heartwater

Preferred Scientific Name

• heartwater

International Common Names

• English: cowdriosis; heartwater, cowdria ruminantium, cowdriosis, in ruminants- exotic; heartwater, ehrlichia ruminantium, in ruminants- exotic
• French: cowdriose

Local Common Names

• Guadeloupe: Mal cadik
• Mali: tiéoudé
• Nigeria: kaboa
• South Africa: dronkgalsiekte; hartwater; nintas

Ehrlichia ruminantium

Heartwater (or cowdriosis) is a tickborne disease of sheep, goats, cattle and some wild ruminants caused by the rickettsia, Ehrlichia ruminantium (previously Cowdria ruminantium). It is a small pleomorphic organism (0.2-2.7 µm) and colonies named morula containing varying numbers are found in the cytoplasm of endothelial cells (Cowdry, 1926; Pienaar, 1970).

According to Neitz (1968), the first record of heartwater was probably made in South Africa by the Voortrekker pioneer, Louis Trichard in 1838. In an entry in his diary on the 9th March 1838 he mentions a fatal disease, ‘nintas’, amongst his sheep, approximately 3 weeks after a massive tick infestation. However, it was only in 1876, almost 50 years later, that the first official report describing heartwater as a generally known disease along the coast and borders of King William’s Town, was presented before the Cattle and Sheep Disease Commission in Grahamstown, South Africa. According to Webb (1877), the disease was introduced into the eastern Cape region at about the same time that William Bowker found a bont tick (Amblyomma hebraeum) on a cow which was imported from northern KwaZulu-Natal (then Zululand) in approximately 1837. Due to confusion with other prevalent conditions of unknown aetiologies at that time, it is difficult to follow the introduction and spread of the disease in Africa. It is, for instance, still not clear whether heartwater is a disease indigenous to the African continent or whether it was imported at some stage, possibly from Madagascar. However, current knowledge suggests that it is a disease of the African mainland. Despite the fact that certain Amblyomma species occur on the Asian and American continents, there is no evidence that the disease exists there.

The first major breakthrough in understanding the disease came when Dixon (1898) and Edington (1898) proved that it could be produced experimentally by inoculating blood from diseased to susceptible animals. Although the causative organism could not be demonstrated in the blood or tissue of diseased animals at the time, it was believed that heartwater was caused by a microorganism (Hutcheon, 1900), possibly a virus (Spreull, 1904). At about the same time Lounsbury (1900) confirmed the long-standing suspicion that the bont tick (A. hebraeum) was the vector in South Africa. However, it was not until 1925 that Cowdry (Cowdry, 1925a; Cowdry, 1925b) successfully demonstrated the organism in tissue of infected animals and ticks. Cowdry named the organism Rickettsia ruminantium but this was later changed to Cowdria ruminantium (Moshkovski, 1947) and finally to E. ruminantium (Dumler et al., 2001).

Traditional rickettsial taxonomy assigned Cowdria ruminantium as the sole member of the genus Cowdria in the tribe Ehrlichieae. This was one of three tribes within the family Rickettsiaceae in the order Rickettsiales which initially encompassed all intracellular bacteria but from which the Chlamydiae were later removed (Moulders, 1984). The obligate intracellular nature of E. ruminantium, coupled with morphological features suggestive of a Chlamydia-like life cycle led to confusion as to its position in the ehrlichial hierarchy (Uilenberg, 1983). In 2001, Dumler et al. defined after 16S ribosomal DNA and groESL gene comparisons that all members of the tribes Ehrlichieae and Wolbachieae had to be transferred to the family Anaplasmataceae and that the family Rickettsiaceae had to be eliminated. In Anaplasmataceae, four genera are present Anaplasma, Ehrlichia, Wolbachia and Neorickettsia. The genus Ehrlichia now includes E. ruminantium (formerly Cowdria ruminantium) but no longer Anaplasma bovis, phagocytophila, and HGE (belonging now to genus Anaplasma) and the genus neorickettsia (including Ehrlichia sennetsu and Ehrlichia risticii). In this reorganization, E. ruminantium is closer to E. chaffeensis, ewingii, muris, ovis and canis.  

