Definition
African horsesickness (AHS) is a highly fatal, viscerotropic,
insect-borne viral disease of horses and mules and generally a subclinical disease in
other Equidae. The clinical signs and lesions result from selective increased vascular
permeability and are characterized by an impairment of the respiratory and circulatory
systems.
Etiology
The etiological agent of AHS is a typical orbivirus measuring
68-70 nm in diameter, and the virion is composed of a double-layered protein shell.
The virus is present in the blood and certain organs such as
spleen, lung, and lymph nodes in reasonably high concentration, whereas only traces are
found in serum, tissue fluids, excretions, and secretions (10). Viremia generally lasts
for about 4-8 days and roughly parallels the febrile reaction. In exceptional cases,
viremia may last as long as 17 days in the horse and 28 days in zebra and donkeys.
The AHS virus is relatively heat stable, particularly in the
presence of protein. It can be stored for at least 6 months at 4° C in saline containing
10 percent serum. Blood in OCG preservative (500 ml glycerin, 500 ml distilled water, 5 g
sodium oxalate, and 5 g carbolic acid) can remain infective for more than 20 years;
lyophilization may preserve infectivity for as long as 40 years. The virus is readily
inactivated at pH values lower than 6.3, but it is relatively stable between values
ranging from 6.5 to 8.5.
Nine distinct serotypes of AHS virus are known, the last of which
was isolated in 1960. This suggests that, despite its segmented genome, the virus can be
regarded as genetically stable and that new serotypes do not readily develop. The present
nine serotypes probably evolved over many centuries.
Host Range
Horses, mules, and donkeys have historically been known as hosts
for AHS virus, as reflected in the name of the disease. In view of the high mortality rate
suffered by horses and mules, these species should be regarded as accidental or indicator
hosts. That AHS failed to establish itself outside the tropical regions of Africa tends to
indicate that neither horses nor mules or donkeys remain long-term carriers of AHS virus
and are therefore not essential for the permanent persistence of the infection in a
particular region. Zebra may fulfill this role, but no irrevocable proof has been found to
substantiate this view.
The dog has long been known to be susceptible to experimental
infection (23). Infection of dogs also readily occurs following ingestion of infected
horse meat (3). However, it is extremely unlikely that this species becomes infected by
insect bites, and it is generally accepted that dogs play no role in the spread or
maintenance of AHS (16).
Camels can ostensibly become inapparently infected with AHS virus,
but few details are available as to the level and duration of viremia in this species and
its role, if any, in the epizootiology of the disease. A high percentage of African
elephant serum samples reacted positively against AHS virus in complement fixation tests
(7), but no neutralizing antibodies could be demonstrated in such samples. No evidence of
virus replication could be found in elephants artificially infected with AHS virus (12).
It can therefore be concluded that the African elephant is not susceptible to infection
and that the putative serological evidence resulted from abnormal reactions of elephant
sera in a complement fixation test.
Geographic Distribution
African horse sickness appears to be endemic in tropical regions
of central Africa from where it regularly spreads southwards to southern Africa. The
Sahara Desert forms a formidable barrier against northward spread. Occasionally the
infection does reach northern African countries, either by spread along the Nile valley or
along the West Coast of Africa. The disease has also occurred outside Africa on a few
occasions, the most notable of which was the major outbreak in the Near and Middle East
from 1959 through 63 and in Spain (1966 and 1987-1990) (15).
In temperate regions such as South Africa, AHS has a definite
seasonal occurrence. The first cases are usually noticed towards midsummer, and the
disease disappears abruptly after the onset of cold weather in autumn. The disease is most
prevalent in warm, low-lying moist areas such as valleys and marshes.
Transmission
African horse sickness is a noncontagious disease, and the virus
was the first shown to be transmitted by midges (Culicoides spp.) (9). The most
significant vector seems to be Culicoides imicola, but other species, such as C.
variipennis, which is common in many parts of the United States, should also be
considered as potential vectors (4).
The virus is transmitted biologically by midges, and these insects
are most active just after sunset and at about sunrise.
Although other insects such as mosquitoes have been implicated as
biological vectors, and large biting flies (e.g., Stomoxys, Tabanus) may
transmit AHS virus mechanically, the role of these insects in the epizootiology of the
disease is regarded as absolutely minimal compared with that played by the Culicoides species.
Generally, midges disperse only a few kilometers from their
breeding sites, but it has been postulated that they can be borne for longer distances on
air currents (21). Analysis of field observations on the progression of outbreaks
indicates that wind-borne spread of midges may assist the short-distance spread of the
disease but that long-distance jumps of the infection are invariably the result of
movement of infected Equidae.
Incubation Period
In experimentally induced cases the incubation period usually
varies between 5 and 7 days, but it may be as short as 2 days and rarely as long as 14
days. Circumstantial evidence indicates that, following natural infection, the incubation
period varies from 7 to 14 days.
Clinical Signs
Four clinical forms of AHS can be distinguished (10).
