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The Rise and Fall of Projet SIDA
Cohen J: , Science 28 November 1997:Vol. 278 no. 5343 pp. 1565-1568. www.sciencemag.org/content/278/5343/1565.full
Kinshasa, Democratic Republic of The CONGO—It's easy to see that many things are missing from Kinshasa General Hospital. Overcrowding is so severe that some patients are forced to share a bed. People are rolled around on World War I-vintage wheelchairs that have only three wheels. Holes in the walls mark the places where electrical boxes have been torn out. Tiles have fallen from the walls and are missing from parts of the floors. In the plaza that separates the wards, multicolored lizards crawl over charred wooden stumps, the remnants of trees that once provided much-needed shade. Except for the cellular phones owned by some doctors, there is no communications system. But there is one, less obvious, thing missing that a decade ago made this hospital, then known as Mama Yemo, a focal point for scientists from Europe, the United States, and Africa: AIDS research.Mama Yemo Hospital was a critical component of Projet SIDA (French for AIDS Project), a Zairian-American-Belgian research program that began in 1984 and quickly shed much light on the emerging epidemic. “The epidemic of AIDS, not only in Africa but in other parts of the world, became known because of the work here,” says cardiologist Bila Kapita, who helped establish the Zairian side of the collaboration. “And many Zairian doctors learned how to do research.” Says Claudes Kamenga, who worked with the program for 5 years and is an epidemiologist in the behavioral research unit at Family Health International in Arlington, Virginia, “Zaire was shining because of Projet SIDA.”
To the dismay of many scientists, however, Projet SIDA suddenly ended in 1991, a victim of the civil unrest that tore Zaire apart in the 1990s. The machine-gun fire that rang through the city that September led to the project's demise and signaled the beginning of the end for Zairian dictator Mobutu Sese Seko, who finally was ousted from power last May. Today, says Kapita, with a mixture of sadness, frustration, resignation, and finality, “Projet SIDA is dead.” As Eugène Nzilambi Nzila, a key clinician in the project from its outset, says: “We don't think about research now.”
Outsiders who launched and ran Projet SIDA provide a glowing eulogy. “It's one of the things I'm really proud of in my life—that I contributed to this project and made it happen,” says Belgian epidemiologist Peter Piot, who now heads UNAIDS, the United Nations AIDS program. James Curran, former acting director of the Division of HIV/AIDS Prevention of the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta, the project's main funder, calls his involvement “a tremendously enlightening experience.” Says Curran, now head of Emory University's School of Public Health in Atlanta: “During many of its early years, it was the preeminent AIDS research project in Africa in terms of number of people involved and quality of research coming out.” Thomas Quinn of the U.S. National Institute of Allergy and Infectious Diseases (NIAID), another key contributor to the project, says, “The number of papers we generated out of there was just incredible.”
But, in spite of its many accomplishments, Projet SIDA—which at its peak had a $4 million annual budget—also provided some object lessons in the difficulties of conducting research in poor, conflict-ridden countries, where the scientific objectives of the studies don't always mesh with urgent public health needs. It also left behind an unexploited legacy: a vast accumulation of blood samples from patients—some of whom are still being followed today—that could offer valuable insights into preventing and treating the disease. And it left in its wake trained medical investigators and technicians who, like Kapita and Nzila, would love to do research once again. “We in Congo are at the heart of the problem,” says Kankienza Muana'mbo, head of the National Institute of Biomedical Research (INRB), which once housed a main Projet SIDA lab. “We have human beings and we have biological materials, but we don't have fresh resources to look at the problem. And we think that doing research here in Congo can bring some solutions for the whole world.”
Spreading HIV/AIDS research
Turn back the clock to the summer of 1983. HIV had just been isolated, but scientists had yet to prove conclusively that it caused the disease. AIDS itself, which had first been recognized 2 years earlier in Los Angeles, was labeled a disease of “the four H's”: homosexuals, heroin addicts, hemophiliacs, and Haitians. Mosquitoes were still a suspected vector of AIDS. And the impact of the disease on the African continent had yet to be described. One afternoon that summer, Quinn and NIAID then-director Richard Krause met at a cafe in Vienna with Piot, who at the time was with Belgium's Institute of Tropical Medicine (ITM). The topic of discussion: hints from a variety of sources that AIDS had struck Zaire.
Piot had seen Zairian patients at the ITM who had AIDS. “I was dying to go to Kinshasa and see what was going on, but I didn't have the money,” says Piot. And Quinn and Krause had recently returned from Haiti, where they learned that many Haitians had worked in Zaire after it became independent from Belgium in 1960, and then were forced out in the '70s. “With that history I said, hey, we've got to get into Zaire,” recalls Krause, now a scientific adviser at the Fogarty International Center, a branch of the U.S. National Institutes of Health (NIH). They decided there and then to form a collaboration. “I was committed to devoting substantial funds to that,” says Krause.
The trio met again that fall in Belgium to map out the collaboration. They were joined by the CDC's Joseph McCormick, who had much experience working in Zaire and had independently received official clearance to investigate AIDS there. On 18 October, Piot, McCormick, and Quinn set out for Kinshasa. “Our first problem,” says Piot, “was to see whether we were welcome or not.” They met with the minister of health, who, says McCormick, spelled out all the other diseases plaguing Zaire. “He said, ‘You're welcome to go look, but this is not going to take on any priority.’” They took that as a green light to meet with Kapita, who then was head of internal medicine at Mama Yemo. “It's really thanks to him that the whole project could start,” says Piot.Not only did Kapita welcome the foreigners, he also deeply impressed them with his independent observations about AIDS, taking them around the wards of Mama Yemo and pointing out patients who he thought had the disease. Analyses of these patients' immune cells proved Kapita right. Says Quinn: “He's probably one of the first Africans to recognize the disease.” The work, which was published in the 14 July 1984 Lancet, also helped clarify the importance of heterosexual spread of the disease. As the authors wrote, “The findings of this study strongly argue that the situation in central Africa represents a new epidemiological setting for this worldwide disease—that of significant transmission in a large heterosexual population.”