 

Economic impact and prevalence

Heartwater is one of the main tickborne diseases together with theileriosis and trypanosomosis in tropical countries. For the Southern Africa Development Community (Angola, Botswana, Malawi, Mozambique, South Africa, Swaziland, Tanzania and Zimbabwe) the losses are estimated around 47.6 millions of dollars per year. Important losses are due to mortality, diminution of productivity in farming systems and cost of treatment (use of antibiotics and acaricides). It is a major, and in some instances, the most important obstacle against introducing high producing animals into Africa with the aim of upgrading or replacing local stock (Uilenberg, 1982a). It is a major disease problem when local animals are, usually for the sake of grazing, moved from heartwater-free to heartwater-infected areas (Neitz, 1967). It remains a problem and a threat in endemic areas especially amongst small stock (Thomas and Mansvelt, 1957). The effect of dipping and environmental changes influences endemic stability, which is often difficult or impossible to manipulate (Bezuidenhout and Bigalke, 1987).

The development of molecular diagnostic tools allows a better estimation of the prevalence of heartwater thanks to detection both in organs from suspected dead ruminants and in ticks. In Burkina Faso, the E. ruminantium prevalence in ticks by pCS20 nested PCR has been evaluated from 3 to 10% depending on the year of tick samplings (Dr Hassane Adakal, personal communication, Adakal et al., 2010b).  Moreover, a study evaluating the efficiency of the inactivated vaccine in field conditions in Burkina Faso allowed identifying the impact of heartwater on susceptible ruminants. In this study, two successive trial assays on susceptible imported sahelian sheep demonstrated that 51% and 53% of unvaccinated sheep died from heartwater (Adakal et al., 2010a). In the Gambia, the seroprevalence rate per site in small ruminants varied from 6.9% and 100% (5 regions) (Faburay et al., 2005). The percentage of E. ruminantium infected Amblyomma ticks collected on 15 different sites, varied strongly from 1.6 to 15.1% depending on the site of sampling (Faburay et al., 2007a). These results showed a gradient risk of increasing heartwater from the East to the West of the Gambia. In Nigeria a study done in 2011 on 7 sites in the south of Nigeria shows a 9.6% of E. ruminantium tick prevalence (Personal communications, Dr Maxwell Opara). In the Caribbean region, only Guadeloupe and Antigua are infected with heartwater. In Guadeloupe, the E. ruminantium tick prevalence is higher (i.e. 19.1% in Marie Galante with 73.8% of herds infested) compared to Antigua 5.8% of E.ruminantium infected ticks with only 2.2% of herds infested (Vachiéry et al., 2008b). These islands still represent a reservoir for ticks and heartwater in the Caribbean. It is a threat to areas such as the American mainland due to migratory birds potentially carrying infected ticks from the Caribbean area where the disease is present. Moreover, potential vectors are present but do not harbour the disease (Uilenberg, 1982b; Uilenberg et al., 1984). It is also a threat to countries where the vectors may be introduced and become established (Wilson and Richard, 1984; Barré et al., 1987).

It will therefore probably remain a disease of major importance until an effective and safe vaccine becomes available.

This disease is on the list of diseases notifiable to the World Organisation for Animal Health (OIE). The distribution section contains data from OIE's WAHID database on disease occurrence. For further information on this disease from OIE, see the website: www.oie.int

blood and circulatory system diseases of large ruminants
blood and circulatory system diseases of small ruminants
nervous system diseases of large ruminants
nervous system diseases of small ruminants
respiratory diseases of large ruminants
respiratory diseases of small ruminants

Macroscopic pathology

Lesions in cattle, sheep and goats are similar, although quite variable in extent and some changes are commoner in certain species than in others. Effusion of body cavities, (hydropericardium, hydrothorax, and, in some cases a degree of ascitis) is a very common change in most fatal cases of heartwater. The transudate is usually transparent or slightly turbid, light yellow fluid that often coagulates on exposure to air. The volume of fluid ranges from 20 ml in goats, about 0.5 litre in sheep to several litres in cattle (Steck, 1928). A hydropericardium, as indicated by the name ‘heartwater’ is a striking change in most animals that die of the disease and is usually more pronounced in sheep and goats than in cattle (Henning, 1956).

Oedema of the lungs is a regular finding and appears to be more severe in most animals that die peracutely from the disease (Pypekamp and Prozesky, 1987). The interlobular septa of the lungs, mediastinum and associated lymph nodes are oedematous and serous frothy fluid oozes from the cut surface of the lung. The trachea and bronchi often contain serofibrinous exudates, and their mucosae are congested, with petechiae and ecchymoses.

Splenomegaly is present although less strikingly in sheep and goats. The cut surface is dark red in colour and has a pulpy consistency. In animals that die peracutely it is often impossible to make a diagnosis on macroscopical lesions alone; splenomegaly, epi- and endocardial haemorrhages are sometimes the only significant changes (Alexander, 1931). Hepatic lesions are less striking with only a mild hepatomegaly present and the gallbladder slightly distended.

