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Keywords:

  • HIV;
  • SIVcpz;
  • Cameroon;
  • Congo;
  • Gabon;
  • Central African Republic;
  • hepatitis C virus;
  • yaws;
  • syphilis;
  • trypanosomiasis
  • VIH;
  • le VIScpz;
  • Cameroun;
  • Congo;
  • Gabon;
  • République Centrafricaine;
  • virus de l’hépatite C;
  • pian;
  • syphilis;
  • trypanosomiase
  • VIH;
  • SIVcpz;
  • Camerúnn;
  • Congo;
  • Gabón;
  • República Central Africana;
  • virus de la hepatitis C;
  • yaws (frambesia;
  • pian);
  • sífilis;
  • tr ipanosomiasis

Summary

  1. Top of page
  2. SummaryObjectifs nobles, conséquences imprévues: Contrôle des maladies tropicales dans les anciennes colonies d’Afrique centrale et de la transmission iatrogène de virus hématogènesObjetivos nobles, consecuencias impredecibles: control de enfermedades tropicales en África Central colonial y la transmisión iatrogénica de virus de transmisión por vía parenteral
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Background  In southern Cameroon, 40–50% of individuals born before 1945 have antibodies against hepatitis C virus (HCV), suggesting massive iatrogenic transmission of at least one blood-borne virus in the region of the world where SIVcpz emerged into HIV-1.

Objective  To estimate the potential role of disease control programs that used intravenous (IV) drugs in the transmission of blood-borne viruses, especially HCV.

Methods  We reviewed, for 1921–1959, records of health services in Cameroun, Oubangui-Chari, Gabon and Moyen-Congo. We calculated the incidence of diseases whose treatment required the administration of IV drugs, and compared these with previously published data on HCV prevalence.

Results  Several IV drugs were used against African trypanosomiasis, leprosy, yaws and syphilis. However, yaws was the only disease whose incidence was high enough so that up to half of some birth cohorts could have acquired HCV. Yaws incidence varied dramatically between regions, and was often >200 per 1000 per year in southern Cameroon, where extremely high HCV prevalence was found. Yaws incidence peaked between 1935 and 1955, a period which coincided with the emergence of HCV and HIV.

Conclusion  Age, geographical and temporal distributions of yaws suggest that the HCV epidemic in Cameroon was driven by campaigns against yaws (and, secondarily, syphilis) using arsenicals and other metallic drugs. The same interventions may have exponentially amplified other blood-borne viruses, including SIVcpz/HIV-1.

Objectifs nobles, conséquences imprévues: Contrôle des maladies tropicales dans les anciennes colonies d’Afrique centrale et de la transmission iatrogène de virus hématogènes

Données de base  Dans le sud du Cameroun, 40 à 50% des personnes nées avant 1945 ont des anticorps contre le virus de l’hépatite C (VHC), suggérant une transmission iatrogène massive d’au moins un virus hématogène dans cette région du monde où le VIScpz a émergé en VIH-1.

Objectif  Estimer le rôle potentiel des programmes de lutte contre les maladies qui ont utilisé des médicaments par voie intraveineuse, dans la transmission de virus hématogènes, en particulier le VHC.

Méthodes  Nous avons analysé pour 1921-1959, les données des services de santé au Cameroun, en Oubangui-Chari, au Gabon et au moyen-Congo. Nous avons calculé l’incidence des maladies dont le traitement nécessitait l’administration de médicaments intraveineuses et avons comparé ces données à celles précédemment publiées sur la prévalence du VHC.

Résultats  Plusieurs médicaments intraveineux ont été utilisés contre la trypanosomiase africaine, la lèpre, le pian et la syphilis. Cependant, le pian est la maladie dont la seule incidence était suffisamment élevée pour que jusqu’à la moitié de certaines cohortes de naissance ait pu acquérir le VHC. L’incidence du pian varie de façon dramatique entre les régions et atteignait souvent au-delà de 200 pour 1000 par an dans le sud du Cameroun où une prévalence extrêmement élevée du VHC a été trouvée. L’incidence du pian a connu un pic entre 1935 et 1955, une période qui a coïncidé avec l’émergence du VHC et du VIH.