In the winter of 1984, the project gained what ended up being a major source of support when CDC epidemiologist Jonathan Mann, a newcomer to AIDS research, visited Piot in Belgium. At the time, Piot was writing a grant proposal to NIAID to launch a joint project. Much to Piot's surprise, Mann said CDC was planning to launch its own project. “Being a pragmatic guy, I said let's work together and see how we can collaborate,” says Piot. CDC became the project's major funder: Of its final $4 million budget, roughly $2.5 million came from CDC, $1 million from NIAID, and $0.5 million from ITM.
Projet SIDA officially began in June 1984 with Mann at its head. In the beginning, it consisted of Mann and two Zairian physicians, Bosenga Ngali and Nzila. Mann emphasizes that they contributed significantly to the direction the nascent project took. “Nzila and Ngali didn't hesitate to say what they thought,” says Mann. “We were in a canoe. And we were all paddling.” They soon were joined by NIAID's Henry “Skip” Francis, who ran the project's lab, and ITM's Bob Colebunders, who headed the clinical work.
In short order, Projet SIDA began addressing the most fundamental of epidemiological questions: How many people were infected? Who got the disease? Was AIDS the same in Zaire as seen elsewhere? Could mosquitoes transmit HIV? The project also helped the country come to terms with its epidemic. “We were living through the time when the government [went from] denying the problem to accepting the problem and dealing with it,” says Francis, who now is the chief of clinical medicine at NIH's National Institute on Drug Abuse. “Jon Mann was politically eloquent and could get the message out without frightening people.” And Zaire's response to AIDS caught the attention of its neighbors, says Colebunders, who is now back at ITM: “It's because of Projet SIDA that the other countries started to talk about AIDS.”
In 1985, Mann recalls attending the first international AIDS conference, held in Atlanta, with Kapita, who had never been to the United States before. “There was such a good feeling of working together,” says Mann. “It was really a new world and we were in it together. In the beginning, we were all discovering everything everyday.”
Grand aspirations and limitations
Mann left in 1986 to head the World Health Organization's new Global Programme on AIDS. He was replaced by Robin Ryder, an epidemiologist who had previously worked in The Gambia. During Ryder's 4-year stint, Projet SIDA branched into many new areas, employing nearly 300 people—only seven of whom were expatriates. In all, says Ryder, who's now at Yale University, Projet SIDA had more than 20 Landcruisers, a better computer system than the one used by the CDC, and state-of-the-art machines that could separate one type of immune system cell from another. “It was a research factory,” says Quinn. Ryder says 15 or so Zairian physicians were the “backbone” of the project. “It was sort of like a plant when you give it water and it really perks up,” says Ryder. “They just thrived.”
A steady stream of scientific insights began to flow from the program, which now included a clinic devoted to the study and treatment of prostitutes. With help from ITM's Marie Laga, Projet SIDA proved that preventing and treating sexually transmitted diseases (STDs) decreases the incidence of new HIV infections. Careful investigations of HIV-infected pregnant women documented the rates of transmission to their infants and attempted to explain why the majority of babies remained virus free. Projet SIDA also rigorously measured both the prevalence of HIV and the rate of new HIV infections in thousands of people, critical work for establishing “cohorts” that can participate in vaccine trials. To date, more than 120 publications have come from Projet SIDA, and more than 1000 abstracts have been presented at scientific meetings.
Yet Projet SIDA was not, in Piot's words, “a honeymoon.” One source of unease was the Zairian government. In 1986, at the second international AIDS conference in Paris, Kapita gave an address about AIDS in Africa at the opening plenary session. A quiet and modest man, Kapita was deeply honored by the opportunity. But after he spoke, a Zairian doctor came up to him with a warning. “You think you're here to be a star,” Kapita recalls being told. “You must know that all you're telling here is being transmitted to Kinshasa. We're waiting to decide what to do with you.”
When Kapita returned to his office at Mama Yemo Hospital, an officer from the Ministry of Health was there waiting, with instructions to take him to prison. Fortunately, a friend in the ministry intervened, and Kapita says he never faced political problems again. But the episode underscores that the difficulties facing AIDS researchers in Zaire went far beyond struggling to find a working phone line or a clean pair of latex gloves.
For many Projet SIDA members, the problems intensified over time. “There were lots of fights,” acknowledges Piot. Oddly, the main battles had little to do with Zaire; instead, they broke out between NIH and CDC.
Tensions between these two research heavyweights, both of which are part of the U.S. Department of Health and Human Services, surfaced from the moment Mann first set up shop in Kinshasa. “Since he spoke fluent French, he had everything worked out with the minister of health that CDC was in charge,” recalls one NIH insider who asked not be named. “That really pissed off NIAID because it was our idea.” Piot says he stayed clear of the power brokering: “I never understood the politics. For me. it was not a real problem. … And after all, CDC has more field experience than NIH.” But the rift between the American agencies was real—and it grew, complicating the difficult decisions that had to be made about research priorities.By the time Ryder took over, the wrangling had become more than a nuisance. “It was the bane of my existence,” says Ryder. “I never had problems with the Africans.” According to Ryder and others, a difference in outlook between the two U.S. agencies fueled the conflict. “People from the CDC were ready to think big, big, big. But ‘big big big’ means there are lots of lab samples to be tested, and NIH ran the lab. So there was some real push and shove because they'd say, ‘You can do the study, but we're not going to do the lab work.’” The NIAID researchers had their own projects that they wanted to pursue, Colebunders and others explain. “They wanted to do more sophisticated virological and immunological work, and that was not the interest of CDC and Zaire itself,” Colebunders says.
