#17,952
We've a fascinating, albeit lengthy and fairly technical preprint this week in Nature Portfolio, which describes a seroprevalence survey looking for influenza antibodies (H1N1, H3N2 & 2 HP H5N1) that was conducted in 2015 on 2,000 residents living in Northern (Malaysian) Borneo.
We've seen similar studies in the past - usually conducted either in the wake of a known H5N1 outbreak or among high risk poultry farmers - which have shown varying rates of presumed previous H5 exposure, including:
- In 2012, in H5N1 Seroprevalence Among Jiangsu Province Poultry Workers, we saw a study that found across three locations tested (Gaochun, Jianhu and Gaoyou counties) the percentage of workers testing positive ranged from zero (Gaochun) to 5.38% (95%CI, 2.19%–10.78%) in Gaoyou.
- In 2011, a study (see Subclinical H5 & H9 Infections In Humans) tested 605 residents in and around Beijing China for antibodies to H5 and H9 avian flu viruses. Of these, just 5 (less than 1%) had antibodies to H9 avian influenza, and only 1 was positive for antibodies to H5.
- In May of 2009 (see Cambodian Study Finds Rare Asymptomatic H5N1 Infections) we saw a study published in the Journal of Infectious Diseases on more than 600 members of a Cambodian village where 2 human H5N1 cases were detected in 2006. Antibody titers showed that only 1% (7 of 674) of the villagers tested had contracted, and fought off, the H5N1 virus. A figure much lower than many had expected.
- In 2004 (see The Thailand Serological Study) 322 poultry farmers (in provinces where H5N1 had been detected) were tested. Researchers found that "no poultry workers had microneutralization titers >80, whereas 7 (2%) had lower titers that did not meet the WHO definition for seropositivity".
In other words, there has always been some degree of ambiguity regarding these seroprevalence surveys.
Today's preprint not only offers methods for improving the accuracy of seroprevalence testing, it reports likely HPAI H5 exposure in some individuals living in a region of northern Borneo which - at that time - had never reported H5N1 in poultry or people
Exposure to poultry - particularly in live bird markets - is often cited as the biggest risk factor for contracting avian flu (see excerpt from WHO assessment below).
For avian influenza viruses, the primary risk factor for human infection appears to be exposure to infected live or dead poultry or contaminated environments, such as live bird markets. Slaughtering, defeathering, handling carcasses of infected poultry, and preparing poultry for consumption, especially in household settings, are also likely to be risk factors.
Today's study suggests that living in close proximity to large numbers of migratory birds could entail some risks as well, and that those people be included in routine surveillance.
A finding that is bolstered by last year's H5N1 infection in Chile, where researchers found:
An epidemiological investigation being conducted by the Ministry of Health ascertained that the patient’s residence is located one block from the seashore where seabirds infected with H5N1 viruses had previously been detected. For that reason, an infection of environmental origin is suspected.
I've only included some excerpts from a much longer report, so follow the link to read it in its entirety. I'll have a brief postscript after the break.
Serological analysis in humans in Malaysian Borneo suggests prior exposure to H5 avian influenza
Hannah Klim, Timothy William, Caolann Brady, Tock Chua, Helena Brazal Monzó, and 10 more
This is a preprint; it has not been peer reviewed by a journal.
https://doi.org/10.21203/rs.3.rs-4021361/v1
This work is licensed under a CC BY 4.0 License
Abstract
Cases of H5 highly pathogenic avian influenzas (HPAI) are on the rise. Although mammalian spillover events are rare, H5N1 viruses have an estimated mortality rate in humans of 60%. No human cases of H5 infection have been reported in Malaysian Borneo, but HPAI has circulated in poultry and migratory avian species transiting through the region.Recent deforestation in Malaysian Borneo may increase the proximity between humans and migratory birds. We hypothesise that higher rates of human-animal contact, caused by this habitat destruction, will increase the likelihood of potential zoonotic spillover events.In 2015, an environmentally stratified cross-sectional survey was conducted collecting geolocated questionnaire data in 10,100 individuals. A serological survey of these individuals reveals evidence of H5 neutralisation that persisted following depletion of seasonal H1/H3 binding antibodies from the plasma.The presence of these antibodies suggests that some individuals living near migratory sites may have been exposed to H5. There is a spatial and environmental overlap between individuals displaying high H5 binding and the distribution of migratory birds. We have developed a novel surveillance approach including both spatial and serological data to detect potential spillover events, highlighting the urgent need to study cross-species pathogen transmission in migratory zones.
