FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Volume 341:929-935 September 23, 1999 Number 13 Next

	Full Text PDF Editorial by Dolin, R. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Enteroviruses can cause outbreaks of hand-foot-and-mouth disease (characterized by vesicular lesions on the hands, feet, and oral mucosa) or herpangina, usually without life-threatening manifestations. In 1998 an epidemic of enterovirus 71 infection caused hand-foot-and-mouth disease and herpangina in thousands of people in Taiwan, some of whom died.

Methods We assessed the epidemiologic aspects of this outbreak. Cases of hand-foot-and-mouth disease or herpangina in ambulatory patients were reported to the Taiwan Department of Health by a mean of 818 sentinel physicians. Severe cases in hospitalized patients were reported by 40 medical centers and regional hospitals. Viruses were isolated by 10 hospital laboratories and the department of health.

Results The sentinel physicians reported 129,106 cases of hand-foot-and-mouth disease or herpangina in two waves of the epidemic, which probably represents less than 10 percent of the estimated total number of cases. There were 405 patients with severe disease, most of whom were five years old or younger; severe disease was seen in all regions of the island. Complications included encephalitis, aseptic meningitis, pulmonary edema or hemorrhage, acute flaccid paralysis, and myocarditis. Seventy-eight patients died, 71 of whom (91 percent) were five years of age or younger. Of the patients who died, 65 (83 percent) had pulmonary edema or pulmonary hemorrhage. Among patients from whom a virus was isolated, enterovirus 71 was present in 48.7 percent of outpatients with uncomplicated hand-foot-and-mouth disease or herpangina, 75 percent of hospitalized patients who survived, and 92 percent of patients who died.

Conclusions Although several enteroviruses were circulating in Taiwan during the 1998 epidemic, enterovirus 71 infection was associated with most of the serious clinical manifestations and with nearly all the deaths. Most of those who died were young, and the majority died of pulmonary edema and pulmonary hemorrhage.

Source Information

From the National Health Research Institutes, Taipei (M.H.); the National Department of Health, Taipei (E.-R.C., K.-H.H., S.-J.T., K.-T.C., S.-F.T.); the National Cheng Kung University Medical Center Virus Laboratory, Tainan (J.-R.W.); and the Chang Gung Medical Center Virus Laboratory, Lin Ko (S.-R.S.) — all in Taiwan.

Address reprint requests to Dr. Ho at the Division of Clinical Research, National Health Research Institutes, 128 Yen-Chiu-Yuan Rd., Section 2, Taipei 115, Taiwan, or at monto{at}mail.nhri.org.tw.

Full Text of this Article

Related Letters:

Outbreaks of Enterovirus 71 Infection
AbuBakar S., Chan Y.-F., Lam S. K., Ho M., Wang J.-R., Shih S.-R.
Extract | Full Text  
N Engl J Med 2000; 342:355-356, Feb 3, 2000. Correspondence

This article has been cited by other articles:

