Elsevier Editorial System(tm) for International Journal of Infectious Diseases
Manuscript Number: IJID-D-12-00792R1
Title: Don't Forget How Severe Varicella Can Be - Complications of varicella in children in a defined
Article Type: Full Length Article
Keywords: varicella, hospitalization, pneumonia, ataxia
Corresponding Author: Dr Ewelina Gowin,
Corresponding Author's Institution: University of Medical Sciences
First Author: Ewelina Gowin
Order of Authors: Ewelina Gowin; Jacek Wysocki, professor; Michal MICHALAK, Md
Aim of this study was the analysis of hospitalizations' causes in children with varicella, based on the
example of defined Polish population.
Retrospective analysis of hospitalizations' causes in children (younger than 18years) with varicella
treated in Infectious Diseases Ward in Children's Hospital in Poznan (Poland) from January 2007 to
June 2012. The described ward serves for almost whole children population of Greatpoland region
(10% of Polish population - almost 600 000 children). The analysis was based on hospital records.
Patients were identified using the international classification of diseases tenth revision (ICD-10). Case
definition consisted of physical evidence of varicella.
A total of 224 children were hospitalized for varicella complications. The median age of admitted
patients was 37.5 months (from 6 days to 17 years). Rates of hospitalizations decreased with age. The
highest were among children during their first year of age. 92% of children were healthy prior to
hospitalization (no chronic diseases). The commonest complication were respiratory tract infections
(26%), followed by skin infections (21%) and neurologic symptoms (18%). The 25 patients (11%) had
more than one complication. The commonest coexisting condition was dehydration and otitis media.
Presented results remind that varicella may to lead to severe, complications in unvaccinated children
and adolescents, and demonstrate the benefits of varicella vaccination. Most children hospitalized with
varicella were immunologically healthy. Meningitis was more common in older children (>6 years of
age). S.pyogenes was the commonest identified bacterial pathogen.
Following Reviewers comments we did an extensive correction of English language in our
article. We ask for the editorial assistance a native speaker dr. Margarita Lianeri. We hope
that now, the article is ready to be published.
I would like to submit an article entitled „Don't Forget How Severe Varicella Can Be -
Complications of varicella in children in a defined Polish population.” written by Ewelina Gowin,
Jacek Wysocki, Michal Michalak. This is an retrospective analysis of hospitalizations' causes in
children with varicella treated in Infectious Diseases Ward in Children's Hospital in Poznan
(Poland) from January 2007 to June 2012. Nowedays most anti-vaccination believers deny the
usefulness of varicella vaccination. Parents and sometimes even doctors having less personal
experience with the disease may change the perception about the risk of varicella. Analysis of
hospitalization causes in patients with varicella from population with high incidence reminds that
varicella is a disease with potentially severe complications. So we are sure that our work is worth
publishinh in International Journal of Infectious Diseases.
*Conflict of Interest Statement
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Don’t Forget How Severe Varicella Can Be – Complications of varicella in children in a defined Polish
Ewelina Gowin1, Jacek Wysocki 2, Michał Michalak3
1Family Medicine Department, Poznan University of Medical Sciences, Poznan, Poland
2Department of Health Promotion, Poznan University of Medical Sciences, Poznan, Poland
3Department of Biostatistics, Poznan University of Medical Sciences, Poznan, Poland
Dr. Ewelina Gowin, MD, PhD.
Family Medicine Department,
49, Przybyszewskiego Str.
60-355 Poznan, Poland
Tel: 48 605 723 017 Fax +48 61 869 11 43
Complications of varicella in a defined Polish population.
