Human monkeypox*

Bull. Org. mond. Santi 1972, 46, 569-576 Bull. Wld Hith Org. Human monkeypox* STANLEY 0. FOSTER,' EDWARD W. BRINK,. DEANE L. HUTCHINS, JOHN M. PIFER,4 BERNARD LOURIE,5 CLAUDE R. MOSER,6 EVELYN C. CUMMINGS,7 O.E.K. KUTEYI,8 REGINALD E. A. EKE,' J. B. TITUS,10 E. ADEMOLA SMITH," JAMES W. HICKS,12 & WILLIAM H. FOEGE13 Between October 1970 and May 1971, six cases of human infection with monkeypox virus were identified in Liberia, Nigeria, and Sierra Leone. Four of the cases were con- firmed by virus isolation and two were diagnosed on the basis of epidemiological and sero- logical investigations. All the cases occurred in unvaccinated individuals. Post-infection serological studies showed high haemagglutination-inhibition and neutra- lizing titres to pox group virus in four of the cases. Repeated challenge vaccination of all cases with potent smallpox vaccine resulted in equivocal reactions. In all, 24 susceptible household contacts were exposed to the infected cases, but none developed disease. All the contacts subsequently responded to vaccination with a primary reaction, thus confirming their susceptibility and ruling out asymptomatic infection. INTRODUCTION Twenty West and Central African countries, as- sisted by the US Agency for International Develop- ment, have successfully completed a 5-year coopera- tive regional programme of smallpox eradication. A combined approach of mass vaccination, surveil- lance, and epidemic control has resulted in a de- crease in reported smallpox cases from 10 896 in 1967 to zero in the 12-month period July 1970-June 1971 (Fig. 1). Intensive surveillance including epidemio- logical and laboratory investigation of reported cases of rash diseases has failed to detect a single case of smallpox in the 20 countries since May 1970. Sur- veillance systems in West and Central African coun- tries have, however, identified 3 cases of a pustular disease, clinically indistinguishable from smallpox, from which a non-variola poxvirus, monkeypox virus, has been isolated. Three additional human monkeypox cases have been found during field inves- tigation. The World Health Organization is currently en- gaged in a worldwide programme to eradicate small- pox by 1975. This programme is based on the assump- tion that the interruption of transmission will bring about eradication of the disease in man. As a previous eradication programme, against yellow fever, had * From the Bureau of Preventive Medicine, National Public Health Service, Republic of Liberia, Monrovia, Liberia; the Ministry of Health, Government of Sierra Leone, Freetown, Sierra Leone; the Epidemiologic Unit, Preventive Division, Federal Ministry of Health, Government of Nigeria, Lagos, Nigeria; and the Center for Disease Con- trol, US Public Health Service, Atlanta, Ga., USA. 1 Medical Epidemiologist, Smallpox Eradication Pro- gram, Center for Disease Control, Atlanta, Ga., USA. " Medical Epidemiologist, Smallpox Eradication Pro- gram, Center for Disease Control, Kaduna, Nigeria. 3 Medical Epidemiologist, Smallpox Eradication Program, Center for Disease Control, Freetown, Sierra Leone. ' Medical Epidemiologist, Smallpox Eradication Pro- gram, Center for Disease Control, Lagos, Nigeria. * Chief, Vesicular Disease Laboratory, Laboratory Divi- sion, Center for Disease Control, Atlanta, Ga., USA. 'Operations Officer, Smallpox Eradication Program, Center for Disease Control, Monrovia, Liberia. 'Chief Medical Officer, Ministry of Health, Freetown, Sierra Leone. I Acting Specialist Epidemiologist, Federal Ministry of Health, Lagos, Nigeria. ' Medical Officer of Health, Aba, East Central State, Nigeria. 1" Director, Preventive Diseases, National Public Health Service, Monrovia, Liberia. "I Specialist Epidemiologist, Federal Ministry of Health, Lagos, Nigeria. U 12 Chief of Operations, Area A, Smallpox Eradication Program, Center for Disease Control, Atlanta, Ga., USA. 1' Director, Smallpox Eradication Program, Centefor Disease Control, Atlanta, Ga., USA. 2832 - 569 S. 0. FOSTER AND OTHERS Fig. 1. Smallpox incidence in West and Central Africa, 1967-71. The shaded area represents the range between the highest and lowest incidence reported during the 5-year period 1962-66. been severely hampered by the detection of non- human reservoirs of infection, WHO has carried out a search for evidence of non-human smallpox trans- mission, especially in primates. Although monkeys have been infected with and have transmitted variola virus experimentally in the laboratory, surveillance