Abstract
Varicella is a highly contagious disease caused by varicella zoster virus. In children, it is generally a mild to moderate illness while it is often more severe in adults, with serious complications as dehydration, pneumonia, bleeding problems, infection or inflammation of the brain, secondary bacterial infections, sepsis, toxic shock syndrome, bone infections, joint infections and deaths. Some groups of adults are at major risk of complications, in particular immunocompromised persons as subjects with impaired humoral immunity and who is receiving systemic steroids, persons who live or work in environments in which transmission of varicella is likely, health-care personnel and pregnant women. After the introduction of Universal Mass Vaccination (UMV), the first mathematical models suggested that vaccination will lead to a shift in the average age at infection from children to adults with an increasing numbers of complicated forms, nevertheless new models predicted that, although an upward shift in the age at infection may occur, the overall morbidity due to varicella is likely to decrease. Current literature seems to suggest that for public health authorities the key action to prevent an increase of varicella incidence among adults is to achieve high vaccination coverage among babies and adolescents in countries who adopted UMV.
Keywords: immunization strategies, risk groups, susceptible adults, Universal Mass Vaccination, varicella
Abbreviations
- UMV
Universal Mass Vaccination
- VZV
varicella zoster virus
- CDC
Center for Disease Control and Prevention
Introduction
Severe acute varicella and its serious complications are not a part of the past but they are dramatically actual.
Varicella is an acute infectious disease caused by varicella zoster virus (VZV), highly contagious and endemic worldwide.1 In children, varicella is generally a mild to moderate and self-limited illness while it is often more severe in adults.2
Recent epidemiological changes make varicella increasingly common in adults and adolescents who together with immunosuppressed individuals and pregnant women are at a higher risk of severe infection and complications.2-3 Seroepidemiological studies showed that the rate of seronegative adults ranged from 1 to 7% and seems higher in countries who adopted universal mass vaccination against varicella.4
Serious complications among adults include dehydration, pneumonia, bleeding problems, infection or inflammation of the brain, secondary bacterial infections, sepsis, toxic shock syndrome, bone infections, joint infections and deaths.5-7
In the scientific literature of the last years there are many case reports of varicella in adults. Pneumonia is the most common complication and cause of death among non immunocompromised adults affected by this illness.5,8-10
Varicella or zoster related vasculopathies are caused by productive viral infection in cerebral arteries and clinical manifestations range from transient ischemic attacks to protracted illness involving both small and large arteries (aneurysm, cerebral and subarachnoid hemorrhage, arterial ectasia).11-15
Varicella infection causes a wide spectrum of neurologic complications.16 Infection of the central nervous system such as encephalitis, meningitis, myelitis or angiitis occurs less frequently in adults but is burden with numerous unfavourable outcomes.17-20 Trigeminal and facial nerves are the most commonly affected nerves in cranial neuropathies and there are only few case reports of patients with lower cranial neuropathy.21,22 Thrombocytopenia is another possible complication of adults varicella even if rare.23
International recommendations and several piece of literature identified some groups of adults as a major risk of varicella infection and complications.
Immunocompromised persons who get varicella can be sick longer than immunocompetent persons and are at risk of developing visceral dissemination leading to pneumonia, hepatitis, encephalitis and disseminated intravascular coagulopathy.24-27 Also susceptible persons with impaired humoral immunity28 and who is receiving systemic steroids for certain conditions, such as asthma, and even if not otherwise immunocompromised are universally recognized as at major risk of varicella infection.29
At increased risk for exposure or transmission of varicella are also persons who live or work in environments in which transmission of VZV is likely (e.g., teachers, day-care employees, residents and staff in institutional settings, college students, inmates and staff members of correctional institutions, and military personnel).30 Outbreaks of varicella get reported quite often in these settings, where the spread of infection may be more rapid and unpredictable.31-34
Nosocomial transmission of VZV is well documented,35-42 and there are specific guidelines for the prevention of nosocomial VZV infection and for infection control in health-care personnel.43-44
Ten to 20 percent of pregnant women who get varicella develop pneumonia, with the chance of death as high as 40%; then prenatal assessment of women for evidence of varicella immunity is recommended.45
A live attenuated varicella vaccine was available since 197446 and in 1996 it was recommended by the American Academy of Pediatrics for American children aged 12 months to 13 years.47
In European Union, only 5 countries universally recommend varicella vaccination for children at national level and 2 at regional level, 17 countries recommend nationwide vaccination for susceptible teenagers and/or susceptible risk groups only.48
In the first years after the introduction of UMV, some mathematical model suggested that vaccination will lead to a shift in the average age at infection from children to adults where risk of complication is greater. The worry is that enough adults with severe varicella will be infected after vaccination to counterbalance the benefit in reduction in children.49-51
In the following years, new models predicted that, although an upward shift in the age at infection may occur, the overall morbidity due to varicella is likely to decrease following mass infant vaccination, even if only when coverage exceeds 70–90%, vaccination is able to reduce varicella transmission sufficiently to decrease both adult and child morbidity.52
A seroepidemiological study carried out in Apulia Region (Italy) that adopted UMV for varicella since 2006, seems to confirm this hypothesis. In a region where high vaccination coverage (>90 %) has been achieved in newborns, the results of the survey excluded clusters of susceptible subjects among adults. Also in vaccination era, the average age of infection did not seem to shift among adults and then the study are able to exclude an increase of case of complicated varicella due to the UMV.4
Future studies have to investigate the impact of the reduction of the natural booster on the incidence of zoster, that theoretically should increase.
