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7 International Aspects of Al:DS and HIV Infection PROJECTIONS OF THE DISEASE OUTSIDE THE UNITED STATES The 159 countries of the world, more than half of which have reported AIDS cases, appear to fall into three categories in regard to AIDS and HIV infection. The first category is made up of developed or relatively developed countries in which the distribution of AIDS and HIV infection resembles the demographic situation in the United States, although the number of reported cases is far fewer than in the United States. The groups most affected in these countries thus far are homosexual men and IV drug users, and heterosexual spread is beginning to be recognized. Such countries include Australia, Canada, Brazil, and the nations of Europe. In general, these countries have health care and public health systems with substantial resources. Many have put into place programs, similar to those in the United States, for controlling the spread of the epidemic through certain routes of transmission (e.g., parenteral). Also, many countries, such as the United Kingdom, have initiated national public education programs on AIDS. The second category comprises developing countries where AIDS and HIV infection seem to occur among sexually active men and women in approximately equal proportions and in their offspring, and therefore where heterosexual spread is presumed to be the predominant mode of transmission. Such countries include, but may not be limited to, those of central Africa and certain countries in the Caribbean, including Haiti. 261

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262 CONFRONTING AIDS These countries have health care and public health systems with inade- quate resources (many can spend only a few dollars per capita annually on all health care). Generally, they have not begun programs to screen blood donations or to provide education to reduce HIV transmission. The third category includes those countries where AIDS or HIV infection is presently reported to be absent or at least rare. Given the modes of transmission of HIV, it is unlikely that these countries are or will remain free of infection or disease. Only some of these countries have health care and public health systems with resources adequate for mounting any programs to cope with AIDS or to reduce transmission. Because diagnosis may not be reliable and reporting is generally inconsistent in many countries, the true number of AIDS cases worldwide cannot be accurately estimated. The number of persons infected with HIV is also difficult to estimate, because few studies of the prevalence of seropositivity have been done and because the ratio of symptomatic to infected persons in developing countries is not known. At the Second International Conference on AIDS held in Paris in June 1986, FIalfdan Mahler, Director General of the World Health Organization (WHO), ventured an estimate of as many as 10 million persons infected with HIV worldwide, with a substantial proportion of these in central Africa (Mahler and Assaad, 19864. Within that region, however, the attention being devoted to studies and disease reporting varies greatly. Therefore, countries reporting the highest disease or infection levels do not neces- sarily have the highest levels or act as the foci of disease spread or origin. Approximate projections for the number of pediatric AIDS cases can be made. In some areas in Africa, about 10 percent of pregnant women are seropositive for HIV, and approximately one-third of infants born to seropositive mothers become infected with HIV within one year after birth. Thus, at least 2 to 4 percent of newborns in these areas may be perinatally infected with HIV. These proportions, if valid for other areas in central Africa, would suggest that if seropositive pregnant women deliver, possibly tens to hundreds of thousands of infants in Africa will die of AIDS in the next decade. The adoption of birth control measures in Africa has not been great for instance, Kenya has the world's highest fertility rate; hence the prospects for education and prevention in this matter seem bleak. If the same proportion of HIV-infected individuals in developing countries can be expected to progress to AIDS as in the United States (at least 25 to 50 percent in 5 to 10 years), then there will probably be millions of deaths from AIDS in central Africa in the next decade unless a treatment is found and rapidly made available. Given the poor prospects for a vaccine in the next five years and probably longer, the fact that the resources for education to reduce risks are almost nonexistent, and the

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INTERNATIONAL ASPECTS 263 fact that no successful models of education to prevent sexually transmit- ted diseases are available, it must be presumed that the situation will significantly worsen in developing countries, as it will in the developed ones. Because AIDS strikes individuals in their most productive adult years, the economic as well as health burdens resulting from HIV infection will be enormous. INTERNATIONAL ORGANIZATIONS In response to the international threat of HIV infection, the World Health Organization has proposed an initiative on AIDS (World Health Organization, 1986a). Its main features are to develop activities in the following ways: Ensure the exchange of information on HIV, its epidemiology, laboratory, and clinical aspects, and prevention and control activities. Prepare and distribute guidelines, manuals, and educational materi als. Assess commercially available HIV antibody test kits, develop a simple, inexpensive test for field application, and establish WHO refer ence reagents. Cooperate with member states in the development of national pro- grams for the containment of HIV infection. Advise member states on the provision of safe blood and blood products. Promote research on the development of therapeutic agents and vaccines, simian retroviruses, and epidemiologic and behavioral aspects of HIV infection. Coordinate collaborative clinical trials of antiviral and other drugs that have been demonstrated in human early-phase trials to show efficacy in the treatment of AIDS or AIDS-related complex. The WHO initiative will also seek additional funds from extrabudgetary sources for the support of national and collective programs of surveillance and epidemiology, laboratory services, clinical support, and prevention and control. In addition to the WHO global program, regional organizations such as the African Regional Bureau of WHO and the Pan American Health Organization, which serves as the WHO regional office for the Americas, . . ~ . are undertaking programs initiated among member countries of their regions. The European Economic Community, in addition to the research and prevention efforts in various individual countries of Western Europe, has established an advisory group of scientists drawn from its 12 member

