The Origins of AIDS

by Pepin

  Jamot had a strong personality, was highly motivated and worked hard. He quickly became known for his favourite slogan: ‘I will wake up the black race.’ He obtained very substantial resources, to the point where his specialised and autonomous sleeping sickness organisation, created in 1926 and based in Ayos, east of Yaoundé, was seen by many in the administration as a state within a state. Jamot answered directly to the governor, and was independent of the chief medical officer of the colony and local administrative authorities. Several egos were bruised in the process. At one point, half of the medical doctors in Cameroun were working under Jamot, who coordinated twenty-eight mobile teams operating throughout the country, with a staff of 17 physicians and 400 healthcare workers.

  He was revered by his subordinates, known as the jamotains, while his approach became the jamotique. In the communities visited, roughly 500 villagers were seen each day. The work was organised like a production line with each member of the team having well-defined roles: bureaucrats took care of the paper work (registries, individual certificates), nurses palpated the necks and marked with a cross the foreheads of those who needed microscopic examinations, a small army of microscopists would examine the blood and lymph node aspirates, yelling when a trypanosome was detected so it could be corroborated by the doctor, while other nurses performed the lumbar punctures for disease-staging on those found to be infected. Eventually, the doctor would prescribe the treatment to be administered by nurses, who would stay behind after the rest of the team had left for the next village. During Jamot’s tenure in Cameroun, 150,000 cases of sleeping sickness were diagnosed and treated. However, when the incidence decreased, some of his medical colleagues wondered whether it was reasonable to spend so much on trypanosomiasis and so little on the fixed health facilities which would provide basic care all year round.

  Jamot published forty scientific papers during his career, a large number for an African-based non-academic doctor. Some contain extremely detailed descriptions of the distribution of trypanosomiasis in Cameroun and of the treatments used. A free thinker, he repeatedly and publicly said that the dramatic epidemics of trypanosomiasis in Cameroun and AEF had been triggered by European colonisation and the forcible displacement of large populations. This freedom of speech did not sit well with his military status. Other conservatives did not appreciate that while remaining legally married to his French wife, who never went to Africa, Jamot lived for many years with a Fulani from north Cameroon whom he married according to tribal customs and with whom he had three children.

  A forceful advocate of disease control in the African colonies, Jamot became well known in France, especially during the Paris colonial exposition of 1931, as the man who conquered sleeping sickness. He was honoured by scientific bodies, received the Légion d’Honneur, and was even nominated for the Nobel. He took advantage of his notoriety to obtain ever-increasing resources for trypanosomiasis control in Cameroun. Even though the incidence was now 90% lower than when he arrived, Jamot had a more ambitious goal: its eradication, which seemed possible given that there was no significant animal reservoir of the parasite.

  His high profile would eventually cost him his job. His many enemies found a good pretext to get rid of him when one of his subordinates decided, apparently on his own, to double or triple the dose of a new arsenical drug, tryparsamide. This went on for more than a year with the result that hundreds of unfortunate patients in the Bafia area became blind, as the drug was toxic to the optic nerve. Jamot’s implication in this disaster remained unclear. The young Bafia doctor was sacked but he protested and an inquiry was held. Jamot, who was then in France, did not show up at the ministry of colonies as requested. This was not appreciated. While on a stopover in Dakar on his way back, colonel Jamot received a telegram. He too had been fired from his post in Cameroun.2–5

  He was sent to organise sleeping sickness control in French West Africa, from a base in Ouagadougou. Jamot spent the next three years crisscrossing this vast territory, finding 70,000 new cases. However, he was caught up in similar disputes with the medical and administrative authorities concerning the importance and degree of autonomy given to the sleeping sickness control organisation. Discouraged by what he viewed as a lack of understanding of the seriousness of the problem, in 1935 Jamot retired from the military and went back to his village in France to work as a general practitioner. A broken man, he died of a stroke a year later.

