Figure 1

Figure 1. Mean daily incidence rates in counties with and without live poultry market closures across waves of influenza A(H7N9) infections, China, 2013–2017. A) Wave 1; B) wave 2; C) wave 3; D)...

Figure 2

Figure 2. Estimated daily incidence rates in counties with various levels of live poultry market closures across waves of influenza A(H7N9) infections, by duration of closure, China, 2013–2017. A) Wave 1; B) wave...

Figure 3

Figure 3. Estimated daily incidence rates in counties with various levels of live poultry market (LPM) closures across waves of influenza A(H7N9) infections, by proportion of closure days during epidemic wave, China, 2013–2017....

The comparison over time of DIRs between counties with and without LPM closures (Figure 1) showed that counties with measures had higher DIRs than counties free of closures during 2013–2017. In wave 5, DIRs decreased over time in counties with closures, whereas DIRs for counties without measures remained fairly high. Comparisons of DIRs for counties with different types (Figure 2) and levels (Figure 3) of LPM closure showed that, with the exception of wave 1 and wave 4, showed that DIRs were significantly lower in counties after closure than before (p<0.001) (Appendix Table 2). The DIRs in counties after LPM closure were also significantly lower than those estimated for counties without closures (p<0.001) (Appendix Table 2). We observed no statistically significant difference between counties with recursive, short-period, long-period, or permanent closures except for counties with recursive, long-period, and permanent closures in wave 2; for counties with short-period and long-period closures in wave 3; and for counties with recursive and long-period closures in wave 5. No DIRs were significantly different among counties with different levels of closing days, but the difference was significant in 25%–75% versus >75% of epidemic wave duration in wave 2.

To further quantify the effectiveness of LPM intervention in each site in wave 5, we compared the reduction in number of daily infections before and after closure among counties with 4 LPM interventions. A total of 142 laboratory-confirmed cases were located in 17 sites in wave 5 (Table 1), which is much higher than the total number of H7N9 cases in these sites in waves 1–4 (n = 116). A compilation of the onset dates of illness for these cases (Appendix Figure 5) shows that, with the exception of 4 study sites where human H7N9 epidemics ended before closing LPMs (study sites 8, 10–11, and 14), there was an observable drop in the number of H7N9 cases after LPM intervention in each site. After LPM closure, Gusu District in Suzhou, with permanent closure, had a higher reduction (97.0%, 95% CI 94.0%–100.0%) than other sites. The mean posterior estimates of the reductions ranged from 48% to 98% in sites with long-period closure. Guangzhou implemented recursive measures at the beginning of the epidemic but had a much lower reduction (34.0%, 95% CI 15.0%–70.0%). Compared with Guangzhou, which had short-period closures in the second intervention (73.0%, 95% CI 53.0%–77.0%), Foshan (96%) and Fuzhou (95%) showed larger relative reductions in the daily number of infections. Overall, the mean reduction in daily number of infections increased successively among sites with recursive, short-period, long-period, and permanent closures (p<0.001) (Appendix Table 3).

When we examined potential for human-to-human transmission, we found that the estimated effective reproduction number was 0.147 (95% CI 0.034–0.285) (Table 2; Appendix Figure 6). The slightly higher daily number of infections estimated by the model incorporating animal-to-human and human-to-human transmission (Appendix Figure 5) also suggests the potential for human-to-human transmission when compared with those estimates in an animal-to-human transmission model (Appendix Figure 7). Sensitivity analyses examined the influence of mean serial interval and of the proportion of unreported cases on the effective reproduction number. A decrease in the effective reproduction number was observed when the mean serial interval increased (Appendix Table 4). After accounting for the seasonality of H7N9 affected by absolute humidity, estimates of the reduction in number of daily infections changed slightly in some sites (Appendix Table 5), which should not be surprising, because the season pattern of H7N9 epidemics may well vary from one site to another (Appendix Figure 4). After we adjusted for the potential effect of the natural transmission dynamics of H7N9 virus, the net effect of LPM closure varied in study sites with long-period (range 0.5%–52.0%) and permanent (45.0%, 95% CI 32.0%–88.0%) closures in wave 5 (Table 3). In all study sites except 1, the differences in reductions in number of infections among sites with and without closures were statistically significant (p<0.001).

LPM closing measures have often been implemented reactively, after the occurrence of human H7N9 cases in a given county (Appendix Figure 8); it is thus not surprising to find generally high DIRs in counties that undertook such measures (Figure 1). However, what matters most is what happened to the DIR and mean daily number of illnesses after these closing measures were taken. Both DIRs and mean daily number of illness onsets decreased in counties or sites following LPM interventions, but the effect varied depending on the type of intervention and epidemic wave.

In general, permanent, long-period, and short-period closures provided comparable estimates in terms of DIR reduction. However, the association between the type and closing levels of LPM measures and DIRs showed different results across waves. For example, the difference in DIRs in counties with different levels of closing days was observed only in wave 2. During this wave, long-period and permanent closures represented the large majority of the measures (82.4% of the closing measures). During wave 5, short-period and recursive closures became available to authorities as potential measures and were implemented more abundantly, especially in cities with few H7N9 cases; thus, long-period and permanent closures represented only 55% of the total closing measures.

For wave 5, we also evaluated the effectiveness of different types of LPM interventions in controlling H7N9 epidemics in several key sites. Overall, the effectiveness of LPM closure varied with the type of the interventions in these sites during 2016–17. Permanent closure was more effective than long-period closure, short-period closure, and recursive closure. The relatively lower effectiveness of short-period closure was observed in wave 5, but the point estimates of the reduction in daily number of infections inferred from the transmission model were consistent with the effectiveness assessment of a 14-day LPM closure (range 53.0%–89.0%) (17). Accompanying the effectiveness assessment of consecutive LPM closure, Yuan et al. (21) quantified the effectiveness of periodic LPM closure together with daily cleaning and disinfection (range −47.0% to 34.0%), which was consistent with our minimum point estimates of the effectiveness of recursive closure.

