Reﬂection and Reaction
a future pandemic from non-human inﬂuenza viruses is a real threat. No one can accurately predict the timing and severity of the next inﬂuenza pandemic, but severe pandemics in the past have resulted in tens of millions of deaths. The prevention and control of the worldwide spread of pandemic inﬂuenza will need improved of animal and human surveillance, early detection and diﬀerentiation of causative viruses, identiﬁcation of new targets for antiviral drugs and control of host immune responses, and the development of universal vaccines for inﬂuenza and secondary bacterial pneumonia.
HZ is an employee of Z-BioMed, a company with products designed for use in inﬂuenza research. LC declares no conﬂicts of interest. 1
2 3 4 5
*Hong Zhang, Ling Chen Department of Respiratory Medicine, Aﬃliated Hospital of Zunyi Medical College, Guizhou Province, China (HZ, LC) and Z-BioMed Inc, Rockville, MD, USA (HZ) [email protected]
Centers for Disease Control and Prevention. Swine inﬂuenza A (H1N1) infection in two children—Southern California, March–April 2009. MMWR Morb Mortal Wkly Rep 2009; 58: 400–02. WHO. Inﬂuenza (Seasonal) April 2009. http://www.who.int/mediacentre/ factsheets/fs211/en/index.html (accessed May 23, 2009). GenBank sequences from 2009 H1N1 inﬂuenza outbreak. http://www.ncbi. nlm.nih.gov/genomes/FLU/SwineFlu.html (accessed May 23, 2009). Zhang Z, Schwartz S, Wagner L, et al. A greedy algorithm for aligning DNA sequences. J Comput Biol 2000; 7: 203–14. Brundage JF, Shanks GD. What really happened during the 1918 inﬂuenza pandemic? The importance of bacterial secondary infectious. J Infect Dis 2007; 196: 1717–18. Morens DM, Taubenberger JK, Fauci AS. Predominant role of bacterial pneumonia as a cause of death in pandemic inﬂuenza: implications for pandemic inﬂuenza preparedness. J Infect Dis 2008; 198: 962–70. Brundage JF, Shanks GD. Deaths from bacterial pneumonia during 1918–19 inﬂuenza pandemic. Emerg Infect Dis 2008; 14: 1193–99. Zhang H. Concerns of using sialidase fusion protein as an experimental drug to combat seasonal and pandemic inﬂuenza. J Antimicrob Chemother 2008; 62: 219–23.
Inﬂuenza in the tropics Compared with temperate countries,1 data on tropical inﬂuenza remain scarce. Russell and colleagues2 suggest that epidemics of new variants of inﬂuenza are seeded into temperate regions from continuously circulating viruses in east and southeast Asia through temporary regionally overlapping epidemics. Inﬂuenza infections happen throughout the year in the tropics; most countries report two peaks in the number of infections associated with rainy seasons.1,3–6 Clinical data on disease characteristics and impact on heath-care services are lacking. The authors of a study i n Thailand7 reported that 11% of people hospitalised with pneumonia were inﬂuenza-positive, with loss of productivity costing an estimated US$23·4 million to $62·9 million over 12 months. An analysis of inﬂuenza in Singapore from 1996 to 2003 concluded that 6·5% of underlying pneumonia and inﬂuenza deaths were attributable to inﬂuenza,8 which is a similar proportion to that in the temperate USA and subtropical Hong Kong, with elderly people being most aﬀected. Both studies showed that inﬂuenza in Thailand and Singapore were underrecognised. Lee and colleagues9 summarised historical records on the three previous inﬂuenza pandemics in Singapore. Excess mortality was estimated as 18 of 1000 population in 1918, 0·47 of 1000 population in 1957, and 0·27 of www.thelancet.com/infection Vol 9 August 2009
1000 population in 1968. Inﬂuenza pandemic mortality rates in Singapore were similar to those in temperate countries. A recent laboratory project at Tan Tock Seng Hospital, a 1200-bed general hospital in Singapore, showed that about 10% of respiratory samples from patients admitted within 48 h period were positive for inﬂuenza by
Inﬂuenza drill in the intensive-care unit of Tan Tock Seng Hospital, Singapore
Reﬂection and Reaction
PCR assay. None of these patients were diagnosed clinically or isolated during hospitalisation, and 60% fulﬁlled the case deﬁnition for inﬂuenza-like illness.10 This highlights the under-recognition and underdiagnosis of inﬂuenza in hospitals. The under-recognition of inﬂuenza has many implications: isolation and absence from work might reduce bidirectional nosocomial transmission between patients and staﬀ, unnecessary antibiotic treatment might fuel the emergence of resistant bacteria, and failure to treat inﬂuenza and its severe complications such as encephalitis or myocarditis. Importantly, public health policy on inﬂuenza vaccination in the tropics is lacking. Tan Tock Seng Hospital is the designated screening centre in Singapore for the detection of swine-origin inﬂuenza A H1N1. From April 27 to May 24, 2009, 300 febrile travellers with respiratory symptoms from aﬀected countries were screened with inﬂuenza PCR assays of nasal and throat swabs. 