Varicella-zoster virus Infection (VZV)

Chickenpox/HERPES ZOSTER

Identification 

            The varicella-zoster virus causes two distinct diseases:

• Chickenpox (varicella) looks like a primary infection.
  • Chickenpox is one of childhood diseases in unvaccinated people. The vaccine can be done from the age of one year.
  • Some vaccinated children can make mitigate, mild, chickenpox forms.
  • In adults, the disease can have serious complications (pneumonia, encephalitis) and can sometimes be fatal. ^[1]CDC. Heymann D.L., Manual de management al bolilor transmisibile. 2012
  • As acute disease, chickenpox is characterized by fever and rash vesicular generalised, pruritic, with 250-500 lesions in different stages of evolution.
  • Characteristic is the occurrence of lesions in waves at the scalp level. The lesions can be on both free and covered tegument, and also on the mucous membranes. ^[2]Cernescu C., Virusologie medicala, Ed Medicala 2008
• Shingles (herpesul zoster) occurs due to the latency of the virus in the body as recurrence.
  • Shingles is a local manifestation of the reactivation of the latent VZV virus infection in the roots of the dorsal nodes.
  • Occurs in 10-20% of people infected with VZV.
  • The eruption is typical and unilateralăși affects only one dermatome.
  • The lesions are identical to the chickenpox.
  • The eruption lasts 7-10 days and heals in 2-14 weeks.
  • Complications occur in 30% of cases, neuralgia post-herpes being the most common. ^[3]CDC. Heymann D.L., Manual de management al bolilor transmisibile. 2012`

In pregnant women

• Most commonly, the infection is symptomatic.
• There is a prodromal phase with headache, fever and generally altered condition, followed by the occurrence of a rash consisting of macules that evolve rapidly to papules and vesicles.
• The lesions appear in waves for 6-10 days.
• Complications may occur, the most common is pneumonia, and rarer are encephalitis, myocarditis, hepatitis or glomerulonephritis. ^[4]Gardella C, Brown ZA. Managing varicella … in pregnancy. Cleve Clin J Med. 2007; 74(4):290-6.
• The shingles of the pregnant women who are transmitted to the fetus, are associated with herpes zoster in the child. ^[5]CDC. Heymann D.L., Manual de management al bolilor transmisibile. 2012*`

In newborn

• If VZV infection occurs at 10-14 postnatal days, there is a risk of severe generalized chickenpox.
• In newborns whose mothers develop chickenpox 5 days previously or two weeks after birth and who do not receive VZIG immunoglobulin or antiviral therapy the mortality rate may reach 30%. ^[6]Shrim A et al. Management of varicella infection (chickenpox) in pregnancy. J Obstet Gynaecol Can. 2012; 34(3):287-92. ^[7]Ramachandra S et al. Fetal varicella syndrome. Indian J Dermatology Venereol Leprol. 2010; 76(6):724.
• The consequences of the infection on the fetus depend on the time of infection.
• Contracting the infection in the first and second trimester of pregnancy leads to congenital varicella syndrome.
• Early pregnancy infection, weeks 0-12, may be associated with fetal death.
• If the infection occurs two weeks prior to childbirth, neonatal chickenpox is occurring.
• If the newborn develops chickenpox at 10-14 days after birth, it is considered intrauterine infection, representing the incubation period. The mortality rate is lower. ^[8]Lamont RFet al. Varicella‐zoster virus (chickenpox) infection in pregnancy. BJOG. 2011; 118(10):1155-62.
• Occasionally, the newborn baby in the shingles appears an eruption varicelliform shortly after herpes zoster and rarely occurs a secondary zoster rash after chickenpox. ^[9]CDC. Heymann D.L., Manual de management al bolilor transmisibile. 2012`'

