Susceptibility of African Green Monkeys (Chlorocebus aethiops sabaeus) to Rickettsia felis, the agent of flea-borne spotted fever

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Flea-borne spotted fever (FBSF) caused by Rickettsia felis, a Gram -ve intracellular bacterium, is a recently described (1994) emerging disease of people that has now been described worldwide. The cat flea is the confirmed biological vector and reservoir although ticks and mosquitoes can harbor R. felis. Since clinical signs of FBSF are non-specific and infections can be asymptomatic, there might be considerable underreporting of the disease. Nevertheless, infections, as determined by PCR of blood, are particularly common in febrile patients in countries in Africa and Asia. To date R. felis has not been isolated from the blood of a FBSF patient. As a newly described disease there are many questions relating to FBSF, including the possibility of other vectors, the pathogenesis and immune responses to infection, and even as to whether R. felis might not be pathogenic and detected only as a symbiont of a human parasite or protozoan. These questions will be resolved as further patient data slowly accumulates and clinical trials may be carried out. However, an appropriate animal model would greatly facilitate and accelerate the investigation of the unanswered questions surrounding FBSF. Unfortunately, the only information on infections in animals, from cats, dogs, guinea pigs, mice, opossums, and rats, indicate none are suitable models. The most likely animal model should be a non-human primate (NHP) as they are more closely related, anatomically and physiologically, to humans. To date the only data on R. felis in NHPs is that the organism can be found in their feces. The aim of our study is to determine if African green monkeys (Chlorocebus aethiops sabaeus) (AGMs) are susceptible to experimental infection (intravenous inoculation) with the LSU strain of R. felis. After infection, AGMs will be monitored for clinical signs, rickettsemia by PCR and culture, antibody responses, and body organ damage and dysfunction. Only the minimum number of animals required to meet the aim of the study will be used, and these will be housed in open-air, dedicated facilities that are insect-proof but closely mirror their natural environment at the study site on the Caribbean island of St Kitts. AGMs that develop severe signs will be given doxycycline, the antibiotic recommended for treatment in people, which will enable a detailed examination of the drug’s efficacy. If AGMs develop very severe signs with a poor prognosis, they will be humanely euthanized and necropsied to determine the pathogenesis of infections. If the AGMs are found susceptible, the data from the study will help researchers to decide if AGMs are suitable models of R. felis infections that can be used in future pathogenesis, transmission, diagnosis, and/or treatment studies.