ORIGINAL RESEARCH * NOUVEAUTES EN RECHERCHE
An anonymous seroprevalence survey of HIV infection among pregnant women in British Columbia and the Yukon Territory Martin T. Schechter,* MD, MSc, PhD; Penny J. Ballem,tt MD, FRCPC; Noel A. Buskard,tf MD, FRCPC; Thinh N. Le,* BSc; Mai Thompson,* MSc; Stephen A. Marion,* MD, MS, MHSc, FRCPC; Michael V. O'Shaughnessy,§ PhD We performed an anonymous seroprevalence survey of human immunodeficiency virus (HIV) type 1 infection through HIV antibody testing of blood samples from 22 512 women aged 15 to 44 years receiving prenatal care in British Columbia and the Yukon Territory from Mar. 15 to Sept. 30, 1989. Of the samples six were confirmed to be HIV positive; this yielded a crude overall seroprevalence rate of 2.7 per 10 000 pregnant women (95% confidence interval [CI] 1.0 to 5.8). All of the positive samples were from women 20 to 29 years of age; four were from Vancouver, one was from Victoria, and one was from elsewhere. The highest seroprevalence rates were among women aged 15 to 29 years in Vancouver and Victoria (7.2 and 9.4 per 10000 pregnant women respectively). Thus, 1 in 1300 pregnant women in that age group in the metropolitan areas of British Columbia was HIV positive. Application of seroprevalence rates to the total female population in British Columbia and the Yukon Territory revealed that as many as 401 women had HIV infection in 1989. Our estimates likely represent the minimum. As a subset of women of childbearing age pregnant women are likely at lowest risk of HIV infection, and so the true number of women 15 to 44 years of age with HIV infection is probably several times higher. Our study has provided a baseline assessment and will be repeated annually to analyse trends in HIV seroprevalence among pregnant women in British Columbia and the Yukon Territory. Nous avons fait une etude anonyme de seroprevalence des infections par le virus d'immunodeficience humaine (VIH) type 1 par l'evaluation des anticorps au VIH de prelevements sanguins de 22 512 femmes agees de 15 a 44 ans en soins prenataux en Colombie-Britannique et au Yukon du 15 mars au 30 septembre 1989. Parmi les echantillons analyses, six se sont averes seropositifs, ce qui donne un taux global brut de seroprevalence de 2,7 par 10 000 femmes enceintes (intervalle de confiance [IC] a 95% de 1,0 a 5,8). Tous les echantillons positifs provenaient de femmes agees de 20 a 29 ans; quatre etaient de Vancouver, une etait de Victoria, et une etait d'une autre localite. Les taux les plus eleves de seroprevalence se situaient chez les femmes agees de 15 a 29 ans a Vancouver et a Victoria (7,2 et 9,4 par 10 000 femmes enceintes respectivement). Ainsi, 1 femme enceinte sur 1300 de ce groupe d'age dans les regions metropolitaines de la Colombie-Britannique etait seropositive. L'application des taux de seroprevalence a la population feminine totale de la Colombie-Britannique et du Yukon a laisse voir que 401 femmes avaient contracte une infection par le VIH en 1989. Nos evaluations representent probablement un minimum. En tant que sous-echantillon des femmes en From *the Department of Health Care and Epidemiology and tthe Department of Medicine, Faculty ofMedicine, University of British Columbia, Vancouver, tthe Canadian Red Cross Society Blood Transfusion Service - Vancouver Centre, and §the Bureau of Laboratories and Research, Federal Centre for AIDS, Department ofNational Health and Welfare, Ottawa
Reprint requests to: Dr. Martin T. Schechter, Faculty of Medicine, University of British Columbia, 5804 Fairview Ave., Vancouver, BC V6T I W5 -
For prescribing information see page 1251
CAN MED ASSOC J 1990; 143 ( 11)
1187
age de procr6er, les femmes enceintes courent probablement le moins de risque d'infection par le VIH, de sorte que le nombre reel de femmes agees de 15 a 44 ans atteintes d'une infection par le VIH est probablement plusieurs fois plus eleve. Notre etude permet une evaluation de base et sera repetee annuellement pour analyser les tendances de la seroprevalence au VIH chez les femmes enceintes en Colombie-Britannique et au Yukon.
S urveillance of human immunodeficiency virus (HIV) type 1 infection in Canada has relied primarily on surveillance of the end-stage condition, acquired immunodeficiency syndrome (AIDS). AIDS surveillance has provided an incomplete and delayed indication of the scope of HIV infection across the country. Accurate estimates of the number of infected Canadians are necessary for several reasons. First, only by establishing such estimates and then monitoring them can one track the rate of change of the epidemic. Second, precise serial estimates within certain transmission groups will be critical in evaluating the effectiveness of various interventions to prevent the spread of HIV. Finally, accurate estimates will allow the rational planning of health resource allocation. Until recently there was no systematic attempt to determine the true prevalence of HIV infection in C'aniada, and all available information on HlV seroprevalence was derived from volunteer studies. Fhese included specific research projects involving homosexual men' 2 or sexually active women,3 provincial testing programs4 and the Canadian Red Cross Society Blood Transfusion Service (CRCSBTS) blood donor screening program.5 For obvious reasons volunteer programs are the most ethical and socially acceptable types of surveillance. Unfortunately, because of the nature of the participation, such programs are known to have a selection bias, which has a critical effect on the utility of the information obtained. In a sexually transmitted diseases (STD) clinic in Albuquerque, NM, a blinded survey revealed that the HIV seroprevalence rate was five times higher among those who refused to participate than among those who did participate in a volunteer HIV antibody testing program.6 In Oregon the introduction of an anonymous option to the state's previously confidential testing program led to a tripling of the demand for testing; moreover, twice as many seropositive people wer e identified in the first 3.5 months after the introduction of this option as in the 3.5 months before the introduction. I To avoid these selection biases investigators have turned to the anonymous seroprevalence survey. The principle is to test leftover samples obtaimed through routine collection for which the personal identifiers have been removed. This method has already been applied successfully in several studies. In Massachusetts in 1987 an anonymous 1188
CAN MED ASSOC J 1990; 143 (1 1)
survey of neonatal blood spots revealed an estimated
2.3 cases of HIV infection per 1000 childbearing women.8 Landesman and associates9 tested 602 cord blood samples from infants born at a New York inner-city hospital and found an HIV seroprevalence rate of approximately 2%. Quinn and collaborators'0 screened 4028 anonymous samples obtained for syphilis testing at an STD clinic in Baltimore and found an HIV seroprevalence rate of 5.2%. Testing of all prenatal blood specimens from women in British Columbia and the Yukon Territory is done at the CRCSBTS - Vancouver Centre. Therefore, we had an opportunity to perform an anonymous seroprevalence survey of about 22 000 women aged 15 to 44 years receiving prenatal care.
