Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious and hemorrhagic disease recently described in China and western Japan. A 71-year-old healthy Japanese woman noticed a tick biting her after harvesting in an orchard and removed it herself. She developed diarrhea, anorexia, and chills eight days later. Because these symptoms continued, she visited a primary care physician 6 days after the onset. Laboratory data revealed thrombocytopenia, leukocytopenia, and elevated liver enzymes. She was then referred to our hospital. Although not completely fulfilling the diagnostic criteria used in a retrospective study in Japan, SFTS was suspected, and we detected SFTS virus in the patient’s blood using RT-PCR. However, she recovered without intensive treatment and severe complications 13 days after the onset. In this report, we present a mild clinical course of SFTS virus infection in Japan in detail.
An outbreak of an unknown infectious disease characterized by high fever, gastrointestinal symptoms, thrombocytopenia, and leukocytopenia occurred between March and July 2009 in China, with a high fatality rate (30%). The emerging infectious disease was named severe fever with thrombocytopenia syndrome (SFTS) based on its clinical characteristics. In 2011, Yu et al. identified a tick-borne infectious disease caused by the SFTS virus (SFTSV), a
In early June, a 71-year-old previously healthy woman, who engaged in agricultural activities in a hilly rural area, noticed a tick biting her left thigh while bathing after harvesting in an orchard. The species of the tick remains unclear. She properly removed the head of the tick herself. However, she suddenly developed watery diarrhea (4-5 times a day), anorexia, and left inguinal lymphadenopathy eight days later. She also felt cold but did not measure her body temperature. Because these symptoms did not improve, particularly her gastrointestinal symptoms, she visited a primary care physician 4 days after the onset of the illness. Laboratory data revealed low platelet and white blood cell counts as well as elevated liver enzymes (Table
Clinical course of hemoglobin, leukocyte and platelet counts, AST, ALT, creatine kinase, LDH, aPTT, prothrombin time, and C-reactive protein after the onset of SFTS.
Laboratory test (reference range) | Day 4 | Day 7 | Day 8 | Day 9 | Day 10 | Day 13 |
---|---|---|---|---|---|---|
Hemoglobin, g/dL (11.5–15.3) | 14.4 | 16.4 | 13.2 | 12.3 | 13.1 | 12.7 |
Leukocyte, ×103/ |
3.0 | 4.9 | 3.9 | 4.2 | 4.2 | 4.4 |
Neutrophil, % (39–73) | NA | 45 | 32 | 61 | 56 | 59 |
Lymphocyte, % (19–50) | NA | 36 | 52 | 29 | 35 | 27 |
Atypical lymphocyte, % (0) | NA | 15 | 3 | 0 | 0 | 0 |
Erythroblast, cell/100 WBC (0) | NA | 1 | 0 | 0 | 0 | 0 |
Platelet, ×103/ |
61 | 73 | 79 | 89 | 241 | 431 |
AST, IU/L (11–35) | 157 | 267 | 192 | 147 | 86 | 42 |
ALT, IU/L (5–35) | 66 | 122 | 97 | 89 | 82 | 56 |
Creatine kinase, IU/L (45–235) | 155 | 207 | 127 | 86 | 52 | 31 |
LDH, IU/L (120–230) | 483 | 577 | 437 | 356 | 284 | 206 |
aPTT, sec (20–35) | NA | 33.8 | 31.3 | 30.5 | 29.3 | 26.9 |
Prothrombin time, INR (0.8–1.2) | NA | 0.88 | 0.89 | 0.92 | 0.98 | 1.03 |
C-reactive protein, mg/dL (0–0.5) | 1.10 | 0.23 | 0.15 | 0.26 | 0.29 | 0.04 |
On admission, the patient had a slight headache, but no fever or neurological symptoms. A left inguinal lymph node was swollen, but indolent, whereas none of the other superficial lymph nodes or tonsils were enlarged. The patient did not exhibit erythema, wheal, or petechial rash. A small tick bite was observed in the lateral aspect of her left thigh (Figure
Laboratory data of a Japanese elderly patient with mild SFTS on the admission.
