by Pepin
Jonathan Mann showed an innate sense of diplomacy, which was remarkable given his lack of previous African experience. He maintained cordial relations with numerous health ministers, who were constantly replaced at the whim of the ‘enlightened leader’ and ‘founding president’ of the Mouvement Populaire de la Révolution. Every one of Projet Sida’s scientific presentations to any group, every one of its publications, had to be pre-approved by the minister. Mann scrupulously followed the rules, which allowed his team to continue doing their research in Kinshasa at a time when it was virtually taboo to mention AIDS in many African capitals. He navigated easily through the muddy waters and vicissitudes of daily life in Zaire, where corruption was rampant and galloping inflation could in a matter of weeks make the salaries of the Projet Sida staff virtually worthless.47
Charismatic, eloquent, energetic and a visionary, Mann soon came to the attention of the director of the WHO, Halfdan Mahler, who, in late 1986, offered him to lead the new WHO Global Programme on AIDS (GPA). Previously WHO had thought AIDS was not its concern since it was limited to particular groups in a few industrialised countries. Realising that this was a huge mistake, it worked hard to make up for lost time. Financially and organisationally, GPA grew like lightning, due in large part to Mann’s skills as a communicator and diplomat and his intense lobbying of donor organisations. GPA expanded from a few employees in 1986 to hundreds in 1990, with an annual budget of over $100 million.44,47
Mann travelled constantly and was active on all fronts. Having no confidence in the WHO’s African bureaucracy in Brazzaville, GPA brought in country-level staff who reported directly to Geneva. The first medium-term plans to fight AIDS were developed by GPA consultants, for implementation by ministries of health, at least in theory. At a first special meeting of dozens of health ministers in London, these politicians understood that AIDS was truly a ‘pandemic’, literally ‘affecting all peoples’. This sounded the death knell for the denial phase – with the tragic exception of South Africa.
Mann’s flamboyant personality and high profile, disregard for the UN’s complex bureaucracy and rules and independence from senior officials would sooner or later cause him grief. When Mahler retired in 1988 and was replaced by Hiroshi Nakajima, it did not take the latter long to put spokes in Mann’s wheels and pressure him to leave. Nakajima was appointed and reappointed largely due to lobbying by Japan, which promised substantial aid to southern hemisphere countries that supported its nominee (and threatened to cancel its aid if they did not). Nakajima would ultimately leave behind him a demoralised organisation that had run out of steam. Tired of all the harassment, Mann resigned amid much ado in 1990.
He was offered a chair at the Harvard School of Public Health, a demotion if a very honourable one. His team published two editions of AIDS in the world, a review of the state of the pandemic. But the main mission he set himself was to champion the fight against AIDS from the perspective of human rights, which he had started to advocate while still at the WHO. Since AIDS is linked to poverty, injustice, exploitation, vulnerability and all kinds of inequities, all these determinants of the epidemic needed to be addressed simultaneously. This was dreaming in technicolour. However, Mann seemed to enjoy the character he had created for himself as a university humanist in a bowtie. In early 1998, he accepted the position of founding dean of the School of Public Health at Drexel University in Philadelphia.48–50
Jonathan Mann was a leading figure in the first decade of the struggle against AIDS in Africa. His epidemiological work in Kinshasa increased our understanding of the magnitude of the problem and of the mechanisms of transmission. His time at the WHO helped to make the international community aware of the extent to which AIDS had already become a global problem. It was not restricted to a few marginal groups in the West, and would continue to spread inexorably through heterosexual sex. His unflagging denunciation of the stigmatisation of and discrimination against those infected with HIV certainly helped the victims to be ultimately accepted by their societies, governments and families.44
He also had a real impact on many developing countries that were initially tempted to bury their heads in the sand and were gradually persuaded to adopt a more intelligent approach. ‘Close down the city!’ the authorities in Oran were ordered when the city was hit by bubonic plague, and many governments (starting with the US) were tempted to react to AIDS the same way, not knowing that it was already much too late: the virus was everywhere. It is impossible to fight a disease if one refuses to admit it exists. Mann managed to get across this simple truth to politicians on all continents.