Congenital varicella syndrome

• Cases of congenital varicella were reported in particular when the mother was infected before week 20 of pregnancy, the risk being 1-2%.
• The biggest risk is between weeks 13-20.
• It is clinically manifested by:
  • Hypoplasia of Limbs,
  • Neurological impairment,
  • Ocular impairment,
  • Skin manifestations. ^[10]Sauerbrei A. Preventing congenital varicella syndrome with immunization. CMAJ. 2011; 183(3):E169-70.
• Neurological anomalies consist of:
  • Microcephaly
  • Hydrocephalus
  • Cerebral atrophy,
  • Mental retardation.
• Ocular disorders consist of:
  • Corioretinitis,
  • Microphthalmia
  • Cataract.
• Gastrointestinal, genitourinary-urinary and cardio-vascular tract malformations may occur. ^[11]Lamont RFet al. Varicella‐zoster … infection in pregnancy. BJOG. 2011; 118(10):1155-62.

Varicella diagnosis in Pregnant woman

• Mainly based on the clinical aspect.
• The confirmatory methods include:
  • Virus isolation on cell cultures,
  • Direct immunofluorescence tests to detect viral antigens,
  • Molecular tests (PCR).
• The collection of the pathological product is carried out from the base of a
• In the age of vaccines, it is sometimes necessary to identify the strains precisely to make a difference if the shingles occurring in a vaccinated person are due to the vaccine or infection with a wild virus.
• Serological tests, antibody detection, are useful in complicated cases or epidemiological studies. It’s not routine. They have the downside that IgG anti-VZV antibodies become detectable one week after the onset of the disease. In addition to the use of ELISA, an increased rate of false negative results (15-20%) is recorded. There are no validated tests for the detection of anti-VZV antibodies of IgM type. In addition to some subjects who have gone through infection may persist a certain IgM titer. ^[12]Smith CK, Arvin AM. Varicella in the fetus and newborn. Semin Fetal Neonatal Med. 2009 Aug; 14(4):209-17.

 

Diagnosis in newborn (neonatal)

• Serological, antibody detection tests may be used, based on methods such as ELISA or indirect immunofluorescence. These have the disadvantage of having a low sensitivity in early diagnosis and cross-reactions may occur with HSV.
• Detection of anti-VZV antibodies of IgM type indicates the presence of active infection.
• The method with the highest sensitivity and specificity is PCR, based on the amplification of viral DNA sequences. ^[13]Sauerbrei A, Wutzler P. Neonatal varicella. J Perinatol. 2001; 21(8):545-9
• PCR from the amniotic fluid is the method used to determine the transmission of the infection to the fetus.
• The prenatal diagnosis of the infection includes the identification of ultrasound signs such as deformations of limbs, hydrocephalus/microcephaly, calcification of soft tissues, etc. ^[14]Lamont RFet al. Varicella‐zoster virus (chickenpox) infection in pregnancy. BJOG. 2011; 118(10):1155-62.`

 

Note Bene. In this document, the laboratory diagnosis was not treated in the VZV infection, but there were several elements related to pregnancy and newborn. For the complete diagnosis of this infection, those interested will be addressing infectionists physicians.

The infectious agent

The varicella-zoster (VZV) virus is a double stranded DNA virus, belonging to the Subfamily alpha herpes viruses, the Herpesviredae family. ^[15]Shrim A et al. Management of varicella infection (chickenpox) in pregnancy. J Obstet Gynaecol Can. 2012; 34(3):287-92*. ^[16]Biskupska M et al. Varicella—a potential threat to maternal and fetal health. Ginekologia Polska. 2017; 88(1):13-9. ^[17]Cernescu C., Virusologie medicala, Ed Medicala 2008`~

Incidence and prevalence

• Chickenpox is an endemic infection in all countries.
• In temperate regions and in the absence of vaccination approximately 90% of the population develop the disease until the age of 15.
• In western Europe the incidence varies between 300 and 1291 to 100 000 inhabitants, and in the east is about 350 to 100 000 inhabitants. ^[18]European Centre for Disease Prevention and Control. Varicella vaccination in the European Union. Stockholm: ECDC; 2015.

