Definition
Congenital arthrogryposis-hydranencephaly (A-H) syndrome is an
infectious disease of the bovine, caprine, and ovine fetus caused by intrauterine
infection and interference with fetal development after transmission to the dam by biting
gnat- or mosquito-transmitted Akabane virus and some other antigenically related members
of the Simbu group of arboviruses (1,7). Fetal infection may cause abortions, stillbirths,
premature births, mummified fetuses, and various dysfunctions or deformities of fetuses or
liveborn neonates. Adult animals are not clinically affected while actively infected with
virus (17).
Etiology
The etiologic agents of congenital A-H syndrome are arboviruses of
the Simbu group of the family Bunyaviridae. Akabane virus was the first member of the
Simbu group to be incriminated in congenital A-H syndrome, but other members (namely Aino,
Peaton, and Tinaroo viruses) have the capacity to produce fetal defects (3,10,13,18). In
recent years, Cache Valley virus, a mosquito-borne member of the Bunyaviridae outside the
Simbu group, has been found to reproduce a similar syndrome in ruminants within the United
States (2). The Simbu group of viruses are spread only by insect vectors. Spread by
contact, infected tissues, exudates, or fomites does not occur.
Host Range
Congenital A-H syndrome associated with Akabane virus and other
Simbu group viruses has been reported only in cattle, sheep, and goats. Although antibody
against these viruses has been detected in horses, no clinical evidence of fetal infection
has been reported. Infections of wild ruminants do occur, and fetal damage must be
considered but has not been reported.
Geographic Distribution
In Japan, the periodic outbreaks of AH syndrome have been reported
since 1949. Enzootic Akabane virus (and presumably other Simbu group virus) activity has
occurred in the northern half of Australia since at least 1931 with occasional temporary
epizootic incursions southward dependent on favorable seasons (18). Reports of A-H
syndrome in Israel (8) and other countries in the Middle East, Cyprus (8,18,19), Korea,
Zimbabwe, and South Africa have been published in the last decade. Serological surveys
indicate that the virus occurs throughout Africa, Asia, and Australia but not Papua New
Guinea, the Pacific Islands, or the Americas.
Transmission
The occurrence of A-H syndrome is seasonally and geographically
restricted. The location and timing of the infection of the fetus during early pregnancy
is consistent with the seasonality of transmission by hematophagous insects. Akabane virus
has been isolated from Aedes vexans and Culex triteeniorhynchus mosquitoes
in Japan; Anopheles funestus mosquitoes in Kenya; Culicoides milnei and C.
imicola in Africa; C. oxystoma in Japan; and C. brevitarsis and C.
wadei gnats in Australia (3,13,17,18). Confirmation of the biologic transmission by
these species is lacking; however, epidemiologic evidence incriminates them. In Australia, C. brevitarsis is believed to be the principal vector of Akabane virus. Cache
Valley virus has been isolated from at least nine different mosquito species, and
antibodies to this virus have been detected in man, as well as wild and domestic animals
in the Americas.
There is no indication that Akabane virus, other Simbu group
viruses or Cache Valley virus is transmitted in any other way than by a vector.
Transmission happens months before disease in the fetus is evident.
Incubation Period
Infection of adult animals produces no overt clinical sign, but
viremia generally occurs 1-6 days after infection. A natural viremia may last 4 to 6 days
before antibodies to Akabane virus are detectable (17). However, infection of pregnant
animals during the first months of gestation may result in fetal infection that is not
apparent until much later in pregnancy or at term (6).
Timing of the infection relative to the stage of gestation is
critical to the development of defects in the fetus. In pregnant sheep, the gestational
period for the occurrence of fetal abnormalities has been shown to vary from 30-36 days to
30-50 days (6,14,15). This variation in the reported results has been ascribed to (a)
differences in the virulence of virus strains used, (b) differences in the passage level
of the virus strain used, or (c) differences caused after growth of the virus in the
arthropod vectors. Inoculation of pregnant cattle with virus between 62 and 96 days of
gestation resulted in fetal lesions; in pregnant goats, the critical period in the
gestational cycle was about 40 days (10,12).
