• 1.

    Simmerman JM, Chittaganpitch M, Erdman D, Sawatwong P, Uyeki TM, Dowell SF, 2007. Field performance and new uses of rapid influenza testing in Thailand. Int J Infect Dis 11: 166171.

    • Search Google Scholar
    • Export Citation
  • 2.

    Wunderli W, Thomas Y, Muller DA, Dick M, Kaiser L, 2003. Rapid antigen testing for the surveillance of influenza epidemics. Clin Microbiol Infect 9: 295300.

    • Search Google Scholar
    • Export Citation
  • 3.

    Rodriguez WJ, Schwartz RH, Thorne MM, 2002. Evaluation of diagnostic tests for influenza in a pediatric practice. Pediatr Infect Dis J 21: 193196.

    • Search Google Scholar
    • Export Citation
  • 4.

    Uyeki TM, 2003. Influenza diagnosis and treatment in children: a review of studies on clinically useful tests and antiviral treatment for influenza. Pediatr Infect Dis J 22: 164177.

    • Search Google Scholar
    • Export Citation
  • 5.

    Uyeki TM, Prasad R, Vukotich C, Stebbins S, Rinaldo CR, Ferng YH, Morse SS, Larson EL, Aiello AE, Davis B, Monto AS, 2009. Low sensitivity of rapid diagnostic test for influenza. Clin Infect Dis 48: e89e92.

    • Search Google Scholar
    • Export Citation
  • 6.

    Blair PJ, Wierzba TF, Touch S, Vonthanak S, Xu X, Garten RJ, Okomo-Adhiambo MA, Klimov AI, Kasper MR, Putnam SD, 2010. Influenza epidemiology and characterization of influenza viruses in patients seeking treatment for acute fever in Cambodia. Epidemiol Infect 138: 199209.

    • Search Google Scholar
    • Export Citation
  • 7.

    Agoritsas K, Mack K, Bonsu BK, Goodman D, Salamon D, Marcon MJ, 2006. Evaluation of the Quidel QuickVue test for detection of influenza A and B viruses in the pediatric emergency medicine setting by use of three specimen collection methods. J Clin Microbiol 44: 26382641.

    • Search Google Scholar
    • Export Citation
  • 8.

    Hurt AC, Alexander R, Hibbert J, Deed N, Barr IG, 2007. Performance of six influenza rapid tests in detecting human influenza in clinical specimens. J Clin Virol 39: 132135.

    • Search Google Scholar
    • Export Citation
  • 9.

    Mehlmann M, Bonner AB, Williams JV, Dankbar DM, Moore CL, Kuchta RD, Podsiad AB, Tamerius JD, Dawson ED, Rowlen KL, 2007. Comparison of the MChip to viral culture, reverse transcription-PCR, and the QuickVue influenza A+B test for rapid diagnosis of influenza. J Clin Microbiol 45: 12341237.

    • Search Google Scholar
    • Export Citation
  • 10.

    Bhavnani D, Phatinawin L, Chantra S, Olsen SJ, Simmerman JM, 2007. The influence of rapid influenza diagnostic testing on antibiotic prescribing patterns in rural Thailand. Int J Infect Dis 11: 355359.

    • Search Google Scholar
    • Export Citation

 

 

 

 

Rapid-Test Based Identification of Influenza as an Etiology of Acute Febrile Illness in Cambodia

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  • U.S. Naval Medical Research Unit No. 2, Jakarta, Indonesia; Communicable Disease Control Department, Ministry of Health, Phnom Penh Cambodia; U.S. Naval Medical Research Unit No. 2, Phnom Penh, Cambodia

Influenza can be manifested as an acute febrile illness, with symptoms similar to many pathogens endemic to Cambodia. The objective of this study was to evaluate the Quickvue influenza A+B rapid test to identify the etiology of acute febrile illness in Cambodia. During December 2006–May 2008, patients enrolled in a study to identify the etiology of acute febrile illnesses were tested for influenza by real-time reverse transcriptase PCR (RT-PCR) and Quickvue influenza A+B rapid test. The prevalence of influenza was 19.7% by RT-PCR. Compared with RT-PCR, the sensitivity and specificity of the rapid test were 52.1% and 92.5%, respectively. The influenza rapid test identified the etiology in 10.2% of enrollees and ≥ 35% during peak times of influenza activity. This study suggests that rapid influenza tests may be useful during peak times of influenza activity in an area where several different etiologies can present as an acute febrile illness.

Several studies have highlighted the use of rapid influenza testing to improve early detection of epidemics and conduct outbreak responses.1,2 Rapid influenza testing can be used to identify patients with influenza in a timely manner and influence clinical treatment.3,4 Although rapid testing for influenza has been demonstrated to be less sensitive when compared with the polymerase chain reaction (PCR),5 it could be an attractive diagnostic tool in resource-limited settings lacking laboratory capabilities to identify influenza by culture or molecular techniques. There is limited data on the use of rapid influenza testing in Southeast Asia and regions where numerous etiologies of acute febrile illness are endemic and could require prompt treatment (e.g., malaria, dengue, typhoid fever).

