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| Credit CDC |
#14,489
As discussed in my last blog, case counts picked up by public health surveillance - while useful - generally only represent the `tip of the iceberg' or - as in the CDC graphic above, the tip of the pyramid.
Between asymptomatic and mildly symptomatic cases who often never seek medical care, misdiagnosed patients, and cases that otherwise slip through the cracks, we never truly know how many people are infected during a disease outbreak.During the first wave of avian H7N9 in China in the spring of 2013, roughly 135 cases were identified. But a subsequent analysis appeared in the Lancet (see Lancet: Clinical Severity Of Human H7N9 Infection) that substantially raised their estimate of the total number of H7N9 cases in China. After citing many limitations to the data, they wrote:
Our estimate that between 1500 and 27 000 symptomatic infections with avian influenza A H7N9 virus might have occurred as of May 28, 2013, is much larger than the number of laboratory-confirmed cases.That's between a 12-fold and 200-fold increase in cases over what had been reported to that point.
If capturing less than 1% of the cases sounds absurd, we've seen similar estimates for other novel flu strains. In 2013 (see CID Journal: Estimates Of Human Infection From H3N2v (Jul 2011-Apr 2012)- estimated that during a time when only 13 cases were reported by the CDC - that the actual number of infections was likely 200 times (or more) higher.
Results. We estimate that the median multiplier for children was 200 (90% range, 115–369) and for adults was 255 (90% range, 152–479) and that 2055 (90% range, 1187–3800) illnesses from H3N2v virus infections may have occurred from August 2011 to April 2012, suggesting that the new virus was more widespread than previously thought.Mathematical models are worthwhile, but a better way to gauge the impact of a specific virus on a population is to conduct a seroprevalence study; to take blood samples from a cross section of society (or representing high risk groups) and to test them for virus specific antibodies.
These blood tests are not fool proof, as some infections (like MERS-CoV) can leave behind a temporary, less robust, antibody signature than others. And with some tests, cross-reactivity with other similar viruses may skew results.But seroprevalence studies can give us a much better, albeit retrospective, idea of the spread of many viral infections. Over the years we've looked at a number of them on avian flu, particularly in Asia and the Middle East.
- 2018's J. Infect & Public Health: High Seroprevalence Of Avian Influenza H9 Among Poultry Professionals In Pakistan, found an overall seroprevalence of 50.3% against H9 viruses.
- In 2016, in JID: High Seroprevalence Of H5N1 Antibodies In Indonesian Poultry Workers, we saw a study that found a remarkable 84% of the sera tested positive for antibody activity against the avian virus, despite a lack of reported serious illness among the 101 workers tested.
- Whereas 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.
Adding this list, this week the CDC's EID Journal published a new seroprevalence study that looks at antibodies for a wide range of avian flu viruses (H9N2, H7N9, H5N1, H6N1, H10N8, etc.) among poultry workers in Southern and Eastern China.
While none of their results reach the lofty heights previously reported among Indonesian and Pakistani poultry workers (see above), this study provides additional evidence of subclinical infection by a wide range of avian viruses.
This is a lengthy, data-rich study, so follow the link to read it in its entirety. When you return I'll have a postscript.
Volume 25, Number 12—December 2019
Research
Avian Influenza A Viruses among Occupationally Exposed Populations, China, 2014–2016
Chuansong Quan1, Qianli Wang1, Jie Zhang, Min Zhao, Qigang Dai, Ting Huang, Zewu Zhang, Shenghua Mao, Yifei Nie, Jun Liu, Yun Xie, Baorong Zhang, Yuhai Bi, Weifeng Shi, Peipei Liu, Dayan Wang, Luzhao Feng, Hongjie Yu, William J. Liu , and George F. Gao
Abstract
To determine the seroprevalence and seroconversion of avian influenza virus (AIV) antibodies in poultry workers, we conducted a seroepidemiologic study in 7 areas of China during December 2014–April 2016.
