Bull. Org. mond. Sante 1 1973, 49, 577-585Buill. Wid Hlth Org.

Transmission of the virus of foot and mouth diseasebetween animals and man*N. ST. G. HYSLOP1

The virus offoot and mouth disease causes severe epizootics in animals and infrequentlyevokes painful, but transient, clinical signs in man. Adults in certain occupational groups andyoung children are particularly exposed to risk. Infected persons may disseminate virusfor up to about 14 days. The virus can be transmittedfrom animals to animals, from animalsto man, from man to animals and, probably, from man to man. Evidence for transfer of thedisease between human and animal populations is reviewed in detail and modern methods ofdiagnosis are described. Predisposing factors play an important role in the development ofovert foot and mouth disease in man. Subclinical infection occurs. The possibility of aerialtransfer of the virus between man and domestic livestock constitutes a hazard, especially tothe latter. Attention is directed to the need for sophisticated diagnostic techniques, torequirements for adequate precautions in the handling and disposal of affected animals, andto hygienic measures for disease control.

INTRODUCTION

Clinically apparent disease follows infection withthe virus of foot and mouth disease (FMD) infre-quently and occurs in circumstances that remain soill-defined that, until comparatively recently, it waswidely believed that human infections never occurred(55, 62, 63, 80). Nevertheless, although textbooks onthe zoonoses (42, 102) described FMD as an infectionof minor importance to man in comparison withsome other viral diseases, a considerable amount ofevidence has accumulated during the past two cen-turies indicating that man is susceptible and that,although clinical manifestations are not frequent,human infection may lead to minor epidemic andperhaps to major epizootic spread. The epizootiologyand epidemiology of FMD were reviewed recently(47). It is now becoming clear that the virus isinfective in low concentrations, at least for cloven-footed animals, when airborne either on dust par-ticles or as a true aerosol; two-way spread betweenman and his domestic livestock is always a possibility

* Data extracted from the author's dissertation, now inthe Harveian Library, Royal College of Physicians, StAndrews Place, London NWI 4LE, England.

1 Principal Scientific Officer, Animal Virus ResearchInstitute, Pirbright, Woking, Surrey, England. Present ad-dress: Head of Immunology, Animal Pathology Division,Health of Animals Branch, Canada Department of Agricul-ture, Animal Diseases Research Institute, Box 1400, Hull,Quebec, Canada.

whenever man is in close contact with infectedanimals.The present report reviews briefly some of the

older records, discusses implications of the moreconvincing accounts of clinical and subclinical humaninfection during recent years, and describes attemptsto isolate virus from volunteers deliberately exposedto infection with FMD.

HISTORY

The first case of FMD reported in man wasprobably that recorded in 1695 by Valentine of Hesse(67). However, the increasing demand for dairyproducts during the Industrial Revolution last cen-tury led to more intensive methods of cattle hus-bandry which were associated with numerous severeepizootics of this and other infectious diseases ofanimals. During the second half of the century manyauthors recorded cases of aphthous diseases in manwhich appeared to have been acquired from animalsaffected with FMD (58, 96, 29, 14). One report (58)concerned 22 cases in man in which consumption ofinfected milk appeared to be a primary factor, andanother (14), summarizing several previous reports,tabulated data relating to 172 cases diagnosed asFMD in man in different parts of Europe. Numerousreports associating the drinking of infected milk withhuman infection were cited by Brush (12), although

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many of these appear to be of doubtful provenance.Nevertheless, one author developed symptoms ofFMD after cutting himself on a broken vial contain-ing FMD virus (69), and another induced FMD in acalf and in guinea-pigs inoculated with humanvesicular fluids (68). Additional instances of humaninfection are contained in the Second, Third andFourth Progress Reports of the Foot and MouthDisease Research Committee of the Ministry ofAgriculture of Great Britain (31, 32, 33).

Notwithstanding the many cases of apparent hu-man infection recorded in the earlier reports, theirauthenticity frequently remains a matter of specula-tion, for reasons to be discussed later. Furthermore,the coincidental appearance of diseases caused byherpesviruses or other agents, at a time of highprevalence of FMD in animals, tends to give rise torumours of human FMD among unsophisticatedpopulations. Thus, the number of authenticatedcases is very small in comparison with the very largenumber of persons who have had contact with FMDvirus (7).

Nevertheless, reliably documented cases of FMDin man have been reported in recent years byinvestigators employing modern diagnostic methods(98, 38, 54, 71, 3, 23, 90, 103), although in severalinstances the infection appears to have been virtuallysymptomless.

