Personal screening for HIV in developing countries

4

Prostate Disease Patient Outcome Research Team. A structured literature review of treatment for localized prostate cancer. Arch Fam Med 1993; 2: 487-93. Whitemore WF. Management of clinically localized prostatic cancer. An unresolved problem. JAMA 1993; 269: 2676-77. Institute of Cancer Research and the Royal Marsden Hospital. Prostate cancer. Report of a meeting of physicians and scientists. Lancet 1993; 342: 901-05. Miller AB. Issues in screening for prostate cancer. In: Miller AB, Chamberlain J, Day NE, Hakama M, Prorok PC, eds. Cancer screening. Cambridge: University Press, 1991: 289-93. Kramer BS, Brown ML, Prorok PC, Potosky AL, Gohagan JK. Prostate cancer screening: what we know and what we need to know. Ann Intern Med 1993; 119: 914-23. Garnick MB. Prostate cancer: screening, diagnosis, and management. Ann Intern Med 1993 118: 804-18. Hulka BS. Cancer screening. Degrees of proof and practical application. Cancer 1988; 62: 1776-80. Morrison AS. Screening in chronic disease. New York: Oxford University Press, 1992. Miller AB. Evaluation of the impact of screening for cancer of the cervix. In: Hakama M, Miller AB, Day NE, eds. Screening for cancer of the uterine cervix. (IARC Sci Publ no 76). Lyon: International Agency for Research on Cancer, 1986: 149-60. Goldbloom R. Periodic health examination, 1991 update: 3. Secondary prevention of prostate cancer. Can Med Assoc J 1991; 145: 413-28. Gerber GS, Chodak GW. Routine screening for cancer of the prostate. J Natl Cancer Inst 1991; 83: 329-35. Gerber GS, Thompson IM, Thisted R, Chodak GW. Disease-specific survival following routine prostate cancer screening by digital rectal examination. JAMA 1993; 269: 61-64. Lange PH. The next era for prostate cancer. Controlled clinical trials. JAMA 1993; 269: 95-96. Lu-Jao GL, Greenberg ER. Changes in prostate cancer incidence and treatment in USA. Lancet 1994; 343: 251-54.

Wennberg JE, and

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13

14 15

16 17

CC, Bruskewitz RC, Littenberg B, Mulley AG,

Wasson JH, Cush

Personal

the

Patient Outcomes Research Team. An

assessment

of radical

prostatectomy. JAMA 1993; 269: 2633-36. 26 Declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjects. Adopted by the 18th World Medical Assembly, Helsinki, Finland, June, 1964. 27 Wald N. Ethical issues in randomized prevention trials. BMJ 1993; 306: 563-65. 28 Fried C. Medical experimentation: personal integrity and social policy. Amsterdam: North-Holland Publishing, 1974. 29 Freedman B. Equipoise and the ethics of clinical research. N Engl J Med 1987; 317: 141-45. 30 Cochrane AL, Holland WW. Validation of screening procedures. Br Med Bull 1971; 27: 3-8. 31 Tagnon HJ. Ethical considerations in controlled clinical trials. In: Buyse ME, Staquet MJ, Sylvester RJ, eds. Cancer clinical trials: methods and practice. Oxford: Oxford University Press, 1984.

screening for HIV in developing countries

Mastro and colleagues’ reportl of female-to-male transmission of HIV-1 in Thailand shows again that with should be human surprises expected immunodeficiency virus (HIV): on the basis of a statistical analysis of young Thai military conscripts, Mastro et al reported that HIV is 30-50 times more infectious for female-to-male transmission than previously estimated. Although reasons remain elusive, they proposed that the higher transmission probability is consistent with national epidemiological patterns of HIV infection. Similar uncertainty over HIV being faced by investigators in Thailand was also voiced in a recent survey of 150 top AIDS researchers.2 They noted that new knowledge about HIV is often at odds with old assumptions. This realisation should also hold true for public health professionals, in their attempt to control the HIV epidemic. Rather than assume that the correct path is known, health officials should remain open to new thoughts and new programmes. Encouraging voluntary and anonymous testing for HIV in the privacy of the home is one such new approach. Since

Department of Epidemiology, University of California Los Angeles, Los Angeles, CA 90024, USA (Prof R R Frerichs DrPH) 960

