Abstract
SummaryDuring the H1N1 influenza pandemic (pH1N1/09) diagnostic algorithms were developed to guide antiviral provision. However febrile illnesses are notoriously difficult to distinguish clinically. Recent evidence highlights the importance of incorporating travel history into diagnostic algorithms to prevent the catastrophic misdiagnosis of life-threatening infections such as malaria.We applied retrospectively the UK pH1N1/09 case definition to a unique cohort of healthy adult volunteers exposed to Plasmodium falciparum malaria or influenza to assess the predictive value of this case definition, and to explore the distinguishing clinical features of early phase infection with these pathogens under experimental conditions.For influenza exposure the positive predictive value of the pH1N1/09 case definition was only 0.38 (95% CI: 0.06–0.60), with a negative predictive value of 0.27 (95% CI: 0.02–0.51). Interestingly, 8/11 symptomatic malaria-infected adults would have been inappropriately classified with influenza by the pH1N1/09 case definition, while 5/8 symptomatic influenza-exposed volunteers would have been classified without influenza (P = 0.18 Fisher's exact). Cough (P = 0.005) and nasal symptoms (P = 0.001) were the only clinical features that distinguished influenza-exposed from malaria-exposed volunteers.An open mind regarding the clinical cause of undifferentiated febrile illness, particularly in the absence of upper respiratory tract symptoms, remains important even during influenza pandemic settings. These data support incorporating travel history into pandemic algorithms.
Highlights
With the advent of the first pandemic of influenza of the 21st century, there was significant concern about the potential impact on healthcare infrastructure of managing pandemic H1N1 infections in traditional settings
For influenza exposure the positive predictive value of the pandemic H1N1 (pH1N1)/09 case definition was only 0.38, with a negative predictive value of 0.27
8/11 symptomatic malaria-infected adults would have been inappropriately classified with influenza by the pH1N1/09 case definition, while 5/8 symptomatic influenzaexposed volunteers would have been classified without influenza (P Z 0.18 Fisher’s exact)
Summary
With the advent of the first pandemic of influenza of the 21st century, there was significant concern about the potential impact on healthcare infrastructure of managing pandemic H1N1 (pH1N1) infections in traditional settings. In the course of separate candidate vaccine efficacy trials carried out by our unit (www.clinicaltrials.gov NCT00890760/NCT00993083), we independently exposed cohorts of unimmunised healthy control volunteers to pathogenic strains of either Plasmodium falciparum (P. falciparum) malaria or influenza A under controlled experimental conditions, and followed them closely in the early phases of infection until clinical diagnosis. These control volunteers were enrolled to ensure the reliability of the respective experimental infections and did not receive any immunisations. These data afford us a unique opportunity to perform a retrospective comparison of the early clinical features that may be of use in differentiating clinically between an often uncomplicated illness in influenza and a potentially life-threatening infection in malaria, and to assess whether the clinical features included in the UK pandemic case definition alone were sufficiently discriminatory
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