Re-Evaluation of Immune Status to Measles, Mumps and Rubella Viruses in the Canada HealthSurvey Population and the Indochinese Refugee PopulationAuthor(s): PETER W. NEUMANN and JOHN M. WEBERSource: Canadian Journal of Public Health / Revue Canadienne de Sante'e Publique, Vol. 75, No.4 (July/August 1984), pp. 270-272Published by: Canadian Public Health AssociationStable URL: http://www.jstor.org/stable/41988852 .

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Re-Evaluation of Immune Status to Measles, Mumps

and Rubella Viruses in the Canada Health Survey

Population and the Indochinese Refugee Population

PETER W. NEUMANN, Dip. Bact., R.M. (CCM) and JOHN M. WEBER, Ph.D., R.M. (CCM)

The Canadians. Canada Health

Part of Survey1 this study

assessed involved

the health immune

status status

of Canadians. Part of this study involved immune status

determination. The results of the immune status to selected vaccine preventable diseases proved surprising. Based on known vaccination practices and expected naturally

Viral Diagnostic Services Division, Bureau of Microbiology, Laboratory Centre for Disease Control, Health Protection Branch, Health and Welfare Canada, Ottawa, Ontario, Canada Author to whom reprint requests and correspondence about the manuscript should be addressed: Dr. John M. Weber, Chief, Viral Diagnostic Services Division, Bureau of Microbiology, L.C.D.C., Tunney's Pasture, Ottawa, Ontario K1A0L2 (613) 992-6590.

acquired infection, higher levels of immunity were antici- pated. In the 15-19 year age group, only 59% were found reactive to measles by the hemagglutination-inhibition (HI) test. Only 55% of the 10-14 year age category was found immune to mumps by CF. The proportion of the population considered immune to rubella by reactivity in the HI test was higher (86% overall and 92% for the 20-34 year old females).

The low levels of immunity reported by the CHS 1 particu- larly for measles and mumps, might reflect the relative insensitivity of the HI and CF tests. Development of the more sensitive SRH tests for measles2, mumps3 and rubella4,

270 Canadian Journal of Public Health Vol. 75, July/ August 1984

Prevalence of antibody to measles , mumps and rubella in population groups in Canada was determined using single radial hemolysis (SRH), the complement fixation (CF) or the hemagglutination-inhibition (HI) test . Sam- ples from the Canada Health Survey (CHS) and from the Indochinese Refugees (ICR) admitted to Canada in 1980 differed with respect to measles reactivity measured by the HI test: 53% (CHS) and 62% (ICR). Corresponding measles SRH reactivity for the two samples was much higher (95% and 99%). Mumps reactivity as measured by the CFtest was 43% (C HS) and 53% (IC R). Correspond- ing levels by SRH were 73% (CHS) and 80% (ICR). More than twice as many ICR in the prime childbearing years (20-34 years) were found non-immune to rubella by H I as in the CHS sample (21% vs 8%). In contrast to the reported equivalence between SRH and HI in rubella serology, these SRH data imply that the CF and HI tests for mumps and measles antibody appear to have greatly underestimated the immunity of the populations sampled.

La prévalence des anticorps de la rougeole, des oreil- lons et de la rubéole a été déterminée dans certains groupes de population au Canada au moyen des tech- niques ď hémolyse radiale simple (H RS), de fixation du

complément (FC) et d'inhibition de l'hémagglutination (IH). Le test 1 H a permis de déterminer que la réactivité à la rougeole de sujets de l'enquête Santé Canada (ESC) et de réfugiés indochinois (RI) admis au Canada en 1980 était différente; les résultats obtenus étaient en effet de 53% chez le premier groupe (ESC) et de 62% chez le second ( RI). L'évaluation de la réactivité à la même mala- die, mesurée chez les deux mêmes groupes de sujets mais cette fois par la méthode H RS, a donné des résultats beaucoup plus élevés (95 et 99% respectivement). La réactivité aux oreillons, mesurée par le test FC, a donné des résultats de 43% chez le premier groupe, et de 53% chez le second , alors que l'évaluation par H RS a donné des taux respectifs de 73 et 80% chez les deux groupes. Par rapport aux sujets de l'enquête Santé Canada, plus de deux fois plus de réfugiées indochinoises âgées de 20 à 34 ans (principale période de procréation) n'étaient pas, selon les résultats du test IH, immunisées en regard de la rubéole (les taux étaient respectivement de 8 et de 21% dans les deux groupes). Contrairement à certaines données publiées signalant une équivalence des résultats sériologiques obtenus pour la rubéole par les méthodes H RS et IH, ces nouvelles données obtenues par la tech- nique H RS laissent entrevoir que les tests FC et IH effectués, pour déceler les anticorps des oreillons et de la rougeole auraient grandement sous-estimé l'immunité réelle des populations échantillonnées.

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permitted the use of this technique to re-examine serum samples from the CHS. In addition, the CF, HI and SRH tests were used to establish measles, mumps and rubella immunity levels in the Indochinese refugees (ICR) admitted to Canada in 1980.