In retrospect, however, Jonathan Mann’s efforts, first at the WHO and then in academia, probably had little impact on the dynamics of the virus. He often talked about three epidemics: first the spread of HIV infections, then AIDS a decade later, swiftly followed by an epidemic of discrimination and rejection. He seems to have become obsessed with the third aspect to the detriment of the first, as if he thought it was impossible to limit the transmission of the pathogen. Public health measures that had a significant impact in the second half of the twentieth century in sub-Saharan Africa were all simple, effective and inexpensive, so that they could be replicated continent-wide: vaccination against measles, oral rehydration, management of respiratory infections and insecticide-treated mosquito bednets. Obviously there was no magic bullet against AIDS, but Mann does not seem to have realised that, especially at the end of the 1980s, millions of infections could have been prevented by the systematic implementation, across the continent, and in southern Africa in particular, of preventive measures targeting prostitutes and their clients. In all infectious disease control programmes, the first step is to identify high-risk groups and focus efforts on these, at least initially. In the case of HIV, this principle was ignored. Pilot projects demonstrated the feasibility and efficacy of interventions for sex workers, but this was never promoted as a programme to be implemented in all cities, big and small, across Africa. Such an intervention, involving the vigorous and often authoritarian imposition of the use of condoms throughout the sex trade, reversed the course of the epidemic in Thailand in the 1990s.
In Algeria, Rieux did not have antibiotics to treat plague sufferers, and it remained unclear whether the experimental serum developed by one of his colleagues was effective. Mann did not have inexpensive antiretrovirals, and the treatments for opportunistic infections that complicated AIDS in Africa were pathetic. The Oran hospital was simply a place to die, like the African hospitals overflowing with AIDS patients at the end of the twentieth century. Many Oran doctors died of the plague contracted on the job, as did physicians, surgeons and nurses in Africa, who got HIV from their patients. And just like Rieux, courageous and compassionate but not knowing how to control the epidemic, Mann seems to have considered the spread of HIV as unstoppable. The genius who created Rieux, Albert Camus, died prematurely in a car accident in 1960. Jonathan Mann died in 1998, in the crash of Swissair Flight 111, on his way to Geneva to attend a conference. Camus’ novel ends with the phrase ‘perhaps the day will come when to the misfortune or enlightenment of humanity, the plague will again bestir its rats and send them forth to die in a happy city’.45
14 Assembling the puzzle
After reviewing the many elements of the puzzle piece by piece throughout this book, it is now time to assemble them into a coherent summary of the events that led to the transformation of SIVcpz into HIV-1, triggering the worst pandemic of modern times. Several pieces of this puzzle are irrefutable, while others remain the most plausible hypotheses explaining parts of the story, given the currently available circumstantial evidence. However, as the years go by, it becomes less and less likely that researchers will uncover novel information that could substantially alter this narrative.
We have seen in Chapter 2 that, for at least several hundred years, the Pan troglodytes troglodytes chimpanzee of central Africa has been infected with a simian immunodeficiency virus, SIVcpz, which is genetically identica
l to HIV-1. The distribution of SIVcpz among chimpanzees in the pre-colonial era was probably not much different from what it is today. Apart from the higher level of threat from humans, the social and sexual behaviour of chimps has not changed over time. SIVcpz is mainly transmitted within well-defined troops of chimpanzees, presumably through sexual intercourse, but only sporadically to other communities, with which contacts are infrequent. This resulted in a heterogeneous distribution of SIVcpz, absent from some communities while infecting a third of the members of other troops. Overall, around 6% of P.t. troglodytes chimps are infected with SIVcpz. Some naturally infected chimps develop a disease reminiscent of AIDS, but only after several years during which their intense sexual promiscuity allowed them to spread the virus. It is clear that the other three subspecies of Pan troglodytes are not the source of HIV-1. The other chimpanzee species, the Pan paniscus bonobo, has been less investigated but there is so far no evidence that it is infected with SIV.1
Human populations of central Africa have been in contact with P.t. troglodytes for as long as they have lived there, around 2,000 years for the Bantus and longer for the pygmies, and in contact with SIVcpz-infected chimps for as long as the virus has been present among apes. Why did not SIVcpz emerge into HIV-1 sooner? First, human contacts with chimpanzee blood may have been less common during the pre-colonial era as the lack of firearms made it more difficult to hunt for apes, and the dearth of even rudimentary roads in densely forested areas reduced the interactions between humans and chimps (Chapter 4). Secondly, the conditions that would later facilitate the large-scale sexual and/or parenteral amplification of SIVcpz/HIV-1 did not yet exist. At the time there was little opportunity for the parenteral transmission of blood-borne viruses, apart from traditional scarifications and ritual circumcisions. And there were no cities where high-risk prostitutes would have sex with more than 1,000 men each year. Thus, when pre-colonial hunters or cooks acquired SIVcpz, such infections remained epidemiological dead ends: the hunter infected his wife or wives, the cook infected her husband, both would die of AIDS ten years later, and that would be the end of it. The number of cases would be too low for the virus to be transported during the slave trade on a scale that would have made it recognisable 300 years later, epidemiologically or phylogenetically, or for the disease to be identified among many others by the pioneers of tropical medicine in the early twentieth century. Then, around 1921, the date of the most recent common ancestor of pandemic HIV-1 strains, the situation changed. Not so much that many more people had contacts with chimpanzee blood, although small firearms were by then readily available, but the mechanisms that would allow the exponential amplification of the infection appeared.
