Table 1.
Global distribution of melioidosis outbreak, incidence, and their reported cases (an overview).
Fig 1.
Global geographical distribution of melioidosis.
The areas of high endemicity in Southeast Asia (Thailand, Vietnam, Cambodia, Malaysia, and Singapore)/Northern Australia. Possible endemic, sporadic areas, environmental isolates only, and unconfirmed travel history/only serology evidence are indicated. However, sporadic cases have been reported throughout the world in Pakistan, India, Bangladesh, Indonesia, Philippines, Sri Lanka, Papua New Guinea, Madagascar, France, Mexico, Brazil, Colombia, Venezuela, Ecuador, the Middle East (Iran), and the Caribbean.
Fig 2.
Schematic representation showing the virulence and pathogenesis of melioidosis infection.
B. pseudomallei is transmitted from its environmental reservoir to lung epithelial cells, where it initially attaches, possibly through bacterial components such as the capsule and type IV pili. Following invasion of epithelial cells, the T3SS-3 effectors assist in vacuolar escape and intracellular motility due to BimA-mediated actin polymerization. The activation of TLR-2, TLR-4, and TLR-5 by bacterial LPS and flagella results in recruitment of innate immune cells, such as neutrophils, macrophages, and natural killer cells. IRAK-M, interleukin-1-associated kinase 3; TLR, toll-like receptor; LPS, lipopolysaccharide; CD14, cluster of differentiation; NF-kB, nuclear factor kappa-light-chain-enhancer of activated B cells; IL, interleukin; TNF-α, tumor necrosis factor alpha; NLRC-4, NRL family CARD domain-containing protein 4; NLRP3, NACHT, LRR, and PYD domain-containing protein 3; ACS, acetyl-CoA synthetases; PCR, polymerase chain reaction.
Fig 3.
Ultrastructural examination of B. pseudomallei used for infection.
(A) Scanning electron microscopy (SEM) image showing Bp before the infection with U-937 cells. (B) Bp-infected cells were examined by a transmission electron microscopy (TEM) with large number of bacilli (Bp) presented in the cytoplasm. Light micrograph showing B. pseudomallei infection of mouse spleen; section stained by Haematoxylin and Eosin (H&E) imaged with different magnification. (C–D) Large abscesses (Abs) with focal areas of necrosis, surrounded by a rim of meshed fibrous tissue (f) are evident after 2 weeks IP challenge with 1.7x105 CFU/ml. The bacterial invasion is more in spleen and liver than kidney. Bp, B. pseudomallei; abs, abscess; f, fibrous tissue; rs, rough surface; s, septa; sb, single bacilli; n, nucleus; ph, phagocytosis.
Fig 4.
Schematic diagram for melioidosis diagnosis and list of sensitive and resistance antibiotics.
There are several factors, such as inactivation of enzyme, target deletion, and drug efflux pumps from the cells mediated by chromosomally encoded genes. Furthermore, the overproduction and point mutations in class A PenA β-lactamase affect some of the important drugs (i.e., ceftazidime and amoxicillin-clavulanic acid) that are responsible for the development of resistance mechanisms. However, the deletion of penicillin binding protein-3 (PBP-3) leads to ceftazidime resistance, and BpeEF-OprC efflux pump overexpression causes doxycycline, trimethoprim, and trimethoprim (TMP)-sulfamethoxazole (SFZ) resistance.
Table 2.
Randomized trials of potential antibiotic treatment in severe melioidosis.
Recommendations for diagnosis, treatment and continuing care of melioidosis based on recent experience and best practice. Antibiotic treatment for severe infection is either intravenous Ceftazidime or Meropenem for several weeks, followed by up to 20 weeks oral treatment with a combination of trimethoprim-sulphamethoxazole and doxycycline.