Article Artikel

Lumpy skin disease in southern Africa: a review of the disease and aspectsof control

P Huntera and D Wallaceb

INTRODUCTIONIn 1929 a new disease of cattle was

reported from Zambia (then NorthernRhodesia)18 that manifested itself by theappearance of skin nodules. Initiallythese were thought to be caused by insectbites, and the condition was referred to asPseudo urticaria.

Fourteen years later, a more severe formof the same disease was described in cattlein Botswana and was given the nameNgamiland Cattle Disease23. By this timethere was evidence to suggest that thecondition was being caused by an infec-tious agent22,23.

The disease continued to spread andresulted in a panzootic that lasted for anumber of years, and affected cattle inmost southern African countries.

By 1944 it had spread to South Africa.The first cases were reported in theMarico District of the Western Transvaal(now North West Province)22 where it wasknown as knopvelsiekte (Afrikaans forlumpy skin disease (LSD)). There wasspeculation that the transport of cattlepromoted the spread of the disease agent,but once watercourses were reached itspread rapidly along low-lying areas,probably by insect vectors. Lumpy skindisease then spread to the former OrangeFree State, Natal, Western Cape andTranskei13. During this period it is esti-mated that 8 million cattle were affected11.Cases then abated, probably owing to the

development of widespread immunity,but a severe outbreak occurred in theEastern Transvaal in 19531954. Epizoot-ics of the disease continued to be reporteduntil 1962. Veterinary researchers identi-fied the aetiological agent as a poxvirusand a vaccine was then developed byattenuation of a field isolate, whichhelped to control further outbreaks25. Forthe following 30 years the incidence ofLSD was very low. Vaccine use droppedto low levels4: as illustrated in Fig. 1, therehas not been sustained use of LSDvaccine. Annual sales have seldom risenabove 2 million doses over the 19841999period (Onderstepoort Biological Prod-ucts sales figures, 1999), a coverage ofroughly 20% of the average cattle popula-

tion of South Africa.During the last decade, higher rainfall

and a low level of overall immunity areprobably indirectly responsible for a re-surgence of the disease, with cases beingreported in the Eastern and WesternCape, where it was last observed in the1950s.

Disease quiescence is probably due tounfavourable climatic conditions thatreduce vector prevalence, with a concom-itant reduction of the host immunitythat later results in extensive outbreaks.However, this aspect of the disease hasnot been investigated.

AETIOLOGYEarly attempts to isolate and character-

ise the aetiological agent of LSD indicatedthat a virus was the causative agent22.However, more than 1 virus was isolatedfrom skin lesions on a number of occa-sions, and these were divided into 3groups: Group I, represented by anorphan virus (bovine herpesvirus-4);Group II, consisting of Allerton virus(bovine herpes mammilitis, or bovineherpesvirus-2); and Group III, containinga virus that resembled vaccinia virus19,25.The orphan virus was found to be non-pathogenic and in most cases resultedfrom mixed infections with the Group III

68 0038-2809 Tydskr.S.Afr.vet.Ver. (2001) 72(2): 6871

aOnderstepoort Biological Products, Private Bag X07,Onderstepoort, 0110 South Africa.

bARC - Onderstepoort Veterinary Institute, Private BagX05, Onderstepoort, 0110 South Africa.

Received: November 2000. Accepted: March 2001.

ABSTRACTThis article reviews some of the important aspects of lumpy skin disease (LSD) that mayimpact on its successful control. A resurgence of the disease in the last decade has high-lighted some constraints of the Neethling strain vaccine, but there is no evidence of vaccinebreakdowns owing to the presence of heterologous field strains. More research is neededon epidemiology and transmission of LSD in South Africa to formulate control measures.

Key words: capripox, control, immunity, lumpy skin disease virus, transmission, vaccine.Hunter P, Wallace D Lumpy skin disease in southern Africa: a review of the disease andaspects of control. Journal of the South African Veterinary Association (2001) 72(2): 6871 (En.).Onderstepoort Biological Products, Private Bag X07, Onderstepoort, 0110 South Africa.

