A Zoonotic Henipavirus in Febrile Patients in China

Publicado en NEJM https://www.nejm.org/doi/full/10.1056/NEJMc2202705

The Hendra virus and the Nipah virus, which belong to the genus henipavirus in the family Paramyxoviridae, are known to infect humans and cause fatal disease; however, other related henipaviruses have been detected in bats, rodents, and shrews. During sentinel surveil-lance of febrile patients with a recent history of animal exposure in eastern China, a phyloge-netically distinct henipavirus, named Langya henipavirus (LayV), was identified in a throat swab sample from one patient by means of metagenomic analysis and subsequent virus iso-lation. The genome of LayV is composed of 18,402 nucleotides with a genome organization that is identical to that of other henipaviruses (Fig. 1A). LayV is most phylogenetically related to Mojiang henipavirus, which was discovered in southern China (Fig. 1B). Subsequent investigation identified 35 pa-tients with acute LayV infection in the Shandong and Henan provinces of China, among whom 26 were infected with LayV only (no other patho-gens were present). These 26 patients presented with fever (100% of the patients), fatigue (54%), cough (50%), anorexia (50%), myalgia (46%), nausea (38%), headache (35%), and vomiting (35%), accompanied by abnormalities of throm-bocytopenia (35%), leukopenia (54%), and im-paired liver (35%) and kidney (8%) function. A serosurvey of domestic animals detected sero-positivity in goats (3 of 168 [2%]) and dogs (4 of 79 [5%]). Among 25 species of wild small animals surveyed, LayV RNA was predominantly detected in shrews (71 of 262 [27%]), a finding that sug-gests that the shrew may be a natural reservoir of LayV. (Additional details of the study are pro-vided in the Supplementary Methods section in the Supplementary Appendix, available with the full text of this letter at NEJM.org.)Although the current study does not fulfill Koch’s postulates, the following findings from the patients with acute LayV infection suggest that LayV was the cause of febrile illness: LayV was the only potential pathogen detected in 26 of the 35 patients (74%) with acute LayV infec-tion; in paired serum samples that were ob-tained from 14 patients during the acute and convalescent phases of infection, the IgG titers in 86% of the convalescent-phase samples were 4 times as high as those in the acute-phase samples; viremia was associated with acute LayV infection; and the patients with pneumonia had higher viral loads than those without pneumonia (mean [±SD] log10-transformed copies per milli-liter, 7.64±0.98 vs. 4.52±1.13). Although human-to-human transmission has been reported for the Nipah virus,5 we found no obvious spatial or temporal aggregation of human cases or the as-signed haplotypes on the basis of three common single-nucleotide polymorphisms (Fig. 1C). There was no close contact or common exposure his-tory among the patients, which suggests that the infection in the human population may be spo-radic. Contact tracing of 9 patients with 15 close-contact family members revealed no close-con-tact LayV transmission, but our sample size was too small to determine the status of human-to-human transmission for LayV. The potential cross-reaction with Mojiang virus should be assessed to improve serologic testing.In our study, a newly identified henipavirus of probable animal origin was associated with febrile illness, a finding that warrants further investi-gation to better understand associated human illness.

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