Burden of varicella in Central and Eastern Europe: findings from a systematic literature review

Figures & data

Table 1. Search strategy in Embase® and MEDLINE® using Embase.com platform.

No.	Query	Description	Results
#1	‘chickenpox’/exp OR varicella:ab,ti OR ‘chicken pox’:ab,ti OR ‘chickenpox’:ab,ti	Disease facet	20,475
#2	‘epidemiology’/exp OR epidemi*:ab,ti OR inciden*:ab,ti OR prevalence:ab,ti	Epidemiology studies facet	3,251,887
#3	#1 AND #2	Combining disease and epidemiology facets	4778
#4	#3 AND ([conference review]/lim OR [editorial]/lim OR [letter]/lim OR [note]/lim OR [review]/lim)	Excluding reviews, letters, commentary, and searches	1177
#5	#3 NOT #4		3601
#6	#5 AND [2012–2016]/py	Studies for all the key regions of interest will be included post-2012: Latin America, Middle East, Eastern Europe, and Asia-Pacific	1046
#7	#5 AND [<1966–2011]/py	Excluding studies prior to 2012 in countries already covered in previous review	2549
#8	argentina OR australia OR brazil OR canada OR chile OR china OR india OR israel OR japan OR korea OR malaysia OR mexico OR ‘new zealand’ OR philippines OR russia OR ‘saudi arabia’ OR ‘south africa’ OR taiwan OR thailand OR vietnam OR ‘czech republic’ OR czechoslovakia OR england OR france OR hungary OR ireland OR poland OR scotland OR ‘slovak republic’ OR slovenia OR turkey OR uk OR ‘united kingdom’ OR wales		15,235,019
#9	#7 NOT #8		1137
#10	#6 OR #9	Final epidemiology review number	2183
#11	‘economics’/de OR ‘economic aspect’/de OR ‘cost’/de OR ‘health care cost’/de OR ‘drug cost’/de OR ‘hospital cost’/de OR ‘health economics’/de OR ‘pharmacoeconomics’/de OR ‘economic evaluation’/exp OR ‘socioeconomics’/de OR ‘health care financing’/de OR ‘low cost’ OR ‘high cost’ OR health*care NEXT/1 cost* OR ‘health care’ NEXT/1 cost* OR cost NEXT/1 estimate* OR ‘fee’/exp OR ‘budget’/exp OR ‘cost variable’ OR unit NEXT/1 cost* OR economic*:ab,ti OR pharmacoeconomic*:ab,ti OR ‘hospital finance’/de OR ‘financial management’/de OR price*:ab,ti OR pricing:ab,ti OR cost* NEAR/3 (treat* OR therap*) OR ‘cost-effectiveness’ OR ‘cost-utility’ OR ‘cost utility’ OR ‘cost benefit’ OR ‘cost minimisation’ OR ‘cost minimization’ OR ‘budget impact’ OR ‘cost consequence’ OR ‘health care utilization’/de OR health*care NEXT/1 (utilisation OR utilization) OR ‘health care’ NEXT/1 (utilisation OR utilization) OR resource NEXT/1 (utilisation OR utilization OR use) OR cost*	Economic burden facet	1,418,584
#12	#1 AND #11	Combining disease and economic facets	1391
#13	#12 AND ([conference review]/lim OR [editorial]/lim OR [letter]/lim OR [note]/lim OR [review]/lim)	Excluding reviews, letters, commentary, and searches	561
#14	#12 NOT #13		830
#15	#14 AND [2012–2016]/py	Studies for all the key regions of interest will be included post-2012: Latin America, Middle East, Eastern Europe, and Asia-Pacific	223
#16	#14 AND [<1966–2011]/py	Excluding studies prior to 2012 in countries already covered in previous review	606
#17	argentina OR australia OR brazil OR canada OR chile OR china OR india OR israel OR japan OR korea OR malaysia OR mexico OR ‘new zealand’ OR philippines OR russia OR ‘saudi arabia’ OR ‘south africa’ OR taiwan OR thailand OR vietnam OR ‘czech republic’ OR england OR france OR hungary OR ireland OR poland OR scotland OR ‘slovak republic’ OR slovenia OR turkey OR uk OR ‘united kingdom’ OR wales		15,141,096
#18	#16 NOT #17		275
#19	#15 OR #18	Final economic review number	498
#20	‘vaccination’/exp OR ‘immunization’/exp OR immunisation:ab,ti OR immunization:ab,ti	Vaccination facet	267,250
#21	#1 AND #20	Combining disease and vaccination facets	5137
#22	#21 AND ([conference review]/lim OR [editorial]/lim OR [letter]/lim OR [note]/lim OR [review]/lim)	Excluding reviews, letters, commentary, and searches will include all countries 2012 onward	1853
#23	#21 NOT #22		3284
#24	#23 AND [2012–2016]/py	Studies for all the key regions of interest will be included post-2012: Latin America, Middle East, Eastern Europe, and Asia-Pacific	932
#25	#23 AND [<1966–2011]/py	Excluding studies prior to 2012 in countries already covered in previous review	2345
#26	argentina OR australia OR brazil OR canada OR chile OR china OR india OR israel OR japan OR korea OR malaysia OR mexico OR ‘new zealand’ OR philippines OR russia OR ‘saudi arabia’ OR ‘south africa’ OR taiwan OR thailand OR vietnam OR ‘czech republic’ OR Czechoslovakia OR england OR france OR hungary OR ireland OR poland OR scotland OR ‘slovak republic’ OR slovenia OR turkey OR uk OR ‘united kingdom’ OR wales		15,141,096
#27	#25 NOT #26		1196
#28	#27 OR #24	Final number for vaccination objective	2128