(SNIP)
Here, we perform a serological survey of human influenza exposure in Sabah, Malaysian Borneo to examine the immunological footprint of H5N1 in the region.
- We present a method for minimizing the impact of influenza subtype cross-reactivity on these serological results.
- We define species distributions of domesticated poultry and migratory wild birds and demonstrate that environmental covariates can be used as proxy to model wild bird contact.
- We additionally identify shared spatial distributions and environmental risk factors between the presence of migratory shorebirds and clade-specific H5N1 seroprevalence using a Bayesian framework.
This study highlights the need to increase surveillance for rare zoonotic diseases at migratory sites and presents an approach for modelling the distributions of serological results and reservoir species.
(SNIP)
Discussion
Our results show evidence of heterogenous serological responses to avian influenza in Sabah. These results are spatially correlated and follow the distribution and habitats of migratory wild birds over domesticated poultry in the region. As contact with avian species is currently necessary for a spillover event, it is critical to consider these migratory sights as key interfaces in stopping the viral spread.
There are shared environmental risk factors between the wild bird distributions and H5 binding (Fig. 4b). The identification of proximity to the sea, low elevation (i.e. sea level) areas, closeness to the forest, and remote areas indicate that we are not only reporting wild migratory shorebirds in their natural habitats16–18, but that these habitats are also areas where binding to the H5 2.3.4 antigen was highest. Shared environmental risk factors and the overlapping spatial distributions between wild birds and H5 binding, suggest that some kind of contact may be occurring between humans and wild birds in these locations. Future studies could collect contemporaneous data on wild bird movements and pathogen presence.
One mechanism of H5 spillover is the spread of the virus from wild birds to domesticated poultry and then into humans36. We can surmise that H5 2.3.4 binding is not related to poultry contact in this study, the inclusion of poultry ownership as a fixed effect did not approve model fit. Although poultry farmers can be at risk of encountering avian influenza36, our findings suggest a need to consider individuals living close to these migratory sites as a part of regular surveillance efforts (Supplemental Fig. 5).
Migratory shorebirds transiting between countries may carry influenza and expose individuals in the surrounding areas to avian viruses. Our results suggest that individuals living within 10km of known migratory locations may have had previously unknown exposure to avian influenza of the 2.3.4 or similar clade. As shorebird habits are being destroyed due to rising sea levels and land use changes, there is an urgent need to consider how this may force zoonotic reservoirs including migratory wild birds into closer contact with humans and increasing the risk of HPAI spillover.
Despite the common assertion (even mentioned in this report) that 60% of those who contract H5N1 have died, that number is based on cases that were sick enough to be hospitalized and lucky enough to be tested.
It is therefore likely that some number of cases (including mild or asymptomatic) go undetected. Perhaps many.
Since we don't have a good handle on the denominator, we can't have a lot of faith in CFR estimates. More reliable seroprevalence techniques could help us better understand that number, as well as track points of entry of the virus into humans.
Ten years ago, HPAI H5 viruses had difficulty persisting in migratory birds (see PNAS: The Enigma Of Disappearing HPAI H5 In North American Migratory Waterfowl). After causing a record breaking epizootic in North America over the winter of 2014-2015, the virus failed to return the following fall.
Over the next few years, the virus underwent several reassortments, which have increased its ability to spread via migratory birds.
- By 2017, HPAI H5 had crossed the equator for the first time and set up shop in South Africa.
- In 2021, HPAI H5N1 began regularly transiting the Atlantic and Pacific flyways (Multiple Introductions of H5 HPAI Viruses into Canada Via both East Asia-Australasia/Pacific & Atlantic Flyways).
- In July 2022, in DEFRA: The Unprecedented `Order Shift' In Wild Bird H5N1 Positives In Europe & The UK, we looked at the unexpected shift in H5N1 infection from mostly Anseriformes (waterfowl, such as ducks, geese, and swans) to Suliformes and Charadriiformes (shore birds) in 2022.
