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Pediatric Lymphocytic Choriomeningitis Virus

  • Author: J Michael Klatte, MD; Chief Editor: Russell W Steele, MD  more...
 
Updated: Jan 12, 2015
 

Background

Lymphocytic choriomeningitis virus (LCMV) is a single-stranded RNA virus of the family Arenaviridae. Other members of Arenaviridae include Lassa, Argentine hemorrhagic fever, Bolivian hemorrhagic fever, and Venezuelan hemorrhagic fever viruses. LCMV causes an asymptomatic infection in its rodent reservoir (eg, mice) and has variable effect on hamster health. It is passed to humans when they inhale, consume, or otherwise contact infected excreta. Typically a febrile, self-limited, biphasic disease, LCMV is a significant teratogen, whose role in congenital infections has only recently gained appreciation.[1] Individuals who are exposed to rodents from living conditions or other exposure, such as pet handlers and laboratory personnel, are at particular risk for infection. Transmission of infection during organ transplantation has been documented.[2, 3]

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Pathophysiology

After transmission of LCMV via inhalation, consumption, cutaneous or mucosal exposure, or organ transplantation, a primary viremia ensues, resulting in extra–CNS seeding and an initial, nonspecific, febrile illness. Several days later, secondary viremia follows and frequently results in CNS involvement and typical meningitis/meningoencephalitis.

The manifestations of the disease are thought to result from the host response to the virus as natural killer cells and cytotoxic T cells respond to infection with the production of interferon and additional inflammatory mediators. No human-to-human transmission occurs, except in congenital disease or organ transplantation. Congenital LCMV infection is typically much more serious than the acquired disease. It can mimic toxoplasmosis and cytomegalovirus (CMV) congenital infection. As in acquired infection, congenital disease is thought to result from T-cell and B-cell–mediated injury to the fetal host. LCMV transmitted in utero likely demonstrates selective neurotropism, targeting the developing fetal brain and retina.[4]

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Epidemiology

Frequency

United States

Seroprevalence was found to be 5% among adults at a sexually transmitted disease clinic in Baltimore, Maryland;[5] 5.4% among those older than 30 years in Birmingham, Alabama;[6] and 0.3% among those younger than 30 years in Birmingham, Alabama.[6] Seroprevalence in upstate New York was 0.4%.[7] Disease is more common in the fall and winter months (when rodents seek shelter indoors), and depends on rodent populations. Prevalence of intrauterine infections is unknown.

International

Disease has been reported in North and South America and Europe. Seroprevalence was 4% in Nova Scotia,[8] 1-3.6% in Argentina,[9] and 1.7% in Spain.[10]

Mortality/Morbidity

Less than 1% of patients with acquired infection have fatal disease, usually encephalitis or massive hemorrhage. By contrast, 35% of congenital infections are believed to result in fetal loss, and mortality in transplant-acquired infection is substantial. Most surviving infants (84%) have neurodevelopmental sequelae, including cerebral palsy, seizures, decreased visual acuity, mental retardation, and progressive hydrocephalus.[11]

Race

LCMV has no racial predilection.

Sex

LCMV has no gender predilection.

Age

Disease is most common among young adults, although infection may occur in individuals of any age.

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Contributor Information and Disclosures
Author

J Michael Klatte, MD Assistant Professor of Pediatrics, Tufts University School of Medicine; Pediatric Infectious Diseases Division, Baystate Medical Center

J Michael Klatte, MD is a member of the following medical societies: American Academy of Pediatrics, Infectious Diseases Society of America, Massachusetts Medical Society, Pediatric Infectious Diseases Society, Society for Healthcare Epidemiology of America

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Russell W Steele, MD Clinical Professor, Tulane University School of Medicine; Staff Physician, Ochsner Clinic Foundation

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, Southern Medical Association

Disclosure: Nothing to disclose.