Materials and methods CRCSBTS prenatal screening program The Vancouver Centre of the CRCSBTS is the only blood transfusion centre for British Columbia and the Yukon Territory. One of the centre's main services is the prenatal screening program for those areas. All pregnant women provide a blood sample at their first prenatal visit for blood grouping and screening for erythrocyte antibodies and hepatitis B surface antigen. Furthermore, all Rh-negative women provide two more prenatal samples for monitoring of erythrocyte alloantibodies. If an antibody is detected further samples may be requested. At the first prenatal visit the physician fills out a requisition form, giving the woman's name, her date of birth, address and husband's name, the physician's name and address, the name of the hospital and the estimated date of admission, the woman's obstetric history and her transfusion history. The blood sample is drawn at a local laboratory. It is then transported in a special cylindrical container by mail or courier to the Vancouver centre, which receives between 250 and 300 samples daily. Any sample arriving without a requisition form is discarded. Those with an incomplete form are discarded and the form returned to the physician with a request for a repeat sample.
Sample selection All samples with a requisition form received by the Vancouver Centre from Mar. 15 to Sept. 30,
1989, were eligible. The sampling period was extended to the end of September primarily because of a nurses' strike lasting about 10 working days during the summer and because of occasional illness among the staff. Two electronic databases were maintained: the nominal file and the coded sample file. As specimens arrived for prenatal screening the woman's name, birth date and census tract were entered into the nominal file, which was then searched for a duplicate entry. If a previous entry was found the current specimen was excluded and sent for routine prenatal screening only. In addition, the computer was programmed to reject 2% of the specimens automatically (through the use of a random number generator). This provided the additional ethical advantage that it is now technically impossible to determine whether a specific woman was tested. If the search revealed no previous sample and the specimen was not rejected it was assigned a code number by the program. A record of the code number, the patient's age and the census tract was automatically created in the coded sample file. The two databases were unlinked in such a way that it was impossible to learn the personal identifier associated with a code number. Each sample was divided into two tubes. One was affixed with an optical scanning label of the code number and sent for HIV antibody testing, and the other was sent for routine prenatal testing.
HIV antibody testing HIV antibody testing was done at the Vancouver Centre with the use of an automated enzymelinked immunosorbent assay kit (DuPont Co., Wilmington, Del.). Samples that yielded a positive result were tested again twice. Those that were reactive at least two out of three times underwent confirmatory testing with the use of the Western blot technique (DuPont Co.) at the Federal Centre for AIDS, Ottawa. Results were considered to be positive only if confirmed by the Federal Centre for AIDS.
Analysis The samples were separated according to three regions: Vancouver (Greater Vancouver Regional District), Victoria (Capital Region District) and other. The small number of samples from women less than 15 years of age or more than 44 years were excluded. The remaining samples were stratified into two census-compatible groups: those from women 15 to 29 years and those from women 30 to 44 years. The seroprevalence rates were expressed as the number of positive samples per 10 000 pregnant women, unless otherwise indicated. Two-sided 95%
confidence intervals (CIs) were calculated with the confidence intervals (Cls) were calculated with the use of the exact binomial distribution.
Ethical review The study received ethical approval from the University of British Columbia Clinical Screening Committee for Research and Other Studies Involving Human Subjects. In addition, we asked the British Columbia Civil Liberties Association for its approval. The existence of the study became a matter of public record through several newspaper and radio interviews.
Results A total of 22 559 samples were obtained. We excluded 14 (0.06%) from women aged 14 years or less and 33 (0.15%) from those aged 45 years or more. None of the excluded samples was positive. We were aware of no instance in which a woman or her physician refused to submit a sample because of the study or requested that the sample not be tested for HIV antibodies. Of the 22 512 specimens 6 were confirmed to be positive. This gave a crude overall HIV seroprevalence rate of 2.7 per 10 000 pregnant women (95% CI 1.0 to 5.8). All of the positive samples were obtained from women between 20 and 29 years of age. Four were from Vancouver, one was from Victoria, and one was from elsewhere. The highest observed seroprevalence rates were among women 15 to 29 years of age in Vancouver and Victoria (7.2 and 9.4 per 10 000 pregnant women respectively) (Table 1). This meant that during the study period about 1 in 1300 pregnant women in that age group in those cities was HIV
positive. We obtained a naive estimate of the total number of infected women in British Columbia and the Yukon Territory by applying the age-specific and region-specific seroprevalence estimates to the number of women in each age group and region. Thus, about 162 women were seropositive during the study period (Table 2). This is a conservative estimate since it assumes a seroprevalence of zero in the age groups and regions that had no seropositive women. After applying the crude seroprevalence rate and its confidence limits to the total female population of British Columbia and the Yukon Territory aged 15 to 44 years we found that an estimated 187 women (95% CI 69 to 401) had HIV infection (Table 2).