Conclusion  L’âge, les distributions géographiques et temporelles du pian suggèrent que l’épidémie de VHC au Cameroun était véhiculée par les campagnes de lutte contre le pian (et secondairement, de la syphilis) avec l’usage de médicaments arsenicaux et autres médicaments métalliques. Les mêmes interventions peuvent avoir amplifié exponentiellement d’autres infections hématogènes, dont le VIScpz et le VIH-1.

Objetivos nobles, consecuencias impredecibles: control de enfermedades tropicales en África Central colonial y la transmisión iatrogénica de virus de transmisión por vía parenteral

Antecedentes  En el sur de Camerún, entre un 40 y 50% de los individuos tenían anticuerpos frente a los virus de Hepatitis C (VHC) antes de 1945, sugiriendo una transmisión iatrogénica masiva de al menos un virus de transmisión parenteral en la región del mundo en donde el virus VIScpz surgió como HIV-1.

Objetivo  Estimar el papel potencial de programas de control de la enfermedad que utilizaron medicamentos intravenosos en la transmisión de virus de transmisión por vía parenteral, especialmente VHC.

Métodos  Para el periodo de 1921-1959, hemos revisado las bases de datos de los servicios sanitarios del Camerún, Oubangui-Chari, Gabon y Moyen-Congo. Hemos calculado la incidencia de enfermedad cuyo tratamiento requería la administración de medicación intravenosa, y hemos comparado esto con datos previamente publicados sobre la prevalencia de VHC.

Resultados  Se utilizaron varios medicamentos intravenosos frente a la tripanosomiasis, lepra, yaws y sífilis. Sin embargo, yaws era la única enfermedad cuya incidencia era lo suficientemente alta como para que al menos la mitad de algunas cohortes de nacidos pudiesen haber adquirido el VHC. La incidencia de yaws variaba de forma dramática entre regiones, y a menudo era de >200 por 1000 por año en el sur de Camerún, en donde se encontró una altísima prevalencia de VHC.

La incidencia de yaws presentó un pico entre 1935 y 1955, un periodo que coincide con el surgimiento del VHC y VIH.

Conclusión  La distribución geográfica, temporal y por edad de yaws, sugiere que la epidemia del VHC en Camerún está relacionada con campañas contra yaws (y de forma secundaria, sífilis) utilizando arsénicos y otros medicamentos metálicos. Las mismas intervenciones podrían haber amplificado exponencialmente otros virus de transmisión por vía parenteral, incluyendo VIScpz/VIH-1.


Introduction

  1. Top of page
  2. SummaryObjectifs nobles, conséquences imprévues: Contrôle des maladies tropicales dans les anciennes colonies d’Afrique centrale et de la transmission iatrogène de virus hématogènesObjetivos nobles, consecuencias impredecibles: control de enfermedades tropicales en África Central colonial y la transmisión iatrogénica de virus de transmisión por vía parenteral
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

The Pan troglodytes troglodytes chimpanzee, source of HIV-1 group M, inhabits only southern Cameroon, Central African Republic, Equatorial Guinea, Gabon and Congo-Brazzaville (Gao et al. 1999; Keele et al. 2006). The events that facilitated the emergence of SIVcpz into HIV-1, from a single cross-species transmission ≈1930 with rapid growth during the following decades (Korber et al. 2000), remain unclear. It is assumed that, for thousands of years, hunters or cooks manipulating chimpanzee meat in Central Africa occasionally got infected with SIVcpz/HIV-1, with no further transmission except between spouses, until colonization and urbanization led to prostitution in cities, with exponential transmission between sex workers and their clients (Buvéet al. 2002).