  There is no doubt that Jamot and his teams saved entire communities from extinction. In some villages in the upper Nyong region east of Yaoundé, up to 97% of the inhabitants were found to have trypanosomiasis during successive surveys, and sleeping sickness was causing more fatalities than all other diseases combined. Other villages, which could not be visited in time by the mobile teams, had been entirely wiped out by the disease: a large part of the population had died, and others had left the area looking for a more secure location. After Jamot’s departure from Cameroon, the concept of disease-specific mobile teams roaming the countryside was adapted for the fight against other tropical diseases, especially yaws and syphilis. But this very dedication and efficacy created tremendous opportunities for the iatrogenic transmission of blood-borne viruses.

  To evaluate the potential contribution of tropical disease control interventions in the spread of viruses, a detailed review was necessary. Fortunately, good archives have survived to this day. Most of these reports were kept at the tropical medicine institute of Marseilles (located, quite appropriately, on the Allée du Médecin-Colonel Jamot): annual reports of the health services for Cameroun Français, Moyen-Congo, Oubangui-Chari, Gabon and AEF. The AEF included Oubangui-Chari, Moyen-Congo, Gabon and Tchad. As the latter is not inhabited by P.t. troglodytes, I collected data for the first three territories (from now on called AEF-3). For Cameroun, the annual reports sent to the League of Nations and United Nations were available at the UN library in Geneva. Additional information was found in annual reviews of communicable diseases in French overseas territories. For each disease of interest except malaria, it was possible to calculate the annual incidence (number of cases per 1,000 inhabitants), which is important for inferring which ones were the most likely factors behind the high prevalence of HCV described in the previous chapter and potentially the emergence of SIVcpz/HIV-1. Denominators used to calculate incidence rates took into account the changes in boundaries between AEF territories and natural growth of these populations (Figure 4). At the time, few diseases were treated with orally administered drugs, so in practice an annual incidence of, say, 10 per 1,000 meant that during this year 1% of the population received a series of injections for the treatment of this specific disease.10–23

  For a long time, treatment of sleeping sickness was based on drugs that contained arsenic, hence their general designation as arsenicals. The same arsenical drugs, or similar compounds, were also used to treat yaws and syphilis, among other infectious diseases. For most of the 1920s, SC atoxyl was widely prescribed, often combined with a second drug given IV, for instance tartar emetic (the drug used in Egypt to treat schistosomiasis). In the 1920s, the introduction of tryparsamide, a drug developed at the Rockefeller Institute, resulted in a dramatic improvement: patients with involvement of the brain could now be cured. Just for 1927–8, 900 kg of atoxyl (about one million injections) and 600 kg of tryparsamide (135,186 SC and 71,903 IV injections) were used in Cameroun by Jamot’s teams. The number of injections declined thereafter (Figure 10), as the control efforts proved effective. After 1928, tryparsamide was usually administered IV while another arsenical drug, orsanine, given SC or IV, was used for early stage cases. In AEF, treatments were standardised through instructions of the médecin-général: twelve weekly SC or IV injections of orsanine if the cerebrospinal fluid was normal, or twelve weekly IV injections of tryparsamide if cerebrospinal fluid was abnormal, to be repeated annually for two more years to ‘consolidate’ the initial treatment. On average, tryparsamide-treated patients received thirty-six IV injections.24–27
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  Such once-a-week regimens were quite manageable as nurses left behind by the mobile teams could rotate between villages, treating all cases in a given village on Mondays, all cases in a second village on Tuesdays and so on, repeating this circuit twelve times. This mobility of practical nurses implied that the procedures for sterilising syringes and needles were minimal. However, they became extremely skilled at giving IV injections, as is evident in a movie about Jamot made in 1932, which can be downloaded from www.creuse-jamot.org/html/1931-1935.html. This film provides an extraordinary illustration of the scope of the sleeping sickness problem in Cameroun and of the methods used for its control.