CLINICAL PICTURE IN MAN

When clinical signs appear in man they generallyresemble those observed regularly in animals, al-though they are often milder in degree. After anincubation period of 2-4 days, premonitory signsappear. These may include headache, pyrexia, shiver-ing, and thirst. Later, pruritus, pharyngitis, tonsillitisand, rarely, gastro-enteritis precede the appearanceof the vesicular lesions. Vesicles vary in size fromthat of a pin-head to large bullae; the vesicularcontents are clear and serous at first, becomingturbid subsequently. The vesicles tend to occursomewhat more frequently on the hands, especiallybetween the fingers, or on the feet than on the lips orin the buccal cavity. When they occur, buccal lesionsare usually small, and the overlying thin tissue soonsloughs to reveal small ulcers with yellow bases; asickly-sweet halitosis is frequently obvious. Salivationmay be prolific and there is considerable discomfort.Regional lymph nodes are often enlarged.

Atypically, conjunctivitis and non-vesicular stom-atitis have been associated with the isolation of

type 0 FMD virus from human blood and saliva(39). Marked conjunctivitis was experienced by thepresent author during his experiments on the expo-sure of cattle and other animals to aerosols of FMDvirus; since the virus was not recovered from con-junctival washings or light scrapings, even whenconcentration methods were employed, the conjunc-tivitis may well have resulted from a hypersensitivityreaction rather than from viral proliferation in theconjunctival cells.

Recovery is usually complete within about 14days, although one case was recorded in a veterina-rian in whom recovery was delayed and a super-vening endocarditis was diagnosed (8). Reports ofdeaths, made by early authors (12), are based onhearsay evidence and should be discounted. FMD inman, if not symptomless, is usually a mild, transient,but uncomfortable malady.

DIAGNOSIS

Diagnosis cannot be made on clinical groundsalone, even when FMD is enzootic in the locality.Isolation of the virus by inoculation of susceptibleanimal species, usually cattle or guinea-pigs (68, 57,77, 78, 89) or, as practised more recently, isolation inpig-kidney or bovine-thyroid cell-cultures, must befollowed by serological identification and assignmentof the strain to one of the 7 immunological types.Further subtyping may facilitate epidemiologicalstudies.However, the initial isolation may be rendered

difficult by the relative or absolute predilection ofcertain strains for a particular animal species, andnegative results after attempts to isolate the virusmay not be significant. Alternatively, vesicles maydevelop in guinea-pigs after inoculation of the virusesof vaccinia, herpes simplex, vesicular stomatitis, andother disease agents. The use of guinea-pigs by earlyworkers for the identification of virus isolated fromhuman vesicular diseases has been superseded bytests in unweaned mice and in cell-cultures, withconsequent improvement in reliability.Antibody may become detectable in the sera of

convalescent patients within 7-30 days of the appear-ance of vesicles, often persisting thereafter for about4 months. One author claimed to have detectedvirus neutralizing antibody in the s2ra of 12 of 28" symptomless " workers in a heavily infected envi-ronment, whereas control sera were devoid of anti-body; some of the sero-positive workers had buccallesions (possibly herpetic in origin) and FMD virus

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was not isolated from any of the personnel (73).Another author detected type 0 antibody in serafrom 5 of 17 laboratory workers and, in 3 of the 5,titres remained elevated after 1 year (90). Yet an-other, who isolated type 0 virus from a clinicalhuman case, recorded that neutralizing antibodieswere detectable for at least 154 days (3).

Currently, the most reliable method available foridentification of infection is the complement-fixation(CF) test (15). In one instance (75), 16 human caseswere cited as being diagnosed by this method. Latermodifications (11, 76, 9, 10, 82, 17) have addedprecision to that test, so that cross-CF tests andcross-protection tests have proved very useful inelucidating subtype relationships between fieldstrains of animal origin (28, 49, 18, 46, 56, 17).Application of these tests may be expected to assist inthe determination of the source of human infections.The majority of cases of human infection have beendiagnosed on serological grounds rather than byvirus isolation; antibodies to type 0 virus are de-tected more frequently than those of types C or A.Haemagglutination or gel diffusion tests may yieldfurther confirmation but are still in the process ofdevelopment.

DIFFERENTIAL DIAGNOSIS

Unqualified acceptance of the majority of theearly reports is precluded by the fact that in the pastthere were no isolation facilities adequate to preventcross-infection between animals used for diagnosisand refined serological tests were not available. Con-ditions to be considered in the differential diagnosisofFMD in man include pompholyx, tinea pedis, ery-thrasma, erythema multiforme, Vincent's angina,aphthous stomatitis of " non-specific " origin, andinfections caused by vaccinia, variola, exotic poxviruses such as monkeypox, herpesviruses, vesicularstomatitis virus, Coxsackievirus A (hand, foot andmouth disease and herpangina), and Coxsackievirus B.Cases of aphthous stomatitis in which neither virusesnor viral antibodies are detectable are encounteredvery frequently in man (F. 0. MacCallum, personalcommunication, 1973); consequently, rare instancesin which stomatitis is caused by FMD virus may bemissed.Hand, foot, and mouth disease, caused by Cox-

sackieviruses A5, AlO, A16, possibly by A2 and A4(2, 79, 25, 19, 1) or by A9 (41), is perhaps most likelyto be confused with FMD on clinical grounds, butthe vesicles tend to be somewhat smaller and more

widely distributed (including over the buttocks). Theformer disease is much more contagious for man,occurring in minor outbreaks or, occasionally, aswidespread epidemics, and is apparently non-patho-genic for his domestic livestock. Like FMD, someCoxsackieviruses are capable of spreading not onlyby direct contact but also as airborne infections (16),in which event distribution might be similar in bothdiseases. Differential diagnosis is completed by viralisolation and serological tests.

