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April 1987, Volume 37, Issue 4

Editorial

SCREENING FOR ANTIBODIES TO HTLV-III/LAV IN OUR POPULATION A WORD OF CAUTION

Mirza Naqi Zafar  ( Zafar Research and Diagnostic Centre. 7/14 Clinic Side, Rimpa Plaza, MA. Jinnah Road, Karachi. )

The human T-ceIl lymphothrophic virus, variously called HTLV—III, lymphadenopathy associated virus (LAV) or acquired immunode­ficiency (AIDS) related virus is believed to be the causative agent of AIDS1. Positivity for the HTLV-III/LAV antibody seems to be an indication of viral infection in most patients with AIDS and most healthy persons who are exposed to the virus1-2 AIDS occurs with increased frequency in homosexual men, intravenous drug abusers, patients with hemophilia, recipients of blood transfusion and close heterosexual contacts of members of these high risk group3. Concern about the risk of transmission of HTLV—III has resulted in large scale screening for its antibody in Western as well as some third world countries4-8  Similar concerns have stimulated many private and some government laboratories in Pakistan to screen for HTLV-III antibodies in our population. A few are screening blood donors as in West9, others are surveying populations and some unfortunately are screening healthy individuals in context of diagnosis of AIDS. The financial and psychosocial repercussions of such widespread testing of asyrnptomatic persons from low-risk groups are well documented in Western experience10 Before we publicise our findings in our population and attach significance to them, it would be worthwhile to survey international seroepidemiology of HTLV-III antibodies and to scrutinise testing procedure available in Pakistan.
Surveyors of AIDS retrovirus seroepidemio­logy in our population should be aware of false positive reactions encountered by others. Bigger et al reported the relation between Malaria and nonspecific positivity in the antibody assays for retroviruses, including HTLV-III due to high\\ antibody titre against Malaria11 Voisky et al from Venezuela reported false positive antibodies to HTLV-III in acute malarial infections both in P. falciparum and P. Vivax and related this to cross-reactivity between Malaria and retrovirus antigens12 In fact they isolated a retrovirus similar to HTLV-HI called SA-RV from a patient with Malaria12. Recently Mendenhall et al re­ported false positive tests for HTLV-III antibodies in alcoholic patients with hepatitis13 Further­more antibodies reactive with HTLV-III/LAV have been detected among healthy subjects not be­longing to any recognised AIDS risk group who live in certain rural regions of Africa8-14 and South America15 Epidemiological survey in Pakistan has shown that Malaria is endemic in our population, Hepatitis B virus is the main causative factor of liver disease, 16 and high prevalence of T-cell leukaemias17  in our population. These facts necessitate that we simultaneously and on ap urgent basis evaluate retrovirus in our population and then attach significance to HTLV-III antibody screening or give diagnostic importanèe to positive tests.
The enzyme-linked immunosorbant assay (ELISA) for detecting antibody to human T-celi lymphothrophic virus HTLV-III is the only avail­able tool in Pakistan. Though this procedure has proved to be a valuable tool in examination of association between exposure to HTLV-III and AIDS and its related complexes18 it gives many false positives in screening of healthy indivi­duals’19-20 and false negatives are seen in early HTLV-III infections.21 Furthermore the presence of anti-nuclear and anti-mitochondrial antibodies, human leucocyte antigen and human T..cell antigen have been highly correlated with false reactivity on the ELISA22. Indeed at times even more specific tests, e.g., Western Blot give false posi­tives19 It follows that laboratories conducting ELISA must also equip themselves with other techniques, i.e., Western Blot, Immunopreci­pitation and Immunofluorescence.
These observations demand caution when screening for HTLV-IIl antibodies in our popula­tion. Since AIDS is a fact that should not be ignored an urgent analysis of retrovirus and their antibodies must be evaluated in our population. It should be done in context of high risk groups3 Malaria, Hepatitis and leukaemia. Those who are screening asymptomatic healthy individuals should prepare themselves for answers to POSITIVES.