 

Source

The man is the only known host. ^[19]Wang L et al. Efficacy of varicella (VZV) vaccination: an update for the clinician. Ther Adv Vaccines. 2016; 4(1-2):20-31.

 

Method of transmission

• Any infected person is contagious and transmits the infection.
• The infection is highly contagious and transmitted by air through the kernels of the drop or through direct contact with the fluid from the blister level. ^[20]Shrim A et al. Management of varicella infection (chickenpox) in pregnancy. J Obstet Gynaecol Can. 2012; 34(3):287-92.~'
• Transmission may be made also indirectly, with objects recently contaminated with vesicular fluid or on the mucous membranes of infected persons.
• Smallpox crusts aren’t infectious!
• Chickenpox is highly contagious, with transmission of up to 100% compared to shingles, the transmission rate of up to 20%.

 

Risk groups

• Any unvaccinated person is susceptible.
• Susceptible to infection and for the development of serious forms are immunosuppressed people, and that is why vaccination is recommended. ^[21]Wang L et al. Efficacy of varicella (VZV) vaccination: an update for the clinician. Ther Adv Vaccines. 2016; 4(1-2):20-31.`
• Has severe forms:
  • Adults
  • Newborns whose mothers are not immune;
  • Patients with leukemia or other forms of cancer;
  • Immunosuppressive patients.

Incubation period

The incubation period varies between 10-21 days, with an average of 14-16 days, can be extended to 28 days by passive immunization against chickenpox, is shorter at immunosuppressed. ^[22]Gardella C, Brown ZA. Managing varicella … in pregnancy. Cleve Clin J Med. 2007; 74(4):290-6.`

 

Infectiousness period

• In chickenpox, the person infected with VZV is contagious 2 days before the eruption and until all lesions has crust.
• At shingles, patients are contagious a week after the occurrence of lesions.
• Susceptible individuals should be considered infectious 10-21 days after exposure. ^[23]Gardella C, Brown ZA. Managing varicella … in pregnancy. Cleve Clin J Med. 2007; 74(4):290-6.'

 

Prophylaxis

Vaccination

• Chickenpox is one of the main causes preventable of death in children.
• Vaccination provides protection of 85%. ^[24]Wang L et al. Efficacy of varicella (VZV) vaccination: an update for the clinician. Ther Adv Vaccines. 2016; 4(1-2):20-31.'
• A great method to prevent chickenpox during pregnancy is vaccination of susceptible women (who have not had chickenpox).
• In women who wish to become pregnant, in the case of a negative history, serological testing is recommended then vaccination, unless it is confirmed that they do not have anti-varicella immunity. ^[25]Gardella C, Brown ZA. Managing varicella … in pregnancy. Cleve Clin J Med. 2007; 74(4):290-6.~
• The varicella vaccine contains a live attenuated virus.
• It is recommended to vaccinate at 12-18 months of life with a first dose and then booster up to 4-6 years. Between doses should be at least 3 months.
• For people with 13 years, two doses of the vaccine are recommended at 4-8 weeks away. Those with a single dose of vaccine are susceptible to making infections with minimal symptoms.
• Vaccination during pregnancy is not recommended, given that there are no studies of the effects on the fetus.
• A woman who is vaccinated should not become pregnant in the next month. However, if this happens, the fetal risk is considered small and is not an indication to stop the pregnancy. ^[26]Sur DK et al. Vaccinations in pregnancy. Am Fam Physician. 2003; 68(2):299-304
• The World Health Organisation recommends vaccination of all health workers or at least those who come into contact with increased risk groups, such as newborn infants under 28 weeks and weighing less than 1000 grams. ^[27]Biskupska M et al. Varicella—a potential threat to maternal and fetal health. Ginekologia Polska. 2017; 88(1):13-9.-
• Vaccination in the first 3 days of an infectant contact may prevent disease from occurring or diminish the symptoms.

