Association of High Orientia tsutsugamushi DNA Loads with Disease of Greater Severity in Adults with Scrub Typhus

Abstract

Orientia tsutsugamushi, the cause of scrub typhus, is a major pathogen in the Asia-Pacific region. The severity of infection ranges from mild features to multiorgan failure and death. The aim of this prospective study was to define the O. tsutsugamushi loads in the blood samples of patients with scrub typhus on the day of hospital admission and to determine whether this was associated with disease severity. Quantitation was performed using a real-time PCR Orientia tsutsugamushi, the cause of scrub typhus, is a major pathogen in the Asia-Pacific region, where it accounts for up to 23% of all febrile episodes (4). Infection commonly presents as an acute febrile illness 7 to 10 days after the bite of an infected larval trombiculid mite (chigger). The major presenting features are fever, severe headache, and myalgia. Other signs and symptoms include rash, lymphadenopathy, hepatosplenomegaly, cough, sore throat, abdominal pain, and central nervous system involvement. The severity of infection ranges from mild features to multiorgan failure and death, which occurs for around 4% of patients presenting to a hospital (10, 21). Severity of illness has been reported to show geographical variability (10), although the basis for this is unknown and has multiple explanations, including differences in host genetic susceptibility or response to infection and variability in the virulence of the organism. A relationship between magnitude of bacteremia and severity of clinical picture has been reported for a range of bacterial infections in both adults and children, based on quantitative bacterial culture (25) and, more recently, molecular techniques (5, 8). A previous study reported the O. tsutsugamushi DNA loads in 7 patients with scrub typhus, as defined by quantitative real-time PCR targeting a gene encoding a 47-kDa protein (20). This ranged from 1,076 to 28,812 DNA copies/l in blood, but clinical features and outcomes were not described (20).The aim of this study was to define the O. tsutsugamushi loads in blood samples taken on the day of hospital admission from a large, unselected population of patients with scrub typhus in northeast Thailand and to compare this with disease severity. MATERIALS AND METHODSPatients with scrub typhus were identified during a prospective study of acute febrile illness in Udon Thani hospital, northeast Thailand, between October 2000 and December 2001, as described previously (21). In brief, the inclusion criteria were an age of Ն15 years, the presence of a fever (Ͼ37.8°C) of unknown cause, and agreements to participate and to attend an outpatient follow-up for a convalescent-phase serum sample at 2 weeks. The exclusion criterion was a blood smear positive for malaria parasites or the presence of other definable infections, such as pneumonia or urinary tract infection. Blood was drawn on admission for aerobic blood culture, serological testing, and molecular diagnostics. The duration of symptoms prior to admission, antibiotic treatment at presentation, and clinical features, including the prese...

Scrub Typhus in Northeastern Thailand: Eschar Distribution, Abnormal Electrocardiographic Findings, and Predictors of Fatal Outcome

“…positive correlation between disease severity and high O. tsutsugamushi DNA by performing PCR targeting on 16S ribosomal RNA gene of O. tsutsugamushi using DNA extracted from admission ethylenediaminetetraacetic acid blood samples, 15 whereas in the present study, four fatal cases had positive PCR targeting on 47-and/or 56-kDa genes in O. tsutsugamushi using DNA extracted from buffy coat. Three of them had O. tsutsugamushi DNA less than 100 copies, whereas the other one had 24,415 copies per 500 ng of human genomic DNA.…”

“…Serology is the mainstay for diagnosing scrub typhus. 2 Patient outcome varies depending on pathogen factors (strain virulence 14 and high bacterial load 15 ), severity of the disease, 16 time to diagnosis, 17 commencement of appropriate treatment, 3 and the presence of drug resistance. 18 This study aims to demonstrate the clinical and laboratory manifestation, particularly eschar distribution and abnormal ECG findings, and the predictors of fatal outcome in scrub typhus patients.…”

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

“…1,7,8 Plasma rickettsial load is associated with disease severity in adults. 9 Clinical characteristics such as older age, underlying diseases, and delay of appropriate antibiotics administration seem to contributes to the severity. 10,11 Laboratory markers such as increased transaminases, hypoalbuminemia, leukocytosis, and elevated serum creatinine have been reported to be associated with the disease severity.…”

Pulmonary Manifestations of Scrub Typhus: Wisdom May Prevail Obstacles

“…The outcome is determined by multiple factors including age of the patient and genetic factors but the virulence of infecting strain of O. tsutsugamushi is believed to be the most important one. Indeed, bacterial proliferation (as opposed to immunopathology) and the time of antibiotic control of the infection are very important predictors of lethality [17,18]. Thus, the delayed treatment leads to complications such as adult respiratory distress syndrome, disseminated intravascular coagulation, acute renal failure, meningoencephalitis and gastrointestinal tract bleeding [17,19].…”