In Guinea-Bissau, HIV-2 infection (compatible with a prolonged survival) was associated with treatment for trypanosomiasis or tuberculosis decades earlier (Pepin et al. 2006). Transmission of hepatitis C virus (HCV) during treatment of schistosomiasis in Egypt illustrated that iatrogenic epidemics can be massive: in some regions, >35% of individuals born before 1965 were infected through intravenous (IV) administration of anti-parasitic drugs with hastily sterilized syringes and needles (Frank et al. 2000). After Egypt, Central Africa has the highest HCV prevalence: 6.0% of adults overall, 13.8% in Cameroon (Madhava et al. 2002). In Yaoundé and some rural areas, ≥40% of elderly individuals are HCV-seropositive (Nerrienet et al. 2005). Although mechanisms have not been delineated, such high prevalence implies iatrogenic transmission. To estimate their potential role in the transmission of blood-borne viruses, we reviewed major disease control programs implemented in Central Africa from 1921 to 1959.

Methods

  1. Top of page
  2. SummaryObjectifs nobles, conséquences imprévues: Contrôle des maladies tropicales dans les anciennes colonies d’Afrique centrale et de la transmission iatrogène de virus hématogènesObjetivos nobles, consecuencias impredecibles: control de enfermedades tropicales en África Central colonial y la transmisión iatrogénica de virus de transmisión por vía parenteral
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

We reviewed annual reports of the health services for Cameroun (this spelling designates the part of contemporary Cameroon under French mandate) (Cameroun Français 1936–1959), Moyen-Congo (Congo-Brazzaville) (Moyen-Congo [Colonie du; Territoire du] 1930–1958), Oubangui-Chari (Central African Republic) (Oubangui-Chari [Colonie de l’; Territoire de l’] 1932–1959), Gabon (Gabon [Colonie du; Territoire du] 1931–1957) and Afrique Équatoriale Française (AEF 1935, 1936–1944, 1945–1956). The AEF Federation regrouped Oubangui-Chari, Moyen-Congo, Gabon and Tchad; as the latter is not inhabited by P. t. troglodytes, we analysed reports of the disease control program for the first three territories (designated AEF-3) (Afrique Équatoriale Française 1947–1958). For Cameroun, we reviewed reports to the League of Nations and United Nations (Gouvernement Français 1921–1938, 1947–1957). Some information was available in reviews of communicable diseases in French colonies, published in medical journals until 1940, and in official reports thereafter (Rousseau et al. 1927–1938; Ministère de la France d’Outre-Mer 1946–1949, 1950–1956). Contradictions between sources were resolved empirically, using numbers provided in the majority of reports.

Results

  1. Top of page
  2. SummaryObjectifs nobles, conséquences imprévues: Contrôle des maladies tropicales dans les anciennes colonies d’Afrique centrale et de la transmission iatrogène de virus hématogènesObjetivos nobles, consecuencias impredecibles: control de enfermedades tropicales en África Central colonial y la transmisión iatrogénica de virus de transmisión por vía parenteral
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Population

Denominators used to calculate annual incidence rates of trypanosomiasis, yaws and syphilis took into consideration changes in boundaries between AEF territories. In Gabon, the population remained stable at ≈400 000, but only because of the transfer of Haut-Ougoué from Moyen-Congo (1947). Moyen-Congo’s population remained stable at ≈700 000, despite this transfer and that of Lobaye (1934) and Haute-Sangha (1940) to Oubangui-Chari. The latter’s population decreased from 1.25 to 0.83 million when Moyen-Logoné and Moyen-Chari were transferred to Tchad (1937), increasing to 1.1 million by 1956. Cameroun’s population increased from 1.9 (1926) to 3.2 million (1958).