PHM, Verbeek ALM, Straatman H, et al. Evaluation of overdiagnosis of breast cancer in screening with mamography: results of the Nijmegen programme. Int J Epidemiol 1989; 18: 295-99. 19 Tulinius H. Latent malignancies at autopsy: a little used source of information on cancer biology. In: Riboli E, Delendi M, eds. Autopsy in epidemiology and medical research (IARC Sci Publ no 112). Lyon: International Agency for Research on Cancer, 1991: 253-61. 20 Black WC, Welch HG. Advances in diagnostic imaging and overestimations of disease prevalence and the benefits of therapy. N Engl J Med 1993; 328: 1237-43. 21 Oesterling JE. Prostate-specific antigen: improving its ability to diagnose early prostate cancer. JAMA 1991; 267: 2236-38. 22 Wilson JMG, Jungner G. Principles and practice of screening for disease. Geneva: World Health Organization, 1968. 23 Johansson JE, Adami HO, Andersson SO, Bergstrom R, Holmberg L, Krusemo UB. High ten-year survival rate in patients with early, untreated prostatic cancer. JAMA 1992; 267: 2191-96. 24 Chodak GW, Thisted RA, Gerber GS, et al. Outcome following conservative management of patients with clinically localized prostate cancer. N Engl J Med 1994; 330: 242-48. 25 Lu-Yao GL, McLerran D, Wasson J, Wennberg JE, for the Prostate 18 Peeters

accurate, acceptable, and inexpensive HIV screening tests, what is needed is political will to make tests available in the private sector and to support the evaluation of widespread self-testing as a control strategy.

there

are

Prevention of HIV transmission are three main HIV transmission from an infected ways prevent partner. The first is to assume that all sexual partners might be infected and use condoms with every penetrative sexual event. With a slippage and breakage rate of 10%, the risk reduction associated with universal condom use would be near 90%,3 although others have estimated condom effectiveness to be nearer 70%.4 The promise of such a striking reduction in virus transmission has made condoms the intervention method of choice of the World Health and other international Organization (WHO) The second discussed organisations. approach being by many workers is a vaccine, which has not yet been developed.5 Even if such a vaccine becomes available, the effectiveness probably would range from 60% shown for the cholera vaccine to 95% for the measles vaccine. A third method that holds great promise is voluntary home testing.6 Depending on the sensitivity of the test and the length of the

For

people to

in

developing countries, there

viraemic but antibody-negative window period, such testing might reduce risk by 95-99% if people use the

information to avoid intercourse with an infected partner. Persons who both test their sexual partner and use condoms would have the lowest risk.

Home testing for HIV Infection Now that assays are available to accurately detect HIV antibodies in saliva/-9home testing is the logical next step for individuals wanting to protect themselves from HIV. WHO recommends testing of blood donations to avoid transmission, and suggests ways to reduce costs of screening in developing countries.1O The development of similar low cost testing strategies should be encouraged in the prevention of spread from an infected sexual partner. Technology already exists to obtain saliva specimens at home with special collection devices.9 With additional changes in the market place, people could send numbered specimens to a local laboratory and receive the results anonymously within a few days. If cost is reasonable, the screening test could be widely sold in the private sector in a distribution network similar to that for condomspharmacies, food stores, or medical clinics. Home testing by its nature would be voluntary and anonymous. Rather than demanding that saliva be evaluated as a diagnostic medium for HIV infection, simple saliva tests should be viewed as screening measures for individuals to identify if they or their sexual partners are probably HIV infected. If the saliva test is positive, subjects should be encouraged to go to a medical practitioner for confirmatory testing with blood. Once self-screening is widely being practised, medical personnel would spend less of their time with HIV-negative persons (ie, the worried well). Home testing would eliminate the need for venipuncture screening facilities and labour-intensive pretest counselling sessions-two components that add greatly to the cost and inconvenience of testing in many developing countries. Instead, health officials could spend more of their scarce resources on people who are actually infected, including diagnostic testing and counselling about treatment and care options, and ways to limit transmission.

