
Fostering Research Collaborations
Worldwide to Combat AIDSJoan Kriess
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Dr. Dorothy Mbori-Ngacha, an IARTP scholar from Kenya, is researching the
role of breastfeeding in mother-to-child transmission of HIV.Ruth Nduati, Grace John, and Dorothy Mbori-Ngacha are conducting a clinical trial to determine the role of breastfeeding in mother-to-child transmission of HIV-1 in Nairobi, Kenya. In this challenging study, HIV- I seropositive pregnant women are randomly assigned to feed their babies breast milk or formula, after which the mother/infant pairs are followed for two years. As with most clinical trials, the major research challenges are to maintain high rates of follow-up and compliance with the intervention. Follow-up is particularly problematic in an urban metropolis in sub-Saharan Africa. In the past two decades Nairobi's population has exploded with an influx of immigrants from rural areas. Many maintain close ties to their former villages and freely travel back to visit pregnant women may come to the city for their deliveries, and then return to their "up-country" homes when their infants are six to 12 months old. Two members of the research staff, both male nurse-counselors, went on an expedition to western Kenya in an attempt to trace women who had been lost to observation. Some of the homes were quite remote, and late in the afternoon they arrived at one, a mud hut with thatched roof. They sat with the husband, who told them he had had five wives. The first had died after a wasting illness, and the second was the one they were seeking. Unfortunately, her baby had died. As dusk was falling, he offered the hospitality of his home, including the companionship of two of his wives for the night. At the risk of offending their host, the nurses accepted the hospitality but declined the services of the wives. It was clear to the nurses that AIDS prevention messages had not penetrated into this part of rural Kenya.
The three pediatricians (two Kenyans and one American) involved with this NIH-funded study in Nairobi all have been scholars in the International AIDS Research and Training Program (IARTP) at the University of Washington. With a focus on epidemiology, they have analyzed data from the trial for their MPH theses. The tracing story is not atypical of other stories told by IARTP scholars, and illustrates the unique difficulties associated with conducting research in developing countries.
The IARTP
Since its inception in 1988, the International AIDS Research and Training Program has hosted 78 scientists from 21 countries. Funded with two grants from the Fogarty International Center, the goal of the IARTP is to further international collaborative AIDS research through scientist exchange and research training. The program includes opportunities for foreign scientists at all levels of training (e.g., MDs, PhDs, laboratory technicians) to come to the University of Washington for sabbaticals ranging from three months to four years. They may enroll in a variety of programs (from MPH and PhD degrees in epidemiology to bench experience in basic science laboratories) in disciplines such as epidemiology, biostatistics, molecular virology, and immunology.The degree programs of IARTP scholars include classes at the University of Washington and research field work (for a minimum of nine months) in their home countries. Upon completion of their programs, IARTP scholars return home and often assume important positions of responsibility within the AIDS research and prevention communities. American faculty, fellows, or students also have opportunities to gain AIDS field research experience in a developing country. To date, 28 investigators from Seattle have been supported to conduct research abroad.
Although our foreign scientist trainees have represented many nationalities, the IARTP focuses on six countries: Kenya, Mozambique, Senegal, Peru, Russia, and Thailand. In these countries, University of Washington faculty members have made a long-term commitment to a collaborative AIDS research program with host institutions.
Research Highlights
Is HIV- I Subtype Associated with Differential Infectivity?The epidemiology of HIV-I in Thailand has been distinctive. Two parallel but separate epidemics evolved, both beginning in the mid to late 1980s, one involving intravenous drug users and the other involving heterosexual spread. Molecular epidemiologic techniques revealed that the drug user epidemic was characterized by subtype B (the predominant) subtype in the United States) and the heterosexual epidemic by subtype E.
Chaiyos Kunanusont, a Thai scholar in the IARTP and a PhD candidate in the Department of Epidemiology, was studying HIV- I concordance among heterosexual couples in Bangkok when the subtype data were published. He then determined HIV-1 subtype of infected participants in his couples study and found that when a man was infected with subtype E, his partner had twice the likelihood of being infected than if he were infected with subtype B. This association persisted after controlling for sexual exposure variables and other confounding factors. These results suggest that HIV- I subtype E may be more efficiently transmitted during heterosexual contact than subtype B. This was the first study to suggest that HIV-1 sub-type may influence infectivity.
To further explore this hypothesis, Dr. Wichai Techasathit, a subsequent IARTP scholar who earned an MPH degree, conducted a follow-up study in Bangkok. He collected semen samples from more than 150 HIV-1 infected men to determine whether the presence or quantity of seminal HIV-1 was associated with viral subtype. He completed the field work in 1996 and the laboratory analysis is in progress. Regardless of outcome, the results should provide another piece of the puzzle in understanding viral factors affecting transmission.