Discussion The anonymous seroprevalence survey is not without controversy. Two of the contentious issues CAN MED ASSOC J 1990; 143 ( 1)
1189
health was held in Ottawa in December 1988 under the auspices of the Federal Centre for AIDS. Seven basic requirements for such surveys were generated from this conference. 1. Access to volunteer HIV antibody testing under conditions of informed consent, counselling before and after testirtg, and confidentiality must exist as a societal prerequisite for all people included in the survey. 2. Only leftover serum samples routinely collected for other purposes must be used. 3. Records must be permanently unlinked before testing so that determination of a person's test results is impossible at any time. 4. The samples must be large enough to prevent identification of the subjects. 5. Information that might lead to the identification of a study subject must not be used. 6. The study must be approved by the relevant ethics review committees. 7. The public must be informed of the research. Because a volunteer program of confidential
surrounding these studies are that informed consent is not obtained from each subject and that there is no means by which people found to be positive can be notified. With regard to the first issue, in its guidelines on research involving human subjects the Medical Research Council of Canada states that "consent is generally unnecessary for research undertaken, for example, on surplus blood, urine, tissue, and similar samples obtained for diagnostic or treatment purposes if the patient is not identifiable and the requirements of the research do not influence the procedures used for obtaining the samples"." We concur that informed consent is not required in anonymous seroprevalence surveys; indeed, if it were required it would reintroduce the volunteer bias. The second issue is somewhat more difficult. To address it and other ethical and legal considerations in the conduct of anonymous unlinked HIV seroprevalence research in Canada a consensus conference involving experts in ethics, law, nursing, medicine, theology, philosophy, epidemiology and public
Fable 1: Seroprevalence rates of human immunodeficiency virus (H IV) infection among pregnant women in British Columbia and the Yukon Territory from Mar 15 to Sept. 30, 1989, by region and age No. of women
Region: age group, yr Vancouver
Total
15-29 30-44
Rate per 1 0 000 pregnant women
HIV positive
.otal
interval
2.0-1 8.5
4r
Victoria 15-29 30-44 Other 15-29 30-44
95% confidence
4 74
0.0
068
9.4
691
0.0
0.2-52. 0.0-53.2
5022,
1.3
0.0-7
,)3 2531
0.0
0.0-- 1
2-)2 5,1x~
2.7
1.0-5.8
4
Table 2: Estimated seroprevalence of HIV infection among all women aged 15 "IC 44 years in British Columbia and the Yukon Territory in 1989 by region and age Region; age
Population-
group. yr Vancouver 15-29
30-44 Victoria 15-29 30-44 Other
7.2
113
0.0
0
29 488 29 742
9.4
28
0.0
0
1.3
21
0.0
0
691 400
otal
2.7
.0-5.8) '[)eterrninea
1190
;-. r r;fi.:
CAN MED ASSOC J 1990; 143 (I 1)
Estimated no. of with HIV infectior (and 95% Cl'/
women
156 776 II57 144
159 452 58 798
15-29 30-44 .4
Rate per 10 000 pregnant women (and 95% Cl)
iln sus1
data
187 (69-401)
HIV antibody testing with counselling before and after has been available to the women in our survey for some years our study clearly met all of those requirements. Although our study avoided volunteer bias there were several other biases that must be acknowledged. Our sampling frame did not include the relatively small number of women who gave birth without any prenatal care and likely most of those who elected to have a therapeutic abortion. Determination of the effect of these omissions must await the results of other anonymous surveys. If there were any effect our seroprevalence rate would most likely represent an underestimate. Our restriction of the analysis to women aged 15 to 44 years did not mean that we considered adolescents under 15 or women over 44 to be at no risk for HIV infection; instead, we did not sample enough women in these age groups to obtain meaningful estimates. Our crude overall seroprevalence rate of 2.7 per 10 000 pregnant women 15 to 44 years of age is about seven times greater than the rate among women 19 to 39 years of age who gave blood during 1988-89 in British Columbia (0.4 per 10 000) (Margaret Elliot, CRCSBTS - Vancouver Centre: personal communication, 1990). This difference highlights the effect of donor self-deferral in the CRCSBTS blood donor program and the inadequacy of blood donor seroprevalence data for epidemiologic purposes. In addition, our estimate of 1 in 1300 pregnant women aged 15 to 29 years in the metropolitan areas of British Columbia having HIV infection is about 42% of the rate among women giving birth to live infants on the island of Montreal;'2 this proportion is consistent with comparative AIDS surveillance data. As of February 1990 the cumulative incidence rate of AIDS among women 15 to 44 years of age in British Columbia was 38% of the corresponding rate in Quebec (19.0 and 49.4 per million population
respectively).13 Our seroprevalence rate, when applied to all women 15 to 44 years of age in British Columbia and the Yukon Territory, showed that as many as 401 women in that age group had HIV infection. However, few women have received treatment for HIV-related illness in British Columbia. The pharmacy at St. Paul's Hospital, Vancouver, has been the only source of zidovudine (AZT) in the province, through a distribution program available to people with AIDS and more recently to those with a CD4 count of less than 0.5 x 109/L. As of February 1990 only six women have received zidovudine, two of whom have died (Dr. W. Alastair McLeod: personal communication, 1990). There are several possible explanations for the low number of women who have received zidovu-
dine. First, the spread of HIV infection has occurred later among women than among men; therefore, women as a whole may be experiencing an earlier stage of illness. However, there is the ominous possibility that most of the spread among women has occurred only very recently and is on the rise. Furthermore, the failure of eligible women to receive treatment may be compounded by a combination of other factors, including misdiagnosis of HIV-related illnesses in women, lack of knowledge regarding available therapies on the part of women and their physicians, unwillingness of women to enter treatment programs at recognized centres and denial. All of these factors have implications for those providing care to women with HIV infection; unfortunately, unless special steps are taken to target women these problems will likely only increase as larger numbers of women progress from the early, asymptomatic phase to the later phases of HIV infection. A fundamental consideration regarding the seroprevalence rates and their application concerns the use of pregnant women to represent all women of childbearing age. We included pregnant women not because of any intrinsic interest in this population but because of the availability of blood samples from them. Pregnant women likely overrepresent women at no risk of HIV infection, such as those in monogamous relationships with uninfected partners. Symmetrically, pregnant women underrepresent those women at highest risk. An example of a woman at high risk who would have been missed by us is one with multiple sexual partners who is using an oral contraceptive and therefore is not likely to use a barrier method, particularly a condom; such a woman would not likely become pregnant (unless the oral contraceptive failed). Another example is a sexually active woman with a history of recurrent STDs and resulting infertility. We likely also missed many infected women whose HIV status was already known; such women should have been counselled about the risks to their offspring, and many may have elected to avoid pregnancy. Given these biases we believe that the estimate of 1 in 1300 pregnant women aged 15 to 29 years with HIV infection in the metropolitan areas is a minimum and should be greeted with alarm. This number is more likely an estimate of asymptomatic HIV infection in a low-risk subset of women in that age group rather than an overall estimate of HIV seroprevalence among women of the same age. We believe that the latter rate could be many times higher. For these reasons the results of neonatal studies8'9"2 and prenatal studies such as ours must be accompanied by estimates obtained from other subsets of women, including, for example, those undergoing therapeutic abortion, attending STD clinics, CAN MED ASSOC J 1990; 143 (I 1)
1191
giving samples for VDRL testing or undergoing routine outpatient laboratory tests. Together these studies could provide a mosaic of results that would allow a more precise estimation of the spread of HIV among women. Our study should be considered not for its generalizability but, rather, for its internal consistency. It has provided a baseline assessment and will be repeated annually with the use of the same 6-month period, the identical sampling frame and the same testing methods to assess trends in HIV seroprevalence among pregnant women in British Columbia and the Yukon Territory. We thank Margaret Elliot and Laurel Slaney for assisting with the research. This study was supported by the CRCS, the Federal Centre for AIDS, grant 6613-1358-AIDS from the National Health Research and Development Program, Department of National Health and Welfare, and a National Health Research Scholar Award given to Dr. Schechter.