• Lin, J.-Y., Li, M.-L., Shih, S.-R. (2008). Far upstream element binding protein 2 interacts with enterovirus 71 internal ribosomal entry site and negatively regulates viral translation. Nucleic Acids Res 0: gkn901v1-gkn901 [Abstract] [Full Text]  
• Arita, M., Wakita, T., Shimizu, H. (2008). Characterization of pharmacologically active compounds that inhibit poliovirus and enterovirus 71 infectivity. J. Gen. Virol. 89: 2518-2530 [Abstract] [Full Text]  
• Lin, J.-Y., Li, M.-L., Huang, P.-N., Chien, K.-Y., Horng, J.-T., Shih, S.-R. (2008). Heterogeneous nuclear ribonuclear protein K interacts with the enterovirus 71 5' untranslated region and participates in virus replication. J. Gen. Virol. 89: 2540-2549 [Abstract] [Full Text]  
• Bible, J. M., Iturriza-Gomara, M., Megson, B., Brown, D., Pantelidis, P., Earl, P., Bendig, J., Tong, C. Y. W. (2008). Molecular Epidemiology of Human Enterovirus 71 in the United Kingdom from 1998 to 2006. J. Clin. Microbiol. 46: 3192-3200 [Abstract] [Full Text]  
• Ho, H.-Y., Cheng, M.-L., Weng, S.-F., Chang, L., Yeh, T.-T., Shih, S.-R., Chiu, D. T.-Y. (2008). Glucose-6-phosphate dehydrogenase deficiency enhances enterovirus 71 infection. J. Gen. Virol. 89: 2080-2089 [Abstract] [Full Text]  
• Gau, S. S.-F., Chang, L.-Y., Huang, L.-M., Fan, T.-Y., Wu, Y.-Y., Lin, T.-Y. (2008). Attention-Deficit/Hyperactivity-Related Symptoms Among Children With Enterovirus 71 Infection of the Central Nervous System. Pediatrics 122: e452-e458 [Abstract] [Full Text]  
• Arita, M., Ami, Y., Wakita, T., Shimizu, H. (2008). Cooperative Effect of the Attenuation Determinants Derived from Poliovirus Sabin 1 Strain Is Essential for Attenuation of Enterovirus 71 in the NOD/SCID Mouse Infection Model. J. Virol. 82: 1787-1797 [Abstract] [Full Text]  
• Lin, T.-L., Li, Y.-S., Huang, C.-W., Hsu, C.-C., Wu, H.-S., Tseng, T.-C., Yang, C.-F. (2008). Rapid and Highly Sensitive Coxsackievirus A Indirect Immunofluorescence Assay Typing Kit for Enterovirus Serotyping. J. Clin. Microbiol. 46: 785-788 [Abstract] [Full Text]  
• Ho, S. Y., Chua, S. Q., Foo, D. G. W., Locht, C., Chow, V. T., Poh, C. L., Alonso, S. (2008). Highly Attenuated Bordetella pertussis Strain BPZE1 as a Potential Live Vehicle for Delivery of Heterologous Vaccine Candidates. Infect. Immun. 76: 111-119 [Abstract] [Full Text]  
• Arita, M., Nagata, N., Iwata, N., Ami, Y., Suzaki, Y., Mizuta, K., Iwasaki, T., Sata, T., Wakita, T., Shimizu, H. (2007). An Attenuated Strain of Enterovirus 71 Belonging to Genotype A Showed a Broad Spectrum of Antigenicity with Attenuated Neurovirulence in Cynomolgus Monkeys. J. Virol. 81: 9386-9395 [Abstract] [Full Text]  
• Chen, K.-T., Chang, H.-L., Wang, S.-T., Cheng, Y.-T., Yang, J.-Y. (2007). Epidemiologic Features of Hand-Foot-Mouth Disease and Herpangina Caused by Enterovirus 71 in Taiwan, 1998 2005. Pediatrics 120: e244-e252 [Abstract] [Full Text]  
• Chen, S.-C., Chang, H.-L., Yan, T.-R., Cheng, Y.-T., Chen, K.-T. (2007). An Eight-Year Study of Epidemiologic Features of Enterovirus 71 Infection In Taiwan. Am J Trop Med Hyg 77: 188-191 [Abstract] [Full Text]  