Clinical Signs
Congenital A-H syndrome is manifested as a seasonally sporadic
epizootic of abortions, stillbirths, premature births, and deformed or anomalous bovine,
caprine, and ovine fetuses or neonates. The pregnant dam has no clinical manifestation at
the time of infection with virus. Sentinel cattle under close observation have no clinical
sign during viremia induced by natural infection. If infection develops during the first
third of pregnancy, gross fetal damage may occur. At the other end of the disease
spectrum, damage to the central nervous system (CNS) may be minor and produce changes in
behavior of the new born or young animal. Dystocia at parturition may occur owing to the
deformities in the fetus. Badly deformed fetuses are usually dead at birth, and the limbs
are locked in the flexed or extended position. Most live neonates have central nervous
system degeneration and muscle lesions that prevent the animal from standing or suckling.
Torticollis, scoliosis, brachygnathism, and kyphosis may coexist with arthrogryposis.
Lesions in the central nervous system are manifested clinically as blindness, nystagmus,
deafness, dullness, slow suckling, paralysis, and incoordination.
Mildly affected calves or lambs may improve their mobility with
time. However, most eventually die by 6 months as a result of blindness and other
neurological defects (5,7,10,12,14,15,17).
Gross Lesions
An individual fetus or newborn may have arthrogryposis and
hydranecephaly or both syndromes. Lesions are associated with damage to the enervation of
the musculature and to the central nervous system. Arthrogryposis is the most frequently
observed lesion. Affected joints cannot be straightened even by application of force
because of ankylosis of the joint in the extended or flexed position (Fig. 23). Torticollis, scoliosis, and brachygnathism are
observed. There may be shallow erosions about the external nares and muzzle and between
the distal digits. Hypoplasia of the lungs and skeletal muscles, fibrinous polyarticular
synovitis, fibrinous navel infection, ophthalmia, cataracts, and presternal steatosis
occur. Within the CNS, hydranencephaly (Fig. 24),
hydrocephalus, agenesis of the brain, microencephaly, porencephaly and cerebellar
cavitation, fibrinous leptomeningitis, fibrinous ependymitis, and agenesis or hypoplasia
of the spinal cord are variously reported (5, 16, 20). The cerebellum appears intact.
Lesions due to Akabane tend to be symmetrical. However, some asymmetry occurs when Aino
virus is involved. Akabane virus was isolated from fetuses of naturally infected pregnant
cows or ewes by the use of predictive serology. When the mothers seroconverted from
negative to positive in Akabane virus neutralization tests, Akabane virus was isolated
from the fetus (4,11).
Morbidity and Mortality
In endemic areas, animals are exposed and become immune before
becoming pregnant; thus, congenital abnormalities are seldom seen in native animals, for
antibodies prevent virus from spreading from the site of the bite to the fetus. However,
when the infected vector spreads (e.g., during an extended humid summer) to an area where
the animals are not immune, A-H syndrome can occur months later in many animals. The
disease can also appear when pregnant animals from a disease-free area are moved into an
endemic area.
There is no reported damage to the dam in congenital A-H syndrome.
Most live-born affected calves, lambs, or kids die shortly after birth or must be
slaughtered for humane reasons. Some mildly affected calves do improve gait and learn to
follow the herd.
Diagnosis
Field Diagnosis
A field diagnosis of congenital A-H syndrome can be made on the
basis of the clinical condition, gross pathologic lesions, and the epidemiology. The
sudden onset of aborted, mummified, premature, or stillborn fetuses with arthrogryposis
and hydranencephaly should be suggestive. The dam will have had no clinical history of
disease. A retrospective study would indicate that the first third of pregnancy occurred
during a time of biting insect activity.
Specimens for Laboratory
The following specimens should collected for virus isolation:
placenta, fetal muscle, cerebrospinal fluid, and fetal nervous tissue; for serology: fetal
or precolostral serum, and serum from the dam. For histopatholgy send pieces of spleen,
liver, lung, kidney, heart, lymph nodes, affected muscle, spinal cord and brain in 10
percent buffered formalin.