EPIDEMIOLOGY

Transmission from animals to manCases in man usually occur singly, although small

outbreaks may develop infrequently. Veterinarians,farm workers and their families, butchers, laboratoryworkers, and livestock auctioneers all appear to beoccupational groups whose risk of infection is in-creased appreciably (65, 64, 98, 91, 84, 54, 34, 81).Several severe clinical cases, with confirmatory sero-logical identification of the virus and good photo-graphic records of the lesions, affecting butchers,cattle attendants, and others, have been described(72, 71); high virus titres were demonstrated and thecourse of seroconversion was followed in repeatedtests.The means by which FMD virus gains access to

man are probably numerous, but ingestion seems tobe the most frequent route of infection. Rarely, merecontact, either direct or indirect, appears to havebeen sufficient (59). Contamination of minor woundsor other skin lesions has frequently bzen incriminated(69, 99, 21, 22, 101) and is a more likely cause. Evenmanicure procedures may cause sufficient abrasion tofacilitate infection.However, a further well documented case, which

occurred in an agricultural contractor's salesman,who had only indirect contact with animals, wasdescribed recently (3). At the time of an outbreak ofFMD among cattle in the vicinity, the patient firstdeveloped malaise and a sore throat, which wasfollowed by crops of vesicles on the hands andbetween the toes. FMD virus infection was confirmedby viral isolation and demonstration of the antibodyspecific for type 0. The virus titre was somewhatlower than might be expected in bovine material. Noclinical signs of infection or antibody titres weredetected in 5 veterinary officers who were working onthe infected premises, but the serum of 1 of 12 mem-bers of the laboratory staff engaged in tests on thisand on cases of animal origin showed a neutralizingtitre of 1: 22 against virus of the same type.

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The potential hazard of ingestion of milk frominfected livestock has been the subject of sporadiccomment in many parts of the world, and multipleoutbreaks have been encountered when groups ofschoolchildren have been supplied with raw milkfrom infected cattle. Milkborne infection has beensuspected since 1834 (58, 12, 67, 70, 35, 88, 20, 54,47). Such dangers as may exist are increased, particu-larly during major epizootics, by the high virus titres(about 105.6 TCID50 per ml) found in milk. Further-more, virus may be secreted by the mammary glandfor at least 33 h before the appearance of clinicalsigns of disease (37). Thus, an outbreak in 1948 wasdescribed involving a milker, a farmer, and 3 chil-dren, who had consumed raw milk collected duringthe incubative stages of the disease (66), and in 1970 atype A22 virus was isolated in similar circumstances(83).However, having regard to the vast amounts of

untreated milk consumed in the past and the widedistribution of the disease, reports of milkborneFMD have been relatively infrequent. The routineheat treatment of virtually all milk now handled bymodern distributive enterprises almost eliminates therisk for urban populations in developed countries.Infection in man has been attributed to butter,buttermilk, cheese, and other dairy products but,because of the susceptibility of most strains ofFMDvirus to denaturation by low pH, acidified productssuch as yoghurt are probably safe.When incubating the disease, livestock also shed

virus in the saliva, urine, faeces, nasal discharges,and tears for several hours before even a tentativeclinical diagnosis becomes possible. Furthermore, inareas where a policy of slaughtering all infected andin-contact animals is not enforced, urinary excretionmay occur intermittently for long periods after ap-parent recovery (100). We have occasionally isolatedthe virus from the kidneys of cattle necropsied atintervals up to 37 days after exposure to infectiveaerosols; it now appears very probable that persis-tent infection of kidney cells may occur in certainanimals.

Recovered animals frequently carry virus for sev-eral months in the pharyngeal region, whence virusmay be recovered by scraping with a cup-probang (6,92, 13), by swabbing, or by biopsy (47). " Carrier "animals excrete small amounts of virus intermittentlybut quite regularly in the saliva, and probably in theexhaled air. Pharyngeal infection may occur withoutclinical signs, and irrespective of the immune statusof the individual; thus, it may occur frequently after

vaccinated cattle have been in contact with the virus.However, " carrier" animals do not appear to ex-crete virus that is fully virulent for neighbouringanimals. On numerous occasions it has been sug-gested that FMD virus might be carried as aninapparent infection in the nasopharynx of subclini-cally infected man (see below).

