The west African Ebola epidemic that began in 2013 exposed deep inadequacies in the national and international institutions responsible for protecting the public from the far-reaching human, social, ...economic, and political consequences of infectious disease outbreaks. The Ebola epidemic raised a crucial question: what reforms are needed to mend the fragile global system for outbreak prevention and response, rebuild confidence, and prevent future disasters?
Summary Background Hand, foot, and mouth disease is a common childhood illness caused by enteroviruses. Increasingly, the disease has a substantial burden throughout east and southeast Asia. To ...better inform vaccine and other interventions, we characterised the epidemiology of hand, foot, and mouth disease in China on the basis of enhanced surveillance. Methods We extracted epidemiological, clinical, and laboratory data from cases of hand, foot, and mouth disease reported to the Chinese Center for Disease Control and Prevention between Jan 1, 2008, and Dec 31, 2012. We then compiled climatic, geographical, and demographic information. All analyses were stratified by age, disease severity, laboratory confirmation status, and enterovirus serotype. Findings The surveillance registry included 7 200 092 probable cases of hand, foot, and mouth disease (annual incidence, 1·2 per 1000 person-years from 2010–12), of which 267 942 (3·7%) were laboratory confirmed and 2457 (0·03%) were fatal. Incidence and mortality were highest in children aged 12–23 months (38·2 cases per 1000 person-years and 1·5 deaths per 100 000 person-years in 2012). Median duration from onset to diagnosis was 1·5 days (IQR 0·5–2·5) and median duration from onset to death was 3·5 days (2·5–4·5). The absolute number of patients with cardiopulmonary or neurological complications was 82 486 (case-severity rate 1·1%), and 2457 of 82486 patients with severe disease died (fatality rate 3·0%); 1617 of 1737 laboratory confirmed deaths (93%) were associated with enterovirus 71. Every year in June, hand, foot, and mouth disease peaked in north China, whereas southern China had semiannual outbreaks in May and September–October. Geographical differences in seasonal patterns were weakly associated with climate and demographic factors (variance explained 8–23% and 3–19%, respectively). Interpretation This is the largest population-based study up to now of the epidemiology of hand, foot, and mouth disease. Future mitigation policies should take into account the heterogeneities of disease burden identified. Additional epidemiological and serological studies are warranted to elucidate the dynamics and immunity patterns of local hand, foot, and mouth disease and to optimise interventions. Funding China–US Collaborative Program on Emerging and Re-emerging Infectious Diseases, WHO, The Li Ka Shing Oxford Global Health Programme and Wellcome Trust, Harvard Center for Communicable Disease Dynamics, and Health and Medical Research Fund, Government of Hong Kong Special Administrative Region.
Summary Background The avian influenza A H7N9 virus has caused infections in human beings in China since 2013. A large epidemic in 2016–17 prompted concerns that the epidemiology of the virus might ...have changed, increasing the threat of a pandemic. We aimed to describe the epidemiological characteristics, clinical severity, and time-to-event distributions of patients infected with A H7N9 in the 2016–17 epidemic compared with previous epidemics. Methods In this epidemiological study, we obtained information about all laboratory-confirmed human cases of A H7N9 virus infection reported in mainland China as of Feb 23, 2017, from an integrated electronic database managed by the China Center for Disease Control and Prevention (CDC) and provincial CDCs. Every identified human case of A H7N9 virus infection was required to be reported to China CDC within 24 h via a national surveillance system for notifiable infectious diseases. We described the epidemiological characteristics across epidemics, and estimated the risk of death, mechanical ventilation, and admission to the intensive care unit for patients admitted to hospital for routine clinical practice rather than for isolation purpose. We estimated the incubation periods, and time delays from illness onset to hospital admission, illness onset to initiation of antiviral treatment, and hospital admission to death or discharge using survival analysis techniques. Findings Between Feb 19, 2013, and Feb 23, 2017, 1220 laboratory-confirmed human infections with A H7N9 virus were reported in mainland China, with 134 cases reported in the spring of 2013, 306 in 2013–14, 219 in 2014–15, 114 in 2015–16, and 447 in 2016–17. The 2016–17 A H7N9 epidemic began earlier, spread to more districts and counties in affected provinces, and had more confirmed cases than previous epidemics. The proportion of cases in middle-aged adults increased steadily from 41% (55 of 134) to 57% (254 of 447) from the first epidemic to the 2016–17 epidemic. Proportions of cases in semi-urban and rural residents in the 2015–16 and 2016–17 epidemics (63% 72 of 114 and 61% 274 of 447, respectively) were higher than those in the first three epidemics (39% 52 of 134, 55% 169 of 306, and 56% 122 of 219, respectively). The clinical severity of individuals admitted to hospital in the 2016–17 epidemic was similar to that in the previous epidemics. Interpretation Age distribution and case sources have changed gradually across epidemics since 2013, while clinical severity has not changed substantially. Continued vigilance and sustained intensive control efforts are needed to minimise the risk of human infection with A H7N9 virus. Funding The National Science Fund for Distinguished Young Scholars.
