STRENGTHENING OF THAILAND'S NATIONAL CAPACITY

Strengthening of Thailand's Biomedical Research Capacity

Donald S. Burke

Walter Reed Army Institute of Research, Rockville, USA

The social, political, and economic dimensions of the HIV/AIDS epidemic in Thailand have recently become clear to the international development community. Publications such as The Global AIDS Disaster: Implications for the 1990s, by the U.S. Department of State,1 and World Development Report 1993: Investing in Health, by the World Ba nk,2 underscore the immediate threat posed by the epidemic. Health research is recognized as indispensable to the process of successful development, as reported in Health Research: Essential Link to Equity in Development, by the Commission on Health Research for Development.3 Training of health professionals is a key ingredient in this process, as outlined specifically for Thailand in Internation al Investment in Human Capital: Overseas Education for Development.4

Recently, Dr. Max Essex, of the Harvard AIDS Institute, and I were asked by the Dean of the Faculty of Graduate Sciences of Mahidol University to review that university's existing graduate training programs in virology and related disciplines such as molecular biology, and to make recommendations for strengthening the curricula in these programs. Particular emphasis was to be given to molecular virology, especially retrovirology. A complete report was submitted to Dr. Monthree Chulasamaya and Dr. Natth Bhamarapravati. Our recommendations follow.

Recommendations for immediate actions (one to two years):

1. Expand the excellent but limited curriculum of didactic HIV/AIDS courses from their current six weeks in the English language international program to a full 16-week semester in the standard curriculum. Serious considerations should be given to making one or more of these HIV/AIDS courses a requirement for a degree in microbiology.
2. Convene a workshop of respected Thai and selected international scientists to review existing knowledge on HIV/AIDS with special emphasis on those features of the epidemic that are unique to Southeast Asia. Then define the two priority research questions for both Thailand and the region.
3. Establish or seek out special sources of funding support for a program of independent research on HIV/AIDS by Thai laboratory scientists, as a way of providing an additional incentive for commitment to work on HIV/AIDS. Individual grants need not be large, but should be secure for several years and of sufficient monetary value to provide essen tial equipment and supplies, on the order of 500,000 Baht ($20,000) per year. A total of five such grants should be established.
4. Establish or seek out special sources of funding support for a program for postgraduate training of Thai scientists in HIV/AIDS laboratory work in North America or Europe. A total of five such training grants should be awarded each year.
5. Submit proposals immediately to Thai governmental and international agencies to strengthen retrovirology. Because of the tremendous importance of the HIV epidemic, the established quality of Mahidol University in related areas, and the need for a reference training center in Southeast Asia, such proposals should be competitive.

Recommendations for medium-term actions (three to five years):

6. Establish a "Center of Excellence in HIV/AIDS Research" or "Mahidol HIV/AIDS Institute" that can serve as a regional center for HIV/AIDS research in Southeast Asia. Such a center would be multidisciplinary and would focus on funding practical solutions to special public health problems in Southeast Asia (as reported by the expert workshop in i tem two above).

Recommendations for long-term actions (five to twenty years):

7. Anticipate that over the next two decades Thailand will become increasingly self-sufficient in vaccine development and in the production of other biological products for use in medicine. Training programs in vaccine development and biologicals production should be established.
8. Anticipate that over the next two decades there will be much closer public-private sector cooperation in Thailand on research and development and the manufacture of products important for public health, such as vaccines. Thailand is now well positioned to capture markets for several vaccines and other biologicals particular to Southeast Asia. Mahidol University should begin forging mutually beneficial relationships with the pharmaceutical industry now.

References

1. U.S. Department of State. The Global AIDS Disaster: Implications for the 1990s. July 1992.
2. World Bank. World Development Report 1993: Investing in Health. Oxford University Press, 1993.
3. Commission on Health Research for Development. Health Research: Essential Link to Equity in Development. Oxford University Press, 1990.
4. Thailand: a case study. In: International Investment in Human Capitol: Overseas Education for Development. Institute for International Education, 1993.

