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Outbreak of henipavirus infection, Philippines, 2014.

ABSTRACT: During 2014, henipavirus infection caused severe illness among humans and horses in southern Philippines; fatality rates among humans were high. Horse-to-human and human-to-human transmission occurred. The most likely source of horse infection was fruit bats. Ongoing surveillance is needed for rapid diagnosis, risk factor investigation, control measure implementation, and further virus characterization.

SUBMITTER: Ching PK

PROVIDER: S-EPMC4313660 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Outbreak of henipavirus infection, Philippines, 2014.

Ching Paola Katrina G PK de los Reyes Vikki Carr VC Sucaldito Maria Nemia MN Tayag Enrique E Columna-Vingno Alah Baby AB Malbas Fedelino F FF Bolo Gilbert C GC Sejvar James J JJ Eagles Debbie D Playford Geoffrey G Dueger Erica E Kaku Yoshihiro Y Morikawa Shigeru S Kuroda Makoto M Marsh Glenn A GA McCullough Sam S Foxwell A Ruth AR

Emerging infectious diseases 20150201 2

During 2014, henipavirus infection caused severe illness among humans and horses in southern Philippines; fatality rates among humans were high. Horse-to-human and human-to-human transmission occurred. The most likely source of horse infection was fruit bats. Ongoing surveillance is needed for rapid diagnosis, risk factor investigation, control measure implementation, and further virus characterization. ...[more]

PMID: 25626011

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Project description:UNLABELLED:Nipah virus and Hendra virus are emerging, highly pathogenic, zoonotic paramyxoviruses that belong to the genus Henipavirus. They infect humans as well as numerous mammalian species. Both viruses use ephrin-B2 and -B3 as cell entry receptors, and following initial entry into an organism, they are capable of rapid spread throughout the host. We have previously reported that Nipah virus can use another attachment receptor, different from its entry receptors, to bind to nonpermissive circulating leukocytes, thereby promoting viral dissemination within the host. Here, this attachment molecule was identified as heparan sulfate for both Nipah virus and Hendra virus. Cells devoid of heparan sulfate were not able to mediate henipavirus trans-infection and showed reduced permissivity to infection. Virus pseudotyped with Nipah virus glycoproteins bound heparan sulfate and heparin but no other glycosaminoglycans in a surface plasmon resonance assay. Furthermore, heparin was able to inhibit the interaction of the viruses with the heparan sulfate and to block cell-mediated trans-infection of henipaviruses. Moreover, heparin was shown to bind to ephrin-B3 and to restrain infection of permissive cells in vitro. Consequently, treatment with heparin devoid of anticoagulant activity improved the survival of Nipah virus-infected hamsters. Altogether, these results reveal heparan sulfate as a new attachment receptor for henipaviruses and as a potential therapeutic target for the development of novel approaches against these highly lethal infections. IMPORTANCE:The Henipavirus genus includes two closely related, highly pathogenic paramyxoviruses, Nipah virus and Hendra virus, which cause elevated morbidity and mortality in animals and humans. Pathogenesis of both Nipah virus and Hendra virus infection is poorly understood, and efficient antiviral treatment is still missing. Here, we identified heparan sulfate as a novel attachment receptor used by both viruses to bind host cells. We demonstrate that heparin was able to inhibit the interaction of the viruses with heparan sulfate and to block cell-mediated trans-infection of henipaviruses. Moreover, heparin also bound to the viral entry receptor and thereby restricted infection of permissive cells in vitro. Consequently, heparin treatment improved survival of Nipah virus-infected hamsters. These results uncover an important role of heparan sulfate in henipavirus infection and open novel perspectives for the development of heparan sulfate-targeting therapeutic approaches for these emerging infections.

Project description:BackgroundAs we reported previously, Getah virus infection occurred in horses at the Miho training center of the Japan Racing Association in 2014. This was the first outbreak after a 31-year absence in Japan. Here, we report a recurrent outbreak of Getah virus infection in 2015, sequential to the 2014 one at the same site, and we summarize its epizootiological aspects to estimate the risk of further outbreaks in upcoming years.ResultsThe outbreak occurred from mid-August to late October 2015, affecting 30 racehorses with a prevalence of 1.5% of the whole population (1992 horses). Twenty-seven (90.0%) of the 30 affected horses were 2-year-olds, and the prevalence in 2-year-olds (27/613 [4.4%]) was significantly higher than that in horses aged 3 years or older (3/1379 [0.2%], P < 0.01). Therefore, the horses newly introduced from other areas at this age were susceptible, whereas most horses aged 3 years or older, which had experienced the previous outbreak in 2014, were resistant. Among the 2-year-olds, the prevalence in horses that had been vaccinated once (10/45 [22.2%]) was significantly higher than that in horses vaccinated twice or more (17/568 [3.0 %], P < 0.01). Horse anti-sera raised against an isolate in 2014 neutralized both the homologous strain and a 2015 isolate at almost the same titers (256 to 512), suggesting that these viruses were antigenically similar. Among horses entering the training center from private surrounding farms in 2015, the seropositivity rate to Getah virus increased gradually (11.8% in August, 21.7% in September, and 34.9% in October). Thus, increased virus exposure due to the regional epizootic probably allowed the virus to spread in the center, similarly to the outbreak in 2014.ConclusionsThe 2015 outbreak was caused by a virus which was antigenically close to the 2014 isolate, affecting mostly 2-year-old susceptible horses under epizootiological circumstances similar to those in 2014. The existence of 2-year-olds introduced from regions free from Getah virus could continue to pose a potential risk of additional outbreaks in upcoming years. Vaccination on private farms and breeding farms would help to minimize the risk of outbreaks.

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Outbreak of henipavirus infection, Philippines, 2014.

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Outbreak of henipavirus infection, Philippines, 2014.

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