The limits of surveillance and reporting
#18,249
While we often hear that there is `no evidence of human-to-human transmission of H5N1 in the United States', it is a statement deserving of an asterisk or three.
* We've seen a handful of confirmed infections where the source of exposure remains unknown.
Twenty-two years ago this month the world's attentions were focused on a different avian flu virus - HPAI H7N7 - which was spreading rapidly through hundreds of poultry farms in the Netherlands, infecting scores of farmers, and which killed a local veterinarian.
While the subtype (H7), and the livestock (poultry), were different, this outbreak has some similarities to the cattle/poultry HPAI H5N1 outbreak we've been following for more than a year in the United States.
In both cases, hundreds of farms were affected, and roughly the same number of people (U.S. 77, Netherlands 83) were confirmed as infected, with conjunctivitis being the major symptom reported. A handful of more serious infections (and 1 death) were reported in each country.
Of course, there are differences. In the Netherlands, through rapid culling, the outbreak was quashed after a little more than 2 months, while the outbreak in the United States continues after more than a year.
And in the Netherlands, a concerted effort was made to test as many people as possible for antibodies to the H7N7 virus, in order to better understand its spread. An analysis (by the RIVM), found the spread of the virus to be much greater than originally reported.
Investigation of risk factors, health, well-being, health-care needs, and preventive measures with regard to poultry farmers and persons involved in controlling the AI H7N7 epidemic in the NetherlandsA Bosman, YM Mulder, JRJ de Leeuw1 , A Meijer, M Du Ry van Beest Holle, RA Kamst, PG van der Velden1 , MAE Conyn-van Spaendonck, MPG Koopmans, MWMM Ruijten
It is estimated that at least one thousand persons were infected with avian flu during the outbreak in the Netherlands in 2003. One-third of the poultry farmers whose holdings were cleared reported stress reactions, fatigue, and depression.
The extensive spread of the virus to humans underscores the importance of measures to prevent poultry-to-human transmission among people handling infected poultry. The possible uncertainty, stress, and anxiety associated with avian flu control demand specific health care attention. A total of 453 people reported symptoms, predominantly conjunctivitis.
Antibodies were found in 59% of family members of infected poultry workers. Of the 500 tested persons who had handled infected poultry, about 50% showed an antibody response.
(Continue . . . )
More than two years after the outbreak, the CDC's EID Journal carried a report describing probable human-to-human transmission of the H7N7 virus.
Human-to-human transmission of avian influenza A/H7N7, The Netherlands, 2003
M Du Ry van Beest Holle, A Meijer, M Koopmans3 CM de Jager, EEHM van de Kamp, B Wilbrink, MAE. Conyn-van Spaendonck, A Bosman
An outbreak of highly pathogenic avian influenza A virus subtype H7N7 began in poultry farms in the Netherlands in 2003. Virus infection was detected by RT-PCR in 86 poultry workers and three household contacts of PCR-positive poultry workers, mainly associated with conjunctivitis.
(SNIP)
In conclusion, our study suggests that human-to-human transmission of HPAI A/H7N7 can occur within household contacts in the absence of contact with infected poultry.
Even if we discount the possibility of human-to-human transmission, the scope of the 2003 outbreak was at least 10 times greater than initially reported. Which, based on previous estimates of outbreaks of novel flu, is likely a low-ball number.
All of which brings us to a preprint (awaiting peer review) of a rapid review of the epidemiological parameters (R0, pathogenicity, serial interval, etc.) of H5N1 based on current data and previously published studies.
This review also compares the 2003 H7N7 outbreak to the current situation in the United States.
While you'll want to follow the link to read this 33-page preprint in its entirety, briefly the authors found evidence suggesting:
- H5N1 in humans currently shows poor transmissibility (Est. R0 < 0.2), but some limited H-2-H transmission may have occurred.
- The U.S. H5N1 virus appears more severe than seasonal flu, but less severe than previous H5N1 outbreaks
- The incubation period for H5N1 is roughly 4 days, which is longer than the ~2 days typical for seasonal flu
- The serial interval for H5N1 is approximately 6 days, compared to ~3 days for human influenza subtypes
Estimates of epidemiological parameters for H5N1 influenza in humans: a rapid review
Jack Ward, Joshua W. Lambert, Timothy W. Russell, James M. Azam, Adam J. Kucharski, Sebastian Funk, Billy J. Quilty, Oswaldo Gressani, Niel Hens W. John Edmunds
doi: https://doi.org/10.1101/2024.12.11.24318702
This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.
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Abstract
Background The ongoing H5N1 panzootic in mammals has amplified zoonotic pathways to facilitate human infection. Characterising key epidemiological parameters for H5N1 is critical should it become widespread.
Aim To identify and estimate critical epidemiological parameters for H5N1 from past and current outbreaks, and to compare their characteristics with human influenza subtypes and the 2003 Netherlands H7N7 outbreak.
Methods We searched PubMed, Embase, and Cochrane Library for systematic reviews reporting parameter estimates from primary data or meta-analyses. To address gaps, we searched PubMed and Google Scholar for studies of any design providing relevant estimates. We estimated the basic reproduction number for the outbreak in the US and the 2003 Netherlands H7N7 outbreak. In addition we estimated the serial interval for H5N1 using data from previous household clusters in Indonesia. We also applied a branching process model to simulate transmission chain size and duration to assess if simulated transmission patterns align with observed dynamics.
Results From 46 articles, we identified H5N1’s epidemiological profile as having lower transmissibility (R0 < 0.2) but higher severity compared to human subtypes. Evidence suggests H5N1 has a longer incubation (∼4 days vs ∼2 days) and serial intervals (∼6 days vs ∼3 days) than human subtypes, impacting transmission dynamics. The epidemiology of the US H5 outbreak is similar to the 2003 Netherlands H7N7 outbreak. Key gaps remain regarding latent and infectious periods.
Conclusions We characterised critical epidemiological parameters for H5N1 infection. The current U.S. outbreak shows lower pathogenicity, but similar transmissibility compared to prior outbreaks. Longer incubation and serial intervals may enhance contact tracing feasibility. These estimates offer a baseline for monitoring changes in H5N1 epidemiology.
(SNIP)
Conclusion
We have assessed and estimated critical epidemiological parameters for human H5N1 based on past and current outbreaks. The outbreak in the US appears to have lower pathogenicity than observed in previous H5N1 outbreaks, and its clinical and epidemiological picture appears more similar to the H7N7 outbreak in the Netherlands in 2003. H5N1 may have a longer incubation period, and serial interval compared to human influenza subtypes.
These characteristics may allow for more effective contact tracing more than is typically the case for influenza (depending on the degree of presymptomatic transmission). Despite these insights, data on H5N1 infections remain sparse and critical gaps remain in our understanding. Addressing these gaps and continually monitoring the epidemiology is imperative to enhance our preparedness and assess whether the risk from these viruses is potentially escalating.
