Scrub Typhus in Chile

The diagnosis of ST is eminently clinical, based on the triad of fever, macular or papular rash, and an inoculation necrotic eschar. The diagnosis is supported by epidemiologic facts and fast recovery after treatment is initiated.¹⁶ Although the diagnosis can be established based on a quick recovery in endemic countries, in areas such as Chile where incidence and distribution are not completely known, it is better to confirm the diagnosis with laboratory tests without delaying treatment. Several testing options exist, including serologic techniques (immunofluorescence or enzyme-linked immunosorbent assay), culture, and detection of the genetic material of Orientia species by PCR. Usually, IgM titers initially are negative, and IgG testing requires paired samples (acute and convalescent) to demonstrate seroconversion and therefore acute infection.¹⁷ Because culture requires a highly specialized laboratory, it is not frequently used. Polymerase chain reaction is recognized as the best confirmation method due to its high sensitivity and because it remains positive for a few days after treatment has been initiated. The specimen of choice is the eschar because of its high bacterial load. The base of the scar and the buffy coat are useful specimens when the eschar is unavailable.^5,17-19

Due to potential complications of ST, empirical treatment with an antibiotic should be started based on clinical facts and never delayed because of diagnostic tests.¹⁸ Classically, ST is treated with a member of the tetracycline family, such as doxycycline, which provides a cure rate of 63% to 100% in ST.⁵

A 2017 systematic review of treatment options for this infection examined 11 studies from Southeast Asia, China, and South Korea (N=957).¹⁶ The review mainly compared doxycycline with azithromycin, chloramphenicol, and tetracycline. No significant difference in cure rate was noted in comparing doxycycline with any of the other 3 antibiotics; most of the studies examined were characterized by a moderate level of evidence. Regarding adverse effects, doxycycline showed a few more cases of gastrointestinal intolerance, and in 2 of 4 studies with chloramphenicol, patients presented with leukopenia.¹⁶ Several studies compared standard treatment (doxycycline) with rifampicin, telithromycin, erythromycin, and levofloxacin individually; similar cure rates were noted between doxycycline and each of those 4 agents.

Therapeutic failure in ST has been reported in several cases with the use of levofloxacin.²⁰ Evidence for this novel antibiotic is still insufficient. Further studies are needed before rifampicin, telithromycin, erythromycin, or levofloxacin can be considered as options.Scrub typhus usually resolves within a few weeks. Left untreated, the disease can cause complications such as pneumonia, meningoencephalitis, renal failure, and even multiorgan failure and death. Without treatment, mortality is variable. A 2015 systematic review of mortality from untreated ST showed, on average, mortality of 6% (range, 0%–70%).²¹ When ST is treated, mortality falls to 0% to 30%.²² Cases reported in Chile have neither been lethal nor presented with severe complications.^4,5

Scrub typhus is an infectious disease common in Asia, caused by O tsutsugamushi and transmitted by chiggers. It should be suspected when a febrile macular or papular rash and a tache noire appear. The diagnosis can be supported by laboratory findings, such as an elevated C-reactive protein level or a slight increase in the levels of hepatic transaminases, and response to treatment. The diagnosis is confirmed by serology or PCR of a specimen of the eschar. Empiric therapy with antibiotics is mandatory; doxycycline is the first option.

First described in Chile in 2011,² ST was seen in a patient in whom disease was suspected because of clinical characteristics, laboratory and histologic findings, absence of prior reporting in South America, and confirmation with PCR targeting the 16S ribosomal RNA Orientia gene from specimens of the eschar. By 2020, 60 cases have been confirmed in Chile, not all of them published; there are no other reported cases in South America.

When comparing the first case in Chile² with our case, we noted that both described classic clinical findings; however, the management approach and diagnostic challenges have evolved over time. Nowadays, ST is highly suspected, so it can be largely recognized and treated, which also provides better understanding of the nature of this disease in Chile. Because this infection is diagnosed mainly by characteristic cutaneous lesions, dermatologists should be aware of its epidemiology, clinical features, and transmission, and they should stay open to the possibility of this (until now) unusual diagnosis in South America.

Acknowledgments
The authors would like to thank the Chilean Rickettsia & Zoonosis Research Group (Thomas Weitzel, MD [Santiago, Chile]; Constanza Martínez-Valdebenito [Santiago, Chile]; and Gerardo Acosta-Jammet, DSc [Valdivia, Chile]), whose study in execution in the country allowed the detection of the case and confirmation by PCR. The authors also thank Juan Carlos Román, MD (Chiloé, Chile) who was part of the team that detected this case.