Management of varicella in neonates and infants

Loading

  1. Sophie Blumental,
  2. http://orcid.org/0000-0003-4460-3420Philippe Lepage
  1. Paediatric Infectious Diseases, Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium
  1. Correspondence to Professor Philippe Lepage; lepagephil{at}skynet.be

Abstract

In countries where vaccination is not implemented, varicella is a mutual ubiquitous disease offering a broad range of clinical presentations. Whereas female parent-to-child perinatal transmission of varicella zoster virus (VZV) can lead to disseminated life-threatening diseases in unimmunised newborns, postnatal conquering will be by and large a source of milder infections. The blueprint and severity of the disease are known to be partly determined by the timing of VZV acquisition during pregnancy with the highest risk menses located around delivery. Management of youngest children after contact with a varicella instance remains difficult for clinicians not only because of unawareness of varicella natural history and risks factors for serious complications, but also considering of the lack of consensus from experts available in the literature. This country of uncertainty often leads to overconsumption of healthcare resources with systematic hospitalisation and unjustified antiviral intravenous therapies. After a curtailed literature review, this article proposes businesslike recommendations considering newborns in various scenarios following a contact with VZV, taking into account the timing and style of virus transmission, the maternal immunological status, the baby'south gestational age and the presence of other underlying atmospheric condition.

  • varicella
  • neonates
  • chickenpox
  • congenital infection
  • acyclovir

This is an open access article distributed in accord with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the employ is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

Statistics from Altmetric.com

  • varicella
  • neonates
  • chickenpox
  • congenital infection
  • acyclovir

Introduction

Varicella is a common ubiquitous disease leading to a broad range of clinical presentations, from mild spontaneously resolving infections to severe complicated episodes requiring hospitalisation and intravenous therapies.1–3 Whereas this infection is fortunately beneficial in the vast majority of cases, it can lead to disseminated life-threatening diseases in unimmunised newborns contaminated around the fourth dimension of delivery, especially in case of prematurity. On the reverse, VZV has been shown to only cause mild disease in babies born from previously immunised mothers who contracted the virus postnatally from infected family contacts.4–eleven

Information technology has been demonstrated that the pattern and severity of child infection depends on the moment of contamination (before, around or after commitment), the maternal immunological status confronting VZV, the gestational age of the baby and the presence of other underlying weather condition.6 7 12 Still, some confusion—and fifty-fifty fright—remains in the direction of youngest infants later a contact with a varicella example mainly due to the unreliability of early clinical presentation in this age group, the significant risk of life-threatening complications in example of perinatal infection and the lack of therapeutic consensus. In daily practise, paediatricians and general practitioners tend too systematically refer to an infectious disease specialist and recommend hospitalisation merely considering of immature patient's historic period rather than considering disease severity.13 Better cognition of varicella natural history, as well as take chances factors for disseminated illness and indications for therapy, is, therefore, mandatory not only to start early treatment in those who demand information technology the most merely likewise to avoid unnecessary hospitalisations and subsequent nosocomial complications in the others.

In this setting, we aim to offer brusk pragmatic recommendations for the management of newborns and infants who were proved to be in contact with VZV infected cases. Subsequently careful literature review, nosotros propose specific therapeutic attitudes in different kinds of a situation defined according to the type and menses of contagion of the babe as well every bit the maternal and baby medical status.

Country of the art

Epidemiology and clinical presentation

Varicella during pregnancy is a rare just potentially serious status able to generate severe maternal and fetal disease every bit well as disseminated infection in newborns. According to a survey in the UK, its incidence turns effectually at to the lowest degree ane/2000 live birth.eleven Equally detailed in tables ane and 2, clinical presentation and severity for the future newborn will depend on the moment where the female parent contracted the virus in relation to the timing of the pregnancy.6 7 A maternal infection occurring during the first 2 trimesters of pregnancy can atomic number 82 to built varicella, which is characterised by disseminated lesions of the skin, eyes, basic and central nervous system of the growing fetus. Congenital varicella will be unfortunately fatal in roughly 30% of the infected babies during the first month of life and the run a risk of embryopathy post-obit built varicella is most ii% in survivors.14 Whether maternal varicella infection in the offset 20 weeks of pregnancy increases the risk of miscarriage remains controversial6 14 xv (table 1).