Keywords: varicella, hospitalization, ataxia, pneumonia,
Click here to view linked References
Don’t Forget How Severe Varicella Can Be – Complications of varicella in children in a defined Polish
This study aimed to analyze causes of hospitalizations in children with varicella, based on a defined Polish
Retrospective analysis of causes of hospitalizations in children (under 18 years old) with varicella treated in the
Infectious Diseases Ward at the Children’s Hospital in Poznan (Poland) from January 2007 to June 2012. The
described ward serves almost the entire child population of the Greater Poland region (10% of Polish population
- almost 600 000 children). The analysis was based on hospital records. Patients were identified using the
international classification of diseases tenth revision (ICD-10). Case definition consisted of physical evidence of
A total of 224 children were hospitalized for varicella complications. The median age of admitted patients was
37.5 months (from 6 days to 17 years of age). Rates of hospitalizations decreased with age. The highest rates
were among children during their first year. 92% of children were healthy prior to hospitalization (no chronic
diseases). The most common complications were respiratory tract infections (26%), followed by skin infections
(21%) and neurologic symptoms (18%). Twenty-five patients (11%) had more than one complication. The most
commonly coexisting conditions were dehydration and otitis media.
The resented results serve to remind us that varicella may to lead to severe complications in unvaccinated
children and adolescents, and demonstrate the benefits of varicella vaccination. Most children hospitalized with
varicella were immunologically healthy. Meningitis was more common in older children (>6 years of age).
Streptococcus pyogenes was the most commonly identified bacterial pathogen.
Keywords: varicella, hospitalization, ataxia, pneumonia,
Don’t Forget How Severe Varicella Can Be – Complications of varicella in a defined Polish population.
According to a 2010 varicella surveillance report from 18 European countries, Poland had the highest incidence
of varicella 1. Each year there are almost 150 000 cases of varicella, in Poland (table 1) 2,3. An increase in the
number of cases is noted every three to four years, with an observable seasonal pattern 2,3,4. In temperate
climates, more cases are seen in the late spring and early summer. Most cases are in children younger than 15
years, and the highest incidence rate is in children aged 1-4 years 1,2,5. Despite a common perception of varicella
infection as a highly contagious but harmless childhood condition, one cannot forget that potentially severe
complications or painful herpes zoster- relapses may occur. Each year in Poland around 0.5% of patients with
varicella require hospitalization 2. This is similar to the American pre-vaccine era, when there were 4 million
varicella cases annually and 0.3% required hospitalization (13 000 cases) 6.
Varicella generates substantial costs for the healthcare system, either through the treatment of complications or
as indirect costs caused by parents’ lost workdays to care for their sick child. The varicella vaccine was
developed in Japan in the 1970s. The efficacy of the two dose schedule is 97% 6,7,8. In the USA, the vaccine has
been administered routinely since 1995 and has resulted in 90% reduction in morbidity 6,7,8.
Most anti-vaccination believers deny the usefulness of varicella vaccination. The decrease in the rates of
varicella in unvaccinated children is a demonstration of herd immunity and is a welcome effect of the vaccine.
Parents and sometimes even doctors having less personal experience with the disease may change the perception
about the risk of varicella. Analysis of hospitalization causes in patients with varicella from a population with
high incidence reminds us that varicella is a disease with potentially severe complications.
The aim of this study was the analysis of causes of hospitalizations in children with varicella, based on a defined
Material and methods
Retrospective analysis of the causes of hospitalizations in children (younger than 18 years of age) with varicella
treated in the Infectious Diseases Ward at the Children’s Hospital in Poznan (Poland) from January 2007 to June
2012.The described Infectious Diseases Ward serves for almost whole children population of the Greater Poland
region. Inhabitants of the region of Greater Poland form 10% of the Polish population (almost 600 000 children).
All children in Poland have mandatory health care insurance.
The analysis was based on hospital records. Patients were identified using the international classification of
diseases tenth revision (ICD-10). Case definition consisted of physical evidence of varicella. Complication was
defined as any health condition which required hospitalization. Diagnosis of varicella was based on clinical
symptoms and signs. Pneumonia was diagnosed based on chest x-ray; meningitis/meningoencephalitis was
diagnosed based on cerebrospinal fluid analysis; ataxia was clinically diagnosed. Bacterial cultures were
obtained in each case suspected of bacterial suprainfection. Thrombocytopenia was defined as platelets lower
than 100x10 9/l, anemia as hemoglobin lower than 6.2mmol/l. Hepatitis was defined as alanine aminotransferase
(ALT) and aspartate aminotransferase (AST) levels raised more than twice the upper limit of the normal range.
