Pandemic (H1N1) 2009 Surveillance and Prevalence of Seasonal Influenza, Singapore

On April 25, 2009, Singapore implemented strict containment measures for pandemic (H1N1) 2009 with enhanced surveillance and hospital isolation. In the first month, seasonal influenza, predominantly virus subtype H3N2, was diagnosed for 32% of patients with acute febrile respiratory illness. Our findings underscore the high prevalence of seasonal influenza in Singapore.

T ropical countries experience infl uenza year round, with 2 peaks corresponding to the rainy seasons (1).
Despite this year-round activity, seasonal infl uenza is often neglected in tropical countries in terms of clinical diagnosis, treatment, and vaccination (2). In Singapore, infl uenza activity usually peaks in June and December (3). The annual all-cause death rate from seasonal infl uenza in Singapore has been estimated at 14.8/100,000 personyears; the proportion of deaths among persons ≥65 years of age is 11.3× higher than that among the general population (4). In addition, previous pandemic infl uenza-related excess deaths in Singapore are comparable to those in temperate countries (5).
In April 2009, a novel infl uenza A virus (H1N1) of swine origin emerged in the United States (6) and triggered alarm about its pandemic potential (7). On June 11, 2009, the World Health Organization announced that the virus had become pandemic; it is now referred to as pandemic (H1N1) 2009 virus (8). We report on enhanced infl uenza surveillance in Singapore that was implemented before the fi rst case of pandemic (H1N1) 2009 was detected on May 26, 2009, and we describe the transition in Singapore from infl uenza cases caused predominantly by seasonal infl uenza to cases caused exclusively by pandemic (H1N1) 2009 virus.

The Study
This surveillance study was approved by the Chairman of Medical Board, Tan Tock Seng Hospital (TTSH), Singapore. The clinical study was approved by the Domain Specifi c Review Board, National Healthcare Group, Singapore.
On April 25, 2009, Singapore's Ministry of Health initiated containment measures in response to pandemic (H1N1) 2009. Travelers returning from affected countries to Singapore with acute febrile respiratory illness were screened at the TTSH emergency department, the designated screening center for pandemic (H1N1) 2009. Thermal screening was conducted at all border entry points, and the mass media publicized nationwide that persons with a risk for pandemic (H1N1) 2009 virus infection based on travel history, fever, and respiratory symptoms should go to the TTSH emergency department for screening. Combined nasal and throat swab specimens were tested with an in-house, gel-based PCR for infl uenza A, H1, H3, H5, N1, and N2. All specimens with subtype H1N1-positive test results underwent in-house, probe-based infl uenza (H1N1) 2009 PCR, and partial sequencing of the matrix gene was conducted to confi rm positive PCR results.
From Two thirds of the patients with infl uenza-positive PCR results met the criteria for infl uenza-like illness (ILI) as defi ned by the US Centers for Disease Control and Prevention (CDC) (9). Patients who met these criteria were more likely than those who did not to have infl uenza-positive PCR results (odds ratio [OR] 8.1, 95% confi dence interval [CI] 4.6-14.3, p = 0.0001). Compared with contacts who had no recent travel, travelers returning from North America were less likely to have infl uenza-positive PCR test results (OR 0.13, 95% CI 0.06-0.27, p = 0.0001).
To enhance detection of pandemic (H1N1) 2009, we obtained nasal and throat swab samples on May 2 and 3, 2009, from all hospitalized patients with clinically suspected pneumonia, regardless of their travel history. The samples were tested by PCR for infl uenza. A total of 146 patients were screened, of whom 21 (14.4%) were positive for infl uenza; 10.3% of the 146 patients had H3N2, 1.4% had seasonal H1N1, and 2.7% had infl uenza B. The median age of these patients was 67 years (range 20-95 years), and their median hospital stay at screening was 1 day (range 0-17 days). Of the patients, 52% were male, and 86% had other illnesses. At the time of admission, 90% of patients had a fever, 76% had a cough, 24% had a sore throat, 52% had rhinorrhea, 24% had myalgia, and 19% had headache. Findings on chest radiographs were abnormal for 10 patients (48%), of whom 5 had fi ndings consistent with pneumonia. All but 1 patient were treated with antimicrobial drugs; none was given antiviral drug therapy. The median hospital stay was 5 days (range 1-38 days). Two patients died; both had multiple illnesses.
In addition, during May 2-8, 2009, as part of nationwide enhanced infl uenza surveillance, nasal and throat swab specimens from patients screened at the TTSH emergency department were tested by PCR for infl uenza virus. The patients had fever or respiratory symptoms but no history of travel to an affected country. Overall, 95 patients were screened, of whom 30 (31.6%) had positive results for infl uenza; 24.2% of the 95 patients had H3N2 and 7.4% had infl uenza B. Fever was reported for 69.5% of the 95 patients, cough for 75.8%, sore throat for 56.8%, rhinorrhea for 58.9%, myalgia for 16.8%, and headache for 44.2%. Of the 30 patients with PCR results positive for infl uenza, 22 (73%) met the criteria for ILI. Compared with patients who did not meet these criteria, patients who did meet them were 3× more likely to have infl uenza-positive PCR results (OR 3.02, 95% CI 1.17-7.75, p = 0.019). Only 6 (6.3%) of the 95 patients had self-reported infl uenza vaccination in the preceding 6 months.
Screening of patients with ILI symptoms continued at the TTSH emergency department, and from May 3 through June 13, 2009, only seasonal infl uenza (predominantly virus subtype H3N2) was detected. Pandemic (H1N1) 2009 was fi rst detected during the week beginning June 14, and the weekly incidence rapidly increased until the week ending July 25, when all infl uenza cases were caused by pandemic (H1N1) 2009 virus (Figure).
By July 25, 2009, a total of 838 patients with pandemic (H1N1) 2009 virus infection had been seen at the TTSH emergency department. The median age of patients was 22 years (range 10-90 years). Fever was reported for 85.3%, cough for 87.2%, sore throat for 55.4%, rhinorrhea for 41.6%, myalgia for 11.1%, and headache for 11.0%; 57% of patients met the CDC criteria for ILI. Patients with pandemic (H1N1) 2009 were signifi cantly younger (p = 0.0001) than patients with seasonal infl uenza, but the proportion with ILI in each group was similar (OR 0.65, 95% CI 0.41-1.04, p = 0.071).