View this table:

  • View inline

Tabular array 1

Clinical presentation of mother and kid varicella according to the timing of VZV acquisition during pregnancy (adapted from Sauerbrei A and Wutzler P. J Perinatol 2001;21:545 6)

View this table:

  • View inline

Tabular array 2

Consequence without antiviral therapy after maternal or neonatal varicella according to the timing of infection effectually birth (adapted from Sauerbrei A and Wutzler P. J Perinatol 2001;21:545 6)

On another hand, neonatal varicella occurs when the mother is infected during the three final weeks of pregnancy6 (tables 1 and two).

There are iii means of VZV mother-to-child manual, divers as follows:

  • Transplacental viremia.

  • Direct contamination during commitment (skin lesions, claret, and so on)

  • Postnatal contamination by respiratory droplets or pare contact with infected vesicles.

When acquired in utero, the severity of varicella disease in the newborn will be determined by the time between maternal infection and delivery (tabular array 1): how long the fourth dimension elapsing between those two and how of import the rate of maternal-specific antibodies transferred through the placental membranes. These antibodies accept been demonstrated to help in controlling of infection in the newborn. Several periods can, therefore, be distinguished, defined as follows:

  • The highest take chances period for the newborn corresponds to a VZV maternal infection contracted merely around delivery (−v days to +2 days). In that case, the babe will be exposed to a loftier viral load but will have no time to acquire enough maternal protective antibodies. In the literature, contagion during this catamenia is consequently associated with a meaning rate of life-threatening disseminated disease in neonates (up to 20%–50% of transmission with a fatality rate of 20%, table ii). The infection generally occurs between the fifth and 10th solar day of life. Fortunately, the fatality rate mentioned in a higher place is now an overestimation since significant advances have been made in intensive cares as well as in antiviral treatments and immunotherapies from the time the studies mentioned above were made.16 This is well illustrated by the results from five other studies where no fatal case was recorded out of 231 babies with VZV perinatal manual cheers to early on administration of specific VZV immunoglobulins.17–21

  • In fetus who were exposed earlier from twenty to 5 days before delivery, neonatal varicella tin also develop, generally around the 0–iv days of life (respective to 9–xv days later on onset of maternal rash). Fortunately, in such cases, subsequent infection is generally mild to moderate, every bit attested past data from tables 1 and 2 (no fatal instance reported).

  • Irrespective of the timing of maternal VZV conquering, infected newborns tin can further develop zoster during the showtime yr of their life. Of note, a zoster infection in a pregnant adult female is free of adventure for the baby since protective maternal antibodies will be transmitted through placental transfer6 (tabular array 1).

Because the long incubation period of VZV (10–23 days), episode presented earlier the tenth–12th day of life can exist considered as a prenatal infection, whereas postnatal acquisition is the most probable when infection starts from the 13th mean solar day of age onwards. In the absenteeism of high prematurity, a varicella infection acquired postnatally during the offset calendar month of life will in the vast bulk of cases lead to mild to moderate diseases.vi 7 Even in infants born from seronegative mothers, no life-threatening clinical presentations volition generally exist encountered as compared with perinatal acquisition only around the fourth dimension of commitment. Whereas both groups are deprived from protective maternal antibodies, the divergence observed in clinical pattern suggests a key role of the newborn cell-mediated immunity in controlling VZV disease. Newborn cell-mediated responses are probable insufficient to hinder haematogenous dissemination after transplacental spread but could hamper viral replication after transmission by the respiratory route.6 14 The importance of the infecting viral load could likewise partially contribute to this ascertainment.

Prevention and treatment

Immune globulins

Efficacy of administration of specific immune globulins in preventing consequences of varicella in healthy subjects has been recognised since 1969.22 However, the role of VZV immune globulins in preventing neonatal infection remains insufficiently demonstrated in the scientific literature. Five studies of which only two were prospective but not randomised17–21 could exist retrieved and concluded that administration of varicella zoster immune globulins (VZIG) to VZV exposed newborns tin prevent roughly l% of symptomatic cases and reduce the severity of infection amongst others. The most astringent diseases in these series were recorded among neonates born within the 5 days of maternal eruption. Still, some cases are published that describe serious and even fatal situations despite VZIG prophylaxis.xi 23–26

Recommended VZIG doses administered through intramuscular injection are:2

  • Newborn<two.0 kg: 125 U.