The Peracute or Pulmonary Form
This form is characterized by very marked and rapidly progressive
respiratory involvement. An acute febrile reaction may be the only clinical sign for a day
or two, reaching a maximum of about 104-106° F (40-41° C). This is followed by various
degrees of respiratory distress. The breathing may increase to 60 or even 75 respirations
per minute, and the animal tends to stand with its forelegs spread apart, its head
extended, and the nostrils fully dilated. Expiration is frequently forced with the abdomen
showing heave lines. Profuse sweating is common, and spasmodic coughing may be observed
terminally with frothy, serofibrinous fluid exuding from the nostrils (Fig. 3). The onset of dyspnea is usually very sudden, and death
often occurs within 30 minutes to a few hours after its appearance.
The Subacute Edematous or Cardiac Form
The incubation period of this form varies between 7 and 14 days,
and the onset of the clinical disease is marked by a febrile reaction of 102-106° F
(39-41° C) that lasts for 3-6 days. Shortly before the decline of the fever,
characteristic edematous swellings appear. These initially involve the supraorbital fossae
and the eyelids (Figs. 4, 5, and 6) and later extend to the lips, cheeks, tongue,
intermandibular space, and laryngeal region. Subcutaneous edema sometimes extends a
variable distance down the neck towards the chest, often obliterating the jugular groove.
Interestingly, no edema of the lower limbs is observed. Terminally, petechial hemorrhages
develop in the conjunctivae and under the ventral surface of the tongue. The animal
becomes very depressed and may lie down frequently but for very short periods only.
Occasionally, signs of colic may develop. Finally, the animal remains prostrate and dies
from cardiac failure about 4-8 days after the onset of the febrile reaction. In cases that
recover, swellings gradually subside within a period of 3-8 days.
The Acute or Mixed Form
This form represents a mixture of the pulmonary and cardiac forms.
Although seldom diagnosed clinically, it is seen at necropsy in the majority of fatal
cases of AHS in horses and mules. The disease manifests itself in various ways. Initial
pulmonary signs of a mild nature that do not progress are followed by edematous swellings
and effusions, and death results from cardiac failure. In the majority of cases, however,
the subclinical cardiac form is suddenly followed by marked dyspnea and other signs
typical of the pulmonary form.
Horsesickness Fever
This is the mildest form and is frequently overlooked in natural
outbreaks. The febrile reaction is usually of the remittent type, with morning remissions
and afternoon exacerbation, and lasts for 3-8 days but rarely exceeds 104° F (40° C).
Apart from the febrile reaction, other clinical signs are rare and inconspicuous. The
conjunctivae may be slightly congested, the pulse rate may be increased, and a certain
degree of anorexia and depression may be present. This form of the disease is usually
observed in donkeys and zebra or in immune horses infected with a heterologous serotype of
AHS virus.
Gross Lesions
The lesions observed at necropsy examination depend largely on the
clinical form of disease manifested by the animal before death (10). In the peracute form
the most characteristic changes are edema of the lungs or hydrothorax (Figs. 7 and 8).
In very peracute cases, extensive alveolar edema and mottled hyperemia of the lungs are
seen, whereas in cases with a somewhat more protracted course extensive interstitial and
subpleural edema is also present, but hyperemia is less evident. Occasionally the lungs
may appear reasonably normal, but the thoracic cavity may contain as much as 8 L of fluid.
Other less commonly observed lesions are periaortic and peritracheal edematous
infiltration, diffuse or patchy hyperemia of the glandular fundus of the stomach,
hyperemia and petechial hemorrhages in the mucosa and serosa of the small and large
intestines (Fig. 9 and 10), subcapsular hemorrhages in the spleen, and congestion
of the renal cortex. Most of the lymph nodes are enlarged and edematous, especially those
in the thoracic and abdominal cavities. Cardiac lesions are usually not conspicuous, but
epicardial and endocardial petechial hemorrhages are sometimes evident.
In the cardiac form the prominent lesion is a yellow gelatinous
infiltration in the subcutaneous and intermuscular fascia primarily of the head, neck, and
shoulders (Fig. 11). Occasionally the
lesion may also involve the brisket, ventral abdomen and rump. Hydropericardium (Fig. 12) is a common feature, and there
are extensive petechial and ecchymotic hemorrhages on the epicardium and endocardium,
particularly of the left ventricle. The lungs are usually normal or only slightly
engorged, and the thoracic cavity rarely contains excess fluid. The lesions in the
gastrointestinal tract are generally similar to those found in the pulmonary form, except
that submucosal edema of the cecum, large colon, and rectum tends to be far more
pronounced.
In the mixed form the lesions seem to represent a combination of
those found in the pulmonary and cardiac forms.
Morbidity and Mortality
In susceptible horse populations, the fatalities range between 70
and 95 percent, and the prognosis is extremely poor. In mules, the mortality rate is about
50 percent and in the European and Asian donkey about 5-10 percent. No mortality is
observed among African donkeys and zebra.
In enzootic regions, the mortality rate is modified in proportion
to the immunity acquired by the equine population as a result of previous vaccination or
exposure to natural infection.