Hospital-based and clinic based influenza surveillance was established to ascertain the etiologies contributing to acute febrile illness in patients in Cambodia.6 We report the performance of a rapid influenza test conducted at the sites of enrollment to identify influenza as an etiology of febrile illness during December 2006–May 2008 in Cambodia. Outpatients were initially recruited from two referral hospitals, but during the course of the study, seven additional healthcare facilities were added; two in August 2007, one in October 2007, one in December 2007, one in February 2007, one in March 2008, and one in April 2008. Study sites were located ≤ 50 km of Phnom Penh in southcentral Cambodia.

Patients were clinically evaluated by a physician or medical assistant and recruited for study participation if they met inclusion criteria: at least 24 hours of fever (a measured tympanic membrane temperature > 38.0°C), were ≥ 2 years of age, and after medical examination, had no obvious source of infection. Influenza-like illness was defined as fever (> 38.0°C) with cough and/or sore throat. Eligible subjects voluntarily enrolled in accordance with an Institutional Review Board protocol approved by U.S. Naval Medical Research Unit No. 2 in compliance with all applicable Federal regulations governing the protection of human subjects and the National Ethics Committee of the Royal Kingdom of Cambodia, Ministry of Health.

For each enrolled patient, one throat and one nasal swab was collected and placed in a vial containing 2–3 mL of virus transport medium. All inoculated vials were kept at 4°C until received by the laboratory 24–72 hours after collection. Medical personnel were trained by study investigators by using the manufacturer's instructions on the proper collection of a nasopharyngeal swab and interpretation of the QuickVue Influenza A+B Test (Quidel Inc., San Diego, CA). Color digital photographs of all rapid test results were taken and forwarded for laboratory supervisor's confirmation. RNA was extracted from nasal and throat swabs by using QIAamp viral RNA mini kits (QIAGEN, Hilden, Germany) according to the manufacturer's instruction and stored at –70°C. Influenza virus genome was detected by using a reverse real-time PCR (Centers for Disease Control and Prevention, Atlanta, GA) developed to detect influenza A and B viruses and influenza A viruses of H1, H3, and H5 subtypes and performed as described.6

A total of 1,327 patients were enrolled during December 2006–May 2008. Among the participants, the median age was 10 years (interquartile range [IQR] = 5–22 years) and 50% were male. The median time of illness prior to presentation for healthcare services was 3 days (IQR = 2–3 days). During this period, 261 (19.7%) enrollees were identified as influenza positive by RT-PCR, and 147 participants were influenza positive by rapid test. Among the 147 rapid test–positive results, 136 had concordant results by RT-PCR. Overall, the sensitivity and specificity of the Quickvue influenza rapid test compared with PCR was 52.1% and 92.5%, respectively. Among the 136 concordant results, 72 (52.9%) were influenza A and 64 (47.1%) were influenza B. Sensitivity for influenza A and B was 47% and 57%, respectively. One case identified as rapid influenza A positive at the field site was later confirmed to be influenza B.

Among PCR-positive influenza patients, the median age of rapid test–positive patients was 8 years (IQR = 5–12 years) and the median age of rapid test–negative patients was 10 years (IQR = 5–17 years). There was a significant difference between the sensitivities of the rapid test between age groups, 56.9% among patients 2–18 years of age and 22.2% among patients > 18 years of age (P = 0.0001). The median day of presentation for health care services was 3 days for rapid test positive-patients (IQR = 2–3 days) and rapid test–negative patients (IQR = 2.5–4 days). A comparison based on day of fever presentation identified a significant difference among patients presenting at days 0–3 (61.1%) and day 4 (22.4%) (P < 0.0001). There was no significant difference in rapid test results based on a clinical presentation with influenza-like illness; 74.8% of rapid test–positive patients and 79.3% of rapid test–negative patients had influenza-like illness (P = 0.39).

Among 1,327 patients enrolled who had an acute febrile illness, use of an influenza rapid test resulted in 136 (10.2%) patients who were diagnosed with influenza at the time of their health care visit. During the peak of influenza activity (August–December 2007),6 influenza rapid tests identified 20–35% of the acute febrile cases as influenza infections. There was a significant difference in the sensitivity of the rapid test when used at times of peak influenza activity compared with when influenza was not circulating (55.6% versus 25.1%, respectively; P = 0.002).

In this study, the overall sensitivity of the influenza rapid test was similar to those of published studies.5,79 The cost of influenza PCR testing (US $21–25/test) and infrastructure requirements prevent its routine clinical use in Cambodia. A laboratory-based surveillance program that monitors influenza activity in a region could determine times to implement rapid testing beyond the influenza surveillance sentinel sites to help manage and diagnose illnesses. Limiting the use of rapid tests (US $7–12/test)10 to times determined by a laboratory-based surveillance program would be a more cost-effective alternative than year-round testing.

This study was conducted in a region endemic to several causes of acute febrile illness (e.g., dengue, malaria, typhoid) that can present with similar symptoms and can make a clinical diagnosis of disease difficult. This study suggests that rapid influenza tests may be useful during peak times of influenza activity or during outbreaks in an area where several different etiologies can present as an acute febrile illness.

