#18,493
In June of this year, in WHO WPRO Reports 2nd H5N6 Case In Fujian, China In 2024, we learned of two fatal H5N6 infections, both hailing from Fujian Province, China, and which occurred within a few weeks of each other.
While the reports we get from China are often bereft of details, they sometimes fill in the gaps in follow-up reports, such as appears this week in China's CDC Weekly.
The two cases, it is now revealed, both resided in Quanzhou City, Fujian Province, China. The first fell ill on April 13th, and the second on May 9th. They lived less than 20 miles apart, and both were treated in the same hospital.
But the epidemiological investigation did not turn up any other links between them, and the viruses were sufficiently different to rule out human-to-human transmission.
While reassuring, they did find a number of worrisome mutations which may increase the virus's ability to infect, and transmit, in humans (see chart below).
While Case A had direct contact with poultry, Case B did not. This has led to the theory that Case B was exposed while walking down a path that came within 8 meters of a poultry shed.
Although direct exposure to infected poultry is the most common route of exposure to avian flu viruses, we've seen a number of cases whose likely exposures were cited as simply living near, or walking past an LBM (see J. Infection: Aerosolized H5N6 At A Chinese LBM (Live Bird Market)).
Case reports have slowed out of China the past few months, but we monitor this virus closely, as HPAI H5N6 continues to be one of the deadlier strains of HPAI H5, with a greater than 50% case fatality rate (among known cases).
I've only posted some excerpts from the China CDC report, so follow the link to read it in its entirety.
Outbreak Reports: Infection Tracing and Virus Genomic Analysis of Two Cases of Human Infection with Avian Influenza A(H5N6) — Fujian Province, China, April–May 2024Yanhua Zhang1; Jingjing Wu1; Qi Lin1; Jianming Ou1; Xiaoqi Qi1; Youxian Zheng2; Fengping Li2; Yuwei Weng1,
Summary
What is known about this topic?
Global human cases of zoonotic influenza A(H5N6) have increased significantly in recent years, primarily due to widespread circulation of clade 2.3.4.4b virus since 2020. Concurrent with this trend, sporadic human infections with clade 2.3.4.4h H5N6 avian influenza virus continue to occur. The high mortality rate associated with H5N6 virus infections has emerged as a critical public health concern.What is added by this report?
Through comprehensive field epidemiological investigations and laboratory analyses, we identified the infection sources for these cases and conclusively ruled out human-to-human transmission. Genetic analyses revealed that while the virus maintains its avian host tropism, it has acquired mutations that may enhance human receptor binding affinity, viral replication capacity, pathogenicity, and neuraminidase inhibitor resistance.What are the implications for public health practice?
The ongoing viral mutations increase the potential for H5 subtype avian influenza viruses to overcome species barriers and cause human epidemics. Enhanced surveillance strategies incorporating advanced technologies, such as metagenomic sequencing, are essential for early risk detection and management. Special attention should be directed toward cancer patients and immunocompromised individuals, who demonstrate increased susceptibility to avian influenza virus infections and require targeted prevention and control measures.
(SNIP)
DISCUSSION
Comprehensive analysis of epidemiological and laboratory data demonstrated that cases A and B were independent events with no epidemiological links. Medical observation of all close contacts revealed no signs of infection, providing strong evidence against human-to-human transmission in both cases.
Environmental investigation plays a crucial role in tracing avian influenza virus infections. Although both cases were associated with poultry illness or mortality prior to symptom onset, initial environmental sampling from the patients’ poultry sheds yielded negative results. This unexpected outcome can be attributed to two factors: the rapid disposal of diseased poultry before patient illness onset, which eliminated environmental viral evidence, and the implementation of thorough disinfection measures by families or health authorities prior to sampling. Nevertheless, viral genetic sequencing analysis of samples from surrounding poultry sheds near Case B provided definitive evidence for outbreak source identification.
The transmission routes differed between the two cases. Case A’s infection likely resulted from direct contact with diseased poultry, while Case B, who had no direct poultry exposure, suggested an alternative transmission pathway. Genetic analysis revealed 100% nucleotide sequence identity between Case B’s virus and samples from poultry shed Z, while distinct genetic differences were observed in viruses from shed Y and local live poultry markets. This evidence strongly indicates shed Z as Case B’s infection source. Although the viruses from both cases showed high sequence similarity, they were not identical, ruling out direct transmission between cases. The absence of infection among close contacts further confirms the lack of human-to-human transmission.
The location of poultry shed Z, approximately 8 meters from Case B’s regular walking route, suggests potential aerosol transmission over this distance. Notably, both cases exhibited compromised immune status: Case A experienced heavy rain exposure before illness onset, while Case B had nasopharyngeal cancer with ongoing chemotherapy and radiotherapy. The absence of symptoms among family members despite potential viral exposure suggests that immunocompromised status may represent a significant risk factor for H5N6 avian influenza virus infection in humans.
While genomic analysis revealed no significant recombination compared to recent H5N6 viruses, several concerning features were identified, including a highly pathogenic HA protein cleavage site and mutations associated with increased virulence, human infection potential, enhanced viral replication, and possible neuraminidase inhibitor resistance. The ongoing H5N1 outbreak in mammals in the United States heightens concerns about potential cross-species transmission and human epidemic risk. Although sustained human-to-human transmission of H5 subtype viruses remains undocumented, these findings underscore the critical importance of enhanced surveillance and robust pandemic preparedness measures.