Strengthening of Thailand's Clinical Research Capacity

Pikul Moolasart and Chana Tanchanpong

Bamrasnaradura Infectious Disease Hospital, Nonthaburi, Thailand

The first AIDS patient in Thailand was diagnosed in 1984. Bamrasnaradura Infectious Disease Hospital opened the first HIV/AIDS inpatient unit in Thailand in 1987. The total number of inpatients with HIV through December 1993 was 1,813 (Table 1[table not available through VINE]). The number of new patients with HIV increases each year. Of the 1,813 inpatients with HIV, 24%--or 436--have died (Table 2). Their ages ranged from 4 months to 72 years. The mortality rate of HIV/AIDS patients at Bamrasnaradura Infectious Disease Hospital seems higher than those in other hospitals because it is a referral hospital for treating HIV/AIDS patients and some of the referred patients were in late stages of illness.

Chronic diarrhea and persistent diarrhea were common clinical presentations of AIDS in both adults and children. The pathogenic organisms isolated in their stools are detailed in Table 3. Salmonella group B was the majority of Salmonella spp. isolated. The other pathogenic organisms were Vibrio cholera non-01, Campylobacter jejuni, Aeromonas hydro phila, and Plesiomonas shigelloides.

The cost of AIDS care of inpatients in Bamrasnaradura Infectious Disease Hospital was roughly evaluated for the six months between June and December 1993. The total cost of AIDS care per admission of 303 cases of HIV/AIDS patients was 918,983 Baht (US$36,759), an average of 3,032.95 Baht (US$121) per case. Drugs accounted for most of the cost; the remaining was for laboratory testing. These figures do not include the cost of protective barriers, disinfectants, and other supporting material and treatments.

Various approaches to clinical research of HIV infection have been carried out in Thailand in conjunction with the care of HIV/AIDS patients. Clinical studies of the epidemiology, clinical presentation, diagnosis, and treatment of AIDS patients were performed in many Thai institutes, including Bamrasnaradura Infectious Disease Hospital. The prelim inary reports of cases, clinical issues, and clinical studies in this hospital are: Pediatric AIDS: Report of Three Cases; Surgical Technique in AIDS Patients; Recommendations for Prevention of the Transmission of HIV in Health Care Settings; and Opportunistic Infections in AIDS Patients.

A number of collaborative studies of Bamrasnaradura Infectious Disease Hospital and other institutions have been performed in this hospital. These studies are:

1. The Clinical Presentation of AIDS in Thailand--collaborating institutions include Bamrasnaradura Infectious Disease Hospital; the HIV/AIDS Collaboration, Bangkok, Thailand; and the U.S. Centers for Disease Control and Prevention (CDC), Atlanta, USA;
2. Comparative Performance of Six Clinical AIDS Case Definitions in Thailand--collaborating institutions include Bamrasnaradura Infectious Disease Hospital, the HIV/AIDS Collaboration, and the CDC;
3. Survivorship of AIDS Patients Attending Bamrasnaradura Hospital, Thailand--collaborating institutions include Bamrasnaradura Infectious Disease Hospital, the HIV/AIDS Collaboration, the CDC, and the Division of Epidemiology, Ministry of Public Health, Thailand;
4. HIV/AIDS Data Collection and Management System--collaborating institutions include Bamrasnaradura Infectious Disease Hospital, the HIV/AIDS Collaboration, and the CDC;
5. Treatment of HIV-Infected Patients with WF-10 (Tetrachlordecaoxygen anion complex, or TCDO)--collaborating institutions include Bamrasnaradura Infectious Disease Hospital and the Kuhne Foundations, Germany;
6. Treatment of HIV/AIDS Patients with Alpha Interferon--collaborating institutions include Bamrasnaradura Infectious Disease Hospital and Siriraj Medical School, Mahidol University, Thailand.

Problems of providing care and conducting clinical research in HIV/AIDS patients at Bamrasnaradura Infectious Disease Hospital primarily stem from personnel, space, and budgetary constraints. Personnel constraints include a lack of personnel to care for patients and to conduct research; excessive workloads; a lack of knowledge and experience in ma nagement, medical technology, and prevention; and fear of the disease. Space is constrained for both patient care and clinical research. Budgetary limitations affect personnel, space, the availability of drugs, the feasibility of universal precautions, and other issues.

