Scrub typhus with sepsis and acute respiratory distress syndrome

Abstract

Scrub typhus is a major infectious threat in the Asia-Pacific region. We report an unusual case of scrub typhus in a patient in Singapore who presented with sepsis and acute respiratory distress syndrome but lacked the pathognomonic eschar. The patient recovered after appropriate diagnosis and doxycycline treatment. Rickettsial diseases should be included in the differential diagnosis of febrile illnesses in regions where the diseases are endemic, and absence of eschar should not be the criterion used to rule out scrub typhus.

Fig 1

Western immunoblot assays of patient serum to detect levels of IgG (A) and IgM (B) antibodies to various pathogens. Lanes: 1, L. interrogans (recombinant LipL32 and LipL41 proteins); 2, Rickettsia conorii (recombinant OmpA protein fragments); 3, C. burnetii (recombinant Com-1 protein); 4, R. typhi (whole-cell antigen from R. typhi strain Wilmington); 5, R. typhi (recombinant OmpB protein fragments); 6, O. tsutsugamushi (recombinant R56 proteins from O. tsutsugamushi strains Karp, Kato, Gilliam, and TA763). The recombinant antigens/whole-cell antigens derived from various pathogens were separated on a 4 to 15% polyacrylamide gel, transferred to a nylon membrane, and probed with patient serum (1:100 dilution) overnight at 4°C. The blot was probed with a horseradish peroxidase-conjugated anti-human IgG or IgM secondary antibody (1:1,000 dilution) and visualized with a chemiluminescence-based detection kit (Amersham). (C) Corresponding protein gel stained with SimplyBlue SafeStain (Invitrogen) showing the presence of recombinant/whole-cell antigens used in a Western blot assay loaded in the same order as in panels A and B. (D and E) Positive-control Western blot assays detecting the antigens (loaded in the same order as in panels A and B) in the serum of a confirmed scrub typhus patient. The patient's scrub typhus was confirmed by a 4-fold titer increase and isolation of O. tsutsugamushi from a serum sample. Panel D shows IgG results, and panel E shows IgM results. The values to the left of panels C to E are molecular sizes in kilodaltons.

Fig 2

Results of a real-time PCR used to detect the presence of O. tsutsugamushi in the patient's blood. The total nucleic acids were extracted from the whole-blood sample (200 μl) and the serum sample (200 μl) with the QIAamp DNA minikit (Qiagen) according to manufacturer's instructions. The samples were then tested with an in-house-developed real-time PCR assay targeting the gene encoding the 56-kDa antigen of O. tsutsugamushi. Shown is the fluorescence profile (relative fluorescence units plotted against cycle numbers) representing positive detection of the O. tsutsugamushi 56-kDa antigen gene in a whole blood sample (sample 2). A serum sample (sample 1) was negative. Negative 1 is the negative control for the serum sample (sample 1), and negative 2 is the negative control for the blood sample (sample 2). The threshold line is shown in red, and the amplification threshold value of 0.257 is indicated.