola virus (EBOV) and CCHFV seropositivity by ELISA and for Rift Valley fever virus (RVFV) by indirect immunofluorescence. Exposure risk factors were evaluated with a structured survey and analysed by multivariable logistic regression.

A qualitative investigation was next carried out to study human-animal-tick interactions through 24 focus group discussions (FGDs) and 31 key informant interviews (KIIs), in six environmentally and socioecologically diverse districts of Uganda. FGDs were conducted in groups of community leaders, men, women and teenagers. Medical doctors, veterinarians, traditional healers, district surveillance officers, and herdsmen were also interviewed as key informants. Data were translated into English, transcribed, and analysed using iterative categorisation.

The final quantitative cohort study used an analytical framework to estimate seroprevalence in the first four of six selected districts of Uganda as part of an interim analysis of the wider AVI study. 1,059 participants were recruited through multi-level randomisation and stratified by age. Serum samples were collected from each participant, and a structured survey was performed, which was informed by the preceding qualitative research. CCHFV antibody testing was carried out to estimate CCHFV exposure and force of infection (FOI) . Multivariable logistic regression was used to evaluate underlying risk factors.

Results:
Overall, seropositivity in the HCWs study was 16% for EBOV, 19% for CCHFV, and 2% for RVFV seropositivity. The highest odds of exposure were noted in Arua district for both EBOV (AOR = 9.01 [95% CI = 5.48-15.4]) and CCHFV (AOR = 4.67 [95% CI = 3.11-7.13]), around hospitals that had no previously documented cases of VHFVs. Overall, HCWs had a lower odds of EBOV exposure than community members (AOR = 0.37 [95% CI0.26-0.51]), as well as of CCHFV exposure (AOR = 0.42 [95% CI 0.31-0.57]). Homemakers and cleaners had the highest seropositivity for EBOV and CCHFV in the respective study groups.

Thirteen district clusters showed notable differences in climate, land use, proximity to wildlife, and subregional locations within Uganda. Six of these were selected for subsequent qualitative and quantitative cohort studies. Participants from both FGDs and KIIs described distinct living conditions and practices, highlighting regional variation.

The majority of the people that we interviewed as part of our qualitative study experienced tick bites, some as frequently as every day. Close contact with animals was common, including cohabitation, largely due to concerns about animal theft. Less frequent but notable practices included slaughtering animals for consumption or sacrifice, drinking blood, and interactions with wild animals during hunting. Slaughtering and butchering were reported if an animal was unwell or had died. Plucking and roasting engorged ticks for consumption was a practice described in the Kaabong and Arua districts of Northern Uganda.

The quantitative study highlighted varying estimated seroprevalence to CCHFV, ranging from 2.2% in Kaabong district to 18.2% in Kasese district. A multivariable analysis, including known risk factors for CCHFV transmission, revealed significant differences in CCHFV seropositivity between study locations (p = 0.002) and age groups (p < 0.001). The FOI showed an accumulation of seropositivity with age, suggesting constant exposure rather than isolated outbreaks.

Discussion
This PhD demonstrates that exposure to VHFVs in Uganda is extremely high, and is shaped by a complex interplay of ecological, occupational, and behavioural factors. In the HCWs study, seropositivity was highest for CCHFV (19%), followed by EBOV (16%) and RVFV (2%). The unexpectedly high odds of exposure in Arua district, where CCHFV has only very rarely been reported, strongly suggests the presence of mild and/or misdiagnosed cases. Elevated risk among homemakers and cleaners, within community members and HCWs respectively, points to occupational exposures that have been largely overlooked. Qualitative findings, including daily tick bites, animal cohabitation, and practices such as tick collection for consumption, underscore the need for context-specific evaluation of risk behaviours in Uganda’s diverse settings. These behaviours represent possible transmission routes for CCHFV and highlight the importance of future studies to quantify their contribution to infection risk, and to identify targeted and culturally appropriate interventions. The serosurvey revealed significant variation in estimated seroprevalence across surveyed districts (ranging between 2.2% and 18.2%), reinforcing previous findings that study location and, therefore, environmental and geographic factors are key drivers of exposure to CCHFV. These insights can support the identification of high-risk regions and guide targeted control strategies for CCHFV transmission, including the implementation of tick control measures and the prioritisation of future vaccine trials.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: Q Science > QR Microbiology > QR355 Virology
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Funder's Name: Wellcome Trust (WELLCOTR)
• Supervisor's Name: Thomson, Professor Emma, Lamberton, Professor Poppy and Davis, Dr. Chris
• Date of Award: 2026
• Depositing User: Theses Team
• Unique ID: glathesis:2026-85729
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 30 Jan 2026 16:28
• Last Modified: 30 Jan 2026 16:47
• Thesis DOI: 10.5525/gla.thesis.85729
• URI: https://theses.gla.ac.uk/id/eprint/85729

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