If the specimens can be delivered to a laboratory within 24 hours,
they should be placed on ice. If delivery will take longer, quickfreeze the specimens and
do not allow them to thaw during transit
Laboratory Diagnosis
Virus isolation should be attempted from placenta, fetal muscle,
or fetal nervous tissue. The chances of success are very low except with a fetus and
placenta aborted before antibodies are generated within an immunocompetent fetus. In the
absence of viral isolations, a serologic diagnosis is usually made by demonstrating
antibodies in precolostral or fetal serum samples. In adult animals, seroconversion or a
demonstrable rise in antibody titer indicates that there was infection. A microtiter
neutralization test and an immunofluorescence test are available for detecting and
assaying antibodies (18). Tissues of the dam are free of virus by the time the damage is
observed in the fetus or newborn. Low titers (<10) in unpaired serum samples should not
be taken as diagnostic because of cross-reaction problems.
Differential Diagnosis
The demonstration that Cache Valley virus, a Bunyavirus that is
ubiquitous within the United States, can cause the A-H syndrome means that serological
tests are essential to distinguish exotic from enzootic etiologies (2). It is a reasonable
assumption that other Bunyaviridae will be proven to be teratogenic in livestock in the
Americas. A variety of nutritional, genetic, toxic, and infectious diseases will produce
fetal wastage and deformities. Fetal brain lesions resulting from bluetongue vaccine virus
infections of pregnant ewes are similar to those produced within the congenital A-H
syndrome. Bluetongue presents the greatest difficulty in the initial differential
diagnosis of hydranencephaly. Bovine virus diarrhea infection can cause cerebellar
dysplasia in calves. Border disease virus infection can cause undersized, excessively
hairy lambs with muscular tremors and skeletal defects. Wesselsbron virus infection can
cause congenital porencephaly and cerebral hypoplasia in calves. Serology of the dam and
fetus will resolve any confusion.
Vaccination
A formalin-inactivated, aluminum phosphate, gel-absorbed vaccine
and an attenuated vaccine have been developed in Japan for Akabane virus. An effective
killed vaccine for Akabane virus has been developed but not marketed in Australia (7,9).
These vaccines induce immunity in the cow or ewe, and the circulating antibodies prevent
the virus from reaching the fetus. The vaccines are used prior to exposure to infected
vectors. Vaccine is no longer available for economic reasons. Immunizing agents for other
Simbu group viruses are not currently available and are not expected to be developed.
Control and Eradication
Techniques for the control of the viral agents that cause
congenital A-H syndrome are those typically recommended for other vector-transmitted
agents. Control of the vector depends upon disruption of breeding sites, reduction of
vector populations with pesticides, and protection of host animals from feeding by the
vectors. In addition to these procedures, animals should be vaccinated before breeding.
Public Health
There is no evidence that humans can be infected by Akabane virus.
GUIDE TO THE LITERATURE
1. COVERDALE, O. R., CYBINSKI, D. H., and ST. GEORGE, T. D. 1979.
A study of the involvement of three Simbu group arboviruses in bovine congenital
arthrogryposis and hydranencephaly in the New England area of New South Wales. Proc. 2d
Symp. Arbovirus Res. Austral., 2:130-139.
2. CHUNG, S. I., LIVINGSTON, C. W., EDWARDS, J. F., GAUER, B. B.,
and COLLISSON, E. W. 1990. Congenital malformations in sheep resulting from in utero
inoculation of Cache Valley virus. Am. J. Vet. Res., 51:1645-1648.
3. CYBINSKI, D. H., and MULLER, M. J. 1990. Isolation of
arboviruses from cattle and insects at two sentinel sites in Queensland, Australia,
1979-85. Aust. J. Zool., 38:25-32.
4. DELLA-PORTA, A. J., O'HALLORAN, M. L., PARSONSON, M., SNOWDON,
W. A., MURRAY, M. D., HARTLEY, W. J.. and HAUGHEY, K. J. 1977. Akabane disease: Isolation
of the virus from naturally infected ovine foetuses. Austral. Vet. J., 53:51-52.
5. HARTLEY, W. J., de SARAM, W. G., DELLA-PORTA, A. J., SNOWDON,
W. A., and SHEPHERD, N. C. 1977. Pathology of congenital bovine epizootic arthrogryposis
and hydranencephaly and its relationship to Akabane virus. Austral. Vet. J.. 53:319-325.