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264 CONFRONTING AIDS countries. This group promotes and funds activities aimed at ensuring "concerted action" among the various member states. RATIONALE FOR U.S. INTERNATIONAL INVOLVEMENT A variety of factors suggest that the United States should be actively involved internationally in efforts to control AIDS and HIV infection. Foreign Policy Considerations Over the last few decades, through a variety of mechanisms, the United States has actively promoted the technological development of less developed countries for economic, altruistic, and political reasons. HIV infection and AIDS are rapidly increasing in prevalence in a number of countries that have traditionally been assisted by U.S. development programs. The disease afflicts individuals in these countries at an age when they are entering or are in their most productive years. If it becomes more widespread, this disease, added to the other problems that beset these countries, may negate the benefits of all the technical assistance otherwise provided. The strongest argument for U.S. involvement in international efforts is that such support would be a logical extension of our existing interests and efforts. Indeed, the effectiveness of other U.S. technical development assistance efforts may be jeopardized if HIV infection and AIDS are allowed to spread unchecked. If the United States and other developed countries fail to vigorously support and, where appropriate, to become involved in efforts to control AIDS and HIV infection at all levels internationally, millions more than those now infected in poorer countries may die of this infection over the next decade or so, because the resources of developing countries to control this and other health problems are grossly inadequate. However, the United States should offer its assistance and expertise in appropriate ways. HIV infection is sexually transmitted and is therefore in some ways a sensitive political and diplomatic subject. But it is also transmitted in other ways, such as through the blood supply and through sharing of needles and syringes. Technical assistance in other sensitive areas has been successfully handled in the past. Also, the increasing willingness of the governments of affected countries to acknowledge the AIDS and HIV problem, as evidenced by reports from a number of developing countries at the Second International Conference on AIDS, bodes well for con- structive U.S. involvement.

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INTERNATIONAL ASPECTS 265 Health Improvement Assistance Technical assistance programs have often included major contributions to efforts in improving health through programs in immunization and nutrition. Despite extremely constrained resources for health in develop- ing countries, there has been some progress for instance, immunization levels have increased. The addition of AIDS and other HIV-related conditions to the lengthy existing agenda of health problems in developing countries imposes a burden that may reverse the hard-won gains. Anecdotal reports from some areas and hospitals suggest that AIDS is already imposing a heavy demand on the health care systems in some developing countries. If so, resources will be unavailable for other health care demands. The occurrence of pediatric AIDS will pose special problems in developing countries to immunization programs one of the major and most successful interventions for health improvement-which currently receive major support from the United States. Data from central African countries suggest that many infants are acquiring HIV infection perina- tally (Mann, 19861. When administered to infants infected with HIV, vaccines, particularly live replicating ones, may precipitate rapid progres- sion to AIDS. In addition, it is theoretically possible that live vaccines might cause severe disease in HIV-infected individuals because of their compromised immunologic state. This has been reported with smallpox vaccine (live vaccinia virus) in a military recruit. However, Halsey et al. (1986) found no evidence of severe disease resulting from other live vaccines (measles, rubella, or BCG Efor tuberculosis]) in Haiti in a small study. This situation needs further study to determine the extent of the theoretical risk. These issues raise a question of how universal immunization programs should be pursued in areas where there are infants likely to have been infected perinatally. Selective or universal screening for HIV might be necessary to avoid precipitating disease in infected infants. If HIV screening is not part of immunization programs, and if many apparently healthy but HIV-infected infants do develop AIDS rapidly after immuni- zation, perceptions that the immunization program itself was the cause of the infants' illnesses might become prevalent, diminishing the willingness of parents to permit immunization of their children. This situation would obviously decrease the control achieved over childhood infectious dis- eases and condemn many children to death and disability from them. Suspension of immunization efforts for fear of harming HIV-infected infants would have the same result. To these concerns must be added the concern for ensuring that immunization programs are carried out in such a way that they do not spread HIV infection through the use of unsterile needles and syringes.