African trypanosomiasis

Sleeping sickness was the first communicable disease for which large-scale control interventions were implemented (Jamot 1920). In Cameroun, incidence peaked at 54 712 new cases in 1928 (Figure 1a). Resources for its control progressively increased: data for 1926–1928 corresponded to a combination of prevalent and incident cases, concentrated in a triangle east of Yaoundé where, in some communities, up to 97% of the population became infected (Letonturier et al. 1924; Jamot 1929, 1932; Vaucel 1941). Later data measured incident cases.

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Figure 1.  (a) New cases of African trypanosomiasis. (b) Use of trypanocidal drugs.

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For most of the 1920s, subcutaneous (SC) atoxyl was widely used, often combined with a second drug given IV, tartar emetic or novarsenobenzol (Letonturier et al. 1924). The introduction of tryparsamide (mid-1920s) represented a dramatic advance: late-stage patients could be cured. For 1927–1928, 900 kg of atoxyl (≈1 million injections) and 600 kg of tryparsamide (135 186 SC and 71 903 IV injections) were used in Cameroun (Jamot 1929). In 1939, 155 676 injections of trypanocidals were administered, a number which declined thereafter (Figure 1b). After 1928, tryparsamide was administered IV while another arsenical, orsanine, given SC or IV, competed with atoxyl for early-stage cases. In AEF-3, treatments were standardized: 12 weekly SC or IV injections of orsanine if CSF was normal, 12 weekly IV injections of tryparsamide if CSF was abnormal, repeated annually for 2 more years to ‘consolidate’ the initial treatment (Muraz 1933). On average, patients treated with tryparsamide received ≈36 IV injections (Vamos 1936). Some patients who relapsed after standard therapy received hétérohémothérapie: the repeated intra-muscular (IM) administration of 10–20 cm3 of whole blood from convalescent patients, to attempt passive immunization (Millous 1936).

Incidence of trypanosomiasis stabilized in Cameroun at ≈3000 cases/year until 1952 (Figure 1a); the drop during World War II reflected reduced resources for case-finding. In AEF-3, incidence peaked in 1937. Apart from the epidemic period in Cameroun, annual incidence rates were inferior to 10 per 1000 (Figure 2a). The number of injections of trypanocidals in AEF-3 followed the same course, peaking at 588 086 in 1937 (Figure 1b). During the years for which detailed information was recorded, 74% of the 3 983 617 injections were given IV (emetic tartar, suramin, tryparsamide, melarsoprol), 3% IM (pentamidine), 13% SC (atoxyl, trypoxyl) and, for 10%, the route is uncertain (orsanine).

image

Figure 2.  (a) Incidence rates of African trypanosomiasis. (b) Incidence rates of yaws. (c) Incidence rates of syphilis.

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A new intervention, pentamidinisation, was launched in 1948: IM pentamidine was administered to the whole population of endemic areas, as a prophylactic measure (Demarchi 1958). Scientists mistakenly thought that its half-life was long enough for a single injection to provide levels sufficient to abort infections that might ensue over the following semester. In the early 1950s, >500 000 injections of pentamidine were given annually (Figure 1b). Pentamidinisation was discontinued as endemic countries approached their independence. The injections were exquisitely painful, unpopular and associated with colonial rule. Furthermore, outbreaks of gas gangrene occurred: pentamidine bulk powder was diluted with locally procured water contaminated with Clostridium spores.

Yaws and syphilis

Yaws, caused by Treponema pallidum subsp. pertenue, is transmitted by non-sexual contact; incidence was highest in children living in forested areas (Cartron 1937; Vaucel 1953). Sexually or vertically transmitted syphilis is caused by T. pallidum subsp. pallidum. Without treatment, both progress to haematogenous dissemination and secondary or tertiary lesions. Both infections were treated with arsenicals, bismuth and, since the mid-1950s, penicillin.

