Christian Drosten1, Benjamin Meyer, Marcel A Müller, Victor M Corman, Malak Al-Masri, Raheela Hossain, Hosam Madani, Andrea Sieberg, Berend Jan Bosch, Erik Lattwein, Raafat F Alhakeem, Abdullah M Assiri, Waleed Hajomar, Ali M Albarrak, Jaffar A Al-Tawfiq, Alimuddin I Zumla, Ziad A Memish. 1. From the Institute of Virology, University of Bonn Medical Center, Bonn (C.D., B.M., M.A.M., V.M.C., A.S.), and Euroimmun, Lübeck (E.L.) - both in Germany; Global Center for Mass Gatherings Medicine, Ministry of Health (M.A.-M., R.F.A., A.M. Assiri, A.I.Z., Z.A.M.), Prince Sultan Military Medical City (A.M. Albarrak), and Alfaisal University (Z.A.M.), Riyadh, Johns Hopkins Aramco Healthcare, Dhahran (J.A.A.-T.), and Regional Laboratory, Ministry of Health, Jeddah (R.H., H.M.) and Riyadh (W.H.) - all in Saudi Arabia; Indiana University School of Medicine, Indianapolis (J.A.A.-T.); the Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands (B.J.B.); and the Division of Infection and Immunity, University College London (UCL), and National Institute for Health Research Biomedical Research Centre, UCL Hospitals, London (A.I.Z.).
Abstract
BACKGROUND: Strategies to contain the Middle East respiratory syndrome coronavirus (MERS-CoV) depend on knowledge of the rate of human-to-human transmission, including subclinical infections. A lack of serologic tools has hindered targeted studies of transmission. METHODS: We studied 26 index patients with MERS-CoV infection and their 280 household contacts. The median time from the onset of symptoms in index patients to the latest blood sampling in contact patients was 17.5 days (range, 5 to 216; mean, 34.4). Probable cases of secondary transmission were identified on the basis of reactivity in two reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays with independent RNA extraction from throat swabs or reactivity on enzyme-linked immunosorbent assay against MERS-CoV S1 antigen, supported by reactivity on recombinant S-protein immunofluorescence and demonstration of neutralization of more than 50% of the infectious virus seed dose on plaque-reduction neutralization testing. RESULTS: Among the 280 household contacts of the 26 index patients, there were 12 probable cases of secondary transmission (4%; 95% confidence interval, 2 to 7). Of these cases, 7 were identified by means of RT-PCR, all in samples obtained within 14 days after the onset of symptoms in index patients, and 5 were identified by means of serologic analysis, all in samples obtained 13 days or more after symptom onset in index patients. Probable cases of secondary transmission occurred in 6 of 26 clusters (23%). Serologic results in contacts who were sampled 13 days or more after exposure were similar to overall study results for combined RT-PCR and serologic testing. CONCLUSIONS: The rate of secondary transmission among household contacts of patients with MERS-CoV infection has been approximately 5%. Our data provide insight into the rate of subclinical transmission of MERS-CoV in the home.
BACKGROUND: Strategies to contain the Middle East respiratory syndrome coronavirus (MERS-CoV) depend on knowledge of the rate of human-to-human transmission, including subclinical infections. A lack of serologic tools has hindered targeted studies of transmission. METHODS: We studied 26 index patients with MERS-CoV infection and their 280 household contacts. The median time from the onset of symptoms in index patients to the latest blood sampling in contact patients was 17.5 days (range, 5 to 216; mean, 34.4). Probable cases of secondary transmission were identified on the basis of reactivity in two reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays with independent RNA extraction from throat swabs or reactivity on enzyme-linked immunosorbent assay against MERS-CoV S1 antigen, supported by reactivity on recombinant S-protein immunofluorescence and demonstration of neutralization of more than 50% of the infectious virus seed dose on plaque-reduction neutralization testing. RESULTS: Among the 280 household contacts of the 26 index patients, there were 12 probable cases of secondary transmission (4%; 95% confidence interval, 2 to 7). Of these cases, 7 were identified by means of RT-PCR, all in samples obtained within 14 days after the onset of symptoms in index patients, and 5 were identified by means of serologic analysis, all in samples obtained 13 days or more after symptom onset in index patients. Probable cases of secondary transmission occurred in 6 of 26 clusters (23%). Serologic results in contacts who were sampled 13 days or more after exposure were similar to overall study results for combined RT-PCR and serologic testing. CONCLUSIONS: The rate of secondary transmission among household contacts of patients with MERS-CoV infection has been approximately 5%. Our data provide insight into the rate of subclinical transmission of MERS-CoV in the home.
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