Additional Contributors

Itzhak Brook, MD, MSc Professor, Department of Pediatrics, Georgetown University School of Medicine

Itzhak Brook, MD, MSc is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society for Microbiology, Association of Military Surgeons of the US, Infectious Diseases Society of America, International Immunocompromised Host Society, International Society for Infectious Diseases, Medical Society of the District of Columbia, New York Academy of Sciences, Pediatric Infectious Diseases Society, Society for Experimental Biology and Medicine, Society for Pediatric Research, Southern Medical Association, Society for Ear, Nose and Throat Advances in Children, American Federation for Clinical Research, Surgical Infection Society, Armed Forces Infectious Diseases Society

Disclosure: Nothing to disclose.

Acknowledgements

Leslie L Barton, MD Professor Emerita of Pediatrics, University of Arizona College of Medicine

Leslie L Barton, MD is a member of the following medical societies: American Academy of Pediatrics, Association of Pediatric Program Directors, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

References
  1. Bonthius DJ. Lymphocytic choriomeningitis virus: an underrecognized cause of neurologic disease in the fetus, child, and adult. Semin Pediatr Neurol. 2012 Sep. 19(3):89-95. [Medline].

  2. Basavaraju S, Kuehnert MJ, Zaki SR, Sejvar JJ. Encephalitis Caused by Pathogens Transmitted through Organ Transplants, United States, 2002-2013. Emerg Infect Dis. September 2014. 20:1443-51. [Medline]. [Full Text].

  3. Schafer IJ, Miller R, Stroher U, Knust B, Nichol ST, Rollin PE. A Cluster of Lymphocytic Choriomeningitis Virus Infections Transmitted Through Organ Transplantation - Iowa, 2013. MMWR Morb Mortal Wkly Rep. March 21, 2014. 63:249. [Medline]. [Full Text].

  4. Anderson JL, Levy PT, Leonard KB, Smyser CD, Tychsen L, Cole FS. Congenital Lymphocytic Choriomeningitis Virus: When to Consider the Diagnosis. J Child Neurol. June 2014. 29:837-42. [Medline]. [Full Text].

  5. Childs JE, Glass GE, Ksiazek TG, et al. Human-rodent contact and infection with lymphocytic choriomeningitis and Seoul viruses in an inner-city population. Am J Trop Med Hyg. 1991 Feb. 44(2):117-21. [Medline].

  6. Park JY, Peters CJ, Rollin PE, et al. Age distribution of lymphocytic choriomeningitis virus serum antibody in Birmingham, Alabama: evidence of a decreased risk of infection. Am J Trop Med Hyg. 1997 Jul. 57(1):37-41. [Medline].

  7. Knust B, Macneil A, Wong SJ, Backenson PB, Gibbons A, Rollin PE, et al. Exposure to lymphocytic choriomeningitis virus, New York, USA. Emerg Infect Dis. 2011 Jul. 17(7):1324-5. [Medline].

  8. Marrie TJ, Saron MF. Seroprevalence of lymphocytic choriomeningitis virus in Nova Scotia. Am J Trop Med Hyg. 1998 Jan. 58(1):47-9. [Medline].

  9. Riera L, Castillo E, Del Carmen Saavedra M, et al. Serological study of the lymphochoriomeningitis virus (LCMV) in an inner city of Argentina. J Med Virol. 2005 Jun. 76(2):285-9. [Medline].

  10. Lledo L, Gegundez MI, Saz JV, et al. Lymphocytic choriomeningitis virus infection in a province of Spain: Analysis of sera from the general population and wild rodents. J Med Virol. 2003 Jun. 70(2):273-5. [Medline].

  11. Bonthius DJ, Wright R, Tseng B, Barton L, Marco E, Karacay B. Congenital lymphocytic choriomeningitis virus infection: spectrum of disease. Ann Neurol. 2007 Oct. 62(4):347-55. [Medline].

  12. Wright R, Johnson D, Neumann M, et al. Congenital lymphocytic choriomeningitis virus syndrome: a disease that mimics congenital toxoplasmosis or Cytomegalovirus infection. Pediatrics. 1997 Jul. 100(1):E9. [Medline].