Strengthening Thailand's capacity for clinical research will help resolve these problems. Our goals should be to encourage key people to take responsibility for organizing and conducting the research; to accumulate specialized knowledge and hire experienced personnel for designing and developing study protocols and methods; to train personnel and specify the appropriate system of research, methods for procedures, medical record-keeping, data collection, analysis, and reporting of study results; to solicit the cooperation of patients for research; to foster cooperation and collaboration among hospitals and multicenters both within this country and with other countries; to provide financial support for the subjects as well as for acquiring personnel, space, and other necessary supplies; and to gain the approval of the ethical board.

Thailand's National AIDS Program: Building a National Response

Prayura Kunasol

Department of Communicable Disease Control, Ministry of Public Health, Bangkok, Thailand

Thailand's National AIDS Program began in 1987 following a cabinet decision to develop a national response to the HIV pandemic. Today, nearly eight years later, the necessary human and financial resources are being mobilized, resulting in a more structured, purposeful, and effective National AIDS Program. In seeking to address the numerous health, social, economic, and human aspects of HIV/AIDS, the program embraces all 15 government ministries, public and private sectors, and community-based and non-governmental organizations, as well as international development agencies.

Among the significant developments of Thailand's National AIDS Program are the following:

Sentinel Surveillance

Thailand initiated a national HIV sentinel surveillance program in June 1989. Since then, data have been collected every six months from a number of different population groups throughout the nation. As reported in numerous international journals and scientific publications, the Thai HIV/AIDS experience might be summarized as a series of waves of infection--sequentially infecting injecting drug users; female sex workers; the non-injecting drug-using male clients of the female sex workers; and finally the low-risk non-prostitute wives and girlfriends of those male clients--now spreading throughout the general population. Thailand's national sentinel surveillance remains an effective tool in creating political awareness and in mobilizing the necessary human and financial resources at the national and international levels.

Health Education and Public Relations

In early 1988 and 1989, HIV/AIDS health education messages were targeted to injecting drug users, male and female sex workers, and men attending sexually transmitted disease (STD) clinics. Various government ministries and non-governmental organizations planned and implemented numerous innovative outreach strategies. Today, HIV/AIDS educational and informational messages are geared to promote more effective behavioral change and social values. Outreach methods include: (1) large-scale, nationwide mass media campaigns through television, radio, and print media; (2) introduction of sex education and life skills into the national educational curriculum for primary and secondary schools, as well as vocational schools, colleges, and universities; and (3) specific community action programs to provide social support for behavioral changes among groups engaging in high-risk behaviors, including sex workers, migrant labor groups, fishermen, and military personnel.

Condom Promotion

One key strategy of Thailand's National AIDS Program has been condom promotion. Condoms are commercially available throughout the country at affordable prices, and government policy has been open and supportive of condom use, both for family planning and STD prevention. Subsidized and free condoms are made available through family planning clinics, drug treatment centers, STD/AIDS clinics, and entertainment places. In 1991, the National AIDS Committee approved a government plan to implement a "100 Percent Condom Use Program" in all provinces. This nationwide initiative combines the unique skills and political networking of provincial governors, police, and public health authorities in addressing the issues of commercial sex, condom use, and the empowerment of women. In addition, the female condom is being introduced into Thailand this year as part of the National AIDS Program and will be distributed throughout the public and private sectors to help ensure greater condom coverage rates, particularly among low-income female sex workers.

Medical Services

Since 1989, all of the more than 800,000 annually donated units of blood are tested for HIV antibodies. To help ensure a safe national blood supply, voluntary blood donors are recruited and donors are asked to self-select. Nearly all hospitals have the means to correctly diagnose and provide appropriate medical care for people with HIV/AIDS. A referral system is used for HIV/AIDS patients employing "continuum of care" policy guidelines. Increasingly, government and non-government personnel are working together with community and religious leaders and other organizations to develop appropriate models for community- and family-based care that will provide humane, voluntary, and compassionate physical, psychological, and social care for people with HIV/AIDS.

