Tianmu Chen

Risk of imported Ebola virus disease in China

BACKGROUND More than 600,000 annual arrivals from Africa, 1.4 billion population and developing health care systems render China at non-negligible risk of imported Ebola virus disease (EVD). METHOD According to the natural history of EVD, we constructed a deterministic SEIR model. Three published EVD outbreaks in Africa were enrolled to calculate the basic reproduction number (R0) of EVD. Scenarios representing unreported and reported (with n weeks delay) imported EVD in China were simulated to evaluate the effectiveness of interventions assumed to be implemented in different periods of the outbreaks. RESULTS Based on previous Africa outbreak incidence datasets, our mathematical model predicted the basic reproduction number of EVD in the range of 1.53-3.54. Adopting EVD prevalence at 0.04-0.16% from the same datasets and estimated missing information and monitoring rates at 1-10%, a total of 6-194 imported cases were predicted. Be a single case left unidentified/unreported, total attack rate was predicted to reach 60.19%-96.74%. Curve fitting results showed that earlier intervention benefits in exponential and linear decrease in prevalence and duration of outbreak respectively. CONCLUSION Based on past outbreak experience in China, there is a need to implement an internet-based surveillance and monitoring system in order to reinforce health policy, track suspected cases and protect the general public by timely interventions.

Investigation of key interventions for shigellosis outbreak control in China.

Shigellosis is a major public health concern in China, where waterborne disease outbreaks are common. Shigellosis-containing strategies, mostly single or multiple interventions, are implemented by primary-level health departments. Systematic assessment of the effectiveness of these measures is scarce. To estimate the efficacy of commonly used intervention strategies, we developed a Susceptible–Exposed–Infectious/Asymptomatic–Recovered–Water model. No intervention was predicted to result in a total attack rate (TAR) of 90% of the affected population (95% confidence interval [CI]: 86.65–92.80) and duration of outbreak (DO) of 89 days, and the use of single-intervention strategies can be futile or even counter-productive. Prophylactics and water disinfection did not improve TAR or DO. School closure for up to 3 weeks did not help but only increased DO. Isolation alone significantly increased DO. Only antibiotics treatment could shorten the DO to 35 days with TAR unaffected. We observed that these intervention effects were additive when in combined usage under most circumstances. Combined intervention “Isolation+antibiotics+prophylactics+water disinfection” was predicted to result in the lowest TAR (41.9%, 95%CI: 36.97–47.04%) and shortest DO (28 days). Our actual Shigellosis control implementation that also included school closure for 1 week, attained comparable results and the modeling produced an epidemic curve of Shigellosis highly similar to our actual outbreak data. This lends a strong support to the reality of our model that provides a possible reference for public health professionals to evaluate their strategies towards Shigellosis control.

Clinical, epidemiological and virological characteristics of the first detected human case of avian influenza A(H5N6) virus

A human infection with novel avian influenza A H5N6 virus emerged in Changsha city, China in February, 2014. This is the first detected human case among all human cases identified from 2014 to early 2016. We obtained and summarized clinical, epidemiological, and virological data from this patient. Complete genome of the virus was determined and compared to other avian influenza viruses via the construction of phylogenetic trees using the neighbor-joining approach. A girl aged five and half years developed fever and mild respiratory symptoms on Feb. 16, 2014 and visited hospital on Feb. 17. Throat swab specimens were obtained from the patient and a novel reassortant avian influenza A H5N6 virus was detected. All eight viral gene segments were of avian origin. The hemagglutinin (HA) and neuraminidase (NA) gene segments were closely related to A/duck/Sichuan/NCXN11/2014(H5N1) and A/chicken/Jiangxi/12782/2014(H10N6) viruses, respectively. The six internal genes were homologous to avian influenza A (H5N2) viruses isolated in duck from Jiangxi in China. This H5N6 virus has not gained genetic mutations necessary for human infection and was suggested to be sensitive to neuraminidase inhibitors, but resistant to adamantanes. Epidemiological investigation of the exposure history of the patient found that a live poultry market could be the source place of infection and the incubation period was 2-5days. This novel reassortant Avian influenza A(H5N6) virus could be low pathogenic in humans. The prevalence and genetic evolution of this virus should be closely monitored.