References 1. Coates RA, Soskolne CL, Read SE et al: A prospective study of male sexual contacts of men with ARC or AIDS: HTLV-III antibody, clinical and immune function status at induction. Can JPublic Health 1986; 177: 26-32 2. Schechter MT, Boyko WJ, Douglas B et al: The Vancouver Lymphadenopathy-AIDS Study: 6. HIV seroconversion in a cohort of homosexual men. Can Med Assoc J 1986; 135: 1355-1360 3. Elmslie K, Romanowski B, Hankins C et al: Canadian collaborative study of women attending sexually transmitted disease clinics [abstr 4064]. Presented at the IVth International Conference on AIDS, Stockholm, June 12-16, 1988
4. AIDS in British Columbia, BC Centre for Disease Control, BC Ministry of Health, Vancouver, 1989 5. Anti-HIV screening in Canadian blood donors. Can Med Assoc J 1986; 135: 901 6. Hull HF, Bettinger CJ, Gallaher MM et al: Comparison of HIV-antibody prevalence in patients consenting to and declining HIV-antibody testing in an STD clinic. JAMA 1988; 260: 935-938 7. Fehrs LJ, Fleming D, Foster LR et al: Trial of anonymous versus confidential human immunodeficiency virus infection. Lancet 1988; 2: 379-382 8. Hoff R, Berardi VP, Weiblen BJ et al: Seroprevalence of HIV among child-bearing women. Estimation by testing samples of blood from newborns. N Engl J Med 1988; 318: 525-530 9. Landesman S, Minkoff H, Holman S et al: Serosurvey of human immunodeficiency virus infection in parturients. JAMA 1987; 258: 2701-2703 10. Quinn TC, Glasser D, Cannon RO et al: Human immunodeficiency virus infection among patients attending clinics for sexually transmitted diseases. N Engl J AMed 1988; 318: 197-203 11. Non-consensual research. In Guidelines on Research Involving Human Subjects, Medical Research Council of Canada. Ottawa, 1987; app C: 26 12. Hankins CA, Laberge C, Lapointe N et al: HIV infection among Quebec women giving birth to live infants. Can Med Assoc J 1990; 143: 885-893 13. 1986 Census -British Columbia, Part 1 (cat 94119), Statistics Canada, Ottawa, 1987 1192
CAN MED ASSOC J 1990; 143 (I 1)
Conferences continuedfrom page 1170 May 12-14, 1991: Canada's National Safety Conference - Safety Starts in Your Community Hamilton, Ont. Canada Safety Council, 6-2750 Stevenage Dr., Ottawa, Ont. KIG 3N2; (613) 739-1535, FAX (613) 739-1566 May 13-14, 1991: Canadian Life Insurance Medical Officers Association 46th Annual Meeting Quebec Dr. J.L. Guy Tremblay, La Solidarite compagnie d'assurance sur la vie, 925, ch. St-Louis, Quebec, QC G1S lCl; (418) 688-8710, ext. 273
May 13-16, 1991: 7th World Congress on Emergency and Disaster Medicine (sponsored by the World Association of Emergency and Disaster Medicine, the Canadian Association of Emergency Physicians and la Societe internationale de medecine de catastrophe) Abstract deadline is Dec. 31, 1990. Palais de Congres, Montreal Ms. Ursula Schwarz, Meeting Secretariat, Kush Medical Communications, 61-6100 Montevideo Rd., Mississauga, Ont. L5N 2N8; (416) 821-3541, FAX (416) 821-8863 May 22-25, 1991: North American Primary Care Research Group 19th Annual Meeting Chateau Frontenac, Quebec
Abstract deadline is Dec. 14, 1990. Dr. Michel Labrecque, chairman, Organizing Committee, NAPCRG-9 1, Continuing Medical Education Office, Faculty of Medicine, Ferdinand-Vandry Pavilion, Laval University, Quebec, PQ GIK 7P4; (418) 656-5958, FAX (418) 656-3442 May 23-24, 1991: 2nd Canadian Epidemiology Research Conference University of Alberta, Edmonton Dr. Colin Soskolne, conference convenor, 13-103 Clinical Sciences Bldg., University of Alberta, Edmonton, Alta. T6G 2G3; (403) 492-6013, FAX (403) 492-0364 June 19-22, 1991: 26th Meeting of the Canadian Congress
of Neurological Sciences Halifax Sheraton Abstract deadline is Jan. 21, 1991. Permanent Secretariat, Canadian Congress of Neurological Sciences, Ste. 810, 906-12 Ave. SW, Calgary, Alta. T2R 1 K7; (403) 229-9544 July 3-5, 1991: Advances in Hydrotherapy II: Movement and Immersion in Water University of Nijmegen, The Netherlands Mrs. J. Koot, Congress office, University of Nijmegen, P0 Box 9111, 6500 HN Nijmegen, The Netherlands; FAX 3 1-80-567-956
An anonymous seroprevalence survey of HIV infection among pregnant women in British Columbia and the Yukon Territory Martin T. Schechter,* MD, MSc, PhD; Penny J. Ballem,tt MD, FRCPC; Noel A. Buskard,tf MD, FRCPC; Thinh N. Le,* BSc; Mai Thompson,* MSc; Stephen A. Marion,* MD, MS, MHSc, FRCPC; Michael V. O'Shaughnessy,§ PhD We performed an anonymous seroprevalence survey of human immunodeficiency virus (HIV) type 1 infection through HIV antibody testing of blood samples from 22 512 women aged 15 to 44 years receiving prenatal care in British Columbia and the Yukon Territory from Mar. 15 to Sept. 30, 1989. Of the samples six were confirmed to be HIV positive; this yielded a crude overall seroprevalence rate of 2.7 per 10 000 pregnant women (95% confidence interval [CI] 1.0 to 5.8). All of the positive samples were from women 20 to 29 years of age; four were from Vancouver, one was from Victoria, and one was from elsewhere. The highest seroprevalence rates were among women aged 15 to 29 years in Vancouver and Victoria (7.2 and 9.4 per 10000 pregnant women respectively). Thus, 1 in 1300 pregnant women in that age group in the metropolitan areas of British Columbia was HIV positive. Application of seroprevalence rates to the total female population in British Columbia and the Yukon Territory revealed that as many as 401 women had HIV infection in 1989. Our estimates likely represent the minimum. As a subset of women of childbearing age pregnant women are likely at lowest risk of HIV infection, and so the true number of women 15 to 44 years of age with HIV