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Background: Growing evidence from East Africa indicates that zoonotic diseases are substantially under diagnosed and under reported, and aetiologies of acute undifferentiated fever (AUF) are often wrongly assumed to be malaria. The associated morbidity, mortality and health care costs of febrile illnesses is made worse by the current limitations of available diagnostic tools and inappropriate use of antimicrobials. Zoonotic diseases, such as leptospirosis, and rickettsial diseases are often misdiagnosed in health care settings and the evidence-base to inform national treatment guidelines is lacking in many African countries. The potentially life-threatening leptospirosis and rickettsiosis are treatable with doxycycline; for rickettsiosis commonly used broad-spectrum beta-lactam antibiotics have no effect.
The objectives of the project are:
(1) To determine the prevalence of, and risk factors for leptospirosis and rickettsiosis in patients visiting a regional hospital in Hoima, Uganda;
(2) To validate and apply point-of-care diagnostics of leptospirosis and rickettsiosis against reference tests;
(3) To identify the Leptospira species circulating among AUF patients by DNA barcoding and whole genome sequencing
Approach and methods: To determine prevalence as well as risk factors for leptospiral and rickettsial illness, patients (n=500) will be recruited over one year in a hospital-based, prospective cross-sectional febrile illness study at Hoima, Western Uganda. We will collect laboratory samples (serum, whole blood and urine) clinical and epidemiological data from hospitalized patients and perform point-of-care (POC) and reference diagnostics. Leptospira species circulating among patients with AUF will be characterized by whole-genome sequencing and left-over samples will be biobanked for future testing of other AUF causing pathogens, such as brucellosis, Q-fever and viruses.
Expected results: The study will serve as a proof-of-concept, providing a high-quality evidence-base for the role of leptospirosis and rickettsiosis in human febrile illnesses in Uganda, identifying case numbers, potential risk factors and potential transmission routes of both pathogens. Additionally, the validation and introduction of a POC rapid diagnostic test (RDT) will support Ugandan clinicians to improve diagnostic certainty for these conditions.
Impact: The project will result in enhanced awareness, improved diagnostic capacity and better understanding of the burden of febrile illnesses of zoonotic origin. Ultimately, these results will improve patient outcomes at the health care level by improving treatment algorithms leading to more people being treated in a timely manner and cured and reducing morbidity and mortality. Accurate diagnosis avoids unnecessary presumptive use of antimalarials and antibiotics potentially reducing the risk for adverse drug reactions, drug-drug interactions, the emergence of drug resistance and generate financial savings from reduced waste on overused drugs. The study will identify risk factors and document behaviours (i.e. contact to wild or domestic animals), provide new information on risky occupational exposures (e.g. rice paddy fields, animal slaughter houses, milking), as well as water sources (i.e. wells, rivers) and particularities around residence in endemic areas (i.e. living in a slum area) among fever patients. Sequencing/bar coding leptospiral DNA will contribute to a conceptual framework that can be used for leptospirosis surveillance, as well as support investigation of transmission pathways and virulence factors, and awareness to reduce transmission and improve control. This multidisciplinary team-oriented international collaboration between Ugandan and Swiss scientists, MSc and PhD students will focus on enhancing knowledge exchange and mutual learning, as well as strengthening scientific capacity in research communities both in Uganda and Switzerland. This network will enable further collaborations and research in the medical and veterinary field. Results will be published and disseminated in the communities.