Although the involved Zairians—who now call themselves Congolese—view the project as hugely successful, they have their own complaints. One critical weakness, says Kakanda Kanjinga—a clinician who, like many of her colleagues, went straight from medical school to a Projet SIDA study—is that the program made little explicit effort to teach locals about research. “When I was at Projet SIDA, I didn't even know I was doing research,” says Kanjinga, who subsequently earned a master's of public health at the University of California, Berkeley. “I really didn't understand the purpose of what we were doing.”
CDC's William Heyward, who took over from Ryder in 1990, says the project was on its way to filling that gap, noting that it helped send a dozen Zairians to the United States for advanced degrees. He and his colleagues had hoped these “team leaders” would then do “trickle down” training. “I feel quite proud about how much we did do,” says Heyward.
Kapita has a different complaint: Projet SIDA paid too much attention to epidemiology and not enough to treatment and prevention. “I'm sorry to tell you that Projet SIDA had very little impact for infected people here,” he says. “It would have been useful for them to ask us about what was the useful thing for us they could do here.” Kapita is particularly disappointed that the Americans and Belgians didn't budget money to screen the blood banks for HIV. “We knew that AIDS was transmitted by blood transfusion, but nothing was done about it,” he charges. Money to clean the country's blood eventually came from the German government's international aid program, Gesellschaft für Technische Zusammenarbeit.
Projet SIDA's limited emphasis on treatment even caught the attention of Mobutu (who died of prostate cancer in September). In the summer of 1988, Jack Whitescarver, former deputy director of NIAID, said he was summoned to the Madison Hotel in Washington, D.C., to meet Mobutu. When he entered the Zairian president's hotel suite, Whitescarver says, “a long line of enormous guys with guns closed in on us” and shunted them over to Mobutu, who wanted to know about treatments. Whitescarver explained that Projet SIDA was addressing the problem. “I've never been so terrified,” he says. “I wasn't sure I was going to get out with my life.”
Piot says those involved with Projet SIDA were acutely aware of the tensions between research needs and public health needs. “That's a big discussion we always had: What is the responsibility of what is primarily a research project working with research funds in terms of doing something for the country?” The cost of screening the blood supply, notes Emory's Curran, turned out to be roughly equal to the entire Projet SIDA budget. Project officials also point out that the clinic for prostitutes, opened in 1988 in the Kinshasa neighborhood of Matonge, helped many by providing drugs for their STDs and condoms and education to prevent them. “Before there was the Matonge clinic, I would get infections all the time and miss work,” confirms “Alpha,” a prostitute who works dance clubs in one of Kinshasa's many downscale neighborhoods. Support from Médecins Sans Frontières (MSF) has kept the clinic alive to this day, and it now serves the public at large.
Salaries for local researchers created another thorny issue—one that often bedevils international research projects. Skyrocketing inflation in 1990 and 1991 drove down the standard $1000 per month salary—which, according to U.S. State Department rules, had to be paid in local currency—to less than $200. “I couldn't live on that,” says Kavuka Luwy Musey, a former Projet SIDA physician who is now at the University of Washington, Seattle. Kanjinga's husband, Yadiul Mukadi, a clinician who was studying tuberculosis treatment with Projet SIDA, says the inflation problems had a dramatic impact on the program. “We had a very bad period where our attention was shifted from talking science to talking salary,” says Mukadi, who now works on TB at the California State Department of Health in Berkeley.
Heyward and his top CDC colleague in Kinshasa, Michael St. Louis, fought hard to solve the currency problem. “That was one of the most terrible things during the time I was there, to watch our colleagues suffer,” says St. Louis. “We knew they were having shrinking buying power and income, but we had these absurd rules. The amazing thing to me was that it didn't have more impact on their work.” Heyward adds, “The State Department was just totally unsympathetic to the problem, and we were just totally frustrated.”
A bad fall
The inflation problem was also tearing apart the rest of the country. In September 1991, Zairian soldiers, angry that they hadn't been paid, decided to turn Kinshasa upside down, leading to widespread looting and mayhem. St. Louis well remembers the night that soldiers started firing their machine guns outside the American compound where he lived with his wife and two infants. “We didn't know what the intent was,” he says. “There was one very scary time when people massed outside our gate and were banging on the door.”
At the Projet SIDA laboratory housed at the INRB, Delfi Messinger, an American zoologist, made a decision that many credit with saving masses of data and samples that had been accumulated. Frightened by the machine-gun fire and people running in the streets, Messinger decided to kill a sheep, put its blood in a 50-cc syringe, and squirt “SIDA” in dripping, meter-high letters on the wall outside the institute. (She repeated this with paint during later periods of unrest.) She also put snakes in cages in front of the entrances to all of the institute's buildings and, to “booby-trap” her car, put a snake in it, too. “It was scary,” says Messinger, who works on the conservation of a rare chimplike ape called a bonobo. “It was worse than a nightmare.”A few days later, with the city under the guard of Belgian paratroopers and the French Foreign Legion, Heyward, St. Louis, and the other Projet SIDA expatriates were evacuated across the Congo River to Kinshasa's sister city of Brazzaville, and they returned to the United States. Eight months later, the CDC and NIH leaders, convinced that the country was still in a quagmire, pulled the plug on Projet SIDA.
To this day, several Congolese researchers cannot understand why the project had to end so abruptly. “I wish they could have tried more to keep that project alive,” says Kamenga. “There should have been more trust in those who were remaining there, the locals. They just assumed because the Americans and Belgians were leaving, they couldn't continue.”
In 1992, Skip Francis, who had left the project 4 years earlier, found himself back in Kinshasa shutting it down. In part because he was a black American, Francis was asked to return and retrieve equipment, half the stored sera, and data. “It was extremely controversial,” says Francis. “You now had a completely Zairian operation, and now [the Americans] are going to send someone back to take half their stuff.”
Francis encountered trouble even before he reached Kinshasa. He took the Brazzaville ferry into Kinshasa, and, at the border, a soldier hit him with a garden hose. He says he “almost got shot,” too. “I had the misfortune to be wearing the pants that military people wear with all the pockets,” says Francis. “A soldier said to me, ‘The pants or you die.’” The soldier settled for $10 instead.