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266 CONFRONTING AIDS Information about the HIV infection situation in many countries is incomplete, as is knowledge of the factors that influence disease progres- sion. Decisions about how to pursue immunization programs without contributing to problems related to HIV need to be made in light of local conditions and existing knowledge. The advisable precautions should be regularly reviewed. Immunization programs must continue to be actively pursued and expanded. However, increases in the prevalence of HIV infection in certain countries will make undertaking such programs logistically and technically more difficult, which will almost certainly make them more expensive. Not all of the tools needed to limit the spread of HIV are available. For example, a cheap, rapid, simple, highly specific, sensitive, and reliable test for HIV infection would be a tremendous aid to studies and health programs in all parts of the world. International Spread of Diseases In a world where millions of people travel readily from country to country and continent to continent, infectious diseases know no national boundaries. The spread of penicillin-resistant gonococci from Southeast Asia to the United States and elsewhere is a recent example of the global spread of sexually transmitted diseases. The mobile nature of today's society has also undoubtedly contributed to the spread of HIV. No country can be held responsible for the spread of an infectious disease, and all governments must contribute to decreasing the spread for the common good. The United States has traditionally recognized a responsibility to promote better health worldwide. For example, at a time when smallpox posed only a small risk to U.S. residents, the United States contributed to control efforts abroad through bilateral arrangements and the WHO program, which eventually led to global eradication of the disease. Eradication of HIV infection is presently not a realistic goal without effective vaccines, and it may never be achievable if the virus has an animal reservoir. Nevertheless, educational programs and other commu- nity efforts must begin immediately to curb the spread of the virus. Opportunities for Mutually Beneficial Research There are additional reasons for U.S. international involvement. HIV poses a major problem for the United States, and there are many aspects of the infection and disease that need to be better understood before control will be achieved. Thus, while supporting local governments in

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INTERNATIONAL ASPECTS 267 present control efforts, the United States can and should contribute to the overall global research effort by supporting studies abroad. Not only is it desirable to understand the disease in all its settings, but new knowledge critical to prevention and treatment may be more readily obtained in situations outside the United States. The extent of perinatal and hetero- sexual transmission in central Africa offers opportunities for U.S. re- search resources to complement local expertise in mutually beneficial investigations. Only by thoroughly investigating the disease in all its settings will the factors become known that are unique to its occurrence in the United States and other countries, and the extent become under- stood to which findings can be extrapolated from one situation to another. -The understanding necessary to achieve control of HIV infection and related conditions will be most rapidly acquired if all of the resources of the international scientific community are brought to bear on the problem. Barriers to international exchange of information and resources should be identified and removed. For example, standardized reagents (e.g., virus stocks) have been identified as desirable (Katz, 19861. When these have been established, they should be made available to non-U.S. investiga- tors. Reciprocity is a desirable feature of such arrangements, and U.S. efforts in this area should supplement and not compete with the efforts of WHO collaborating centers. Agencies and Organizations with International Responsibilities or Operations Certain agencies of the U.S. government have special international responsibilities or may be able to make contributions to the global effort to control the epidemic. The Agency for International Development sponsors technical assistance programs in a number of countries, includ- ing many health improvement programs in areas such as immunization. That agency, through its DIATECH program of diagnostic development, and the Food and Drug Administration, through its expertise in diagnos- tics and blood safety, could contribute to the development of sorely needed tools or to training. Many commercial organizations in the United States also have consid- erable expertise in diagnostics, therapeutics, and vaccine development that could be put to the service of the international effort to control HIV infection and AIDS. A further reason for U.S. involvement is that many federal agencies and other organizations require that their personnel visit or reside in other countries where HIV infection may be relatively prevalent. Policy con- siderations deriving from this situation relate either to the possibility that such service places an employee at risk of infection or to the need to