Congestion and/or oedema of the mucosa of the abomasum are regularly seen in cattle, but are less common in sheep and goats. Enterorrhagia (small and large intestine) is present in a small percentage of domestic ruminants, particularly Jersey cattle.

The lymph nodes are moderately swollen in most animals. The cut surface is moist and petechiae are often present, especially in the retropharyngeal, submaxillary, cervical, bronchial and mediastinal lymph nodes (Alexander, 1931). Petechiae are frequently visible on mucous membranes of tissues including those of the urinary bladder, vagina, epi- and endocardium and conjunctiva.

The nervous symptoms observed in affected animals are usually attributed to oedema of the brain, although it is often difficult and sometimes impossible to detect swelling of the brain macroscopically. Occasionally, the entire brain, but particularly the gyri of the cerebellum may be strikingly swollen and severe oedema of the brain may even result in a partial prolapse (herniation) of the cerebellum through the foramen magnum. Most animals that die of heartwater show congestion and oedema of the meninges. There is an accumulation of excessive fluid in the subarachnoid space and thickening of the choroids plexus, which has a dull greyish appearance. In some animals petechiae and ecchymoses and sometimes sugillations are evident in the midbrain, brain stem and cerebellum (Pienaar et al., 1966).

Histopathology

Comprehensive studies on the histopathological changes of heartwater were made by Steck (1928), Alexander (1931) and Pienaar et al. (1966).

Lungs: An alveolar and interstitial oedema occurs in most animals but is not always discernible histopathologically.

Kidneys: Nephrosis of varying degree, is a common change in domestic ruminants that die of heartwater. The observations of (Steck, 1928) of a multifocal lymphocytic interstitial nephritis occurring in cattle, sheep and goats could not be confirmed in subsequent studies (Uilenberg, 1983).

Variable numbers of E. ruminantium colonies are discernable in the cytoplasm of endothelial cells, particularly those of the brain and lungs. Cowdry (1926) and Steck (1928) frequently also observed colonies in the endothelial cells of glomerular capillaries. As a general rule, however, these colonies are difficult to find in haematoxylin- and eosin-stained sections.

Brain: Lesions in the brain of cattle, sheep and goats were described by (Pienaar et al., 1966) and are characterized by changes compatible with oedema, such as widened perivascular spaces which sometimes contain oedematous fluid or protein droplets; swollen, often necrotic, astrocytes; swollen axons, and multifocal microcavitations and haemorrhages affecting mainly the midbrain, brain stem, cerebral white matter and cerebral peduncles. A perivascular accumulation of cells, mainly macrophages and a few neutrophils, and occasionally a vasculitis were observed in all the bovines and in only about 50% of the sheep. A diffuse meningitis, mainly macrophages, was present in a few bovines only. In the majority of animals a fibrinuous chorioditis occurred and occasionally mutifocal glial nodules, mainly confined to the neutrophil around small blood vessels, were apparent in sheep and cattle. Brain lesions in recumbent animals often comprise different degrees of status spongiosus and in severe cases the white matter of the entire brain may be affected.

Other organs: in most animals that die of heartwater the hepatic changes are inconspicuous; the lymph nodes are congested and oedematous; and congestion is the only splenic change.

Several species of game are susceptible to heartwater, but reports on the pathological changes in game that died of heartwater are limited and in most cases lesions are very similar to that described in domestic animals (Young and Basson, 1973; Prozesky, 1987).

Transmission electron microscopical studies of the lung lesions in sheep and goats reveal the presence of minor cytopathic changes in endothelial cells. Apart from mild swelling of mitochondria and endoplasmic reticulum, no other changes occur in most parasitized alveolar endothelial cells. Non-parasitized endothelial cells are sometimes swollen, or even necrotic, and are separated from their basement membranes. Oedema of blood vessel walls is infrequently seen (Prozesky and Plessis, 1985a; Prozesky and Plessis, 1985b).

In all suspected cases a diagnosis of heartwater must be confirmed by the demonstration of Ehrlichia organisms in Giemsa-stained preparations made from the hippocampus.

The pathogenesis of the disease is still poorly understood, but the following hypotheses have been proposed.

