Severe illness caused by Rickettsia sibirica subspecies sibirica BJ-90 infection, China

Dear Editor, Human infection of Rickettsia sibirica subsp. sibirica was first described in Russian Far East in the 1930s.1 Since then, this spotted fever group (SFG) rickettsiosis has been found across a large territory of north Asia, including Russia, China, and Mongolia and Kazakhstan.2–5 Common clinical manifestations include fever, headache, weakness, myalgia, rash, eschar, and lymphadenopathy. The disease is usually mild, rarely related to severe complications, and nonfatal. R. sibirica subsp. sibirica BJ-90, a variant of R. sibirica, was first isolated from Dermacentor sinicus in China in 1990,6,7 and has recently been detected in a patient with multiorgan dysfunction.8 Here we report two cases with severe illness caused by R. sibirica subsp. sibirica BJ-90 in northern China. An 81-year-old woman from Harbin City was admitted to Mudanjiang Forestry Central Hospital in northern China on June 2013 (Supplementary Figure S1), with fever (temperature, up to 39.0 °C), fatigue, myalgias, and arthralgia for 7 days, and a hyperpigmented maculopapular rash for 3 days (Figure 1). She reported having a tick bite at the waist when taking a walk in a public park 3 days before illness onset. During the third days of symptoms, she received treatment with cephalosporin and ibuprofen, but her condition did not improve. On admission, blood test abnormalities included: leukocytosis (white blood cell count, 18.1× 109/L), thrombocytopenia (platelet count, 49× 1012/L), neutrocytosis (neutrophil count, 13.8× 109/L); increased levels of liver enzymes (alanine aminotransferase, 73 U/L; aspartate aminotransferase, 86 U/L), glutamyl transpeptidase (95 U/L), creatinine (525 μmol/L), urea nitrogen (44.2 mmol/L), uric acid (648 μmol/L), high-sensitivity C-reactive protein (72 mg/L), and β2-macroglobulin (25 mg/L); decreased levels of albumin (26.0 g/L), cholinesterase (3,192 U/L), calcium (1.6 mmol/L), and carbon dioxide combining power (15 mmol/L). Urine tests showed an elevated level of erythrocytes (80 cells per μL) and total protein (0.3 g/L). Chest radiograph showed increased lung markings, and ultrasonic examination revealed cholecystitis, and hepatic and renal diffuse changes. The patient was intravenously treated with doxycycline based on the clinical symptoms and the preceding tick bite. 2 days after admission, the patient’s leukocytosis, thrombocytopenia, neutrocytosis, blood biochemistry abnormalities, and hepatic and renal dysfunction did not improve (Supplementary Table S1); her condition deteriorated with oliguria, chest distress, rising heart rate, and oedema legs. The patient was subsequently administered with respirator and supportive treatment, but she deteriorated further and developed coma. The patient died 5 days after hospitalization. A 62-year-old woman from Beijing City was admitted to Beijing Chao-Yang Hospital in northern China on June 2016 (Supplementary Table S1), with fever (temperature, up to 39.0 °C), fatigue, dizziness, tinnitus, and chest distress for 6 days, and a sporadic petechial rash for 2 days (Figure 1). The patient reported that she noted a tick bite at the left armpit 2 days before illness onset. The laboratory findings on admission were as follows: leukopenia (white blood cell count, 3.7 × 109/L), thrombocytopenia (platelet count, 82× 1012/L), lymphopenia (lymphocyte count, 0.4 × 109/L); increased levels of liver enzymes (alanine aminotransferase, 220 U/L; aspartate aminotransferase, 386 U/L), lactate dehydrogenase (772 U/L), hydroxybutyrate dehydrogenase (557 U/L), C-reactive protein (78 mg/L), and D-Dimer (6.31 mg/L); and decreased levels of albumin (34.8 g/L). Urine tests showed an elevated level of erythrocytes (10 cells/μL) and total protein (0.25 g/L). Computed tomography showed thickening of left pleura and slight hydropericardium, and ultrasonic examination revealed cyst of right kidney. 3 days later, she developed oedema legs. After treated with oral minocycline for 7 days, the patient’s clinical manifestations and laboratory abnormalities resolved, except slightly increased levels of lactate dehydrogenase and hepatic aminotransferases. Because the patients presented with typical rash and had a recent history of tick bite, SFG rickettsiae was considered as the causative agent. 0.2 mL EDTA-anticoagulant blood samples were obtained from the patients before initiation of therapy, and DNA was extracted with the Blood Mini Kit (Qiagen, Germantown, USA) according to the manufacturer’s instructions. A nested PCR targeting the citrate synthase gene (gltA) was performed as previously described.9 For further confirmation, the outer membrane protein A gene (ompA) was