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heartwater

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Datasheet

heartwater

Summary

  • Last modified
  • 21 June 2022
  • Datasheet Type(s)
  • Animal Disease
  • Preferred Scientific Name
  • heartwater
  • Overview
  • 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) a...

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Pictures

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PictureTitleCaptionCopyright
A bovine with cowdriosis in lateral recumbancy with extended legs
TitleSymptoms
CaptionA bovine with cowdriosis in lateral recumbancy with extended legs
Copyright©Onderstepoort Journal of Veterinary Research. With permission of the editor.
A bovine with cowdriosis in lateral recumbancy with extended legs
SymptomsA bovine with cowdriosis in lateral recumbancy with extended legs©Onderstepoort Journal of Veterinary Research. With permission of the editor.
Hydrothorax in a sheep with cowdriosis.
TitlePathology
CaptionHydrothorax in a sheep with cowdriosis.
Copyright©Onderstepoort Journal of Veterinary Research. With permission of the editor.
Hydrothorax in a sheep with cowdriosis.
PathologyHydrothorax in a sheep with cowdriosis.©Onderstepoort Journal of Veterinary Research. With permission of the editor.
Hydropericardium in a sheep with cowdriosis.
TitlePathology
CaptionHydropericardium in a sheep with cowdriosis.
Copyright©Onderstepoort Journal of Veterinary Research. With permission of the editor.
Hydropericardium in a sheep with cowdriosis.
PathologyHydropericardium in a sheep with cowdriosis.©Onderstepoort Journal of Veterinary Research. With permission of the editor.
Petechiae are visible on the conjunctiva of a bovine with cowdriosis.
TitlePathology
CaptionPetechiae are visible on the conjunctiva of a bovine with cowdriosis.
Copyright©Onderstepoort Journal of Veterinary Research. With permission of the editor.
Petechiae are visible on the conjunctiva of a bovine with cowdriosis.
PathologyPetechiae are visible on the conjunctiva of a bovine with cowdriosis.©Onderstepoort Journal of Veterinary Research. With permission of the editor.
Cowdria ruminantium (heartwater) organisms in a Giemsa-stained brain smear (original x3000).
TitleHistology
CaptionCowdria ruminantium (heartwater) organisms in a Giemsa-stained brain smear (original x3000).
Copyright©Onderstepoort Journal of Veterinary Research. With permission of the editor.
Cowdria ruminantium (heartwater) organisms in a Giemsa-stained brain smear (original x3000).
HistologyCowdria ruminantium (heartwater) organisms in a Giemsa-stained brain smear (original x3000).©Onderstepoort Journal of Veterinary Research. With permission of the editor.
Cow with signs of a central nervous system disturbance.
TitleSymptoms
CaptionCow with signs of a central nervous system disturbance.
Copyright©USDA-2002/Foreign Animal Diseases Training Set/USDA-Animal and Plant Health Inspection Service (APHIS)
Cow with signs of a central nervous system disturbance.
SymptomsCow with signs of a central nervous system disturbance.©USDA-2002/Foreign Animal Diseases Training Set/USDA-Animal and Plant Health Inspection Service (APHIS)
Hydopericardium.
TitlePathology
CaptionHydopericardium.
Copyright©USDA-2002/Foreign Animal Diseases Training Set/USDA-Animal and Plant Health Inspection Service (APHIS)
Hydopericardium.
PathologyHydopericardium.©USDA-2002/Foreign Animal Diseases Training Set/USDA-Animal and Plant Health Inspection Service (APHIS)
Brain smear from a goat. Colonies of Cowdria ruminantium are the granular blue areas in the cytoplasm of the capillary endothelial cells.
TitleHistology
CaptionBrain smear from a goat. Colonies of Cowdria ruminantium are the granular blue areas in the cytoplasm of the capillary endothelial cells.
Copyright©USDA-2002/Foreign Animal Diseases Training Set/USDA-Animal and Plant Health Inspection Service (APHIS)
Brain smear from a goat. Colonies of Cowdria ruminantium are the granular blue areas in the cytoplasm of the capillary endothelial cells.
HistologyBrain smear from a goat. Colonies of Cowdria ruminantium are the granular blue areas in the cytoplasm of the capillary endothelial cells.©USDA-2002/Foreign Animal Diseases Training Set/USDA-Animal and Plant Health Inspection Service (APHIS)
Excessive fluid in the thoracic cavity and pulmonary oedema; note the distended interlobular septa.
TitlePathology
CaptionExcessive fluid in the thoracic cavity and pulmonary oedema; note the distended interlobular septa.
Copyright©USDA-2002/Foreign Animal Diseases Training Set/USDA-Animal and Plant Health Inspection Service (APHIS)
Excessive fluid in the thoracic cavity and pulmonary oedema; note the distended interlobular septa.
PathologyExcessive fluid in the thoracic cavity and pulmonary oedema; note the distended interlobular septa.©USDA-2002/Foreign Animal Diseases Training Set/USDA-Animal and Plant Health Inspection Service (APHIS)
Deer with signs of a central nervous system disturbance.
TitleSymptoms
CaptionDeer with signs of a central nervous system disturbance.
Copyright©USDA-2002/Foreign Animal Diseases Training Set/USDA-Animal and Plant Health Inspection Service (APHIS)
Deer with signs of a central nervous system disturbance.
SymptomsDeer with signs of a central nervous system disturbance.©USDA-2002/Foreign Animal Diseases Training Set/USDA-Animal and Plant Health Inspection Service (APHIS)

