J. Infect. Diseases: Human Clusters Of H7N9 In China - March 2013 to June 2015

#12,771


Although the vast majority of H7N9 infections have been attributed to direct or indirect contact with infected birds - particularly at live bird markets - we've seen scattered reports of small clusters where human-to-human transmission has been considered a possibility. 

Details on these clusters, often provided in WHO updates, have been slim - particularly since early in 2015 when China abruptly stopped detailed reporting on cases (see H7N9: No News Is . . . . Curious).

While reporting from China has gotten considerably better since January of this year, we still aren't seeing the kind of epidemiological case detail we were seeing during the first two epidemic waves (2013-2014). 

Although a record number of cases have been reported during this 5th Epidemic wave (n=766), only the `sickest of the sick' are hospitalized and tested, and so the actual number of human infections is believed to be much larger. 

All of which brings us to a new study, published this past week in the Journal of Infectious Diseases, which examined the known details on 21 H7N9 clusters (involving 22 contacts) from the first three waves, and found that at least 12 infections were likely the result of human-to-human transmission, another 4 were considered `possible', while 6 were determined to be unlikely.

First the abstract and link to the study (which, alas, is behind a paywall) then I'll return with a bit more.

J Infect Dis. 2017 Sep 15;216(suppl_4):S548-S554. doi: 10.1093/infdis/jix098.

Clusters of Human Infections With Avian Influenza A(H7N9) Virus in China, March 2013 to June 2015.

Liu B1, Havers FP2, Zhou L1, Zhong H3, Wang X4, Mao S5, Li H6, Ren R1, Xiang N1, Shu Y7, Zhou S8, Liu F9, Chen E10, Zhang Y1, Widdowson MA2, Li Q1, Feng Z11.

Author information
Abstract

Multiple clusters of human infections with novel avian influenza A(H7N9) virus have occurred since the virus was first identified in spring 2013. However, in many situations it is unclear whether these clusters result from person-to-person transmission or exposure to a common infectious source.

We analyzed the possibility of person-to-person transmission in each cluster and developed a framework to assess the likelihood that person-to-person transmission had occurred. We described 21 clusters with 22 infected contact cases that were identified by the Chinese Center for Disease Control and Prevention from March 2013 through June 2015.

Based on detailed epidemiological information and the timing of the contact case patients' exposures to infected persons and to poultry during their potential incubation period, we graded the likelihood of person-to-person transmission as probable, possible, or unlikely. We found that person-to-person transmission probably occurred 12 times and possibly occurred 4 times; it was unlikely in 6 clusters. Probable nosocomial transmission is likely to have occurred in 2 clusters.

Limited person-to-person transmission is likely to have occurred on multiple occasions since the H7N9 virus was first identified. However, these transmission events represented a small fraction of all identified cases of H7N9 human infection, and sustained person-to-person transmission was not documented.

Some of these cases have been previously discussed in this blog, including:

EID Journal: Nosocomial Co-Transmission Of H7N9 & H1N1pdm09 

Study: Probable Nosocomial Transmission Of H7N9 In China

It is worth noting that since 2015, the H7N9 virus has undergone significant changes, both genetically, and in its behavior. In 2015's EID Journal: The Transmission Potential Of A(H7N9) In China, the authors found that while no evidence of sustained transmission was detected, they noted:

• `evidence of a small but significant amount of transmission between humans in the first and second waves’
• `evidence of increased transmission potential in the second wave

While in May of 2016, in EID Journal: Human Infection With H7N9 During 3 Epidemic Waves - China, researchers found patients hospitalized in the 2nd and 3rd wave with severe H7N9 tended to be younger, and from more rural areas, than those from the 1st wave.

They also found that the risk of death among hospitalized patients was greater in the second and third waves, although that varied between provinces.

Earlier this month, in the MMWR's  Update: Increase in Human Infections with Novel Asian Lineage Avian Influenza A(H7N9) Viruses During the Fifth Epidemic — China, October 1, 2016–August 7, 2017, the authors wrote about more recent changes in the virus:

During the fifth epidemic, mutations were detected among some Asian H7N9 viruses, identifying the emergence of high pathogenic avian influenza (HPAI) viruses as well as viruses with reduced susceptibility to influenza antiviral medications recommended for treatment. Furthermore, the fifth-epidemic viruses diverged genetically into two separate lineages (Pearl River Delta lineage and Yangtze River Delta lineage), with Yangtze River Delta lineage viruses emerging as antigenically different compared with those from earlier epidemics.

Because of its pandemic potential, candidate vaccine viruses (CVV) were produced in 2013 that have been used to make vaccines against Asian H7N9 viruses circulating at that time. CDC is working with partners to enhance surveillance for Asian H7N9 viruses in humans and poultry, to improve laboratory capability to detect and characterize H7N9 viruses, and to develop, test and distribute new CVV that could be used for vaccine production if a vaccine is needed.

While H7N9 hasn't managed to adapt well enough to human physiology to transmit efficiently, the CDC's IRAT system ranks the newly emerged Yangtze River Delta lineage along with the original Pearl River Delta Lineage (see Updating the CDC's IRAT (Influenza Risk Assessment Tool) Rankings) at the top of their list of viruses with the greatest pandemic potential.