 

Administration of Immunoglobulins against chickenpox (VZIG or VariZIG)

• If a pregnant susceptible to the virus is exposed to VZV it is recommended to administer specific immunoglobulins (anti-varicella zoster VZIG or VariZIG) prepared from the plasma of normal blood donors with increased titers of anti-vzv antibodies, in the first 72-96 hours after the exposure, after this period there are no studies on efficacy. ^[28]Shrim A et al. Management of varicella infection (chickenpox) in pregnancy. J Obstet Gynaecol Can. 2012; 34(3):287-92.-
• Immunoglobulins may also be given to newborns whose mothers have signs of chickenpox a week before birth or 2-3 days after birth. ^[29]Sauerbrei A, Wutzler P. Neonatal varicella. J Perinatol. 2001; 21(8):545-9.-
• Mothers and newborns with chickenpox or possibly infected should be isolated.
• No treatment is recommended in the case of neonatal chickenpox if the mother’s eruption occurred more than 7 days before birth. ^[30]CDC. Heymann D.L., Manual de management al bolilor transmisibile. 2012-*

Birth to the woman infected with VZV

Is carried out naturally

 Breastfeeding

There are no contraindications.

Treatment

• All pregnant women with chickenpox should be treated.
• Treatment involves the administration of Acyclovir 800 mg 5 times daily or Valacyclovir 1g 3 times a day.
• Pneumonia is a serious varicella complication. When observing the first signs of pneumonia, Acyclovir 10-15 mg/kg should be administered at 8 hours by intravenous route.
• Acyclovir decreases viral replication and reduces the risk of transplacental transmission of infection.
• Infants with chickenpox may also be treated with Acyclovir by intravenous route. ^[31]Gardella C, Brown ZA. Managing varicella … in pregnancy. Cleve Clin J Med. 2007; 74(4):290-6.| ^[32]Lamont RF et al. Varicella‐zoster virus (chickenpox) infection in pregnancy. BJOG. 2011; 118(10):1155-62.

 Bibliography

1. Gardella C, Brown ZA. Managing varicella zoster infection in pregnancy. Cleve Clin J Med. 2007; 74 (4): 290-6.
2. Shrim A, Koren G, Yudin MH, Farine D. Management of varicella infection (chickenpox) in pregnancy. J Obstet Gynaecol Can. 2012; 34 (3): 287-92.
3. Ramachandra s, Metta AK, Haneef NS, Kodali S. Foetal varicella syndrome. Indian J dermatologisty Venereol Leprol. 2010; 76 (6): 724.
4. Lamont RF, Sobel JD, Carrington D, Mazaki ‐ Tovi S, Kusanovic JP, Vaisbuch E, Romero R. Varicella ‐ zoster virus (chickenpox) infection in pregnancy. BJOG. 2011; 118 (10): 1155-62.
5. Sauerbrei A. Preventing congenital varicella syndrome with immunization. CMAJ. 2011; 183 (3): E169-70.
6. Smith CK, Arvin AM. Varicella in the fetus and newborn. Neonatal foetal semen. 2009 Aug; 14 (4): 209-17.
7. Sauerbrei A, Wutzler P. Neonatal varicella. J Perinatol. 2001; 21 (8): 545-9.
8. Biskupska M, Małecka i, Stryczyńska-Kazubska J, Wysocki J. Varicella — a potential threat to maternal and fetal health. Ginekologia Polska. 2017; 88 (1): 13-9.
9. Wang L, Zhu L, Zhu H. Efficacy of Varicella (VZV) Vaccination: An update for the clinician. Ther ADV Vaccines. 2016; 4 (1-2): 20-31.
10. European Centre for Disease Prevention and Control. Varicella vaccination in the European Union. Stockholm: ECDC; 2015.
11. Sur DK, Wallis DH, O’Connell TX. Vaccinations in pregnancy. I got the Physician. 2003; 68 (2): 299-304.
12. Cernescu C., Medical Virology, Ed Medicala 2008
13. CDC. Heymann D.L., management Manual of communicable diseases. 2012