A zoonotic henipavirus in febrile patients in China

For the editor:

Genetic and epidemiological characterization of LayV.

Panel A shows the organization of the Langya henipavirus (LayV) genome. The diagram is drawn to scale and the scale bar is displayed at the bottom. The abbreviation nt stands for nucleotides. Panel B shows the phylogenetic analysis of LayV. The tree was constructed based on the complete amino acid sequence of the RNA-directed RNA polymerase (the L protein) of LayV and other recognized species of the family Paramyxoviridae using the method of maximum likelihood. Recognized species of the Paramyxoviridae family were included in the analysis. LayV sequences obtained from humans and shrews are marked with red and blue, respectively. The scale bar indicates the number of nucleotide substitutions per site. A bootstrap test (1000 replicates) was performed and bootstrap values ​​are shown. CedV refers to Cedar virus, DARV Daeryong virus, GAKV Gamak virus, GhV Ghana virus, HeV Hendra virus, HeV Genotype 2 HeV, MojV Mojiang virus, NiV Nipah virus and SDQD Shandong Qingdao. Panel C shows the provincial location, occupation, sex, and temporal pattern of patients with confirmed LayV infection.

Hendra virus and Nipah virus, which belong to the henipavirus genus of the Paramyxoviridae family, are known to infect humans and cause fatal diseases; however, other related henipaviruses have been detected in bats, rodents, and shrews.1-4 During sentinel surveillance of febrile patients with a recent history of animal exposure in eastern China, a phylogenetically distinct henipavirus, named Langya henipavirus (LayV), was identified in a throat swab from a patient through metagenomic analysis and subsequent virus isolation. The LayV genome is composed of 18,402 nucleotides with a genomic organization identical to that of other henipaviruses (Figure 1A).1 LayV is most phylogenetically related to the Mojiang henipavirus, which was discovered in southern China (Figure 1B).3

A subsequent investigation identified 35 patients with acute LayV infection in Shandong and Henan provinces of China, of whom 26 were infected with LayV only (no other pathogens were present). These 26 patients presented with fever (100% of patients), fatigue (54%), cough (50%), anorexia (50%), myalgia (46%), nausea (38 %), headache (35%), and vomiting (35%), accompanied by abnormalities of thrombocytopenia (35%), leucopenia (54%), and hepatic (35%) and renal failure (8%). A serological survey of domestic animals detected seropositivity in goats (3 out of 168 [2%]) and dogs (4 out of 79 [5%]). Among the 25 species of small wild animals studied, LayV RNA was mainly detected in shrews (71 out of 262 [27%]), a finding that suggests that the shrew may be a natural reservoir of LayV. (Additional study details are provided in the Additional Methods section of the Supplementary Appendix, available with the full text of this letter on NEJM.org.)

Although the current study does not fulfill Koch’s postulates, the following findings from patients with acute LayV infection suggest that LayV was the cause of febrile illness: LayV was the only potential pathogen detected in 26 of 35 patients (74%) with acute LayV infection; in paired serum samples from 14 patients during the acute and convalescent phases of infection, IgG titers in 86% of the convalescent samples were 4 times higher than those of the acute phase samples; viremia was associated with acute LayV infection; and patients with pneumonia had higher viral loads than those without pneumonia (average [±SD] Logten-transformed copies per millilitre, 7.64±0.98 vs 4.52±1.13). Although human-to-human transmission has been reported for Nipah virus,5 we found no obvious spatial or temporal aggregation of human cases or assigned haplotypes based on three common single nucleotide polymorphisms (Figure 1C). There was no close contact or common exposure history among the patients, suggesting that infection in the human population may be sporadic. Contact tracing of 9 patients with 15 close contact family members revealed no close contact transmission of LayV, but our sample size was too small to determine the status of human-to-human transmission of LayV. Potential cross-reaction with Mojiang virus should be evaluated to improve serological testing.

In our study, a newly identified henipavirus of probable animal origin was associated with febrile illness, a finding that warrants further investigation to better understand the associated human illness.

Xiao-Ai Zhang, Ph.D.
Hao Li, Ph.D.
Beijing Institute of Microbiology and Epidemiology, Beijing, China

Fa-Chun Jiang, BS
Qingdao Municipal Center for Disease Control and Prevention, Qingdao, China

Feng Zhu, Ph.D.
Duke – National University of Singapore School of Medicine, Singapore, Singapore

Yun-Fa Zhang, BS
Jin-Jin Chen, M.Sc.
State Key Laboratory of Pathogens and Biosecurity, Beijing, China

Chee-Wah Tan, Ph.D.
Duke – National University of Singapore School of Medicine, Singapore, Singapore

Danielle E. Anderson, Ph.D.
Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia

Hang Fan, Ph.D.
Beijing Institute of Microbiology and Epidemiology, Beijing, China

Li-Yan Dong, M.Sc.
Qingdao Municipal Center for Disease Control and Prevention, Qingdao, China

Chang Li, Ph.D.
Changchun Institute of Veterinary Medicine, Changchun, China

Pan-He Zhang, M.Sc.
Yue Li, BS
Heng Ding, B.S.
Li-Qun Fang, Ph.D.
Beijing Institute of Microbiology and Epidemiology, Beijing, China
[email protected]

Lin-Fa Wang, Ph.D.
Duke – National University of Singapore School of Medicine, Singapore, Singapore
[email protected]

Wei Liu, MD
Beijing Institute of Microbiology and Epidemiology, Beijing, China
[email protected]

Supported in part by a grant (81825019) from the National Natural Science Foundation of China. The work at Duke–National University of Singapore was supported by grants (FRN2012FRNCRP001-056 and FRN2016FRNNSFC002-013) from the National Research Foundation and by a grant (OFLCG19mai-0034) from the National Council for Medical ResearchSingapore.

The disclosure forms provided by the authors are available with the full text of this letter on NEJM.org.

Drs. X.-A. Zhang and H. Li and Mr. Jiang contributed equally to this letter.

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