  13. Cohen BE, Durstenfeld A, Roehm PC. Viral Causes of Hearing Loss: A Review for Hearing Health Professionals. Trends Hear. July 2014. 18:1-17. [Medline]. [Full Text].

  14. Macneil A, Ströher U, Farnon E, Campbell S, Cannon D, Paddock CD, et al. Solid organ transplant-associated lymphocytic choriomeningitis, United States, 2011. Emerg Infect Dis. 2012 Aug. 18(8):1256-62. [Medline]. [Full Text].

  15. Knust B, Stroher U, Edison L, Albarino CG, Lovejoy J, Armeanu E, et al. Lymphocytic Choriomeningitis Virus in Employees and Mice at Multipremises Feeder-Rodent Operation, United States, 2012. Emerg Infect Dis. February 2014. 20:240-7. [Medline]. [Full Text].

  16. Cordey S, Sahli R, Moraz ML, Estrade C, Morandi L, Cherpillod P, et al. Analytical validation of a lymphocytic choriomeningitis virus real-time RT-PCR assay. J Virol Methods. 2011 Oct. 177(1):118-22. [Medline].

  17. Ortiz-Riano E, Ngo N, Devito S, Eggink D, Munger J, Shaw ML, et al. Inhibition of Arenavirus by A3, A Pyrimidine Biosynthesis Inhibitor. J Virol. January 2014. 88:878-89. [Medline]. [Full Text].

  18. Shedlock DJ, Talbott KT, Cress C, Ferraro B, Tuyishme S, Mallilankaraman K, et al. A highly optimized DNA vaccine confers complete protective immunity against high-dose lethal lymphocytic choriomeningitis virus challenge. Vaccine. 2011 Sep 9. 29(39):6755-62. [Medline]. [Full Text].

  19. Folk S, Steinbecker S, Windmeyer J, Macneil A, Campbell S, Rollin PE. Lymphocytic choriomeningitis with severe manifestations, Missouri, USA. Emerg Infect Dis. 2011 Oct. 17(10):1973-4. [Medline].

  20. Souders HT, Byler D, Marupudi N, Patel R, McSherry G. Protracted Symptoms in Lymphocytic Choriomeningitis: A Case Report. J Child Neurol. April 2014. 1-4. [Medline].

  21. AAP. Lymphocytic choriomeningitis. Red Book: 2009 Report of the Committee on Infectious Diseases. 28th. Elk Grove Village, IL: American Academy of Pediatrics; 2009. 437-8.

  22. Al-Zein N, Boyce TG, Correa AG, Rodriguez V. Meningitis caused by lymphocytic choriomeningitis virus in a patient with leukemia. J Pediatr Hematol Oncol. 2008 Oct. 30(10):781-4. [Medline].

  23. Albarino CG, Palacios G, Khristova ML, et al. High diversity and ancient common ancestry of lymphocytic choriomeningitis virus. Emerg Infect Dis. 2010 Jul. 16(7):1093-100. [Medline].

  24. Bale JF Jr. Congenital infections. Neurol Clin. 2002 Nov. 20(4):1039-60, vii. [Medline].

  25. Barton LL. Lymphocytic choriomeningitis virus: a neglected central nervous system pathogen. Clin Infect Dis. 1996 Jan. 22(1):197. [Medline].

  26. Barton LL, Hyndman NJ. Lymphocytic choriomeningitis virus: reemerging central nervous system pathogen. Pediatrics. 2000 Mar. 105(3):E35. [Medline].

  27. Barton LL, Mets MB. Congenital lymphocytic choriomeningitis virus infection: decade of rediscovery. Clin Infect Dis. 2001 Aug 1. 33(3):370-4. [Medline].

  28. Barton LL, Mets MB. Lymphocytic choriomeningitis virus: pediatric pathogen and fetal teratogen. Pediatr Infect Dis J. 1999 Jun. 18(6):540-1. [Medline].