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268 CONFRONTING AIDS ensure that individuals who are diagnosed with HIV-related conditions receive appropriate care. As described in the next section, the major involuntary situations resulting in risk of infection would be accidents or illnesses requiring emergency medical treatment in local foreign facilities, where infection with HIV might occur as a result of the transfusion of blood from an infected donor or from the use of unsterile implements such as needles and syringes. Policies on these issues need to be developed in light of knowledge of local circumstances and the possibility that some individuals (e.g., hemophiliacs) may be more likely to require emergency treatments. In regard to employees abroad who are identified as infected with HIV, policies need to be formulated taking into account the individual's capacity to fulfill work-related responsibilities, the access to appropriate local care for HIV- related conditions, and local sensitivities to the presence of such persons, even though they may pose no health risk to others. Agencies for which such issues are a particular concern are obviously the U.S. Department of State (including the Agency for International Development), the Peace Corps, and the U.S. Department of Defense. Private sector organizations with similar concerns would include any business or nonprofit groups (e.g., foundations, relief organizations, or churches) that have employees stationed abroad. Importation The U.S. government has recently proposed adding clinical AIDS to the list of "dangerous contagious diseases" for which aliens may be denied admission to the United States. This action acknowledges the risk that such people may pose to sexual contacts and the burden that they may put on the U.S. health care system. It overlooks, however, the risk posed by the larger number of seropositive aliens without AIDS and, more important, the vastly larger number of U.S. citizens already infected with the virus, who are the most likely source of infection for others in the United States. If much effort goes into excluding infected people from the United States, it will waste resources that could otherwise go to more effective control measures. It may also result in other countries establish- ing restrictions on travel from the United States. INFECTION RISKS OUTSIDE THE UNITED STATES Sexual Exposure Sexual relations probably account for the largest amount of transmis- sion of the virus both inside and outside of the United States. In a recent

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INTERNATIONAL ASPECTS 269 review, Mann (1986) concludes that the dominant mode of HIV transmis- sion among adults in Africa is sexual, involving heterosexual, bidirec- tional transmission of the virus. If other factors e.g., intercurrent sexually transmitted diseases or the disruption of cervical, vaginal, or penile epithelial integrity enhance the efficiency of sexual transmission, it has not been proved. Also, the proportions of sexually active adult men and women already infected in the general population are unknown. In addition, HIV infection has become a major problem among female prostitutes in many parts of the world, with prevalence rates as high as 80 percent in some areas. Business travelers, military personnel, and others who have sexual intercourse with prostitutes are at risk of infection. Transmission of HIV between homosexual men is also well docu- mented abroad, both in developed and certain developing countries. It must be presumed to be possible wherever behavior involving risk of infection is practiced. However, the risk of infection in different parts of the world will vary with the prevalence of HIV infection, knowledge of which is incomplete. Knowledge of the frequency with which homosexual behaviors occur in different countries and cultures is also incomplete, and information may not be reliable because of problems of conducting sexual behavior research, especially cross-culturally. In conclusion, people who live in or travel to countries where HIV infection is prevalent and who engage in sex with partners whose HIV infection status is not reliably known run a very real risk of infection. That risk is likely to increase sharply as international rates of infection rise, but it clearly can be avoided by abstaining from sexual relations with unknown individuals or lessened by following "safer sex" practices. Exposure Through Blood Transfusion Contamination of blood transfusions with HIV poses a decided risk of infection in many parts of the world, the exceptions being the countries (such as those of Western Europe) that have taken precautions with blood donations and have applied the serologic test to blood banking. The risk varies with the prevalence of HIV infection among donors. In central Africa, 5 to 10 percent or greater prevalence of HIV infection among donors as measured by the serologic test has been reported (Mann, 1986~. Thus, the risk to transfusion recipients is significant. In one study nearly 10 percent of AIDS patients reported at least one transfusion in the three years prior to onset of disease. Transfusions were twice as common among those infected as among those uninfected (Mann, 19861. The WHO has issued guidelines on prevention of HIV transmission by transfused blood or blood products (World Health Organization, 1986d).