  Some trypanosomiasis patients who relapsed after standard therapy also received hétérohémothérapie: the repeated IM administration of 10–20 cc of whole blood from convalescent patients. The idea was that this blood contained high levels of antibodies against trypanosomes, which would be useful to patients who had difficulty getting rid of the parasite. Although this was certainly a good method for transmitting viral infectious agents (because the quantity of blood deliberately administered was much larger than whatever was inadvertently left in a syringe after it was flushed), it was probably not used on more than 1,000 patients.13,28

  Data on the incidence of various diseases must be viewed with caution from a purely epidemiological perspective because year-to-year variations may reflect the more or less intense efforts made to find cases rather than true changes. For instance, the rising incidence of sleeping sickness in Cameroun around 1928 reflected the increasing resources devoted to its control: mobile teams explored areas where hitherto most cases had remained undiagnosed, unreported and untreated. However, even if imperfect for reconstructing disease dynamics, these data reflect accurately the numbers of patients treated with injectable drugs given for specific diseases.

  In Cameroun, the incidence of sleeping sickness peaked at 54,712 new cases in 1928 (Figure 10). The disease was concentrated in a triangle east of Yaoundé (Akonolinga, Abomg-Mbang and Doumé) where in some communities almost everyone had to be treated. The incidence then decreased and stabilised at around 3,000 cases per year until 1952. The decline during WWII reflected reduced human and material resources for case-finding, as several of the medical officers were mobilised into general Leclerc’s Free French Forces.24,25,29,30

  Figure 10 Incidence of African trypanosomiasis (sleeping sickness) in Cameroun Français and AEF-3, and use of trypanocidal drugs.

  Adapted from Pepin.10

  In AEF-3, incidence of trypanosomiasis peaked in 1937 and the number of injections of trypanocidal drugs followed the same course, peaking at a staggering 588,086 injections. During the years for which detailed information is available, 74% of the 3.9 million injections used in the treatment of sleeping sickness were given IV (tartar emetic, suramin, tryparsamide, melarsoprol), 3% IM (pentamidine), 13% SC (atoxyl, trypoxyl) and for 10% the route is uncertain (orsanine). As discussed in the previous chapter, the IV injections provided the best opportunities for the transmission of blood-borne viruses.10

  Apart from the short epidemic period in Cameroun, the annual incidence rates of trypanosomiasis were lower than 10 per 1,000 inhabitants (Figure 11). Thus the number of individuals who could have been iatrogenically infected with blood-borne viruses during trypanosomiasis treatment in colonial Cameroun was substantial (about 222,000), but not high enough by itself to result in the extremely high prevalence of hepatitis C (more than 40%) described much later throughout southern Cameroon, which must have resulted from a combination of interventions rather than from a single one.

  However, we need just one of the trypanosomiasis patients to have been infected with SIVcpz, acquired while manipulating chimpanzee carcasses, to initiate a chain of transmission that could have exponentially amplified the number of infected individuals. And the peak period for trypanosomiasis incidence and its injectable treatments, the late 1920s, corresponded closely, give or take a few years, to the dating of the most recent common ancestors of HIV-1 group M.

  A new intervention, pentamidinisation, was launched in 1948. IM pentamidine, then a novel drug, was administered to the whole population of endemic areas as a preventive measure. Pentamidine was later used in the treatment of Pneumocystis pneumonia and, as seen in the introduction, an abnormal blip in its use played a role in the recognition of AIDS as a new disease in the US in 1981. Scientists of the colonial era mistakenly thought that pentamidine persisted long enough in the blood for a single injection to provide levels sufficient to abort infections with trypanosomes that might ensue over the following semester. In reality, there was little pentamidine remaining in the body two weeks later. In the early 1950s, more than half a million injections of pentamidine were given annually in French territories of central Africa (Figure 10). Pentamidinisation contributed to a further reduction in the incidence of sleeping sickness, not because it was truly preventive, but because single-dose pentamidine was curative for patients with recently acquired, often asymptomatic, trypanosomiasis.31