  29. Barton LL, Mets MB, Beauchamp CL. Lymphocytic choriomeningitis virus: emerging fetal teratogen. Am J Obstet Gynecol. 2002 Dec. 187(6):1715-6. [Medline].

  30. Bergthaler A, Flatz L, Hegazy AN, Johnson S, Horvath E, Löhning M, et al. Viral replicative capacity is the primary determinant of lymphocytic choriomeningitis virus persistence and immunosuppression. Proc Natl Acad Sci U S A. 2010 Nov 22. [Medline]. [Full Text].

  31. Bonthius DJ, Karacay B. Meningitis and encephalitis in children. An update. Neurol Clin. 2002 Nov. 20(4):1013-38, vi-vii. [Medline].

  32. Bonthius DJ, Nichols B, Harb H, Mahoney J, Karacay B. Lymphocytic choriomeningitis virus infection of the developing brain: critical role of host age. Ann Neurol. 2007 Oct. 62(4):356-74. [Medline].

  33. Bonthius DJ, Perlman S. Congenital viral infections of the brain: lessons learned from lymphocytic choriomeningitis virus in the neonatal rat. PLoS Pathog. 2007 Nov. 3(11):e149. [Medline].

  34. Brief report: Lymphocytic choriomeningitis virus transmitted through solid organ transplantation--Massachusetts, 2008. MMWR Morb Mortal Wkly Rep. 2008 Jul 25. 57(29):799-801. [Medline].

  35. CDC. Interim guidance for minimizing risk for human lymphocytic choriomeningitis virus infection associated with rodents. MMWR Morb Mortal Wkly Rep. 2005 Aug 5. 54(30):747-9. [Medline].

  36. CDC. Lymphocytic choriomeningitis virus infection in organ transplant recipients--Massachusetts, Rhode Island, 2005. MMWR Morb Mortal Wkly Rep. 2005 Jun 3. 54(21):537-9. [Medline].

  37. CDC. Survey of lymphocytic choriomeningitis virus diagnosis and testing--Connecticut, 2005. MMWR Morb Mortal Wkly Rep. 2006 Apr 14. 55(14):398-9. [Medline].

  38. CDC. Update: interim guidance for minimizing risk for human lymphocytic choriomeningitis virus infection associated with pet rodents. MMWR Morb Mortal Wkly Rep. 2005 Aug 19. 54(32):799-801. [Medline].

  39. Centers for Disease Control and Prevention. Notes from the field: lymphocytic choriomeningitis virus infections in employees of a rodent breeding facility--Indiana, May-June 2012. MMWR Morb Mortal Wkly Rep. 2012 Aug 17. 61(32):622-3. [Medline].

  40. Charrel RN, Retornaz K, Emonet S, et al. Acquired hydrocephalus caused by a variant lymphocytic choriomeningitis virus. Arch Intern Med. 2006 Oct 9. 166(18):2044-6. [Medline].

  41. de la Torre JC. Reverse genetics approaches to combat pathogenic arenaviruses. Antiviral Res. 2008 Dec. 80(3):239-50. [Medline].

  42. de Lamballerie X, Fulhorst CF, Charrel RN. Prevalence of antibodies to lymphocytic choriomeningitis virus in blood donors in southeastern France. Transfusion. 2007 Jan. 47(1):172-3. [Medline].

  43. de Ory F, Avellón A, Echevarría JE, Sánchez-Seco MP, Trallero G, Cabrerizo M, et al. Viral infections of the central nervous system in Spain: a prospective study. J Med Virol. 2013 Mar. 85(3):554-62. [Medline].

  44. Droebner K, Klein B, Paxian S, Schmid R, Stitz L, Planz O. The alternative NF-kappaB signalling pathway is a prerequisite for an appropriate immune response against lymphocytic choriomeningitis virus infection. Viral Immunol. 2010 Jun. 23(3):295-308. [Medline].