infection is probably several times higher. Our study has provided a baseline assessment and will be repeated annually to analyse trends in HIV seroprevalence among pregnant women in British Columbia and the Yukon Territory. Nous avons fait une etude anonyme de seroprevalence des infections par le virus d'immunodeficience humaine (VIH) type 1 par l'evaluation des anticorps au VIH de prelevements sanguins de 22 512 femmes agees de 15 a 44 ans en soins prenataux en Colombie-Britannique et au Yukon du 15 mars au 30 septembre 1989. Parmi les echantillons analyses, six se sont averes seropositifs, ce qui donne un taux global brut de seroprevalence de 2,7 par 10 000 femmes enceintes (intervalle de confiance [IC] a 95% de 1,0 a 5,8). Tous les echantillons positifs provenaient de femmes agees de 20 a 29 ans; quatre etaient de Vancouver, une etait de Victoria, et une etait d'une autre localite. Les taux les plus eleves de seroprevalence se situaient chez les femmes agees de 15 a 29 ans a Vancouver et a Victoria (7,2 et 9,4 par 10 000 femmes enceintes respectivement). Ainsi, 1 femme enceinte sur 1300 de ce groupe d'age dans les regions metropolitaines de la Colombie-Britannique etait seropositive. L'application des taux de seroprevalence a la population feminine totale de la Colombie-Britannique et du Yukon a laisse voir que 401 femmes avaient contracte une infection par le VIH en 1989. Nos evaluations representent probablement un minimum. En tant que sous-echantillon des femmes en From *the Department of Health Care and Epidemiology and tthe Department of Medicine, Faculty ofMedicine, University of British Columbia, Vancouver, tthe Canadian Red Cross Society Blood Transfusion Service - Vancouver Centre, and §the Bureau of Laboratories and Research, Federal Centre for AIDS, Department ofNational Health and Welfare, Ottawa
Reprint requests to: Dr. Martin T. Schechter, Faculty of Medicine, University of British Columbia, 5804 Fairview Ave., Vancouver, BC V6T I W5 -
For prescribing information see page 1251
CAN MED ASSOC J 1990; 143 ( 11)
1187
age de procr6er, les femmes enceintes courent probablement le moins de risque d'infection par le VIH, de sorte que le nombre reel de femmes agees de 15 a 44 ans atteintes d'une infection par le VIH est probablement plusieurs fois plus eleve. Notre etude permet une evaluation de base et sera repetee annuellement pour analyser les tendances de la seroprevalence au VIH chez les femmes enceintes en Colombie-Britannique et au Yukon.
S urveillance of human immunodeficiency virus (HIV) type 1 infection in Canada has relied primarily on surveillance of the end-stage condition, acquired immunodeficiency syndrome (AIDS). AIDS surveillance has provided an incomplete and delayed indication of the scope of HIV infection across the country. Accurate estimates of the number of infected Canadians are necessary for several reasons. First, only by establishing such estimates and then monitoring them can one track the rate of change of the epidemic. Second, precise serial estimates within certain transmission groups will be critical in evaluating the effectiveness of various interventions to prevent the spread of HIV. Finally, accurate estimates will allow the rational planning of health resource allocation. Until recently there was no systematic attempt to determine the true prevalence of HIV infection in C'aniada, and all available information on HlV seroprevalence was derived from volunteer studies. Fhese included specific research projects involving homosexual men' 2 or sexually active women,3 provincial testing programs4 and the Canadian Red Cross Society Blood Transfusion Service (CRCSBTS) blood donor screening program.5 For obvious reasons volunteer programs are the most ethical and socially acceptable types of surveillance. Unfortunately, because of the nature of the participation, such programs are known to have a selection bias, which has a critical effect on the utility of the information obtained. In a sexually transmitted diseases (STD) clinic in Albuquerque, NM, a blinded survey revealed that the HIV seroprevalence rate was five times higher among those who refused to participate than among those who did participate in a volunteer HIV antibody testing program.6 In Oregon the introduction of an anonymous option to the state's previously confidential testing program led to a tripling of the demand for testing; moreover, twice as many seropositive people wer e identified in the first 3.5 months after the introduction of this option as in the 3.5 months before the introduction. I To avoid these selection biases investigators have turned to the anonymous seroprevalence survey. The principle is to test leftover samples obtaimed through routine collection for which the personal identifiers have been removed. This method has already been applied successfully in several studies. In Massachusetts in 1987 an anonymous 1188
CAN MED ASSOC J 1990; 143 (1 1)
survey of neonatal blood spots revealed an estimated
2.3 cases of HIV infection per 1000 childbearing women.8 Landesman and associates9 tested 602 cord blood samples from infants born at a New York inner-city hospital and found an HIV seroprevalence rate of approximately 2%. Quinn and collaborators'0 screened 4028 anonymous samples obtained for syphilis testing at an STD clinic in Baltimore and found an HIV seroprevalence rate of 5.2%. Testing of all prenatal blood specimens from women in British Columbia and the Yukon Territory is done at the CRCSBTS - Vancouver Centre. Therefore, we had an opportunity to perform an anonymous seroprevalence survey of about 22 000 women aged 15 to 44 years receiving prenatal care.