• Ooi, M. H., Solomon, T., Podin, Y., Mohan, A., Akin, W., Yusuf, M. A., del Sel, S., Kontol, K. M., Lai, B. F., Clear, D., Chieng, C. H., Blake, E., Perera, D., Wong, S. C., Cardosa, J. (2007). Evaluation of Different Clinical Sample Types in Diagnosis of Human Enterovirus 71-Associated Hand-Foot-and-Mouth Disease. J. Clin. Microbiol. 45: 1858-1866 [Abstract] [Full Text]  
• Chang, L.-Y., Huang, L.-M., Gau, S. S.-F., Wu, Y.-Y., Hsia, S.-H., Fan, T.-Y., Lin, K.-L., Huang, Y.-C., Lu, C.-Y., Lin, T.-Y. (2007). Neurodevelopment and Cognition in Children after Enterovirus 71 Infection. NEJM 356: 1226-1234 [Abstract] [Full Text]  
• Huang, M.-C., Wang, S.-M., Hsu, Y.-W., Lin, H.-C., Chi, C.-Y., Liu, C.-C. (2006). Long-term Cognitive and Motor Deficits After Enterovirus 71 Brainstem Encephalitis in Children. Pediatrics 118: e1785-e1788 [Abstract] [Full Text]  
• Liu, M.-L., Lee, Y.-P., Wang, Y.-F., Lei, H.-Y., Liu, C.-C., Wang, S.-M., Su, I.-J., Wang, J.-R., Yeh, T.-M., Chen, S.-H., Yu, C.-K. (2005). Type I interferons protect mice against enterovirus 71 infection. J. Gen. Virol. 86: 3263-3269 [Abstract] [Full Text]  
• Arita, M., Shimizu, H., Nagata, N., Ami, Y., Suzaki, Y., Sata, T., Iwasaki, T., Miyamura, T. (2005). Temperature-sensitive mutants of enterovirus 71 show attenuation in cynomolgus monkeys. J. Gen. Virol. 86: 1391-1401 [Abstract] [Full Text]  
• Spanakis, N, Manolis, E N, Tsakris, A, Tsiodras, S, Panagiotopoulos, T, Saroglou, G, Legakis, N J (2005). Coxsackievirus B3 sequences in the myocardium of fatal cases in a cluster of acute myocarditis in Greece. J. Clin. Pathol. 58: 357-360 [Abstract] [Full Text]  
• Chang, L.-Y., Chang, I-S., Lu, C.-Y., Chiang, B.-L., Lee, C.-Y., Chen, P.-J., Wang, J.-T., Ho, H.-N., Chen, D.-S., Huang, L.-M., and the Kawasaki Disease Research Group, (2004). Epidemiologic Features of Kawasaki Disease in Taiwan, 1996-2002. Pediatrics 114: e678-e682 [Abstract] [Full Text]  
• Nagata, N., Iwasaki, T., Ami, Y., Tano, Y., Harashima, A., Suzaki, Y., Sato, Y., Hasegawa, H., Sata, T., Miyamura, T., Shimizu, H. (2004). Differential localization of neurons susceptible to enterovirus 71 and poliovirus type 1 in the central nervous system of cynomolgus monkeys after intravenous inoculation. J. Gen. Virol. 85: 2981-2989 [Abstract] [Full Text]  
• Shih, S.-R., Tsai, M.-C., Tseng, S.-N., Won, K.-F., Shia, K.-S., Li, W.-T., Chern, J.-H., Chen, G.-W., Lee, C.-C., Lee, Y.-C., Peng, K.-C., Chao, Y.-S. (2004). Mutation in Enterovirus 71 Capsid Protein VP1 Confers Resistance to the Inhibitory Effects of Pyridyl Imidazolidinone. Antimicrob. Agents Chemother. 48: 3523-3529 [Abstract] [Full Text]  
• Wang, Y.-F., Chou, C.-T., Lei, H.-Y., Liu, C.-C., Wang, S.-M., Yan, J.-J., Su, I.-J., Wang, J.-R., Yeh, T.-M., Chen, S.-H., Yu, C.-K. (2004). A Mouse-Adapted Enterovirus 71 Strain Causes Neurological Disease in Mice after Oral Infection. J. Virol. 78: 7916-7924 [Abstract] [Full Text]  
• Fu, Y C, Chi, C S, Chiu, Y T, Hsu, S L, Hwang, B, Jan, S L, Chen, P Y, Huang, F L, Chang, Y (2004). Cardiac complications of enterovirus rhombencephalitis. Arch. Dis. Child. 89: 368-373 [Abstract] [Full Text]  
