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Journal of Clinical Microbiology, April 2009, p. 1166-1171, Vol. 47, No. 4
0095-1137/09/$08.00+0     doi:10.1128/JCM.01905-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Using a Field Quantitative Real-Time PCR Test To Rapidly Identify Highly Viremic Rift Valley Fever Cases{triangledown}

M. Kariuki Njenga,1* Janusz Paweska,2 Rose Wanjala,1 Carol Y. Rao,3 Matthew Weiner,4 Victor Omballa,1 Elizabeth T. Luman,5 David Mutonga,6 Shanaaz Sharif,6 Marcus Panning,7 Christian Drosten,7 Daniel R. Feikin,1 and Robert F. Breiman1

International Emerging Infections Program, U.S. Centers for Disease Control and Prevention—Kenya, Nairobi, Kenya,1 National Institute for Communicable Diseases, Sandringham, South Africa,2 Epidemiology Intelligence Service, U.S. Centers for Disease Control and Prevention, Atlanta, Georgia,3 Naval Medical Research Unit 3, Cairo, Egypt,4 Global Immunization Division, U.S. Centers for Disease Control and Prevention, Atlanta, Georgia,5 Ministry of Health, Nairobi, Kenya,6 Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany7

Received 2 October 2008/ Returned for modification 17 December 2008/ Accepted 17 January 2009

Approximately 8% of Rift Valley fever (RVF) cases develop severe disease, leading to hemorrhage, hepatitis, and/or encephalitis and resulting in up to 50% of deaths. A major obstacle in the management of RVF and other viral hemorrhagic fever cases in outbreaks that occur in rural settings is the inability to rapidly identify such cases, with poor prognosis early enough to allow for more-aggressive therapies. During an RVF outbreak in Kenya in 2006 to 2007, we evaluated whether quantitative real-time reverse transcription-PCR (qRT-PCR) could be used in the field to rapidly identify viremic RVF cases with risk of death. In 52 of 430 RVF cases analyzed by qRT-PCR and virus culture, 18 died (case fatality rate [CFR] = 34.6%). Levels of viremia in fatal cases were significantly higher than those in nonfatal cases (mean of 105.2 versus 102.9 per ml; P < 0.005). A negative correlation between the levels of infectious virus particles and the qRT-PCR crossover threshold (CT) values allowed the use of qRT-PCR to assess prognosis. The CFR was 50.0% among cases with CT values of <27.0 (corresponding to 2.1 x 104 viral RNA particles/ml of serum) and 4.5% among cases with CT values of ≥27.0. This cutoff yielded 93.8% sensitivity and a 95.5% negative predictive value; the specificity and positive predictive value were 58% and 50%, respectively. This study shows a correlation between high viremia and fatality and indicates that qRT-PCR testing can identify nearly all fatal RVF cases.


* Corresponding author. Mailing address: Global Disease Detection Program, Centers for Disease Control and Prevention—Kenya, Unit 64112, APO, AE 09831. Phone: 254-20-2713008. Fax: 254-20-2714745. E-mail: Knjenga{at}ke.cdc.gov

{triangledown} Published ahead of print on 26 January 2009.


Journal of Clinical Microbiology, April 2009, p. 1166-1171, Vol. 47, No. 4
0095-1137/09/$08.00+0     doi:10.1128/JCM.01905-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.