What is the pathophysiology of scrub typhus?

Updated: Apr 19, 2018
  • Author: David J Cennimo, MD, FAAP, FACP, FIDSA, AAHIVS; Chief Editor: Russell W Steele, MD  more...
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Answer

O tsutsugamushi, the pathogen that causes scrub typhus, is transmitted to humans through the bite of an infected chigger (see the image below), the larval stage of Leptotrombidium mites. These 6-legged, 0.2-mm larvae are not host specific and feed for 2-10 days on the skin fluids of the host. Wild rats serve as the natural reservoir for the chiggers (and represent a risk factor for human infection [2] ), but they are rarely infected with O tsutsugamushi. [3] When the chiggers feed on humans, infection occurs.

Chigger. Image taken from "Food and Environmental Chigger. Image taken from "Food and Environmental Hygiene Department" Web site and is reproduced under license from the Government of Hong Kong Special Administrative Region.

Orientia is also transmitted transovarially in mites and can unbalance the sex ratio of offspring in favor of females, further propagating infection. [3, 11] Chigger activity and subsequent human infection rates are determined by the particular Leptotrombidium species present (eg, akamushi, deliense, or pallidum), as well as by local conditions. Not surprisingly, positive correlations have been noted between chigger population abundance and human cases of scrub typhus. [12]

In tropical regions, scrub typhus may be acquired year round. In Japan, the chigger of Leptotrombidium akamushi is only active between July and September, when the temperature is above 25°C (77°F). In contrast, Leptotrombidium pallidum, which is found over a wide range, is active at temperatures of 18-20°C (64.4-68°F), from spring into early summer and autumn). [3, 13]

Humans acquire scrub typhus when an infected chigger bites them while feeding and inoculates O tsutsugamushi pathogens. The bacteria multiply at the inoculation site, and a papule forms that ulcerates and becomes necrotic, evolving into an eschar, with regional lymphadenopathy that may progress to generalized lymphadenopathy within a few days. In experimental infection, humans developed an acute febrile illness within 8-10 days of the chigger bite. Bacteremia was present 1-3 days before onset of fever. [14]

As in rickettsial diseases, perivasculitis of the small blood vessels occurs. The endothelium is involved; however, the basic histopathologic lesions suggest that macrophages might be more affected. [15]

O tsutsugamushi stimulates phagocytosis by the immune cells, and then escapes the phagosome. It replicates in the cytoplasm (see the image below) and then buds from the cell. The bacteria are able to harness the microtubule assembly inside the human cell for movement. Antibody-opsonized bacteria are still able to escape the phagosome but cannot effectively move on the microtubule; as a result, overall infectivity is decreased. [3]

Transmission electron micrograph depicts peritonea Transmission electron micrograph depicts peritoneal mesothelial cell of mouse that had been experimentally infected intraperitoneally with Orientia tsutsugamushi. Several organisms are visible within mesothelial cell's cytoplasm.

Scrub typhus may disseminate into multiple organs through endothelial cells and macrophages, resulting in the development of fatal complications. [16, 17] In 2009, an apparent association was reported apparent between high O tsutsugamushi blood polymerase chain reaction (PCR)-determined DNA loads and disease severity. [18]


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