Research and Vaccine Development

Thailand has been actively involved in many clinical, epidemiologic and socio-behavioral research studies on HIV/AIDS. Various government ministries, private research institutes, policy-forming think tanks, and non-governmental organizations have designed and carried out an impressive number of studies, many of which have been published in interna tional scientific journals. Thailand is also actively participating in the global effort to develop and evaluate HIV/AIDS vaccines. The Ministry of Public Health, working through a number of multidisciplinary committees, is responsible for overall planning, implementation, and oversight of HIV/AIDS vaccine research in Thailand. A National Plan for HIV/AIDS Vaccine Development and Evaluation has been developed and endorsed by the World Health Organization for support in strengthening national institutions by providing specialized training and necessary equipment and supplies. Several proposed vaccine trials have already been granted scientific and ethical clearance for implementation.

Thailand's National AIDS Program actively seeks a strategy of open and honest dialogue among all concerned parties, as the Royal Thai Government is convinced that respect for human rights and preservation of the dignity of people with HIV/AIDS is vital to the success of any national AIDS program. Indeed, these principles complement and support eff ective public health practices. In Thailand, we have sought to avoid discriminatory actions in the provision of services, employment, and travel. Non-governmental and community-based organizations have been particularly effective partners in fostering a spirit of understanding, tolerance, and compassion for people with HIV/AIDS, as well as in addr essing the related issues of child prostitution and abuse to women. These are extremely complicated issues, but challenges that Thailand can and must face.

Activities of the HIV/AIDS Collaboration in Thailand

Timothy D. Mastro and Khanchit Limpakarnjanarat

HIV/AIDS Collaboration, Bangkok, Thailand

The HIV/AIDS Collaboration was created in 1990 as a joint activity of the Thailand Ministry of Public Health (MOPH) and the U.S. Centers for Disease Control and Prevention (CDC). The collaboration conducts research and related activities on HIV-1 infection and AIDS in Thailand both to improve understanding of the disease and the dynamics of HIV-1 spread in Thailand and to provide a scientific basis for the development and evaluation of interventions to prevent and control HIV-1/AIDS. Areas of activity include epidemiology, behavioral Science, operational research, and laboratory investigation.

The Coordinating Committee for AIDS Prevention and Control, under the MOPH, and the international activity branch of the Division of HIV/AIDS at the CDC's National Center for Infectious Diseases have formal oversight responsibility for the HIV/AIDS Collaboration. Research protocols are reviewed by the Ethical Review of Research Committee at the MO PH and the Institutional Review Board at the CDC.

In conjunction with a number of in-country collaborators, the initial work of the HIV/AIDS Collaboration was instrumental in describing the early phase of the HIV-1 epidemic in Thailand.1 A 1991 study of the genetic diversity of HIV-1 isolates in Thailand identified the presence of two distinct Thailand genotypes, A and B,2 which have been classif ied within global HIV-1 subtypes E and B, respectively. This study established that subtype E isolates predominate in people with sexually acquired infection and that subtype B strains account for most infections in injecting drug users (IDUs). These observations indicated that the explosive epidemic of HIV-1 infection among Bangkok IDUs in 1990 w as not epidemiologically linked to the much larger epidemic of heterosexual transmission that began in 1989. The development of specific serologic immunoassays based on V3 loop peptides from Thailand genotypes A and B has proved useful in serotyping Thai specimens.3 The HIV/AIDS Collaboration has serotyped more than 1,500 HIV-1-positive specimens from a variety of studies. These data have further confirmed that subtype E predominates among people with sexual risk factors in all regions of the country.

The HIV/AIDS Collaboration has conducted two major studies of HIV-1 transmission in northern Thailand. In collaboration with the Royal Thai Third Army in Phitsanuloke and the Armed Forces Research Institute of Medical Sciences, a two-year prospective cohort study of more than 1,000 army conscripts identified the importance of other sexually transmitted diseases (STDs) and sex with female prostitutes as risk factors for HIV-1 infection among young men.4,5 Data from this study have been used to develop an HIV-1/AIDS peer education intervention program for young men on military bases. In Chiang Rai, in conjunction with the Provincial Health Office and the Chiang Rai Regional Hospital, an ongoing open cohort study of more than 400 female prostitutes has defined the high prevalence of other STDs6 and has described a very high rate of HIV-1 incidence in young brothel-based women.7 Improved STD management and HIV-1/AIDS counseling are being evaluated in this setting.