The Projet SIDA team was none too happy to see him. “Basically, they hadn't had a lot of communication [from the Americans],” says Francis. “They were extremely upset. I remember very vividly that first meeting: You had 10 Zairians yelling at me in two languages. It was an agonizing process.” During the next few days, the Zairians told Francis which pieces of equipment they wanted to keep and which ones they didn't think they could use. They also shared data and sera that ended up being used in further studies done in the United States.
Musey, who was the lab leader then, wishes they had adopted “a more responsible attitude” with Francis. “Skip was a very nice person and said, ‘This is what I'm asked to take. What do you think?’” remembers Musey. “The key was how can we get something if we give them the samples? That's where we failed one more time. We needed to give the samples and get something in return, like funding for 5 years so we can continue to do research even at low levels of, say, $50,000 a year.”
Francis, for his part, wishes the United States had a more visionary approach to conducting research in countries like Zaire, where there's great sensitivity about foreign scientists doing “safari research”—swooping in, bagging the data, and leaving. “The way we're committed to do research, we're always going to be at risk for safari research because we work in blocks of 5 years,” says Francis, noting that the U.K.'s Medical Research Council has funded foreign projects for 25 years.
Mukadi thinks the CDC in particular made a “big mistake” by not continuing to fund the project. “They could at least have kept some life there,” he says, noting that the Belgians and MSF have continued to send some support. “People were coming to work every day even if they didn't have salary. They kept coming. … There are some people I know who are very angry.”
Heyward says, “It's a shame that it happened this way,” but stresses that the agency could not figure out a way to keep sending in money, which had to go through the U.S. Embassy. “If you have to point the finger at anyone for the way Projet SIDA ended, it was President Mobutu,” says Heyward. “It wasn't CDC or the U.S. government's fault. We would love to have Projet SIDA today.”
A painful part of Projet SIDA's denouement is that almost everyone involved at the end was delighted with the direction the program was taking. Zaire was one of four developing countries that, with the World Health Organization's imprimatur, was readying itself for trials of AIDS vaccines—trials that would have relied heavily on Projet SIDA. The Zairian researchers were maturing as well, with many of the bright lights ready to return from their training in the United States. As Francis says, “Over time, we would have done more things for the Zairians, and over time, it would have been more and more of a Zairian project.”
McCormick, who left the CDC in 1995 and now heads the new epidemiology program at France's Pasteur Institute, still holds out hope for the project. “I wonder if Projet SIDA could be revived,” he says. “If Nzila's still there, there are many things to be done that are important. That's a reasonable question to ask.”
Nzila is still there. Last month, he showed a visitor to the Matonge clinic a computer print-out that lists 26 prostitutes, followed by the project since 1988, who have never become infected with HIV. Nzila well recognizes that only a few other similar cohorts of “exposed, uninfected” people have been identified, and researchers have studied them intensively looking for clues that might help determine how the immune system can thwart infection—information that might be the key to an AIDS vaccine. He says they still have stored sera from these women that could be analyzed. “We can't do research,” shrugs Nzila. “You have to have a lot of money to expand.”
Still, Nzila and several Congolese researchers now in the United States hope they'll soon be able to find funds for a collaborative project. And Nzila wants AIDS vaccine researchers to consider once again staging efficacy trials in his country. “If they think they're ready, we'll get ready,” says Nzila. “It's important for us to be involved so we will not be outside of the loop.”
Prevention of transfusion-associated HIV transmission in Kinshasa, Zaire: HIV screening is not enough
When these criteria were applied in retrospect to our population, 12.9% of the transfusions in the paediatric age group and 20.6% of the transfusions in the adult age group did not meet the criteria.
Blood transfusions are undertaken for different reasons in Kinshasa than in developed countries, because of a high background prevalence of anaemia and the high incidence of symptomatic life-threatening malaria in the paediatric age group. Acute blood loss accounts for an important number of transfusions among pregnant women only.
The fact that most transfusions are carried out in emergencies, in a blood transfusion centre which may lack sufficiently trained staff, and that the blood for transfusion has been shown to have a high background prevalence of HIV infection, malaria, hepatitis B and syphilis , explains why blood transfusion is still hazardous in Kinshasa. Compared with European blood bank statistics, where the incidence of all transfusion reactions is estimated to be 2%, and that of severe haemolytic reactions to be two out of 210 000 [ 19-22], we found the incidence of complications after blood transfusion to be much as 15.5% in Kinshasa, a very high percentage. Considering the high incidence of transfusion-related complications, and that blood transfusion will remain an important factor for the transmission of HIV and other infections in Africa, it is essential to limit transfusions to life-saving situations [2,23].
Our data suggest that more effective control of malaria, improved child health and antenatal/obstetric care could reduce the demand for blood transfusions dramatically. The workshop to discuss the findings of this study resulted in the elaboration and acceptance of guidelines in Kinshasa and two nearby health zones as a preliminary step to improving transfusion practice. Validation of these criteria depends on continued evaluation and will be one of the functions of the recommended National Blood Transfusion Committee which was recently established.
Assuring that blood supplies can be safely used in Africa will involve more than HIV testing alone. It requires a multifaceted approach, including efforts to avoid unnecessary transfusions.
Dr. Bosenge N'Gaty died in a tragic car accident in July, 1989. His presence is strongly missed by his colleagues.
