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Five years ago, large numbers of farmers in central China began falling victim to an mysterious disease marked by high fever, gastrointestinal disorder and an appalling mortality rate as high as 30 percent in initial reports. Investigators from the Chinese Center for Disease Control and Prevention hurried to the scene of the outbreak. On the basis of DNA evidence, they quickly concluded that it had been caused by human granulocytic anaplasmosis, a bacteria transmitted by tick bites.
Now, though, subsequent studies have shown that original conclusion was incorrect, and that a previously unknown and dangerous virus has been responsible for seasonal outbreaks of the disease in six of China's most populated provinces.
"We expected to find a bacterial infection behaving in an unexpected way human anaplasmosis has a less than one percent fatality rate in the U.S., and it rarely causes abdominal pain or vomiting or diarrhea," said Dr. Xue-Jie Yu of the University of Texas Medical Branch at Galveston, lead author of a paper on the discovery now appearing in the "online advance" section of the New England Journal of Medicine. "Instead, we found an unknown virus."
Researchers have dubbed the newly discovered pathogen Severe Fever with Thrombocytopenia Syndrome virus, and placed it in the Bunyaviridae family, along with the hantaviruses and Rift Valley Fever virus. Later investigation has placed its mortality rate at 12 percent, still alarmingly high.
Yu, a specialist in tick-borne bacteria like the species responsible for HGA, first suspected that a virus might be responsible for the outbreaks after close examination of patients' clinical data showed big differences from symptoms produced by HGA, and blood sera drawn from patients revealed no HGA or HGA antibodies.
Yu became certain that a virus was at fault after sera taken from patients retained its ability to kill cells, despite being passed through a filter that blocked all bacteria. Still, initial genetic tests failed to generate a match with a known pathogen.
"Clearly, we had a virus, but what virus?" Yu said. "I told the people I was working with that they needed to be even more careful, because we were working with an unknown."
That caution seemed appropriate when electron microscope studies of deactivated virus particles revealed what appeared to be a hantavirus associated in Asia with hemorrhagic fever and in the Americas with a deadly pulmonary syndrome. But when Yu and his colleagues managed to extract the virus' entire genetic code, they found that it didn't match any other known virus.
When researchers from the Chinese Center for Disease Control and Prevention led by study author Dr. Yu Wang analyzed sera taken from 241 symptomatic patients from Henan, Hubei, Shandong, Anhui, Jiangsu and Liaoning provinces, they found 171 contained either the previously unknown virus itself or antibodies against it. In addition, the scientists found the virus in 10 out of 186 ticks collected from farm animals in the area where the patients lived.
"This seems to be a tick-borne disease, and the disease comes out when the ticks come out, from late March to late July," Yu said. "Fortunately, even though the full life cycle is not clear, we know that for the virus humans are a dead end we don't have human-to-human transmission as we did with SARS."
Other authors of the New England Journal of Medicine paper include UTMB Health visiting scientist Dr. Yan Liu, professor Vsevolod Popov, professor Dr. David Walker and research associate Dr. Lihong Zhang; Dr. Qun Li, Wen-Wu Yin, Hang Zhou and Dr. Zi-Jian Feng of the Chinese Center for Disease Control and Prevention; Dr. Mi-Fang Liang, Jian-Dong Li, Dr. Yu-Lan Sun, Quan-Fu Zhang, Chuan Li, Dr. Yan-Ping Zhang, Wei Wu, Qin Wang, Shi-Wen Wang, Jing-Dong Song, Tao Wan, Li-Na Sun, Dr. Tao Hong and Dr. De-Xin Li of the State Key Laboratory for Molecular Virology and Genetic Engineering, National Institute for Viral Disease Control and Prevention; Shou-Yin Zhang, Dr. Rong Hai, Biao Kan, Kang-Lin Wan, Dr. Huai-Qi Jing, Dr. Jin-Xin Lu, Jin-Rong He, Jing-Shang Zhang and Xiu-Ping Fu of the State Key Laboratory for Infectious Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention; Fa-Xian Zhan, Xu-Hua Guan and Dr. Jia-Fa Liu of the Hubei Province CDC; Dr. Xian-Jun Wang and Zhen-Qiang Bi of the Shandong Province CDC; Dr. Guo-Hua Liu of the Henan Province CDC; Dr. Jun Ren of the Anhui Province CDC; Dr. Hua Wang of the Jiangsu Province CDC; Dr. Zhuo Zhao of the Liaoning Province CDC; and Dr. Yu Zhang of the Hubei Province Department of Health.
The China Mega-Project for Infectious Diseases, the Western Regional Center of Excellence for Biodefense and Emerging Infectious Diseases and the Chinese Recruitment Program of Global Experts provided support for this research.