The Effectiveness of Age-Specific Isolation Policies on Epidemics of Influenza A (H1N1) in a Large City in Central South China

During the early stage of a pandemic, isolation is the most effective means of controlling transmission. However, the effectiveness of age-specific isolation policies is not clear; especially little information is available concerning their effectiveness in China. Epidemiological and serological survey data in the city of Changsha were employed to estimate key model parameters. The average infectious period (date of recovery – date of symptom onset) of influenza A (H1N1) was 5.2 days. Of all infected persons, 45.93% were asymptomatic. The basic reproduction number of the influenza A (H1N1) pandemic was 1.82. Based on the natural history of influenza A (H1N1), we built an extended susceptible-exposed-infectious/asymptomatic-removed model, taking age groups: 0–5, 6–14, 15–24, 25–59, and ≥60 years into consideration for isolation. Without interventions, the total attack rates (TARs) in each age group were 42.73%, 41.95%, 20.51%, 45.03%, and 37.49%, respectively. Although the isolation of 25–59 years-old persons was the most effective, the TAR of individuals of aged 0–5 and 6–14 could not be reduced. Paradoxically, isolating individuals ≥60 year olds was not predicted to be an effective way of reducing the TAR in this group but isolating the age-group 25–59 did, which implies inter-age-group transmission from the latter to the former is significant. Isolating multiple age groups increased effectiveness. The most effective combined isolation target groups were of 6–14 + 25–59 year olds, 6–14 + 15–24 + 25–59 year olds, and 0–5 + 6–14 + 25–59 + ≥60 year olds. The last of these isolation schemas reduced the TAR of the total population from 39.64% to 0.006%, which was exceptionally close to the effectiveness of isolating all five age groups (TAR = 0.004%).

Evidence-Based interventions of Norovirus outbreaks in China

BackgroundIn resource-limited settings where laboratory capacity is limited and response strategy is non-specific, delayed or inappropriate intervention against outbreaks of Norovirus (NoV) are common. Here we report interventions of two norovirus outbreaks, which highlight the importance of evidence-based modeling and assessment to identify infection sources and formulate effective response strategies.MethodsSpatiotemporal scanning, mathematical and random walk modeling predicted the modes of transmission in the two incidents, which were supported by laboratory results and intervention outcomes.ResultsSimulation results indicated that contaminated water was 14 to 500 fold more infectious than infected individuals. Asymptomatic individuals were not effective transmitters. School closure for up to a week still could not contain the outbreak unless the duration was extended to 10 or more days. The total attack rates (TARs) for waterborne NoV outbreaks reported in China (n = 3, median = 4.37) were significantly (p < 0.05) lower than worldwide (n = 14, median = 41.34). The low TARs are likely due to the high number of the affected population.ConclusionsWe found that school closure alone could not contain Norovirus outbreaks. Overlooked personal hygiene may serve as a hotbed for infectious disease transmission. Our results reveal that evidence-based investigations can facilitate timely interventions of Norovirus transmission.

Transmissibility of the Influenza Virus during Influenza Outbreaks and Related Asymptomatic Infection in Mainland China, 2005-2013.

We collected 2768 Influenza-like illness emergency public health incidents from April 1, 2005 to November 30, 2013reported in the Emergency Public Reporting System. After screening by strict inclusion and exclusion criteria, there were 613 outbreaks analyzed with susceptible–exposed–infectious/asymptomatic–removed model in order to estimate the proportion of asymptomatic individuals (p) and the effective reproduction number (Rt). The relation between Rt and viral subtypes, regions, outbreak sites, populations, and seasons were analyzed. The mean values of p of different subtypes ranged from 0.09 to 0.15, but could be as high as up to 0.94. Different subtypes, provinces, regions, and sites of outbreak had statistically significantly different Rt. In particular, the southern region also manifested different Rt by affected population size and seasonality. Our results provide China and also the rest of the world a reference to understand characteristics of transmission and develop prevention and control strategies.

