Response to Pandemic Influenza A (H1N1) 2009 Dukhyoung Lee, PhD Director of the Disease Prevention Center Korea Centers for Disease Control and Prevention Ministry of Health and Welfare The World Health Organization (WHO) announced the emergence of new influenza-like illness on April 24, 2009 (WHO, 2009a). On April 27, the WHO changed pandemic phase 3 to pandemic phase 4; two days later the alert level was raised to phase 5. The WHO declared pandemic (phase 6) on June 11 (WHO, 2009b). From April 2009 to August 1, 2010, more than 214 countries and territories worldwide reported laboratory-confirmed cases including 18,449 fatal cases to the WHO (WHO, 2010). In Korea, more than 3/4 million laboratoryconfirmed cases, 270 of them died with influenza, were reported by the end of August 2010 (KCDC, 2010a). In the Republic of Korea, national disaster phase alerts are categorized into four levels; concern, caution, alert and severe. On April 28, when the first probable patient was identified, the Korea Health Ministry elevated the national disaster phase alert from concern to caution (Figure 1; Lee et al, 2010a). The phase was elevated to alert on July 21 when community outbreaks were detected, and to severe, on November 3 when there was a sharp increase in the number of reported patients. During the early phase of the pandemic, the main strategy was containment through quarantine and patient isolation. Surveillance systems in schools and medical facilities were put into action, and all confirmed cases were investigated. However, when the community outbreaks were detected in June, the policy switched from containment to mitigation. National stockpile of antiviral agents were released extensively for the mitigation. Existing influenza sentinel surveillance system monitored the size of the epidemic. Investigations were carried out for each fatal case and any case suspected of antiviral resistance. A local pharmaceutical company produced both adjuvant and non-adjuvant influenza vaccines. Vaccination was conducted based on availability and feasibility as following schedule for medical personnel from Oct 27, 2009; for school children and students from November 11 (KCDC, 2010b); for preschool children from December 7; for pregnant women from December 21; and for patients with chronic disease from January 18, 2010; for healthy elderly from January 25. Almost 13 million people or 15 million doses were vaccinated. National stockpile of antiviral agents were supplied free of charge throughout the pandemic. Before August 20, antiviral agents were prescribed through community health centers to patients with acute febrile respiratory illness (AFRI) who had a history of travel abroad or a history of contact with a confirmed patient. However, after August 20, when the number of community-acquired cases increased, antiviral agents were prescribed to any patients with AFRI symptoms. From August 20 to October 28, 2009, patients received antiviral agents at 455 designated hospitals and at 1,574 designated pharmacies on physician s prescription. Starting on October 28, when there was sharp increase in the overall number of patients, antiviral agents were provided at the designated hospitals and the designated pharmacy was expanded to all 20,109 pharmacies throughout the country. Physicians were allowed to prescribe antiviral agents to AFRI patients without confirmation
Influenza Like Illness diagnosis. All pharmacies and designated hospitals reported their daily use of antiviral agents to the Korea Centers for Disease Control and Prevention (KCDC) through an internetbased antiviral agent management program. 50 40 Vaccination for Medical Personnel (10/27) Provide Antiviral Agent at all Pharmacies (10/28) 2008-2009 2009-2010 Vaccination for Students (11/11) 30 20 10 Operate the Designated Hospital Containment (8/21) (Quarantine, Isolation) (4/28) Mitigation (Treatment) (7/29) Expand the Candidate for Antiviral Agent Administration (9/1) Vaccination for Patients with Chronic Disease (1/18) Vaccination for Healthy Adults (1/25) 0 4 5 6 7 8 9 10 11 12 1 2 3 Month National Disaster Phase Alert Caution (4/28-7/20) Alert (7/21-11/2) Severe (11/3-12/10) Alert (12/11-3/7) Caution (3/8-3/31) WHO Pandemic 4 Phase Phase 5 (4/29-6/10) Phase 6 (11/3-12/10) Main Strategy Containment (Quarantine, Isolation) Mitigation (Treatment) Mitigation (Vaccination) Figure 1. Main Strategy for the Response to Pandemic Influenza A(H1N1) 2009 in Korea
