by Pepin
The early spread
Here we will review how, from its central African crucible, HIV managed to disseminate throughout Africa, at the same time as it did so across the Atlantic. But first we need to review two epidemiological terms. As explained in Chapter 1, ‘incidence’ is a measure of new cases of HIV that occur among previously uninfected subjects over a period of time. The same individuals have to be tested repeatedly: this is time-consuming, expensive and rarely used. ‘Prevalence’ is the proportion of individuals who have HIV at some point in time, a snapshot that indicates the current distribution. As the median interval between HIV infection and death in Africa is about ten years, measures of HIV prevalence reflect an accumulation of individuals infected from as little as a few weeks ago to more than ten years earlier. Over time, prevalence in a population increases if the number of new infections since the previous survey was greater than the number of individuals who died from HIV or other causes. Prevalence decreases when the reverse occurs, i.e. the number of deaths is higher than the number of new infections.
Information about the dynamics of HIV-1 in the 1960s–1970s can be inferred by analyses of archival samples, as well as by surveys carried out in the first few years after the identification of HIV-1. Among samples from the adult population, not a single case of HIV-1 was found in Gabon or among the Congo-Brazzaville pygmies. It is surprising, however, that two cases of HIV-2 infection were found in 1967 in samples from Gabon, a country not endemic for this retrovirus, and one wonders what the results would be if these sera were tested with modern methods. No HIV-infected person was identified among 250 individuals at the Yonda leprosarium of the DRC, whose blood had been stored since 1969. The HIV-1 positive samples from that early period came from Kinshasa where 0.25% of women attending a well-baby clinic in 1970 were HIV-1-infected, and from the village of Yambuku where prevalence was 0.8% in 1976. By 1980, among a similar group of Kinshasa mothers, 3.0% were HIV-1-infected.1–4
Thus in countries inhabited by the P.t. troglodytes source of HIV-1, prevalence probably remained minimal for most of the fifty years that followed cross-species transmission around 1921, too low to be detected in more than a handful of retrospectively diagnosed cases but high enough for the virus to persist. This is not contradictory. In Western Europe and North America, HIV-1 prevalence in the general adult population has remained around 0.1–0.2% for the last twenty-five years, and it is the much more effective transmission within small subgroups (gay men, injection drug users) which allows HIV-1 not to disappear. In central Africa between 1921 and 1970, HIV-1 prevalence was probably of the same order of magnitude for the overall adult populations but higher among the core groups of urban free women and their clients and among patients attending specific health institutions where iatrogenic transmission occurred. These sanctuaries allowed HIV-1 to persist, and eventually to disseminate when conditions were ripe.
In 1980–4, not a single case was found among adults from the Sangha region of Congo-Brazzaville or the Campo area of Cameroon. At the same time, in Lambaréné (the region of Gabon of Albert Schweitzer fame), three cases of HIV-1 infection were documented among 1,407 patients attending the hospital and one more among 1,313 adults living there. In 1984–5, in Franceville and other rural regions of Gabon, only three out of 1,648 villagers were HIV-1 infected. We can be pretty sure that Gabon, despite its large population of P.t. troglodytes, is not the site where HIV-1 emerged: prevalence thirty years ago was too low, especially considering that sampling patients attending health institutions overestimated the true prevalence.3–5
In 1985–6, among samples of 300–500 individuals representative of the adult (fifteen to forty-four years) male and female population, HIV-1 prevalence remained minimal in rural Gabon, Equatorial Guinea, Yaoundé, Douala and smaller cities of Cameroon (all around 0.3%) as well as in Port-Gentil (0.5%). However, prevalence was 1.4% in Franceville, 1.8% in Libreville, 4.4% in Bangui and 4.6% in Brazzaville. In the same cities, HIV-1 prevalence among pregnant women was either identical to the former measures (Brazzaville, Bangui, rural Gabon), a bit higher (Yaoundé: 1.3%) or a bit lower (Libreville: 0.5%). This modest prevalence in Douala and Yaoundé suggests that these urban centres were not involved in the early dissemination of the virus. In Kinshasa, among pregnant women, hospital employees and blood donors tested in 1984–5, prevalence varied between 5 and 8%, figures which were similar to those documented in Brazzaville, reflecting the strong links between the twin cities.4,6