Safe blood transfusions in
The occurrence of AIDS among patients previously treated with blood transfusions led to a number of changes in the blood transfusion services (BTS) in developed countries. Since AIDS in these parts of the world is associated with high-risk sexual behaviour and intravenous drug use, exclusion of potential blood donors based on these risk factors was instituted in 1982-1983. Efficient screening techniques for HIV antibodies were implemented in 1985-1986. In addition, improved techniques for preparation of blood components, which can maintain their biological activity during storage for several days (platelets), weeks (red blood cells), or even months (fresh frozen plasma), have been developed over the last 10 years. Effective transfusion therapy with these blood components has been established, using only blood units which test negative in the screening assays for syphilis, hepatitis B, HIV and, more recently, hepatitis C. Quality assurance programmes have been an integral part of the blood programmes in developed countries, covering essential aspects ranging from recruitment of blood donors and production and control of blood units to safe administration routines and their reporting.
These approaches have resulted in very low risk of transfusion-associated HIV transmission in developed countries [1-5]. There is still a remote risk of HIV infection in people who receive blood screened as neg¬ative for HIV-antibody [6-12]. Nevertheless, an annual decrease in risk rates by more than 30% between 1985 and 1987 has been reported [13-14]. Using data from over 17 million American Red Cross donations, Cum-mings et al.  estimate that the probability of con¬tracting HIV infection in 1987 was 1/153000 per unit transfused.
In contrast to the situation in the developed countries, blood transfusion in sub Saharan Africa carries a high and even increasing risk to the recipient of acquiring HIV and other blood-transmitted infections, such as hepatitis B, hepatitis C, syphilis and malaria [15-17]. The risk of transmitting HIV and other infectious diseases varies considerably depending on prevalence rates of the blood donor population [16,18,19]. Seroprevalence rates for anti-HIV-1, hepatitis B surface antigen (HbsAg) and syphilis (Treponema pallidum haemagglutination; TPHA) in a large central African blood bank were reported to be 4.8, 13.1 and 13.3%, respectively , compared with 0.004, 0.03 and 0.06% among volunteer donors in American blood banks .
National blood transfusion programmes
Unfortunately, strategies which have proved highly effective in securing a safe blood supply in developed countries are difficult to implement in many central African countries. It is important to realize that the supply of safe blood transfusion as part of a national health-care system is costly and requires the development of a national blood programme. It is the responsibility of the national blood programmes to develop strategies which address the following key areas: donor recruitment and control of blood units, regional cooperation, training of personnel, development of guidelines to: use of blood and blood products and their implementation, cooperation with development programmes and financial aspects of operations. Such programmes have already been shown to be highly effective in some countries .
The World Health Organization (WHO) Global Blood Safety Initiative (GBSI) was formed to address these important needs and to assist member countries in the developing world to improve BTS with the goal of developing 'integrated blood transfusion systems' appropriate to the countries' health-care systems. This assistance is dedicated to ensuring the sustainability of the programme, and combines availability of expertise and financial donor funding for the programme in its development phase.
Recruitment of blood donors and screening for infectious agents
The present situation in most countries in
The need for recruitment and retention of safe, voluntary blood donors cannot be overemphasized. However, modem blood banking is neither technically nor economically feasible in most African countries. They frequently lack facilities for blood banking, equipment, regular supplies, sufficiently trained staff and financial resources and must therefore depend largely on fragmentary support from international organizations. All these factors contribute to unsafe operation and limited HIV screening of donated blood [ 16,26].
Screening of blood and blood products to ensure the prevention of transmission of HIV in the developing world has been a major priority for the WHO Global Programme on AIDS (GPA).
However, HIV testing alone cannot be successful without addressing other important aspects of blood transfusion in order to provide safe blood and blood prod ucts. WHO/GPA recognizes the urgent need for rapid intervention strategies and has developed specific objectives.
The cornerstone of a safe blood supply is a safe donor population. Strategies to assist developing countries to carry out the difficult task are being developed by convening informal meetings of experts from developed and developing countries. Recommendations will be made by carrying out a feasibility study in three regions, Africa, Asia and the
Testing of all blood donations for HIV (and other infectious agents) using simple or rapid tests or enzyme-linked immunosorbent assays (ELISA) will be encouraged. Simple/rapid tests in particular will be recommended where there is no established blood bank system and blood may be needed for emergency use.
Trstining of existing staff at centres where blood transfusions are carried out, especially training of trainers in short courses, is seen as an important activity. Training of trainers in the
Education of the prescribers of blood transfusion is an important objective to ensure appropriate use of blood to reduce unnecessary blood transfusions and to encourage the use of plasma volume substitutes where necessary.
Practice of blood transfusion
Despite the high prevalence of HIV infection among blood donors in
Pregnant women in tropical
The clinical outcome of blood transfusions in African countries is often doubtful when treating acute complications in chronic anaemia, which is the most frequent indication for transfusion in children. The frequency of severe complications in one recent study was as high as 15.5% of all blood transfusions administered to children under the age of 5 years . In
In summarizing the overall serious and difficult situation, it must be stressed that the present prevalence rates of anti-HIV among available blood donors call for extreme care in adhering to strict indications for treatment with blood transfusions, since the associated risks may easily outweigh the benefits of transfusion for most patients severalfold.
The major strategies [32-39] to be considered in the control of transfusion-associated AIDS and other infections in developing countries and in
In developed countries autologous blood transfusion for selected patients is a medically sound procedure and may eliminate the risk of disease transmission [20,22,40].
Preoperative deposit, perioperative haemodilution and intraoperative blood salvage have all been covered in recent publications from WHO/GBSI . Autologous blood salvage is most useful in elective or planned surgical procedures.
Preoperative autologous blood donation (PABD) requires accurate record keeping, labelling, and adequate facilities for collection and storage. A well-organized blood transfusion service is essential. Costs of PABD are much higher than homologous blood transfusion. PADB blood may be the only blood available in the hospital blood bank. This will cause an ethical dilemma where blood transfusion is considered life-saving in emergency situations which involve an unrelated patient, . HIV infection involving PABD may increase risks to staff and should not be stored in the same refrigerator as normal, voluntary blood donations. The use of acute isovolemic haemodilution (preoperative), intraoperative salvage and postoperative salvage provides a practical approach to an autologous blood programme in almost all settings.