In Cameroun, incidence of yaws increased dramatically in 1936, decreased during World War II, peaked at 172 693 cases in 1950, and slowly declined (Figure 3a). For syphilis, a less-marked biphasic pattern was seen. Throughout this period, annual incidence rates of yaws varied between 24 and 56 per 1000; incidence of syphilis was lower, between 12 and 35 per 1000 (Figure 2b,c). In AEF-3, yaws peaked at 96 898 cases in 1954, while syphilis peaked earlier (1938) at 66 445 cases. Incidence rates of yaws were much lower in Tchad than in AEF-3 or Cameroun, while there was little geographic variation for syphilis (Figures 2b,c). Incidence rates of yaws and syphilis were highest in Gabon (data not shown). Diagnoses of yaws were reasonably accurate given the prominence of cutaneous signs. Although many diagnoses of tertiary syphilis, made without serology, were doubtful, these patients were treated as if they had syphilis.

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Figure 3.  (a) New cases of yaws and syphilis. (b) Use of antitreponemal drugs.

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Table 1 summarizes annual incidence rates of yaws and syphilis in selected regions of Cameroun (Figure 4). Details on regional incidence provided in reports varied from year to year. There was little regional variation in incidence rates of syphilis, between 10 and 40 per 1000. However, there were dramatic variations in the incidence of yaws, sometimes >200 per 1000 per year in southern regions (Ntem, Kribi, Sanaga-Maritime) compared with <1 per 1000 in northern regions (Nord-Cameroun, Adamoua, Bénoué).

Table 1.   Annual incidence rates of yaws and syphilis per 1000 inhabitants in selected regions of Cameroun
 NtemSanaga MaritimeKribiNyong and SanagaHaut-NyongMbamLom and Kadei BénouéNord-Cameroun
YawsSyphilisYawsSyphilisYawsSyphilisYawsSyphilisYawsSyphilisYawsSyphilisYawsSyphilisYawsSyphilisYawsSyphilis
1937 45166    26    17    22
1938 39123    10    7    16
1939140401011012920111831152681980.1120.214
194080 11311230 131536 34 12     
194188301114255 1314242337 147 10 10
194211530167521816151122434471411 9 9
1943101311955248161315 29557168 7 12
1944 36 8 30 23   8 8 9 10
1945 401437344292637 22 9   10 11
19462084222211299252940   10   13 14
1947 47 10 31 45   10   13 17
1948 43 8 57 38   15   11 17
1949       40       10 17
1950275 263 323 56 32 112   0.9 0.1 
image

Figure 4.  Administrative regions of Cameroun Français during the colonial era.

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Several therapeutic regimens were used: (i) arsenicals: either IV novarsenobenzol (3–8 injections), IV fontarsol (8–15 injections), IM acetylarsan, IM sulfarsenol (3–8 injections) or oral stovarsol (for children); (ii) bismuth salts (6–10 IM injections) (Joyeux 1944; Montel 1945; Vaucel 1952). Mercury salts (IV or IM) were used mainly for syphilis. Combination therapies were used to shorten duration. Overall, patients received fewer injections than planned as some absconded when their cutaneous lesions improved. Data on antitreponemal drugs were more complete for Cameroun, where use of parenteral arsenicals increased dramatically, up to 688 750 vials in 1952 (Figure 3b), in parallel with incidence and better funding after the war. Overall, 51% of parenteral arsenicals were administered intravenously. For bismuth salts, Figure 3b shows numbers of pre-prepared vials. However, most of bismuth came as bulk powder, diluted locally with water. For 1952–1954, consumption was reported as 2.04–2.15 million cm3 annually; presuming an average of 4 cm3 per injection (Joyeux 1944; Montel 1945), this corresponded to ≈500 000 injections per year. In AEF-3, use of parenteral arsenicals doubled to 394 189 vials in 1949; there is little information about bismuth. Mercury salts, cheaper but more toxic, were abandoned in 1951.

