Discovering a Novel Viral Pathogen in China

Published - Written by Jennifer Zeis

An acute febrile illness had befallen rural Chinese farmers, and initial assessments suggested it was killing 30 percent of those it infected.

Between late March and mid-July 2009, more than 240 patients in rural areas of Central and Northeast China were hospitalized with fever (38°C or higher), thrombocytopenia (platelet count, <100,000 per cubic millimeter), leukocytopenia, and multiorgan dysfunction.

In early June, seven days after illness onset, a blood sample was obtained from a patient from Xinyang City in Henan Province. At that time, researchers designed a strategy to isolate the pathogen, and inoculated multiple cell lines susceptible to both viral and rickettsial agents, in order to see if the disease was caused by the widely-distributed Anaplasma phagocytophilum. It wasn’t – these bacterium were not detected in the blood samples from this patient and the majority of patients.

A novel virus, however, was isolated. As described in this week’s NEJM, they named it severe fever with thrombocytopenia syndrome due to a bunyavirus (SFTSV).

The first SFTSV was isolated in 2009 from a 42-year-old farmer from the Henan Province. The next year, the vast majority (96%) of lab-confirmed SFTS cases occurred from May to July, and almost all cases (97%) occurred in farmers living in wooded and hilly areas and working in the fields before the disease hit.

Also in 2010, researchers used a strategy similar to the preceding year’s to isolate an additional 11 virus strains. From these strains, researchers sequenced the virus’s whole genome. These sequences showed that SFTSV was related to prototypic viruses of Bunyaviridae. All told, the presence of this virus, specific antiviral antibodies, or both, were confirmed in 171 patients who met the case definition for SFTS in Central and Northeast China from June 2009 through September 2010.

In their discussion, researchers explain they found other evidence that suggested they were seeing a novel phlebovirus in the Bunyaviridae family. One notable example is that cellular changes to DH82 cells were observed a month after SFTSV’s cell monolayers were inoculated with white cells from the patient. Only SFTSV particles affected DH82.

Mosquitoes were initially eyed as a disease vector, and they were commonly found in the patients’ home environment. After the molecular screening of 5,900 mosquitoes, though, the viral RNA of SFTS was not found.  But this RNA was found in 10 of 186 ticks of the of the species Haemaphysalis longicornis that were collected from domestic animals in the areas where the patients lived.  “The ticks,” the researchers write, “may be a candidate vector of SFTSV.”

The authors note that they do not fulfill Koch’s postulates for establishing a causal relationship between a microbe and a disease in their entirety, but their findings are consistent with the hypothesis that SFTS is caused by a newly identified bunyavirus.  “It is most likely that SFTS had been prevalent in China for some time,” they write, “but it had not been identified.”

In an editorial, Heinz Feldmann of the NIAID agrees. Koch’s postulates for establishing causal relationships between pathogens and disease are “largely fulfilled,” he writes, “with the exception of the most difficult postulate: an animal model to reiterate that relationship.” But moreover, says Feldmann, “The identification of SFTSV is a prime example of the rapid discovery of a truly emerging infectious disease and its cause.”

NEJM deputy editor Dr. Lindsey Baden says the findings presented here are quite important. “This discovery, of a truly novel pathogen causing severe disease and its potential mode of transmission,” he said, “allows for public health intervention to both prevent infection and potentially treat disease.”