Development of a novel Guinea pig model that mimics human relapsing fever disease.

Relapsing fever (RF) Borrelia are vector-borne pathogens that cause severe clinical manifestations. While RF Borrelia can be transmitted by lice and hard ticks, soft ticks transmit most RF Borrelia species. The unique biology of soft ticks causes concerns for future RF outbreaks. While soft ticks have three developmental stages, which is similar to hard ticks, they also have 2-7 instar nymphal stages and can feed multiple times as adults resulting in a 10–20-year life span. RF Borrelia are maintained in the tick through the molt to each new life stage and can be transovarially transmitted from mother to offspring creating >10 opportunities for a single tick to transmit a RF Borrelia infection. In humans, RF Borrelia repeatedly reach high densities in the blood (spirochetemia) and cause recurring febrile illness, neurologic complications, and perinatal death. Upon initiation of antibiotic treatment, 30-50% of patients experience an acute exacerbation of symptoms known as Jarisch- Herxheimer reaction (JHR). Unfortunately, due to the lack of a cost-effective animal model that mimics human RF disease, we do not understand the mechanisms leading the severe clinical manifestations caused by RF Borrelia. Mice are the most commonly used animals to study RF Borrelia infection and pathogenesis, but mice are a limited disease model because they do not become hyperthermic during RF Borrelia infection. Nonhuman primates develop fever during periods of spirochetemia, but are too expensive to routinely use for rigorous studies. In this R03 application, we propose to develop the Guinea pig model to study RF disease. A historical study described Guinea pigs as viable hosts for Borrelia hermsii and Borrelia turicatae, the two Borrelia species that cause the most RF disease in North America. Both B. hermsii and B. turicatae repeatedly reached high densities in Guinea pig blood, and Guinea pigs become hyperthermic during spirochetemic episodes. Due to a lack of follow-up studies, the RF Borrelia-Guinea pig model remains largely uncharacterized in terms of pathogenesis, disease pathology, and JHR development. We hypothesize Guinea pigs will model human RF disease by inducing hyperthermia during spirochetemic episodes, producing pro-inflammatory cytokines during infection, and developing signs of JHR following antibiotic administration. To test this, we will assess B. hermsii and B. turicatae pathogenesis in Guinea pigs through quantification of spirochetemia, asses clinical signs of RF disease by measuring weight loss and body temperature of Guinea pigs and quantify cytokine production and tissue damage caused by B. hermsii and B. turicatae infection (Aim 1). We will also evaluate the development of JHR in Guinea pigs by measuring body temperature and quantifying cytokine levels after antibiotic treatment (Aim 2). Our thorough characterization of the RF Borrelia-Guinea pig model is critical to finding a relevant animal model to perform mechanistic and intervention studies to help mitigate the severe clinical manifestations cause by RF Borrelia. Project Number: 1R03AI196485-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Allergy and Infectious Diseases (NIAID) | Principal Investigator: Michael Curtis | Institution: BAYLOR COLLEGE OF MEDICINE, HOUSTON, TX | Award Amount: $160,500 | Activity Code: R03 | Study Section: Special Emphasis Panel[ZRG1 IIDB-N (80)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R03AI19648501