Summary Background The ongoing yellow fever epidemic in Angola strains the global vaccine supply, prompting WHO to adopt dose sparing for its vaccination campaign in Kinshasa, Democratic Republic of ...the Congo, in July–August, 2016. Although a 5-fold fractional-dose vaccine is similar to standard-dose vaccine in safety and immunogenicity, efficacy is untested. There is an urgent need to ensure the robustness of fractional-dose vaccination by elucidation of the conditions under which dose fractionation would reduce transmission. Methods We estimate the effective reproductive number for yellow fever in Angola using disease natural history and case report data. With simple mathematical models of yellow fever transmission, we calculate the infection attack rate (the proportion of population infected over the course of an epidemic) with various levels of transmissibility and 5-fold fractional-dose vaccine efficacy for two vaccination scenarios, ie, random vaccination in a hypothetical population that is completely susceptible, and the Kinshasa vaccination campaign in July–August, 2016, with different age cutoff for fractional-dose vaccines. Findings We estimate the effective reproductive number early in the Angola outbreak was between 5·2 and 7·1. If vaccine action is all-or-nothing (ie, a proportion of vaccine recipients receive complete protection VE and the remainder receive no protection), n -fold fractionation can greatly reduce infection attack rate as long as VE exceeds 1/ n . This benefit threshold becomes more stringent if vaccine action is leaky (ie, the susceptibility of each vaccine recipient is reduced by a factor that is equal to the vaccine efficacy). The age cutoff for fractional-dose vaccines chosen by WHO for the Kinshasa vaccination campaign (2 years) provides the largest reduction in infection attack rate if the efficacy of 5-fold fractional-dose vaccines exceeds 20%. Interpretation Dose fractionation is an effective strategy for reduction of the infection attack rate that would be robust with a large margin for error in case fractional-dose VE is lower than expected. Funding NIH-MIDAS, HMRF-Hong Kong.
Summary Background Transmission of the novel avian influenza A H7N9 virus seems to be predominantly between poultry and people. In the major Chinese cities of Shanghai, Hangzhou, Huzhou, and ...Nanjing—where most human cases of infection have occurred—live poultry markets (LPMs) were closed in April, 2013, soon after the initial outbreak, as a precautionary public health measure. Our objective was to quantify the effect of LPM closure in these cities on poultry-to-person transmission of avian influenza A H7N9 virus. Methods We obtained information about every laboratory-confirmed human case of avian influenza A H7N9 virus infection reported in the four cities by June 7, 2013, from a database built by the Chinese Center for Disease Control and Prevention. We used data for age, sex, location, residence type (rural or urban area), and dates of illness onset. We obtained information about LPMs from official sources. We constructed a statistical model to explain the patterns in incidence of cases reported in each city on the basis of the assumption of a constant force of infection before LPM closure, and a different constant force of infection after closure. We fitted the model with Markov chain Monte Carlo methods. Findings 85 human cases of avian influenza A H7N9 virus infection were reported in Shanghai, Hangzhou, Huzhou, and Nanjing by June 7, 2013, of which 60 were included in our main analysis. Closure of LPMs reduced the mean daily number of infections by 99% (95% credibility interval 93–100%) in Shanghai, by 99% (92–100%) in Hangzhou, by 97% (68–100%) in Huzhou, and by 97% (81–100%) in Nanjing. Because LPMs were the predominant source of exposure to avian influenza A H7N9 virus for confirmed cases in these cities, we estimated that the mean incubation period was 3·3 days (1·4–5·7). Interpretation LPM closures were effective in the control of human risk of avian influenza A H7N9 virus infection in the spring of 2013. In the short term, LPM closure should be rapidly implemented in areas where the virus is identified in live poultry or people. In the long term, evidence-based discussions and deliberations about the role of market rest days and central slaughtering of all live poultry should be renewed. Funding Ministry of Science and Technology, China; Research Fund for the Control of Infectious Disease; Hong Kong University Grants Committee; China–US Collaborative Program on Emerging and Re-emerging Infectious Diseases; Harvard Center for Communicable Disease Dynamics; and the US National Institutes of Health.