Fig 1: The use of LSD vaccine during the period 19841999.

virus. Allerton virus was found to bewidespread in cattle throughout SouthAfrica and its clinical signs were oftenconfused with those of true LSD asdescribed by Thomas and Mare in 194522.Experimental inoculation of cattle withpurified Group III virus proved that thisvirus was the true agent of LSD in cattle asdescribed in Botswana in 194323 and inSouth Africa in 194522.

One of the first purified Group III virusisolates was a South African isolatenamed the Neethling-isolate. The virusbecame officially known throughoutAfrica as lumpy skin disease virus (typeNeethling)1,25, or more simply lumpy skindisease virus (LSDV).

LSDV belongs to the family Poxviridaeand shares the genus Capripoxvirus withsheep pox (type member) and goat poxviruses. All 3 members of the genusCapripoxvirus are antigenically similar,sharing a common precipitating antigen,which permits the use of heterologousvirus for protection. For example, inKenya a sheep pox virus isolate is used forcontrolling LSD in cattle7. Capripoxvirusisolates collected from Africa over a30-year period appear to be geneticallystable on the basis of restriction endo-nuclease digestion analysis of theirDNA16. A similar comparative study ofLSDV (SA-Neethling) field isolatescollected between 1945 and 1959 with theSouth African vaccine strain supportedtheir results24. Only minor differences inthe highly variable terminal regions of thegenomes were observed. There is further-more no evidence of antigenic variationof LSDV field isolates9. A recent studyshowed that the Neethling vaccine straincross-neutralised with LSD field strains(P Hunter and I Louw, unpubl. data, 2000)(See Table 1).

EPIDEMIOLOGY

TransmissionField evidence has indicated the in-

volvement of insect vectors as the main

mode of transmission and the virus wasisolated from 2 species of biting flies,Stomoxys calcitrans and Musca confiscata, inthe 1960s26. Experimental transmission ofthe disease was first achieved using thestable fly S. calcitrans in 198717. Since thestable fly is associated with intensivefarming and is the mechanical transmitterof the protozoal diseases Anaplasmamaginale and Besnoitia besnotii20 in SouthAfrica, it is highly likely that it transmitsLSDV in the field. Other biting insectsmay be involved but no recent researchhas been done on this aspect of the dis-ease in South Africa.

ClimateExtensive epizootics of LSD have been

associated with periods of high rainfalland concomitant high levels of insectactivity22. The disease is reported to occurthroughout mild winters into the follow-ing summers, with a peak of activityduring late summer/autumn. Theseobservations are consistent with the idealrequirements for the rapid increase of theputative insect vector populations.

Southern Africa is subject to the climato-logical phenomenon known as El Nio-Southern Oscillation (ENSO), whichresults in the alternation of periods ofunusually high rainfall with periodsof drought. Abnormally high rainfallperiods have been shown to accompanyan increased incidence of African horse-sickness5, but the relationship of thisdisease to LSD has never been analysed.

Natural host reservoirsGame animals have been proposed as

natural reservoirs of LSDV, but experi-mental infection of impala and giraffe28

caused severe clinical disease resulting indeath, indicating that these species arenot natural, long-term maintenance hostsand may be at risk from the disease underfavourable conditions. However, in thesame study, young buffalo and adultwildebeest (gnu) were also experimen-tally infected, and failed to react clinically

or show a rise in subsequent antibodytitres. Antibodies to LSDV have been de-tected in wild-caught buffalo, although,the incidence was low10. In some reports,low serological prevalence of antibodiesto the virus has been taken as an indica-tion that game are not maintenance hostsof the disease14. As free-living game aregenerally subject to a high degree of selec-tion pressure from both predation anddisease, it has been difficult to elucidatetheir exact role in the epidemiology ofLSD.

It is also not known whether small live-stock play any role in the epidemiology ofthe disease in southern Africa.

CLINICAL DISEASENatural cases of LSD are manifested

initially by lachrymation, fever, loss ofappetite, and disinclination to move. Theskin nodules appear later at roughly 10days after the initial temperature reac-tion, distributed all over the body andaccompanied by swelling of the lymphnodes. Soft yellow-grey nodules andulcers also occur in the mucous mem-branes of the mouth, nose, respiratorytract and the reproductive organs, andsubcutaneous swellings on the legs areoften seen4,22 (Fig. 2). Seven to 10 daysafter their first appearance, the nodulesstart to break away and form scabs, whichultimately fall off. Secondary bacterial in-fection can lead to suppurating ulcers andabscesses. In extreme cases lesions in therespiratory tract may lead to suffocation,or secondary infections may ultimatelylead to the death of the animal.