HIV In Thailand Thailand is facing a major HIV epidemic, which is well documented by an innovative sentinel surveillance programme. Despite much technical and financial assistance, the epidemic has continued to confound experts with its persistently rising prevalence in most sentinel groups. The prevalence of infection in lower-class sex workers has risen strikingly from about 5 % in June, 1989, to over 30 % in June, 1993. The rate has been equally alarming among males at sexually transmitted disease (STD) clinics and higher-class sex workers, rising from a low of 1-2 % to a high of 8-10% during 1989-93. Finally, the most frightening increase of all has occurred in women at antenatal clinics who showed a low prevalence of 01% in June, 1989, and 4 years later are edging towards 2% (information from the Division of Epidemiology, Thai Ministry of Public Health). Other recent studies of young men entering the military in the northern region of Thailand have reported HIV prevalence of 12-15%, supporting the notion that the epidemic is gaining momentum and that existing control strategies are not successful, most notably in the general population.ll,12 The rapid expansion of the epidemic has occurred at a time when Thailand has substantial funding and technical

assistance to support control efforts.13 Funds have come from the active national economy and from international donor agencies. Like most government health agencies, the Thais have followed the HIV control suggestions of WHO and various non-governmental organisations-namely, screening of blood, promoting early treatment of sexually transmitted diseases, health education of the public about ways to prevent HIV transmission, sterilisation of blood injecting equipment, and promotion and sale of inexpensive condoms, especially to commercial sex workers .5,14 Testing of people for HIV antibodies was not judged a desirable option in Thailand, but it is done in a small way by some insurance companies, private practitioners, and a few anonymous testing centres run by the Red Cross and other organisations. As a result, most Thai citizens, like most populations in developing countries, have no way of knowing whether they or their sexual partners are infected with the virus.

Transmission In couples If infection with the HIV-1 strain reported by Mastro and associates’ occurs before marriage in Thailand, the susceptible partner will soon become infected. On the assumption of a transmission probability of 0 031 per coital event,! 91 coital events per year, 5% condom use, and a condom slippage or breakage rate of 10%,3 there is a 91 % chance that the sexual partner will be infected during the first year of marriage. Of course, steps can be taken to avoid becoming infected. In view of present policies, couples in Thailand will probably be unaware of each other’s HIV infection status. Thus condoms could be recommended for every coital act. Most married Thais, however, do not favour this approach. Only 5% of Thai married couples use condoms on a regular basis (information from the Thai Red Cross and Chulalongkorn University), suggesting that condoms are viewed as both a hindrance to conception and an unnecessary intrusion into the intimacy of marriage. If inexpensive HIV home tests are available, the couple has another option. They could screen each other for the presence of HIV antibodies and then act on the findings. A screening test should be an important component of partner selection so that marriage can start as a union between two uninfected persons. Such screening would prevent men from marrying HIV-infected women who return home after spending several years as a commercial sex worker. It would also prevent women from marrying men who have experimented in their youth with illicit intravenous drugs, anal intercourse with other men, or the services of

prostitutes. Once married, a monogamous woman faces the danger of being infected by her promiscuous or drug-using husband. If he shows signs or symptoms of an STD or fresh needle-marks, she could again quietly screen him at home for HIV or she could insist he always use a condom for sexual intercourse. It is also possible that the act of testing makes both partners more aware that either might become infected and, thus, view more favourably the practice of monogamy.

Conclusions What is evident from the dramatic emergence of the HIV epidemic is that people in Thailand, as in other developing countries facing such epidemics, have few alternatives other than premarital screening and monogamy for saving their country from social and economic disaster. It is time to 961

reconsider old ideas and questionable assumptions about what will and will not work. It is time for public health officials in developing countries to join with the private sector and evaluate the cost and effectiveness of home testing for HIV infection.

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References 1

2

Mastro TD, Satten GA,

Nopkesorn T, Sangkharomya S, Longini IMJ. Probability of female-to-male transmission of

11

HIV-1 in

Thailand. Lancet 1994; 343: 204-07. Cohen J. AIDs research: the mood is uncertain. Science 1993; 260:

12

1254-55.

3 4 5

Trussell J, Warner DL, Hatcher RA. Condom slippage and breakage rates. Fam Plan Perspect 1992; 24: 20-23. Weller SC. A meta-analysis of condom effectiveness in reducing sexually transmitted HIV. Soc Sci Med 1993; 36: 1635-44. Kallings LO. HIV infection in the nineties. Vaccine 1993; 11: 525-28.