in smallpox endemic areas has failed to detect variola infection in natural primate populations (Hahon & McGavran, 1961; Noble & Rich, 1969). In 1958, Magnus identified a pox disease in Cyno- molgus monkeys in Copenhagen (Magnus et al., 1959). The etiological agent, known as monkeypox, has since been identified in animal colonies in the USA (Sauer el al., 1960; Prier & Sauer, 1960; McConnell et al., 1964) the Netherlands (Peters, 1966), and France (Milhaud et al., 1969). The virus has also been isolated in tissue cultures prepared from monkey kidney (Gispen & Kapsenberg, 1968). Prior to the recognition ofmonkeypox virus, seven episodes of pox disease in monkeys had been des- cribed (Arita& Henderson, 1968). In four outbreaks, a direct association with human smallpox had been reported, but in only one outbreak was a poxvirus isolated (Anderson, 1861; Schmidt, 1870; Bleyer, 1922; Gispen, 1949). As techniques for poxvirus differentiation were not available at the time of that isolation, and as the isolate has since been lost, it is not possible to prove conclusively whether it or the other reported outbreaks of pox disease in monkeys were due to smallpox, monkeypox, or to another virus. In addition to the cases of human monkeypox dis- cussed in this paper, one further case has been iden- tified in Zaire (Ladnyi et al., 1972; Marennikova et al., 1972). CLINICAL MANIFESTATIONS In West Africa, four cases of human monkeypox infection have been diagnosed by virus isolation (cases 1, 4, 5, and 6). Two additional cases (cases 2 and 3) have been diagnosed on epidemiological and serological grounds. The clinical information on the six cases, none of which was fatal, is summarized in Table 1. Case I A 4-year-old unvaccinated female (L.T.) from Boudua, Liberia, became ill on 10 September 1970, with a " severe cold " manifest by fever, sore throat, and malaise. On 13 September, she developed a generalized rash and was admitted the following day to the district hospital in Zwedru as a suspected case of smallpox. Examination on 18 September, the fifth 2600 2400 2200 2000- 1800- io 1200 C 1600- 800 600 400- 200- O I 11 , -I I. a I .I aI _ l- J FMAMJ J AS ON.DJ FMAMJ J ASO N DJ FM AMJ J AS ON DJ FMAMJJ ASON DJF MA J AS OND 1967 1968 1969 1970 1971 wa o1087 I - - 570 HUMAN MONKEYPOX Table 1. Clinical cases of human monkeypox infection, Liberia, Nigeria, and Sierra Leone, 1970-71 Vacntio Prdrm Seeiy DurationCase Country Village Age Sex sVaccintion Date of rash nPrdrayme OSheva of rash history in days of rash a ~~(days) I Liberia Boudua 4 F Negative 13 Sept. 70 3 ++ 24 2 Liberia Boudua 4 M Negative 12 Sept. 70 1 + 4 3 Liberia Boudua 6 F Negative 13 Sept. 70 2-3 + 4 4 Liberia Tarr 9 M Negative 2 Oct. 70 7 ++ 21 5 Sierra Leone Aguebu 24 M Negative 1 Dec. 70 3-4 +++ 28 6 Nigeria Aba 4 F Negative 19 May 71 J 5 +++ 26 a + Mild + + Moderate + + + Severe day of rash, revealed an afebrile, uncomfortable child with a diffuse vesiculopustular rash of peri- pheral distribution. The lesions were discrete with rare coalescence, were deep-seated, and were present on the palms and on the soles of the feet. The collection of specimens was difficult because of the viscosity of the pustular fluid and the adhesiveness of the scabs. Fig. 2 shows the skin lesions as photo- graphed on the eighth day of rash. Adjacent lesions were all in the same state; cropping was not observed. A follow-up examination on 13 December showed a healthy, active child with scattered hyperpigmented spots on the face and extremities. No pitted scars were seen. Case 2 A 4-year-old unvaccinated male (I. G.) from Boudua, Liberia, developed a low-grade fever on 11 September 1970. The following evening a mild vesicular rash, consisting of approximately 10 scat- tered lesions, was noted. These lesions cleared in 3-5 days and left no scars or pigment changes. Fig. 2. Human monkeypox: eighth day of rash in 4-year-old female, Boudua, Liberia. 