  • Newborn>two.0 kg: 250 U.

Whereas VZIG is bachelor and recommended in the USA, many European countries cannot hands benefit from such therapy, and therefore require alternatives to prevent neonatal varicella. Many European procedures, hence, include regular intravenous immune globulins (IVIG) (400 mg/kg in one case) in combination or not with acyclovir. Efficacy of this treatment has been supported past a study assessing 15 newborns considered at loftier risk of severe presentation after a maternal infection occurring in the risky menstruum (from 7 days before to 5 days after delivery).27 All of them received 500 mg/kg immediately after nascence or after the infective contact, with or without intravenous acyclovir. Acyclovir was started vii days after the first day of onset of maternal eruption and kept for five days. None of the 10 newborns receiving IVIG therapy plus intravenous acyclovir presented with symptomatic varicella.27

Acyclovir

No controlled clinical trials have evaluated the efficacy of acyclovir handling in neonatal varicella.28 However, well-nigh experts recommend this drug in the management of newborn varicella illness since acyclovir is almost the only antiviral medication efficient against herpes viruses for which sufficient pharmacokinetic/dynamic information and safety profile are available in neonates. Recent studies with acyclovir have suggested that current dosing regimens may not consequence in therapeutic central nervous system concentrations. More frequent dosing may, therefore, be required for at term neonates.29

Applied recommendations for a newborn/infant in contact with VZV

Case scenario i: the mother is the source of contamination

1a. Worst case scenario: mother starting varicella symptoms between D−5 and D+2 around commitment: perinatal infection

As detailed in a higher place, the prevalence of life-threatening disease when infection occurs in the period effectually delivery is the highest and justifies heavy protective measures and preventive therapy immediately after birth, even in a fully asymptomatic newborn. Timing of therapy is conditioned past the long period of incubation characterising VZV infection (viral dissemination and consequent rash occurring between 9 and fifteen days afterwards the infective contact, which is considered here to be the showtime twenty-four hour period of maternal eruption).

Therapeutic recommendations

  • Go on newborn and mother for at least 3 days hospitalised (with airborne and contact precautions for both).

  • Care for the infant with either VZIG (see dosage above) or, if unavailable, IVIG 400 mg/kg as shortly as possible within the first 48–96 hours later nascence.

  • If the child does not accept any other comorbidity and is fully asymptomatic and the parents are reliable, mother and baby could leave the hospital betwixt assistants of immune globulins and acyclovir therapy.

  • Treat the baby with intravenous acyclovir 30 mg/kg/day divided into 3 doses, from day 7 afterward the onset of maternal rash and administrate during x days.

  • In instance, no peripheral venous admission could exist placed to give intravenous acyclovir despite several attempts, the antiviral treatment could be started orally pending the child is fully asymptomatic and remains nether careful medical surveillance. A cardinal line should only be recommended in instance of clinical worsening.

  • In the rare case, the newborn will develop varicella symptoms despite handling, administer acyclovir for at to the lowest degree three weeks and search for underlying weather condition (congenital immunodeficiency, metabolic disease, viral resistance, and then on).

ane.b Female parent starting varicella symptoms from D+3 to D+28 after delivery: postnatal infection

As detailed in tables 1 and 2, the risk for newborn infection is also high justifying preventive therapy just the risk of infection leading to severe disease is much lower.

Therapeutic recommendations

  • Treat the baby with acyclovir per bone (PO) 80 mg/kg/day divided into four doses from 24-hour interval seven afterward the onset of maternal rash and administer during 7–ten days.

  • Indication and elapsing of hospitalisation (with airborne and contact precautions) should be discussed in each case depending on mother and kid clinical status, parental compliance and social setting. If any doubt, hospitalisation with optimal medical surveillance are warranted during the take chances flow.