  45. Emonet S, Retornaz K, Gonzalez JP, de Lamballerie X, Charrel RN. Mouse-to-human transmission of variant lymphocytic choriomeningitis virus. Emerg Infect Dis. 2007 Mar. 13(3):472-5. [Medline].

  46. Farmer M, Sebire G. Genetic mimics of congenital lymphocytic choriomeningitis virus encephalitis. Ann Neurol. 2008 Sep. 64(3):353-5. [Medline].

  47. Fischer SA. Emerging viruses in transplantation: there is more to infection after transplant than CMV and EBV. Transplantation. 2008 Nov 27. 86(10):1327-39. [Medline].

  48. Fischer SA, Graham MB, Kuehnert MJ, et al. Transmission of lymphocytic choriomeningitis virus by organ transplantation. N Engl J Med. 2006 May 25. 354(21):2235-49. [Medline].

  49. Foster ES, Signs KA, Marks DR, et al. Lymphocytic choriomeningitis in Michigan. Emerg Infect Dis. 2006 May. 12(5):851-3. [Medline].

  50. Greenhow TL, Weintrub PS. Your diagnosis, please. Neonate with hydrocephalus. Pediatr Infect Dis J. 2003 Dec. 22(12):1099, 1111-2. [Medline].

  51. Hinson ER, Joshi NS, Chen JH, et al. Viperin is highly induced in neutrophils and macrophages during acute and chronic lymphocytic choriomeningitis virus infection. J Immunol. 2010 May 15. 184(10):5723-31. [Medline].

  52. Jamieson DJ, Kourtis AP, Bell M, Rasmussen SA. Lymphocytic choriomeningitis virus: an emerging obstetric pathogen?. Am J Obstet Gynecol. 2006. 194:1532-6. [Medline].

  53. Kang SS, McGavern DB. Lymphocytic choriomeningitis infection of the central nervous system. Front Biosci. 2008 May 1. 13:4529-43. [Medline].

  54. Kim JV, Kang SS, Dustin ML, McGavern DB. Myelomonocytic cell recruitment causes fatal CNS vascular injury during acute viral meningitis. Nature. 2008 Nov 16. [Medline].

  55. Knust B, Holman RC, Redd J, Mehal JM, Grube SM, MacNeil A, et al. Lymphocytic choriomeningitis virus infections among american indians. Emerg Infect Dis. Feb 2013. 19(2):328-329.

  56. Kotton CN. Zoonoses in solid-organ and hematopoietic stem cell transplant recipients. Clin Infect Dis. 2007 Mar 15. 44(6):857-66. [Medline].

  57. Ledesma J, Fedele CG, Carro F, et al. Independent lineage of lymphocytic choriomeningitis virus in wood mice (Apodemus sylvaticus), Spain. Emerg Infect Dis. 2009 Oct. 15(10):1677-80. [Medline].

  58. Lin AA, Wojciechowski SE, Hildeman DA. Androgens suppress antigen-specific T cell responses and IFN-? production during intracranial LCMV infection. J Neuroimmunol. 2010 Sep 14. 226(1-2):8-19. [Medline].

  59. Mets MB. Eye manifestations of intrauterine infections. Ophthalmol Clin North Am. 2001 Sep. 14(3):521-31. [Medline].

  60. Mets MB, Chhabra MS. Eye manifestations of intrauterine infections and their impact on childhood blindness. Surv Ophthalmol. 2008 Mar-Apr. 53(2):95-111. [Medline].

  61. Mueller SN, Langley WA, Li G, et al. Qualitatively different memory CD8+ T cells are generated after lymphocytic choriomeningitis virus and influenza virus infections. J Immunol. 2010 Aug 15. 185(4):2182-90. [Medline].

  62. Oldstone MB. Biology and pathogenesis of lymphocytic choriomeningitis virus infection. Curr Top Microbiol Immunol. 2002. 263:83-117. [Medline].