Chronic disease was defined as any disease requiring ongoing medical treatment. The reason for and length of
hospitalization, patient’s age, health status, chronic diseases, and duration of varicella symptoms at the time of
admission were analyzed.
The relationship between analyzed data was performed by Pearson’s linear correlation coefficient. The
significance of the obtained coefficient was checked by t-Student test. The comparison between analyzed groups
was done by analysis of variance. In cases where significant difference was observed, post-hoc Tukey test was
performed in order to determine homogenous groups. Normality of analyzed data was checked by Shapiro-
Wilks test; second assumption – homogeneity of variances was analyzed by Levene’s test. Data were analyzed
using statistical package Statistica 10 (StatSoft Inc.) All tests were considered significant at p<0.05.
Over the study period from January 2007 to June 2012, 224 children were hospitalized in the Infectious Diseases
Ward at the Children’s Hospital in Poznan for varicella complications. A total of 249 complications were
observed (table 2). The number of hospitalizations in each year is shown in table 1. A seasonal pattern was
observed, with 82% of hospitalizations in the period from December through June and the highest admission rate
from April to June. This seasonality was evident in each year of the study period and in all age groups. The
median hospitalization length was six days (from 2 to 25 days).
The median age of admitted patients was 37.5 months (from 6 days to 17 years). Rates of varicella related
hospitalizations decreased with age. The highest rates were among children during their first year of life.
Children younger than four years comprised 63% of hospitalized patients. Six cases of varicella in newborns
were observed, with half of these infections transmitted from mothers. Statistically significant differences in the
age of children with different complications were observed (details figure 1, table 3).
The male to female ratio of hospitalized children was 1.2:1 (121 males and 103 females). 92% of children were
healthy prior to hospitalization (no chronic diseases). A history of asthma was obtained from six patients, and all
of them experienced complications from the respiratory tract. Atopic dermatitis was noted in 5 patients, epilepsy
in 5. There was one patient with nephrotic syndrome, one with rheumatoid arthritis and one withcongenital heart
failure. The median time between onset of varicella exanthema and admission to hospital was 3 days (0-14days).
The most frequent complication was respiratory tract infection (details in tables 4, 5). Radiographically proven
pneumonia was diagnosed in 35 patients (16%). This was the most frequent complication in the youngest group.
Other respiratory tract infections were bronchitis, otitis media, and laryngitis.
Skin infections such as urticaria, erythema multiforme, and pyogenic dermatitis were the next common reason
for hospitalization. Bacterial etiology was established in 13 cases (seven cases of Streptococcus pyogenes and six
of Staphylococcus aureus). Over the study period there were two cases of sepsis (0.9%). Blood and skin cultures
were positive for S.pyogenes. Sepsis appeared on the fifth day of varicella infection. Both children were
immunocompetent, aged 50 and 72 months.
Central nervous sytem complications were observed in 35 patients (16%): 11 had meningoencephalitis, 6 had
ataxia, and 8 had febrile convulsions. Patients with meningoencephalitis were significantly older than the rest of
the group (p<0.001) (table 3).
Twenty-five patients (11%) had more than one complication. The most frequently coexisting conditions were
dehydration and otitis media. Other reasons for admission are described in table 4. The distribution of reasons for
admission in different age groups is indicated in figure 1.
The number of hospitalizations over the study period was different in the different years studied, and reflects
changes in incidence rates. The lowest incidence rate was in 2008. The observed seasonal pattern of
hospitalization reflects the seasonal incidence that is commonly observed 4. Compared with other literature data,
a group of 224 patients hospitalized over the period of 5 years is quite significant 9,10,11.
The median age of 3.12 years of all varicella hospitalized patients corresponds well with the literature data
9,12,13,14. In our study, most of the admitted patients were younger than four years old and 90% of the patients
were younger than ten years old. This reflects the epidemiological trend in varicella morbidity. The varicella
virus is one of most contagious viruses, and even treatment with acyclovir doesn’t stop droplet spreading. The
infectiveness of the varicella virus reaches 80-90% of household contacts, so contact usually results in infection.