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270 CONFRONTING AIDS The recommendations urge self-exclusion from blood donation by per- sons at risk for HIV infection; testing of donated blood for HIV antibodies; improved antenatal care as a means of reducing the demand for blood; giving transfusions only when medically justified; using blood components rather than whole blood or plasma where appropriate; educating and selecting donors; and reviewing the manufacturing proto- cols of blood products to assess the acceptability of the product. Also, the WHO plans to provide reference materials for the evaluation and stan- dardization of laboratory tests, establish uniform criteria for the treatment and testing of blood products, and revise its criteria to take new manufacturing and screening procedures into account. However, many of the countries that have not adopted procedures to prevent HIV transmis- sion through blood transfusions lack the laboratory, financial, or trained personnel needed to institute such measures. The risk of infection from blood transfusions in certain parts of the world is significant. But the application of currently available serologic tests will be possible only in some situations, since it is expensive for developing countries and requires highly trained personnel to apply and confirm. Simpler serologic tests, giving sensitive and specific results rapidly and reliably, are essential before widespread efforts to control HIV transmission via the blood supply in developing countries will be practicable. IV Drug Use Transmission of HIV by sharing of IV drug use equipment is well documented and undoubtedly can happen wherever this practice occurs. The risk of infection in any area will depend on the prevalence of HIV infection, which will in turn depend on when the virus was introduced into the IV drug-using population and the frequency with which needle and syringe sharing is practiced. In certain areas, such as sub-Saharan Africa, there is widespread agreement that nonmedical (illicit) IV drug use is extremely rare (Mann, 19861. Use of Unsterile Needles and Implements In Africa, injections administered for medical purposes may be a route of exposure. In one study of HIV infection, seropositive children one to two years of age whose mothers were seronegative had a mean of 44 reported lifetime injections (excluding vaccinations), as compared with 23 injections for children who were seronegative. In adults an association has been observed between the prevalence of seropositivity in hospital

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INTERNATIONAL ASPECTS 271 workers in Kinshasa, Zaire, and the number of injections received (Mann 1986). Among adults, interpretation of the data relating to infection is compli- cated by the possibility that injections were received as early treatment for HIV-related symptoms or for sexually transmitted diseases, which may be independent risk factors for exposure to HIV (Mann, 1986~. Evidence from needlesticks among health care workers suggests that viral transmission through skin penetration by contaminated needles is relatively inefficient. There has been speculation that the use of unsterile implements in medical settings, ritual scarification, or female circumcision (genital mutilation) has the potential for HIV transmission. Mann et al. (1986a) have reported data suggesting an association, possibly indirect, between HIV infection and scarification, but the weight of evidence on the distribution of female circumcision and the findings from epidemiologic research on HIV in general suggest that they play at most a minor role in the spread of the epidemic (Hrdy, 1986; Mann, 19861. Lack of Evidence for Transmission by Insect Vectors and Casual Contact There is no evidence to support the hypothesis of HIV transmission by insect vectors or through casual contact in developing (or developed) countries. Notwithstanding a report that regions in DNA of various insects from central Africa are homologous with HIV proviral DNA (Becker et al., 1986), other sources of data suggest that vectorborne or casual contact transmission is unlikely. The age distribution of observed cases peaking in infants and young adults but relatively absent among children between 1 and 14 years of age-is not consistent with either insect or casual transmission. Also, studies of nonspousal household contacts of AIDS patients and controls have revealed no differences in rates of HIV seropositivity. All observed infections among household contacts have been explicable on the basis of sexual or perinatal trans- mission (Mann et al., 1986b). Finally, the relative inefficiency of acciden- tal needlestick transmission, the relatively small volume of blood carried by most common vectors such as mosquitoes, and the low blood titer of HIV all suggest that mechanical transmission by insects is unlikely (Zuckerman, 19861. Conclusions The risks of exposure to HIV by the various routes of transmission discussed above vary in different countries. In all settings, the dominant

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272 CONFRONTING AIDS risk is probably sexual intercourse (heterosexual or homosexual), but the risk from contaminated blood transfusion in some areas is very real. American foreign travelers or residents abroad should be apprised of the risk they face. INTERNATIONAL RESEARCH OPPORTUNITIES The differences in epidemiologic patterns of HIV infection among countries offers a remarkable opportunity to define modes of spread and the effectiveness of alternative control strategies by concentrating re- sources where they could be most effectively used. Direct studies of the risk of heterosexual transmission would be useful but are hard to conduct in the United States because the number of heterosexual cases is small. Central Africa, where heterosexual transmission seems to predominate, may offer an opportunity for such studies. Collaborative studies could define the relative ease of transmission from man to woman and from woman to man, the rate of transmission in varied sexual practices, and the effectiveness of different modifications of sexual behavior on the progression of the epidemic. The presence of large numbers of infected women of childbearing age offers both the opportu- nity and the need to study the factors affecting transmission from mother to child and the natural history of infection in children. The problem of mother-to-child transmission of HIV in Africa is potentially great, but to date relatively few pediatric cases of AIDS have been recognized there. Given the frequency of AIDS and HIV seropositivity in women of childbearing age, programs of identifying infected women and counseling them about the risk of transmission may, if effective, prevent rapid spread of the epidemic into the next generation. Studies of cohorts of infected and uninfected women who go on to have children may also help define cofactors that increase the probability of infection or illness in their offspring and lead to ways to intervene and lower those risks. Studies are also needed of seroconversion and risk factors in children born to seronegative mothers to identify the manner in which they became infected. In Southeast Asian cities with a low prevalence of infection, techniques for prevention and control of the disease early in the course of a possible epidemic could be tested. Spread of infection from prostitutes into the general population could be studied in those countries in which cases were first seen in prostitutes. There is great need for systematic surveillance of HIV infection in Africa and other developing countries. Knowledge of the present preva- lence of the disease and of trends in its incidence would enable better allocation of local and international resources for control. It would also