The Center for Disease Control and Prevention (CDC) conveys recommendations about immunization schedule for varicella in adults aged 19 y and older. All adults without evidence of immunity to varicella should receive 2 doses of single-antigen varicella vaccine or a second dose if they have received only 1 dose.30
The vaccination strategy is based on giving “appropriate occasion,” enrolling and encouraging physicians that take care of patients at high risk (such as gynecologist or oncologist) and occupational health physicians, especially in health trusts. This is consistent with a “personal health” perspective.
In the public health perspective, mathematical models and serosurvey seems to suggest that to prevent an increase of varicella incidence among adults, the key action is to achieve high vaccination coverage among babies and adolescents in countries who adopted UMV. This could become a priority for national and international public health authorities.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
References
- 1.Center for disease control and prevention. Prevention of varicella: Recommendations of the Advisory Committee on Immunization Practices (ACIP) MMWR 2007; 56(RR04):1-40. [PubMed] [Google Scholar]
- 2.Tunbridge AJ, Breuer J, Jeffery KJ. Chickenpox in adults - clinical management. J Infect 2008. August;57(2):95-102; http://dx.doi.org/ 10.1016/j.jinf.2008.03.004 [DOI] [PubMed] [Google Scholar]
- 3.Steiner I, Kennedy PG, Pachner AR. The neurotropic herpes viruses: herpes simplex and varicella-zoster. Lancet Neurol 2007. November;6(11):1015-28; http://dx.doi.org/ 10.1016/S1474-4422(07)70267-3 [DOI] [PubMed] [Google Scholar]
- 4.Tafuri S, Gallone MS, Cappelli MG, Gallone MF, Larocca AM, Germinario C. A seroprevalence survey on varicella among adults in the vaccination era in Apulia (Italy). Vaccine 2014. November 12;32(48):6544-7; http://dx.doi.org/ 10.1016/j.vaccine.2014.08.088 [DOI] [PubMed] [Google Scholar]
- 5.Heininger U, Seward JF. Varicella. Lancet 2006; 368: 1365-76; PMID:17046469; http://dx.doi.org/ 10.1016/S0140-6736(06)69561-5 [DOI] [PubMed] [Google Scholar]
- 6.Boëlle PY, Hanslik T. Varicella in non-immune persons: incidence, hospitalization and mortality rates. Epidemiol Infect 2002. December;129(3):599-606; http://dx.doi.org/ 10.1017/S0950268802007720 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Center for disease control and prevention. Varicella related deaths among adults – United States. MMWR 1997; 46(19);409-412. [PubMed] [Google Scholar]
- 8.Joseph CA, Noah ND. Epidemiology of chickenpox in England and Wales, 1967 – 85. Br Med J (Clin Res Ed) 1988;296(6623): 673-6; PMID:3128363; http://dx.doi.org/ 10.1136/bmj.296.6623.673 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Mendes MD, Yeh-Li H, Romano TG, Santos EV, Hirota AS, Kono BM, Felicio MF, Park M. Varicella associated acute respiratory distress syndrome in an adult patient: an example for extracorporeal respiratory support in Brazilian endemic diseases. Rev Bras Ter Intensiva 2014. December;26(4):410-415 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Lee WA, Kolla S, Schreiner RJ, Hirschl RB, Barlett RH. Prolongedextracorporal life support (ECLS) for varicella pneumonia. Crit Care Med 1997; 25(6):977-82; PMID:9201050; http://dx.doi.org/ 10.1097/00003246-199706000-00014 [DOI] [PubMed] [Google Scholar]