571 S. 0. FOSTER AND OTHERS Case 3 A 6-year-old unvaccinated female (M.T.) from Boudua, Liberia, had a mild illness consisting of a 2-3-day febrile prodrome followed by a 3-5-day episode of rash. The rash consisted of 10 scattered vesicular lesions. Case 4 A 9-year-old unvaccinated male (G.G.) from Tarr, Liberia, developed a rash on 2 October 1970, and was isolated on the family farm. When examined on 10 October, the ninth day of rash, the boy had a generalized vesiculopustular rash with all lesions appearing in the same stage. The lesions were firm, deep-seated, and measured approximately 0.75 cm in diameter. The lesions on the face and lower extremi- ties had been broken by local treatment. The rash had a peripheral distribution with greatest involve- ment of the face, arms, and legs. Scattered lesions were present on the back, abdomen, and buttocks. Lesions were noted on the palms and on the soles of the feet. The patient had a warm tender mass in the right submaxillary area, which produced a general- ized swelling of the right side of the face. A pustular lesion was present in the right cornea. The submaxil- lary mass, diagnosed as a bacterial abscess, was treated with penicillin. A follow-up examination on 26 October, the 25th day of rash, showed areas of depigmentation, a right-corneal scar, a subsiding submaxillary mass, and an active child. The areas of depigmentation were again noted on 20 November. Reexamination on 16 December revealed a 4-mm right-corneal scar. Case 5 A 24-year-old single, unvaccinated male (B.K.) from Aguebu, Sierra Leone, became ill with severe headache, fever, stiff neck, and cough on 26 Novem- ber 1970. Four days later he developed a generalized rash and was seen at the Moyamba Hospital, where the lesions were described as " pustular " and the diagnosis of smallpox was made. Examination on the tenth day of rash revealed a moderately ill man with a generalized pustular rash. Approximately half of the scabs had desquamated by 17 December, the 22nd day of rash. Reexamination of the patient on 1 January 1971, the 37th day of rash, showed residual hypopigmented lesions 3-12mm in diameter, surrounded by 1-2 mm areolae of hyperpigmenta- tion. Three to four shallow pits were noted on the face. Case 6 A 4-year-old unvaccinated girl from Ihie Umuduru, Aba, Nigeria, developed fever, malaise, headache, sweating, and severe prostration on 14 April 1971. Five days later she developed a maculopapular rash that appeared initially on the distal extremities. On 13 April, the fourth day of rash, the child was isolated at Aba General Hospital with a clinical diagnosis of smallpox. Examination of the patient on 18 April, the eighth day of rash, showed a weak, feverish, lethargic, and toxic child who was unable to stand. There was a generalized pustular rash with lesions 3-5 mm in diameter. These pustules were firm, deep, discrete, and were not tender. The rash involved all areas of the body including the palms and the soles of the feet. EPIDEMIOLOGY Cases 1, 5, and 6 were identified by the communi- cable disease surveillance systems in Liberia, Sierra Leone, and Nigeria, respectively (Fig. 3). As each case occurred in an area that had been free ofknown smallpox transmission for at least one year, imme- diate investigation and control procedures were ini- tiated on verification of the clinical diagnosis; these included: (1) the collection of specimens for labora- tory diagnosis, (2) the identification and vaccination of susceptible contacts, (3) an active search for un- reported cases, (4) an estimation of village smallpox immunity by scar survey, and (5) the vaccination of the susceptible population. Case 5 occurred in an area vaccinated in 1969. The other cases occurred in areas scheduled for vaccination during 1971. Fig. 3. Location of human monkeypox. cases in Africa. 572 HUMAN MONKEYPOX Case 1 lived in Boudua Town, a remote village of 27 people located in the tropical rain forest of north- eastern Liberia. Investigation of the contacts of the index case demonstrated the simultaneous occurrence of vesicular disease in two playmates, case 2 and case 3. As cases 1, 2, and 3 developed rashes at the same time, it is probable that infection resulted from a common exposure. As case 2 had been out of the village on 20-28 August, 16-24 days prior to the onset of rash, exposure must have occurred during the 16-day period from 29 August to 13 September. Except for the death of case 1's great-grandmother from a " stomach illness " on 9 September, no expo- sure to a sick person, either resident or visitor, could be recalled by any of the residents of Boudua Town. At the time of the illnesses in cases 1, 2, and 3, 9 of the 23 residents of Boudua Town were classified as susceptible to poxvirus infection by the absence of a history of, or scarring from, smallpox disease or smallpox vaccination. None of the susceptible per- sons developed disease and all responded with a primary type of major reaction when vaccinated 2-4 weeks after exposure. When poxvirus particles had been identified with an electron microscope and the agar