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INTERNATIONAL ASPECTS 273 identify opportunities for research that might have international implica- tions. As noted above, WHO has set up an AIDS program that will work with ministries of health in surveillance and control activities. The role of WHO as coordinator can complement bilateral agreements that several European and U.S. agencies have initiated with local governments or . . . universities. Investigation of the existence of cofactors (risk modifiers) for the acquisition and progression of infection and disease in both the United States and abroad is an example of opportunities for research in devel- oping countries, but it also exemplifies an area in which particular care will be needed in extrapolating findings to the U.S. situation. It will be important to determine if any bacterial or parasitic disease endemic in Africa increases the probability of HIV infection and AIDS. Also, the differences in epidemiology of classical and aggressive Kaposi's sarcoma in Africa (as well as the differential susceptibility to Kaposi's sarcoma of male homosexuals compared with other AIDS patients in the United States) suggest the value of looking for an infectious agent or risk factor of aggressive Kaposi's sarcoma separate from HIV. The heavy burden of parasitic and other infectious agents borne by many African populations generally and the distinctive infectious disease patterns seen in African AIDS patients suggest the importance of exam- ining in far greater detail the interaction of HIV with a variety of infectious agents. It seems clear that the immunodeficiency characteristic of AIDS results in the presentation of AIDS patients with disseminated infections with agents common there, such as Mycobacterium tuberculo- sis. However, studies may show that chronic or repeated infections (for example, with malaria or enteric bacteria) increase the probability that latent infection with HIV may become manifest, or that infections that breach the skin or mucous membranes may predispose to HIV infection in the first place. Recent identification of additional human retroviruses in western Africa (see Chapters 2 and 6), one of which appears similar to a virus identified in wild monkeys, suggests that extensive investigation of primate and human retroviruses is warranted in all areas of sub-Saharan Africa. Support for establishing surveillance systems for HIV infection and programs for prevention of transmission and disease could result not only in definition and control of the AIDS problem but also in a model for surveillance and control of other infectious and noninfectious diseases in developing countries. Working through bilateral projects with individual countries or through multilateral arrangements, as with WHO, the United States could leverage its support of AIDS research and control to further public health practice internationally. Any research conducted by U.S. investigators in other countries, .

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274 CONFRONTING AIDS particularly developing ones, is extremely sensitive, and this is especially true of research on sexually transmitted diseases. It is necessary that such research be done in truly collaborative fashion and in a manner that takes account of local cultural or social mores. Guidelines for such efforts should be developed to ensure that the long-term prospects for collabo- rative efforts are not damaged by cultural or political insensitivities. THE U.S. CONTRIBUTION TO INTERNATIONAL EFFORTS The United States has contributed greatly to the understanding of AIDS and HIV infection through its investment in domestic research. The mandates of various federal agencies recognize that the health of U.S. citizens can benefit from studies abroad. Hence, investigators supported by the Centers for Disease Control, the National Institutes of Health, and the Department of Defense have been involved in collaborative epidemi- ologic, serologic, and virologic studies of AIDS and HIV infection at various sites around the world, particularly in sub-Saharan Africa but also in Europe and Southeast Asia. Until the fall of 1985 the Agency for International Development of the Department of State the only federal agency with a direct mandate to be involved in international health activities had no specific policy with regard to support of activities related to AIDS or HIV infection. (It should be noted that some countries affected by AIDS do not meet the general conditions for support from the Agency for International Development e.g., Brazil, Tanzania.) In November 1985, however, its administrator, M. Peter McPherson, committed the agency to involvement in inter- national efforts on the problem. This commitment resulted in an an- nouncement in June 1986 of the provision to WHO of $2 million in FY 1986 (Agency for International Development, 19861. Of this amount, $1 million was to be a contribution to the central WHO effort to establish a global surveillance system, to provide epidemiologic and laboratory consultants to member countries, and to ensure the safety of the blood supply. The other $1 million would go directly to WHO's regional office for Africa in Brazzaville, Congo, to support WHO surveillance and educational activities in Africa with the assistance of the Centers for Disease Control. The plans of the regional office for Africa are to provide some basic support in most African countries and in four to six countries to establish pilot programs to establish diagnostic capabilities and report- ing of AIDS and HIV infection and to assist these countries in establishing public health prevention and control activities for AIDS. In addition to the monetary commitment to WHO, the Agency for