- 11.Gilden D1, Cohrs RJ, Mahalingam R, Nagel MA. Varicella zoster virus vasculopathies: diverse clinical manifestations, laboratory features, pathogenesis, and treatment. Lancet Neurol 2009. August;8(8):731-40; http://dx.doi.org/ 10.1016/S1474-4422(09)70134-6 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Nagel MA, Cohrs RJ, Mahalingam R, Wellish MC, Forghani B, Schiller A, Safdieh JE, Kamenkovich E, Ostrow LW, Levy M, et al.. The varicella zoster virus vasculopathies. Clinical, CSF, imaging, and virologic features. Neurology 2008;70:853-60; PMID:18332343; http://dx.doi.org/ 10.1212/01.wnl.0000304747.38502.e8 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Miyazaki Y, Riku Y, Goto Y, Mano K, Yoshida M, Hashizume Y. VZV vasculopathy associated with myelo-radiculoganglio-meningoencephalitis: an autopsy case of an immunocompetent 66-yearold male. J Neurol Sci 2008;275:42-45; PMID:18757065; http://dx.doi.org/ 10.1016/j.jns.2008.07.019 [DOI] [PubMed] [Google Scholar]
- 14.Bhayani N, Ranade P, Clark NM, McGuinn M. Varicella-zoster virus and cerebral aneurysm: case report and review of the literature. Clin Infect Dis 2008;47:e1-3; PMID:18491962; http://dx.doi.org/ 10.1086/588842 [DOI] [PubMed] [Google Scholar]
- 15.Shibusawa M, Motomura S, Hidai H, Tsutsumi H, Fujita A. Varicella infection complicated by marked thrombocytopenia. Jpn J Infect Dis 2014;67(4):292-4; PMID:25056076; http://dx.doi.org/ 10.7883/yoken.67.292 [DOI] [PubMed] [Google Scholar]
- 16.Steiner I, Kennedy PG, Pachner AR. The neurotropic herpes viruses: herpes simplex and varicella-zoster. Lancet Neurol. 2007. November;6(11):1015-28; http://dx.doi.org/ 10.1016/S1474-4422(07)70267-3 [DOI] [PubMed] [Google Scholar]
- 17.Pasedag T, Weissenborn K, Wurster U, Ganzenmueller T, Stangel M, Skripuletz T. Varicella Zoster Virus Meningitis in a Young Immunocompetent Adult without Rash: A Misleading Clinical Presentation. Case Rep Neurol Med 2014;2014:686218; PMID:25614843 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Leahy T. R., Webb D. W. M., Hoey H., Butler K.M., “Varicella zoster virus associated acute aseptic meningitis without exanthem in an immunocompetent 14-year-old boy,” Pediatric Infectious Disease J 2008; 27, 4, pp. 362-363; PMID:18316987; http://dx.doi.org/ 10.1097/INF.0b013e318160ee11 [DOI] [PubMed] [Google Scholar]
- 19.Habib A., Gilden D., Schmid D. S., Safdieh J., “Varicella zoster virus meningitis with hypoglycorrhachia in the absence of rash in an immunocompetent woman,” J NeuroVirol 2009; 15 2, pp. 206-8; PMID:19255900; http://dx.doi.org/ 10.1080/13550280902725550 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Klein N. C., McDermott B., Cunha B. A., “Varicella-zoster virus meningoencephalitis in an immunocompetent patient without a rash,” Scandinavian J Infectious Diseases 2010, 42 8:631-3; PMID:20214542; http://dx.doi.org/ 10.3109/00365540903510716 [DOI] [PubMed] [Google Scholar]
- 21.Kawabe K1, Sekine T, Murata K, Sato R, Aoyagi J, Kawase Y, Ogura N, Kiyozuka T, Igarashi O, Iguchi H, Fujioka T, Iwasaki Y. A case of Vernet syndrome with varicella zoster virus infection. J Neurol Sci 2008. July 15;270(1–2):209-10; http://dx.doi.org/ 10.1016/j.jns.2008.03.005 [DOI] [PubMed] [Google Scholar]
- 22.Hayashi T1, Murayama S, Sakurai M, Kanazawa I. Jugular foramen syndrome caused by varicella zoster virus infection in a patient with ipsilateral hypoplasia of the jugular foramen. J Neurol Sci 2000. January 1;172(1):70-2; http://dx.doi.org/ 10.1016/S0022-510X(99)00263-4 [DOI] [PubMed] [Google Scholar]
- 23.Massano J, Ferreira D, Toledo T, Mansilha A, Azevedo E, Carvalho M. Stroke and multiple peripheral thrombotic events in an adult with varicella. Eur J Neurol 2008;15:e90-91; PMID:18717719; http://dx.doi.org/ 10.1111/j.1468-1331.2008.02267.x [DOI] [PubMed] [Google Scholar]