gel test on specimens submitted from case 1 gave a positive result, a search for undetected smallpox transmission was launched. Liberian National Public Health Ser- vice personnel, assisted by local government officials, conducted a village-to-village active surveillance- assessment-vaccination programme in the northern two-thirds of Grand Gedeh County. This county has a population of 63 000 people living in remote villages in an area of about 18 000 km". Less than 10% of the population live in places accessible by motor road; the remainder of the population is reached over bush paths at distances up to 64 km. Active surveillance was directed towards the detection of smallpox cases that had occurred in the previous 12 months. Of 19 025 people examined by the sur- veillance agents, 15 suspect cases of pox disease were identified. Follow-up investigation of these cases identified varicella or other non-pox diagnosis in all cases except case 4. Case 4 lived in Tarr Town in adjoining Niabo Clan and developed his rash on 2 October, 21/2 weeks after the first three cases. Although the two infected towns lie approximately 19 km apart, contact be- tween the two groups is limited because of adminis- trative, linguistic, and traditional differences. Despite intensive interrogation, no direct or indirect contact between the infected cases or other people from the Table 2. Susceptibility of household and village con- tacts of monkeypox cases, Liberia, Nigeria, and Sierra Leone, 1970-71 Household Village contacts No.e suscep- rcentage No PercentagetiblNo.e susceptible No- susceptibleti ble ~~~~~~tible 1 23a 6 26 21 8 38 2 2 1 50 21 8 38 3 5 0 0 18 9 50 4 7 2 28 129 62 48 5 6 3 50 23 17 74 6 29 12 29 344 153 44 total ] 72 24 - 29 1556 257 45 a Includes Zwedru compound and hospital room contacts. towns could be established. Similar surveillance, in- vestigation, and vaccination programmes were car- ried out in Sierra Leone and Nigeria where direct inspection of all individuals living within an 8-km radius of the infected compound failed to identify additional cases of pox disease. The pox-susceptibility status of household and village contacts of the six cases, as estimated by scar surveys, is summarized in Table 2. None of these persons experienced a smallpox-like infection and thus no human-to-human transmission of infection could be demonstrated. DIAGNOSIS Virus was isolatedfrom 4 of the 6 cases (Table 3). The characterization of the isolates as monkeypox virus is described in a paper by Lourie et al. (1972). Sera were collected from four of the six patients (Table 4). SEARCH FOR NON-HUMAN SOURCE OF INFECTION With the identification of monkeypox virus, inves- tigation was directed towards the identification of an animal source for the human infections. All the cases had a limited exposure to domestic animals, including dogs, cats, poultry, sheep, goats, and pigs. Residential or farm contact with household rodents and bats was also possible. Cases 1-5 lived in the tropical rain forest where hunting ofgame was common. Monkeys 573 S. 0. FOSTER AND OTHERS Table 3. Pox virus identification in human monkeypox cases, Nigeria, Liberia, and Sierra Leone, 1970-71 Vesicular fluid Crusts Case EM CAM EM TAG CAM 1 + + + + + 2 NT NT NT NT NT 3 NT NT NT NT NT 4 + + - - - 5 + + + + + 6 NT NT + + + * EM = electron microscope examination for pox virus; AG - agar gel; CAM = pox virus isolation at 72 h on chorioallantoic membrane of embryonated eggs; + = positive; - = negative; NT - not tested. and duiker were the most frequent game animals and served as the main sources of animal protein. No evidence of definite exposure to sick animals, wild or domestic, could be obtained in any of the cases. Cases 4 and 5 occasionally consumed freshly killed monkeys for food. During the field investigation cases 1, 2, and 3 were observed to play with internal organs removed from recently killed monkeys. How- ever, no evidence of definite monkey contact could be established for any of the 5 cases in the 3 weeks prior to the onset of rash disease. Although monkeys have occasionally been observed near the village of case 6, monkeys are not eaten there and monkey exposure was highly unlikely. Serological surveys for poxvirus antibody have been undertaken as a means of estimating the preva- Table 4. Serological data on monkeypox cases, Liberia and Sierra Leone, 1970 No. of days between Vaccinia Herpes VariCase onset of C_FI cella rash and HAI CF AG Neut. (CF) specimen 1 90 64 8 + <8 <8 2 13 64 <8 - 