Heartwater is a rickettsial disease of ruminants in sub-Saharan Africa and the Caribbean that is transmitted by Amblyomma ticks. Endothelial cell infection leads to loss of vascular integrity, resulting in body cavity effusions and edema in the CNS. The disease is characterized by fever, respiratory distress, neurological abnormalities, and sudden death. Diagnosis is best confirmed by PCR assay. Early treatment with oxytetracycline can be effective. Vaccine research is ongoing, but no effective vaccination strategy currently exists; prevention is based on control of the tick vector.
Heartwater is an infectious, noncontagious, tickborne rickettsial disease of ruminants. It occurs only in areas infested by ticks of the genus Amblyomma, including regions of sub-Saharan countries and the islands of Madagascar and Réunion, as well as the Caribbean, where it has been formally detected in Guadeloupe and Antigua. In the Caribbean, heartwater is transmitted by Amblyomma variegatum, and possible transmission to the mainland threatens the production animal industry of regions from northern South America to Central America and the southern US.
In endemic areas of southern Africa, the mortality rate due to heartwater can be as much as 90% in susceptible ruminants.
All domestic ruminants (cattle, sheep, and goats) and wild ruminants (deer, springbok, giraffes) are susceptible to heartwater, and European species (Bos taurus) are generally more susceptible than indigenous African breeds (Bos indicus). Wild animals seem susceptible to infection and play a reservoir role in the disease.
Heartwater is a notifiable disease listed by the World Organisation for Animal Health (WOAH).
Etiology and Transmission of Heartwater
The organism that causes heartwater is an obligate intracellular bacterium, previously known as Cowdria ruminantium. Molecular evidence led to reclassification of several organisms in the order Rickettsiales, and it is now classified as Ehrlichia ruminantium.
Under natural conditions, E ruminantium is transmitted by Amblyomma tick species. Amblyomma variegatum is the most important heartwater vector, with a worldwide distribution. Amblyomma hebraeum is also a good vector, present in South Africa. Other Amblyomma spp threaten the mainland US with heartwater introduction.
The ticks that host E ruminantium become infected during either the larval or nymphal stage and transmit the infection during one of the subsequent stages (trans-stadial transmission). Because transovarial transmission is not common among the ticks, the overall infection rate within the tick population remains relatively low.
Immunity to heartwater appears to be chiefly, if not exclusively, cell mediated, because spleen cells from an immune donor inoculated into susceptible recipients protect them, whereas serum from an immune donor fails to protect recipients when challenged. There is no, or only partial, cross-protection between different strains of E ruminantium.
Pathogenesis of Heartwater
The pathogenesis of heartwater has not been fully elucidated. The organism probably infects the host from the tick's saliva while the tick is feeding. Studies are under way to elucidate the bacterial cycle of E ruminantium in ticks and the mechanisms of transmission to susceptible hosts.
Once in the host, E ruminantium can first replicate within the regional lymph nodes and then be disseminated via the bloodstream to invade endothelial cells of blood vessels elsewhere in the body. In domestic ruminants, endothelial cells of the brain appear to be the predilection site.
E ruminantium can often be found in colonies (commonly but mistakenly referred to as morulas) within the cytoplasm of endothelial cells. Colonies can vary in size, as can the individuals that reside in them. Generally, small individuals are found in larger colonies, and vice versa. The smaller individuals, usually referred to as "elementary bodies," are the infective stage; the larger individuals, called "reticulated bodies," are the proliferative stage.
During the febrile stage of heartwater infection, and for a short time after, the blood of infected animals is infective to susceptible animals. Clinical signs and lesions are associated with functional injury to the vascular endothelium, resulting in increased vascular permeability without recognizable histological or even ultrastructural pathological changes. The concomitant fluid effusion into tissues and body cavities precipitates a decrease in arterial pressure and general circulatory failure.
The lesions in peracute and acute cases of heartwater are hydrothorax, hydropericardium, edema and congestion of the lungs and brain, splenomegaly, petechiae and ecchymoses on mucosal and serosal surfaces, and occasionally hemorrhage into the GI tract, particularly the abomasum. The typically straw-colored effusions are high in large-molecular-weight proteins, including fibrinogen; hence, this fluid readily clots on exposure to air. The amount of effusion, particularly in body cavities, is not necessarily proportional to the number of parasitic colonies detected in endothelial cells.
Clinical Findings of Heartwater
The clinical signs of heartwater are dramatic in the peracute and acute forms. In peracute cases, animals can die within a few hours after developing a fever, and sometimes animals die without any apparent clinical signs. Some affected animals display exaggerated respiratory distress or paroxysmal seizures. In the acute form, animals often show anorexia and listlessness, along with congested and friable mucous membranes.
Courtesy of Dr. Tony Shakespeare.
Courtesy of Dr. Tony Shakespeare.
Courtesy of Dr. Tony Shakespeare.
Courtesy of Dr. Tony Shakespeare.
Courtesy of Dr. Tony Shakespeare.
Courtesy of Dr. Tony Shakespeare.
Courtesy of Dr. Tony Shakespeare.
Courtesy of Dr. Tony Shakespeare.