Table 2. Summary of published studies on varicella in CEE.

Source	Country	Study design	Data source	Time frame	Setting	Population	Sample size	Outcomes	Key findings
EUVAC 2010 [24]	Multiple: Bulgaria, Croatia, Cyprus, Czech Republic, Estonia, Finland, Greece, Hungary, Italy, Latvia, Lithuania, Malta, Poland, Romania, Slovakia, Slovenia, Spain, UK	Database/Registry analysis	Surveillance system and questionnaire from 32 countries participating in EUVAC.NET (2007)	2000–2007	General population?	All age groups	NR	Incidence, notifications	592,681 varicella cases reported in 2010 from 18 countries that provided data from mandatory notification systems Highest incidences in Poland, Czech Republic, Estonia, and Slovenia Of cases with known vaccination status, 99.5% were unvaccinated
Hoxha et al, 2010 [26]	Albania	Retrospective	Patients admitted to University Hospital Center	Jan 2004–Dec 2008		Healthy children (<14 years)	68	Length of hospitalization, risk factors, complications	Mean hospitalization of 5.2 days Children aged 1–6 years most affected by complications, which were bacterial overinfections, neurological symptoms, and varicella pneumonia
Robo et al, 2015 [17]	Albania	Prospective	Case reports during varicella outbreaks	2014	General population		186	Seroprevalence	92.5% of cases reported in children <14 years Most occurred during spring and summer (67%) No complications reported 31% of blood samples (N = 9) tested positive for VZV IgM
Komitova et al, 2014 [30]	Bulgaria	Retrospective	Cases admitted to Plovdiv University Hospital, Infectious Diseases Clinic	Jan 2009 – Dec 2013	Inpatients	Children	22	Complications	RTI, thrombocytopenic purpura, cerebellar ataxia, sepsis, and scarlet fever reported Mean hospitalization of 5.7 days
Bakasun and Pahor, 2014 [23]	Croatia	Cross-sectional	Department of Epidemiology, PHI of Rijeka District	1977–2012	General population		321,007	Incidence and distribution of varicella cases	Epidemics reported regularly Highest incidence of 1642 per 100,000 inhabitants registered in 1987 Lowest incidence of 247 per 100,000 inhabitants was registered in 2001 Children aged 5–9 years most affected
Vilibic-Cavlek et al, 2012 [21]	Croatia	Retrospective	Referrals to CNIPH for virology testing	2007–2011		Women of reproductive age (16–45 years)	638	Seroprevalence	IgG seroprevalence of 84.3% Significant increase in IgG seropositivity with increasing age A high proportion (15.7%) of women of child-bearing age are susceptible to VZV
Gowin et al, 2013 [25]	Poland	Retrospective	Hospital records of patients admitted to Children’s Hospital, Poznan, Poland	Jan 2007–Jun 2012	Hospital	Children (<17 years)	224	Causes of hospitalization	Median age of admitted patients was 37.5 months Rates of hospitalization decreased with age 92% of children healthy prior to hospitalization RTI, skin infections, and neurological symptoms the most common complications
Lipke et al, 2013 [27]	Poland	Retrospective	NIPH-NIH, GIS	2013	General population		172,855	Incidence	Incidence in 2011 was 448.7 per 100,000 inhabitants, a reduction from 480.4 per 100,000 inhabitants in 2010 Highest incidence reported in children aged 5–9 years (3708.7/100,000)