500 <8 <8 3 12 16 <8 - 128 <8 <8 4 8 128 16 + 1 024 16 <8 5 14 160 16 + 450 <8 <8 HAI = haemagglutination inhibition; CF = complement fixation; AGj= agar gel; Neut. = neutralization. Table 5. Poxvirus haemagglutination inhibition and neutralizing antibody titres of 18 monkey sera collected from Grand Gedeh County, Liberia HAl titre Nitre Species No. tite_ <8 8 1 :30 Cerpithecus buttikoferi 5 3 2 1 Cercopithecus cambe/li cambelli 5 5 Procolubus badius bad/us 1 1 Procolubus verus 1 1 Colubus polykomos polykomos 1 1 Cercop/thecus diana diana 2 1 1 Cercocebus torguatus atys 1 1 Cercopithecus nict/tans stampfli 1 1 Perodictius potto potto 1 1 lence of pox infection. Studies carried out by the World Health Organization on over 2 000 monkey sera collected from Chad, from Malaysia, and from primate laboratories have failed to identify serological evidence of poxvirus infection (Arita et al., 1972). As part of the current investigation, serological speci- mens were obtained from selected species ofmonkeys collected in the Boudua and Tarr areas of Liberia (Table 5). Five animals had low level HAI titres to pox virus and one animal, a Cercopithicus buttikoteri from Tarr Town, had a neutralizing titre of 1: 30 to vaccinia virus in LLcMK2 cells. The specificity of these low titres has not been determined. Sera have also been collected from cooperating labora- tories in 6 countries (Table 6). DISCUSSION Human monkeypox had not been recognized prior to 1970. At the time of initiation of the West African regional smallpox eradication programme in 1966, vesicular diseases were diagnosed on clinical criteria and an estimated 5 % of smallpox cases were officially reported. During 1967 and 1968, regional efforts were directed towards the identification and control of smallpox outbreaks. A total of 40 pox isolates collected during this period have been tested for monkeypox and all have been reconfirmed as variola. Since 1969, every reported case of suspect pox disease has received the thorough epidemiological and labo- ratory investigation necessary to identify a low fre- 574 HUMAN MONKEYPOX 575 Table 6. Pox virus haemagglutination titre from selected African mammals No. of No. of HAISource Animal speci- posi- titre mens tives Ivory Coast a monkeys 38 2 1: 5 1 40 Chad b mammals 189 3 1: 5 1 *40 1 :80 Senegal c rodents 54 0 Sierra Leone d chimpanzees 16 4 1: 5 (3) 1:10 (1) Liberia e chimpanzee 2 0 Nigeriaf patas monkeys 55 0 a Institut d'Hygibne, Abidjan. b Veterinarian Institute, Farcho. c Institut Pasteur, Dakar. d Ministry of Health, Freetown. e Imported into USA. f West African Council for Medical Research, Lagos. quency non-variola pox disease such as monkeypox. Although human infection with monkeypox could be a new occurrence, it is most probable that the developments in surveillance of the smallpox eradica- tion programne have brought about the recognition of human monkeypox. Between October 1970 and May 1971, six cases of human infection with monkeypox virus were identi- fied in three West African countries, Liberia, Nigeria, and Sierra Leone. Four of the cases were confirmed by virus isolation and two were diagnosed on the basis of epidemiological and serological investiga- tions. All cases occurred in unvaccinated individuals. Post-infection serological studies showed high HAI and neutralizing titres to pox group virus in cases 2-5. Repeated challenge vaccination of all cases with potent smallpox vaccine resulted in equivocal reac- tions. This lack of a response to post-infection vac- cination is consistent with laboratory studies that show cross-protection between vaccinia, variola, and monkeypox viruses (Gispen et al., 1967). In all, 24 susceptible household contacts were exposed to the infected cases, but none developed disease. All the contacts subsequently responded to vaccination with a primary reaction, thus confirming their susceptibility and ruling out asymptomatic infection. If monkeypox in West Africa is as infective as smallpox, which has an infection rate of 37 cases per 100 susceptible household exposures, 9 cases of monkeypox would have been expected among the 24 contacts (Foster & Smith, 1970). This difference between the number of expected and observed cases is highly significant and indicates that monkeypox has a much lower rate of human-to-human transmis- sion than smallpox, possibly zero. Human monkeypox appears to be the result of chance infection of man with an animal virus. The natural reservoir, pattern of transmission, and route of infectivity