Human Melioidosis

Abstract

The causative agent of melioidosis, Burkholderia pseudomallei, a tier 1 select agent, is endemic in Southeast Asia and northern Australia, with increased incidence associated with high levels of rainfall. Increasing reports of this condition have occurred worldwide, with estimates of up to 165,000 cases and 89,000 deaths per year. The ecological niche of the organism has yet to be clearly defined, although the organism is associated with soil and water. The culture of appropriate clinical material remains the mainstay of laboratory diagnosis. Identification is best done by phenotypic methods, although mass spectrometric methods have been described. Serology has a limited diagnostic role. Direct molecular and antigen detection methods have limited availability and sensitivity. Clinical presentations of melioidosis range from acute bacteremic pneumonia to disseminated visceral abscesses and localized infections. Transmission is by direct inoculation, inhalation, or ingestion. Risk factors for melioidosis include male sex, diabetes mellitus, alcohol abuse, and immunosuppression. The organism is well adapted to intracellular survival, with numerous virulence mechanisms. Immunity likely requires innate and adaptive responses. The principles of management of this condition are drainage and debridement of infected material and appropriate antimicrobial therapy. Global mortality rates vary between 9% and 70%. Research into vaccine development is ongoing.

Keywords: Burkholderia pseudomallei; melioidosis.

FIG 1

Twenty-five countries with the highest predicted melioidosis incidence and predicted increase in prevalence of the major risk factor, diabetes mellitus.

FIG 2

Gram stain demonstrating “safety pin” appearance. Magnification, ×100.

FIG 3

Colonial morphology of B. pseudomallei. Shown are B. pseudomallei cultures on ASH (left) and HBA (right) at 24 h (top) and 48 h (bottom).

FIG 4

Comparison of B. pseudomallei and B. thailandensis spectra using the Vitek MS.

FIG 5

Susceptibility characteristics of B. pseudomallei. AMC, amoxicillin-clavulanate; CN, gentamicin; SXT and TS, trimethoprim-sulfamethoxazole. Double zone of susceptibility were seen with SXT.

FIG 6

A simplified schematic representation of the B. pseudomallei intra- and intercellular life cycles. Initial nonphagocyte host cell attachment occurs via flagella, type 4 pili, and adhesins BoaA and BoaB. Cellular invasion is facilitated by the T3SS, which injects effector proteins, including BopA, BopE, BipB, BipC, and BipD. During internalization the bacterium is enveloped by the host cell in an endocytic vesicle or endosome. Survival within the endosome occurs via multiple processes, including production of a protease inhibitor, ecotin. Escape from the endosome is mediated by the T3SS and subsequent upregulation of biosynthesis pathways, including purine, histidine, fatty acid, and amino acid, aid in replication within the cytosol. Bacilli may localize to nuclei or form a BimA-dependent actin tail used for motility and intercellular spread. The T6SS forms a bridge between host cells and transfers effector proteins which aid the formation of MNGC.