The decline in the number of human infections with H7N9 virus varied among study sites. In addition to being a factor of the type of the intervention, the variations in these declines may have been influenced by the underlying natural transmission dynamics of H7N9. After adjusting for absolute humidity, the most dominant environmental driver for influenza seasonality, the reduction in number of infections did not change significantly in any one of the study sites. Therefore, overall estimates of the effect of LPM closure is unlikely to be confounded by those climatic factors. However, we cannot exclude the possibility that the effectiveness of LPM closure may be delayed because of climatic factors at a specific time, as low temperature and higher humidity always drive the spread of H7N9 virus. In addition, we cannot definitively exclude other unknown seasonal confounders, such as the seasonality of poultry movement. Available evidence supports the seasonal effects of poultry movement on human infection with H5N1 virus around Chinese New Year (22). Although we found no quantitative evidence that seasonal variation in poultry trade played a role in human infection with H7N9 virus, the fact that the high-risk season of the H7N9 epidemic was consistent with the peak time of poultry trade around Chinese New Year is notable.

Limited human-to-human transmissibility of H7N9 virus was previously observed during waves 1–4 (3). Our low estimates of reproduction number in wave 5 were consistent with previous descriptive analysis of possible clusters of human infection with H7N9 virus (3,23), confirming that human-to-human transmissibility of H7N9 virus remained unsustainable.

Other factors, such as societal economic costs and residents’ behavior toward banning live poultry trade, may affect the effectiveness of LPM closure (24) and lead to a displacement effect. LPM closure has threatened the wholesale and retail market chain (25); local authorities in epidemic areas even tried to control the spread of H7N9 virus by banning live poultry trade. Consequences of such interventions included loss of consumer confidence, decreases in prices of poultry products, and loss of market shares. In an attempt to reduce adverse effects in economic, less disruptive interventions were introduced, such as rest days, banning live poultry overnight, or periodic cleaning and disinfection (26,27). These LPM interventions proved to be less effective (28).

Besides LPM interventions, several key measures (e.g., culling known infected poultry and direct contacts, vaccinating poultry, or improving biosecurity for poultry-handling practices) have been taken to control zoonotic infection with H7N9 viruses (29). These measures are always applied in parallel and have gradually changed human behaviors related to the management, transportation, and trade of poultry. Specifically, traditional poultry handling and trade practices have been replaced by central slaughtering and frozen poultry products in major cities in China, which may have substantially reduced the risk of human exposure to infected poultry. The government of China implanted vaccination of poultry against H7N9 virus to control the 2017–18 epidemic wave after the surge in the reported number of cases in wave 5. The introduction of this H5/H7 bivalent inactivated vaccine substantially reduced the number of cases in the 2017–18 epidemic wave (30), although its effectiveness needs to be further assessed quantitatively.

This study has several limitations. First, the timing of the implementation of LPM closures in relation to the progress of the H7N9 epidemic was not considered in the effectiveness assessment of LPM closures, which would lead to an overestimation of the effects of LPM closure if LPM interventions were implemented after the epidemic peak. The incidence reduction might also not be comparable in cities with LPM interventions implemented before reaching the epidemic peak with those implemented near the end of the epidemic. Second, our findings focus only on human cases occurring in urban and semiurban areas in China in wave 5, ignoring H7N9 cases in rural areas, where LPMs are rarely located. More rural cases were reported in wave 5 than in previous epidemic waves, and exposure to poultry in farms and backyards were the main sources of these rural human cases (9,31). Therefore, LPM closure might be less effective in controlling H7N9 epidemics in these rural areas, and other effective interventions (e.g., vaccination of poultry) need to be further explored. Third, because of the ecologic nature of our study, some anthropogenic factors may have acted as potential confounders that can bias our findings, such as the number of LPM visitors, frequency of LPM visits, improvements in biosecurity for poultry-handling practices, or which live bird species were found in LPMs. These factors and LPM interventions have always existed in parallel, so we cannot rule out the possibility that differences in the reduction in the daily number of infections among different sites may be partially explained by these anthropogenic factors, especially in sites with recursive or short-period closures. To more precisely differentiate the effectiveness of each type of LPM interventions, future studies could incorporate additional datasets to try to separate the effects of LPM closure from the natural transmission dynamics of H7N9 virus and other anthropogenic factors. Furthermore, the estimate of the reproduction number in this study relies on the assumption that this parameter is constant among locations. Although the estimate of this parameter did not involve the geographic locations of these cases and the likelihood that these human cases might have been in contact, the estimate was consistent with previous epidemiologic studies (3,23).

A number of research questions need to be further clarified in future studies. Rhe optimal time and duration to implement LPM closure to balance the economic loss and transmission risk reduction needs further investigation, combined with a time-varying force of infection. Moreover, it could be possible to estimate key epidemiologic parameters (e.g., animal-to-human transmissibility and reproduction number) by considering the spatial–temporal dynamics of H7N9 epidemics in poultry and related environments, potential market functioning effects, and the frequency of human exposure to H7N9 virus to explain the differences in effectiveness.

In conclusion, the characteristics of LPM interventions can potentially affect their effectiveness. Although possibly more challenging from an operational point of view, permanent and long-period closures were found to be more effective in reducing human H7N9 cases during waves 1–5. In the long term, structural changes in the poultry value chain linked to permanent LPM closure may be required to maintain sufficient effectiveness of interventions and prevent the occurrence of H7N9 epidemics.