A Brief History of the Major Rickettsioses in the Asia–Australia–Pacific Region: A Capstone Review for the Special Issue of TMID

The rickettsioses of the “Far East” or Asia–Australia–Pacific region include but are not limited to endemic typhus, scrub typhus, and more recently, tick typhus or spotted fever. These diseases embody the diversity of rickettsial disease worldwide and allow us to interconnect the various contributions to this special issue of Tropical Medicine and Infectious Disease. The impact of rickettsial diseases—particularly of scrub typhus—was substantial during the wars and “police actions” of the last 80 years. However, the post-World War II arrival of effective antibiotics reduced their impact, when recognized and adequately treated (chloramphenicol and tetracyclines). Presently, however, scrub typhus appears to be emerging and spreading into regions not previously reported. Better diagnostics, or higher population mobility, change in antimicrobial policies, even global warming, have been proposed as possible culprits of this phenomenon. Further, sporadic reports of possible antibiotic resistance have received the attention of clinicians and epidemiologists, raising interest in developing and testing novel diagnostics to facilitate medical diagnosis. We present a brief history of rickettsial diseases, their relative importance within the region, focusing on the so-called “tsutsugamushi triangle”, the past and present impact of these diseases within the region, and indicate how historically, these often-confused diseases were ingeniously distinguished from each another. Moreover, we will discuss the importance of DNA-sequencing efforts for Orientia tsutsugamushi, obtained from patient blood, vector chiggers, and rodent reservoirs, particularly for the dominant 56-kD type-specific antigen gene (tsa56), and whole-genome sequences, which are increasing our knowledge of the diversity of this unique agent. We explore and discuss the potential of sequencing and other effective tools to geographically trace rickettsial disease agents, and develop control strategies to better mitigate the rickettsioses.


BC
Hippocrates defines typhus -as "fever with a confused state of the intellect -a tendency to stupor". [1] 430 BC Thucydides and Hippocrates first describe epidemic typhus cases. [2] 313 BC First clinical accounts of Tsutsugamushi disease in the "Zhouhofang", a Chinese clinical manual. Description of regional vector mites, no linkage to transmission [3] 15 th century Epidemic typhus and endemic typhus (Tabardillo) rages in Europe.
No distinction made between different forms of typhus [4] 1485−1551 The five epidemics known as the 'English Sweat' occur in the United Kingdom.
Based on clinical appearance of characteristic skin rash [14] 1762 James Lind (1716−1794) promotes hygienic measures during typhus outbreaks to reduce mortality.
The basis of the name 'Tsutsugamushi disease' [15] 1812−1813 Napoleon suffers the greatest loss of troops in eastern Europe to epidemic typhus (and Trench Fever).
Post-mortem hyperplastic nodules in Peyer's patches [11,18] 1843 Craigie and Hendersen differentiate relapsing fevers clinically and pathologically from (epidemic) typhus Post-mortem observations in autopsies [12,19] Charles Murchison epidemiologically emphasizes the contagious nature of typhusassociation of epidemics with poor hygienic standards [20] 1878 First account of Tsutsugamushi disease from Japan to be published in Europe by Theobald Palm.
Reported as Shima-mushi, or Island insect disease [21] 1898 Brill Disease-an outbreak of atypical typhus, what Brill called abortive-typhoid in New York [22,23] 1906 Howard T. Ricketts  Later revealed as R. honei, a spotted fever group rickettsia [38] Maxcy and Havens describe murine typhus as an endemic form of sporadic typhus.
Based on entomological, cross-immunity and clinical criteria.
Localization in the Descement's membrane of rabbit eyes. [46] 1931 Dyer proves Maxcy right-murine typhus is transmitted by rat fleas.
Based on New Guinea strain (Karp), did not work in Malaya. [48−51] 1947 Discovery of Chloromycetin, a derivative from Actinomyces bacteria Cured chick embryos infected with rickettsiae [52] 1948 Smadel demonstrates chloramphenicol as an effective chemotherapy for scrub typhus.