Counselling any patient for a proposed predeposit autologous blood programme must be considered ethically, confidentially and sympathetically, particularly in those cases where patients are confirmed HIV-positive.
The frequent occurrence of severe anaemia requiring iron and folk acid supplementation makes implementation of predeposit autologous blood programmes difficult. However, this procedure should be encouraged for planned operations. Intraoperative blood salvage using simple, inexpensive equipment may be life-saving. Preoperative haemodilution, using colloids and crystalloids, is used increasingly in developed countries and should also be suitable in developing countries.
Blood transfusion committees
In most African countries, blood transfusion is indicated only when the life of the patient is at serious risk . Situations where blood transfusion may be necessary include severe anaemia leading to incipient cardiac failure, profound hypovolernic stock when the blood pressure and oxygenation cannot be maintained; severe neonatal jaundice.
Despite the increase in demand for blood transfusion in
A transfusion was considered not to be indicated when the patients presented without clinical signs of severe anaemia, defined for paediatric patients as pulse > 120/min, presence of dyspnoea and disturbed consciousness, and for adults as pulse > 100/min, presence of dyspnoea, disturbed consciousness and systolic blood pressure < lOOmmHg .
Application of rigorous guidelines for the indication of blood transfusion reduced the number of blood transfusions in the paediatric ward of a large Central African hospital from 16352 in 1986 to 3981 in 1989, without any observed increase in mortality [42,43].
Each blood transfusion service should reexamine transfusion practices. A reappraisal of the necessity for blood transfusions is essential. Blood transfusion committees should be created and the blood transfusion practice reviewed at a regular basis. Efforts should be undertaken to increase the knowledge of practising physicians about transfusion medicine and recipi ents should be adequately informed about the risks of blood transfusion. All possible steps should be taken to avoid unnecessary blood transfusion and to en courage alternative treatment modalities using saline, plasma expanders and albumin solutions for acute hy-povolaemia .
Reducing the need for blood transfusion
Coinfection with more than one organism is common in poor countries; most infants and children dying in
Acute obstetrical haemorrhage can often be prevented by giving special attention to women at risk during pregnancy. Services at primary health-care clinics, antenatal clinics, 'under-fives' clinics, sickle cell clinics and vaccination programmes should be improved. All programmes directed at improving general living con ditions, nutritional status and socioeconomic status might have a considerable impact on the need for blood transfusion.
Special attention should be given to malaria as one of the major reasons for blood transfusion in child hood. The importance of malaria is increasing because of the rise of drug-resistant forms of Plasmodium fal-ciparum infection . Malaria-control programmes should therefore be strengthened and considered to have an important impact on the HIV transmission by decreasing the demand for blood transfusion.
Quality assurance in blood banking
WHO has elaborated a strategy for developing countries which is designed to improve laboratory conditions and thus reduce transmission of HIV and other infections by blood transfusion [33-38]. The implementation of this strategy meets various constraints, the most important of which are financial and economic problems.
Blood banks and decentralized screening programmes are feasible when supported by international donor organizations . At the BTS at Nakasero (Kampala, Uganda) the cost of each unit of HIV-negative hepatitis B surface antigen-negative blood was 21.5 ECU (US$25) in 1989 .
International development programmes should concentrate on the sustainability of an intervention. Continuous evaluation should be carried out and proven systems of quality control should be integrated in all programmes. In
Blood donor recruitment is also a useful vehicle for disseminating information on HIV infection . Rapid, easy and economical screening tests for antibodies to HIV have recently been developed [26,52-55]. These screening tests are designed for countries where laboratory standards and quality of trained staff are low and which therefore demand tests which are easy to carry out and interpret. They have proved to be very sensitive and highly specific  and can be used at a health district level, when proper quality control is assured [46,56]. Yet even these tests require proper supervision and should be carried out by well-trained primary health-care personnel in order to guarantee the strict confidentiality of test results. All transfused blood should be screened for HIV whenever possible.
Potential blood donors might thus serve as a useful population for surveillance even if, due to selection of donors, the HIV infection rate among donors does not reflect that of the general population [17,57,58]. Clinical examination and self-deferral of high-risk donors has proved to be of limited value in
Counselling of donors
HIV screening should be mandatory for all blood donations. It is important that all blood donors are carefully counselled on the possible outcome of the test result, so-called 'predonation counselling'.
Proper guidelines have to be developed on how test results should be interpreted, especially when Westem blot is not feasible or specialized laboratories performing Western blot with adequate proficiency are inaccessible . Combining the results of two HIV screening assays might be an alternative to Western blot .
Postdonation counselling may not be performed by the blood transfusion services, which may already have limited resources and be unable to guarantee the requisite quality of blood. Nevertheless HIV positive blood donors are an important health risk to the general public and should be identified and educated to change their personal behaviours [61 ]. Therefore, special facilities for counselling and clinical examination should be established. Referral systems need to be developed to ensure confidentiality and appropriate follow-up.
Each sub-Saharan country must develop its own national blood transfusion policy. Objective, realistic and comprehensive transfusion guidelines have to be formulated and implemented. The overall aim of these strategies is to minimize the occurrence of blood transfusion-associated AIDS in
medicine should receive support and take sustainability of blood programmes into consideration. Focusing on improvement of general health  and strengthening the efforts to further develop primary health care would reduce the need for blood transfusion in developing countries.
AIDS and cofactors of HIV transmission in Africa
Helmut Jaeger, International Journal of Experimental and Clinical Chemotherapy 1992 (3): 185-I86
Abstract: In Africa, HIV is predominantly spread by heterosexual intercourse. Other sexually transmitted diseases (STD) facilitate the dissemination of HIV and core groups are playing an important role in HIV epidemiology. Parenteral transmission of HIV in Africa must still be considered a major problem. The main strategies of AIDS prevention in Africa are reinforcement of STD control programes and health education of the general public, targeting intervention programes on core groups, and improvement of the quality of general medical care including save blood supplies.