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Frerichs RR, Seymour E. More on office-based testing for HIV. N Engl J Med 1993; 328: 1717. Frerichs RR, Htoon MT, Eskes N, Lwin S. Comparison of saliva and serum for HIV surveillance in developing countries. Lancet 1992; 340: 1496-99. Frerichs RR, Eskes N, Htoon MT. Validity of three saliva assays for HIV-antibodies. J Acq Immun Def Syndr 1994; 7: 522-24. Tamashiro H, Constantine NT. Serological diagnosis of HIV infection using oral fluid samples. Bull WHO (in press). Tamashiro H, Maskill W, Emmanuel J, Fauquex A, Sato P, Heymann D. Reducing the cost of HIV antibody testing. Lancet 1993; 342: 87-90. Nelson KE, Celentano DD, Suprasert S, et al. Risk factors for HIV infection among young adult men in northern Thailand. JAMA 1993; 270: 955-60. Nopkesorn T, Mastro TD, Sangkharomya S, et al. HIV-1 infection in young men in northern Thailand. AIDS 1993; 7: 1233-39. Bamber SD, Hewison KJ, Underwood PJ. A history of sexually transmitted diseases in Thailand: policy and politics. Genitourin Med 1993; 69: 148-57. Weniger BG, Limpakarnjanarat K, Ungchusak K, et al. The epidemiology of HIV infection and AIDS in Thailand. AIDS 1991; 5 (suppl 2): S71-S85.

BOOKSHELF

of beta-blockers in dilated cardiomyopathy, and descriptions of the Basic science and clinical aspects.-Edited by Judith K Gwathmey, G Maurice Briggs, investigational use of a number of Paul DAllen. New York: Marcel Dekker. 1993. Pp 714.$195. ISBN 0-824787722. preclinical cardioactive agents. : Despite the excellence of most of the contributions the monograph perpeHeart failure affects large numbers of tuates the gulf between clinical and techniques of basic science to the will individuals with a devastating morof heart failure basic research in cardiology by failing problem ultimately and benefit in care. The to bidity and mortality widespread bring patient integrate molecular approaches. economic consequences. The cause in theme it presents is therefore timely. Development of such links many The authors are mostly from the east most patients is myocardial infarction would regard as being key to a further ern seaboard of the United States but with a decrease in the bulk of funcincrease in our understanding of this tional muscle; but this is just the include other international authoriand indeed other aspects of heart disease. There is, for example, no beginning. There follows a series of ties. The book provides the essential that include a for who wants a mention of the application of transgeanyone compensatory changes background of transition in the cardiac phenotype review the mechannic comprehensive technology, and the absence of with the clinical manifestations of isms of excitation-contraction even passing reference to such an initial compensatory hypertrophy coupling in normal and abnormal important potential avenue of attack later leading to progressive pump failmyocardium and, to my mind, it is one from a book that sets out to give a of the best available on that subject ure. However, the disease is heterobalanced view of the leading edge of also from the Excitation-contraction basic heart failure research is unoutset, affecting (see geneous individual cells of the failing heart in fortunate. coupling and cardiac contractile force, Dordrecht: Kluwer, 1991). The cover- : different ways. Extensive efforts have This volume then is an outstanding been directed at improving treatment is wide but is in and age particularly good comprehensive review of the basic and have resulted, particularly followthe description of the processes physiology and pathophysiology of cardiac contraction and the pharmadetermining calcium movements during the use of vasodilator therapy, in better functional status and prognosis. ing the cardiac cycle. The mechanisms cological influences thereupon. Howof signal transduction from the cell ever, my recommendation must be Nevertheless, there remain significant qualified by disappointment that the problems in the management of surface, to produce changes in the with heart of focus is so overwhelmingly on these failure, especially patients strength the heartbeat, are covered those with severe symptoms and a high in fine detail. There are also chapters topics. The way forward in better risk of ventricular arrhythmias. on related and important topics such understanding of the basis of the clinical condition will be to integrate Further refinement of therapy will as the regulation of vascular smooth the with a better basic cell molecular come undermuscle the contraction, power allowed by molecular bioonly structure of ion channels, and some logy into the domains of traditional standing of the disorder. To unravel the complex processes involved at the physiology, biochemistry, and pharaspects of applied pharmacology, molecular and cellular level will reespecially as these relate to phosphomacology. This agenda, which offers influthe best hope for further understandthe full of diesterase inhibition and to the laboratory range quire research techniques. ences of nitric oxide. The clinical ing of heart disease in general, is not and Heart failure: basic science addressed here. aspects referred to in the title are very clinical aspects, part of a superb series briefly mentioned and include the Andrew Grace from Marcel Dekker, starts from this ubiquitous chapter on diastolic and University of Cambridge, Department of Biochemistry, Cambridge CB2 1QW, UK premise-that the application of the systolic heart failure, a chapter on the

Heart failure

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use