ACKNOWLEDGMENTS:

We thank the clinicians and medical staff at the field sites in Cambodia for their assistance in enrolling and sampling patients and laboratory personnel at the U.S. Naval Medical Research Unit No. in Phnom Penh and the Centers for Disease Control and Prevention for participating in the study.

  • 1.

    Simmerman JM, Chittaganpitch M, Erdman D, Sawatwong P, Uyeki TM, Dowell SF, 2007. Field performance and new uses of rapid influenza testing in Thailand. Int J Infect Dis 11: 166171.

    • Search Google Scholar
    • Export Citation
  • 2.

    Wunderli W, Thomas Y, Muller DA, Dick M, Kaiser L, 2003. Rapid antigen testing for the surveillance of influenza epidemics. Clin Microbiol Infect 9: 295300.

    • Search Google Scholar
    • Export Citation
  • 3.

    Rodriguez WJ, Schwartz RH, Thorne MM, 2002. Evaluation of diagnostic tests for influenza in a pediatric practice. Pediatr Infect Dis J 21: 193196.

    • Search Google Scholar
    • Export Citation
  • 4.

    Uyeki TM, 2003. Influenza diagnosis and treatment in children: a review of studies on clinically useful tests and antiviral treatment for influenza. Pediatr Infect Dis J 22: 164177.

    • Search Google Scholar
    • Export Citation
  • 5.

    Uyeki TM, Prasad R, Vukotich C, Stebbins S, Rinaldo CR, Ferng YH, Morse SS, Larson EL, Aiello AE, Davis B, Monto AS, 2009. Low sensitivity of rapid diagnostic test for influenza. Clin Infect Dis 48: e89e92.

    • Search Google Scholar
    • Export Citation
  • 6.

    Blair PJ, Wierzba TF, Touch S, Vonthanak S, Xu X, Garten RJ, Okomo-Adhiambo MA, Klimov AI, Kasper MR, Putnam SD, 2010. Influenza epidemiology and characterization of influenza viruses in patients seeking treatment for acute fever in Cambodia. Epidemiol Infect 138: 199209.

    • Search Google Scholar
    • Export Citation
  • 7.

    Agoritsas K, Mack K, Bonsu BK, Goodman D, Salamon D, Marcon MJ, 2006. Evaluation of the Quidel QuickVue test for detection of influenza A and B viruses in the pediatric emergency medicine setting by use of three specimen collection methods. J Clin Microbiol 44: 26382641.

    • Search Google Scholar
    • Export Citation
  • 8.

    Hurt AC, Alexander R, Hibbert J, Deed N, Barr IG, 2007. Performance of six influenza rapid tests in detecting human influenza in clinical specimens. J Clin Virol 39: 132135.

    • Search Google Scholar
    • Export Citation
  • 9.

    Mehlmann M, Bonner AB, Williams JV, Dankbar DM, Moore CL, Kuchta RD, Podsiad AB, Tamerius JD, Dawson ED, Rowlen KL, 2007. Comparison of the MChip to viral culture, reverse transcription-PCR, and the QuickVue influenza A+B test for rapid diagnosis of influenza. J Clin Microbiol 45: 12341237.

    • Search Google Scholar
    • Export Citation
  • 10.

    Bhavnani D, Phatinawin L, Chantra S, Olsen SJ, Simmerman JM, 2007. The influence of rapid influenza diagnostic testing on antibiotic prescribing patterns in rural Thailand. Int J Infect Dis 11: 355359.

    • Search Google Scholar
    • Export Citation

Author Notes

*Address correspondence to Matthew R. Kasper, Department of Bacteriology, U.S. Naval Medical Research Unit 6, Lima, Peru, Unit 3230, DPO, AA 34031. E-mail: matthew.kasper@med.navy.mil

Financial support: This study was supported in part by grants from the Influenza Division of the U.S. Centers for Disease Control and Prevention and the U.S. Department of Defenses' Global Emerging Infection Systems, a division of the Armed Forces Health Surveillance Center.

Disclosure: Several of the authors are military service members. This work was prepared as part of our official duties. Title 17 U.S.C. §105 provides that “Copyright protection under this title is not available for any work of the United States Government.” Title 17 U.S.C. §101 defines a U.S. Government work as a work prepared by a military service member or employee of the U.S. Government as part of that person's official duties.

Authors' addresses: Matthew R. Kasper, Shannon D. Putnam, and Patrick J. Blair, Department of Bacteriology, U.S. Naval Medical Research Unit 6, Lima, Peru, Unit 3230, DPO, AA, E-mails: matthew.kasper@med.navy.mil, shan.putnam@med.navy.mil, and Patrick.blair@med.navy.mil. Ly Sovann, Communicable Disease Control Department, Ministry of Health, Phnom Penh Cambodia, E-mail: sovann_ly@online.com.kh. Chadwick Y. Yasuda and Thomas F. Wierzba, U.S. Naval Medical Research Unit No. 2, Phnom Penh, Cambodia, E-mail: twierzba@ivi.int.

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