Conclusions
Each year in the United States, seasonal infl uenza accounts for >200,000 hospitalizations and 41,000 deaths, and it is the seventh leading cause of death (10). The effect of seasonal infl uenza in the tropics is less well studied. In Thailand, infl uenza was detected in 11%-12.5% of patients with community-acquired pneumonia and in 23% of outpatients with ILI (11,12).
Enhanced infl uenza surveillance in Singapore in response to pandemic (H1N1) 2009 yielded a high prevalence of seasonal infl uenza: 28.3% (85 of 300) among returning travelers and their contacts with respiratory symptoms, 14.4% (21 of 146) among hospitalized patients with suspected pneumonia, and 31.6% (30 of 95) among patients self-reporting to the TTSH emergency department with fever and respiratory symptoms but without a history of travel to affected countries. These fi ndings refl ect the peak local infl uenza season (2,(4)(5). The risk of having seasonal infl uenza was lower among travelers returning from North America, a fi nding that was consistent with the timing of the peak local infl uenza season and the noninfl uenza season in the Northern Hemisphere.
Of 21 patients with infl uenza-positive PCR results, only 5 had radiographic evidence of pneumonia despite having a pneumonia diagnosis based on an acute history of fever and cough. No patients, including those with positive test results, were treated with antiviral drugs. This fi nding, in addition to low infl uenza vaccine coverage in Singapore, refl ects the underappreciation of infl uenza by doctors in this country.
Of note, 67%-73% of the patients with infl uenzapositive PCR results met the CDC ILI criteria during the study period; this fi nding may guide testing for seasonal infl uenza during peak infl uenza seasons in May-June and December. Its value in nonpeak seasons, however, requires further evaluation because infl uenza occurs year-round in the tropics (1). Temperature >38°C and either cough or sore throat (13) were the most specifi c screening criteria and had the best positive predictive value; temperature of 37.5°C and either cough, sore throat, or rhinorrhea were the most sensitive screening criteria and had the best negative predictive value for infl uenza (Table).
Our fi ndings highlight a high prevalence of seasonal infl uenza during peak times in Singapore; the prevalence is comparable to that during typical infl uenza seasons in temperate countries in the Southern Hemisphere. This prevalence underscores the need for not neglecting seasonal infl uenza and for a more robust surveillance system to be in place for community and hospital monitoring in Singapore. Dr Leo is clinical director of the Communicable Disease Centre, Tan Tock Seng Hospital, Singapore. Her research interests include HIV, dengue, infl uenza, and other emerging infectious diseases.