• Chang, L.-Y., Tsao, K.-C., Hsia, S.-H., Shih, S.-R., Huang, C.-G., Chan, W.-K., Hsu, K.-H., Fang, T.-Y., Huang, Y.-C., Lin, T.-Y. (2004). Transmission and Clinical Features of Enterovirus 71 Infections in Household Contacts in Taiwan. JAMA 291: 222-227 [Abstract] [Full Text]  
• Chen, Y.-C., Yu, C.-K., Wang, Y.-F., Liu, C.-C., Su, I.-J., Lei, H.-Y. (2004). A murine oral enterovirus 71 infection model with central nervous system involvement. J. Gen. Virol. 85: 69-77 [Abstract] [Full Text]  
• Chen, K.-S., Lin, K.-L., Wang, H.-S., Hsia, S.-H., Lin, T.-Y., Lin, P.-Y. (2003). Transcranial Doppler Sonography in the Early Stage of Critical Enteroviral Infection. J Ultrasound Med 22: 1061-1066 [Abstract] [Full Text]  
• Nolan, M. A., Craig, M. E., Lahra, M. M., Rawlinson, W. D., Prager, P. C., Williams, G. D., Bye, A. M.E., Andrews, P. I. (2003). Survival after pulmonary edema due to enterovirus 71 encephalitis. Neurology 60: 1651-1656 [Abstract] [Full Text]  
• Le Thi Huong, D, Andreu, M R, Duhaut, P, Godeau, P, Piette, J C (2003). Intra-alveolar haemorrhage in temporal arteritis. Ann Rheum Dis 62: 189-190 [Full Text]  
• Singh, S., Chow, V. T. K., Phoon, M. C., Chan, K. P., Poh, C. L. (2002). Direct Detection of Enterovirus 71 (EV71) in Clinical Specimens from a Hand, Foot, and Mouth Disease Outbreak in Singapore by Reverse Transcription-PCR with Universal Enterovirus and EV71-Specific Primers. J. Clin. Microbiol. 40: 2823-2827 [Abstract] [Full Text]  
• Kuo, R.-L., Kung, S.-H., Hsu, Y.-Y., Liu, W.-T. (2002). Infection with enterovirus 71 or expression of its 2A protease induces apoptotic cell death. J. Gen. Virol. 83: 1367-1376 [Abstract] [Full Text]  
• Wang, J.-R., Tuan, Y.-C., Tsai, H.-P., Yan, J.-J., Liu, C.-C., Su, I.-J. (2002). Change of Major Genotype of Enterovirus 71 in Outbreaks of Hand-Foot-and-Mouth Disease in Taiwan between 1998 and 2000. J. Clin. Microbiol. 40: 10-15 [Abstract] [Full Text]  
• Bendig, J. W. A., O'Brien, P. S., Muir, P. (2001). Serotype-Specific Detection of Coxsackievirus A16 in Clinical Specimens by Reverse Transcription-Nested PCR. J. Clin. Microbiol. 39: 3690-3692 [Abstract] [Full Text]  
• McMinn, P., Lindsay, K., Perera, D., Chan, H. M., Chan, K. P., Cardosa, M. J. (2001). Phylogenetic Analysis of Enterovirus 71 Strains Isolated during Linked Epidemics in Malaysia, Singapore, and Western Australia. J. Virol. 75: 7732-7738 [Abstract] [Full Text]  
• Caro, V., Guillot, S., Delpeyroux, F., Crainic, R. (2001). Molecular strategy for 'serotyping' of human enteroviruses. J. Gen. Virol. 82: 79-91 [Abstract] [Full Text]  
• Tsai, H.-P., Kuo, P.-H., Liu, C.-C., Wang, J.-R. (2001). Respiratory Viral Infections among Pediatric Inpatients and Outpatients in Taiwan from 1997 to 1999. J. Clin. Microbiol. 39: 111-118 [Abstract] [Full Text]  
• Rotbart, H. A., Hayden, F. G. (2000). Picornavirus Infections: A Primer for the Practitioner. Arch Fam Med 9: 913-920 [Abstract] [Full Text]  
• AbuBakar, S., Chan, Y.-F., Lam, S. K., Ho, M., Wang, J.-R., Shih, S.-R. (2000). Outbreaks of Enterovirus 71 Infection. NEJM 342: 355-356 [Full Text]  
• (1999). Epidemic Enterovirus 71 Disease. JWatch Infect. Diseases 1999: 4-4 [Full Text]  
• Dolin, R. (1999). Enterovirus 71 -- Emerging Infections and Emerging Questions. NEJM 341: 984-985 [Full Text]