Siennicka et al, 2009 [18]	Poland	Prospective	Serum samples from across Poland	1995–2004		1–19 years	1300	Seroprevalence	Overall seroprevalence estimated at 76.6% in those aged 1–19 years Seroprevalence correlated with age (p < 0.0001)
Kuchar et al, 2013 [31]	Poland	Retrospective	Patients admitted to Department of Paediatric and Infectious Diseases (Wroclaw)	2005–2010	Inpatients	Children <18 years	237	Complications	11.8% of children in the cohort were hospitalized with varicella-related respiratory complications None of the children were previously immunized against varicella Mean hospitalization of 5.4 ± 2.0 days
Arama et al, 2005 [22]	Romania	Retrospective	Patient records from IPH in Bucharest	1986–2004			371	Incidence, patient groups	Incidence of varicella increased from 110 per 100,000 inhabitants in 1986 to 369 per 100,000 inhabitants in 1995 Between 2000 and 2004, 49% of cases were in children aged <10 years and 77% in children aged <15 years
Mijailovic et al, 2011 [32]	Serbia	Retrospective	Patients treated at Clinical Centre of Kragujevac	2002–2006	Inpatient	All age groups	390	General frequency of pneumopathies and types of lung changes	25.9% of patients had clinical and/or radiological picture of a varicella pneumopathy. The incidence of varicella pneumopathy was lowest in the age groups of 0–7 and 8–14 years (10.9%), and highest in the age group of >30 (41.6%). The research group comprised 70 males (69.3%) and 31 females (30.7%).
Sočan et al, 2010 [20]	Slovenia	Cross-sectional	Serum samples	2006	General population	0–97 years	3689	VZV IgG antibodies	Overall, 85.6% of serum samples were seropositive Over 90% of children aged 8 years tested positive for VZV 2.8% of serum samples among women of childbearing age were seronegative
Socan and Berginc, 2008 [19]	Slovenia	Retrospective	Blood samples from university students	Nov 2006			256	Vaccination, history of MMR/pertussis	Immunity to varicella established in 97.6% participants
Sočan and Blasko, 2007 [28]	Slovenia	Database/Registry analysis	Notification data	1996–2005		All age groups	NR	Incidence, notifications	Annual notifications ranged from 9120 to 15,538 (incidence: 456 per 100,000 inhabitants to 777 per 100,000 inhabitants) Majority of cases reported (75%) in pre-school children <7 years Low rate of serious complications
Socan et al, 2001 [29]	Slovenia	Retrospective	Case reports; demographic data	1979–1998		All age groups	321,227	Incidence	Reported varicella cases ranged from 11,086 (in 1994) to 21,141 (in 1987) Over last 10 years, highest incidence reported in children aged 1–2 years
Socan, 2010 [35]	Slovenia	Database/Registry analysis	Mandatory notifiable communicable diseases dataset (SURVIVAL), consultations in primary care dataset (ZUBSTAT) and hospitalizations dataset (BOLOB)	1997–2006	General population	General population (all age groups)	128,222	Incidence, notifications	168,089 cases were recorded via ZUBSTAT, and 128,222 cases by SURVIVAL On average, 76.2% were notified Notified incidence was highest for preschool children Low number of hospitalized cases; 74% were reported

CEE, Central and Eastern Europe; CNIPH, Croatian National Institute of Public Health; EUVAC, European surveillance network for selected vaccine-preventable diseases; GIS, Główny Inspektorat Sanitarny (Chief Sanitary Inspectorat); IgG, Immunoglobulin G; IgM, Immunoglobulin M; IPH, Institute of Public Health; MMR, measles, mumps, rubella; NIPH-NIH, National Institute of Public Health-National Institute of Hygiene; NR, Not reported; PHI, Public Health Institute; RTI, Respiratory tract infection; VZV, Varicella zoster virus.

Figure 1. Flow of studies through the review process.

Figure 2. Seroprevalence (with 95% confidence intervals) of VZV IgG antibodies* in Croatian women of reproductive age [21].

IgG, Immunoglobulin G; VZV, Varicella zoster virus.*By commercial enzyme-linked immunosorbent assay. n = positive for VZV IgG antibodies; N = total number tested.

Figure 3. Incidence rate of varicella per 100,000 inhabitants in CEE (2000–2010) [24].

CEE: Central and Eastern Europe.

Figure 4. Seasonality of varicella in Croatia (1977–2012). Reproduced, with permission, from Vjekoslav Bakašun and Đana Pahor, ‘Epidemiological Patterns of Varicella in the Period of 1977 to 2012 in the Rijeka District, Croatia’, Epidemiology Research International, vol. 2014, Article ID 193,678 [23].

Figure 5. Percentage of persons of all ages with varicella who were hospitalized across CEE (2008–2010) [24].

Table 3. Recommendations for varicella vaccination in different CEE populations.

Country	Target group
Cyprus	Children at 13–18 months and at 4–6 years (private sector only) Susceptible individuals and/or high-risk groups and susceptible health care workers
Estonia	Medical-risk group Susceptible persons Persons with acute lymphocytic leukemia in remission Persons with leukemia (recommended for seronegative children aged under 12 years) Candidates for organ transplantation (recommended for seronegative children aged under 12 years) Persons before chemotherapy (recommended for seronegative children aged under 12 years)
Latvia	Universal vaccination (single-dose) at 15 months
Lithuania	Children and susceptible individuals (private sector only) Susceptible health care workers Before solid organ transplantation with no signs of immunity against varicella Household contacts of allogenic bone marrow transplantation recipients HIV infected persons with CD4 count >200/mm^3
Poland	Specific-risk group Medical-risk group Susceptible persons Seronegative women of childbearing age Immunocompromised persons (mandatory for children aged under 12 years) Persons with acute lymphocytic leukemia in remission (mandatory for children aged under 12 years) Persons infected with HIV (mandatory for children aged under 12 years) Persons before chemotherapy (mandatory for children aged under 12 years) Seronegative family members of high-risk children (mandatory for children aged under 12 years) Seronegative close contacts of immunosuppressed individuals (mandatory for children aged under 12 years)
Slovakia	Patients before biological therapy or chemotherapy (e.g. idiopathic bowel diseases, rheumatic diseases, oncologic diseases) Candidates for organ transplantation Seronegative women with planned pregnancy Seronegative close contacts of high-risk patients Susceptible health care workers
Slovenia	Medical-risk group Persons with acute lymphocytic leukemia in remission Candidates for organ transplantation Seronegative family members of high-risk children Susceptible health care workers Recommended for children who have not had varicella prior to starting immunosuppressive treatment Close contacts of immunocompromised individuals

CEE: Central and Eastern Europe; HIV: human immunodeficiency virus.

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