Monday, January 09, 2017

Beneath The H7N9 Pyramid


The announcement this morning from China (via Hong Kong's CHP) that the number of  Mainland H7N9 cases in December was nearly 5 times greater than what had previously been reported - and in this first week of January this year's tally now exceeds last year's entire epidemic season (n=121) - will undoubtedly raise some concerns.

The lack of specifics on these cases makes it impossible to know what may be behind this surge. A colder, wetter winter?  A change in the virus? It is even possible that changes in China's surveillance and testing procedures could be picking up a greater percentage of cases this year than they did last year. 

The numbers detected and reported - even under the best of circumstances - are inevitably only a subset of the total number of cases in the community.  H7N9 - like other viral infections - can produce a wide spectrum of illness, ranging from severe and life threatening to mild or even asymptomatic.

So only those sick enough to seek medical treatment in a hospital are likely to be tested (the exception being contacts of a known case tested as part of an epidemiological investigation).  What percentage that might be, is frankly, unknown.

In 2013 we saw several attempts to estimate the likely number of H7N9 cases in China.

In April of that year, in H7N9: Trying To Define The Size Of The Iceberg, University of Hong Kong researchers announced that they believed the actual number of cases was at least twice the number being reported. 

A few weeks later, the Eurosurveillance Journal  carried a rapid communications from researchers at the University of Hong Kong, where they announced the likely number of cases to be several times higher than reported.

8, Issue 19, 09 May 2013
Preliminary inferences on the age-specific seriousness of human disease caused by avian influenza A(H7N9) infections in China, March to April 2013
B J Cowling , G Freeman, J Y Wong, P Wu, Q Liao, E H Lau, J T Wu, R Fielding, G M Leung
Between 31 March and 21 April 2013, 102 laboratory-confirmed influenza A(H7N9) infections have been reported in six provinces of China. Using survey data on age-specific rates of exposure to live poultry in China, we estimated that risk of serious illness after infection is 5.1 times higher in persons 65 years and older versus younger ages.

Our results suggest that many unidentified mild influenza A(H7N9) infections may have occurred, with a lower bound of 210–550 infections to date.
(Continue . . .)

By mid-summer, another analysis (by the same researchers) 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.  In this new study (after citing many limitations to the data) they write:

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. The accuracy of these estimates is unknown, and subject to debate, but it is all but certain that the official case counts under-represent the real burden of H7N9, perhaps by a sizable margin.

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.

Whether China is capturing and reporting 1%, 10%  or even 50% of the actual cases, the simple truth is whatever number is being reported is invariably wrongAt best, the numbers we have are an indication of how fast cases are spreading, and where they are turning up - and even then we have to take them with a sizable grain of salt.

Given the lack of transparency and dearth of case details coming out of Mainland China, our best early warning system is likely to be Hong Kong's CHP, which conducts rigorous epidemiological investigations on all imported cases, and has been very good about releasing the results promptly.

While it is important to watch these cases in China carefully, it is probably even more important for us to monitor Hong Kong's reactions to them.  

Meanwhile, Crof, Sharon Sanders and the newshounds on FluTrackers, the staff at CIDRAP, and I will continue to collect what information we can and try to make sense of it.  But the numbers are - and have long been - confusing, incomplete, and only a broad indicator of what the virus is up to.

Stay tuned.