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H7N9 Sequence Identity In Baiyun Cluster
Recombinomics Commentary 14:00
March 11, 2014

Transmission of avian influenza A H7N9 virus from father to daughter: A report of limited person to person transmission
The above title of characterization sheets from three H7 sequences released at Genbank by the Guangzhou CDC supports earlier reports that this cluster raised concerns of human to human transmission (H2H) in Guangdong Province.  One sequence, A/Guangzhou/1/2014, is from the index case (29M) who was a tofu vender who lived in the Baiyun District of Guangzhou. A second H7 sequence, A/Guangzhou/2/2014, from his daughter (5F), was identical at all 1683 positions.  Moreover, an environmental bird flu sequence,
A/environment/Guangzhou/1/2014, from a cutting board at a nearby wet market, was also an exact match.  The father developed symptoms on January 3, while his daughter developed symptoms on January 14.  The 11 day gap in disease onset dates strongly supports H2H transmission, as does the exact match in the two H7 sequences.

This family represented the first reported cluster in Guangdong Province, and represented a profile that was repeated multiple times in the following days.  The index case was reported in the January 11 update at the Guangdong Health and Family Planning Committee (HFPC) website, which noted that the 29M case was from Baiyun district in Guangzhou, had a family name of Pan, and had a disease onset date of January 3.  The January 18 update described a child (5F) with a disease onset date of January 14, who was also from the Baiyun District, had the same family name (Pan), but who was characterized as having a “mild” presentation.

Both cases were also described in WHO H7N9 updates (January 14 and January 20, respectively) and the update on the daughter noted that hospitalization of the 5F was on January 15, one day after disease onset.  WHO characterized her condition as “stable”.  The hospitalization one day after disease onset of a mild or stable case is unusual, since there are millions of children in southern China who have mild flu-like symptoms in January.  The rapid hospitalization and H7N9 testing of this case strongly suggested that she was a contact of a confirmed H7N9 case, which was fully supported by her family name and location, which matched the earlier case (29M), even though neither the Guangdong HFPC reports nor the WHO updates noted that the 5F was a contact of the 29M.

Subsequent local media reports noted that the 5F was the daughter of the 29M, but cited potential common source exposures.  However, the best metric for distinguishing between common source and H2H transmission is disease onset dates.  Common source infections usually have a similar disease onset date, while H2H transmissions usually have glaring gaps in disease onset dates, such as the 11 days between onset dates for the father and daughter.

Although this cluster was the first familial H7N9 cluster in southern China, media coverage outside oif China was abysmal.  The lack of coverage was due in part by the failure of the Guangdong HFPC or WHO to note that the 5F was a contact/daughter of the index case.  However, the pattern involving a critically ill adult followed by H7N9 confirmation in a child who shared the same family name, was characterized as having mild or stable disease, and was from the same location as the adult, was frequent in southern China, including 3 Guangdong familial clusters in Huaiji, and a nearby cluster in Guangxi involving import from Guangdong and onward transmission.  Although this latter cluster was acknowledged by the Guangxi website and WHO, and was more widely described in media outside of China, the Guangdong and Hunan clusters were not, even though familial clusters are an early indicator of human adaptation.

Such adaptation is also supported by the receptor binding domain change of Q226L, the PB2 adaptation represented by E627K, as well as the increased frequency of H7 R56K, as well as the PA change of L336M.

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