  • In the rare case, the newborn will develop varicella symptoms despite preventive therapy, consider—co-ordinate to clinical evolution and severity—to hospitalise and switch to intravenous acyclovir for at least 3 weeks and search for underlying atmospheric condition (congenital immunodeficiency, metabolic affliction, viral resistance, then on).

ane.c Mother starting varicella symptoms from D−xx to D−half-dozen before delivery

There are no published recommendations for this specific situation. It is common knowledge that such newborns can develop symptomatic varicella and even present with apparent pare lesions at nativity. Yet, as presented in table 1, the infection will be by and large mild (no fatal case reported). Our good opinion in such case would be to administer preventive therapy to prevent severe disease but to tailor information technology according to the clinical pattern, divers equally follows:

  • Go on newborn and mother for at to the lowest degree 3 days hospitalised (with airborne and contact precautions for both).

  • Treat the baby with either VZIG (see dosage higher up) or, if unavailable, IVIG 400 mg/kg as soon as possible (within the starting time 48–96 hours later nascence).

  • If the child does not take whatsoever other comorbidity and is fully asymptomatic and the parents are reliable, mother and baby could leave the hospital later assistants of immune globulins. If whatsoever dubiety, hospitalisation with optimal medical surveillance are warranted during the risk flow (outset week of life).

  • If vesicles are present at birth or appear, add together acyclovir PO lxxx mg/kg/twenty-four hours divided into four doses and maintain over vii days (according to clinical evolution) and hospitalise the baby for surveillance. Duration of hospitalisation (with airborne and contact precautions) should exist discussed in each instance depending on mother and kid clinical status, parental compliance and social setting.

Case scenario two: high prematurity

Similar recommendations to Section 1.a should be applied in instance of contact with varicella from any origin (maternal or non) in the following groups:

  • Extremely preterm babies (gestational age (GA)<28 weeks) regardless of the maternal VZV serological status.

  • Very-preterm (GA 28–32 weeks) and moderate-preterm to tardily-preterm (GA 32–37 weeks) babies born from an unimmunised mother.

Case scenario three: asymptomatic newborn in contact with VZV from whatever infected subject area

Since transmission of VZV occurs not only through direct pare contact with vesicles just mainly through the airborne route (droplets nuclei), an 'infective contact' with a VZV-infected person is defined equally having whatsoever close contact together, such every bit a shut indoor contact (eg, in the aforementioned room) or face-to-face contact. However, experts differ in their opinion about the elapsing of the infective contact: whereas some suggest 5 min, others require upwards to i hr.2 Of notation, this is dissimilar for zoster-infected person with which only a skin contact with the lesions will be a source of contamination. A VZV-infected subject field is considered potentially contaminant until all his skin vesicles are crusted.

In this scenario, the mother immunological condition against VZV will determine the run a risk of infection and affliction in her baby.

The starting time step is careful anamnesis of the mother to confirm or not history of varicella. If no previous varicella could exist guaranteed, and so a serological testing should be done to the mother and the baby carefully observed pending the results.

  • The mother is proved seropositive:

    • Very depression take a chance of disease in the baby.

    • No treatment should be provided.

    • Observance of the baby at home and encourage parents to come dorsum if any clinical sign or symptom appears in the 2 weeks later on contact.

    • If symptoms or signs of varicella, refer to the section Case scenario 4.

  • The female parent is proved seronegative or refuses testing:

    • Care for the babe with acyclovir PO 80 mg/kg/solar day divided into 4 doses to outset seven days after infective contact and administer during 7 days.

    • Careful surveillance of the baby during the run a risk period. Indication and duration of hospitalisation (with airborne and contact precautions) should be discussed in each example depending on child clinical condition, parental compliance and social setting. If any doubtfulness, hospitalisation with optimal medical surveillance are warranted during the risk catamenia.

    • If symptoms or signs of varicella, refer to the section Case scenario 4.

Case scenario 4: infant<i month of age presenting with clinical signs of varicella

  • First of all, in every newborn presenting with fever and varicella vesicles, the presence of viral eruption should not automatically rule out a concomitant bacterial infection and precaution should prevail. A full workup to exclude bacterial late-onset infection should exist realised depending on infant's clinical and biological status:

    • In every newborn with fever>38.5° or elevated C-Reactive Protein (CRP) or contradistinct clinical status:

      • Perform full microbiological workup (including lumbar puncture)

      • Treat with wide intravenous antibiotics in addition to acyclovir (meet beneath) until obtaining culture results.

