Credit CDC
# 7829
The yardstick by which the epidemic potential of a virus is measured is called the R0 (R naught) or Basic Reproductive Number. Essentially, the number of new cases in a susceptible population likely to arise from a single infection.
With an R0 below 1.0, a virus (as an epidemic) begins to sputter and dies out.
Above 1.0, and an epidemic can have `legs’.
Some viruses have extremely high R0s. Measles and pertussis are extremely communicable, and fall between 12 and 18. In comparison, seasonal influenza runs from about 1.7 to to 2.1 (cite Quantifying the transmissibility of human influenza and its seasonal variation in temperate regions).
The R0 can be difficult to gauge properly, particularly very early in an outbreak, because it requires a lot of good epidemiological data. Often unknown (at least until serological studies can be conducted) is the rate of mild or asymptomatic infection with a virus, and that can skew the results. The R0 can also vary with time, meaning that the transmissibility of a virus today may be different from its transmissibility next week, or next month.
Still, even with these limitations, estimates of the R0 can help us understand the epidemic (or even pandemic) potential of a virus.
Which brings us to an open access study, that appears in BMC Medicine (h/t Sharon Sanders on FluTrackers), that looks at the transmission potential of the H7N9 virus, using confirmed cases from last spring. The authors – based on the 132 lab confirmed cases - estimate the virus to have a low R0 - well below 1.0 – suggesting a low epidemic potential.
Encouraging results, although there remains significant uncertainty over the total number of H7N9 infections in China last spring (I’ll return with more on that potential complication, after the abstract).
Transmission potential of influenza A/H7N9, February to May 2013, China
Gerardo Chowell, Lone Simonsen, Sherry Towers, Mark A Miller and Cécile Viboud
Background
On 31 March 2013, the first human infections with the novel influenza A/H7N9 virus were reported in Eastern China. The outbreak expanded rapidly in geographic scope and size, with a total of 132 laboratory-confirmed cases reported by 3 June 2013, in 10 Chinese provinces and Taiwan. The incidence of A/H7N9 cases has stalled in recent weeks, presumably as a consequence of live bird market closures in the most heavily affected areas. Here we compare the transmission potential of influenza A/H7N9 with that of other emerging pathogens and evaluate the impact of intervention measures in an effort to guide pandemic preparedness.
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Results
Estimates of R for the A/H7N9 outbreak were below the epidemic threshold required for sustained human-to-human transmission and remained near 0.1 throughout the study period, with broad 95% credible intervals by the Bayesian method (0.01 to 0.49). The Bayesian estimation approach was dominated by the prior distribution, however, due to relatively little information contained in the case data. We observe a statistically significant deceleration in growth rate after 6 April 2013, which is consistent with a reduction in A/H7N9 transmission associated with the preemptive closure of live bird markets. Although confidence intervals are broad, the estimated transmission potential of A/H7N9 appears lower than that of recent zoonotic threats, including avian influenza A/H5N1, swine influenza H3N2sw and Nipah virus.
Conclusion
Although uncertainty remains high in R estimates for H7N9 due to limited epidemiological information, all available evidence points to a low transmission potential. Continued monitoring of the transmission potential of A/H7N9 is critical in the coming months as intervention measures may be relaxed and seasonal factors could promote disease transmission in colder months.
The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.
Addressing some of the uncertainties in their calculations, the authors write:
Information regarding the reservoir of A/H7N9 and the natural history of this disease is still limited, as would be the case for any emerging zoonosis with limited prior experience. It is intriguing that 23% of A/H7N9 cases do not report any prior contact with poultry (suggesting R is approximately 0.23), and yet clusters are extremely infrequent (suggesting R closer to 0).
These conflicting findings could be reconciled with additional information on the prevalence of asymptomatic infections; unfortunately, recent serological information is currently lacking. Overall, all R estimation methods tend to produce high uncertain ranges for A/H7N9.
Regular readers of this blog are aware that over the summer, we saw several studies that estimated the likely number of H7N9 cases to be much higher than the 132 laboratory confirmed cases used in this analysis. The problem is, with just about every illness or infection, only a fraction of the cases – usually the most severe – are identified.
And it doesn’t matter whether we are talking about seasonal influenza, West Nile Virus, Salmonella, or avian flu.
Last April, 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. This from Bloomberg News.
H7N9 Cases May Be Double Known Figure, Hong Kong Researchers Say
By Natasha Khan - Apr 22, 2013 3:46 AM ET
H7N9 bird flu may have infected twice as many people as the 103 cases reported, an analysis by researchers at the University of Hong Kong showed.
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
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.
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.
Admittedly a wide range, and without comprehensive serological studies, impossible to prove one way or the other. If I had to guess, my money would be on the lower end of the range. But that’s strictly a guess on my part.
And that’s the rub. Without really good data, we are forced to make assumptions. And if the data is incomplete, or the assumptions wrong, that can skew the results.
Ambiguities aside, the fact that only a few small clusters were documented and we haven’t seen ongoing transmission of the virus over the summer, makes for a pretty good prima facie case that the virus’ R0 last spring was less than 1.0.
Whether the virus retains this low R0, or becomes better adapted to mammalian hosts in the days, weeks, or months ahead is the question that keeps public health officials up at night.