6. HASHINGUCHI, Y., NANBA, K., and KUMAGAI, T. 1979. Congenital
abnormalities in newborn lambs following Akabane virus infection in pregnant ewes. Natl.
Inst. Anim. Hlth. Q. (Tokyo), 19:1-11.
7. INABA, Y., and MATUMOTO, M. 1981. Congenital
Arthrogryposis-Hydranencephaly Syndrome, in Virus Diseases of Food Animals. Vol. II:
Disease Monographs, E. P. J. Gibbs, ed. San Francisco: Academic Press, pp. 653-671.
8. KALMAR, E., PELEG, B. A., and SAVIR, D. 1975.
Arthrogryposis-hydranencephaly syndrome in newborn cattle, sheep and goats -Serological
survey for antibodies against the Akabane virus. Refuah Vet., 32:47-54.
9. KIRKLAND, P. D., and BARRY, R. D. 1986. The economic impact of
Akabane virus and the cost effectiveness of vaccination in New South Wales. Proc. 4th
Symp. Arbovirus Res. Austral., 4:229-232.
10. KUROGI, H., INABA, Y., TAKAHASHI, E., SATO, K., GOTO, Y., and
OMORI, T. 1977. Experimental infection of pregnant goats with Akabane virus. Nat. Inst.
Anim. Hlth Q. (Tokyo), 16:1-9.
11. KUROGI, H., INABA, Y., TAKAHASHI, E., SATO, K., OMORI, T.,
MIURA, T., GOTO, Y., FUJIWARA, Y., HATANO, Y., KODAMA, K., FUKUYAMA, S., SASAKI, N., and
MATUMOTO, M. 1976. Epizootic congenital arthrogryposis-hydranencephaly syndrome in cattle:
Isolation of Akabane virus from affected fetuses. Arch. Virol., 51:5674.
12. KUROGI, H., INABA, Y., TAKAHASHI, E., SATO, K., SATODA, K.,
GOTO, Y., OMORI, T., and MATUMOTO, M. 1977. Congenital abnormalities in newborn calves
after inoculation of pregnant cows with Akabane virus. Infect. Immun., 17:338-343.
13. McPHEE, D. A., PARSONSON, I. M., and DELLA-PORTA, A. J. 1982.
Development of a chicken embryo model for testing the teratogenic potential of Australian
bunyaviruses. Proc. 3d Symp. Arbovirus Res. Austral., 3:127-134.
14. PARSONSON, I.M., DELLA-PORTA, A. J., and SNOWDON, W.A. 1977.
Congenital abnormalities in newborhn lambs after infection of pregnant sheep with Akabane
virus. Infect. Immun., 15:254-262.
15. PARSONSON, I.M., DELLA-PORTA, A. J., and SNOWDON, W.A. 1981.
Developmental disorders of the fetus in some arthropod-borne virus infections. Am. J.
Trop. Med. Hyg., 30:660-673.
16. PARSONSON, I.M., DELLA-PORTA, A. J., and SNOWDON, W.A. 1981.
Akabane virus infection in the pregnant ewe. 2. Pathology of the foetus. Vet. Microbiol.,
6:209-224.
17. ST. GEORGE, T.D., STANDFAST, H.A., and CYBINSKI, D.H. 1978.
Isolations of Akabane virus from sentinel cattle and Culicoides brevitarsis. Austral. Vet.
J., 54:558-561.
18. ST. GEORGE, T.D., and STANDFAST, H.A. 1989. Simbu Group
Viruses with Teratogenic Potential, in The Arboviruses: Epidemiology and Ecology
lV, T.P. Monath, ed. Boca Raton, Fl.: CRC Press, pp. 145-166.
19. SELLERS, R.F., and HERNIMAN, K.J. 1981. Neutralizing
antibodies to Akabane virus in ruminants in Cyprus. Trop. Anim. Hlth. Prod., 13: 57-60.
20. WHITTEM, J. H. 1957. Congenital abnormalities in calves:
arthrogryposis and hydranencephaly. J. Pathol. Bacteriol., 73:375-387.
T. D. St. George, D.V.Sc., 15 Tamarix St., Chapel Hill, Queensland
4069, Australia
|