In past years the peak incidence was in early school age children. Now, due to the common use of preschool care
facilities, most children have contact with the virus earlier in their lives. The highest hospitalization rates were
during the first year of life, which has also been observed in other studies 1,15.
The type of complication depends on patient age. The youngest children had pneumonia, with skin infection and
meningitis/ meningoencephalitis in the oldest group. This can be explained by the hypothesis that neurological
symptoms such as encephalitis and meningitis are caused by autoimmune reactions triggered by the presence of
the virus. Progression of neurologic symptoms is observed even on acyclovir treatment, and improvement occurs
after steroid administration. PCR of cerebral fluid is negative. Older children are thought to be more susceptible
to antibody-mediated inflammatory reactions, whereas younger, less immunocompetent patients are more
frequently affected by bacterial suprainfections of the skin or the respiratory tract 16,17.
The commonest observed complications were infections of the respiratory tract. This is consistent with American
data from the pre-vaccination era 15,16. Respiratory tract infections were present in younger children, and usually
developed at the beginning of the varicella infection 16.
The high frequency of respiratory tract complications reflects the virus’s biology. The virus enters the host
through the respiratory tract and then spreads in the bloodstream. A cytopathic effect of the varicella virus on
alveolar epithelium causes pneumonia. Desquamated alveolar cells contribute to poor gas exchange. In the
analyzed group there were no cases of respiratory insufficiency, which can be contributed to the introduction of
acyclovir therapy early in the course of the disease.
Based on the literature, it is known that the most common complications of varicella are bacterial skin infections
(observed in 5% of our patients) 9,10,17,18. Low rate of hospitalization due to bacterial skin infections can be
explained by the fact than in countries with high hygiene standards most skin infections can be treated in
outpatient clinics and only the most severe cases lead to hospitalization. The most frequently identified bacterial
pathogen was S.pyogenes. The increase in S.pyogenes skin infections has been observed since the 1990s, while
S.aureus was the leading cause prior to that time 10,12,18.
Hematological complications are observed in 1-2% of children with varicella 19. Patients usually remain
asymptomatic. Like many other thrombocytopenias and anemias during viral infections, those in patients with
varicella are transient and require no treatment. Laboratory tests are not performed routinely in patients with
varicella. It can therefore be assumed that the number of hematological complications is underestimated, because
only a few patients require hospitalization.
Manifestation of neurological symptoms is very worrisome for caregivers, so they usually seek medical help
immediately. In our study, children with neurologic complications, especially cerebellar ataxia or
meningoencephalitis, were admitted to hospital later in the course of their disease than children with other
complications. This is consistent with literature data 20,21. The incidence of neurologic complications among
hospitalized children varies from 8-38% 20,21. There are some studies in which neurologic complications are the
most frequent cause of hospitalization12.The percentage in admitted patients depends on their age group. A
higher percentage of neurologic complications can be observed in the partly vaccinated population as a
consequence of the shift of incidence to older groups. In the studied group, all cases of
meningitis/meningoencephalitis occurred in children older than 57 months, and 87.5% in children older than
In our study, 12% of patients had more than one complication. The most common co-existing condition was
dehydration – present in all age groups. Difficulties in oral intake due to mucosal involvement, symptoms of
gastroenteritis and fever all together may cause dehydration. Five cases of hepatitis were observed, but no Reye’s
syndrome, as salicylates are withheld from children and only few cases of Reye’s syndrome have been observed
since the1990s 22.
The low number of patients with immundeficiencies, similar to the data presented in studies from other
countries, can be explained by the effectiveness of preventive measures such as acyclovir therapy or vaccinations
1,23. Children with previously diagnosed immunodeficiencies usually receive oral acyclovir at the level of
ambulatory care. In Poland, since 2009, vaccinations for patients with immunodeficiencies and their siblings are
compulsory (free of charge).