Survey: In 1991 the prevalence of HIV-1 in Africa was estimated at 6 million infections. In addition, 800,000 adults and 500,000 children are suffering from AIDS in Africa (MERSON 1991). An unknown, but nevertheless probably considerable number of not infected siblings of HIV seropositive women became or will become orphans during early childhood. The prevalence of HIV-1 infected women between 15 and 49 years of age was estimated at 2,500 per 100.000 (CHIN 1990). In 1990 the HIV-1 prevalence in Central Africa was reported to be higher than 10 % in some urban population groups with low risk for HIV infection and up to 80% in population groups carrying extremely high risks for HIV infection (AMAT-ROZE et al. 1990; TORREY and WAY 1990). The HIV-1 sero-prevalence in various Central and East African studies was found to be 5,5 %-22,5 % for pregnant women, 35,0 %-80,0% for female prostitutes, 16,4 %-42,5 % for male STD-patients, 16,4 %-62,5 % for female STD-patients, and 32,2 %-35,2 % for long-distance truck drivers (NKOWANE 1991). Parenteral transmission by blood transfusions and injections is considered to be considerably less important than the sexual transmission of HIV. But given the large number of injections administered by health care personnel in and out health care settings under poor conditions of general hygiene (SCHEIBER et al. 1991) and the difficulties to provide safe blood supplies (N'TlTA et al. 1991), parenteral transmission may be contributing significantly to HIV infection in Africa. The predominant mode of HIV transmission in Africa is heterosexual contact. The role of other sexually transmitted diseases (STD) enhancing the spread of HIV infection has been studied in various prospective, controlled research settings in Africa since 1987. In 1989 a significant association between the acquisition of a genital ulcer (the majority being chancroid) and later HIV seroconversion has been demonstrated in male clients of female prostitutes in Nairobi/Kenya (CAMERON et al. 1989). The relative risks of HIV-1 seroconversion (adjusted after multivariate analysis) in the presence of another STD were found to be 3.3-4.7 (genital ulcers) (CAMERON et al. 1989; Plummer et al. 199la), 4.4 (genital herpes) (HOLMBERG et al. 1988), 2.7 and 3.2 (Chlamydia infection) (LAGA et al. 1990; PLUMMER et al. 1991a), and 2.7 (Trichomonas vaginalis) (LAGA et al. 1990). STD may cause disruption of the normal epithelial barrier or microulcerations in the mucosa and increase the pool of lymphozytes and macrophages (targets or carriers of the human immunodeficiency virus). Similarly, the perinatal HIV transmission is enhanced in the presence of chorionamnionitis (RYDER and TEMMERMANN 1991). In Africa the spread of HIV is very heterogeneous in different population groups and most rapid in small subpopulations ("core groups"): mobile, urban males, (temporarily) separated from their families, like longdistance truck drivers, soldiers, miners, seasonal workers etc., and female prostitutes. Urbanization, selected male migration to major cities in search for work, disruption of rural agrarian life and traditional values, famine, poverty, and war are leading to a large number of single men (or men having left their spouses in rural areas) and a smaller urban lower stratum of women willing to sell sex for survival. Intervention programs in Africa concerning heterosexual transmission are focusing on STD control and core group populations. If these programs are to succeed, they must be implemented in cooperation with the targeted population. Victimization by passing laws, rounding up core group members, and punitive interventions are misguided and have been found to be ineffective in Africa (PLUMMER et al. 1991 b).
Voluntary Blood Donor Recruitment: A Strategy to Reduce Transmission of HIV-1, Hepatitis-B and Syphilis in Kinshasa, Zaire
H. Jager", K. Nsekab, B. Goussard', C.-M. Kabeyad, G. Rauhaus", G. Peyerl", J.-J. Salaunc, R. Korte" Infusionstherapie 1990 (17):224-226
We evaluated the use of voluntary blood donor recruitment in Kinshasa, Zaire, as a means of reducing transmission of HIV-1 and other infectious agents by blood transfusion. Between January 1. 1989, and April 7, 1989, 2,237 blood donors were enrolled in the study at the transfusion centre of the Mama Yemo Hospital. Each donor was tested for antibodies to HIV-1 confirmed by IFA and Western blot, Treponema pallidum, antibodies to hepatitis B virus (HBV) core antigen and screened for the presence of the HBV surface antigen. Test results were related to the data of the blood donors: age. sex. haematocrit, voluntary blood donor, family member donor, paid donor. The serological results of all donors for Anti-HIV-1, Anti-HBc. HBsAg and TPHA were 4.8%, 70.9%, 13.1% and 13.3% respectively. Lower seroprevalence rates were found among voluntary blood donors. However, only TPHA seroprevalence was significantly lower in voluntary blood donors (8.4%, 23/275) compared with paid donors (15.2%, 87/571) (p<0.01). A greater proportion of voluntary donors provides a store of blood which allows more extensive screening of blood for HIV-1 and other infectious diseases. Voluntary blood donor recruitment is critical for the provision of safe blood supplies in Kinshasa.
Gegenstand der Untersuchung ist die Bedeutung der Blutspenderwer-bung fur die Verminderung des Übertragungsrisikos von HIV-1 und anderen Krankheitserregern in Kinshasa, Zaire. 2237 Blutspender wurden vom 1. Januar bis 7. April 1990 in der Blutbank des Krankenhauses «Mama Yemo» untersucht. In den Spenderserien wurden Hepatitis B Oberflachenantigene (HBs) und Antikörper gegen das Kernantigen (Anti-HBc) nachgewiesen sowie Antikörper gegen HIV-1 (bestätigt in Immunofluoreszenz und Western blot) und gegen Treponema pallidum (TPHA). Die Testergebnisse wurden zu folgenden Spenderinformationen in Bezug gesetzt: Hämatokrit. Alter, Geschlecht und Art des Blutspenders (freiwilliger Blutspender, bezahlter Blutspender, Blutspender aus der Familie des Empfängers). Es fanden sich folgende seropositive Testergebnisse: Anti-HIV-1 (4,8%), Anti-HBc (70,9%), HBsAg (13.1%), TPHA (13,3%). Freiwillige Blutspender zeigten geringere Seroprävalenzen, die jedoch nur im TPHA signifikant niedriger (8,4%, 23/275) als bezahlte Spender (15,2%, 87/571) lagen. Blutvorratshaltung ist die Voraussetzung für eine sorgfältige Untersuchung des Blutes auf HIV-1 und andere Krankheitserreger. Sie ist nur durch die Steigerung des Anteils freiwilliger Spender möglich. Blutspenderwerbung ist daher in Kinshasa unabdingbar für eine sichere Transfusionspraxis.