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INTERNATIONAL ASPECTS 275 International Development's Bureau of Science and Technology Office of Health established in August 1986 a position to monitor and coordinate AIDS activities. A federal interagency working group on the international aspects of AIDS and HIV infection also meets periodically. It is convened under the auspices of the U.S. Department of State. It is the committee's understanding from its discussions with represen- tatives of the Department of State and the Agency for International Development that the primary focus of these agencies' support to international activities will be through WHO. AIDS-related requests for technical assistance or support from foreign governments will be directed to that organization. However, the committee believes that bilateral or multinational activ- ities involving the United States outside the WHO program will be essential to enhancing the prospects for control of the disease. It agrees that to be most effective these must be coordinated with WHO's efforts. But a multiplicity of innovative activities may be needed to find the best ways to successfully tackle the problem, and a diversity of approaches would be useful in the search. Bilateral or multinational efforts can usefully complement the WHO program for a number of reasons: 1. The WHO program is new and in the early phases of organization. It has a small staff and thus far has received less than 20 percent of the funds estimated to be required for the 1986-1987 biennium (World Health Organization, 1986b; J. Mann, World Health Organization, personal communication, 19861. Support for the program is still under consider- ation by a number of potential donors (Lancer, 1986; World Health Organization, 1986b,c). However, the need for action in some countries is urgent: all opportunities to supplement the WHO program, as it becomes established and expands, should be acted upon as soon as possible because of the seriousness of the epidemic. 2. The focus of the WHO program is prevention and control of AIDS and HIV infection. There will be opportunities for productive freestand- ing research projects or research projects that could usefully be coupled to prevention and control efforts but that do not fall within the scope of the WHO program. These could be pursued bilaterally, with funding from agencies such as the National Institutes of Health, the Centers for Disease Control, and the Department of Defense, as well as the Agency for International Development. 3. Many U.S. investigators or institutions with expertise in the study of AIDS or other infectious diseases have direct links with counterparts in

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276 CONFRONTING AIDS affected countries. These links provide the opportunity to respond rapidly to needs identified by the governments of such countries. The committee further believes that efficient coordination and use of resources can be achieved by international exchange of information on national activities, perhaps with WHO as a central clearinghouse. CONCLUSIONS AND RECOMMENDATIONS AIDS and HIV infection pose a new global health problem that will affect most adversely the poorer developing countries, where health systems are least able to cope with the increased burden on resources. The impact of the epidemic could stall or reverse progress that has been achieved in health and economic areas e.g., in child survival in many developing countries. The initial phases of data collection on the disease met with some reluctance in acknowledging the presence and magnitude of the problem. However, establishment of the WHO program and increasing recognition of the seriousness of the situation, as evidenced by reports from various countries at the Second International Conference on AIDS, have opened up opportunities for the United States to play a role worldwide in efforts to control HIV infection and AIDS. The United States should be a full participant in international efforts. U.S. involvement should be both through support of WHO programs and through bilateral arrangements in response to the needs and opportunities in individual countries. It should also be pursued in a fashion that is acceptable to host governments in these collaborating countries. The Agency for International Development is to be commended for moving rapidly to provide $2 million to the WHO to support efforts to control AIDS, but much more money will certainly be needed. Increased contributions to international efforts in this area are needed through a variety of mechanisms for instance, support of the World Health Organization, support of collaborative research (for example, through the National Institutes of Health, the U. S. Department of Defense, and the Centers for Disease Control), and support of bilateral technical assistance agreements. Given the magnitude of the problem, particularly in central Africa and increasingly in Latin America, and the variety of reasons warranting U.S. participation in international efforts, the committee believes that the United States should make clear its commitment to global prevention and control of AIDS and HIV infection. By 1990, the total funding flowing to international efforts directed toward AIDS-related research and prevention should reach $50 million