Vaccinations against varicella are an efficient way to fight varicella infections. Based on German and American
examples, the efficacy and cost-effectiveness of vaccinations has been demonstrated, with vaccination of more
than 75% of the target population reducing morbidity in 80% of that population 15,18,19,24. With lower coverage,
the average age of infection, as well as the number of severe cases, will increase,.7 That is why the World Health
Organization (WHO) advises vaccinations against varicella only when high coverage (more than 75% of the
target population) is possible. The coverage of the measles, mumps, rubella(MMR) vaccine is used as a
predictive measure. Poland is a good candidate for population varicella vaccination because MMR vaccine
uptake is greater than 75%.2
In a situation in which a low coverage is achieved, vaccination may lead to a shift of the disease to older age
groups. This phenomenon was observed in the case of MMR vaccinations. 1,19 Herd immunity, which is good for
diseases that are dangerous at the early stages of life, is harmful in the case of varicella. Infection in older age
groups is connected to a greater risk of complications, especially neurological.
Financial barriers are an important factor in determining the uptake of a vaccine. Reducing financial barriers is
an effective strategy for increasing vaccination coverage rates.
The children in our study group weren’t vaccinated. In 2012, free of charge vaccinations for children attending
nurseries were introduced in Poland. Varicella vaccination coverage in this population is far from advised, as it
may lead to a change in the varicella incidence pattern in the next years. Lower rates of varicella cases may lead
to weaker stimulation of cellular immunity and a higher incidence of herpes zoster in children who had varicella
infection. The two strategies that are cost effective in reducing varicella cases are early immunization, including
children less than one year of age, and adolescent immunization. 25,26,27
Analysis of defined population-based hospital discharge data appears to be a feasible, simple, and potentially
sensitive way to monitor varicella complications. However, there are several limitations to the use of such data.
The number of severe cases is reliable but the number of less severe cases may be underestimated, as many
complications are managed at the level of primary care. The decision for hospitalization is based on the primary
care physician’s clinical judgment as there are no strict referral criteria.
In conclusion, most children hospitalized with varicella complications were immunologically healthy and the
most frequent causes for admission were complications involving the respiratory tract. Our results indicate that
the type of varicella complication depends on the patient’s age, with meningoencephalitis more common in older
children (>6 years of age). Although the peak incidence of varicalla is among patients aged 4-5 years, the highest
hospitalization rate is in the youngest age group, in which vaccination cannot be used. The only way to protect
these infants is to perform routine population vaccination and to decrease the probability of coming into contact
with the virus during the first year of life. The presented results may remind parents and doctors that varicella
may to lead to severe, potentially life threatening, complications in unvaccinated children and adolescents, and
may also demonstrate the benefits of varicella vaccination.
The editorial assistance of Dr. Margarita Lianeri is acknowledged
Conflict of Interest/Funding: None
Meldunki epidemiologiczne lata 2007-2011 Narodowy Instytut Zdrowia Publicznego. PZH Warszawa.
Państwowa inspekcja sanitarna, Wojewódzka stacja sanitarno epidemiologiczna. Ocena stanu
sanitarnego i sytuacja epidemiologiczna województwa wielkopolskiego w roku 2011. Poznan, Marzec, 2012.
Miller ER, Kelly HA. Varicella infection – Evidence for peak activity in summer months. J Infect.
Smukalska E, Dura B. Powikłania ospy wietrznej u dzieci jako przyczyna hospitalizacji. Przegl
Epidemiol. 2004; 58: 134–8.
Staat MA, Meinzen-Derr J, Welch T, Roberts NE, Jamison L, Gerber MA, Morrow AL. Varicella-
related hospitalization and emergency department visit rates, before and after introduction of varicella vaccine,
among white and black children in Hamilton County, Ohio. Pediatrics. 2006;117:833-9.
Galil K, Brown C, Lin F, Seward J. Hospitalizations for varicella in the United States, 1988 to 1999.
Pediatr Infect Dis J. 2002; 21:931-5.
Shapiro ED, Vazquez M, Esposito D, Holabird N, Steinberg SP, Dziura J, LaRussa PS, Gershon AA.
