【medical-news】NEJM：军事医学科学院曹务春等发现新发蜱媒立克次体病（二）

Rickettsia sibirica Subspecies sibirica BJ-90 as a Cause of Human Disease

Article
To the Editor:



In May 2012, a 64-year-old farmer was admitted to Mudanjiang Forestry Central Hospital in Mudanjiang, China, after 4 days of fever, chills, asthenia, insomnia, headache, anorexia, nausea, and vomiting. He recalled a tick bite on the back of his right hand 4 days before the onset of the illness. His medical history was notable for a surgical operation for intestinal obstruction 20 years previously. On admission, his temperature was 40°C, with a pulse of 119 beats per minute and blood pressure of 110/80 mm Hg. Physical examination showed confluent pale-pink maculae widely distributed on his trunk and four limbs (see Fig. 1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). Electrocardiography showed sinus tachycardia with a premature ventricular beat. Initial laboratory tests indicated lymphopenia (0.8×109 cells per liter), thrombocytopenia (101.0×109 cells per liter), elevated serum levels of alanine aminotransferase (108.2 U per liter) and aspartate aminotransferase (136.7 U per liter), proteinuria, an increased level of cerebrospinal fluid protein (0.7 g per liter), and a decreased level of cerebrospinal fluid glucose (2.2 mmol per liter). He received doxycycline at a dose of 100 mg twice daily, since this syndrome with rash suggested an infection with rickettsiae of the spotted fever group. He recovered and was discharged from the hospital 15 days after the initiation of therapy.
To identify a potential cause of his illness, we investigated rickettsiae of the spotted fever group species as possible etiologic agents. We used polymerase-chain-reaction amplification of the conserved citrate synthase gene (gltA) and spotted fever group-restricted outer-membrane protein A gene (ompA), followed by sequencing from the blood sample obtained from the patient before the initiation of therapy. Both gltA and ompA sequences amplified from the patient were identical to the corresponding fragments of Rickettsia sibirica subspecies sibirica BJ-90. The phylogenetic analyses based on 1050-bp gltA and 325-bp ompA sequences revealed that the agent clustered with other R. sibirica subspecies and was most closely related to R. sibirica subspecies sibirica246, which had been isolated from Dermacentor nuttalli in Russia (Figure 1 FIGURE 1 Phylogenetic Analysis of Rickettsiae Species.). In serum samples obtained from the patient, the titers of IgM and IgG antibodies against R. sibirica on indirect immunofluorescence assay increased from 1:32 and 1:64, respectively, in the acute phase to 1:4096 for IgM and for IgG in the convalescent phase.
The study of this case was approved by the institutional review board of the Chinese Academy of Military Medical Sciences. The patient provided written informed consent.
R. sibirica subspecies sibirica BJ-90 was initially isolated from D. sinicus in China in 1990,2,3 and it was detected in D. silvarum in Russia. Our case shows that this organism can cause human disease. Unlike patients infected with R. sibirica and R. heilongjiangensis in the same geographic region, this patient was severely ill with multiorgan dysfunction. Further investigation of the epidemiologic and clinical features of R. sibirica subspeciessibirica BJ-90 is required to distinguish it from other known tickborne infections.