It has been established that FMD virus mayremain fully infective, under optimal conditions, forquite long periods whilst suspended in air, either ondust particles (93, 26) or as true aerosols (44, 45, 43).The present author has found that, after intratrachealintubation, cattle might become infected by aerosolscontaining less than 100 and probably less than 10TCID50 of virus. The apparent survival period ofairborne virus depends partly on the amount ex-creted, partly on strain characteristics, and partly onambient conditions of relative humidity, tempera.ture, and light. Rainfall may wash some of the virusout of aerial suspension. Occasionally, animals ex-.posed to airborne virus may undergo only a mild orsubclinical form of the disease; alternatively, clinicalsigns may develop only after a prolonged period ofincubation (47, 30). Possibly this phenomenon resultsfrom encapsidation ofFMD viral ribonucleic acid byprotein of the coat-substance of enteroviruses, or ofother viruses that may be present in the respiratorytract (94, 30). Whatever the cause, unsuspectedairborne virus plays a very important part in thedissemination of the disease (47).During an outbreak characterized by numerous

instances of airborne spread among animals, a caseof clinical FMD in a woman was attributed toairborne virus (60), and several other instances haveoccurred in which strong suspicion existed thatairborne virus was implicated in human clinicaldisease. 101.3 ID50 of virus was recovered from thenose of a volunteer who talked for 2 minutes withcolleagues who had inspected infected animals (85);the man remained clinically normal. Acquisition ofinapparent infection with airborne virus, withoutclose contact with infected animals, has been encoun-tered under experimental conditions (see below).Although there is little or no epidemiological

evidence in support (24), it has been suggested thathuman infection may follow the use of vaccinia"l ymph ", inadvertently prepared from animals inthe incubative stages of FMD (57, 61), in very muchthe same way that glandular products derived fromslaughterhouses might spread the disease amonganimals (I. A. Galloway, personal communication,1965). However, the replacement of vaccinia lympb

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of animal origin by the tissue-culture propagatedproduct for smallpox prophylaxis will eliminate therisk in the future.The frequency of FMD in man appears to be low

and it is evident that predisposing factors must play acrucial part in the initiation of clinical signs. Thesefactors remain largely undetermined but, amongother possibilities, crowding and debility (74),wounds (69, 99, 21), and a high exposure intensity(84) must be considered important; the reports ofmany authors indicate that children develop clinicalinfection more readily than adults. In addition tominor wounds, pre-existing skin conditions, such asdermatitis, keratomata, or tinea, appear to facilitatethe establishment of the virus.

Experimental human infectionAs long ago as 1834, three European veterinarians,

Hertwig, Mann, and Villain, developed vesicularlesions after each voluntarily drank 1 quart of milkfrom an infected cow (67). The clinical diseaseexperienced by Pape (69), following a laboratoryaccident, has been mentioned, though Lebailly (55),Nicolle & Balozet (62), and Magnusson (57) failed toinfect volunteers by inoculation of types 0, A, or Cvirus.More frequently, serological evidence of successful

infection has been claimed after attempts to initiateFMD by parenteral inoculation but, despite theobservations of Popa et al. (73) on seroconversionamong nearly 50% of workers in an infected environ-ment, demonstration of significant levels of antibodyis not achieved regularly. Accidental self-inoculationis by no means rare and, in an unpublished experi-ment, the author infiltrated intracutaneously andsubcutaneously the interdigital areas of one hand,and the nail-bed zone of two fingers, with an Africanstrain of virus. The virus, passaged once in pig-kidney cell culture, was fully virulent for animals. Amild erythema resulted, possibly as a response to pig-kidney cell material, but neither vesicles norhumoral antibody of the homologous type weredetected.The author and several of his colleagues at the

Animal Virus Research Institute, Pirbright, England,and elsewhere, have been exposed inadvertently, ordeliberately by inhalation through a face mask, toaerosols of FMD virus in high concentration. Clini-cal manifestations of the disease were never ob-served, although virus was recovered on numerousoccasions from the upper respiratory tract by nasaland pharyngeal washing or swabbing. With a single

exception, no serological indications of infectionwere detected among these groups of investigators;in the single case, a transient antibody response oflow but increasing titre (1: 8 at 14 and 1: 64 at 21and at 30 days respectively) was detected in neutral-ization tests against type SAT 1 virus (strain Tur323/62) following exposure of the subject to aerosolsof that virus. Because no clinical signs were observed,this must be regarded as only dubious evidence ofsusceptibility. However, in a subsequent experiment(85), one person developed neutralizing titres of 2.4and 2.6 after exposure to type C virus (Noville) but,again, clinical disease was not reported.

Possibly, prolonged contact or repeated subclinicalinfection with virus of a single type is necessarybefore even serological evidence of infection becomeswell established in " normal " human subjects in theabsence of predisposing factors. Thus, after 20months' contact with virus in a vaccine-producingunit, 6 of 15 persons showed elevated serum antibodytitres (50). Another researcher detected serologicalresponses in about 30% of laboratory workers afteronly 2-3 months' exposure (90) but, elsewhere, longperiods spent in similar environments have notinduced a high proportion of reactions.