The Role of Pharmacies in Diagnosis and Treatment of STDs in Latin America
Over the past decade, compelling evidence has emerged that sexually transmitted diseases (STDs) are important cofactors; for the sexual transmission of HIV, and public health experts now believe that STD control is an essential component of successful HIV prevention programs. The current challenge is to implement STD management and prevention in developing countries with limited resources.
In Latin America, many persons with STD symptoms seek care at a pharmacy rather than at a clinic or doctor's office. Dr. Patricia Garcia, a Peruvian IARTP scholar, evaluated the performance of 180 randomly selected pharmacies in Lima in managing four common STD syndromes. Four medical students and two actors were trained as simulated patients. They visited each of the pharmacies and presented standardized histories of urethritis or genital ulcer disease in men, or vaginal discharge or pelvic inflammatory disease in women. In more than 75% of the simulated patient visits, the pharmacy worker offered a medication. However, in fewer than 5% of cases was the treatment considered adequate according to the World Health Organization guidelines for the syndromic management of STDs. Recommendations for partner treatment or condom use were each made during fewer than 10% of the simulations. Given the important role of pharmacies in STD management, an intervention program aimed at strengthening treatment and counseling skills seemed warranted.
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Dr. Joan Kreiss, top row left, with several 1997 IARTP scholars, (clockwise from top right): Dr. Patricia Garcia (Peru), Dr. Cesar Nunez (Honduras), Dr. Cesar Cargino (Peru), Dr. Joshua Kimani (Kenya).
Dr. Garcia then randomly assigned pharmacies to an educational intervention, a one-day workshop in the syndromic management of STDs. In a subsequent evaluation of performance that used simulated patients, the pharmacy workers improved with regards to counseling (e.g., recommendations for partner treatment and sexual abstinence during treatment), but showed no significant improvement in use of appropriate antimicrobials. These results suggest that an expanded educational program may be required to effect a substantive change in STD management in the pharmacy sector. Model Programs
The University of Washington is one of I I American universities with Fogarty-funded international AIDS training programs. Now in their tenth year, these programs are a model for international research training for developing countries. In light of their success, the Fogarty International Center has developed analogous programs in the areas of environmental and occupational health, population, and emerging infectious diseases; field research opportunities for young minority students through the Minority International Research Training Program; and a small grant program for collaborative research between U.S. and foreign scientists.With the continued spread of the HIV pandemic and the disproportionate burden carried by less developed countries, the need for continued scientific collaboration between U.S. scientists and those in developing countries remains important. As we move into the next millennium, the IARTP will increasingly focus its emphasis on prevention research (e.g., efficacy trials of interventions to reduce sexual and perinatal HIV transmission) and the development of independent research capacity in the target countries.
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Recommended Reading Selected Publications from IARTP Scholars
Bwayo J, Plummer F Omari M, et al: HIV infection in long-distance truck drivers in East Africa. Arch Intern Med 1994; 154:1391-96.
Clemetson D, Moss GB, Willerford D, et al: Detection of HIV DNA in cervical and vaginal secretions: Prevalence and correlates among women in Nairobi, Kenya. JAMA 1993; 269:2860-64.
Kamenga M, deCock K, St Louis M, et al: The impact of human immunodeficiency virus infection on the clinical presentation and response to therapy of pelvic inflammatory disease: A case control study in Abidjan, Ivory Coast. Am J Obstet Gynecol 1995; 172:919-25.
Kunanusont C, Foy HM, Kreiss JK, et al: HIV- I subtypes and male-to-female transmission in Thailand. Lancet 1995; 345:1078-83.
Langley CL, Benga-De E, Critchlow CW, et al: HIV-1, HIV-2, human papillomavirus infection and cervical neoplasia in high risk African women. AIDS 1996; 10:413-17.
Nduati RW John GC, Richardson BA, et al: HIV- I infected cells in breast milk: Association with immunosuppression and vitamin A deficiency. J Infect Dis 1995; 172:1461-68.
Sanchez J, Gotuzzo E, Escamilla J, et al: Gender differences in sexual practices and sexually transmitted infections among adults in Lima, Peru. Am J Public Health 1996; 86:1098-1106.
Vaz RG, Kreiss JK, Gloyd S: Syphilis and HIV infection among prisoners in Maputo, Mozambique. Intl J STD AIDS 1995; 6:42-46.
Author
Joan Kreiss, M.D., M.S.P.H., is a professor in the departments of Epidemiology and Medicine and director of the International AIDS Research and Training Program at the University of Washington.
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Created: 3/16/98 Updated: 7/15/99