Diagnosis
Field Diagnosis
During the early febrile phase of AHS, a field diagnosis may be
virtually impossible. However, a presumptive diagnosis should be possible once the
characteristic clinical signs have developed and, more particularly, at necropsy.
Specimens for the Laboratory
Confirmation of a presumptive diagnosis is based on virus
isolation and identification. This is of particular importance whenever outbreaks occur
outside the enzootic regions. The AHS virus can be isolated quite readily from blood
collected during the early febrile phase (preferably in heparin or else in other
anticoagulants) as well as from spleen, lung, and lymph nodes collected at necropsy (10).
Specimens for virus isolation should be shipped to the laboratory
refrigerated, NOT FROZEN.
Horses that survive infection develop specific antibodies within
10-14 days after infection that reach a peak about 10 days later. It is always advisable
to use paired (acute and convalescent phase) serum samples. Serological tests can
demonstrate AHS antibodies for 1 to 4 years after infection.
Differential Diagnosis
The clinical signs of AHS, particularly when not fully developed,
may be confused with other infections, notably equine encephalosis and equine viral
arteritis (EVA). The former disease occurs under the same epizootiological conditions as
AHS, and in South Africa the two diseases frequently occur simultaneously. Horses
suffering from equine encephalosis usually do not have characteristic lung edema or
subcutaneous edema, and the mortality rate is considerably lower than in AHS.
Severe cases of EVA may readily be confused with AHS. The presence
of ventral edema (in EVA), particularly of the lower limbs, and the much lower mortality
rate should allow differentiation. In countries where piroplasmosis occurs, the early
stage of this disease, before blood parasites can be demonstrated and anemia develops, may
be confused with AHS.
The necropsy lesions of AHS can be confused with those found in
cases of purpura hemorrhagica. In the latter condition, the hemorrhages and edema seem to
be more severe and widely distributed than in AHS and usually involve the limbs and lower
abdomen. The highly sporadic occurrence of purpura also aids in differentiation.
Vaccination
The work of Alexander and de Toit (1,2) has resulted in the
development of a live attenuated vaccine that has been used successfully for several
decades. However, the adaptation of the virus to the brains of adult mice resulted in a
neurotropic vaccine that occasionally caused encephalitis in horses mules and particularly
in donkeys (20). This necessitated an alternate and safer method of attenuation achieved
by plaque selection in Vero cell cultures (11). The vaccine currently used in South Africa
consists of two quadrivalent vaccines that are administered 3 weeks apart. Strategic
reserves of monovalent vaccines are also maintained.
Extensive work is presently under way to develop potent
inactivated and recombinant vaccines that should widen the choice in the near future.
Control and Eradication
Preventive Measures
The most important means of introducing AHS into a hitherto
disease free country is by the introduction of equid animals incubating the disease. Zebra
and African donkeys that do not develop any clinical sign of disease are particularly
dangerous. Equid animals imported from infected countries should be quarantined in
insect-proof facilities at the point of entry. At present, there is a minimum 60-day
quarantine period for horses brought into the United States from Asia, Africa, and the
Mediterranean countries.
Once the disease is introduced into a country, several preventive
measures should be taken to prevent further spread and eventually to eradicate the scourge
in the shortest possible time. It is essential to isolate and identify the causal virus,
but it is imperative that control measures be implemented even before the final diagnosis
has been made.
Officials should delineate area of control, taking into
consideration geographical borders such as mountains and rivers. The movement of all equid
animal within, into, and out of the control zone should be stopped and this restriction
rigidly enforced. Furthermore, all equid animals should be stabled, at least from dusk to
dawn, and sprayed with insect repellents to reduce the risk of insects feeding on the
animals. If sufficient stabling facilities are not available, barns could be used. Even if
not insect-proof, such housing will reduce the risk of infection. Additionally, the rectal
temperatures of all equid animals in the zone should be taken regularly (preferably twice
daily) to detect infected animals as early as possible because overt disease is generally
preceded by viremia for about 3 days. Animals with fever should be killed or housed in
insect-free stables until the cause of the fever has been established.
Once the diagnosis has been finalized, vaccination of all
susceptible animals with the relevant monovalent AHS vaccine should be considered. This
decision will be guided largely by the success of measures already taken.
Natural Immunity
Animals that recover from the disease develop a solid life-long
immunity against the infecting virus and a partial immunity against heterologous
serotypes. Foals from immune dams have a passive immunity that may protect them for up to
6 months.
Public Health
There is no evidence that man can become infected with field
strains of AHS virus, either through contact with infected animals or from working in
laboratories. However, it has been shown that certain neurotropic vaccine strains may
cause encephalitis and retinitis in humans following transnasal infection (22).
GUIDE TO THE LITERATURE
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2. ALEXANDER, R.A., and DU TOIT, P.J. 1934. The immunization of
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Baltus J. Erasmus, B.V.Sc., Onderstepoort, Veterinary Institute,
P. O. Onderstepoort, Republic of South Africa
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