Pathogenesis of percutaneous infection of goats with Burkholderia pseudomallei: clinical, pathologic, and immunological responses in chronic melioidosis

Abstract

Melioidosis is a severe suppurative to granulomatous infection caused by Burkholderia pseudomallei. The disease is endemic to South-East Asia and Northern Australasia and is also of interest as a potential biological weapon. Natural infection can occur by percutaneous inoculation, inhalation or ingestion, but the relative importance of each route is unknown. Experimental infection models using mice have shown inhalation to be the most lethal route of exposure, but few studies have examined the pathogenesis of percutaneous infection despite its presumptive importance in natural disease. Caprine models are useful in the study of melioidosis because goats are susceptible to natural infection by B. pseudomallei, display similar epizootiology/epidemiology to that of humans within the endemic range and develop similar pathologic lesions. Percutaneous inoculation with 10(4) CFU of B. pseudomallei produced disease in all experimental animals with rapid dissemination to the lungs, spleen and kidneys. Initial fever was brief, but temperatures did not return to pre-infection levels until day 18, concurrent with a dramatic lymphocytosis and the transition to chronic disease. Distribution and appearance of gross pathologic and radiographic lesions in goats were similar to caprine aerosol infection and to reported human disease. The similarities seen despite different routes of infection suggest that host or bacterial factors may be more important than the route of infection in disease pathogenesis. The nature of melioidosis in goats makes it amenable for modelling additional risk factors to produce acute clinical disease, which is important to the study of human melioidosis.

Case-control investigation on the risk factors of melioidosis in small ruminant farms in Peninsular Malaysia

“…; Sprague and Neubauer ; Soffler et al . ) with asymptomatic carriage reported in pigs (Choy et al . ).…”

“…These authors suggested a possibility of these animals acting as amplification hosts for the bacteria. However, some authors suggested that the organism is highly pathogenic to most mammals (Thomas 1981;Choy et al 2000;Sprague and Neubauer 2004;Soffler et al 2014) with asymptomatic carriage reported in pigs (Choy et al 2000). An alternative explanation presented by Kaestli et al (2009) was that the digging and foraging activities of the animals may lead to increased soil aeration (Inglis et al 2001) and water infiltration (Garkaklis et al 2003) thereby increasing the survival of B. pseudomallei in the soil.…”

Human Melioidosis

“…Numerous animal models of infection with B. pseudomallei have been developed. These include the nematode Caenorhabditis elegans, small mammals such as rats, hamsters, and commonly used mice (including BALB/c for acute and C57BL/6 for chronic infection modelling), and large mammals such as goats, pigs, and nonhuman primates (363)(364)(365)(366). The murine model has been found to be the most applicable, with the type of mouse, route of infection, and infecting dose all adaptable to help mimic various disease states encountered in humans (367,368).…”

Characterization of pathogenesis of and immune response to Burkholderia pseudomallei K96243 using both inhalational and intraperitoneal infection models in BALB/c and C57BL/6 mice

“…There has been significant effort invested in developing appropriate animal models of melioidosis (i.e. mice, rats, hamsters, goats, and non-human primates) [ 26 – 30 ]. Small animal models, specifically the BALB/c and C57BL/6 mouse models, have been used to mimic both the acute and chronic stages of B .…”