Читать книгу The African AIDS Epidemic - John Iliffe - Страница 10

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Origins

The earliest convincing evidence of the human immunodeficiency virus (HIV) that causes the acquired immune deficiency syndrome (Aids) was gathered in 1959 amidst the collapse of European colonial rule in Africa. In January 1959 rioters briefly seized control of the African townships of Leopoldville, the capital of the Belgian Congo, shocking its rulers into frantic decolonisation. In the same year an American researcher studying malaria took blood specimens from patients in the city. When testing procedures for HIV became available during the mid 1980s, 672 of his frozen specimens from different parts of equatorial Africa were tested. Only one proved positive. It came from an unnamed African man in Leopoldville, now renamed Kinshasa. The test was confirmed by the Western Blot technique – generally considered the most reliable method – and by different procedures in three other laboratories.¹ Although nothing of this kind can be absolutely certain, there are strong grounds to believe that HIV existed at Kinshasa in 1959 and that it was rare.

One importance of the Kinshasa case is to establish a date by which HIV existed, but in itself the case does not imply that the Aids epidemic began in western equatorial Africa. If that unnamed African had been the first person ever infected with HIV, it would have been an incredible coincidence. Once Aids was recognised as a medical condition early in the 1980s, researchers found several early accounts of patients whose recorded symptoms had resembled it.² Luc Montagnier, whose laboratory first identified HIV, thought that the earliest case had been an American man who died in 1952 after suffering fever, malaise, and especially the pneumocystis carinii pneumonia that afflicted later American Aids patients,³ but no blood had been stored for later testing and the symptoms demonstrated only suppression of the immune system, for which there could have been reasons other than HIV. The same was true of a Japanese Canadian who died in 1958 and a Haitian American in 1959. More convincing was the case of a fifteen-year-old, sexually active American youth who died in 1969 with multiple symptoms including an aggressive form of Kaposi’s sarcoma, a tumour common in later Aids patients. His stored blood tested positive for HIV by Western Blot, but the finding was later questioned. Other possible early cases were found in western equatorial Africa. There was no stored blood by which to confirm a specialist’s retrospective diagnosis of Aids in an African woman who was hospitalised at Lisala on the middle Congo in 1958 and died in Kinshasa four years later after suffering wasting and Kaposi’s sarcoma. But a Norwegian seaman contracted HIV some time before 1966, possibly while visiting Douala on the coast of Cameroun in 1961–2, and later infected his wife and child; all three retrospectively tested HIV-positive, although with a form of the virus different from that found in Kinshasa in 1959.

These cases are intriguing and were the bases for early controversy about the origins of HIV, but they reveal little except that it existed but was rare in the 1950s. The real grounds for believing that the dominant form of the virus originated in western equatorial Africa, probably in the broad area of Cameroun and the Democratic Republic of Congo (DR Congo), lie in three other directions. One is that HIV clearly results from the transmission to human beings of the ancient and related simian immunodeficiency virus (SIV), an infection of African monkeys that had also spread to chimpanzees.⁴ That such an animal disease should pass to humans is not surprising, because several major human infectious diseases are contracted from animals, notably plague, sleeping sickness, yellow fever, some forms of influenza, and, most recently, Creutzfeldt-Jakob’s Disease.⁵ How such a transmission took place with HIV will never be known, but one possibility may have been infection by blood in the course of hunting as men penetrated the equatorial forest. One study of 1,099 people engaged in hunting and butchering in Cameroun, published in 2004, found ten who had contracted simian viruses, although in this case not HIV.⁶ Aids is a by-product of the human mastering of the natural environment that has been the core of African history.