When penicillin became available, older drugs were not abandoned immediately. In 1957, of 91 032 syphilis cases in Cameroun, 6% were treated with penicillin alone; others received metallic drugs alone (72%) or in combination with penicillin (23%); for yaws (105513 cases), corresponding proportions were 43%, 46% and 11%. High incidence of yaws persisted despite millions of injections of metallic drugs, decreasing only after the introduction of long-acting penicillin, which allowed treatment of early cases, their asymptomatic contacts and, in some communities, all children.

Leprosy

Some leprosy patients never received pharmacological treatment and were merely segregated. Figure 5a summarizes numbers of leprosy patients who were indeed treated. In Cameroun, from the late 1930s, a serious therapeutic effort was made. In AEF-3, policy was not to bother with leprosy until sulfones were introduced in the early 1950s: the extraordinary numbers of patients then treated corresponded to accumulated prevalent cases. Initially, extracts of chaulmoogra, an Indian medicinal plant, were the main agents, given mostly IM (2–3 times a week for the first year, then weekly for several years) but also orally, rectally, IV or within lesions (Montel 1945). Chaulmoogra was either provided as bulk oil locally diluted, or in pre-prepared vials. From the early 1930s to the late 1940s, many leprosy patients in Cameroun received IV methylene blue concomitantly with IM chaulmoogra (Montel 1945). The intended regimen of 30–60 IV injections over 1 year was often stopped prematurely because of adverse effects. Another medicinal product, aqueous Caloncoba, was given IV as an adjuvant to chaulmoogra (Vaucel 1952). In 1939, out of 5025 leprosy patients for whom therapeutic details were provided, 20% received chaulmoogra monotherapy, 24%Caloncoba monotherapy, 13% methylene blue monotherapy and others received various combinations of these. Caloncoba and methylene blue progressively lost favour in Cameroun. Sulfones proved dramatically superior. Non-compliant patients received a depot solution prepared in chaulmoogra oil, administered fortnightly. By 1957, all Cameroonian leprous received sulfones, 80% orally and 20% IM.

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Figure 5.  (a) Cases of leprosy under treatment. (b) New cases of tuberculosis.

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Other endemic diseases

In the 1930–1940s, <1000 cases of schistosomiasis were reported annually in Cameroun, ≈2000 in AEF-3. By 1954, this increased to 2232 in Cameroun, 11 236 in AEF-3; most patients were untreated as the adverse effects of IM antimonials or IV emetine seemed worse than symptoms of the infection (Gaud 1955). No parenteral drug was used against filariasis. Most cases corresponded to Loa loa or Dipetanolema perstans found incidentally during examinations for malaria or trypanosomiasis, and were left untreated until oral diethylcarbamazine was introduced for loaisis. Onchocerciasis was uncommon; the only attempt for its mass treatment with IV suramin took place in Tchad.

Tuberculosis was remarkably uncommon until 1950: <500 cases annually in Cameroun, <1000 in AEF-3 (Figure 5b), and no treatment was offered. Later, reported incidence increased dramatically, coinciding with the introduction of chemotherapy (streptomycin, INH, PAS). Most patients received IM streptomycin daily for the first month, then 2–3 times per week for 18–24 months (Brunel 1958). Introduction of effective treatments may have increased the number of patients seeking a diagnosis or the supply of diagnostic tests. In Cameroun, streptomycin consumption increased from 100 (1949) to 511 941 g (1959).

Vaccines

Most vaccines administered were against smallpox (since the early 1920s) or yellow fever (mid-1940s). The latter was a ‘scratch vaccine’ given intradermally (ID) simultaneously with the former (Echenberg 2005). Policy was to re-immunize everybody every 4–6 years. Year-to-year variations (Figure 6) depended on vaccines availability, perceived threat and opportunities for immunization by mobile teams.

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Figure 6.  Number of individuals vaccinated against smallpox and yellow fever.