  63. Oldstone MB. Lessons learned and concepts formed from study of the pathogenesis of the two negative-strand viruses lymphocytic choriomeningitis and influenza. Proc Natl Acad Sci U S A. 2013 Mar 12. 110(11):4180-3. [Medline]. [Full Text].

  64. Perkins JD. Another donor derived pathogen to watch out for. Liver Transpl. 2006 Sep. 12(9):1432-3. [Medline].

  65. Peters CJ. Lymphocytic choriomeningitis virus--an old enemy up to new tricks. N Engl J Med. 2006 May 25. 354(21):2208-11. [Medline].

  66. Pérez-Ruiz M, Navarro-Marí JM, Sánchez-Seco MP, Gegúndez MI, Palacios G, Savji N, et al. Lymphocytic Choriomeningitis Virus-associated Meningitis, Southern Spain. Emerg Infect Dis. 2012 May. 18(5):855-8. [Medline].

  67. Rawlinson WD, Hall B, Jones CA, et al. Viruses and other infections in stillbirth: what is the evidence and what should we be doing?. Pathology. 2008 Feb. 40(2):149-60. [Medline].

  68. Rodrigo WW, de la Torre JC, Martínez-Sobrido L. Single-Cycle Infectious Lymphocytic Choriomeningitis Virus To Study Hemorrhagic Fever Arenaviruses. J Virol. 2010 Dec 1. [Medline].

  69. Rojek JM, Perez M, Kunz S. Cellular entry of lymphocytic choriomeningitis virus. J Virol. 2008 Feb. 82(3):1505-17. [Medline].

  70. Romero JR, Newland JG. Viral meningitis and encephalitis: traditional and emerging viral agents. Semin Pediatr Infect Dis. 2003 Apr. 14(2):72-82. [Medline].

  71. Sauter C, Sauter BV. LCMV transmission by organ transplantation. N Engl J Med. 2006 Oct 19. 355(16):1737; author reply 1737-8. [Medline].

  72. Schulte DJ, Comer JA, Erickson BR, et al. Congenital lymphocytic choriomeningitis virus: an underdiagnosed cause of neonatal hydrocephalus. Pediatr Infect Dis J. 2006 Jun. 25(6):560-2. [Medline].

  73. Sejvar JJ. The evolving epidemiology of viral encephalitis. Curr Opin Neurol. 2006 Aug. 19(4):350-7. [Medline].

  74. Theiler RN, Rasmussen SA, Treadwell TA, Jamieson DJ. Emerging and zoonotic infections in women. Infect Dis Clin North Am. 2008 Dec. 22(4):755-72, vii-viii. [Medline].

  75. Thomsen AR. Lymphocytic choriomeningitis virus-induced central nervous system disease: a model for studying the role of chemokines in regulating the acute antiviral CD8+ T-cell response in an immune-privileged organ. J Virol. 2009 Jan. 83(1):20-8. [Medline].

  76. Tyler KL. Emerging viral infections of the central nervous system: part 1. Arch Neurol. 2009 Aug. 66(8):939-48. [Medline].

  77. Tyler KL. Neurological infections: advances in therapy, outcome, and prediction. Lancet Neurol. 2009 Jan. 8(1):19-21. [Medline].

  78. Uhlmann EJ, Storch GA. Viral encephalitis. Lab Med. June, 2001. 32(6):317-23. [Full Text].

  79. Wilson EB, Brooks DG. Translating insights from persistent LCMV infection into anti-HIV immunity. Immunol Res. 2010 Dec. 48(1-3):3-13. [Medline].

  80. Zinkernagel MS, Bolinger B, Krebs P, Onder L, Miller S, Ludewig B. Immunopathological basis of lymphocytic choriomeningitis virus-induced chorioretinitis and keratitis. J Virol. 2009 Jan. 83(1):159-66. [Medline]. [Full Text].

  81. Zuniga EI, Hahm B, Oldstone MB. Type I interferon during viral infections: multiple triggers for a multifunctional mediator. Curr Top Microbiol Immunol. 2007. 316:337-57. [Medline].

 
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