SIV has been transmitted from animals to humans at least eleven times and probably many more. There are two forms of the human disease: HIV-1, which is responsible for the global Aids epidemic, and HIV-2, which is less virulent and infectious and is virtually confined to the West African coast between Senegal and Côte d’Ivoire. HIV-2, discussed in Chapter 6, is closely related to the SIV common in the sooty mangabey monkeys of that region. By 2005, HIV-2 infections had been divided into eight groups, each believed to have resulted from a separate transmission. Only two of these groups, lettered A and B, had established themselves as human epidemics, suggesting that many unsuccessful transmissions may also have taken place in the past.⁷ By contrast, the animal virus most similar to (although still quite distant from) HIV-1 and probably ancestral to it is the SIV occasionally harboured by a species of chimpanzee (Pan troglodytes troglodytes) whose natural territory is the forest of Gabon, Equatorial Guinea, Central African Republic, Cameroun, and Congo-Brazzaville, somewhat north of Kinshasa. Three groups of HIV-1 have been identified and lettered M, N, and O. Each group must result from a separate transmission of SIV, because on a family tree of the virus they are separated by intervening SIV strains. Group M is responsible for the global epidemic that by 2005 had infected about 60 million people. Group O is equally virulent and may be at least equally old, having infected the Norwegian seaman during the 1960s, but it remained largely confined to the vicinity of Cameroun, even there causing fewer than 10 per cent of HIV cases in the early 2000s. Group N was probably a later transmission and remained very rare; in 2005 only seven cases were known, all in Cameroun.⁸

The fact that the likely viral ancestor of HIV-1 has been found only in the chimpanzees of western equatorial Africa is one of the three reasons for thinking that the virus originated there. The second reason is that only that region harboured not only all three groups of HIV-1 but all the subgroups of the dominant group M.⁹ The significance of this point arises from the nature of the virus.¹⁰ The human immunodeficiency virus is almost inconceivably small: one ten-thousandth of a millimetre in diameter. It consists of a package of genetic information (a genome) surrounded by a protein envelope, the whole containing nine genes, whereas a human being has 30,000–40,000. Like all viruses, HIV has no life of its own but is a parasite of cells, drawing its life from theirs. Transmitted from one body to another by blood, genital fluids, or human milk, the virus becomes attached to certain types of cells, the most important being the CD4 helper T-cells that activate the body’s immune system. The virus enters a cell and integrates its genetic information into its host’s, using the cell’s life to reproduce itself, which is the sole function of a virus. In doing so the virus destroys the host cell – and hence ultimately the immune system – while producing an immense number of new viruses to attack further cells. The process from entry into a cell to the production of new viruses takes on average about two days, so that HIV passes through some 180 generations a year. Moreover, the reproduction process is prone to error, because HIV’s genetic information is in the form of RNA (ribonucleic acid) and must be converted into the DNA (deoxiribonucleic acid) composing the cell’s genome. The combination of speed and error in reproduction means that HIV mutates at about 1 per cent per year, or a million times faster than is normal in evolution.¹¹

One consequence of this rapid mutation was that when the M group of HIV-1 was analysed during the 1980s and 1990s, it displayed great diversity. Using a range of specimens from Africa, North America, and Europe, researchers identified ten subgroups that differed from one another in their composition by up to 30 per cent. They were lettered A, B, C, D, F1, F2, G, H, J, and K.¹² All subgroups were found only in western equatorial Africa, although it may be more accurate to say that the fullest range of diversity existed only there, because the viruses identified in the DR Congo, in particular, show as much diversity within supposed subgroups as between them. This suggests that HIV group M evolved and diversified in the broad Congo region before certain strains were carried elsewhere to create differentiated subgroups by what is called a founder effect.¹³ At all events, there is a fundamental distinction between the great diversity of strains in western equatorial Africa and the domination of one or two subgroups (sometimes in combination) in every other region of the world: A and D in eastern Africa; a combination of A and G in West Africa; B in Europe and North America; C in southern Africa, Ethiopia, and India.¹⁴