remain unknown. Animals infected with monkeypox virus develop high antibody titres that persist for months and probably years (Wenner et al., 1968; Gispen, personal communication 1). Antibody studies on sera collected from animals in Liberia (Table 5) and West Africa (Table 6) have shown low-level HI titres in a small number of animals. Although these titres are much lower than those seen in infected animals and may be due to nonspecific inhibiting factors further studies, includ- ing neutralization tests, are required. Surveys of the mammalian population in Liberia and Nigeria are being carried out at present to identify the animal reservoir of infection. Animal infection with variola virus has been pos- tulated as a possible threat to the achievement of worldwide smallpox eradication. Since monkeypox is transmitted by man to only a slight extent if at all, it cannot be considered a direct threat to smallpox eradication. However, the identification of a clinical syndrome indistinguishable clinically and serologi- cally from smallpox points to the importance of obtaining a viral diagnosis from all suspected cases of smallpox in countries in which eradication has been, or is about to be, achieved. Diagnosis of monkeypox as smallpox could falsely invalidate methods and programmes used in the achievement of eradication. The progress of smallpox eradication in West Africa, which has given great impetus to the worldwide eradication programme, could have been jeopardized if the etiology of the cases reported in this paper had not been identified. Misdiagnosis of smallpox as monkeypox could lead to failures in uncovering undetected transmission and to a failure of eradication. Thus, the discovery of human mon- keypox emphasizes the need for surveillance and full epidemiological and laboratory investigation of all cases of pox disease in the worldwide eradication programme. 1 Gispen, personal communication, cited by Arita et al. (1972). 576 S. 0. FOSTER AND OTHERS RESUME MONKEYPOX CHEZ L'HOMME D'octobre 1970 i mai 1971, durant les operations de surveillance succ6dant a la campagne d'6radication de la variole men6e avec succes dans 20 pays d'Afrique occi- dentale et centrale, on a decouvert 6 cas d'infection humaine par le virus du monkeypox au Lib6ria, au Nig6ria et en Sierra Leone; 4 ont et6 identifi6s par isole- ment du virus et 2 apr6s une enquete 6pid6miologique et serologique. Tous les cas sont survenus chez des sujets non vaccin6s contre la variole. Chez 4 malades gravement atteints, les prodromes et les manifestations cliniques de I'affection 6taient indiscemables de ceux de la variole. Les epreuves courantes de laboratoire - examen au microscope electronique, precipitation en milieu g6lifi6, ensemence- ment sur membrane chorio-allantolde d'embryon de poulet - ont permis d'isoler 4 souches de poxvirus a partir de materiel (serosite de vesicules, croutes) recueilli chez les patients. Des tests compl6mentaires ont e necessaires pour les identifier comme 6tant des virus du monkeypox. L'examen s6rologique pratique chez 4 convalescents a decele des titres 6leves d'anticorps inhibant 1'hemagglu- tination et neutralisants pour le groupe des poxvirus. Chez tous les malades, la vaccination antivariolique pratiqu6e i plusieurs reprises a donn6 des reactions 6quivoques. L'enqu8te 6pid6miologique a rev6l6 que 3 des cas 6taient survenus dans le meme village, et resultaient probablement d'une exposition commune a l'infection. Aucune atteinte de monkeypox n'a ete observ6e parmi un total de 24 contacts; tous ont Wt6 vaccines avec succ6s contre la variole, ce qui atteste leur r6ceptivit6 et exclut l'6ventualite d'une infection asymptomatique. Le monkeypox chez l'homme semble r6sulter d'une infection fortuite par un virus animal dont on ne connait ni le reservoir ni le mode de transmission. Lors d'enquetes serologiques sur des primates et autres mammif6res afri- cains, on a trouv6 des titres d'anticorps tr&s inferieurs a ceux que suscite l'infection experimentale par le virus du monkeypox. Les implications de la decouverte de cas humains de monkeypox au regard des programmes d'6radication de la variole sont examin6es. REFERENCES Anderson, I. (1861) Study offever, London, J. Churchill, p. 180 Arita, I. et al. (1972) Bull. Wid Hlth Org., 46, 625 Arita, I. & Henderson, D. A. (1968) Bull. Wid Hith Org. 39, 277-283 Bleyer, J. C. (1922) Munch. med. Wschr., 69, 1009 Foster, S. 0. & Smith, E. A. (1970) J. Nigeria med. 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