Effects of early oseltamivir therapy on viral shedding in 2009 pandemic influenza A (H1N1) virus infection.

BACKGROUND: Pandemic influenza (H1N1) 2009 is susceptible to oseltamivir. There are few reports on its clinical and virologic response to oseltamivir. METHODS: During the pandemic containment response in Singapore, all patients with positive polymerase chain reaction (PCR) results for pandemic influenza (H1N1) 2009 were hospitalized, given oseltamivir for 5 days, and discharged when daily PCR results for combined nasal and throat swab samples became negative. Six patients had concurrent positive viral culture and PCR results. RESULTS: The median age of the first 70 consecutive patients was 26 years (interquartile range, 21-38 years); 60% were men, and 29% had comorbidity. The mean time (+/-SD) from illness onset to hospital admission was 3+/-2 days. Influenza-like illness was noted in 63% of patients. Fever occurred in 91%, cough in 88%, sore throat in 66%, and rhinorrhea in 53% of patients. The mean duration (+/-SD) of viral shedding from illness onset was day 6+/-2 days. Viral shedding persisted beyond 7 days in 37% of patients. Clinical features and viral shedding were similar between those with and without comorbidity, except the former had more cough and lower oxygen saturation. Patients receiving oseltamivir on days 1 to 3 of illness had significantly shorter viral shedding duration, compared with those treated from day 4 onwards (P < .05). The mean durations (+/-SD) of positive PCR and viral culture results were 5+/-8 and 4+/-18 days, respectively, for 6 patients with concurrent positive viral culture and PCR results. CONCLUSIONS: Prolonged viral shedding was noted in young immunocompetent adults with mild pandemic influenza (H1N1) 2009 despite receipt of oseltamivir. When prescribed during the first 3 days of illness, oseltamivir shortened the duration of viral shedding.

Implications of discordance in world health organization 1997 and 2009 dengue classifications in adult dengue.

BACKGROUND: Revised dengue guidelines were published by the World Health Organization (WHO) in 2009 addressing severe dengue cases not classified by dengue hemorrhagic fever (DHF) and shock syndrome (DSS). METHODS AND PRINCIPAL FINDINGS: We conducted a retrospective cohort study to compare WHO 2009 and 1997 classifications using 1278 adult dengue cases confirmed by polymerase chain reaction assay from Singapore epidemics in 2004 and 2007 (predominantly serotype 1 and 2 respectively).DHF occurred in 14.3%, DSS 2.7% and severe dengue 16.0%. The two WHO dengue classifications were discordant in defining severe disease (p<0.001). Five DSS patients (15%) were classified as non-severe dengue without warning signs. Of severe dengue patients, 107 did not fulfil DHF criteria. Of these, 14.9% had self-resolving isolated elevated aminotransferases, 18.7% gastrointestinal bleeding without hemodynamic compromise and 56.1% plasma leakage with isolated tachycardia. We compared both guidelines against requirement for intensive care including the single death in this series: all six had severe dengue; only four had DHF as two lacked bleeding manifestations but had plasma leakage. Increasing length of hospitalization was noted among severe cases with both classifications but the trend was only statistically significant for WHO 2009. Length of hospitalization was significantly longer for severe plasma leakage compared with severe bleeding or organ impairment. Requirement for hospitalization increased using WHO 2009 from 17.0% to 51.3%. CONCLUSIONS: While the WHO 2009 dengue classification is clinically useful, we propose retaining criteria for plasma leakage and hemodynamic compromise from WHO 1997, and refining definitions of severe bleeding and organ impairment to improve clinical relevance having found that differences in these accounted for the discordance between classifications. Findings from our retrospective study may be limited by the study site - a tertiary referral center in a hyperendemic country - and should be evaluated in a wider range of geographic settings.

Clinical relevance and discriminatory value of elevated liver aminotransferase levels for dengue severity.

BACKGROUND: Elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) is prominent in acute dengue illness. The World Health Organization (WHO) 2009 dengue guidelines defined AST or ALT ≥ 1000 units/liter (U/L) as a criterion for severe dengue. We aimed to assess the clinical relevance and discriminatory value of AST or ALT for dengue hemorrhagic fever (DHF) and severe dengue. METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively studied and classified polymerase chain reaction positive dengue patients from 2006 to 2008 treated at Tan Tock Seng Hospital, Singapore according to WHO 1997 and 2009 criteria for dengue severity. Of 690 dengue patients, 31% had DHF and 24% severe dengue. Elevated AST and ALT occurred in 86% and 46%, respectively. Seven had AST or ALT ≥ 1000 U/L. None had acute liver failure but one patient died. Median AST and ALT values were significantly higher with increasing dengue severity by both WHO 1997 and 2009 criteria. However, they were poorly discriminatory between non-severe and severe dengue (e.g., AST area under the receiver operating characteristic [ROC] curve=0.62; 95% confidence interval [CI]: 0.57-0.67) and between dengue fever (DF) and DHF (AST area under the ROC curve=0.56; 95% CI: 0.52-0.61). There was significant overlap in AST and ALT values among patients with dengue with or without warning signs and severe dengue, and between those with DF and DHF. CONCLUSIONS: Although aminotransferase levels increased in conjunction with dengue severity, AST or ALT values did not discriminate between DF and DHF or non-severe and severe dengue.

Pandemic (H1N1) 2009: clinical and laboratory findings of the first fifty cases in Singapore.

INTRODUCTION: Since the fi rst imported case on 26 May 2009, pandemic (H1N1) 2009 has spread from travellers and has resulted in sustained community transmission. Singapore began with a strict containment policy where all suspected and confirmed cases of pandemic (H1N1) 2009 were admitted for testing. We describe here the clinical and laboratory characteristics of the fi rst 50 adult cases with confirmed pandemic (H1N1) 2009. MATERIALS AND METHODS: A review was conducted of medical notes of adult patients with confirmed pandemic (H1N1) 2009 by polymerase chain reaction assay from combined nasal and throat swabs admitted to the Communicable Disease Centre, Tan Tock Seng Hospital. RESULTS: From 26 May to 18 June 2009, 50 patients with a median age of 27 years old were admitted at a median of 3 days from illness onset. Half were male and all were travellers arriving in Singapore. Non-Singaporean citizens (38%) and other ethnic groups (40%) were over-represented. History of fever was reported in 90% and respiratory symptoms in 92%. Gastrointestinal symptoms were uncommon, present in 4% only. Temperatures on presentation of >or=38.0 degrees C, >or=37.8 degrees C and >or=37.5 degrees C were present in 48%, 56% and 76%, respectively. Only 46% of patients met the United States Centers for Disease Control and Prevention (US CDC) case definition of influenza-like illness (ILI). Clinical and laboratory findings were unremarkable for the majority. All cases were treated with oseltamivir and had uncomplicated recovery. CONCLUSION: Pandemic (H1N1) 2009 had mild clinical and laboratory findings in immunocompetent patients. Use of the US CDC ILI criteria alone would have detected less than half of confirmed cases.

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

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.