LSD should be differentiated fromAllerton (herpes) virus infection, whichalso causes skin nodules, so-called false,or pseudo lumpy skin disease. Pseudolumpy skin disease is characterised by aless prominent, flat skin lesion, whichresolves rapidly and is accompanied by amild transient fever3 (Fig. 2).

Experimental infection can be invokedby the subcutaneous, intradermal or in-travenous route. The different routes giverise to varying rates of infection, generali-sation of infection being seen morefrequently with intravenous infections8.

In field and experimental cases, 1050%of animals fail to develop generaliseddisease6,8,21. This is attributed to genetic re-sistance determined by major histo-compatibility complexes (MHC) found onthe cell surfaces of individual animals2. Incattle, these cell surface antigens havebeen shown to be associated with resis-tance to a number of diseases. This mayalso play a role in the response to vaccina-tion (see Vaccination and Immunity).

Resistance to LSD in cattle does notappear to be related to breed since both

0038-2809 Jl S.Afr.vet.Ass. (2001) 72(2): 6871 69

Table 1: Cross-neutralisation of South African LSDV field isolates with the vaccine strainNeethling T61E19.

AntiseraAntigenb Neethling 220/90 50/97 248/93 103/91 58/93

T61E19

Neethling T61E19 120a 40 80 40 20 60220/90c 120 120 80 40 80 80103/91c 120 40 40 80 160 160248/93c 80 80 120 160 160 12058/93c 160 20 160 40 120 24050/97c 30 120 160 60 160 60

aDilutions expressed as reciprocal of titre.bNeutralisation performed using 100 TCID50.cLSDV field isolates.

Bos taurus and B. indicus cattle can exhibiteither severe or mild clinical signs of thedisease. Speculation that the severity ofthe disease is related to different strains ofLSDV has been discounted by research-ers, who suggest that the route of vectorfeeding is a more likely determinant,since experimental intravenous infectioncauses a higher percentage of generalisedinfections8.

Reports of field outbreaks indicate thatvery young calves, lactating and mal-nourished animals develop the mostsevere infections, probably due to im-paired cellular immunity.

ECONOMIC IMPACTAlthough the mortality rate caused by

LSD is usually low, the disease is of majoreconomic importance owing to produc-tion losses27. Dairy cattle are severelyaffected, experiencing a 50% drop in milkproduction, secondary mastitis originat-ing from the development of lesions on

the teats and loss of some quarters of theudders. Cows may abort in the course ofthe disease. General debilitation, loss offertility of bulls and severe damage tohides are other serious sequelae of thedisease12.

VACCINATION AND IMMUNITYIn LSD-endemic areas such as South

Africa, vaccination is the only viablemeans of control. The South Africanvaccine was developed by attenuation ofa field isolate in tissue culture and on thechorioallantoic membranes of embryo-nated hens eggs26. Immunity to LSD ischiefly cell-mediated, but antibodies are auseful measure of response to vaccina-tion15. Antibodies appear 10 days post-vaccination and reaches a peak 30 dayslater. A local response to the vaccine isusually correlated with good antibodyproduction. As with infection with viru-lent wild-type virus, some bovines arerefractory to LSD vaccination, failing to

develop a local reaction or detectablelevels of antibodies. These animals arenevertheless immune when challenged26.A field investigation into the responsive-ness of cattle to successive vaccinationsrevealed that 3/30 cows fail to sero-convert. One of these cows produced acalf that died of LSD at 2 weeks of age,apparently owing to lack of colostral anti-body secretion (H. Aitchison, unpubl.data, 1997). This may account for somereports of vaccine failure in young calvesof vaccinated dams.

The attenuated South African vaccinestrain has been shown to protect againstclinical disease26 but experiences duringthe outbreaks in 1990/91 have challengedthe assertion that immunity to LSD islife-long, and more frequent vaccinationis now recommended15.

