Monday, November 14, 2022

Zoonoses & Pub. Health: Influenza D Virus Exposure Among US Cattle Workers: A Call for Surveillance

Credit NIAID


When I began this blog 17 years ago there were 3 recognized types of influenza; Influenza A, B, and C.  Influenza A - due to its ability to reassort with other flu viruses, and its perceived greater severity - was considered the biggest threat to public health.  

Influenza B was treated like a weak sibling, and influenza C was scarcely mentioned at all.

Over time, we've come to understand that influenza B can be every bit as severe as influenza A (see Influenza B: A Virus Not To Be Underestimated), and while little studied and rarely tested for, Influenza C can also produce significant morbidity and mortality (see Hong Kong: A Severe Pediatric Case Of Influenza C).

In 2011, a 4th influenza type was discovered; Influenza D.

We first learned of this new flu early in 2013 when researchers reported finding a novel influenza virus in swine from Oklahoma - initially classified as a novel Influenza virus - but which would later be designated as Influenza D.

Their research – published PLoS Pathogens – was called Isolation of a Novel Swine Influenza Virus from Oklahoma in 2011 Which Is Distantly Related to Human Influenza C Viruses, and it immediately caused a stir in the flu research community. 
The authors found that this new (provisional) influenza C virus could infect, and transmit, in both ferrets and pigs. 

The following year, in mBio: Characterizing A Novel Influenza C Virus In Bovines & Swine, cattle were added to the list, and now appears to be the virus's primary reservoir.

In 2019's, J. Clinical Med. : A Review Of The Emerging Influenza D Virus, the authors wrote:

The mixed reports for IDV infections in humans further make it important to study the zoonotic potential of IDV, especially in people with occupational exposure to susceptible livestock. Since IDV shows potential to infect a wide range of host after IAVs, its zoonotic potential is a global concern.
Also in 2019, we saw the detection of Influenza D Virus Infection in Dromedary Camels, Ethiopia and the Detection of a New Genetic Cluster of Influenza D Virus in Italian CattleSimply put, the more we look, the more we find. 

All of which brings us to a new report, published in Zoonoses and Public Health, which describes a new seroprevalence study of cattle workers, where they found evidence (via a nasal wash) of daily exposure to the virus. 

I've included the link, abstract, and discussion from this report, but you'll want to read it in its entirety.  I'll have a brief postscript when you return. 

First published: 12 November 2022


Although cattle are a reservoir for influenza D virus (IDV), little is known about human exposure to IDV. We assessed IDV exposure and associated health effects among United States dairy workers, a population at heightened risk of cattle zoonoses. In prospective, cross-shift sampling of 31 workers employed at five large-herd dairy operations in two states, we found evidence of IDV in the nasal washes of 67% of participants at least once during the 5-day study period. IDV exposure was not associated with respiratory symptoms in these workers. These findings suggest that IDV is present in dairy cattle environments and can result in worker exposure.

  • Influenza D virus (IDV) is an emerging genus of zoonotic influenza virus identified commonly in dairy cattle, although little is known about human exposure.
  • More than 2/3 of dairy workers in a longitudinal, cross-shift study (n = 31) had an IDV-positive nasal wash at least once during the study period.
  • IDV was not associated with respiratory symptoms in this study, and the ‘silent’ nature of carriage reinforces the need to actively monitor spillover of this pathogen to humans.
More than two-thirds of dairy workers enrolled this prospective, a cross-shift study had molecular evidence of IDV exposure, and this exposure appears transient. IDV-positive nasal washes were obtained from workers at all dairies sampled, suggesting widespread occupational exposure in this industry. Overall, these findings suggest that dairy workers experience chronic IDV exposure, but that the pathogen is a transient constituent of the nasal microbiome. IDV exposure was not associated with respiratory symptoms, and to date, there is no evidence that IDV causes clinical disease in humans.

In our study, we identified concurrent positive dairy worker nasal washes with IAV, ICV and IDV, each of which has been recognized to infect cattle. (Sreenivasan et al., 2019; Zhang et al., 2018) The relevance of pathogen-pathogen interactions within the respiratory microbiome of livestock workers is an important area for future study.

We recovered avian IAV from aerosol monitoring. This finding likely reflects inter-species interaction within open dairy operations, where wild birds are known to frequent. Cross-species transmission of avian influenza viruses poses risks for IAV pandemic emergence, and our observations highlight the ongoing need for influenza surveillance in these facilities. The role of livestock facilities as ‘mixing bowls’ for multiple influenza viruses remains an important consideration. Collecting information on contact between avians and domesticated animals—and potential human exposures to multiple species at work—is a key priority in future research to elaborate on the role of industrial livestock facilities in the generation of novel viruses.

This study is limited by its small size, which reduced our ability to infer occupational risk factors. Sequencing IDV was challenging due to the lack of established and optimized assays for amplifying and subtyping IDV. It remains possible that IDV carriage identified here is a function of community, and not occupational exposure, despite an understanding of IDV's animal reservoir. Data on IDV carriage within the dairy herds would clearly have strengthened our understanding of the role of occupation in these exposures but was beyond the scope of this small study. Information on animal contact at home or otherwise outside of primary work would have strengthened our understanding of pre-shift IDV positives, but in the context of a small sample, this information was difficult to interpret. Likewise, serology on these workers would have also advanced our understanding of IDV exposure in this population. These issues remain important areas for follow-up study. Our work is strengthened by cross-shift and repeated sampling using paired environmental and respiratory samples, granting a robust understanding of exposure within large-herd dairy operations.

Our findings suggest that IDV is present in dairy cattle environments and can result in worker exposure. As IDVs have been detected across geographical areas, it is prudent to conduct surveillance for emergent, and possibly more virulent, IDVs that may cause human disease.

Although it has never been demonstrated that Influenza D can cause symptomatic illness in humans, in 2016 - in Serological Evidence Of Influenza D Among Persons With & Without Cattle Exposure - researchers did report finding a high prevalence of antibodies against Influenza D (IDV) among people with cattle exposure. They wrote:

IDV poses a zoonotic risk to cattle-exposed workers, based on detection of high seroprevalence (94–97%). Whereas it is still unknown whether IDV causes disease in humans, our studies indicate that the virus may be an emerging pathogen among cattle-workers.
While the zoonotic threat from Influenza D appears minimal right now, this is obviously a virus that continues to evolve, and to spread globally in a variety of hosts.  

Add in its ability to infect, and transmit, in pigs and ferrets - and the apparent continual exposure of cattle-workers - and this virus is worthy of greater attention.