At the time, Kigali, the capital of Rwanda, had the highest HIV-1 prevalence in the world: between 15 and 20% among blood donors, factory employees and hospital workers, 50% among STD patients and 80% or more among prostitutes. Bujumbura, the capital of Burundi, was not far behind, with 16% of pregnant women infected. The gender imbalance that we described in Léopoldville as the main driver of prostitution also existed in Kigali. In 1972, out of the 60,000 inhabitants of this small town, 2,000 were free women selling sexual services: the city was basically a large brothel. By the early 1980s, the male/female ratio among adults aged twenty to thirty-nine years was 1.57 in Kigali, 1.50 in Nairobi and 1.39 in Bujumbura compared to 0.98 in Kinshasa. In Kigali, the excess of males was driven largely by local customs rather than by the former coloniser’s policies (which is why it persisted long after freedom from colonial rule). Traditionally in Rwanda, men marry at a much older age than women, and the age group corresponding to the unmarried cohort was also the one that moved to the capital in search of a better life. Since marriage or other types of romantic consortship were impossible, sex was purchased and the supply followed the demand. Of the 10,000 inhabitants of Butare, the second largest city of Rwanda and the site of its national university, 293 were prostitutes, 80% of whom were already HIV-1-infected in 1983–4, as were 28% of men presenting with an STD. The lack of male circumcision further fuelled transmission.4,7–11
Nobody kept ancient collections of sera which could have been tested to document when the virus arrived. However, in Rwanda, 85% of isolates belong to subtype A while, in Burundi, 81% belong to subtype C. This marginal diversity implies that the virus was certainly introduced in Kigali and Bujumbura a long time after Léopoldville. The explosive epidemics in these two small adjacent countries resulted from the introduction from the Congo basin of two different founder HIV-1 subtypes, with very successful subsequent dissemination locally. The dramatic prevalences reflected a high incidence in the previous years rather than a slow spread.12–14
In the DRC, by 1986 the virus was widespread. For instance, among sex workers in small towns of the Equateur province, prevalence varied between 9% and 13%. In the remote Nioki hospital where I had worked, 2% of blood donors and 3% of trypanosomiasis patients were HIV-1-infected, and having travelled to Kinshasa was the strongest risk factor. In Kimpese, a Protestant mission 225 kilometres west of Kinshasa, 4% of pregnant women were HIV-1-infected, with considerable diversity and a predominance of subtype A, much like in the capital. Such diversity with a predominance of subtype A was also noted in Mbuji-Mayi, Kisangani and Bwamanda while at the extreme south-east of the country, in Lubumbashi near the Zambian border, 1,400 kilometres from Kinshasa, subtype C accounted for 51% of isolates, suggesting a more recent introduction of the virus. Because of the decay of the roads, travel between Lubumbashi and Kinshasa had to be by plane, much more expensive than the river boat to Kisangani.15–19
Surveys of sex workers during the late 1980s revealed high prevalences in Kinshasa (27–40%), Brazzaville (34%) and Pointe-Noire (46%), an intermediate prevalence in Bangui (12–21%), but much lower figures in Douala (6.5%) and Yaoundé (7.5%). As prostitutes represent a sentinel population in which HIV (along with other sexually transmitted pathogens) is amplified at the outset of an epidemic, these data suggest that the virus was introduced into this core group earlier in Kinshasa, Brazzaville and Pointe-Noire than in the major cities of Cameroon. Once more, Cameroon can be ruled out as the site of the early spread of the virus, even if ‘patient zero’ might v
ery well have been Cameroonian.4
From its DRC bridgehead, the virus slowly managed to propagate into other regions of the continent. Using molecular methods, it was estimated that HIV-1 reached parts of East Africa in the 1970s, where subtype A was probably introduced from the Zairean city of Kisangani. By the mid-1980s, the virus had infected 1–2% of pregnant women in Nairobi and Dar es Salaam, 8% in Lusaka and 11% in Kampala.4,20
Meanwhile, HIV-1 subtype C spread to southern Africa via Lubumbashi in the Katanga province of the DRC, through adjacent Zambia. In Zimbabwe, HIV-1 group C was introduced in the early 1970s; after a short period of slow growth, the number of infected individuals expanded rapidly during 1979–81, coinciding with the return of tens of thousands of refugees and freedom fighters at the end of the liberation struggle. The best documentation of the emergence of HIV-1 comes from the Karonga district of northern Malawi, where a large collection of blood samples had been collected for long-term studies of leprosy. Of about 1,000 adults bled in 1981, none was HIV-infected. The following year, 4 of 4,354 specimens (0.1%) were HIV-reactive. By 1988, 1.1% of adults were HIV-infected. Testing of these archived samples showed that initially (1982–4) HIV-1 subtypes A, C and D were introduced, with subsequent explosive growth of subtype C but only limited spread of the others, reinforcing the idea that subtype C might be more transmissible. Later, history would repeat itself: the gender imbalance in the mining towns of South Africa led to rapid HIV transmission between prostitutes and miners, who brought it back, during their annual leaves, to their home areas in South Africa, Mozambique, Lesotho and Swaziland. This epidemic would eventually dwarf all others.20–23