Summary Novel influenza viruses continue to emerge, posing zoonotic and potentially pandemic threats, such as with avian influenza A H7N9. Although closure of live poultry markets (LPMs) in mainland ...China stopped H7N9 outbreaks temporarily, closures are difficult to sustain, in view of poultry production and marketing systems in China. In this Personal View, we summarise interventions taken in mainland China, and provide evidence for other more sustainable but effective interventions in the live poultry market systems that reduce risk of zoonotic influenza including rest days, and banning live poultry in markets overnight. Separation of live ducks and geese from land-based (ie, non-aquatic) poultry in LPM systems can reduce the risk of emergence of zoonotic and epizootic viruses at source. In view of evidence that H7N9 is now endemic in over half of the provinces in mainland China and will continue to cause recurrent zoonotic disease in the winter months, such interventions should receive high priority in China and other Asian countries at risk of H7N9 through cross-border poultry movements. Such generic measures are likely to reduce known and future threats of zoonotic influenza.
Summary Background The novel influenza A H7N9 virus emerged recently in mainland China, whereas the influenza A H5N1 virus has infected people in China since 2003. Both infections are thought to be ...mainly zoonotic. We aimed to compare the epidemiological characteristics of the complete series of laboratory-confirmed cases of both viruses in mainland China so far. Methods An integrated database was constructed with information about demographic, epidemiological, and clinical variables of laboratory-confirmed cases of H7N9 (130 patients) and H5N1 (43 patients) that were reported to the Chinese Centre for Disease Control and Prevention until May 24, 2013. We described disease occurrence by age, sex, and geography, and estimated key epidemiological variables. We used survival analysis techniques to estimate the following distributions: infection to onset, onset to admission, onset to laboratory confirmation, admission to death, and admission to discharge. Findings The median age of the 130 individuals with confirmed infection with H7N9 was 62 years and of the 43 with H5N1 was 26 years. In urban areas, 74% of cases of both viruses were in men, whereas in rural areas the proportions of the viruses in men were 62% for H7N9 and 33% for H5N1. 75% of patients infected with H7N9 and 71% of those with H5N1 reported recent exposure to poultry. The mean incubation period of H7N9 was 3·1 days and of H5N1 was 3·3 days. On average, 21 contacts were traced for each case of H7N9 in urban areas and 18 in rural areas, compared with 90 and 63 for H5N1. The fatality risk on admission to hospital was 36% (95% CI 26–45) for H7N9 and 70% (56–83%) for H5N1. Interpretation The sex ratios in urban compared with rural cases are consistent with exposure to poultry driving the risk of infection—a higher risk in men was only recorded in urban areas but not in rural areas, and the increased risk for men was of a similar magnitude for H7N9 and H5N1. However, the difference in susceptibility to serious illness with the two different viruses remains unexplained, since most cases of H7N9 were in older adults whereas most cases of H5N1 were in younger people. A limitation of our study is that we compared laboratory-confirmed cases of H7N9 and H5N1 infection, and some infections might not have been ascertained. Funding Ministry of Science and Technology, China; Research Fund for the Control of Infectious Disease and University Grants Committee, Hong Kong Special Administrative Region, China; and the US National Institutes of Health.
