Severity Predictors in Eschar-Positive Scrub Typhus and Role of Serum Osteopontin

Abstract

We prospectively evaluated severity predictors in terms of host, microorganism, and treatment factors in 153 eschar-positive scrub typhus patients. Severity was assessed with the Acute Physiology and Chronic Health Evaluation (APACHE) II score (< 10 versus ≥ 10) and predefined criteria of severe complications. Genotypes of Orientia tsutsugamushi were determined. Independent risk factors for severity (APACHE II score ≥ 10) were old age, diabetes mellitus, serum osteopontin > 100 ng/mL, and a group of underlying diseases (congestive heart failure, cerebrovascular disease, chronic liver disease, bronchial asthma, and chronic obstructive lung diseases). Anemia (≤ 10 g/dL) and C-reactive protein > 10 mg/dL were indicators of current severity. Neither the delay in antibiotics administration nor strain types (Boryong, Taguchi, or Kanda/Kawasaki) contributed to the severity. The risk factors for severe complications were similar. Serum osteopontin > 100 ng/mL had a negative predictive value of 96% for severe complications. This marker can be used to rule out severe disease status.

Outcome of Intravenous Azithromycin Therapy in Patients with Complicated Scrub Typhus Compared with That of Doxycycline Therapy Using Propensity-Matched Analysis

“…These cases were associated with age (Ն60 years), presentation without eschar, and laboratory findings such as white blood cell counts of Ͼ10,000/mm 3 and serum albumin levels of Յ3.0 g/dl. In a multicenter study conducted in the Republic of Korea, Park et al (12) reported that 10% of eschar-positive scrub typhus patients had central nervous system, respiratory, cardiac, or renal complications or septic shock. In the present study, complicated scrub typhus was observed in 28.1% of scrub typhus patients and 35% of hospitalized scrub typhus patients, consistent with the findings of previous studies (10 to 43%) (11,12).…”

“…In a multicenter study conducted in the Republic of Korea, Park et al (12) reported that 10% of eschar-positive scrub typhus patients had central nervous system, respiratory, cardiac, or renal complications or septic shock. In the present study, complicated scrub typhus was observed in 28.1% of scrub typhus patients and 35% of hospitalized scrub typhus patients, consistent with the findings of previous studies (10 to 43%) (11,12). Our results, as well as data from previous studies, show that complications in patients with scrub typhus are not uncommon.…”

“…Complicated scrub typhus was defined by the following conditions (11,12): (i) shock, defined by a systolic blood pressure of Ͻ90 mm Hg or a fall in systolic blood pressure of Ͼ40 mm Hg; (ii) acute kidney injury, defined by a serum creatinine increase of Ͼ2.0-fold or a glomerular filtration rate decrease of Ͼ50% from baseline; (iii) pneumonia with parenchymal lung lesions on a chest radiograph and cough or dyspnea; (iv) acute respiratory distress syndrome, defined by a ratio of arterial partial oxygen tension as a fraction of inspired oxygen of Ͻ200 mm Hg in the presence of bilateral infiltrates on a chest radiograph; (v) meningoencephalitis with neurologic symptoms and evidence of infection of the central nervous system, based on imaging studies or cerebrospinal fluid (CSF) counts of Ͼ5 leukocytes/mm 3 ; (vi) gastrointestinal bleeding; and (vii) cholecystitis, defined by the presence of Murphy's sign and radiological evidence of gallbladder inflammation. Mortality was defined as scrub typhus related if there was no other definite cause of death (15).…”

“…For this reason, azithromycin is considered an appropriate alternative for mild to moderate scrub typhus in areas where doxycycline-resistant scrub typhus is prevalent (8), and also for children under 8 years of age or in women during pregnancy (9), where doxycycline is contraindicated. However, there are few clinical data on the efficacy of different antibiotics for the treatment of severe, life-threatening scrub typhus (10), despite the fact that complicated cases of scrub typhus are not uncommon (11)(12)(13). Moreover, the efficacy of azithromycin for the treatment of severe complicated scrub typhus is largely unknown, because all randomized clinical trials using macrolides to date have excluded severe or complicated cases (5)(6)(7).…”

Unusual Genotypic Distribution of Orientia tsutsugamushi Strains Causing Human Infections on Jeju Island

“…Although the Gilliam and Karp serotypes are reportedly more common in the central part, 1,8 the Boryong type predominates in the southern part of South Korea. 4,9 In addition, Kato, Neimeng-65, and Kawasaki genotypes have been identified in South Korea. 10 Although a prior study reported that the Boryong genotype rather than the Karp genotype predominated on Jeju Island, 7 we found that the Taguchi type was also common on Jeju Island.…”