Improving the clinical diagnosis of influenza--a comparative analysis of new influenza A (H1N1) cases

Abstract

Background: The presentation of new influenza A(H1N1) is broad and evolving as it continues to affect different geographic locations and populations. To improve the accuracy of predicting influenza infection in an outpatient setting, we undertook a comparative analysis of H1N1(2009), seasonal influenza, and persons with acute respiratory illness (ARI) in an outpatient setting.

Methodology/principal findings: Comparative analyses of one hundred non-matched cases each of PCR confirmed H1N1(2009), seasonal influenza, and ARI cases. Multivariate analysis was performed to look for predictors of influenza infection. Receiver operating characteristic curves were constructed for various combinations of clinical and laboratory case definitions. The initial clinical and laboratory features of H1N1(2009) and seasonal influenza were similar. Among ARI cases, fever, cough, headache, rhinorrhea, the absence of leukocytosis, and a normal chest radiograph positively predict for both PCR-confirmed H1N1-2009 and seasonal influenza infection. The sensitivity and specificity of current WHO and CDC influenza-like illness (ILI) criteria were modest in predicting influenza infection. However, the combination of WHO ILI criteria with the absence of leukocytosis greatly improved the accuracy of diagnosing H1N1(2009) and seasonal influenza (positive LR of 7.8 (95%CI 3.5-17.5) and 9.2 (95%CI 4.1-20.3) respectively).

Conclusions/significance: The clinical presentation of H1N1(2009) infection is largely indistinguishable from that of seasonal influenza. Among patients with acute respiratory illness, features such as a temperature greater than 38 degrees C, rhinorrhea, a normal chest radiograph, and the absence of leukocytosis or significant gastrointestinal symptoms were all positively associated with H1N1(2009) and seasonal influenza infection. An enhanced ILI criteria that combines both a symptom complex with the absence of leukocytosis on testing can improve the accuracy of predicting both seasonal and H1N1-2009 influenza infection.

Figure 1. Date of presentation of adult H1N1(2009) and seasonal influenza cases by epidemiological week.

Note that there was inconsistent testing for influenza strains other than H1N1(2009) after 11 June 2009 (Week 23), and the data for seasonal influenza is hence censored after week 23.

Figure 2. Receiver operating characteristic curves.

(A) H1N1 versus acute respiratory illness, where Area under the receiver operating characteristic curve (AUROC) values are 0.839 for multivariate logistic regression model using symptoms and signs only, and 0.874 when adding laboratory and chest radiograph (CXR) findings. (B) seasonal influenza versus acute respiratory illness. AUROC values are 0.842 for symptoms and signs only, and 0.893 when adding laboratory and CXR findings.