- 24.Feldman S, Hughes WT, Daniel CB. Varicella in children with cancer: Seventy-seven cases. Pediatrics. 1975. September;56(3):388-97 [PubMed] [Google Scholar]
- 25.Müller I, Aepinus C, Beck R, Bültmann B, Niethammer D, Klingebiel T. Noncutaneous varicella-zoster virus (VZV) infection with fatal liver failure in a child with acute lymphoblastic leukemia (ALL). Med Pediatr Oncol 2001. August;37(2):145-7; http://dx.doi.org/ 10.1002/mpo.1186 [DOI] [PubMed] [Google Scholar]
- 26.Matsuzaki A, Suminoe A, Koga Y, Kusuhara K, Hara T, Ogata R, Sata T, Hara T. Fatal visceral varicella-zoster virus infection without skin involvement in a child with acute lymphoblastic leukemia. Pediatr Hematol Oncol. 2008. Apr-May;25(3):237-42; http://dx.doi.org/ 10.1080/08880010801938215 [DOI] [PubMed] [Google Scholar]
- 27.Centers for Disease Control and Prevention (CDC). Notes from the field: severe varicella in an immunocompromised child exposed to an unvaccinated sibling with varicella–Minnesota , 2011. MMWR 2012; 61(28);541-541. [PubMed] [Google Scholar]
- 28.LaRussa P, Steinberg S, Gershon AA. Varicella vaccine for immunocompromised children: results of collaborative studies in the United States and Canada. J Infect Dis 1996. November;174 Suppl 3:S320-3 [DOI] [PubMed] [Google Scholar]
- 29.Takahashi M, Kamiya H, Baba K, Ozaki T, Horiuchi K. Clinical experience with Oka live varicella vaccine in Japan. Postgrad Med J 1985;61 (Suppl):61-7; PMID:3014479 [PubMed] [Google Scholar]
- 30.Kim DK, Bridges CB, Harriman KH. Advisory committee on immunization practices recommended immunization schedule for adults aged 19 years or older - United States, 2015. MMWR Morb Mortal Wkly Rep 2015. February 6;64(4):91-2 [PMC free article] [PubMed] [Google Scholar]
- 31.Hepburn NC, Brooks TJ. An outbreak of chickenpox in a military field hospital–the implications for biological warfare. J R Soc Med 1991. December;84(12):721-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Zimmerman L, Fajardo M, Seward J, Ludwig S, Johnson J, Wharton M. Varicella susceptibility and validity of history among US. Coast Guard recruits: an outbreak-based study. Mil Med 2003. May;168(5):404-7 [PubMed] [Google Scholar]
- 33.Lai CC, Chen SC, Jiang DD. An outbreak of varicella among schoolchildren in Taipei. BMC Public Health 2011. April 12;11:226; http://dx.doi.org/ 10.1186/1471-2458-11-226 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Daskalaki I, Thermitus R, Perella D, Viner K, Spells N, Mohanty S, Lopez A, Johnson C. Varicella outbreak in a daycare: challenges and opportunities for preventing varicella outbreaks in this setting. Pediatr Infect Dis J 2014. April;33(4):420-2; http://dx.doi.org/ 10.1097/INF.0000000000000127 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Morens DM, Bregman DJ, West CM, Greene MH, Mazur MH, Dolin R, Fisher RI. An outbreak of varicella-zoster virus infection among cancer patients. Ann Intern Med 1980;93:414-9; PMID:6254415; http://dx.doi.org/ 10.7326/0003-4819-93-3-414 [DOI] [PubMed] [Google Scholar]
- 36.Gustafson TL, Shehab Z, Brunell PA. Outbreak of varicella in a newborn intensive care nursery. Am J Dis Child 1984;138:548-50; PMID:6720640 [DOI] [PubMed] [Google Scholar]
- 37.Hyams PJ, Stuewe MC, Heitzer V. Herpes zoster causing varicella (chickenpox) in hospital employees: cost of a casual attitude. Am J Infect Control 1984;12:2-5; PMID:6561002; http://dx.doi.org/ 10.1016/0196-6553(84)90064-6 [DOI] [PubMed] [Google Scholar]
- 38.Shehab ZM, Brunell PA. Susceptibility of hospital personnel to varicella-zoster virus. J Infect Dis 1984;150:786; PMID:6491384; http://dx.doi.org/ 10.1093/infdis/150.5.786 [DOI] [PubMed] [Google Scholar]