Materials and methods CRCSBTS prenatal screening program The Vancouver Centre of the CRCSBTS is the only blood transfusion centre for British Columbia and the Yukon Territory. One of the centre's main services is the prenatal screening program for those areas. All pregnant women provide a blood sample at their first prenatal visit for blood grouping and screening for erythrocyte antibodies and hepatitis B surface antigen. Furthermore, all Rh-negative women provide two more prenatal samples for monitoring of erythrocyte alloantibodies. If an antibody is detected further samples may be requested. At the first prenatal visit the physician fills out a requisition form, giving the woman's name, her date of birth, address and husband's name, the physician's name and address, the name of the hospital and the estimated date of admission, the woman's obstetric history and her transfusion history. The blood sample is drawn at a local laboratory. It is then transported in a special cylindrical container by mail or courier to the Vancouver centre, which receives between 250 and 300 samples daily. Any sample arriving without a requisition form is discarded. Those with an incomplete form are discarded and the form returned to the physician with a request for a repeat sample.
Sample selection All samples with a requisition form received by the Vancouver Centre from Mar. 15 to Sept. 30,
1989, were eligible. The sampling period was extended to the end of September primarily because of a nurses' strike lasting about 10 working days during the summer and because of occasional illness among the staff. Two electronic databases were maintained: the nominal file and the coded sample file. As specimens arrived for prenatal screening the woman's name, birth date and census tract were entered into the nominal file, which was then searched for a duplicate entry. If a previous entry was found the current specimen was excluded and sent for routine prenatal screening only. In addition, the computer was programmed to reject 2% of the specimens automatically (through the use of a random number generator). This provided the additional ethical advantage that it is now technically impossible to determine whether a specific woman was tested. If the search revealed no previous sample and the specimen was not rejected it was assigned a code number by the program. A record of the code number, the patient's age and the census tract was automatically created in the coded sample file. The two databases were unlinked in such a way that it was impossible to learn the personal identifier associated with a code number. Each sample was divided into two tubes. One was affixed with an optical scanning label of the code number and sent for HIV antibody testing, and the other was sent for routine prenatal testing.
HIV antibody testing HIV antibody testing was done at the Vancouver Centre with the use of an automated enzymelinked immunosorbent assay kit (DuPont Co., Wilmington, Del.). Samples that yielded a positive result were tested again twice. Those that were reactive at least two out of three times underwent confirmatory testing with the use of the Western blot technique (DuPont Co.) at the Federal Centre for AIDS, Ottawa. Results were considered to be positive only if confirmed by the Federal Centre for AIDS.
Analysis The samples were separated according to three regions: Vancouver (Greater Vancouver Regional District), Victoria (Capital Region District) and other. The small number of samples from women less than 15 years of age or more than 44 years were excluded. The remaining samples were stratified into two census-compatible groups: those from women 15 to 29 years and those from women 30 to 44 years. The seroprevalence rates were expressed as the number of positive samples per 10 000 pregnant women, unless otherwise indicated. Two-sided 95%
confidence intervals (CIs) were calculated with the confidence intervals (Cls) were calculated with the use of the exact binomial distribution.
Ethical review The study received ethical approval from the University of British Columbia Clinical Screening Committee for Research and Other Studies Involving Human Subjects. In addition, we asked the British Columbia Civil Liberties Association for its approval. The existence of the study became a matter of public record through several newspaper and radio interviews.
Results A total of 22 559 samples were obtained. We excluded 14 (0.06%) from women aged 14 years or less and 33 (0.15%) from those aged 45 years or more. None of the excluded samples was positive. We were aware of no instance in which a woman or her physician refused to submit a sample because of the study or requested that the sample not be tested for HIV antibodies. Of the 22 512 specimens 6 were confirmed to be positive. This gave a crude overall HIV seroprevalence rate of 2.7 per 10 000 pregnant women (95% CI 1.0 to 5.8). All of the positive samples were obtained from women between 20 and 29 years of age. Four were from Vancouver, one was from Victoria, and one was from elsewhere. The highest observed seroprevalence rates were among women 15 to 29 years of age in Vancouver and Victoria (7.2 and 9.4 per 10 000 pregnant women respectively) (Table 1). This meant that during the study period about 1 in 1300 pregnant women in that age group in those cities was HIV
positive. We obtained a naive estimate of the total number of infected women in British Columbia and the Yukon Territory by applying the age-specific and region-specific seroprevalence estimates to the number of women in each age group and region. Thus, about 162 women were seropositive during the study period (Table 2). This is a conservative estimate since it assumes a seroprevalence of zero in the age groups and regions that had no seropositive women. After applying the crude seroprevalence rate and its confidence limits to the total female population of British Columbia and the Yukon Territory aged 15 to 44 years we found that an estimated 187 women (95% CI 69 to 401) had HIV infection (Table 2).