Transmission from man to animals

Whether man may remain a " carrier " of FMDvirus in the accepted sense for long periods is verydoubtful; there is certainly no reason, at present, tosuspect that such persons play an important part inthe epizootiology of the disease. Nevertheless, me-chanical transfer of virus on the hands and on theclothing of persons who have handled infected ani-mals, implements, bedding, meat, milk, etc., has beenregarded for many years as one of the more potentmechanisms by which the disease is spread. There isalso some evidence that virus may be present, fromtime to time, in human stomach contents, urine, andfaeces (52, 53). The presence of virus has beendetected frequently on bandages and other dressingsapplied to minor wounds of butchers and otherworkers who handle infected animals. Unless precau-tions are taken, hands and clothing may remaincontaminated with viable virus for several days.More significantly, however, FMD virus has been

recovered from uncovered wounds and other lesions,often of a granulomatous nature, on the bodies ofhuman subjects. Such infected lesions have beenincriminated both as the portal of entry leading tothe clinical infection of man and as a source ofinfection for domestic livestock. Many authors (27)

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N. ST. G. HYSLOP

have attributed outbreaks in animals to virus dissem-inated by infected human patients.During preliminary experiments on airborne trans-

mission ofFMD under African conditions (43), viruswas recovered from nasal swabs taken from theauthor and other persons working in loose-boxescontaining infected cattle; that virus was infective foranimals by parenteral injection on two occasions.Similarly, type SAT 1 virus was recovered in subse-quent experiments at Pirbright, England, after sub-jects had exhaled deeply into an air sampler, andtraces of the 7 serological types of virus have beenrecovered from the upper respiratory tract of humanbeings (N. St. G. Hyslop, unpublished observations,1967). Quantitatively better and more reproducibleresults have been obtained by inoculating nasalwashings into cultures of calf-kidney cells (85, 86).When persons who had examined infected pigssneezed, coughed, and talked in rooms housingsusceptible cattle, one of the cattle developed FMDafter an extended incubation period of 14 days (87).FMD virus has been recovered from the human

respiratory tract for periods exceeding 1 day after thelast contact with infected animals. Thus, there iscircumstantial and direct evidence that infected hu-man beings may constitute a source of considerabledanger to susceptible livestock.

PUBLIC HEALTH ASPECTS

The present author has compiled a bibliographycontaining some 400 reports of alleged FMD andclinically similar syndromes in man; other authorshave also prepared bibliographies (5, 51, 97).The observations described above indicate the

existence, in varying degrees of probability, of thetransmission of FMD virus (a) from animals toanimals, (b) from animals to man, (c) from man toanimals, and (d) from man to man. The last-men-tioned type of transmission is, perhaps, the leastlikely to give rise to clinical disease, but all appearto present potential hazards when conditions arefavourable. Exposure to virus of only very shortduration may initiate clinical FMD in animals.

Pigs are now known to liberate very large amountsof virus, but quickly reveal clinical signs of thedisease. The greatest danger of dissemination occurswhen the disease affects sheep. In ovine species,clinical signs may be minimal, and careful examina-tion of large flocks in hilly country is often difficult;however, spread to those human populations who donot habitually consume raw sheep's milk or improp-

erly cooked mutton is not very likely. By contrast,secretion of virus in cow's milk, especially during thepreclinical stages of infection, presents a danger toboth animals and man, although human milkborneinfection in urban populations is virtually eliminatedby the routine pasteurization processes extensivelyemployed in Western Europe and North America.On infected premises, persons handling animals,

carcasses, and debris may be exposed to some addi-tional risk of infection, particularly if cuts andabrasions are not protected adequately. However,apart from possible infection by airborne transmis-sion, control and eradication legislation in mostcivilized countries is sufficient to afford a high degreeof protection to the general population, by prohibit-ing the movement of infected stock or potentiallyinfected persons except under restrictions designed tominimize dissemination of the virus. Nevertheless, itmust be remembered that persons clinically affectedwith FMD appear to carry virus for up to about 14days, and virus may be recovered from the nasalpassages of apparently normal persons for up to36 h after exposure.

In Great Britain, evidence recorded by numerouswitnesses in a Report to the Ministry of Agriculture,Fisheries and Food and the Ministry of Health (40)did not indicate any requirement for additionalprecautions against human infection, and systematicsearches for infected persons during an epizooticwere considered unjustified.

Nevertheless, physicians and others who encountersuspicious human lesions during an outbreak ofFMD in a locality should be aware of the possibilityof human infection and, consequently, should takewhatever precautions may be practicable to isolatethe patient pending confirmation of the condition,and should notify the relevant human and animalhealth authorities.