In the following pages, I will try to estimate the probability that a number of events did or did not occur. There are many sources of error and many assumptions had to be made. Therefore, these figures should be seen as generally indicative of what may have happened rather than as precise mathematical measures. Even if one doubles or halves this or that number, it does not materially alter the conclusions.
We have seen in Chapter 4 that, around 1921, 1.35 million adults lived in areas inhabited by P.t. troglodytes: Cameroun Français, Gabon, Moyen-Congo, Oubangui-Chari, Guinea Espanola, the Cabinda enclave of Angola and the small part of the Belgian Congo that lies north of the Congo River. Presuming that the frequency of exposure to chimpanzee blood was the same as in recent times, 0.1% of these adults had been exposed to blood potentially containing SIVcpz at least once in their lives. If we multiply the total number of adults by 0.1% and multiply this by the 5.9% SIVcpz prevalence among P.t. troglodytes chimps, we can calculate that eighty adults were exposed to the virus while hunting or handling chimpanzee carcasses. With a 1% risk of transmission during occupational exposure through the skin, we end up with one human infected from chimps, or three if transmission per exposure was closer to 3% (these estimates of risk of transmission are based on extrapolations from healthcare workers exposed to HIV-infected blood). To facilitate the subsequent calculations, let us use the median number and say that in 1921 there were two SIVcpz-infected humans, probably both men, living in one of the countries inhabited by P.t. troglodytes.1–2
Then, if we were to assume that urbanisation and urban prostitution were the only amplifying mechanisms (the current standard theory on the emergence of HIV-1), we need one of these SIVcpz-infected hunters to infect a first prostitute in a colonial city, perhaps Yaoundé, Bangui, Libreville, Brazzaville or Léopoldville, for a chain of sexual transmission to be initiated. A number of factors made such a process a bit unlikely. First, the proportion of the population of central Africa that lived in urban areas around 1921 was at most 5%. Second, those who were more likely to be SIVcpz-infected, the illiterate villagers who had occupational contacts with chimpanzees, must have been less prone to move into urban areas than individuals with at least a few years of primary school education, who spoke some French and could be hired by the colonial administration, private companies or expatriates. Third, not all men living in the cities had sex with prostitutes. So if we start with two SIVcpz-infected men, assume a 2.5% probability of moving to a colonial city, and also assume that half of the city dwellers bought sex from free women, the probability that at least one of the two might have had sex with a free woman would be something like one in forty. However, the probability of male-to-female transmission of HIV-1 is not 100%. There are many serodiscordant couples in Africa (and elsewhere), in which one remains seronegative despite hundreds of unprotected intercourses with the seropositive spouse. In general, the risk of HIV-1 transmission is estimated at about one per 1,000 intercourses. Transmission is more effective, however, in the presence of an STD, especially those causing genital ulcers, and if the man is not circumcised. If we assume that the SIVcpz-infected man had repeated intercourses over many years with free women, the cumulative probability of at least one forward transmission of HIV-1 would be around 50%. So the 1:40 probability becomes 1:80. It is entirely possible that this did occur and that the pandemic was in essence caused by an unpredictable factor: bad luck.