REFERENCES

1. Broder, S. and Galio, R.C.A pathogenic retro­virus (HTLV-III) linked to AIDS. N. Engl. J. Med., 1984; 311 : 1292.
2. ‘Casareale, D., Dewhurst, S., Sonnobend , J., Sinangil, F., Putio, D.T. and Voisky DJ. Pre­valence of AIDS—Associated retrovirus and antibodies among male homosexuals at risk for AIDS in Greenwich Village. Aids Res., 1985; 1: 407.
3. Current Trends. Update on acquired iminuno deficiency syndrome (AIDS)— United States MMWR., 1985; 34: 507.
4. American Association of Blood Banks. CDS. revises AIDS case definition-results of HTLV III test kits reported from Blood centres across United States. Blood Bank Weekly, 1985; 1:1.
5. Cheinsong-Popov, R., Weiss, R.A., Daigleish, A., Tedder, R.S., Shanson, D.C., Jeffries, DJ., Ferns, R.B. et al. Prevalence of antibody to Human T-lymphothrophic virus type III in AIDS and AIDS-risk patients in Britain. Lancet, 1984;2: 477
6. Voisky, D.J., Rodriguez, L. and Dewhurst, S. Antibodies to acquired Immunodcflciencysyndrome (AIDS) associated virus (HTLV-III/LAV) in Venezuelan populations. AIDS Res 1986;2 :79.
7. Schubach, J., Hailer, 0. and Vogt, M. Antibodies to HTLV-III in Swiss patients with AIDS and pre-AIDS and in groups at risk for AIDS. N. Engl. J Med., 1985; 312: 265.
8. Bigger, R.J. The AIDS problem in Africa. Lancet, 1986;1: 79.
9. Provisional Public Health Service inter-agency recommendations for screening donated blood and plasma for antibody to the virus causing acquired immunodeficicucy syndrome. MMWR., 1985;34: 1-5.
10. Osterhoim, M.T., Bowman, R.J., Chopek, M.W., McCullough, J.J., Korlath, JA. and Polesky, H.F.  Screening donated blood and plasma for HTLV-III antibody. Facing more than one crisis. N. Engi. J. Med., 1985; 312:1185.
11. Bigger, R.J., Gigase, P.L., Melbye, M., et al. ELISA HTLV retrovirus antibody reactivity associated with malaria and immune complexes in healthy Africans. Lancet, 1985; 2:5 20.
12. Voisky, D.J., WU, Y.T., Stevenson, M., Dew-hurst, S., Sinangil, F., Merina, F., Rodriguez,L. Venezuelan patients with acute malarial infec­tions. N. Engi. j Med., 1986; 314: 647.
13. Mendenhall, C.L., Rosette, GA., Grossman, CJ., Rouster, S.D., Weesner, R. and Dumaswala, U. False positive tests for HTLV-III antibodies in alcoholic patients with hepatitis. N. Engl. J. Med., 1986; 314:921.
14. Bigger, RJ., Melbye, M., Kestens, L., deFeyter, M., Saxthger, C,. Bonder, A.J., Paluko, L., Blattner,WA. and Gigase,P.L. Seroepidemiology of HTLV-III antibodies in a remote population of eastern Zaire. Br.  Med. J.(Clin. Res.), 1985; 290:808.
15. Rodriguez, L., Dewhurst, S., Sinangil, F., Merino, F., Godoy, G. and Volsky, D.J. Antibodies to  HTLV-I11/LAV among Aboriginal Amazonian Indians in Venezuela. Lancet, 1985; 2: 1098.
16. Ahmed, M., Quraishi, M.S. and Zuberi, SJ. Hepatitis Bs Antigenemia-role in the epidemio­logy of liver disease. JPMA., 1979; 29:23.
17. Zafar, M.N. and Zaidi, S.H. Acid phosphatase positive T4ymphoblastic (T-ALL) in Pakistani children. JPMA., 1985; 35: 6.
18, Sarngadharan, M.G., Popovic, M., Bruch, L., Schupbach, J and Gallo, R.C. Antibodies reactive with human T4ymphothropic retro­virusis (HTLV-III) in the serum of patients with AIDS. Science, 1984;224:  506.
19. Saag, M.S. and Britz, J. Asymptomatic blood doinor with a false positive Western Blot. N. Engi. J. Med., 1986; 314: 118.
20. Patricia Watson Martin,M.S.,Burger,D .R.,Caouete, S.,Goldstejn,A.S, and Peetoom,F. Importance of confirmatory tests after stronglr positive HTLV­III screening tests. N. Engi. 3. Med., 1986; 314:1577.
21. Marlink, R.G., Allan, J.S., Mclane, M.F., Essex, M., Anderson, K.C. and Groopman, J.E. Low sensitivity  of ELISA testing in early HIV infection. N. Engl. J. Med., 1986; 315: 1549.
22. Britz, J.A., Zimmerman, D.H., Mundon, F., 0’ Connor, T., Bush G.Virgo. HTLV III ELISA a sensitive and specific test for the detection of antibodies to TLV-III. In. de la Maza L.M. ED: International Symposium of Medical Viro­logy. 1985. Hillsdale NJ. Lawense Erlbau.m Associates.

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