TREATMENT

Since the disease is self-limiting, treatment issymptomatic and palliative in man, although thepossibility of complications caused by potentialsecondary invading organisms must be considered.Treatment is contraindicated in animals, eradicationby slaughter being desirable.

CONCLUSIONS

From the data cited, it must be concluded thattransfer of FMD virus between animals and manoccurs more frequently than was suspected in the

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FOOT & MOUTH DISEASE 583

:ast. Clinical disease in man occurs only infrequentlyind is mediated by predisposing factors that have not,et been fully determined. Lesions closely resemble:hose seen in animals and cause marked discomfort,mlthough recovery tends to be uneventful. Neverthe-

less, inapparent infection, which probably occursfrequently and does not necessarily evoke a serologi-cal response of readily detectable magnitude, un-doubtedly constitutes a hazard to domestic livestockand, possibly, to other human beings.

ACKNOWLEDGEMENT

The author thanks Dr F. 0. MacCallum for reading the manuscript and for several very valuable suggestions.

RESUME

TRANSMISSION DU VIRUS DE LA FIEVRE APHTEUSE ENTRE LES ANIMAUXET L'HOMME

Chez l'homme, les manifestations cliniques de la fievreiphteuse sont tres semblables A celles observ6es chez'animal. Des diagnostics de cas humains fondes sur les;ignes cliniques ont ete formules depuis quelque 300 ans,nais seules les observations recentes, faisant appel aux:echniques modernes de culture et de s6rologie pour leliagnostic differentiel, sont considerees comme suffisam-inent probantes. Les methodes de diagnostic sont decrites,t des considerations epidemiologiques sont presentees-onfirmant l'importance des infections humaines.La frequence de la fievre aphteuse cliniquement appa-

*ente est relativement faible chez l'homme, mais certainsgroupes professionnels (veterinaires, fermiers, bouchers,tc.) sont particulierement exposes et la maladie a e)bservee chez de jeunes enfants apres consommation deait cru infecte. Des facteurs predisposants mal definisouent un role dans l'apparition de la maladie aver6e.Des etudes experimentales de la fievre aphteuse, dont les

resultats sont discutes, ont ete effectuees chez 1'homme.Des observations recentes indiquent que l'infectionhumaine inapparente est plus frequente qu'on ne lecroyait. La dissemination du virus par la voie aerienne estun facteur important de propagation de la maladie parmiles animaux et probablement aussi A I'homme. Le viruspeut etre transmis de l'animal A l'animal, de l'animalA l'homme, de l'homme A l'animal et de l'hommeA 1'homme. Les infections humaines subcliniques sontconsiderees comme une source importante, quoiquesouvent meconnue, d'epizooties au sein des populationsanimales.Le diagnostic de fievre aphteuse doit etre specialement

envisag6 lorsque des malades sont porteurs de lesionsvesiculeuses et qu'il existe des foyers locaux d'infectionchez l'animal, et lorsqu'on releve des antecedents decontact avec des produits animaux en provenance de paysetrangers ou l'affection est enddmique.

REFERENCES

1. ADLER, J. L. ET AL. Amer. J. Dis. Childr. 120: 309-313 (1970).

2. ALSOP, J. ET AL. Brit. med. J., 2: 1708-1712 (1960).3. ARMSTRONG, R. ET AL. Brit. med. J., 4: 529-530

(1967).4. BACHRACH, H. L. Ann. Rev. Microbiol., 22: 201

(1968).5. BALASSA, B. Bibliography of foot and mouth disease

in man, Greenport, Long Island, N.Y., USA,USDA Plum Island Animal Disease LaboratoryLibrary, 1965.

6. VAN BEKKUM, J. G. ET AL. Tijdschr. v. Diergeneesk.,84: 1159-1167 (1959).

7. BETTS, A. 0. Vet. Rec., 64: 640-641 (1952).8. BOYLE, V. Vet. J., 78: 428-429 (1922).

9. BRADISH, C. J. & BROOKSBY, J. B. J. gen. Microbiol.,22: 405-415 (1960).

10. BRADISH, C. J. ET AL. J. gen. Microbiol., 22: 392-404(1960).

11. BROOKSBY, J. B. The technique of complement-fixation in foot and mouth disease research,London, Her Majesty's Stationery Office, 1952(ARC Report Series, No. 12).

12. BRUSH, E. F. J. Amer. med. Assoc., 40: 1700-1704(1903).

13. BURROWS, R. J. Hyg. Camb., 64: 81-90 (1966).14. BusSENIUS, K. & SIEGEL, J. Zlb. klin. Med., 32: 147-

187 (1897).15. CIUCA, A. J. Hyg., 28: 325-329 (1929).

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16. COUCH, R. B. ET AL. Amer. J. Epidemial., 91: 78-86(1970).