Summary Background Characterisation of the severity profile of human infections with influenza viruses of animal origin is a part of pandemic risk assessment, and an important part of the assessment ...of disease epidemiology. Our objective was to assess the clinical severity of human infections with avian influenza A H7N9 virus, which emerged in China in early 2013. Methods We obtained information about laboratory-confirmed cases of avian influenza A H7N9 virus infection reported as of May 28, 2013, from an integrated database built by the Chinese Center for Disease Control and Prevention. We estimated the risk of fatality, mechanical ventilation, and admission to the intensive care unit for patients who required hospital admission for medical reasons. We also used information about laboratory-confirmed cases detected through sentinel influenza-like illness surveillance to estimate the symptomatic case fatality risk. Findings Of 123 patients with laboratory-confirmed avian influenza A H7N9 virus infection who were admitted to hospital, 37 (30%) had died and 69 (56%) had recovered by May 28, 2013. After we accounted for incomplete data for 17 patients who were still in hospital, we estimated the fatality risk for all ages to be 36% (95% CI 26–45) on admission to hospital. Risks of mechanical ventilation or fatality (69%, 95% CI 60–77) and of admission to an intensive care unit, mechanical ventilation, or fatality (83%, 76–90) were high. With assumptions about coverage of the sentinel surveillance network and health-care-seeking behaviour for patients with influenza-like illness associated with influenza A H7N9 virus infection, and pro-rata extrapolation, we estimated that the symptomatic case fatality risk could be between 160 (63–460) and 2800 (1000–9400) per 100 000 symptomatic cases. Interpretation Human infections with avian influenza A H7N9 virus seem to be less serious than has been previously reported. Many mild cases might already have occurred. Continued vigilance and sustained intensive control efforts are needed to minimise the risk of human infection. Funding Chinese Ministry of Science and Technology; Research Fund for the Control of Infectious Disease; Hong Kong University Grants Committee; China–US Collaborative Program on Emerging and Re-emerging Infectious Diseases; Harvard Center for Communicable Disease Dynamics; US National Institute of Allergy and Infectious Disease; and the US National Institutes of Health.
A series of large serological studies is needed to answer the ultimate question of how many individuals in a population have become infected-the appropriate denominator for estimates of severity of ...infection. Because seroconversion is delayed relative to infection and undertaking large numbers of reliable serological assays in real time is challenging,11 such surveys might not be informative immediately, but could become most useful in the late phases of an influenza season and in preparation for subsequent epidemic waves.
Summary Background Two large trials have reported contradictory results at 1 year after thrombus aspiration in ST elevation myocardial infarction (STEMI). In a 1-year follow-up of the largest ...randomised trial of thrombus aspiration, we aimed to clarify the longer-term benefits, to help guide clinical practice. Methods The trial of routine aspiration ThrOmbecTomy with PCI versus PCI ALone in Patients with STEMI (TOTAL) was a prospective, randomised, investigator-initiated trial of routine manual thrombectomy versus percutaneous coronary intervention (PCI) alone in 10 732 patients with STEMI. Eligible adult patients (aged ≥18 years) from 87 hospitals in 20 countries were enrolled and randomly assigned (1:1) within 12 h of symptom onset to receive routine manual thrombectomy with PCI or PCI alone. Permuted block randomisation (with variable block size) was done by a 24 h computerised central system, and was stratified by centre. Participants and investigators were not masked to treatment assignment. The trial did not show a difference at 180 days in the primary outcome of cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure. However, the results showed improvements in the surrogate outcomes of ST segment resolution and distal embolisation, but whether or not this finding would translate into a longer term benefit remained unclear. In this longer-term follow-up of the TOTAL study, we report the results on the primary outcome (cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure) and secondary outcomes at 1 year. Analyses of the primary outcome were by modified intention to treat and only included patients who underwent index PCI. This trial is registered with ClinicalTrials.gov , number NCT01149044. Findings Between Aug 5, 2010, and July 25, 2014, 10 732 eligible patients were enrolled and randomly assigned to thrombectomy followed by PCI (n=5372) or to PCI alone (n=5360). After exclusions of patients who did not undergo PCI in each group (337 in the PCI and thrombectomy group and 331 in the PCI alone group), the final study population comprised 10 064 patients (5035 thrombectomy and 5029 PCI alone). The primary outcome at 1 year occurred in 395 (8%) of 5035 patients in the thrombectomy group compared with 394 (8%) of 5029 in the PCI alone group (hazard ratio HR 1·00 95% CI 0·87–1·15, p=0·99). Cardiovascular death within 1 year occurred in 179 (4%) of the thrombectomy group and in 192 (4%) of 5029 in the PCI alone group (HR 0·93 95% CI 0·76–1·14, p=0·48). The key safety outcome, stroke within 1 year, occurred in 60 patients (1·2%) in the thrombectomy group compared with 36 (0·7%) in the PCI alone group (HR 1·66 95% CI 1·10–2·51, p=0·015). Interpretation Routine thrombus aspiration during PCI for STEMI did not reduce longer-term clinical outcomes and might be associated with an increase in stroke. As a result, thrombus aspiration can no longer be recommended as a routine strategy in STEMI. Funding Canadian Institutes of Health Research, Canadian Network and Centre for Trials Internationally, and Medtronic Inc.
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