24·0% (72) of the travellers had inﬂuenza A H3N2, 1·6% (5) had seasonal inﬂuenza A H1N1, and 2·7% (8) had inﬂuenza B. A oneoﬀ hospital-wide screening of patients with a diagnosis of pneumonia showed 10·3% (15) had inﬂuenza A H3N2, 1·4% (2) had seasonal inﬂuenza A H1N1, and 2·7% (4) had inﬂuenza B. This adds to the evidence of the inﬂuenza burden in Singapore. So far, containment is the national strategy in response to the initial stage of swine-origin inﬂuenza A H1N1 outbreak. A 2005 position paper from WHO11 promoted inﬂuenza awareness and vaccination among healthcare workers and targeted high-risk populations. However, outside North America and western Europe, only about 100 million doses of inﬂuenza vaccine were distributed in 2003. At Tan Tock Seng Hospital, only 76% of health-care workers voluntarily accepted free inﬂuenza vaccination in 2008. Reducing the risk of community-acquired pneumonia and mortality in immunocompetent elderly people through vaccination requires further study.12,13 Antiviral therapy and prior vaccination within 6 months of infection were associated with shorter hospital stays in Hong Kong.14 However, spontaneous emergence and spread of inﬂuenza strains is a cause for concern.15 Although inﬂuenza A H3N2 predominated in Singapore in 2008, the His274Thr mutation that conferred oseltamivir resistance to was detected in about 80% of inﬂuenza A H1N1. The presence of this mutation further
complicates treatment options because early inﬂuenza diagnosis is needed for treatment to be eﬀective: detection of oseltamivir resistance is now needed to decide the choice of antiviral agents. Widespread oseltamivir resistance in seasonal inﬂuenza A H1N1 might undermine pandemic preparedness based on the stockpiling of oseltamivir. Learning from past inﬂuenza pandemics and aware of its geographical proximity to a possible site of origin for the next pandemic, Singapore has implemented antiviral and prepandemic strategies for the stockpiling of inﬂuenza vaccine. As clinicians and epidemiologists, we hope to better understand inﬂuenza disease burden, its disease characteristics in a rapidly ageing population, optimum treatment strategies, and public health measures for the prevention and control of seasonal and pandemic inﬂuenza. *Yee-Sin Leo, David C Lye, Angela Chow Departments of Infectious Diseases (Y-SL, DCL) and Clinical Epidemiology (AC), Communicable Disease Centre, Tan Tock Seng Hospital, Singapore [email protected]
We declare that we have no conﬂicts of interest. We would like to express our gratitude to the Corporate Communications Department of Tan Tock Seng Hospital for providing the photograph. 1 2 3 4 5 6 7 8 9 10 11 12
Hampson AW. Epidemiological data on inﬂuenza in Asian countries. Vaccine 1999; 17: S19–23. Russell CA, Jones TC, Barr IG, et al. The global circulation of seasonal inﬂuenza A (H3N2) viruses. Science 2008; 320: 340–46. Beckett CG, Kosasih H, Ma’roef C, et al. Inﬂuenza surveillance in Indonesia: 1999–2003. Clin Infect Dis 2004; 39: 443–49. Hasegawa G, Kyaw Y, Danjuan L, et al. Inﬂuenza virus infections in Yangon, Myanmar. J Clin Virol 2006; 37: 233–34. Nguyen HL, Saito R, Ngiem HK, et al. Epidemiology of inﬂuenza in Hanoi, Vietnam, from 2001 to 2003. J Infect 2007; 55: 58–63. Doraisingham S, Goh KT, Ling AE, et al. Inﬂuenza surveillance in Singapore: 1972–86. Bull World Health Organ 1988; 66: 57–63. Simmerman JM, Lertiendumrong J, Dowell SF, et al. The cost of inﬂuenza in Thailand. Vaccine 2006; 24: 4417–26. Chow A, Ma S, Ling AE, et al. Inﬂuenza-associated deaths in tropical Singapore. Emerg Infect Dis 2006; 12: 114–21. Lee VJ, Chen MI, Chan SP, et al. Inﬂuenza pandemics in Singapore, a tropical, globally connected city. Emerg Infect Dis 2007; 13: 1052–57. CDC. Overview of inﬂuenza surveillance in the United States. http:// www.cdc.gov/ﬂu/weekly/pdf/overview.pdf (accessed April 7, 2009). WHO. Inﬂuenza vaccines. Wkly Epidemiol Rec 2005; 80: 279–87. Jackson ML, Nelson JC, Weiss NA, et al. Inﬂuenza vaccination and risk of community-acquired pneumonia in immunocompetent elderly people: a population-based, nested case-control study. Lancet 2008; 372: 398–405. Simonsen L, Taylor RJ, Viboud C, et al. Mortality beneﬁts of inﬂuenza vaccination in elderly people: an ongoing controversy. Lancet Infect Dis 2007; 7: 658–66. Lee N, Chan PK, Choi KW, et al. Factors associated with early hospital discharge of adult inﬂuenza patients. Antivir Ther 2007; 12: 501–08. Moscona A. Global transmission of oseltamivir-resistant inﬂuenza. N Engl J Med 2009; 360: 953–56.
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