We used viral isolation and reverse transcription PCR to detect AIVs in specimens from live poultry markets. We analyzed 2,124 serum samples obtained from 1,407 poultry workers by using hemagglutination inhibition and microneutralization assays.
We noted seroprevalence of AIV antibodies for subtypes H9N2, H7N9, H6N1, H5N1-SC29, H5N6, H5N1-SH199, and H6N6. In serum from participants with longitudinal samples, we noted seroconversion, with >4-fold rise in titers, for H9N2, H7N9, H6N1, H5N1-SC29, H6N6, H5N6, and H5N1-SH199 subtypes. We found no evidence of H10N8 subtype.
The distribution of AIV antibodies provided evidence of asymptomatic infection. We correlated AIV antibody prevalence in live poultry markets with increased risk for H7N9 and H9N2 infection among poultry workers.
(SNIP)
Discussion
(Excerpt)
We observed higher prevalence for certain AIV subtypes and seroprevalence for certain AIV antibodies in live poultry markets, providing further evidence of cross-species transmission from birds to humans. Since the H7N9 outbreaks of 2013, consensus that AIV was transmitted from birds to humans led the government of China to implement epidemic control measures. The measures, such as closing live poultry markets during influenza season, cleaning and disinfecting live poultry markets daily, and vaccinating poultry, have effectively reduced the chances for human exposure to AIV-contaminated environments and ill poultry (38,39). Our results demonstrate that epidemic control measures aimed at live poultry markets, including their closure, can be highly effective in human AIV infection control (9,38).
Many participants with seropositivity were residents of southern and eastern provinces. Several determinants could account for this observation. First, the high density of live poultry markets, high population density, and expansive live poultry transportation network in these regions could favor large-scale and transboundary AIV spread in poultry, thereby increasing the risk for human infection (40). Second, these regions are rich in water resources, including the Yangtze and Pearl Rivers, as well as many lakes, which are natural habitats for waterfowl and wild birds that serve as natural hosts for various AIV subtypes, including H5Nx and H9N2 viruses, and that continually generate biological threats to public health (41,42). Studies suggest that migratory birds play a role in the evolution and spread of various zoonotic agents, and southeast China is located along the East Asian-Australian flyway, a migratory route for many bird species (43,44).
Our study had several limitations. Despite serious efforts to collect samples from the same participants during follow-up sampling, movement of vendors and poultry workers from target poultry markets reduced the possibility of obtaining paired samples. In addition, the relatively small sample size and use of only 1 location for the control group, Beijing in 2015, could be potential sources of bias.
In conclusion, our study provides serologic evidence of subclinical human AIV infection in an occupationally exposed population of poultry workers and corresponding AIV infection risk factors.
Because novel influenza viruses continue to emerge, our results show the need for enhanced etiologic surveillance of AIVs in live poultry markets and humans. Implementing poultry vaccination would also reduce human infection risk. Finally, our results demonstrate the need for active surveillance to foresee dynamic AIV epidemics and inform influenza vaccine development.
Dr. Quan was a medical doctor at the National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China during the study. His primary research interests include etiology and serology of influenza viruses and other emerging and reemerging viruses.
Despite the reassuring lack of avian flu reports out of China - due in large measure to their massive H5+H7 poultry vaccination campaign which began in 2017 - the avian flu threat has not gone away.
New viruses can emerge fairly often, and older subtypes can - over time - evolve far enough away from the existing vaccine to re-emerge.Last April, in OFID: Avian H5, H7 & H9 Contamination Before & After China's Massive Poultry Vaccination Campaign, we saw evidence that other avian viruses - particularly H9N2 - have surged in the wake of the H5+H7 vaccination campaign.
And lastly, the remarkable transparency displayed by China during the first two waves of H7N9 (2013-2014) has given way to more cryptic, and less frequent, updates over the past few years.
All of which means that while we enjoy this lull, we shouldn't assume it will last forever.