Another major ongoing activity is a maternal-infant HIV-1 transmission study conducted in Bangkok in collaboration with Rijvithi and Children's Hospitals, MOPH, and Siriraj Hospital at Mahidol University. To date, more than 300 HIV-1-infected pregnant women have been enrolled in this study. Additional sub-studies are investigating HIV-1-related pl acental pathology and the risk factors and risk perceptions of the husbands of HIV-1-positive women.

Since 1991, the HIV/AIDS Collaboration has been working with Bamrasnaradura Infectious Disease Hospital (BIH) to examine the clinical presentation of AIDS in Thailand. In 1993, an HIV-1/AIDS data management system was established at BIH to allow for the comprehensive analysis of data from patients with HIV-1 infection. Studies at BIH and in Chiang Rai have led to a better understanding of the interaction between HIV-1 and tuberculosis in Thailand. In Chiang Rai, a pilot project has been started to offer isoniazid preventive therapy to HIV-1-infected people to reduce the risk of tuberculosis.

Recently completed studies have investigated blood donor deferral criteria for Thailand8 and HIV-1 incidence among blood donors and IDUs. An earlier study conducted with the Bangkok Metropolitan Administration, Thanyarak Hospital, MOPH, and the Office of the Narcotics Control Board estimated that approximately 12,000 HIV-1-infected IDUs live in Bangkok.9 In 1994, a cohort study of IDUs in Bangkok will be started by the Bangkok Metropolitan Administration, Siriraj Hospital, the Division of Epidemiology at MOPH, and the HIV/AIDS Collaboration. This study will be used to evaluate HIV-1 interventions among IDUs.

These and other studies conducted by the HIV/AIDS Collaboration can be classified into three broad areas of interest:

1. HIV-1 transmission--how does it occur and how is it prevented?
2. The AIDS epidemic in Thailand--what does it look like and how can opportunistic infections, especially tuberculosis, be prevented?
3. HIV-1 virology--what are the characteristics of the strains found in Thailand?

It is hoped that these and future collaborative activities will lead to improved means of reducing the impact of HIV-1 and AIDS in Thailand.

References

1. Weniger BG, Limpakarnjanarat K, Ungchusak K, et al. The epidemiology of HIV infections and AIDS in Thailand. AIDS 1991;5(suppl 2):S71-S85.
2. Ou C-Y, Takebe Y, Weniger BG, et al. Independent introduction of two major HIV-1 genotypes into distinct high-risk populations in Thailand. Lancet 1993;341:1171-74.
3. Pau C-P, Lee-Thomas S, Auwanit W, et al. Highly specific V-3 peptide enzyme immunoassay for serotyping HIV-1 specimens from Thailand. AIDS 1993;7:337-40.
4. Nopkesorn T, Mastro TD, Sangkharomya S, et al. HIV-1 infection in young men in northern Thailand. AIDS 1993;7:1233-39.
5. Mastro TD, Satten GA, Nopkesorn T, Sangharomya S, Longini IM Jr. Probability of female-to-male transmission of HIV-1 in Thailand. Lancet 1994;343:204-7.
6. Limpakarnjanarat K, Mastro TD, Yindeeyoungyeon W, Schmid S, Sarafian S, Weniger BG. STDs in female prostitutes in northern Thailand. IX International Conference on AIDS, Berlin, Germany, June 1993 (abstract PO-C10-2820).
7. Limpakarnjanarat K, Mastro TD, Pau C-P, Young N, Korattana S, Weniger BG. Prevalence and incidence of Thai HIV-1 genotypes in a cohort of female prostitutes in northern Thailand. IX International Conference on AIDS, Berlin, Germany, June 1993 (abstract PO-C02-44350).
8. Kitayaporn D, Bejrachandra S, Chongkolwatana V, Chandanayingyong D, Weniger BG. Potential deferral criteria predictive of HIV-positivity among blood donors in Thailand. Transfusion 1994;34:152-7.
9. Mastro TD, Kitayaporn D, Weniger BG, et al. Estimating the number of HIV-infected injecting drug users in Bangkok, Thailand, by capture-recapture method. Am J Public Health (in press).