The exact number of H1N1 patients was estimated like this. The daily number of incident patients could be estimated from the daily amount of prescribed antiviral agents, the proportion of antiviral agent prescription and the proportion of confirmed H1N1 among patients with AFRI, and by retrospective adjustment of average time lag between onset of symptom and antiviral agent prescription Approximately 3 million patients (6.2% of total population in Korea) were prescribed with antiviral agents. The antiviral agent prescription rate was higher in preschool children (3-6 years old) and schoolchildren and adolescents (7-19 years) than in other age groups (Table 1). Oseltamivir was prescribed to around 3 million (96.9%) patients and zanamivir to around 10 thousand patients. The prescription rate was the highest in the national capital region and in the Southeast (Figure 2). Additionally, the rate was higher in urban areas than in rural areas. And the regional differences were consistent across all age groups (Figure 3). Table 1. Demographic Characteristics of Cases Variable Category Total Population Korea in Antiviral Agent Prescription Case Antiviral Agent Prescription Rate (%) Age <3 1,381,293 154,497 11.19 3-6 1,848,284 435,582 23.57 7-19 8,505,042 1,322,626 15.55 20-49 24,129,290 896,404 3.72 50-64 8,641,528 182,714 2.11 65 5,267,708 95,965 1.82 Sex male 24,929,939 1,542,255 6.19 female 24,843,206 1,545,533 6.22 Total 49,773,145 3,087,788 6.20
Figure 2. Antiviral Agent Prescription Rate by Region
8/21 8/28 9/4 9/11 9/18 9/25 10/2 10/9 10/16 10/23 10/30 11/6 11/13 11/20 11/27 12/4 12/11 12/18 12/25 1/1 1/8 1/15 1/22 1/29 2/5 2/12 2/19 2/26 3/5 3/12 3/19 3/26 4/2 4/9 4/16 4/23 Cases Figure 3. Antiviral Agent Prescription Rate by Region and Age Group The amount of antiviral agents prescribed rose sharply from mid-october, peaking on October 30 and decreased starting in mid-november (Figure 4). The gradient of the curve was sharper during the increasing period than in decreasing period. On October 30, 132,459 patients were prescribed with antiviral agents; however, the number of incident patients peaked on October 28 when slightly more incident cases (133,264) were assumed to have occurred. 140,000 Antiviral Agent Prescription 120,000 Adjusted Incident Patients* 100,000 80,000 60,000 40,000 20,000 0 Date Figure 4. Daily Antiviral Agent Prescription and Incident Patients from Aug 21, 2009 to Apr 24, 2010 After pandemic was over, KCDC is trying to solve several serious problems that were identified during the response in 2009. In order to expand the national isolation units or wards, 5 hospitals were designated additionally. Furthermore KCDC supported 76 hospitals to establish isolation out-patient department (OPD) and 34 hospitals to expand isolation intensive care units (ICU). Additionally, isolation rooms have been constructed and laboratories have been upgraded in three national quarantine stations. Bio-safety level (BSL) 3 laboratories have been established in 16 Provincial Research Institutes of Public Health and Environment. KCDC is also planning to build the BSL 4 laboratory complex on its campus. In addition internet based medical resource management system is being developed to increase the effectiveness of national isolation bed utilization and antiviral agent management. Throughout the response we experienced challenges, missed opportunities, limited preparedness turned full preparedness, and mostly luck based advantage. I will share them in my presentation. Reference Korea Centers for Disease Control and Prevention (KCDC). Analysis of reported pandemic influezna(a/h1n1 2009) virus infections in Korea -From April, 2009 through August, 2010-. Public Health Weekly Report 2010a;3:637-42 (Korean) Korea Centers for Disease Control and Prevention (KCDC). 2009-2010 Influenza A(H1N1) vaccination program in Korea. Public Health Weekly Report 2010b;3:357-60 (Korean)
Lee DH, Shin SS, Jun BY, Lee JK. National level response to pandemic (H1N1) 2009. J Prev Med Public Health 2010a;43:99-104 (Korean) World Health Organization (WHO). Influenza-like illness in the United States and Mexico [Internet]. 2009a Apr 24. Available from: URL:http://www.who.int/csr /don/2009_04_24 /en/index.html World Health Organization (WHO). World now at the start of 2009 influenza pandemic [Internet]. 2009b Jun 11. Available from: URL:http://www.who.int/mediacentre/news /statements/2009/h1n1_pandemic_phase6_20090611/en/index.html World Health Organization (WHO). Pandemic (H1N1) 2009 - update 112. 2010 Aug 6. Available from: URL:http://www.who.int/csr/don/2010_08_06/en/index.html