Respiratory distress with heartwater slowly develops along with neurological signs such as hyperesthesia, a high-stepping gait, exaggerated blinking, and chewing movements. Terminally, prostration with bouts of opisthotonos; pedaling, thrashing, or stiffening of the limbs; and seizures occur (see videos). Diarrhea occurs occasionally. In subacute cases of heartwater, the clinical signs are less marked and CNS involvement is inconsistent.
Diagnosis of Heartwater
Clinical signs
PCR assay
Histological evaluation
Serological testing
Heartwater must be differentiated from a wide range of infectious and noninfectious diseases, especially plant toxicoses, that manifest with CNS signs. In acute cases in endemic areas, clinical signs alone may suggest the diagnosis; for a definitive diagnosis, however, the presence of causative bacteria circulating in the blood must be demonstrated by molecular tools.
The presence of E ruminantium colonies in the cytoplasm of capillary endothelial cells is also proof of heartwater; however, it is difficult to demonstrate. Historically, this presence was demonstrated with squash smears of cerebral or cerebellar gray matter stained with Romanowsky-type stains (see endothelial cell image).
Courtesy of Dr. A. S. Shakespeare.
Molecular identification of E ruminantium is the most powerful tool to identify the pathogen. The pCS20 quantitative real-time PCR assay is now well optimized and documented, and it allows the detection of the heartwater pathogen in the blood of clinically affected animals, in the organs of dead animals, and in ticks. It is fast, sensitive, specific, and suitable for high-throughput tests.
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Serological tests for heartwater are also available; however, they should be considered only at the herd level for epidemiological or retrospective studies. There are several such tests (based on MAP1 proteins), varying in specificity and sensibility. Some pan-species ELISAs can also be used for epidemiological studies.
Treatment, Control, and Prevention of Heartwater
Antimicrobials
Vaccination
Tick control
Heartwater can be treated with antimicrobials; however, they are effective only if administered at the onset of clinical signs. It is sometimes suggested to treat the entire herd if clinical cases occur in several animals.
Oxytetracycline (10–20 mg/kg, IV slowly or IM, every 24 hours for a minimum of 3 days or until fever abates) is usually curative if administered early in the course of heartwater infection. The higher dosage of oxytetracycline (20 mg/kg, IV slowly) can be successful if initiated late during the febrile reaction or when clinical signs are evident.
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A minimum of three daily doses of oxytetracycline should be administered in heartwater cases even if the patient's temperature normalizes; if fever persists, oxytetracycline treatment should continue for fourth and fifth days. If the fever still does not abate, a trimethoprim-sulfonamide (15 mg/kg, IM, every 24 hours) can be successful; however, the use of sulfonamides is prohibited in lactating dairy cattle in the US. Local regulations regarding the withdrawal times for milk and meat after treatment with short- or long-acting oxytetracycline, or with sulfonamides, must be obeyed.
Corticosteroids have been administered as supportive care (prednisolone, 1 mg/kg, IM) for heartwater; the effectiveness and rationale for their use are debated.
Diazepam (0.2–0.5 mg/kg, IV; or 0.5–1 mg/kg, IM, repeated every 10 minutes for up to 3 doses) may be required to control seizures. Affected animals must be kept quiet in a cool area with soft bedding and must be completely undisturbed; any stimulation can trigger seizures and subsequent death.
Vaccination should help with the control of heartwater; however, several strategies have been tested, and none have yet proved satisfactory. Inactivated or recombinant vaccines with various adjuvants provide only homologous or relative protection. Attenuated vaccines sometimes offer low heterologous protection, but not enough to be accepted by breeders.
The infection-treatment method (injection of a dose of live bacteria, followed by treatment before the onset of clinical signs) can produce some immunity to heartwater; however, it is difficult to apply in the field and very expensive on a large scale. The major challenge is the high genomic plasticity and regional variability of E ruminantium.
Studies are under way to develop and evaluate new heartwater vaccine strategies. These strategies will probably take into account the geographical area, with surveillance and strain typing tools for the production of rapidly available "regional" vaccines.
Because heartwater is transmitted by ticks, one of the most effective preventive methods remains regular treatment of animals with acaricides.
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Key Points
Heartwater is an acute, fatal, noncontagious, tick-borne rickettsial infection of ruminants, occurring in sub-Saharan Africa and the Caribbean.
The disease is characterized by a sudden fever, neurological signs, and a high mortality rate, especially in small ruminants.
Diagnosis is based on the presence of the infected vector or molecular identification of the pathogen.
There is no effective vaccine against heartwater; control is based on preventing infestation by the Amblyomma tick vector.
For More Information
World Organisation for Animal Health (WOAH). Heartwater. Terrestrial Manual. 2018;chap 3.1.9.
Marcelino I, Holzmuller P, Stachurski F, et al. Ehrlichia ruminantium, the causal agent of heartwater. In: Thomas S, ed. Rickettsiales: Biology, Molecular Biology, Epidemiology, and Vaccine Development. Springer; 2016:241-280.
Meyer DF, Moumène A, Rodrigues V. Microbe profile: Ehrlichia ruminantium—stealthy as it goes. Microbiology. 2023;169(11). doi:10.1099/mic.0.001415