Discussion The anonymous seroprevalence survey is not without controversy. Two of the contentious issues CAN MED ASSOC J 1990; 143 ( 1)
1189
health was held in Ottawa in December 1988 under the auspices of the Federal Centre for AIDS. Seven basic requirements for such surveys were generated from this conference. 1. Access to volunteer HIV antibody testing under conditions of informed consent, counselling before and after testirtg, and confidentiality must exist as a societal prerequisite for all people included in the survey. 2. Only leftover serum samples routinely collected for other purposes must be used. 3. Records must be permanently unlinked before testing so that determination of a person's test results is impossible at any time. 4. The samples must be large enough to prevent identification of the subjects. 5. Information that might lead to the identification of a study subject must not be used. 6. The study must be approved by the relevant ethics review committees. 7. The public must be informed of the research. Because a volunteer program of confidential
surrounding these studies are that informed consent is not obtained from each subject and that there is no means by which people found to be positive can be notified. With regard to the first issue, in its guidelines on research involving human subjects the Medical Research Council of Canada states that "consent is generally unnecessary for research undertaken, for example, on surplus blood, urine, tissue, and similar samples obtained for diagnostic or treatment purposes if the patient is not identifiable and the requirements of the research do not influence the procedures used for obtaining the samples"." We concur that informed consent is not required in anonymous seroprevalence surveys; indeed, if it were required it would reintroduce the volunteer bias. The second issue is somewhat more difficult. To address it and other ethical and legal considerations in the conduct of anonymous unlinked HIV seroprevalence research in Canada a consensus conference involving experts in ethics, law, nursing, medicine, theology, philosophy, epidemiology and public
Fable 1: Seroprevalence rates of human immunodeficiency virus (H IV) infection among pregnant women in British Columbia and the Yukon Territory from Mar 15 to Sept. 30, 1989, by region and age No. of women
Region: age group, yr Vancouver
Total
15-29 30-44
Rate per 1 0 000 pregnant women
HIV positive
.otal
interval
2.0-1 8.5
4r
Victoria 15-29 30-44 Other 15-29 30-44
95% confidence
4 74
0.0
068
9.4
691
0.0
0.2-52. 0.0-53.2
5022,
1.3
0.0-7
,)3 2531
0.0
0.0-- 1
2-)2 5,1x~
2.7
1.0-5.8
4
Table 2: Estimated seroprevalence of HIV infection among all women aged 15 "IC 44 years in British Columbia and the Yukon Territory in 1989 by region and age Region; age
Population-
group. yr Vancouver 15-29
30-44 Victoria 15-29 30-44 Other
7.2
113
0.0
0
29 488 29 742
9.4
28
0.0
0
1.3
21
0.0
0
691 400
otal
2.7
.0-5.8) '[)eterrninea
1190
;-. r r;fi.:
CAN MED ASSOC J 1990; 143 (I 1)
Estimated no. of with HIV infectior (and 95% Cl'/
women
156 776 II57 144
159 452 58 798
15-29 30-44 .4
Rate per 10 000 pregnant women (and 95% Cl)
iln sus1
data
187 (69-401)
HIV antibody testing with counselling before and after has been available to the women in our survey for some years our study clearly met all of those requirements. Although our study avoided volunteer bias there were several other biases that must be acknowledged. Our sampling frame did not include the relatively small number of women who gave birth without any prenatal care and likely most of those who elected to have a therapeutic abortion. Determination of the effect of these omissions must await the results of other anonymous surveys. If there were any effect our seroprevalence rate would most likely represent an underestimate. Our restriction of the analysis to women aged 15 to 44 years did not mean that we considered adolescents under 15 or women over 44 to be at no risk for HIV infection; instead, we did not sample enough women in these age groups to obtain meaningful estimates. Our crude overall seroprevalence rate of 2.7 per 10 000 pregnant women 15 to 44 years of age is about seven times greater than the rate among women 19 to 39 years of age who gave blood during 1988-89 in British Columbia (0.4 per 10 000) (Margaret Elliot, CRCSBTS - Vancouver Centre: personal communication, 1990). This difference highlights the effect of donor self-deferral in the CRCSBTS blood donor program and the inadequacy of blood donor seroprevalence data for epidemiologic purposes. In addition, our estimate of 1 in 1300 pregnant women aged 15 to 29 years in the metropolitan areas of British Columbia having HIV infection is about 42% of the rate among women giving birth to live infants on the island of Montreal;'2 this proportion is consistent with comparative AIDS surveillance data. As of February 1990 the cumulative incidence rate of AIDS among women 15 to 44 years of age in British Columbia was 38% of the corresponding rate in Quebec (19.0 and 49.4 per million population
respectively).13 Our seroprevalence rate, when applied to all women 15 to 44 years of age in British Columbia and the Yukon Territory, showed that as many as 401 women in that age group had HIV infection. However, few women have received treatment for HIV-related illness in British Columbia. The pharmacy at St. Paul's Hospital, Vancouver, has been the only source of zidovudine (AZT) in the province, through a distribution program available to people with AIDS and more recently to those with a CD4 count of less than 0.5 x 109/L. As of February 1990 only six women have received zidovudine, two of whom have died (Dr. W. Alastair McLeod: personal communication, 1990). There are several possible explanations for the low number of women who have received zidovu-
dine. First, the spread of HIV infection has occurred later among women than among men; therefore, women as a whole may be experiencing an earlier stage of illness. However, there is the ominous possibility that most of the spread among women has occurred only very recently and is on the rise. Furthermore, the failure of eligible women to receive treatment may be compounded by a combination of other factors, including misdiagnosis of HIV-related illnesses in women, lack of knowledge regarding available therapies on the part of women and their physicians, unwillingness of women to enter treatment programs at recognized centres and denial. All of these factors have implications for those providing care to women with HIV infection; unfortunately, unless special steps are taken to target women these problems will likely only increase as larger numbers of women progress from the early, asymptomatic phase to the later phases of HIV infection. A fundamental consideration regarding the seroprevalence rates and their application concerns the use of pregnant women to represent all women of childbearing age. We included pregnant women not because of any intrinsic interest in this population but because of the availability of blood samples from them. Pregnant women likely overrepresent women at no risk of HIV infection, such as those in monogamous relationships with uninfected partners. Symmetrically, pregnant women underrepresent those women at highest risk. An example of a woman at high risk who would have been missed by us is one with multiple sexual partners who is using an oral contraceptive and therefore is not likely to use a barrier method, particularly a condom; such a woman would not likely become pregnant (unless the oral contraceptive failed). Another example is a sexually active woman with a history of recurrent STDs and resulting infertility. We likely also missed many infected women whose HIV status was already known; such women should have been counselled about the risks to their offspring, and many may have elected to avoid pregnancy. Given these biases we believe that the estimate of 1 in 1300 pregnant women aged 15 to 29 years with HIV infection in the metropolitan areas is a minimum and should be greeted with alarm. This number is more likely an estimate of asymptomatic HIV infection in a low-risk subset of women in that age group rather than an overall estimate of HIV seroprevalence among women of the same age. We believe that the latter rate could be many times higher. For these reasons the results of neonatal studies8'9"2 and prenatal studies such as ours must be accompanied by estimates obtained from other subsets of women, including, for example, those undergoing therapeutic abortion, attending STD clinics, CAN MED ASSOC J 1990; 143 (I 1)
1191
giving samples for VDRL testing or undergoing routine outpatient laboratory tests. Together these studies could provide a mosaic of results that would allow a more precise estimation of the spread of HIV among women. Our study should be considered not for its generalizability but, rather, for its internal consistency. It has provided a baseline assessment and will be repeated annually with the use of the same 6-month period, the identical sampling frame and the same testing methods to assess trends in HIV seroprevalence among pregnant women in British Columbia and the Yukon Territory. We thank Margaret Elliot and Laurel Slaney for assisting with the research. This study was supported by the CRCS, the Federal Centre for AIDS, grant 6613-1358-AIDS from the National Health Research and Development Program, Department of National Health and Welfare, and a National Health Research Scholar Award given to Dr. Schechter.