      • In case a source of bacterial infection will exist identified, consider a switch to narrow spectrum antibody.

    • If the baby presents with a confirmed varicella diagnosis and fever<38.v°C, no inflammatory syndrome besides as no altered clinical status after exam past a senior paediatrician:

      • Hospitalise under conscientious medical surveillance without extra invasive workup/antibiotic treatment.

      • Treat with acyclovir (run across below).

      • Add other exams or handling if new symptoms/signs or worsening.

  • Equally for varicella treatment, assistants of acyclovir is e'er recommended. Way of administration depends on mother immunological status against VZV:

    • Mother with a confirmed medical history of varicella:

      • Low risk of severe varicella disease.

      • Care for the baby with acyclovir PO lxxx mg/kg/solar day divided into iv doses.

      • Hospitalisation according to clinical presentation (fever, altered full general status, severe eruption, suspected bacterial superinfection, and so on) and social setting (parental incompliance and and so on).

    • Female parent with no history of varicella or status unknown:

      • Mandatory hospitalisation.

      • Treat the infant with acyclovir for a minimum of seven days. Start with acyclovir intravenous 30 mg/kg/day divided into three doses for moderate to astringent cases and switch to acyclovir PO every bit presently equally observing significant clinical improvement. Treat directly with acyclovir PO 80 mg/kg/day divided into four doses for balmy clinical presentations.

Case scenario v: infant>one calendar month of age presenting with clinical signs of varicella

In infants anile >one month having no underlying medical condition and presenting with uncomplicated varicella, the administration of acyclovir is non systematically recommended, irrespective of the mother VZV immunological status. Decision of prescribing an antiviral treatment should exist based on the clinical blueprint and severity of infection (child full general status, importance of rash, presence of neurological complications or superinfection, and so on).

Similarly to what detailed in the section Example scenario 4, the presence of a varicella at admission does not exclude a concomitant bacterial infection and so that febrile children should exist managed carefully in searching other possible causes of fever when appropriate.

Practice not forget family unit vaccination…

All seronegative subjects in contact with a newborn with VZV infection should be offered immunisation (two doses with a minimum of 6 weeks between injections) unless contraindicated (infants and immunodeficient persons) inside the 72 hours of the infectious contact. This recommendation is especially important for adolescents and adults who are at major gamble of severe disease presentation.

Conclusions

Despite numerous advances over the concluding decades, management of varicella in the youngest remains a challenge in daily exercise and quality studies on this topic are express.

Whereas experts concur that contamination around delivery deserves ambitious preventive therapy regarding the risk of life-threatening illness in newborns, attitudes in other situations involving postnatal infections are eminently variable and source of confusion.

In order to avoid unnecessary hospitalisations and treatments simply considering the likelihood of severe infectious episode at some points, we suggest the management of a newborn after a VZV contact should not be driven just by the historic period group but rather tailored case by example following careful cess of the type of viral manual, the take a chance factors of serious disease and above all the babe clinical status.

References

  1. ane.↵
  2. 2.↵
  3. 3.↵
  4. 4.↵
  5. 5.↵
  6. half dozen.↵
  7. 7.↵
  8. 8.↵
  9. ix.↵
  10. x.↵
  11. 11.↵
  12. 12.↵
  13. 13.↵
  14. 14.↵
  15. xv.↵
  16. 16.↵
  17. 17.↵
  18. 18.↵
  19. 19.↵
  20. 20.↵
  21. 21.↵
  22. 22.↵
  23. 23.↵
  24. 24.↵
  25. 25.↵
  26. 26.↵
  27. 27.↵
  28. 28.↵
  29. 29.↵

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Centre's RightsLink service. You volition be able to get a quick price and instant permission to reuse the content in many dissimilar ways.

Copyright information:

© Writer(s) (or their employer(s)) 2019. Re-apply permitted under CC By-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open up access article distributed in accordance with the Creative Eatables Attribution Non Commercial (CC Past-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the apply is non-commercial. Meet: http://creativecommons.org/licenses/by-nc/four.0/.