17. DARBYSHIRE, J. H. ET AL. J. Hyg. Camb., 70: 171-180 (1972).

18. DAVIE, J. Proceedings of a meeting of the researchgroup, European Commission for the Control ofFoot and Mouth Disease, Pirbright, 1966, Rome,Food and Agriculture Organization, 1966.

19. DUFF, M. F. Brit. med. J., 2: 661-664 (1968).20. DIDOVETS, S. R. Veterinariya, Moscow, 37: 16-19

(1966).21. DUGLOSZ, H. Brit. med. J., 1: 189-190 (1943).22. DUGLosz, H. Brit. med. J., 1: 251-252 (1968).23. EISSNER, G. ET AL. Deut. med. Woch., 92: 830-832

(1967).24. FLAum, A. Acta path. microbiol. Scand., 16: 197-213

(1939).25. FLEWETT, T. H. ET AL. J. clin. Path., 16: 53 (1963).26. FOGEDBY, E. G. ET AL. Nordisk. Vet., 12: 490-498

(1960).27. FRtJHWALD, 0. Fleischwirtsch., 3: 62-63 (1951).28. GALLOWAY, I. A. ET AL. Proc. Soc. exp. Bio. Med.,

69: 59-84 (1948).29. GLAISTER, A. F. Lancet, 201-203 (1896).30. GRAVES, J. H. ET AL. J. inf. Dis., 124: 270-276

(1971).31. GREAT BRITAIN, MINISTRY OF AGRICULTURE, FooT

AND MouTH DISEASE RESEARCH COMMI1'EE. Secondprogress report, London, His Majesty's StationeryOffice, 1927.

32. GREAT BRITAIN, MIMNsmY OF AGRICULTURE, FOOTAND MouTH DISEASE RESEARCH COMMITTEE. Thirdprogress report, London, His Majesty's StationeryOffice, 1928.

33. GREAT BRITAIN, MINISTRY OF AGRICULTURE, FOOTAND MOuTH DISEASE RESEARCH COMMITTEE. Fourthprogress report, London, His Majesty's StationeryOffice, 1931.

34. GUTSCH, G. Zlb. Hyg. Grenzgeb., 11: 447-448(1965).

35. HAMMERSCHMMDT, J. Zlb. Ges. Hyg., 5: 355 (1924).36. HESs, W. R. ET AL. Am. J. vet. Res., 21: 1104 (1960).37. HEDGER, R. S., & DAWSON, P. S. Vet. Rec., 87: 186-

188; 213 (1970).38. HEING, A., & NEUMERKEL, H. Deut. Ges. Wes., 19:

485-490 (1964).39. HOLM, P. Maanedsskr. Dyrlaeg., 61: 236-241 (1950).40. HowIE, J. W. & WEIPERS, W. L. Bull. Off. int.

Epizoot., 67: 745-751 (1967).41. HUGHES, R. 0. Lancet, 2: 751-752 (1972).42. HULL, T. G. Diseases transmitted from animals to

man, Springfield, Ill., USA, Thomas, 1963.43. HYSLOP, N. ST. G. J. comp. Path. Therap., 73: 265-

276 (1963).44. HYSLOP, N. ST. G. J. comp. Path. Therap., 75: 111-

118 (1965).45. HYSLOP, N. ST. G. J. comp. Path. Therap., 75: 119-

126 (1965).

46. HYSLOP, N. ST. G. Proceedings of the 18th WorldVeterinary Congress, Paris, 1967, I, 396.

47. HysLOp, N. ST. G. The epizootiology and epidemio-logy of foot and mouth disease. In: Advances inveterinary science, 1970. New York & London,Academic Press, 1970.

48. HysLop, N. ST. G. Trop. An. Hlth. Prod., 4: 28-40(1972).

49. HysLop, N. St. G. ET AL. J. Hyg. Camb., 61: 217-230 (1963).

50. IFITIMOVICI, R. ET AL. Proceedings of the 18th WorldVeterinary Congress, Paris, 1967, I, 219.

51. SOUBERT, L. & MACKOWIAK, C. La fievre aphteusespontanee, Lyon, France, Merieux, 1968.

52. KLING, C. & HOJER, A. Comptes rend. Soc. Biol.,Paris, 94: 618-620 (1926).

53. KLING, C. Comptes rend. Soc. Biol., Paris, 131: 478-481 (1939).

54. KOBUSIEWICZ, T. ET AL. Bull. Of. int. Epizoot., 61:1617-1629 (1964).

55. LEBAILLY, C. Comptes rend. Acad. Sci., Paris, 172:1140-1145 (1921).

56. LUCAM, F. ET AL. Bull. Off. int. Epizoot., 75: 1-20(1971).

57. MAGNussoN, H. Bull. Off. int. Epizoot., 3: 916-921(1930).

58. McBRIDE, J. A. Brit. med. J. 2: 536-542 (1869).59. MCLEOD, K. Brit. med. J. 1: 300 (1943).60. MIcHELsEN, E. Report to a meeting of the European

Commission for the Control of Foot and MouthDisease, Lindholm, Denmark, 1968, Rome, Foodand Agriculture Organization.