Would the odds have been different if the first chains of sexual transmission had not occurred in the cities but in the camps housing the unfortunate men conscripted into forced labour for building the Congo–Océan railway, as described in Chapter 3? If we exclude those from Tchad (no P.t. troglodytes), about 110,000 men from Moyen-Congo and Oubangui-Chari were forced to work on the railway between 1921 and 1932, which was roughly 16% of all adult men living within the P.t. troglodytes habitat. If we do the same maths as above, we end up with a 1:7 probability that one of them was infected with SIVcpz. Let us say that half had sex with local free women, but for a shorter period (unlike the urban migrants, most CFCO workers would not spend much more than a year or two in situ), thus with a lower risk of forward transmission. So we would probably end up with the same type of odds, something like 1:40 or 1:80.3
However, this chain of events would have been infinitely more likely, even unavoidable, if there had been, somewhere in one of these countries, an initial phase of parenteral amplification of SIVcpz/HIV-1 through re-usable syringes and needles for the treatment of tropical diseases. For this to happen, we would need one of the two SIVcpz-infected men to be diagnosed with a tropical disease and to receive an IV drug. For villagers, this was much more probable than migrating to a city and infecting a prostitute. They did not have to move at all: the mobile disease control teams came to their villages with their microscopes, syringes, needles and drugs. For the Congo–Océan workers, rudimentary hospitals provided care along the railway, and many workers would need their services, however primitive these were.
Opportunities for the parenteral transmission of blood-borne viruses first arose with the campaigns against sleeping sickness, then with the early treatments of leprosy, at exactly the right place and time (Chapter 8). A few years later, massive iatrogenic transmission of HCV occurred in south Cameroon through the parenteral treatment of m
alaria when fixed health centres and hospitals, which could administer intravenous quinine, were established in the 1930s. In some regions, transmission of HCV may have been enhanced by large-scale campaigns for the control of yaws and syphilis, which used mostly parenteral drugs. The areas highly endemic for malaria and yaws happened to correspond to the forested areas inhabited by P.t. troglodytes. For instance in the Ntem, Kribi and Sanaga-Maritime regions of Cameroun, as well as in most of Gabon and Moyen-Congo, population incidence of yaws was often greater than 200 per 1,000 per year between 1930 and 1950, and most humans would be bitten by a mosquito carrying the malaria parasite every other day. Over a period of a few years, almost the entire population, including our two SIVcpz-infected individuals, would be treated with injectable drugs.
The efficacy of transmission of SIVcpz from one patient to another would have been comparable to what has been described in many parts of the world, mostly after 1981, among drug addicts. As reviewed in Chapter 7, once the virus is introduced into such groups who share syringes and needles, it spreads quickly, and up to 50% of addicts can acquire HIV-1 within a few years.4 Transmission of HIV-1 is ten times more effective through the sharing of needles and syringes than via sexual intercourse because the minute quantity of blood from the first user which remained in the syringe or needle is then injected IV, directly into the next user’s blood, where HIV-1 can easily spread to the latter’s lymphocytes. When a second person, an addict or, in our case, another individual treated for the same tropical diseases, developed primary HIV-1 infection, a very high degree of viraemia ensued, reaching 105 to 107 viral copies per ml. After two or three weeks at this level, viraemia slowly decreased over four to six months until it reached a steady state, generally around 104 viral copies per ml. During this brief peak, the second person’s blood was highly infectious so that the risk of transmission to a third person must have been higher than 1% per episode of needle/syringe sharing. Further injections of antitreponemal, antitrypanosomiasis or antimalarial drugs with the syringe or needle used for this second patient would expose to HIV-1 other patients who were treated on the same or following day. Inevitably, a third person would become infected, further increasing the risk for the other patients treated at the same health facility or disease control mobile clinic. The tragic iatrogenic epidemics of HIV-1 in Romania and Libya, which, long after HBV, HCV and HIV were identified, occurred in countries with far more resources than those available in central Africa during the early twentieth century, demonstrated the potentially devastating efficacy of health care in spreading HIV-1 parenterally.