  A description of the pentamidinisation procedures gives an idea of the potential for transmission of blood-borne pathogens:

  The principles of mass production and time and motion study should be applied to ensure the maximum speed and efficiency in getting through, say, 250 injections in a morning. The man actually giving the injection should merely have to turn around in order to hand over his used syringe and take a freshly charged one. As he turns back again, a freshly iodined buttock, and the appropriate dose, should present themselves before him.32

  Pentamidinisation was discontinued as endemic countries approached their independence. The injections were extremely painful, unpopular and associated with colonial rule. And as the incidence of trypanosomiasis declined further, priority was given to more pressing health needs, such as leprosy which had hitherto been neglected. Furthermore, outbreaks of gas gangrene (an infection that causes necrosis of the muscles, with a very high mortality rate) occurred in Gabon, Cameroun and Oubangui-Chari. Pentamidine bulk powder was diluted with locally procured water, some of which had been contaminated with Clostridium spores, which are very hard to kill. Dozens of deaths among healthy individuals as a consequence of a preventive intervention were unacceptable to local populations.

  One of these iatrogenic tragedies, in Nkoltang, Gabon, where fourteen pentamidine recipients died of gas gangrene in 1952, provided an extraordinary example of the work of colonial spin doctors. While the inquiry revealed in confidential documents that the fault lay with the French nurse who did not properly sterilise the water that he had secured from a local source, which was itself contaminated with surface water, the official reports blamed the unfortunate recipients who were alleged to have applied some mud at the site of the injection as a pain- relieving method. This makes us wonder whether other iatrogenic complications, for instance outbreaks of ‘inoculation hepatitis’, would have been reported.33–34

  Treponemes and metallic drugs

  Chronologically, after trypanosomiasis, yaws and syphilis were the next diseases for the treatment of which huge numbers of injections were administered. They are caused by two subspecies of the same bacterium, Treponema pallidum, and are referred to as treponemal diseases, treated with antitreponemal drugs. Yaws, caused by Treponema pallidum pertenue, is transmitted by non-sexual direct contacts. Its principal manifestation, skin lesions, can be spectacular, but there are few long-term complications. Its incidence was highest in children living in the forested areas of central Africa. In some populations mothers were deliberately infecting their children by inducing contacts with obvious cases so that their kids would develop immunity to yaws. On the other hand, sexually transmitted syphilis is caused by Treponema pallidum pallidum. It causes ulceration of the genitalia, after which it disseminates via the bloodstream, also causing skin lesions and later involvement of other organs including the aorta and the brain. Both infections were treated with arsenic-, bismuth- or mercury-based compounds and, since the mid-
1950s, penicillin. Diagnoses of yaws were reasonably accurate because of the prominence of cutaneous signs. Although many diagnoses of syphilis, made without testing by nurses with only basic training, were doubtful (according to the health officials who wrote the reports), these patients were treated as if they indeed had syphilis.35–36

  Figure 11

  Incidence rates (per 1,000 inhabitants per year) of African trypanosomiasis, yaws and syphilis in Cameroun Français, AEF-3 and Tchad.

  Adapted from Pepin.10

  In Cameroun, the incidence of yaws increased dramatically in 1936, decreased transiently during WWII, peaked at 172,693 new cases in 1950 and slowly declined thereafter (Figure 12). For syphilis, a less marked biphasic pattern was seen. Throughout this period, annual incidence rates of yaws varied between 24 and 56 per 1,000 inhabitants; incidence of syphilis was lower, between 12 and 35 per 1,000 (Figure 11). In AEF-3, yaws peaked at 96,898 cases in 1954, while syphilis peaked earlier. Incidence rates of yaws were much lower in Tchad than in AEF-3 or Cameroun, while there was little geographic variation for syphilis (Figure 11). Incidence rates of yaws and syphilis were highest in Gabon, where the ecological conditions facilitated the transmission of the former disease, while behaviours facilitated the latter.