61. MoTAs, C. S. Bull. Off. int. Epizoot., 4: 774-785(1930).

62. NICOLLE, C. & BALOZET, L. Comptes rend. Acad.Sci., Paris, 197: 374-376 (1933).

63. NICOLLE, C. & BALOZET, L. Arch. Inst. Pasteur(Tunis), 22; 193-197 (1935).

64. NIXoN, J. H. Brit. med. J., 2: 3993 (1937).65. NORDHEIM, F. Deut. med. Woch., 1: 170 (1921).66. Nuzzi, A. F. Acta. med. Ital., 3: 127-128 (1948).67. O'BRIEN, C. M. Vet. J., 69: 547-552 (1913).68. PANACERA, A. Clin. Vet. Milan, 45: 251-254 (1922).69. PAPE, J. Ber. Tier. Woch., 33: 354 (1921).70. PETIT, H. Rev. Path. comp., 19: 7-8 (1919).71. PILZ, W. & GARBE, H. G. Zlb. Bakt. Parasit. Inf.

Hyg. Abt. Orig., 198: 154-157 (1965).72. PILZ, W. ET AL. Vet-Med. Nachr., 4: 224-229 (1962).73. POPA, M. ET AL. Lucr. Inst. Pasteur Bucuresfi, 7: 79-

86 (1963).74. POTTING, K. Zlb. Vet. Kunde., 27: 266-267 (1915).75. REYN, A. Acta. path. Scand., 17: 145-171 (1940).76. RICE, C. E. & BROOKSBY, J. B. J. Immunol., 71: 300-

310 (1953).77. RICHTER, W. Arch. Dermatol. Syph. Ber., 176: 575-

578 (1938).78. RINJARD, P. ET AL. Bull. Acad. Vet. Fr., 12: 325-338

(1939).

FOOT & MOUTH DISEASE 585

79. ROBINSON, C. R. ET AL. Canad. med. J., 79: 615-621(1958).

80. RoCHAIX, A. & DELBOS, J. Rev. Hyg., Paris, 60: 321-330 (1938).

81. ROHRER, H. Bibliogr. Agr., 32: 95 (1967).82. ROUMIANTZEFF, M. ET AL. Bull. Soc. vet., Lyon, 68:

161-170 (1965).83. SALAZHOV, E. L. ET AL. Zh. Mikrobiol. Epidem.

Immunobiol., 1970, 6: 87-90 (1970).84. SCHWANN, J. Berufsdermatosen, 11: 309-319 (1963).85. SELLERS, R. F. ET AL. J. Hyg., Camb., 68: 565-573

(1970).86. SELLERS, R. F. ET AL. Lancet, 1: 1238 (1971).87. SELLERS, R. F. ET AL. Vet. Rec., 89: 447-449 (1971).88. SHABANOV, A. N. & KOLESNIKOV, N. V. In: Hand-

book for assistant surgeons, Moscow, 1958.89. STENSTROM, T. Acta med. Scand., 107: 372-390

(1941).90. SUHR-RASMUSSEN, E. Ugeskr. Laeg., Denmark, 130:

1619-1621 (1968).91. SULUZYCKI, C. Czas. stomat., 8: 1-9 (1955).92. SUTMOLLER, P. & GAGGERO, C. A. Vet. Rec., 77:

968-969 (1965).93. THORNE, H. V. & BURROWS, T. M. J. Hyg., Camb.,

58: 409-414 (1960).

94. TRAUTMAN, R. & SUTMOLLER, P. Virology, 44: 537(1971).

95. TRAUM, J. In: A review of selected Soviet articles onfoot and mouth disease, Berkeley, Calif., USA,University of California, 1958.

96. TUKE, G. T. Brit. med. J., 115-116 (1893).97. USKAVITCH, R. Foot and mouth disease in man: a

bibliography, Greenport, Long Island, N.Y., USA,USDA, Plum Island Animal Disease LaboratoryLibrary, 1971.

98. VETTERLEIN, W. Arch. exp., Vet-Med., 8: 541-564(1954).

99. WALDMANN, 0. Proceedings of the 19th Interna-tional Congress of Dermatology, Budapest, 1936,vol. 2, pp. 1-5.

100. WALDMANN, 0. ET AL. Zlb. Bakt. (Orig)., 121: 19-32 (1931).

101. WALL, H. Zbl. tropen. Med. u. Parasit., 4: 26-31(1953).

102. WARREN, J. In: Horsfall & Tamm, ed. Viral andrickettsial infections of man, 4th ed., Philadelphia& Toronto, Lippincott, 1965.

103. WISNIEWSKI, J. & JANKOWSKA, J. Bull. vet. Inst.Pulawy., 12: 16-18 (1968).