Vaccine breakdowns investigated byone of the authors in the last few years arediscussed below: Vaccination of animals already incubating

the disease: this is a common occurrencesince farmers only become aware of thepresence of the disease once skinnodules appear in some animals. By thistime, much of the herd may already beincubating the disease. Vaccination isthen too late to protect these animals.Inadequate needle hygiene can in factspread the disease during the vaccina-tion process, resulting in the diseaseappearing to occur almost simulta-neously in a large number of animals.

Confusion with pseudo lumpy skin diseasecaused by Allerton virus: this herpes virusis also vector transmitted and is preva-lent at the same time of the year as LSD.The shape of the lesions, severity of thedisease and the isolation of virus fromskin biopsy samples can distinguishbetween the 2 conditions.

LSD in calves: vaccinated cows thatdevelop an antibody response will con-fer maternal immunity to LSD by meansof colostrum and this lasts for roughly 6months26. Calves may develop LSD atthis age if they are not vaccinatedtimeously. However, there is evidencethat cows that do not mount a humoralresponse will not be able to protect sus-ceptible calves.Other cases of vaccine failure seen

have been due to the mishandling of thevaccine through exposure to sunlight andhigh temperatures or storage after recon-stitution.

DISCUSSIONAfter an absence of the disease during

the 1960s1990s, there has been a resur-gence of LSD and it has become as wide-spread as it was when it initially reachedepidemic proportions in the 1950s. Since

70 0038-2809 Tydskr.S.Afr.vet.Ver. (2001) 72(2): 6871

Fig. 2: Comparison of skin lesions caused by lumpy skin disease (top) and Allerton (bottom)viruses. Note that skin lesions caused by Allerton virus are more flattened than thosecaused by LSDV, which tend to be more nodular.

0038-2809 Jl S.Afr.vet.Ass. (2001) 72(2): 6871 71

the disease is probably spread by bitingflies, which are unlikely to serve aslong-term maintenance hosts, it is un-known how the disease is maintainedduring interepedemic periods. Certainspecies of game animals might maintainthe virus, but as yet not enough evidenceis available to confirm their involvementin the epidemiology of the disease. It isalso unknown what possible role smalllivestock might play. In South Africa,LSDV has never been isolated in the fieldfrom goats or sheep, although, underlaboratory conditions, the virus is able togrow to high titres in lamb cells.

LSD has spread extensively in SouthAfrica in recent years. Favourable climaticfactors for the reproduction and spread ofprobable insect vectors has been impli-cated. The low level of vaccination duringthe period before the outbreak in 1990/91and in subsequent years was insufficientto prevent spread of the disease, althoughthe transport of infected animals almostcertainly exacerbated the situation. Moreextensive, sustained and timeous use ofvaccine is required to reduce the preva-lence and spread of the disease.

Recent South African field isolatestested in cross-neutralisations with theNeethling vaccine strain indicate thatthere is no lack of protection betweenfield and vaccine strains. Most vaccinefailures investigated were caused by in-frequent or improper use of the vaccine.The failure/inability of some cattle tomount a humoral response to LSDV maycause deaths in young calves due to lackof colostral antibody production.

Research into vectors and epidemiol-ogy of LSD in South Africa is essential forbetter disease control in the country andthe subregion. The excellent molecular re-search tools available for detection ofLSDV in possible vectors and potentialcarrier hosts will facilitate this type ofresearch. Recent work on the biology ofpox viruses may allow the creation ofmore effective LSD vaccine strains whichcould overcome host immune strategiesand maternal antibody interference,which are constraints at present. LSDV is

also a useful vector for the genes of otherorganisms such as bovine ephemeralfever, and this approach may give rise to anew vaccine within the next decade.

ACKNOWLEDGEMENTWe thank the Department of Veterinary

Tropical Diseases of the Faculty of Veteri-nary Science, University of Pretoria, forsupplying the field strains of LSDV for thecross-neutralisation studies.

