Ursula Höfle
Contracted Lecturer, member of the SaBio Group at the Institute for Game and Wildlife Research (IREC) (CSIC-UCLM-JCCM)
A study published in Eurosurveillance as a result of collaboration between Animal Health and Public Health authorities clarifies the known cases of detection of HPAI H5N1 virus in humans in Spain. The study reports how in the course of investigations associated with an outbreak of avian influenza on a chicken farm, two workers tested positive for HPAI genetic material in nasopharyngeal swabs during the initial screening of all workers on the farm or involved in the slaughter of birds and subsequent cleaning. He also reports that the workers had no symptoms and that all subsequent tests were negative. In addition, the workers did not develop antibodies to the virus.
The study puts the event in the context of the current epizootic of this virus in wild and domestic birds in Europe and Spain, and provides the references for accessing the sequences obtained from the detections in the workers and birds on the farm. They also make a comparison between the sequences obtained from farm birds and workers in search of any sign of virus adaptation to the human host, finding only three differences to which they do not attribute any effect on the transmissibility or pathogenicity of the virus.
They conclude that it was not an infection as such (which implies entry of the virus into respiratory tract cells and replication and amplification, and this in turn would have generated an antibody response in humans). Rather, they postulate that what has been detected is possible environmental contamination (genetic material of the virus present in dust deposited in the respiratory tract of workers), and that in order not to create false alarms it is necessary to employ surveillance protocols that detect only real infections as such.
This is a transparent and robust study that clearly demonstrates the advantages and disadvantages of the extremely sensitive and accurate molecular tools we have at hand today for the diagnosis of certain infections. It shows that the results obtained by these tests can only be interpreted in context with the situation on the ground and when and how the samples were taken.
The study is in line with evidence that to date there is no adaptation of the virus to infect humans or to transmit between humans. It underlines the importance of distinguishing between the detection of genetic material of a pathogen and the confirmation of an actual infection.
The study shows that it is very important not to confuse detection of genetic material with infection. We have become accustomed to polymerase chain reaction (PCR) as a means of diagnosis because of covid-19, however, a positive PCR alone does not actually confirm that the specific fragment of the genetic material of what we are looking for is present. That is, it does not in itself confirm an infection, as the pathogen in question may be only on the surface without being able to cause an actual infection, in the environment, or it may be completely degraded and unable to replicate. To speak of an infection it is necessary to interpret the PCR result in conjunction with other data such as the presence of symptoms, another PCR spaced over time that re-detects the agent, or even an isolation or the development of antibodies.
The study points out that, by implementing testing of occupationally exposed persons in a generic way, genetic material of the virus that may be in the environment or even in the nasal cavity or larynx of the patient in combination with inhaled dust particles is detected, and that considering a positive PCR as diagnostic may create a false alarm.
I see two direct implications. On the one hand, the number of human "cases" caused by H5N1 is reduced, as it is not confirmed in the two individuals in this study, but on the other hand it does confirm exposure. This should reinforce the acceptance of the need to follow biosecurity and personal protection measures for all farm workers.
On the other hand, the results of the study are a call for caution and the importance of the design of surveillance programmes and the correct interpretation of data. In this case, if samples from asymptomatic exposed people are taken and tested too early, they may be misinterpreted as infection/transmission to humans, results that are only due to the high efficiency of currently available diagnostic techniques.