Effectiveness of 2 doses of varicella vaccine in children. J Infect. Dis. 2011; 203: 312-5.
Dubos F, Grandbastien B, Hue V, Martinot A. Epidemiology of hospital admissions for paediatric
varicella infections: a one-year prospective survey in the pre-vaccine era. Epidemiol Infect. 2007;135: 131-8.
Ziebold C,von Kries RD, Lang R, Weigl J. Schmitt HJ. Severe complications of varicella in previously
healthy children in Germany: A 1-year survey. Pediatrics 2001; 108 79-83.
Maharshak N, Somekh E. Hospitalization for varicella in central Israel. Acta Paediatr Scand
Jaeggi A, Zurbruegg RP, Aebi C.Complications of varicella in a defined central European population.
Arch Dis Child. 1998;79:472–7.
Liese JG, V. Grote V, Rosenfeld E, Fischer R, Belohradsky BH, Kries RV.
The burden of varicella complications before the introduction of routine varicella vaccination in
Germany. Pediatr Infect Dis J. 2008;27:119-124.
Grimprel E, Levy C,de La Rocque F. Paediatric varicella hospitalisations in France: A nationwide
survey. Clin Microbiol Infect. 2007;13:546-9.
Lopez AS, Zhang J, Brown C, Bialek S. Varicella-related hospitalizations in the United States, 2000-
2006: the 1-dose varicella vaccination era. Pediatrics. 2011;127:238-45.
Hervas D, Henales V, Yeste S, Figuerola J, Hervas J. How frequent is varicella-associated pneumonia
in children? Eur J Clin Microbiol Infect Dis 2011;30:435–7.
Patel RA, Binns HJ, Shulman ST. Reduction in pediatric hospitalizations for varicella-related invasive
group A streptococcal infections in the varicella vaccine era. Pediatrics. 2004;144:68-74.
Aebi C, Ahmed A, Ramilo O. Bacterial complications of primary varicella in children. Clin. Infect. Dis.
1996; 23, 698 -705.
EUVAC.NET Surveillance of Varicella and Herpes Zoster in Europe, 2010. Available online at
complications in otherwise healthy children hospitalized for varicella. Vaccine.2011; 29: 1534-7.
Rack AL, Grote V, Streng A, Belohradsky BH, Heinen F, Kries R, Liese JG. Neurologic Varicella
Complications Before Routine Immunization in Germany. Pediatric Neurology. 2010;42:40-8.
Kleinschmidt-DeMasters BK, Gilden DH. Varicella-zoster virus infections of the nervous system—
Clinical and pathologic correlates. Arch Pathol Lab Med.2001; 125:770-80.
Seward JF, Watson BM, Peterson CL. Varicella disease after introduction of varicella vaccine in the
United States, 1995-2000. JAMA 2002.287: 606-11.
Nguyen HQ, Jumaan AO, Seward JF. Decline in mortality due to varicella after implementation of
varicella vaccination in the United States. N. Engl. J. Med.2005. 352: 450 -8.
World Health Organization, Varicella Vaccine. Available at:
Banz K, Wagenpfeil S, Neiss A , Goertz A, Staginnus U, Vollmar J, Wutzler P. The cost-effectiveness
of routine childhood varicella vaccination in Germany. Vaccine 2003; 21: 1256–67.
Bonanni P, Boccalini S, Bechini A, Banz K. Economic evaluation of varicella vaccination in Italian
children and adolescents according to different intervention strategies: the burden of uncomplicated hospitalized
cases. Vaccine 2008;26: 5619–26.
Wutzler P, Neiss A, Banz K, Goertz A, Bisanz H. Can varicella be eliminated by vaccination? Potential
clinical and economic effects of universal childhood varicella immunisation in Germany. Med Microbiol
Immunol 2002; 191:89-96.
Bozzola E, Quondamcarlo A, Krzysztofiak A, Pandolfi E, Lancella L, Tozzi A. Haematological
Figure 1. Frequency of commonest complications in diferent age groups. Download full-text