REFERENCES1. Alexander R A, Plowright W, Haig D A 1957

Cytopathogenic agents associated withlumpy-skin disease of cattle. BulletinEpizootic Diseases of Africa 5: 489492

2. Amills M, Raiya V, Norimine J, Lewin H A1998 The major histocompatibility complexof ruminants. Revue Science et Techniques17(1): 108120

3. Barnard B J H 1994 Pseudo lumpy skin dis-ease/bovine herpes mammilitis. In CoetzerJ A W, Thomson G R, Tustin R C (eds) Infec-tious diseases of livestock with special referenceto southern Africa. Oxford University Press,Cape Town: 942945

4. Barnard B J H, Munz E, Dumbell K,Prozesky L 1994 Lumpy skin disease. InCoetzer J A W, Thomson G R, Tustin R C(eds) Infectious diseases of livestock with specialreference to southern Africa. Oxford Univer-sity Press, Cape Town: 604612

5. Baylis M, Mellor P S, Meiswinkel R 1999Horse sickness and ENSO in South Africa.Nature 397: 574

6. Capstick P B 1959 Lumpy skin disease experimental infection. Bulletin of EpizooticDiseases of Africa 7: 5162

7. Carn V M 1993 Control of capripox infec-tion. Vaccine 11(31): 12751279

8. Carn V M and Kitching R P 1995 The clinicalresponse of cattle experimentally infectedwith lumpy skin disease (Neethling) virus.Archives of Virology 140: 503513

9. Davies F G, Otema C 1981 Relationships ofcapripox viruses found in Kenya with twoMiddle Eastern strains and some orthopoxviruses. Research in Veterinary Science 31:253255

10. Davies, F G, 1991 Lumpy skin disease, anAfrican Capripoxvirus disease of cattle.British Veterinary Journal 147: 489503

11. Diesel A M 1949 The epizootiology oflumpy skin disease in South Africa. Proceed-ings 14th International Veterinary Congress,London 2: 492500

12. Green H F 1959 Lumpy skin disease itseffect on hides and leather and a compari-son in this respect with some other skin

diseases. Bulletin Epizootic Diseases ofAfrica 7: 6374

13. Haig D A 1957 Lumpy skin disease. BulletinEpizootic Diseases of Africa 5: 421430

14. Hedger R S, Hamblin C 1983 Neutralizingantibodies to lumpy skin disease virus inAfrican wildlife. Comparative Immunologyand Microbiology of Infectious Diseases 6(3):209213

15. Kitching R P 1996 Lumpy skin disease. InManual of standards for diagnostic tests andvaccines (3rd edn). Office International despizooties, Paris, France

16. Kitching R P, Bhat P P and Black D N 1989The characterization of African strains ofCapripoxvirus. Epidemiology and Infection102: 335343

17. Mellor P M, Kitching R P, Wilkinson P J 1987Mechanical transmission of Capripox virusand African swine fever virus by Stomoxyscalcitrans. Research in Veterinary Science 43:109112.

18. Morris J P A 1931 Pseudourticaria. Depart-ment Animal Health Report, NorthernRhodesia

19. Munz E K, Owen N C 1966 Electron micro-scopic studies on lumpy skin disease virustype Neethling. Onderstepoort Journal ofVeterinary Research 33: 38

20. Nevill E M 1997 Vectors: Muscidae. InCoetzer J A W, Thomson G R, Tustin R C(eds) Infectious diseases of livestock with specialreference to southern Africa. Oxford Univer-sity Press, Cape Town: 5361.

21. Perlman L J 1993 Molecular characteriza-tion of the lumpy skin disease virusgenome. MSc thesis. University of CapeTown

22. Thomas A D, Mare C v E 1945 Knopvel-siekte. Journal of South African VeterinaryMedical Association 16: 3643

23. Von Backstrom U 1945 Ngamiland cattledisease: preliminary report on a new dis-ease, the etiological agent being probably ofan infectious nature. Journal of South AfricanVeterinary Medical Association 16: 2935

24. Wallace D B 1994 Genomic characterizationof southern African isolates of Capripoxand Avipox viruses. MSc thesis, Universityof Cape Town

25. Weiss K E 1963 Lumpy skin disease. InEmerging Diseases of Animals, FAO Agricul-tural Studies 61: 179201

26. Weiss K E 1968 Lumpy skin disease. VirologyMonographs 3: 112282.

27. Woods J A 1988 Lumpy skin disease a re-view. Tropical Animal Health and Production20: 1117

28. Young E, Basson P A, Weiss K E 1970 Experi-mental infection of giraffe, impala, andCape buffalo with lumpy skin disease virus.Onderstepoort Journal of Veterinary Research37: 7988