After infection of the host with E. ruminantium, initial replication of the organisms appears to take place in reticuloendothelial cells and macrophages in the regional lymph nodes. From here the organisms are disseminated via the blood stream to invade endothelial cells of blood vessels of various organs where further multiplication occurs (Plessis, 1970). Endothelial cell parasitization coincides with the onset of fever. There is an increased vascular permeability allowing the seepage of plasma proteins which result in transudation through the serous membranes with resultant tissue oedema (Brown and Skowronek, 1990) and effusion into body cavities. This causes the drastic fall in blood volume before death (Clark, 1962). Oedema of the brain is responsible for the nervous signs, hydropericardium contributes to cardiac dysfunction during the terminal stages of the disease and progressive pulmonary oedema and hydrothorax result in asphyxiation (Uilenberg, 1971; Owen et al., 1973). Amstel et al. (1988a, b) found normal arterial carbon dioxide tension in calves with experimentally induced heartwater, with a tendency towards alkalosis, an increased pulmonary dead space and fluctuations in venous admixture. In the terminal stages of the disease there was a marked decrease in stroke volume and cardiac output.

The pathogenesis of vascular permeability remains speculative as the intracytoplasmic development of the organisms seems to have little detectable cytopathic effect upon the endothelial cells (Pienaar, 1970), and there is also no apparent correlation between the number of parasitized cells in the pulmonary blood vessels and the severity of the pulmonary oedema (Prozesky and Plessis, 1985a; Jackson and Neitz, 1932). It has been proposed that an endotoxin (Amstel et al., 1988a) and increased cerebrospinal fluid pressure (Brown and Skowronek, 1990) play a role in the development of lung oedema.

The course of the disease can vary from a peracute form marked by sudden death with little or no clinical signs, to a chronic form, characterized by a transitory fever, followed by natural recovery. Small ruminants (sheep and goats, particularly Angora goats) appear to be most susceptible. A similar course, to a varying degree, is also seen in cattle.

In general the prognosis is especially poor for imported or exotic cattle and small ruminants. Peracute and acute forms are usually fatal. Few ruminants survive once nervous symptoms have appeared. Case mortalities vary from 5% to virtually 100% depending on the strain of E. ruminantium involved, the locality, season and host breed.

Factors relating to the tick vector, causative organism, and vertebrate host are important in the epidemiology of heartwater. These include possible immunological strain differences of E. ruminantium, availability of wild animal reservoir hosts or vectors for the organisms, infection rate in ticks, age and genetic resistance of domestic ruminant populations, seasonal changes influencing tick abundance and activity, and the intensity of tick control (Uilenberg, 1983).

Although there is a lack of information on the development of E. ruminantium there is some evidence that the parasite undergoes a sequential development in both the vertebrate and invertebrate hosts (Plessis, 1982; Kocan et al., 1987a). The organism replicates mainly by binary fission, and possibly by endosporulation (Pienaar, 1970). It appears that the reticulate bodies are predominately proliferative, while the elementary bodies represent the infective stage (Jongejan et al., 1990). Transmission electron microscope studies of in vitro-cultivated organisms demonstrated the presence of intracellular reticulate bodies 2 to 4 days after infection and intermediate bodies 4 to 5 days after infection. Large numbers of elementary bodies are seen after rupture of endothelial cells 5 to 6 days after infection (Jongejan et al., 1990 and 1991).

The host Amblyomma spp. ticks become infected during the larval and nymphal stages when they feed on infected domestic and wild ruminants, and possibly also on certain game birds and reptiles while E. ruminantium is circulating in the blood of these hosts. Nymphae and adult ticks transmit E. ruminantium to susceptible hosts without losing the infection. Intrastadial transmission has been demonstrated (Andrew and Norval, 1989), but transovarial transmission has only been reported once under laboratory conditions and probably does not occur in nature (Bezuidenhout and Jacobsz, 1986). The development cycle of the organism in the tick and the infectivity of successive stages of the tick are poorly understood. It is thought that after an infected blood meal, initial replication of the organism takes place in the intestinal epithelium of the tick and that the salivary glands eventually become parasitized (Kocan et al., 1987b). Transmission of the parasite to the vertebrate host probably takes place either by regurgitation of their gut contents or through the saliva of the tick while feeding. The minimum period required for transmission of the parasite after tick attachment is between 27-38 hours in nymphs and 21-75 h in adults (Bezuidenhout, 1988).

The main vectors of heartwater are Amblyomma variegatum and A. hebraeum, although a number of other Amblyomma spp. have been shown experimentally to be able to transmit the organism. A. maculatum, occurring in the USA is also capable of transmitting the disease (Uilenberg, 1982b). Not all are equally good vectors, and their importance in the transmission of heartwater depends not only on their vector competence, but also on their distribution and association with domestic stock (Uilenberg, 1983). Furthermore, the activity and abundance of the ticks is influenced by temperature and humidity (Petney et al., 1987). Ticks can acquire the infection from the host from about the time of the febrile reaction for up to 361 days, or even longer (Andrew and Norval, 1989) and probably retain their infectivity for life (Neitz, 1968; Ilemobade, 1976). Infection rates in ticks vary, from 0-44.9% for males, 20-36.1% for females and 0-13.4% for nymphs, depending on the season and the locality in which they are collected (Plessis, 1985; Plessis and Malan, 1987b; Norval et al., 1990).