At the other end of the continent, the economic metropolis of Abidjan was the hub around which HIV-1 disseminated in West Africa. Testing of stored samples did not show evidence of HIV-1 before 1980, while two persons were infected with HIV-2 in 1966. The viruses then spread exponentially among sex workers, half of whom were infected by the mid-1980s. Quickly, HIV-2 was superseded by HIV-1, whose sexual transmission is more effective, and the dominant HIV-1 strain came to be CRF02_AG, which was rare in the DRC but relatively common in Gabon and Cameroon, implying a northward progression towards West Africa. Abidjan, a booming city that attracted migrants, especially male agricultural workers from Burkina and Ghanaian female sex workers, was the only major city in West Africa with a gender imbalance. Its male/female ratio among adults aged twenty to thirty-nine was 1.23 in 1983 (1.38 in 1955), compared to ratios close to 1.0 in urban Ghana, Senegal, Mali and Benin. Prostitution flourished, the best possible breeding ground for HIV-1.4,11,24
To summarise, during the 1970s and into the early 1980s, the virus disseminated silently but relentlessly throughout the African continent, at about the same time that it crossed the Atlantic to establish a foothold first in Haiti, and then in the US. At this stage, its subsequent transformation into a global epidemic became unavoidable.
The subsequent spread
As the number of infected persons had expanded considerably, there could now be multiple introductions of the virus into various other parts of the world, rather than single founder effects. The same methods that allowed a reconstruction of the epidemic history in Africa, Haiti and the US were deployed to track down retrospectively what had occurred elsewhere. The history of the global and mainly post-1981 dissemination of HIV-1 could fill a whole book. I will present here just a brief overview of selected foci, as an illustration of the epidemiological genius of this retrovirus and of the power of currently available tools in evolutionary biology.
Starting in the early 1980s, HIV-1 group B was successfully re-exported from the US to Western Europe, through several channels. First, there were multiple introductions by European homosexuals who vacationed in San Francisco or New York (and a few in Port-au-Prince), or the other way around by American gay men who had a good time in Europe. As an example, in the United Kingdom, between 1981 and 1987 there were at least six independent successful introductions of HIV-1 group B followed by exponential transmission within the gay community until the early 1990s, while several other introductions became epidemiological dead ends. Second, the exportation of unheated contaminated plasma: HIV prevalence among haemophiliacs of various European countries in the late 1980s paralleled the proportion of their coagulation factors that had been imported from the US. And third, through drug addicts, a small fraction of whom were rich enough to inject their heroin or cocaine on both sides of the Atlantic. Within these three Western European subpopulations, nearly all HIV-1 infections were initially caused by subtype B, which could only have originated from the US. The same country also re-exported HIV-1 to Canada, most of Latin America, Australia and even to the white gay community of South Africa.25–29
Although some other subtypes were introduced at roughly the same time, it is only in the 1990s that non-B subtypes spread within Western Europe. These infections were initially documented among travellers and migrants from endemic countries, especially sub-Saharan Africa. Eventually, in some European countries, non-B subtypes managed to get transmitted within the local population and became predominant. For instance in Greece, subtype A is now the most common subtype, having been imported from East Africa and re-exported to Albania.30–31
Meanwhile in India, the country with currently the third highest number of HIV-infected individuals in the world (after South Africa and Nigeria), HIV was first recognised in 1986, but certainly had been present for a few years. It spread swiftly, especially among the core group of sex workers and their clients, but also among intravenous drug users. Subtype C represents around 95% of all Indian HIV-1 infections, and seems to have been introduced from South Africa, which is not surprising given the latter country’s large Indian population that must travel intermittently to its homeland.32–36
