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Fever with Thrombocytopenia Associated with a Novel Bunyavirus in China
Abstract and Commentary
By Dean L. Winslow, MD, FACP, FIDSA
Chief, Division of AIDS Medicine, Santa Clara Valley Medical Center; Clinical Professor, Stanford University School of Medicine
Dr. Winslow is a speaker for Cubist Pharmaceuticals and GSK, and is a consultant for Siemens Diagnostic; this article originally appeared in the May issue of Infectious Disease Alert.
Synopsis: A severe fever with thrombocytopenia syndrome (SFTS) was recognized in China beginning in 2009. A novel virus, SFTS bunyavirus, was isolated from patients meeting the case definition of this syndrome.
Source: Yu Y-J, et al. Fever with thrombocytopenia associated with a novel bunyavirus in China. N Engl J Med 2011;364:1523-1532.
Due to heightened surveillance of acute febrile illness in China, a severe illness associated with thrombocytopenia and multi-system organ involvement was recognized beginning in 2009. Anaplasma phagocytophilium was originally suggested as a cause but the pathogen was not detected in most patients. Blood samples from patients meeting the case definition were used to inoculate a variety of cells in culture, viral RNA was detected by PCR, and the pathogen was subsequently characterized by electron microscopy and nucleic acid sequencing. Enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA), and neutralization assays were developed and were used to document seroconversion of patients to the novel pathogen.
A novel virus, designated SFTS bunyavirus, was isolated from 171 patients, ages 39-83 years, from six provinces in China. These patients presented with an illness characterized by fever (100%), abdominal pain (49%), thrombocytopenia (95%), leucopenia (86%), and clinical and laboratory evidence of multi-system organ dysfunction in many cases. Eleven of 81 patients who had adequate clinical data available for study died. The cell line tested, which appeared to have the greatest sensitivity for SFTS virus infection, was DH82 (a canine macrophage cell line). Sequence analysis revealed the novel virus was a member of the genus phlebovirus in the Bunyavirus family.
This is an interesting report from the world's most populous country and is a testament to the first rate epidemiologic and laboratory research that now exists in China. While this newly described SFTS illness, and the novel bunyavirus that is its etiologic agent, appears to define a distinct syndrome, it is not sufficiently distinctive to exclude other infections in the differential diagnosis. Other infections would potentially include rickettsial infections, anaplasmosis, leptospirosis, and several viral infections such as dengue and various hemorrhagic fever with renal syndromes. The vector for SFTS is not yet known, but most phleboviruses are associated with sandflies. Other phleboviruses are known to be transmitted by ticks and Rift Valley fever is transmitted by Aedes species mosquitoes. SFTS RNA has been detected in a small number of Ixodidae species ticks and this has been proposed as a candidate vector.