The World Health Organization has elaborated a strategy for developing countries which is designed to reduce transmission of HIV and other infections by blood transfusion . Special attention is given to means that avoid unnecessary transfusions: voluntary donor recruitment is encouraged [1-3]. In Kinshasa the implementation of strict transfusion guide lines proved both practical and effective [4, 5). Examination of blood donors and self-deferral were found to be of limited value in selecting high risk donors . Emphasis was, therefore, placed on increased replacement of paid donors by voluntary donors whenever possible.
In September 1988, only 1.1% of all blood donors were voluntary in Kinshasa's largest blood bank , compared with 12.3% during the study period. In Kinshasa most blood transfusions are performed in emergencies. They are rarely requested for selective interventions. Stored blood is in short supply, necessitating the use of rapid test assays for HIV-1screening  as blood samples routinely screened by the Elisa test are often not available. In the present study, we aimed to estimate the risk of transmitting HIV-1, hepatitis-B and syphilis by blood transfusion in Kinshasa and to determine whether this risk could be reduced by encouraging voluntary blood donor recruitment.
Material and Methods
In 1987, the GTZ (Deutsche Gesellschaft fur Technische Zusammenarbeit, Eschborn, FRG) began to rehabilitate two blood banks in Kinshasa. Recruitment of voluntary blood donors began in October, 1988. Blood bank personnel regularly instructed church attendants, factory workers and Red-Cross personnel on the benefits of voluntary blood donors (decreased HIV transmission due to blood transfusion). Between January 1, 1989, and April 7, 1989, 2,237 blood donors were enrolled in the study at the blood transfusion centre of the Mama Yemo Hospital, Kinshasa, Zaire. The donors were divided into three groups:
Age. sex and haematocrit (HCT) results of all donors were registered. Sera from all donors were screened for antibodies against Human Immunodeficiency Virus 1 (dupont de Nemours Hivcheck, Bad Homburg, FRG. and Behring Enzygnost Anti-HIV Micro, Marburg, FRG), Hepatitis B-Virus (Behring Enzygnost Anti HBc. Marburg, FRG), Treponema pallidum (Behring Cellognost Syphilis, Marburg, FRG) and tested for HBs-Antigen (Behring HBsAg Micro, Marburg, FRG). When test results were positive or doubtful in one anti-HIV-1 screening test, the donor was deferred and the serum tested for confirmation by Immunofluorescence assay (H9-V3 vs H9 non infected, J. Bernard, Institut Godinod. Reims, France) and Western blot (LAV-Blot 1 Diagnostics Pasteur. Paris. France) at the Institut National de Recherche Biomedicale/Kinshasa, ZaTre. Sera were considered positive for which one anti-HIV-1 screening test was positive and the result was subsequently confirmed in both IFA and Western blot . Anti-HBc and HBsAg screening tests were repeated if test results were within 10% of the calculated O.D. (optical density) cut-off. Only clearly reactive sera (O.D. greater than 10% calculated cut-off) were declared positive for HBV core antibody or HBV surface antigen. Treponema pallidum haemaglutination assay was considered positive when haemaglutination was observed with subsequent confirmation at a dilution of 1:32 by a second test. With the exception of TPHA, IFA and Western blot, all tests were performed with sera which had not been frozen. The rapid test assay (Dupont de Nemours Hivcheck)  was performed by different technicians on a 24h basis. All other tests were carried out regularly by the same technicians. The uncorrected Chi-Square and Mantel-Haenszel's test were used to assess the strengths of association for categorical variables.
2,237 blood donors were enrolled in the study; 12.3% (n = 275) voluntary donors, 62.2% (n = 1,391) family member donors and 25.5% (n = 571) paid donors. Of all the donors, 9.2% (n = 206) were women and 90.8% (n = 2,031) were men. The average age of the blood donors was 31.8 years (SD: 7.9) for women and 33.3 years (SD: 8.2) for men. The average HCT was 33.7% (SD: 15.9) for women and 40.7% (SD: 10.9) for men. The seroprevalence rates of confirmed anti-HIV-1 antibodies, anti-HBV core antibodies, HBV surface antigen, and anti-treponemal antibodies are shown in Table 1. Seropositivity did not vary by sex but differed by age (Table 2). Lower seroprevalence rates of anti-HIV-1, anti-HBc, HBsAg and anti-treponemal antibodies were found among voluntary blood donors. However, the difference were not significant between donor groups, except for TPHA results, where voluntary donors had significantly lower positivity than paid donors (Table 3). A total of 163 (7.3%) blood samples were not transfused. 128 (5.7%) deferrals of potential donors were caused by at least one reactive anti-HIV-1 screening assay. 35 (1.6%) blood samples were found to be positive for HBsAg but negative foranti-HIV-1 and eliminated. 247 blood samples (11%) HBsAg reactive and negative for anti-HIV-1 had already been transfused before test results became available.
A programme designed to promote voluntary blood donation increased the proportion of lower risk donors from 1.1% to 12.3% in a 6 month period. Efforts should be made to encourage the use of voluntary blood donors rather than paid blood donors for three reasons: