Risk factors for varicella susceptibility among refugees to Toronto, Canada


I Background
II Methods
III Results
IV Discussion
V Conclusions

Submitted by

  • Geneviève Cadieux, Public Health & Preventive Medicine Resident, Dalla Lana School of Public Health, University of Toronto
  • Vanessa Redditt, Department of Family and Community Medicine, University of Toronto
  • Daniela Graziano, Faculty of Health Sciences, McMaster University
  • Meb Rashid, Department of Family and Community Medicine, University of Toronto; and Crossroads Clinic, Women's College Hospital

I Background

About 250,000 immigrants arrive in Canada every year; of those, close to 30,000 are refugees and refugee claimants [1]. In 2013, the top countries from which refugees claimants originated included China, Syria, Pakistan, Somalia, Eritrea, Afghanistan, Sri Lanka, and Hungary [2]. Canadian immigration legislation requires that all refugees and refugee claimants receive an immigration medical examination [3]. The purpose of this examination is to assess potential burden of illness, and to screen for public health risks (specifically tuberculosis, syphilis, and HIV); this examination is not designed to provide clinical prevention services [4]. Refugees to Canada frequently face barriers to local health services [1,5] and experience an increased risk of morbidity and mortality, especially from infectious diseases and their complications [6].

One such infectious disease is chickenpox (varicella). Varicella occurs at an older age in tropical climates [7], and the risk of complications, hospitalization and death from varicella increases with age [8–10]. Migrants to North America and Europe are not routinely immunized against varicella; therefore, migrants from tropical climates are more likely to be susceptible to varicella than Canadians [11,12]. As a result, more cases of varicella occur among the foreign-born than among those born in Canada [13], and several outbreaks of severe varicella have occurred among young adult migrants [14–20].

Strategies for preventing varicella among migrants can be grouped into five approaches; ranked from most to least costly, they are: 1) universal immunization of all migrants, 2) selective immunization of high-risk migrants (without serotesting), 3) no intervention, 4) universal serotesting of all migrants followed by immunization of susceptible individuals, and 5) selective serotesting of high-risk migrants followed by immunization of susceptible individuals [21]. Therefore, implementing the most cost-effective approach requires the accurate identification of migrants at increased risk of varicella susceptibility. In this cost-effectiveness study [21], the only risk factor for varicella susceptibility used to identify which migrants to serotest was the absence of a history of chickenpox.

However, several risk factors for varicella susceptibility have been investigated among migrants, including younger age [11,12], tropical climate [12], shorter time since arrival [12], absence of a clinical history of chickenpox [22,23], lower household crowding [12], lower population density, rural area of residence [24], and lower socio-economic status. However, refugees differ from other classes of migrants in that they are more likely to have experienced persecution [25]; as a result, their migration trajectories likely involved living conditions with crowding and/or poor sanitation (e.g., refugee camps) that foster the spread of infectious diseases like varicella [14,26,27]. Previous studies of varicella susceptibility have not focused specifically on refugees. The objectives of the present study were: 1) to estimate the prevalence of varicella susceptibility among refugees to Toronto, Canada, and 2) to identify risk factors for varicella susceptibility among these refugees.

II Methods

Study design, setting, and population
This was a retrospective review of the electronic health records (EHR) of all refugees and refugee claimants rostered at Crossroads Clinic from its opening on December 1, 2011 until June 23, 2014 (2.5 years). Crossroads Clinic provides full primary care services exclusively to refugees and refugee claimants during their first two years in Toronto. After this period, patients are connected with a family doctor in their community. Crossroads Clinic is affiliated with the Department of Family Medicine at the University of Toronto, and located at Women’s College Hospital.

Data collection
All patient encounters at Crossroads Clinic are logged using an EHR (Practice Solutions Software Inc.). Review of the EHR was performed using a standardized questionnaire; some answers were obtained through programmed searches of standardized variable fields (e.g., varicella serology, date of birth) whereas others required manual review of free-text entries (e.g., country of origin, date of arrival to Canada). All chart review data was entered into an anonymized Excel spreadsheet; a separate lookup table was used to link patient’s anonymized study identifier with their medical record number. All chart review data was encrypted and kept in a safe location.

Varicella susceptibility
A laboratory requisition including varicella serology was provided to patients at the time of the initial visit to Crossroads Clinic; blood samples were drawn that same day or shortly thereafter. All varicella serology testing was performed by the Ontario Public Health Laboratory. For the purposes of the present study, non-reactive tests were categorized as varicella susceptible, whereas reactive and indeterminate tests were categorized as varicella non-susceptible. Refugees with missing varicella serology were excluded from multivariate regression analyses.

Potential risk factors for varicella susceptibility
Potential risk factors for varicella susceptibility included age, sex, education level, time since arrival in Canada, country of birth, country of origin, secondary migrant status (i.e., country of origin different from country of birth), as well as geographic region, climate, population density, Human Development Index (HDI) and Gross Domestic Product (GDP) per capita of both country of birth and country of origin. Age was calculated by subtracting the patient’s documented date of birth from the date of the initial visit to Crossroads Clinic. Sex was obtained from the patients’ EHR. Country of birth and country of origin (i.e., the last country resided in before immigrating to Canada) were documented as free-text in the EHR. Geographic regions of country of birth and country of origin were assigned using the World Bank’s classification of development regions. Climate of the country of birth and country of origin were assigned using a previously published reference table [12]; this reference table assigns a single climate (in which ≥50% of the country’s population lives) to each country. Population density and GDP per capita of the country of birth and country of origin (measured as the number of persons per square kilometer of land area) was obtained from the World Bank [28]. HDI of the country of birth and country of origin was obtained from the United Nations Development Programme [29]. Highest educational attainment was obtained from the EHR and classified as child aged less than 18 years, or as adult with no education, some elementary school education, some secondary school education, some post-secondary school education or missing educational level. Time since arrival in Canada was calculated by subtracting the patient’s date of arrival in Canada (as documented in the EHR) from the date of their initial visit to Crossroads Clinic. Refugees with missing values for any of these potential predictors of varicella susceptibility were excluded from multivariate regression analyses.

Statistical analyses
The prevalence of varicella susceptibility was calculated with 95% confidence intervals (CI) among all patients who underwent serology testing. Multivariate logistic regression analyses, adjusting for all potential risk factors, were used to identify risk factors for varicella susceptibility. All analyses were conducted with SAS version 9.3 (SAS Institute Inc., USA).

This project was reviewed and approved by the Research Ethics Board of the Toronto Academic Health Sciences Network.

III Results

A total of 1,063 patients were rostered at Crossroads Clinic during the study period, of which 56.3% were female. Among the adults, 53 (5.0%) had no formal education or some primary education, 417 (39.2%) had some secondary education, and 245 (23.0%) had some post-secondary education. Refugees rostered at Crossroads Clinic were born in 87 different countries. A total of 669 (62.9%) refugees had the same country of birth and country of origin, and 898 (84.5%) had the same region of birth and region of origin. About one in five refugees (21.1%) were born in a country with a tropical climate. On average, refugees had been in Canada for six months (SD 7.2 months) at the time of their first visit to Crossroads Clinic.

A total of 812 (77%) refugees had varicella serology available. The 2011 recommendation of the Canadian Collaboration for Immigrant and Refugee Health is to vaccinate all persons aged 12 years or younger without serotesting [30] (30); 161 of 251 (64.1%) refugees without varicella serology were children aged 12 years or younger. Among the 812 refugees who underwent serology testing, 64 were susceptible to varicella, for a varicella susceptibility prevalence of 7.9% (95% confidence interval [CI] 6.1, 9.7). Among refugees susceptible to varicella, the median age was 17 years and the age range was 0–42 years. We found that 25 (33.3%) of 75 refugees aged 12 years and younger were susceptible to varicella.

A total of 782 refugees without missing data were included in the regression analyses; these refugees were similar to the total population of refugees rostered at Crossroads Clinic, except for their age. In accordance with the 2011 recommendation of the Canadian Collaboration for Immigrant and Refugee Health [30], children aged 12 and younger were less likely to have undergone varicella serology testing. Multivariate regression analyses revealed that refugees born in a country with tropical climate were three times more likely to be susceptible to varicella than those born in a country with a non-tropical climate. Also, younger refugees were more likely to be susceptible to varicella; varicella susceptibility decreased by 8% with every additional year of age.

IV Discussion

This study sought to 1) estimate the prevalence of varicella susceptibility, and 2) identify risk factors for varicella susceptibility among refugees newly arrived to Toronto, Canada. We found the prevalence of varicella susceptibility among refugees rostered at Crossroads Clinic to be 7.9%. In comparison, a population-based seroprevalence study of the general population in the USA has a similar temperate climate, estimated varicella susceptibility to be 2.2%, 95% CI (1.7%-2.9%) [31]. Other recent studies of immigrants and refugees to Montreal and the United States found 6% and 3% of individuals to be susceptible to varicella, respectively [12,32]. With respect to risk factors for varicella susceptibility, we found that refugees from tropical climates were three times more likely to be susceptible to varicella; this is consistent with results from a study of immigrants to Montreal [12]. It is not well understood why varicella occurs at an older age in the tropics; hypotheses to explain this common observation include virus inactivation at higher temperatures and epidemiologic interference from other viruses [24]. We also found that refugees' likelihood of being susceptible to varicella decreased by 8% with every additional year of age. Increasing varicella immunity with increasing age is a widely observed trend [10].

Our identification of age and tropical climate of birth as important risk factors for varicella susceptibility should inform future efforts to prevent varicella incidence among refugee populations. For example, the latest recommendations from the Canadian Collaboration for Immigrant and Refugee Health [30] concerning varicella advise universal immunization of all refugees aged 12 years and younger; however, in our sample, two-thirds of children aged 12 years and younger were already immune to varicella, therefore following this recommendation would likely lead to unnecessary immunization. Future research should identify the combination of risk factors that best predicts varicella susceptibility among refugees; this would likely include age and climate of birth. A varicella susceptibility "risk score" could be estimated, and risk scores could be categorized to help guide preventive interventions: e.g., low risk – no intervention, moderate risk – serotest then immunize if susceptible, high risk – immunize without serotesting.

V Conclusions

Through a large retrospective review of the electronic health records of all refugees rostered at Crossroads Clinic in Toronto, Canada, we found that younger refugees and refugees from tropical climates were more likely to be susceptible to varicella. A combination of these and other risk factors for varicella susceptibility, perhaps summarized as a "risk score", should be taken into account to maximize the cost-effectiveness of varicella prevention among refugees.

For more information, the full article is available at http://link.springer.com/article/10.1007%2Fs10903-015-0313-y.


  1. Gushulak B, Pottie K, Hatcher Roberts J, Torres S, DesMeules M. Migration and health in Canada: health in the global village. CMAJ 2011 June 9;183(12):E952-E958.
  2. REHAAG, S. 2013 Refugee Claim Data and IRB Member Recognition Rates. http://ccrweb.ca/en/2013-refugee-claim-data. Accessed 4-8-2015.
  3. Statutes of Canada. Immigration and Refugee Protection Act. http://laws-lois.justice.gc.ca/eng/acts/I-2.5/page-1.html. Accessed 4-8-2015.
  4. Citizenship and Immigration Canada. Panel Members' Handbook 2013 . http://www.cic.gc.ca/English/resources/publications/dmp-handbook/index.asp . Accessed 3-25-2015.
  5. SanMartin C, Ross N. Experiencing Difficulties Accessing First-Contact Health Services in Canada. Healthcare Policy 2006 January;1(2):103-19.
  6. DesMeules M, Gold J, McDermott S, Cao Z, Vissandjée B, Kliewer E, Mao Y. Disparities in mortality patterns among Canadian immigrants and refugees, 1980–1998: results of a national cohort study. Journal of Immigrant Health 2005;7(4):221-32.
  7. Sengupta N, Breuer J. A global perspective on the epidemiology and burden of varicella-zoster virus. Current Pediatric Reviews 2009;5:207-28.
  8. Choo P, Donahue J, Manson J, Platt R. The epidemiology of varicella and its complications. J Infect Dis 1995 September;172(3):706-12.
  9. Galil K, Brown C, Lin F, Seward J. Hospitalizations for varicella in the United States, 1988 to 1999. Pediatric Infectious Diseases Journal 2002 October;21(10):931-5.
  10. Heymann DL. Varicella/Herpes Zoster. In: Heymann DL, editor. Control of Communicable Diseases Manual. 20 ed. Washington, D.C.: American Public Health Association Press; 2015. p. 669-75.
  11. Barnett E, Christiansen D, Figueira M. Seroprevalence of Measles, Rubella, and Varicella. Clinical Infectious Diseases 2002 August 15;35:403-8.
  12. Greenaway C, Boivin J, Cnossen S, Rossi C, Tapiero B, Schwartzman K, Olson S, Miller M. Risk factors for susceptibility to varicella in newly arrived adult migrants in Canada. Epidemiol Infect 2014 August;142(8):1695-707.
  13. Okrainec K, Vissandjee B, DesMeules M, Holcroft C, Bartlett G, Greenaway C. Epidemiology of Varicella Infection Among the Foreign Born in Quebec. Canadian Journal of Infectious Disease and Medical Microbiology 2010;21(4):173-230.
  14. Haas E, Dukhan L, Golstein L, Lyandres M, Gdalevich M. Use of vaccination in a large outbreak of primary varicella in a detention setting for African immigrants. Int Health 2014;6:203-7.
  15. Centers for Disease Control and Prevention (CDC). Public Health Dispatch: Varicella Outbreaks among Mexican Adults -- Alabama, 2000. MMWR Morb Mortal Wkly Rep 2000 August 18;49(32):735-6.
  16. Longfield JN, Winn RE, Gibson RL, Juchau SV, Hoffman PV. Varicella outbreaks among Army recruits in Puerto Rico. Varicella susceptibility in a population from the tropics. Ann Intern Med 1990 May;150(5):970-3.
  17. Gabutti G, Fedele A, Aprile V, Guido M, Lopalco P. Immigration flows and new epidemiological evidence in southern Italy. Vaccine 2003 January 17;21(5-6):399-400.
  18. Kjersem H, Jepsen S. Varicella among immigrants from the tropics, a health problem. Scand J Soc Med 1990 September;18(3):171-4.
  19. Deny P, Leport C, Jestin C. Chickenpox in one hundred Sri Lankan immigrants in France. Médecine et maladies infectieuses 1986;16:595-8.
  20. Hastie I. Varicella-zoster virus affecting immigrant nurses. Lancet 1980;2:154-5.
  21. Merrett P, Schwartzman K, Rivest P, Greenaway C. Strategies to Prevent Varicella among Newly Arrived Adult Immigrants and Refugees: A Cost-Effectiveness Analysis. Clinical Infectious Diseases 2007 April 15;44:1040-8.
  22. Christiansen D, Barnett E. Comparison of varicella history with presence of varicella antibodies in refugees. Vaccine 2004;22:4233-7.
  23. MacMahon E, Brown LJ, Bexley S, Snashall DC, Patel D. Identification of potential candidates for varicella vaccination by history: questionnaire and seroprevalence study. BMJ 2004 September 4;329(7465):551-2.
  24. Mandal B, Mukherjee P, Murphy C, Mukherjee R, Naik TN. Adult Susceptibility to Varicella in the Tropics Is a Rural Phenomenon Due to Lack of Previous Exposure. J Infect Dis 1998;178(Suppl 1):S52-S54.
  25. United Nations HIgh Commissioner for Refugees (UNHCR). Convention and protocol relating to the status of refugees. http://www unhcr org/3b66c2aa10 html 1951;Available from: URL: http://www.unhcr.org/3b66c2aa10.html
  26. Shimakawa Y, Camelique O, Ariyoshi K. Outbreak of chickenpox in a refugee camp of Northern Thailand. Conflict and Health 2010;4(4).
  27. Mishra AK, Gorbacheva O, Hasan MMT, Rimal N. Varicella (Chickenpox) outbreak in Bhutanese refugee camps in Eastern Nepal. Int J Infect Dis 2010;14(suuplement 1):e134.
  28. The World Bank. Data: Population density (people per sq. km of land area). http://data.worldbank.org/indicator/EN.POP.DNST. Accessed 4-5-2015.
  29. United Nations Development Programme. Human Development Index (HDI). http://hdr.undp.org/en/content/human-development-index-hdi. Accessed 10-18-2015.
  30. Pottie K, Greenaway C, Feightner J, Welch V, Swinkels H, Rashid M, Narasiah L, Kirmayer L, Ueffing E, MacDonald N, Hassan G, McNally M, Khan K, Buhrmann R, Dunn S, Dominic A, McCarthy A, Gagnon A, Rousseau C, Tugwell P, and coauthors of the Canadian Collaboration for Immigrant and Refugee Health. Evidence-based clinical guidelines for immigrants and refugees. CMAJ 2011 September 6;183(12):E824-E925.
  31. Lebo EJ, Kruzson-Moran DM, Marin M, Bellini WJ, Schmid S, Bialek SR, Wallace GS, McLean HQ. Seroprevalence of measles, mumps, rubella and varicella antibodies in the United States population, 2009-2010. Open Forum Infectious Dis 2015 February 20;2(1):ofv006.
  32. Leung J, Lopez A, Mitchell T, Weinberg M, Lee D, Thieme M, Schmid D, Bialek S. Seroprevalence of Varicella-Zoster Virus in Five US-Bound Refugee Populations. J Immigrant Minority Health 2015;17:310-3.