Comparative experimental subcutaneous glanders and melioidosis in the common marmoset (Callithrix jacchus)

Abstract

Glanders and melioidosis are caused by two distinct Burkholderia species and have generally been considered to have similar disease progression. While both of these pathogens are HHS/CDC Tier 1 agents, natural infection with both these pathogens is primarily through skin inoculation. The common marmoset (Callithrix jacchus) was used to compare disease following experimental subcutaneous challenge. Acute, lethal disease was observed in marmosets following challenge with between 26 and 1.2 × 10(8) cfu Burkholderia pseudomallei within 22-85 h. The reproducibility and progression of the disease were assessed following a challenge of 1 × 10(2) cfu of B. pseudomallei. Melioidosis was characterised by high levels of bacteraemia, focal microgranuloma progressing to non-necrotic multifocal solid lesions in the livers and spleens and multi-organ failure. Lethal disease was observed in 93% of animals challenged with Burkholderia mallei, occurring between 5 and 10.6 days. Following challenge with 1 × 10(2) cfu of B. mallei, glanders was characterised with lymphatic spread of the bacteria and non-necrotic, multifocal solid lesions progressing to a multifocal lesion with severe necrosis and pneumonia. The experimental results confirmed that the disease pathology and presentation is strikingly different between the two pathogens. The marmoset provides a model of the human syndrome for both diseases facilitating the development of medical countermeasures.

Characterization of lesion formation in marmosets following inhalational challenge with different strains of Burkholderia pseudomallei

“…Thin sections (4 lm) were cut and stained with haematoxylin and eosin for histopathological analysis. Immunohistochemistry (IHC) was performed as previously described (Nelson et al 2014) on selected tissues (liver, spleen, lungs and the inoculation site) for the detection of bacterial antigen, T cells (CD3 + ), B cells (CD79 + ), macrophages and neutrophils (NEUs) (MAC387 + ) and inducible nitric oxide synthase (iNOS + ). A semiquantitative scoring system was established to allow comparison (Table 1).…”

“…Melioidosis presented as a rapid, acute disease (Nelson et al . , ). This model was further exploited in this study in order to compare the virulence and lesion characteristics in lethal disease caused by one of four strains of B. pseudomallei (HBPUB10303a, HBPUB10134a, 1026b and K96243).…”

“…Melioidosis has previously been investigated in marmosets using B. pseudomallei strain 13392 [originally thought to be strain K96243 (Nelson et al 2013)]. Melioidosis presented as a rapid, acute disease (Nelson et al 2011(Nelson et al , 2014. This model was further exploited in this study in order to compare the virulence and lesion characteristics in lethal disease caused by one of four strains of B. pseudomallei (HBPUB10303a, HBPUB10134a, 1026b and K96243).…”

Dose‐dependant acute or subacute disease caused byBurkholderia pseudomalleistrain NCTC 13392 in a BALB/c aerosol model of infection

“…Currently most MCMs for melioidosis are evaluated in animal models for their effectiveness against acute disease; the mouse model being the most widely used (Warawa, ) although larger animal models have been evaluated for instance: Rhesus macaques (Yingst, Facemire et al . 2014); African Green monkeys (Yeager et al ) and marmosets (Nelson et al ; Nelson et al ; Nelson et al ). Aerosolized doses of <10 CFU per animal B. pseudomallei NCTC 13392 caused a lethal infection by day 3–4 in marmosets, indicating these animals are highly susceptible to this strain (Nelson et al ; Erratum, ).…”

Novel multi-component vaccine approaches for Burkholderia pseudomallei

“…The SGMVD has recommended that if the vaccine will be used against naturally acquired melioidosis, the addition of a diabetic mouse model to the testing vaccination scheme will be recommended because populations suffering from diabetes, particularly type 2, are at increased risk of acquiring melioidosis [2,25]. Other NHP models for meliodosis, for example involving marmosets, have been reported [30,31] but not yet used to evaluate vaccine candidates. There is a report of the testing of a melioidosis vaccine candidate in rhesus macaques [27] and glanders vaccine candidates have also been tested in this species [28,29].…”