Abstract
Burkholderia pseudomallei is the causative agent of melioidosis, which is a Gram negative, facultative intracellular bacterium. Disease is prevalent in SE Asia and in northern Australia, as well as in other tropical and subtropical regions. Recently, there is an increasing awareness of the importance of bacterial ingestion as a potential route of infection, particularly in cases of unexplained origin of the disease. The marmoset is a New World Monkey (NWM) species that is being developed as an alternative NHP model to complement the more traditionally used Old World Monkeys (OWM). Models have been developed for the traditional routes of disease acquisition, subcutaneous and inhalational. This manuscript details the development and characterisation of an ingestion model of melioidosis. Dose-ranging study assessed the lethality of B. pseudomallei and disease progression was assessed by euthanizing animals at predetermined time points, 12, 36, 48 and 54 hours post-challenge. Challenge doses of greater than 6.2 x 106 cfu resulted in an acute, lethal, febrile disease. Following challenge the lung was the first organ, outside of the gastrointestinal tract, to become colonised. Enteritis (duodenitis, ileitis and/or jejunitis) was observed in sections of the small intestine from animals that succumbed to disease. However, the most severe pathological features were observed in the mesenteric lymph nodes from these animals. These findings are consistent with lymphatic draining as route of dissemination.
Highlights
Burkholderia pseudomallei is the causative agent of melioidosis, which is a Gram negative, facultative intracellular bacterium that is classified as a as HHS/CDC Tier 1 agents (7 CFR Part 331, 9 CFR Part 121, and 42 CFR Part 73)
All data is from Study 2, natural history study, except for the “Terminal” timepoint where data from animal’s challenged with either 6.2 or 6.8 x 106 cfu of B. pseudomallei has been included for comparison
This study has shown that elevation of CD64+ in blood is linked to disease, and is significantly increased before the animals show clinical signs
Summary
Burkholderia pseudomallei is the causative agent of melioidosis, which is a Gram negative, facultative intracellular bacterium that is classified as a as HHS/CDC Tier 1 agents (7 CFR Part 331, 9 CFR Part 121, and 42 CFR Part 73). Disease is prevalent in SE Asia and in northern Australia but is increasingly becoming a major cause of morbidity and mortality in other tropical and subtropical countries [1]. Disease presentation and mortality is believed to be associated with a number of parameters including bacterial strain, inoculation dose, route of entry and host factors [3,4]. B. pseudomallei has been isolated from drinking water in both Thailand and Northern Australia [5]. There is a high correlation between presence of bacteria in the drinking water and acquisition of melioidosis by ingestion [6]. Ingestion of the bacteria is suggested to be the cause of the incidence of melioidosis-related parotitis in children in Thailand, and possibly other parts of south east Asia, that is not observed in Australia [7,8]. Incidence of ingestion in animals is highly suspected, and parotid infection has been observed in pigs that drank water from infected bore holes [9]
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