Unlike many other viruses, such as influenza, HIV strains do not supplant one another at intervals but evolve and differentiate as they pass from one human body to another. Modern medical science can distinguish in great detail between these strains and reconstruct their genetic relationships. This makes it possible to write a history of HIV and its epidemic dispersal in a way that may be impossible for any other disease, using evidence from stored blood and living bodies. The first part of this book outlines such a history for the African continent. Moreover, medical science holds out at least the possibility of dating this history. It is plausible to argue that HIV mutates so extensively that its overall mutation is at a regular speed, which can be calculated from the evolutionary distance between classified specimens taken at known dates. This ‘molecular clock’ can then suggest dates for major events in the evolutionary sequence, such as the separation of one subgroup from another. One such calculation from 144 dated specimens was published in 2000, using massive computing capacity at Los Alamos. It suggested that the last common ancestor of HIV-1 group M – the point at which the subgroups of the global epidemic began to differentiate – lay around the year 1931, and with more confidence between 1915 and 1941. Since the researchers knew that the genes composing the HIV genome mutate at different speeds, they compared this calculation, based on the most mutable envelope gene, with a calculation from a less mutable gene, which suggested a 1934 date. The researchers checked their procedure further by independently dating the earliest HIV specimen taken at Kinshasa in 1959, which had been identified as an early version of the D subgroup shortly after its separation from the B subgroup. The computer dated it between 1957 and 1960.¹⁵ In 2001 another research team published similar calculations based on different specimens; they dated the last common ancestor of group M to 1937 (by the envelope gene) or 1920 (by the least mutable gene). The second research team also suggested that HIV-1 group M separated from the strain of SIV ancestral to that in modern chimpanzees around 1675, or with more confidence between 1590 and 1761.¹⁶ It would be unwise at this stage to attach too much importance to this date.

Among the many uncertainties surrounding these findings, the most relevant here is whether the notion of a molecular clock is invalidated by another feature of viral evolution known as recombination. A person can be infected by more than one strain of HIV. If that occurs, viruses of different subgroups may enter the same cell and, in the process of integrating their genetic material with the host’s, may produce a new strain of virus combining elements from two or more subgroups. (SIV is subject to the same process and the original simian virus transmitted to humans as the ancestor of HIV-1 group M is itself believed to have been a recombinant form.)¹⁷ Although the strain identified in 1959 appears not to have been a recombinant, one of the earliest recovered from the DR Congo in 1976 was, and it is even possible that supposedly discrete subgroups were products of recombination at a stage so early as to be no longer identifiable.¹⁸ Recombinants can combine with other recombinants, creating immense genetic heterogeneity, especially in the western equatorial region where the epidemic is oldest and the diversity of subgroups is greatest. Certain recombinant forms, however, have been especially successful. By 2005, 16 had been classified as circulating recombinant forms (CRFs), for each of which at least three distinct specimens had been analysed. The most successful were CRF01_AE, the dominant form of HIV in South-East Asia, and CRF02_AG, responsible for at least two-thirds of West African HIV infections.¹⁹ Recombination is probably at least as important as mutation in accelerating the evolution of HIV, but its implications for dating based on a molecular clock are complex and obscure. By blurring differences between subgroups it might make evolutionary events seem more recent than they really were, but by multiplying the number of strains it might make the events seem more ancient than they were. The two teams who estimated dates for the differentiation of the M group tried to exclude the effects of recombination, but geneticists feared that the problem was more difficult and that conclusions based on a molecular clock ‘may be of very limited value’.²⁰

However uncertain their findings, attempts to date the epidemic clarified several problems in its history. Together with the identification of the 1959 case in Kinshasa, they effectively ruled out the theory, propounded in Edward Hooper’s fascinating book, The River, that the HIV-1 epidemic had been caused by a polio immunisation campaign in the Congo region during 1957–60 that allegedly used a vaccine bred on SIV-infected chimpanzee kidneys – a theory also contradicted by negative tests on surviving vaccine samples.²¹ Instead, attempts at dating stimulated interest in the interwar period when the diversification of group M supposedly began. Noting that the earliest known HIV cases in Africa all occurred in francophone territories, researchers highlighted colonial innovations there that might have converted occasional viral transmissions into a disease capable of epidemic expansion: penetration of the forest for hunting, rubber collection, and logging; increased viral transmission through labour concentrations and vaccine campaigns against sleeping sickness and smallpox; and the adaptation of the virus to humans through rapid passaging by arm-to-arm inoculation that would have the effect of accelerating evolution.²² No direct evidence linking these innovations to HIV had been published by 2005, but the problem of how a simian virus might become capable of causing a human epidemic attracted the attention of other researchers. HIV-1 group N and at least six transmissions of HIV-2 had not become sufficiently transmissable or infectious as to cause epidemics. These were the forms of HIV most similar to SIV, so it appeared that the mere transmission of SIV to humans was unlikely to cause widespread disease; the virus must have evolved from SIV to HIV within human bodies, and it must have done so for the first time and perhaps more or less simultaneously in two groups of HIV-1 and two of HIV-2. Preston Marx and others argued that the chance of this happening naturally was ‘vanishingly small’. Instead, rejecting the 1931 date for the diversification of the M group but accepting 1959 as the first documented HIV case, they suggested that SIV had been converted into HIV by rapid passaging through African populations during the 1950s, owing to the introduction of supposedly disposable (but often in practice re-used) syringes to inject penicillin and other new medications. Between 1952 and 1960 annual world output of syringes increased from 8 million to something approaching 1,000 million.²³