METHOD AND MATERIALS

Measles HI tests were conducted by the method of Ger- shon and Krugman.5 The procedure for the rubella HI test is described by Halonen et al.6 Mumps CF was performed by the micro-Kolmer method.7

In the SRH test, sera are added to wells in an agarose gel containing antigen-sensitized red blood cells. In the pres- ence of complement, sera produce areas of hemolysis pro- portional to the concentration of specific antibody. Measles SRH conducted on CHS sera was performed using methods and materials provided by Robert Devine, and the staff of the Provincial Laboratory of Public Health, Edmonton, Alberta. Measles SRH testing of the ICR sera was per- formed in that laboratory. The mumps SRH test was per- formed using the method of Grillner and Blomberg.3

Since SRH and HI tests have been shown to give compar- able results,4 only the HI test was used for rubella immune status determination. In a sample of 189 ICR sera, 188 produced identical immune status results by both HI and SRH. With the exception of rubella in the CHS report where ̂1:8 was considered to indicate inadequate protec- tion, sera reactive for the three viruses at ̂ 1:8 dilutions in the CF and HI tests were considered predictive of immunity. The CHS reported that 93% of those persons having a titre of^l:8 had a titre of < 1 :8. Therefore, for ease of compari- son, CHS figures for rubella in this report have been adjusted to reflect this; that is, the percentage of individuals reported as having a titre of ̂ 1 :8 has been multiplied by 0.93 to yield the percentage considered to be antibody negative. Moreover, the CHS data contained a percentage for which antibody titres were designated "unknown". Hence all CHS data cited in this report have been adjusted to show only results from tests with known titres. For measles and mumps SRH, hemolytic zone diameters >5.0 mm exceeded that resulting from occasional non-specific reactivity and were considered to represent real antibody and hence immunity.

Canada Health Survey Population. An age-sex standard- ized sub-sample of 106 sera was drawn from the 912 sera which had been tested for measles antibody by HI in the CHS. The percentage positive for measles HI antibody in the sub-sample was 52%. These were re-tested by SRH. Similarly SRH was performed on 153 serum samples selected from the 1,068 sera tested by CF for mumps anti- body determination. The mumps sub-sample chosen gave 56% reactivity by CF.

Indochinese Refugees. All of the approximately 12,000 ICR admitted to Canada via Longue Pointe (Montreal, Quebec) during the first six months of 1980, were bled and tested for hepatitis B markers by Chaudhary et a/.8 A sample

of 1080 of these were screened for measles, mumps and rubella antibody using the CF and HI tests. Equal numbers of randomly selected males and females for age groups 10-19, 20-29 and 30-39 years were chosen. A sub-sample of 163 randomly drawn sera from individuals with the same age-sex distribution was re-tested using measles SRH; 61% of the sub-sample was reactive by HI. Similarly an addi- tional sub-sample of 1 22 sera from the 1 080 sera was chosen for mumps SRH testing. This sub-sample was 56% reactive by CF.

RESULTS

Measles The Canada Health Survey data on measles immunity

indicated that only 53% of the Canadian population sample was reactive by HI and hence considered to be immune. However, 95% of sera tested by SRH were reactive (Table I). Differing abilities of the two tests to detect measles reactive antibody in the ICR sample were observed (62% reactive by HI; 99% by SRH). No striking differences between males and females were seen in either population. In the ICR samples tested, fewer individuals in the 30-39 year categories had antibody (55%) by HI than in the younger age groups where 66% ( 10-19 years) and 64% (20-29 years) had reactive antibody. The one non-reactive serum by SRH was from a 21 year old female.

Mumps The percentage of reactive individuals in both the CHS

and ICR samples tested by CF was considerably less than that found with SRH (Table II). In the CHS sample 43%

TABLE I Presence of Antibody to Measles as Determined by Single Radial Hemolysis (SRH) and Hemagglutination-inhibition (HI) Tests in Canada Health Survey (CHS) and Indochinese

Refugee (ICR) Population Samples

Population and Numbers (Percentages) CHS ICR

Antibody Antibody Test Positive Negative Positive Negative "HI 483 (53)* 429 (47)* 670 (62) 410(38) SRH 101 (95) 5 (5) 162 (99) 1 (1) ♦Figures from Canada Health Survey1

TABLE II Presence of Antibody to Mumps as Determined by Single Radial Hemolysis (SRH) and Complement-fixation (CF) Tests in Canada Health Survey (CHS) and Indochinese

Refugee (ICR) Population Samples Population and Numbers (Percentages)

CHS ICR Antibody Antibody

Test Positive Negative Positive Negative ~CF 459 (43)* 609 (57)* 567 (53) 513 (47) SRH 1 1 1 (73) 42 (27) 98 (80) 24 (20) ♦Figures from Canada Health Survey1

July/August 271

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were reactive by CF whereas 73% were positive by SRH. In the ICR sera examined, 80% were reactive by SRH but only 53% by CF. The existence of detectable mumps antibody in both the ICR and CHS sera appeared to be unrelated to the age or sex of the individual.

Rubella In the three age groups (Table III), the CHS showed an

increase in percentage of antibody positive females with increasing age. The ICR data showed no such trend, but in all age categories the proportion of individuals with antib- ody to rubella was lower than in the corresponding CHS figures.

In the prime childbearing years (20-34 years) the percen- tage in the ICR sample lacking detectable rubella antibody was more than twice that of the CHS. Of the ICR males in the same age group, 83% were reactive. The CHS did not examine males in this age group.

DISCUSSION

Individuals in the CHS population sample had a much higher level of immunity to rubella than that found in the ICR sample (Table III) and this difference increases with age. In the 20 to 34 year age category 2 1 % of the ICR women sampled were non-immune compared to 8% of the CHS females. The increasing level of immunity with age in the Canadian sample may reflect efforts to vaccinate susceptible adolescents and women in their early childbearing years or it may also indicate development of immunity through expo- sure to rubella by natural infection. That no such trend of increased immunity with age occurs in the ICR data may reflect the previously inadequate rubella vaccination pro- grams for potential mothers in this population or a reduced risk of exposure.

TABLE III Presence of Rubella Hemagglutination-Inhibiting (HI)

Antibody in Canada Health Survey (CHS) and Indochinese Refugee (ICR) Population Samples (Females Only)

Population and Numbers (Percentages) Age (years) CHS* ICR

Antibody Antibody Positive Negative Positive Negative

10- 19 469 (85) 83 (15) 139 (77) 41 (23) 20- 24 220(90) 25 (10) 74(76) 24(24) 25 - 34 440 (94) 28 (6) 157 (80) 38 (20) 20- 34 660 (92) 53 (8) 231(79) 62 (21) ♦Figures from The Canada Health Survey1 adjusted to reflect the CHS observation that 93% of those persons having a titre of ̂1:8 have a titre of <1:8.

These results demonstrate that the prevalence of humoral antibody (and inferred immunity) to measles and mumps

may be underestimated by conventional serological methods (H I and CF). However, the data indicating a much higher rate of detection of mumps or measles antibody by SRH compared to CF and H I testing does not cast doubt on the technical adequacy of the original CHS testing since a similar relationship was observed in an independent popula- tion sample (ICR). Moreover, these data do not preclude the use of CF or HI tests in diagnostic serology, where changes from seronegativity to seropositivity post-infection are usu- ally dramatic. Nevertheless, where decisions regarding vac- cination programs are to be based upon data collected from immune status surveys, it is imperative that the data be accurate. Therefore, tests with high negative predictive value are required; that is, they must be accurate in measur- ing the actual susceptible population. With such tests, absence of detectable antibody usually infers susceptibility, although as indicated by the early CHS data, lack of anti- body detection is not necessarily synonomous with susceptibility.

Data obtained by retesting serum samples taken from the CHS and retested by SRH indicate that less than half as many individuals as was previously thought1 may be sus- ceptible to mumps or measles infections. If the goal of measles elimination is to be met, a sensitive surveillance method is needed to detect non-immune portions of a popu- lation so that vaccination programs can be directed to truly susceptible individuals.

Acknowledgements We are grateful to Barbara Benning, Theresa Sapp and Lewis Massad for technical

assistance and to D. Kennedy and P. Varughese for comments on the manuscript.

REFERENCES I. Health and Welfare Canada and Statistics Canada. The Health of

Canadians. Report of the Canada Health Survev. June, 1981. 2. Wesselen L. Demonstration of antibodies to measles virus by hemolysis-

in-gel (HIG) test. Scan J Infect Dis 1978; 10: 15-20. 3. Grillner Land Blomberg J. Hemolysis-in-geland neutralization tests for

determination of antibodies to mumps virus. J Clin Microbiol 1 976; 4: 11-15.

4. Neumann PW and Weber JM. Single radial hemolysis test for rubella immunity and recent infection. J Clin Microbiol 1983; 17: 28-34.

5. Gershon AA and Krugman S. In: Lennette EH and Schmidt NJ, eds. Diagnostic procedures for viral, rickettsial and chlamydial infections. Washington: American Public Health Association, 1979: 665-693.

6. Halonen PE, Ryan J M and Stewart JA. Rubella hemagglutinin pre- pared with alkaline extraction of virus grown in suspension culture of BHK-21 cells. Proc Soc Exp Biol Med 1967; 125: 162-167.

7. Lennette EH, Melnick JL and Magoffin RL. In: Lennette EH, Spauld- ing RH and Truant JP, eds. Manual of clinical microbiology, second edition. Washington: American Society fór Microbiology, 1974: 667-677.

8. Chaudhary RK, Nicholls ES and Kennedy DA. Prevalence of hepatitis B markers in Indochinese refugees. Can Med Assoc J 1981; 125: 1243-1246.

Received: September 23, 1983 Accepted: November 22, 1983

272 Canadian Journal of Public Health Vol. 75

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