Throughout south and south-east Asia, intravenous drug use played a major role in the dissemination of several subtypes of HIV-1 along heroin trafficking routes. In Thailand, a variant of subtype B (Thai B or B’) and the recombinant CRF01_AE were introduced simultaneously and recognised around 1985–7. The former, imported from North America or Europe, spread among IDUs while the latter, originating from Africa, disseminated via heterosexual transmission. Exponential spread among IDUs and female prostitutes followed almost immediately, in 1988–9. Eventually CRF01_AE had much more success and became the predominant strain, even among IDUs, which allowed it to be re-exported quickly to Vietnam, while B’ reached Myanmar.37–40
In China, phylogenetic analyses showed that HIV-1 subtype B’ was introduced around 1985 or shortly thereafter through intravenous drug users, from the Golden Triangle region, the opium-producing area that covers the boundaries of Burma, Laos, Thailand and China. A few years later, around 1991, the same subtype reached the cohorts of paid plasma donors, among which it propagated exponentially, as described in Chapter 12.41–42
Beyond these main events, a large number of country-specific or risk group-specific importations of each and every subtype and recombinant have been documented across the six continents, from the remote regions of Brazil to the former republics of the Soviet Union. Never in human history has the global dissemination of a pathogen been studied so thoroughly. This bewildering diversification of the virus will make it even harder to develop an effective vaccine, or at least one that could be distributed globally.
The response
We will now examine the early response to this emerging pandemic through a short biography of one of its most prominent and colourful characters. Jonathan Mann was born in Boston in 1947. He studied history at Harvard and did a year of political science (1967–8) in Paris. We do not know if he was affected by the French student rebellion in May 1968 (‘No forbidding allowed’), but his proficiency in French would serve him well in the future. He obtained his MD in 1974. Having received a scholarship from the Public Health Service, he had to work for the government for two years and he entered the Epidemic Intelligence Service training programme of the Centers for Diseas
e Control. He was sent to Santa Fe and soon gave up his plans to become an ophthalmologist.43,44
As a public health doctor in New Mexico, he developed an interest in viral hepatitis, rabies, botulism, measles and especially bubonic plague, which had fascinated him since he was a teenager, when he had read Albert Camus’ masterpiece The plague. According to his sister, Jonathan identified with the hero Dr Rieux, as he struggles against the devastating epidemic, which symbolises fascism, the corruption of minds and evil. The plague was mildly endemic in the American south-west, and Mann devoted a dozen scientific articles to it.43,45
In 1984, the CDC needed an epidemiologist who spoke French to head up an AIDS research project, ‘Projet Sida’, in Kinshasa, Zaire. Looking for a new challenge, Mann got the job, which would change his life. He only stayed two years but it was a very productive period. Projet Sida was a collaboration between American, Belgian and Congolese institutions, the first long-term, Africa-based research project devoted exclusively to this new disease. Prior to that, embryonic AIDS research in Africa was of the ‘safari’ type: expeditions of a few weeks to gather specimens, which were then processed in the West. Projet Sida set up a laboratory in Kinshasa and other resources to analyse locally its findings. Mann and his team, many of whom were young Congolese doctors without any research experience, published about twenty articles on the epidemiology of HIV-1 in Kinshasa. Their work may seem rudimentary today but at the time it systematically broke new ground.46,47
Projet Sida showed that the main mode of transmission of the virus in Africa was heterosexual sex, which debunked the theories inherited from the early years of the epidemic in industrialised countries, where this mode of infection was thought to be ineffective. The impact was devastating: it meant that every sexually active person was at risk. The prevalence of HIV-1 in Kinshasa was 5–8% in the general adult population, already a generalised epidemic, and the first to be characterised. The Projet Sida team also began to document that Congolese children acquired the infection from their mothers and sometimes from blood transfusions, but not from mosquitoes. The populations studied included not just the patients and staff at Hôpital Mama Yemo but also prostitutes, 27% of which were HIV-1-infected. Project SIDA also investigated the role of medical injections in HIV transmission. Several of their studies documented that HIV-infected individuals had received more injections than seronegatives, but they could not tell which came first, HIV or the injections.