References 1. Coates RA, Soskolne CL, Read SE et al: A prospective study of male sexual contacts of men with ARC or AIDS: HTLV-III antibody, clinical and immune function status at induction. Can JPublic Health 1986; 177: 26-32 2. Schechter MT, Boyko WJ, Douglas B et al: The Vancouver Lymphadenopathy-AIDS Study: 6. HIV seroconversion in a cohort of homosexual men. Can Med Assoc J 1986; 135: 1355-1360 3. Elmslie K, Romanowski B, Hankins C et al: Canadian collaborative study of women attending sexually transmitted disease clinics [abstr 4064]. Presented at the IVth International Conference on AIDS, Stockholm, June 12-16, 1988
4. AIDS in British Columbia, BC Centre for Disease Control, BC Ministry of Health, Vancouver, 1989 5. Anti-HIV screening in Canadian blood donors. Can Med Assoc J 1986; 135: 901 6. Hull HF, Bettinger CJ, Gallaher MM et al: Comparison of HIV-antibody prevalence in patients consenting to and declining HIV-antibody testing in an STD clinic. JAMA 1988; 260: 935-938 7. Fehrs LJ, Fleming D, Foster LR et al: Trial of anonymous versus confidential human immunodeficiency virus infection. Lancet 1988; 2: 379-382 8. Hoff R, Berardi VP, Weiblen BJ et al: Seroprevalence of HIV among child-bearing women. Estimation by testing samples of blood from newborns. N Engl J Med 1988; 318: 525-530 9. Landesman S, Minkoff H, Holman S et al: Serosurvey of human immunodeficiency virus infection in parturients. JAMA 1987; 258: 2701-2703 10. Quinn TC, Glasser D, Cannon RO et al: Human immunodeficiency virus infection among patients attending clinics for sexually transmitted diseases. N Engl J AMed 1988; 318: 197-203 11. Non-consensual research. In Guidelines on Research Involving Human Subjects, Medical Research Council of Canada. Ottawa, 1987; app C: 26 12. Hankins CA, Laberge C, Lapointe N et al: HIV infection among Quebec women giving birth to live infants. Can Med Assoc J 1990; 143: 885-893 13. 1986 Census -British Columbia, Part 1 (cat 94119), Statistics Canada, Ottawa, 1987 1192
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Conferences continuedfrom page 1170 May 12-14, 1991: Canada's National Safety Conference - Safety Starts in Your Community Hamilton, Ont. Canada Safety Council, 6-2750 Stevenage Dr., Ottawa, Ont. KIG 3N2; (613) 739-1535, FAX (613) 739-1566 May 13-14, 1991: Canadian Life Insurance Medical Officers Association 46th Annual Meeting Quebec Dr. J.L. Guy Tremblay, La Solidarite compagnie d'assurance sur la vie, 925, ch. St-Louis, Quebec, QC G1S lCl; (418) 688-8710, ext. 273
May 13-16, 1991: 7th World Congress on Emergency and Disaster Medicine (sponsored by the World Association of Emergency and Disaster Medicine, the Canadian Association of Emergency Physicians and la Societe internationale de medecine de catastrophe) Abstract deadline is Dec. 31, 1990. Palais de Congres, Montreal Ms. Ursula Schwarz, Meeting Secretariat, Kush Medical Communications, 61-6100 Montevideo Rd., Mississauga, Ont. L5N 2N8; (416) 821-3541, FAX (416) 821-8863 May 22-25, 1991: North American Primary Care Research Group 19th Annual Meeting Chateau Frontenac, Quebec
Abstract deadline is Dec. 14, 1990. Dr. Michel Labrecque, chairman, Organizing Committee, NAPCRG-9 1, Continuing Medical Education Office, Faculty of Medicine, Ferdinand-Vandry Pavilion, Laval University, Quebec, PQ GIK 7P4; (418) 656-5958, FAX (418) 656-3442 May 23-24, 1991: 2nd Canadian Epidemiology Research Conference University of Alberta, Edmonton Dr. Colin Soskolne, conference convenor, 13-103 Clinical Sciences Bldg., University of Alberta, Edmonton, Alta. T6G 2G3; (403) 492-6013, FAX (403) 492-0364 June 19-22, 1991: 26th Meeting of the Canadian Congress
of Neurological Sciences Halifax Sheraton Abstract deadline is Jan. 21, 1991. Permanent Secretariat, Canadian Congress of Neurological Sciences, Ste. 810, 906-12 Ave. SW, Calgary, Alta. T2R 1 K7; (403) 229-9544 July 3-5, 1991: Advances in Hydrotherapy II: Movement and Immersion in Water University of Nijmegen, The Netherlands Mrs. J. Koot, Congress office, University of Nijmegen, P0 Box 9111, 6500 HN Nijmegen, The Netherlands; FAX 3 1-80-567-956
