APPENDIX 2 Enteroviruses • Possibly patients undergoing hematopoietic cell transplant Disease Agent: Vector and Reservoir Involved: • Human enteroviruses, species A-D (Polioviruses, Cox- sackieviruses, Echoviruses), and Rhinoviruses • None Disease Agent Characteristics: Blood Phase: • Family: Picornaviridae; Genus: Enterovirus (Poliovi- • Not well characterized for majority of serotypes rus 1 is the type species.) • Based on polio model, primary infection occurs with • Virion morphology and size: Nonenveloped, icosahe- viral replication in the GI tract and draining lymph dral nucleocapsid symmetry, spherical particles, nodes. A brief period of viremia with very low levels of 30 nm in size virus occurs approximately 2-9 days following infec- • Nucleic acid: Linear, nonsegmented, positive-sense, tion in about 25% of all infections. However, a major single-stranded RNA, 7.4-7.5 kb in length viremia occurs following amplification of the virus • Physicochemical properties: Labile to heat at 60°C for in the reticuloendothelial tissues with subsequent 60 minutes or 100°C for 5 minutes; sensitive to guani- development of clinical manifestations in target dine and disoxaril; relatively resistant to 70% ethanol, organs. 5% Lysol, quaternary ammonium compounds; insen- sitive to ether, chloroform, and deoxycholate (a bile Survival/Persistence in Blood Products: acid) at room temperature; retains infectivity at pH • Unknown 3.0 but labile at pH 1.0; sensitive to 0.3% formalde- hyde, glutaraldehyde, sodium hypochlorite, and UV Transmission by Blood Transfusion: light; drying on surfaces significantly reduces virus titers • Theoretically possible but not demonstrated • Enterovirus RNA sequences were detected by RT-PCR Disease Name: in 19 minipools containing 95 component donor samples from 83,600 Scottish blood donors corre- • Many; see “Primary disease symptoms.” sponding to a donor prevalence of at least 0.023%. Priority Level Infectivity was not evaluated, and transmission was not investigated. Sequences were not detected in clot- • Scientific/Epidemiologic evidence regarding blood ting factor concentrates. safety: Theoretical • Public perception and/or regulatory concern regard- Cases/Frequency in Population: ing blood safety: Absent • Public concern regarding disease agent: Absent • Ubiquitous with regional and seasonal epidemics • Young children are the most important transmitters Background: of enteroviruses, especially within households • Ubiquitous with wide variety of clinical although the incidence is low in the first 4-6 months manifestations; sporadic epidemics; many show sea- of life in developing countries as a result of maternal sonal variation protective antibody. As a result, children are more likely to develop significant symptomatology. Common Human Exposure Routes: • Disease is more prevalent among lower socioeco- • Predominantly fecal/oral transmission but also may nomic populations and those living in urban areas. spread via respiratory secretions and by direct contact Disease is more common among males at a male-to- (e.g., conjunctivitis) female ratio between 1.2 and 2.5:1. Likelihood of Secondary Transmission: Incubation Period: • Moderate/high via gastrointestinal/respiratory shed- • Not well characterized; major viremia thought to ding. This may not apply to parenterally acquired occur 6-9 days after exposure but may occur earlier infection. and persist longer. Major symptoms occur after the viremia, which disseminates infection to target At-Risk Populations: organs. • Neonates, young children, patients with congenital • For poliovirus, the incubation period is estimated to and acquired B cell deficiencies (including acquisi- be 9-12 days (range: 5-35 days) and 11-17 days (range: tion following treatment with rituximab) 8-36 days) until the onset of paralysis. Volume 49, August 2009 Supplement TRANSFUSION 75S APPENDIX 2 Likelihood of Clinical Disease: Agent-Specific Screening Question(s): • In adults, the majority of infections are • No specific question is in use. asymptomatic. • Not indicated because transfusion transmission has • The incidence and severity of symptoms is higher in not been demonstrated children, especially neonates. • No sensitive or specific question is feasible. • Among susceptibles, only about 1 in 200 poliovirus Laboratory Test(s) Available: infections result in paralytic disease. • No FDA-licensed blood donor screening test exists. Primary Disease Symptoms • NAT increasingly used for diagnosis (generic • Enteroviruses can cause many clinical syndromes, enterovirus and subtype-specific assays are available including: in research and public health labs) ᭺ Poliomyelitis, paralysis, aseptic meningitis, • Serologic assays available but not useful as screen encephalitis • Culture possible for some agents, not useful as screen ᭺ Pleurodynia, myositis, myocarditis, pericarditis, Currently Recommended Donor Deferral Period: chronic heart disease ᭺ Exanthems, herpangina, hand, foot, and mouth • No FDA Guidance or AABB Standard exists. disease • Prudent practice would be to defer donor until signs ᭺ Upper and lower respiratory illness and symptoms are resolved. ᭺ Hemorrhagic conjunctivitis Impact on Blood Availability: ᭺ Diabetes mellitus ᭺ Severe neonatal infection with hepatitis. • Agent-specific screening question(s): Not applicable • Laboratory test(s) available: Not applicable Severity of Clinical Disease: Impact on Blood Safety: • Acute infection: Severity varies with age and immu- • Agent-specific screening question(s): Not applicable nocompetence of patient. • Laboratory test(s) available: Not applicable ᭺ Adults: Usually asymptomatic or only mild symptoms Leukoreduction Efficacy: ᭺ Neonates: Usually mildly symptomatic but may be severely affected and infection may be fatal. • Unlikely to be effective, as RNA has been detected in Enteroviruses are a common cause of fever in plasma. neonates. The likelihood of severe sequelae Pathogen Reduction Efficacy for Plasma Derivatives: varies. • Implicated as a cause of insulin-dependent diabetes • Nonenveloped viruses, so solvent/detergent would mellitus, possibly via an immune response mecha- be ineffective. nism, although it is unclear how often this occurs • Probably susceptible to heat inactivation • Chronic infection: Suspected to occur in some target Other Prevention Measures: organs, e.g., polio, heart disease. Frequency and clini- cal significance is undetermined, except chronic • With the exception of poliovirus, no widely available enteroviral meningoencephalitis in B cell immunode- vaccine. ficiency can be lethal. Suggested Reading: Mortality: 1. Chakrabarti S, Osman H, Collingham KE, Fegan CD, Milligan DW. Enterovirus infections following T-cell • It varies with age and agent but is uncommon where depleted allogeneic transplants in adults. Bone critical care medicine is available. Mortality occurs Marrow Transplant 2004; 33:425-30. mainly in neonates; it may occur in immunodeficient 2. Chang LY,Tsao KC, Hsia SH, Shih SR, Huang CG, Chan patients. WK, Hsu KH, Fang TY, HuangYC, Lin TY.Transmission Chronic Carriage: and clinical features of enterovirus 71 infections in household contacts in Taiwan. JAMA 2004;291:222-7. • Unknown, but may occur in immunosuppressed 3. Modlin JF. Chapter 250—Enteroviruses: coxsackievi- patients. ruses, echoviruses, and newer enteroviruses. In: Long Treatment Available/Efficacious: SS, editor: Principles and practice of pediatric infec- tious diseases, 3rd ed. Philadelphia: Churchill Living- • None stone, 2008. p. 1149-57. 76S TRANSFUSION Volume 49, August 2009 Supplement APPENDIX 2 4. Padate BP,Keidan J. Enteroviral meningoencephalitis outcomes of enterovirus infections in young infants. in a patient with non-Hodgkin’s lymphoma treated Pediatr Infect Dis J 2005;24:546-50. previously with rituximab. Clin Lab Haematol 2006; 8. Welch J, Maclaran K, Jordan T, Simmonds P. Fre- 28:69-71. quency, viral loads, and serotype identification of 5. Pallansch M, Roos R. Enteroviruses: polioviruses, cox- enterovirus infections in Scottish blood donors. sackieviruses, echoviruses and newer enteroviruses. Transfusion 2003;43:1060-6. In: Knipe DM, Howley PM, editors. Fields virology, 5th 9. Welch JB, McGowan K, Searle B, Gillon J, Jarvis LM, ed. Philadelphia: Lippincott Williams & Wilkins; 2007. Simmonds P. Detection of enterovirus viraemia in p. 839-93. blood donors. Vox Sang 2001;80:211-5. 6. Racaniello VR. Picornaviridae: the viruses and their 10. Zeichhardt H, Grunert H-P. Enteroviruses: poliovi- replication. In: Knipe DM, Howley PM, editors. Fields ruses, coxsackieviruses, echoviruses and enterovi- virology, 5th ed. Philadelphia: Lippincott Williams & ruses 68-71. In: Cohen J, Powderly WG, Opal SM, Wilkins; 2007. p. 795-838. editors. Infectious diseases, 2nd ed. London: Elsevier 7. Rittichier KR, Bryan PA, Bassett KE, Taggart EW, Health Sciences; 2003. p. 1993-2006. Enriquez FR, Hillyard DR, Byington CL. Diagnosis and Volume 49, August 2009 Supplement TRANSFUSION 77S.