Influenza A (H1N1) transmission by road traffic between cities and towns

Influenza A (H1N1) was spread widely between cities and towns by road traffic and had a major impact on public health in China in 2009. Understanding regulation of its transmission is of great significance with urbanization ongoing and for mitigation of damage by the epidemic. We analyzed influenza A (H1N1) spatiotemporal transmission and risk factors along roads in Changsha, and combined diffusion velocity and floating population size to construct an epidemic diffusion model to simulate its transmission between cities and towns. The results showed that areas along the highways and road intersections had a higher incidence rate than other areas. Expressways and county roads played an important role in the rapid development stage and the epidemic peak, respectively, and intercity bus stations showed a high risk of disease transmission. The model simulates the intensity and center of disease outbreaks in cities and towns, and provides a more complete simulation of the disease spatiotemporal process than other models.

Development and Evaluation of a Real-Time RT-PCR Assay for Detection of a Novel Avian Influenza A (H5N6) Virus

As of Aug 25, 2017, 17 incidences of human infection and 6 deaths due to the novel H5N6 virus have been reported in China. Genetic analysis of the viral genome revealed that this reassortant virus is highly pathogenic to poultry, and that the virus has a risk of transmission to humans. Accordingly, the development of a rapid, sensitive, and specific molecular diagnostic assay is critical for public health. In this study, a real-time reverse-transcription PCR (RT-PCR) assay was developed to specifically detect the novel H5N6 virus, with primer pairs targeting the hemagglutinin and neuraminidase gene sequences of this virus. RNA was extracted from throat swab specimens from patients with influenza-like illness (ILIs), and environmental samples were collected from live poultry markets (LPMs) for H5N6 virus detection by real-time RT-PCR. The method was demonstrated to enable specific detection of the avian H5N6 virus, with no cross-reactivity with seasonal influenza viruses (H1N1, H1N1 pdm09, H3N2 or B); H5N1, H7N9, H9N2 viruses; or other human respiratory viruses. The detection limit of the assay was 1.0 × 101 copies per reaction for N6 and 1.0 × 102 copies per reaction for H5 assays. The assay is a powerful tool for rapid, sensitive, and specific detection of H5N6 virus infection in specimens derived from humans, animals, and the environment.

Clinical and epidemiological characteristics of a young child infected with avian influenza A (H9N2) virus in China

Three cases of the avian influenza A (H9N2) virus have been documented in Changsha, which is a large city that has nine districts and a population of 7.04 million in central South China. Among these patients, one was a girl and two were boys. The ages of the patients were 9 months, 2 years, and 15 years. Two cases of H9N2 were detected in September, 2015 and one was detected in 2017. Two patients were children who had not reached the age for kindergarten and one was a student. These three cases were all mild and were detected in a sentinel hospital of the Chinese Influenza Surveillance System. We describe the clinical and epidemiological features of the youngest patient with H9N2 in 2017 and the surveillance results of the H9N2 virus in live poultry markets in Changsha. From January 2014 to December 2017, 4212 samples were collected in live poultry markets in Changsha, among which 25.81% (1087/4212) were H9N2-positive. Public health concerns should be addressed for emerging H9N2 virus infection, and more strategies should be performed before this virus mutates to be more transmissible and highly pathogenic.

Simulation of key interventions for seasonal influenza outbreak control at school in Changsha, China:

Objective To use a mathematical model to simulate an influenza outbreak in a school in order to assess the effectiveness of isolation (Iso), antiviral therapeutics, antiviral prophylactics (P), vaccination prior to the outbreak, and school closure (for 1 [S1w], 2 or 3 weeks). Methods This study developed a susceptible–exposed–infectious/asymptomatic–recovered model to estimate the effectiveness of commonly used interventions for seasonal influenza outbreaks in school. Results The most effective single-intervention strategy was isolation with a total attack rate of 1.99% and an outbreak duration of 30 days. The additional effectiveness of antiviral therapeutics and prophylactics and vaccination (prior to the outbreak) strategies were not obvious. Although Iso+P, P+Iso+S1w, four-, and five-combined intervention strategies had commendable effectiveness, total attack rate decreased only slightly, and outbreak duration was shortened by 9 days maximum, compared with the single-intervention isolation strategy. School closure for 1, 2 or 3 weeks was futile or even counterproductive. Conclusion Isolation, as a single intervention, was the most effective in terms of reducing the total attack rate and the duration of the outbreak.