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Discussion

  1. Top of page
  2. SummaryObjectifs nobles, conséquences imprévues: Contrôle des maladies tropicales dans les anciennes colonies d’Afrique centrale et de la transmission iatrogène de virus hématogènesObjetivos nobles, consecuencias impredecibles: control de enfermedades tropicales en África Central colonial y la transmisión iatrogénica de virus de transmisión por vía parenteral
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

In several areas of southern Cameroon, a cohort effect was demonstrated, with HCV prevalence ≈40–50% among people born before 1945, ≈15% for those born in 1960 and 3–4% if born after 1970 (Nerrienet et al. 2005). In several studies (Delaporte et al. 1994; Louis et al. 1994; Kowo et al. 1995; Nkengasong et al. 1995; Njouom et al. 2003; Nerrienet et al. 2005; Laurent et al. 2007), HCV prevalence plateaus at the same point, corresponding to year of birth ≈1935 (Figure 7). Phylogenetic analyses revealed that populations of HCV-infected individuals started increasing exponentially 1920 for genotype 4, and ≈1940 for genotypes 1 and 2 (Njouom et al. 2007). Its heterosexual transmission being ineffective, this indicates massive iatrogenic transmission.

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Figure 7.  HCV prevalence in birth cohorts from various sites in Cameroun. Curves from Nditam, Yokadouma, Yaoundé, Ntem and Mekas are reproduced from a previous publication (Nerrienet et al. 2005); others were prepared from prevalences provided elsewhere (Louis et al. 1994; Nkengasong et al. 1995; Laurent et al. 2007).

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Healthcare workers exposed to HCV have a higher risk of infection when a hollow-bore needle was placed in the index patient’s vein and when the injury is deeper (Yazdanpanah et al. 2005). Extrapolating to the potential iatrogenic transmission between patients, the risk must have been higher with IV, intermediate with IM, lower with SC or ID injections, and proportional to the number of injections. Thus, risk per patient must have been higher for trypanosomiasis cases treated with IV tryparsamide (≈36 injections) or leprosy patients given IV methylene blue or Caloncoba plus IM chaulmoogra. Transmission was probably more effective during biannual pentamidine IM injections than ID immunizations every 5 years. In Africa, Brazil and Asia, leprosy patients treated in the remote past are more likely than controls to be infected with HCV, Hepatitis B virus and HTLV-1 (Moudgil & Irshad 1988; Verdier et al. 1990; Denis et al. 1994; Lechat et al. 1997; Moraes Braga et al. 2006). However, the proportion of Cameroonians ever treated for trypanosomiasis or leprosy was much lower than the 40–50% who became HCV-infected.

Within Cameroon, populations with a high HCV prevalence come from Yaoundé or communities in the rain forest (Figures 4 and 7). Several arguments suggest that this HCV epidemic was driven mostly by campaigns against yaws, and to a lower extent by syphilis treatments using the same metallic drugs. First, the sheer numbers: from the mid-1930s till the late 1950s, 3–5% of the whole population of Cameroun was treated for yaws each year, and 1–3% for syphilis. Over three decades, a large proportion of the population was treated for a treponemal infection. Indeed, in some regions, the whole population developed yaws within a few years (Table 1). Second, the age distribution: yaws was more common among children who had the opportunity to survive until the mid-1990s. Third, the sharp rise in incidence of yaws in Cameroun after 1935 corresponds chronologically to what can be inferred to be the period of highest HCV transmission. Fourth, the geographic distribution of HCV closely corresponds to the historical distribution of yaws whose incidence was much higher in coastal and forested regions (Ntem, Sanaga Maritime, Kribi) than in northern savannas (Table 1). Most study sites with a high HCV prevalence were located in Ntem region (Figure 4). Conversely, regions with a lower HCV prevalence (Mbam, Lom and Kadei) had a low incidence of yaws. There is a discrepancy for Nyong and Sanaga region (Yaoundé and surrounding areas), where HCV prevalence is high despite a relatively low historical incidence of yaws. However, in 1957 only 36% of inhabitants of Yaounde were born locally (Cameroun [État du] 1958). Migrants may have acquired HCV before moving to the capital city.