These theories remained theories, but they indicated the kinds of evolutionary stages that may have produced HIV: probably multiple transmissions of SIV from sooty mangabey monkeys in West Africa over a long period; perhaps less frequent transmissions of the rarer chimpanzee virus in western equatorial Africa; its evolution into HIV within human bodies, whether over some centuries or through the unintended effects of medical interventions; and its emergence by 1959 as a virus capable of causing a global human epidemic.

Yet a difficulty remained: there was no visible epidemic in 1959, nor for another twenty years. The likely reasons lay in three characteristics of the virus. First, as viruses go, HIV is difficult to transmit. Whereas influenza – ‘the sickness of the air’, as it was called in Ethiopia in 1918 – can be transmitted aerially to anyone close enough to inhale it, HIV can be contracted only by absorption of blood, genital fluids, or milk from an infected human body. In heterosexual intercourse – the chief means of transmission in Africa – the chance of infection in one sexual act between otherwise healthy partners has been variously estimated at between 1 in 10,000 and 1 in 500.²⁴ To create and sustain an epidemic, therefore, requires special circumstances, but the chance of transmission increases substantially if either partner has a sexually transmitted disease or if the already-infected partner is in a particularly infectious condition. This is the case shortly after infection, when a person is perhaps eight or ten times more infectious than usual, and in the last stages of the disease, when infectivity is even greater.²⁵

The difficulty of transmitting HIV relates to the second likely reason for the slow emergence of a visible epidemic, which was the very gradual development of the disease within human bodies. For a few weeks after infection the virus has the advantage of surprise: viral load rises rapidly, lasting damage may be done to the immune system, and there may be feverish symptoms, perhaps often mistaken for malaria. Thereafter the immune system counter-attacks and an evenly matched war of attrition takes place in which HIV produces up to 10 billion new viral particles and destroys up to 2 billion CD4 helper T-cells each day. In HIV-1 this incubation period varies considerably but may last in adults for an average of nine or ten years – the period measured by a careful study in Uganda – before the immune system is so weakened that Aids supervenes. Death in untreated patients then follows almost invariably and relatively quickly, in an average of perhaps nine or ten months.²⁶ The infected person remains infectious throughout the disease. This long incubation period with only sporadic symptoms distinguishes HIV/Aids from previous epidemic diseases, renders it especially dangerous to human life, makes it difficult to check, ensures that it does not burn itself out, and, as will be seen, has given the Aids epidemic its unique character. As a comparison, the incubation period of influenza is not nine years but one to three days, while that of plague in Britain, considered unusually long and therefore dangerous, may have averaged about 30 days.²⁷ ‘What is serious,’ a West African villager said of HIV, ‘is that this disease is silent, hypocritical, visible only when the damage is already irreparable.’²⁸

There was a third reason why the potentially epidemic virus that existed in 1959 did not breed a visible epidemic for another twenty years. HIV/Aids does not kill but destroys the immune system’s capacity to resist other opportunistic infections that are ultimately fatal. Some of these, notably tuberculosis, were infections already current in the region concerned, so that it may not have been easy to discern that a new disease was present. Retrospectively, however, these opportunistic infections are the signs that first reveal the emerging HIV epidemic. Their appearance in western equatorial Africa during the 1970s is the third reason – alongside the location of the simian ancestor and maximum diversity of subgroups – to believe that the HIV epidemic originated there.