- 39.Weitekamp MR, Schan P, Aber RC. An algorithm for the control of nosocomial varicella-zoster virus infection. Am J Infect Control 1985;13:193-8; PMID:2998229; http://dx.doi.org/ 10.1016/0196-6553(85)90057-4 [DOI] [PubMed] [Google Scholar]
- 40.Krasinski K, Holzman RS, LaCouture R, Florman A. Hospital experience with varicella-zoster virus. Infect Control 1986;7:312-6; PMID:3011693 [DOI] [PubMed] [Google Scholar]
- 41.Haiduven-Griffiths D, Fecko H. Varicella in hospital personnel: a challenge for the infection control practitioner. Am J Infect Control 1987;15:207-11; PMID:3674538; http://dx.doi.org/ 10.1016/0196-6553(87)90097-6 [DOI] [PubMed] [Google Scholar]
- 42.Park CS, Kim DS, Kim KH. Varicella outbreak in the patients during group therapy: seroprevalence in a healthcare system during breakthrough varicella occurrence. Clin Exp Vaccine Res 2013. July;2(2):140-3; http://dx.doi.org/ 10.7774/cevr.2013.2.2.140 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 43.Garner JS. Guidelines for isolation precautions in hospitals. Infect Cont Hosp Epid 1996;17:54-80 [DOI] [PubMed] [Google Scholar]
- 44.Bolyard EA, Tablan OC, Williams WW. Pearson ML, Shapiro CN, Deitchmann SD. Guideline for infection control in healthcare personnel, 1998: Hospital Infection Control Practices Advisory Committee. Infect Cont Hosp Epid 1999;19:407-63; http://dx.doi.org/ 10.2307/30142429 [DOI] [PubMed] [Google Scholar]
- 45.Zhang HJ, Patenaude V, Abenhaim HA. Maternal outcomes in pregnancies affected by varicella zoster virus infections: Population-based study on 7.7 million pregnancy admissions. J Obstet Gynaecol Res 2015. January;41(1):62-8; http://dx.doi.org/ 10.1111/jog.12479 [DOI] [PubMed] [Google Scholar]
- 46.Takahashi M, Otsuka T, Okuno Y, Asano Y, Yazaki T. Live vaccine used to prevent the spread of varicella in children in hospital. Lancet 1974. November 30;2(7892):1288-90 [DOI] [PubMed] [Google Scholar]
- 47.Centers for Disease Control and Prevention (CDC). Immunization of Adolescents: Recommendations of the Advisory Committee on Immunization Practices, the American Academy of Pediatrics, the American Academy of Family Physicians, and the American Medical Association MMWR 1996; 45(RR-13). [PubMed] [Google Scholar]
- 48.European Centre for Disease Prevention and Control Varicella vaccine in the European Union Stockholm: ECDC; 2014 Stockholm, April 2014. Available at: http://www.ecdc.europa.eu/en/publications/Publications/Varicella-guidance-2014-consultation.pdf, accessed on 15thJune2014 [Google Scholar]
- 49.Halloran ME, Cochi SL, Lieu TA, Wharton M, Fehrs L. Theoretical epidemiologic and morbidity effects of routine varicella immunization of preschool children in the United States. Am J Epidemiol 1994. July 15;140(2):81-104 [DOI] [PubMed] [Google Scholar]
- 50.Health Canada. Varicella vaccine: Summary of a Canadian Consensus Conference. Paediatr Child Health 1999 Oct; 4(7):449-450. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 51.Brisson M, Edmunds WJ, Gay NJ, Law B, De Serres G. Modelling the impact of immunization on the epidemiology of varicella zoster virus. Epidemiol Infect 2000. December;125(3):651-69; http://dx.doi.org/ 10.1017/S0950268800004714 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 52.Brisson M, Edmunds WJ, Gay NJ. Varicella vaccination: impact of vaccine efficacy on the epidemiology of VZV. J Med Virol. 2003;70 Suppl 1:S31-7; PMID:12627484; http://dx.doi.org/ 10.1002/jmv.10317 [DOI] [PubMed] [Google Scholar]