The same north-south gradient in yaws incidence was observed in AEF, mirrored by a higher HCV prevalence in southern areas (Delaporte et al. 1993; Louis & Kemmegne 1994). HCV prevalence is 3–6 times lower in Pygmies than in Bantous (Louis et al. 1994; Kowo et al. 1995), perhaps reflecting less intense uptake of medical interventions among the former. There is also a north-south gradient in HTLV-1 prevalence, suggesting that this retrovirus may have been transmitted iatrogenically during yaws campaigns (Delaporte et al. 1989; Louis et al. 1993). Reports of health services give neither indication as to how re-usable syringes and needles were sterilized between patients (presumably, by ebullition or dry heat) nor as to how many times a syringe/needle could be used on any given day. Most injections were given by practical nurses with limited scientific training. Given the huge caseloads, the sterilization process may have been shortcut or bypassed, as in Egypt (Frank et al. 2000). Ignored earlier, textbooks from the late 1940s described ‘serum hepatitis’ after medical interventions including, in Europe, arsenical treatment of syphilis, yellow fever vaccine, transfusions and administration of convalescent sera (Levaditi & Lépine 1948). There is no evidence that medical officers in Central Africa were aware of these risks.

If interventions for the control of tropical diseases led to massive HCV transmission in Cameroun and AEF-3 in the middle of the 20th century, the same procedures could have exponentially amplified HIV-1, from a single hunter/cook occupationally infected with SIVcpz to several thousand patients treated with arsenicals or other drugs, a threshold beyond which sexual transmission could prosper. This hypothesis has been proposed around the introduction of injectable penicillin in the 1950s (Drucker et al. 2001). The current review adds: (i) detailed information on parenteral drugs used specifically in countries inhabited by P. t. troglodytes; (ii) information about parenteral drugs in the pre-antibiotic era, when both HIV-1 and HCV emerged (1920–1960); (iii) data on drugs used intravenously, associated with a higher risk of transmission of blood-borne viruses than drugs or vaccines given IM, SC or ID; (iv) identification of interventions against yaws as the driving force in iatrogenic transmission of HCV in Cameroon, at an ecological level.

In retrospect, the massive transmission of HCV in Cameroun during medical interventions, and possibly the emergence of SIVcpz into HIV-1, was due to a lag of 50 years between the availability of antiparasitic and antitreponemal drugs and awareness of modes of transmission of blood-borne viruses. Hopefully, this should make scientists more prudent and humble when developing novel interventions.

Acknowledgements

  1. Top of page
  2. SummaryObjectifs nobles, conséquences imprévues: Contrôle des maladies tropicales dans les anciennes colonies d’Afrique centrale et de la transmission iatrogène de virus hématogènesObjetivos nobles, consecuencias impredecibles: control de enfermedades tropicales en África Central colonial y la transmisión iatrogénica de virus de transmisión por vía parenteral
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

We are grateful to: Aline Pueyo, Institut de Médecine Tropicale du Service de Santé des Armées, Marseille, for providing access to many of these reports; Daniel-Guy Boisvert, Johanne Nadeau, Lucie Kandu and Eric Pepin for assistance in obtaining other reports and publications; Christian Audet for graphics. This study was funded by the Canadian Institutes for Health Research, Associated Medical Services and the Fonds de Recherche en Santé du Québec (Réseau de Recherche en Santé des Populations).

References

  1. Top of page
  2. SummaryObjectifs nobles, conséquences imprévues: Contrôle des maladies tropicales dans les anciennes colonies d’Afrique centrale et de la transmission iatrogène de virus hématogènesObjetivos nobles, consecuencias impredecibles: control de enfermedades tropicales en África Central colonial y la transmisión iatrogénica de virus de transmisión por vía parenteral
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References
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