The existence of antigenically different stocks of E. ruminantium with varying virulence has been demonstrated. There is also variable cross-protection between these different varieties (Jongejan et al., 1988; Plessis et al., 1989). The introduction of animals which are immune to a particular variant of E. ruminantium into an endemic area where a different variety occurs may therefore result in cases of heartwater.

Various factors such as species, breed, age, degree of natural resistance and immune status play a role in determining whether asymptomatic or overt disease will develop in a susceptible host after infection. Young calves, lambs and kids possess a non-specific resistance which is independent of the immune status of the dam and is of short duration: the first 4-6 weeks of life in calves and only the first week in lambs and kids (Neitz and Alexander, 1941; Alexander et al., 1946; Uilenberg, 1981; Plessis et al., 1987). The susceptibilities of different breeds of cattle and sheep vary. Some sheep breeds, such as the Blackhead Persian, possess a certain degree of natural resistance (Alexander, 1931; Uilenberg, 1983). Angora goats are highly susceptible to heartwater and their immunity is of short duration (Plessis et al., 1983). Genetic resistance, which is due to a recessive sex-linked gene, has been demonstrated in Creole goats in Guadeloupe (Matheron et al., 1987).

Wild ruminants such as the blesbok (Damaliscus dorcas phillipsi) and black wildebeest, as well as helmeted guinea fowl, leopard tortoise (Geochelone pardalis) and scrub hare have been shown to harbour E. ruminantium subclinically for long periods and may therefore play a role as source of infection for ticks (Petney and Horak, 1988).

Most authorities regard heartwater in southern Africa as an economically important disease. Uilenberg (1983) ranked it second only to East Coast fever and tsetse-transmitted trypanosomosis. Neitz (1968) stated that in endemic areas, mortalities due to heartwater were three times as great as those due to babesiosis and anaplasmosis. However, there have been no definitive studies designed to quantify this importance. Recently, under the auspices of the UF/USAID/SADC heartwater research project, a study was undertaken to evaluate the economic impact of heartwater in Zimbabwe. The total annual losses were estimated at US $5.6 million (Mukhebi et al., 1999). Annual economic losses per animal in the commercial production system in Zimbabwe were 25 times greater than losses in the communal system. The greatest components of economic loss were acaricide costs (76%), followed by milk loss (18%) and treatment cost (5%). However, no other reliable figures are available on the economic impact of heartwater in the region.

The fact that E. ruminantium can be grown in human endothelial cells (Totté et al., 1993) has led to speculation that cowdriosis might be a zoonosis. But to date, no evidence from the field supports this (Kelly et al., 1992).

Drug Treatment

A variety of drugs have been used with varying success against E. ruminantium (Amstel and Oberem, 1987). Treatment of heartwater during the early febrile stages presents very few problems and recovery can be expected when either sulphonamides or tetracyclines are used at generally accepted dose rates. Tetracyclines are nowadays recognized as more effective than sulfonamides. The successful treatment of field cases of heartwater remains a problem because of the advanced stage of the disease in which the animal is usually presented and because of ineffective supportive therapy. Drugs active in reducing oedema (Shakespeare et al., 1998), stabilization of membranes and blocking effect of vasoactive compounds released with cellular death could be considered (Amstel and Oberem, 1987).

Chemoprophylaxis

This is a procedure by which a series of tetracycline injections is used to protect susceptible animals against heartwater when they are introduced into an endemic area (Purnell, 1987). In goats it is advocated that short-acting tetracyclines be administered at a dosage rate of 3 mg/kg body weight on 10, 20, 30, 45 and 60 days after introduction, but that the animals should not be dipped until after 60 days (Gruss, 1981). Similarly, injections of long-acting tetracycline formulations (10-20 mg/kg body weight) given on days 7, 14 and 21, or even on only two occasions (days 7 and 14) in cattle are sufficient to protect them from contracting heartwater, while at the same time allowing them to develop a natural immunity (Purnell, 1987). The success of this regime is dependent on all the animals becoming naturally infected with heartwater during the time that they are protected by the drug. With fluctuating infection rates in ticks under different ecological conditions this approach may fail.