|
|
White blood cell | 4,900/ |
Neutrophil | 45.0% |
Lymphocyte | 36.0% |
Monocyte | 4.0% |
Eosinophil | 0.0% |
Basophil | 0.0% |
Atypical lym. | 15.0% |
Erythroblast | 1 cell/100 WBC |
Red blood cell | 561 × 104/ |
Hemoglobin | 16.4 g/dL |
Hematocrit | 47.7% |
Platelet | 7.3 × 104/ |
|
|
aPTT | 33.8 sec |
PT (%) | 166% |
PT-INR | 0.88 |
Fibrinogen | 246 mg/dL |
FDP | 4.34 |
|
|
Creatinine | 0.90 mg/dL |
BUN | 22.0 mg/dL |
Sodium | 136 mEq/L |
Potassium | 3.9 mEq/L |
Chloride | 97 mEq/L |
AST | 267 IU/L |
ALT | 122 IU/L |
ALP | 202 IU/L |
|
52 IU/L |
T-Bil | 0.5 mg/dL |
LDH | 577 IU/L |
Creatine Kinase | 207 IU/L |
Total Protein | 6.2 g/dL |
Albumin | 3.5 g/dL |
CRP | 0.23 mg/dL |
Glucose | 196 mg/dL |
Endotoxin | <2 pg/mL |
Procalcitonin | 0.207 |
Ferritin | 1713 ng/mL |
Soluble IL-2R | 1235 U/mL |
HbA1c | 5.7% |
IgG | 1035 mg/dL |
IgA | 129 mg/dL |
IgM | 34 mg/dL |
Anti-nuclear antibody | <40 |
HBs antigen | (—) |
HCV antibody | (—) |
HIV antibody | (—) |
TPHA | (—) |
|
|
>1.030 | |
pH | 6.5 |
Protein | (2+) |
Sugar | (—) |
Ketone | (—) |
Occult blood | (1+) |
Lym.: lymphocyte; WBC: white blood cells; PT: prothrombin time; FDP: fibrin/fibrinogen degradation products; BUN: blood urea nitrogen; ALP: alkaline phosphatase;
Clinical signs of an elderly patient with SFTSV infection. (a) A tick bite was found on the left thigh. (b) Microscopic findings of Giemsa staining of bone marrow showed platelet-specific hemophagocytes. (c) Contrast-enhanced computed tomography showed left inguinal lymphadenopathy alone.
Detection of Japanese SFTSV mRNA using a conventional one-step RT-PCR method. Clinical specimen by RT-PCR: lane 1: our patient’s blood sample; lane 2: negative control (NTC); lane 3: positive control (PC) (SFTSV strain HB29 viral RNA). Primer sets numbers 1 and 2 amplified the gene coding SFTSV NP, and the sizes of these products were 458 bp and 461 bp, respectively.
In a retrospective study performed in Japan, SFTS was defined as a case in which all of the following seven requirements were met: (1) fever of 38°C or higher, (2) digestive symptoms, (3) thrombocytopenia, (4) leukocytopenia, (5) elevated AST/ALT/LDH levels, (6) no other clear cause, and (7) intensive care required or death [
In the initial medical examination, it was difficult to distinguish the present case from a
The clinical course of SFTS has largely been divided into 4 stages: (1) incubation, (2) fever stage, (3) MOF stage, and (4) convalescence [
The viral load of SFTSV in peripheral blood decreases slightly in survivors with the infection, whereas a high titer level of 108 copies/mL or more leads to fatal outcomes [
As of June 2014, SFTS has been confirmed in areas to the west of our hospital (particularly in the Kyushu and Shikoku regions) [
Several cases of severe SFTS were reported between 2011 and 2012 in the Xinyang region in China [
Here we described a patient with a mild clinical course of SFTSV infection in the easternmost area of Japan. Mild cases may not be diagnosed in routine clinical practice and thus may be overlooked. Therefore, the incidence of SFTSV infection may be higher than reported. Early diagnosis, effective treatment, and prevention need to be established to prevent future endemic spread of SFTSV infection.
The authors declare that they have no conflict of interests.