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INTERNATIONAL ASPECTS 277 per year on a continuing basis. This amount is about 2.5 percent of the total expenditures that the committee recommends be spent annually in the United States for these purposes. Increased funding should be provided to the WHO program on the basis of demonstrated capacity to use such funds productively. Increased funds for research or technical assistance programs or projects abroad should be provided on the basis of review procedures involving individuals familiar with the conditions, such as the local availability and quality of laboratory resources and personnel, under which such projects are undertaken. The committee found that there was no tabulation or assessment of the extent and nature of work being undertaken on HIV-related condi- tions by U.S. investigators in other countries or of their collaborations with foreign researchers. It therefore recommends that an evaluation be initiated immediately to assess and coordinate the roles and responses of the various U.S. federal agencies, private voluntary groups, and founda- tions interested in international efforts on AIDS and HIV and to identify all work currently under way. Efforts to use funds and other resources of the United States, other industrialized countries, and the WHO would be aided by the establish- ment of national data bases or clearinghouses on AIDS and HIV-related work being undertaken in or involving collaboration with foreign coun- tr~es. These groups should communicate regularly with WHO. Pending the more formal establishment of information centers, the office of the AIDS coordinator of the Public Health Service should serve as a clearinghouse for information on U.S. international activities on AIDS and HIV infection and should be provided with the resources to play a greater role in the United States' international efforts. REFERENCES Agency for International Development. 1986. U.S. Aid Assists World Health Organization to Control Global AIDS. News Release, June 13, 1986, Washington, D.C. Becker, J.-L., O. Hazan, M.-T. Neugeyere, F. Rey, B. Spire, F. Barre-Sinoussi, A. Georges, L. Teulieres, and J. C. Chermann. 1986. Infection of insect cell lines by HIV, agent of AIDS, and evidence for HIV proviral DNA in insects from central Africa. C. R. Acad. Sci. (Paris) 303:33-36. Halsey, N. A., R. Boulos, M. Robert-Guroff, J. Hughes, E. Holt, J. Rohde, and C. Boulos. 1986. Measles vaccination of infants born to LAV/HTLV-III positive mothers. P. 49 in Abstracts of the Second International Conference on AIDS, Paris, June 23-25, 1986. Hrdy, D. 1986. Sexual preferences and other cultural practices contributing to the spread of AIDS in Africa. Background paper. Washington, D.C.: Committee on a National Strategy for AIDS. Katz, S. O. 1986. Summary of a Workshop of AIDS Vaccine Development. Presented at the

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278 CONFRONTING AIDS Workshop on AIDS Vaccine Development, National Institutes of Health, Bethesda, Md., July 28-29, 1986. Lancer. 1986. WHO's efforts to contain AIDS. Lancet 1:1167. Mahler, H., and F. Assaad. 1986. The World Health Organization's programme on AIDS. P. 5 in Abstracts of the Second International Conference on AIDS, Paris, June 23-25, 1986. Mann, J. M. 1986. Epidemiology of LAV/HTLV-III in Africa. Paper presented at the Second International Conference on AIDS, Paris, June 23-25, 1986. Mann, J. M., H. Francis, T. C. Quinn, P. K. Asila, N. Bosenge, N. Nzilamb~, K. Bile, M. Tamfum, K. Ruti, P. Plot, J. McCormick, and J. W. Curran. 1986a. Surveillance for AIDS in a central African city: Kinshasa, Zaire. JAMA 255:3255-3259. Mann, J. M., T. C. Quinn, H. Francis, N. Nzilambi, N. Bosenge, K. Bila, J. B. McCormick, K. Ruti, P. K. Asila, and J. W. Curran. 1986b. Prevalence of HTLV-III/LAV in household contacts of patients with confirmed AIDS and controls in Kinshasa, Zaire. JAMA 256:721- 724. World Health Organization. 1986a. WHO Activities for the Prevention and Control of Acquired Immunodeficiency Syndrome. Geneva: World Health Organization. World Health Organization. 1986b. Global Strategy for the Prevention and Control of Acquired Immunodeficiency Syndrome: Projected Needs for 1986-1987. Geneva: World Health Organization. World Health Organization. 1986c. Meeting of Participating Parties for the Prevention and Control of Acquired Immunodeficiency Syndrome. Geneva: World Health Organization. World Health Organization. 1986d. WHO meeting and consultation on the safety of blood and blood products. WHO Weekly Epidemiol. Rec. 18:138-140. Zuckerman, A. J. 1986. AIDS and insects. Br. Med. J. 292:1094-1095.