Identity

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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

Overview

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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 of 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 detected in the blood or tissue of diseased animals at the time, it was believed that heartwater was caused by a micro-organism (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). After 16S ribosomal RNA and groESL gene comparisons, Dumler et al. (2001) defined that all members of the tribes Ehrlichieae and Wolbachieae should be transferred to the family Anaplasmataceae and the genus Ehrlichia was emended to include Ehrlichia ruminantium (formerly Cowdria ruminantium). The family Anaplasmataceae currently includes Ehrlichia, Anaplasma, Aegyptianella, Neorickettsia, Wolbachia, ‘Candidatus Neoehrlichia’ and ‘Candidatus Xenohaliotis’ (Thomas et al., 2016).

Phylum: Proteobacteria

Class: Alphaproteobacteria

Order: Rickettsiales

Family: Anaplasmataceae

Genus: Ehrlichia

Species: Ehrlichia ruminantium

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 moved from heartwater-free to heartwater endemic 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 nested PCR (pCS20 gene region) has been evaluated from 3% to 10% depending on the year of tick samplings (Dr Hassane Adakal, personal communication; Adakal et al., 2010a). 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., 2010b). In The Gambia, the seroprevalence rate per site in small ruminants varied from 6.9% and 100% (five 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 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., 2008a). 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). In South Africa, heartwater is not a notifiable disease, therefore there is no detailed up to date data on the prevalence or economic impact, but it does have a noticeable impact on the economy. It will 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 Organization 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

Host Animals

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Animal nameContextLife stageSystem
Aepyceros melampusWild host
Ammotragus lervia (aoudad)Domesticated hostAll Stages
Antidorcas marsupialisWild host
Axis axis (Indian spotted deer)Experimental settings; Wild host
Bos indicus (zebu)Domesticated hostAll Stages
Bos taurus (cattle)Domesticated hostAll Stages
Boselaphus tragocamelusWild host
Bubalus bubalis (Asian water buffalo)Wild hostAll Stages
Capra hircus (goats)Domesticated hostAll Stages
Cervus damaExperimental settings; Wild host
Cervus timorensisExperimental settings; Wild host
Connochaetes gnouWild host
Connochaetes taurinusWild host
Damaliscus albifronsWild host
Diceros bicornisWild host
Geochelone pardalisExperimental settings
Giraffa camelopardalisWild host
Hemitragus jemlahicusWild host
Kobus ellipsiprymnusWild host
Lepus saxatilisExperimental settings
Loxodonta africanaExperimental settings
Mastomys couchaWild host
NumidaExperimental settings
Odocoileus virginianusExperimental settings; Wild host
Ovis aries (sheep)Domesticated hostAll Stages
Ovis orientalisDomesticated hostAll Stages
Rhabdomys pumilioExperimental settings; Wild host
Syncerus cafferWild hostAll Stages
Tragelaphus oryxWild host
Tragelaphus spekiiWild host
Tragelaphus strepsicerosWild host

Hosts/Species Affected

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All the domestic representatives of the family Bovidae are susceptible to clinical disease. The susceptibility of the different breeds of domestic ruminants, however, varies, Bos indicus [zebu] and Nguni (in South Africa) breeds being generally more resistant than European breeds (Bonsma, 1981; Uilenberg, 1983). The resistance of the local indigenous zebu breeds in Africa is probably inherited as a result of natural selection. Asian buffalo, Bubalus bubalis, are also susceptible to heartwater. Although sheep are more susceptible to heartwater than cattle, there is also a variation between breeds and the Blackheaded Persian possesses a certain degree of natural resistance (Uilenberg, 1983). The most sensitive species to heartwater is the goat, especially the Angora goats in South Africa (Latif et al., 2020). Wild ruminants including Cervidae, Bovidae and Giraffidae are also susceptible to E. ruminantium infection.

The South African buffalo, bleskbok, black wildebeest, helmeted guinea fowl, leopard tortoise and scrub hare are known to harbour E. ruminantium subclinically and constitute a tick-pathogen reservoir. Of all the indigenous African wild ruminant species, only the eland, blesbok, springbok and black wildebeest have been reported to develop clinical disease (Oberem and Bezuidenhout, 1987).

A knowledge of the susceptibility of wild ruminants to heartwater is important where farmers re-introduce ruminant game species into heartwater endemic areas. Wild ruminants also play a role as sources of infection for ticks, particularly in endemic areas where stringent tick control in domestic animals is practiced.

Laboratory mice are also susceptible to E. ruminantium, however, the pathogenicity of the different strains of Ehrlichia to mice varies significantly (MacKenzie and McHardy, 1987). Ball3 and Welgevonden strains are pathogenic for mice. The multimammate mouse (Mastomys coucha) (MacKenzie and McHardy, 1987) and the striped mouse (Rhabdomys pumilio) (Hudson and Henderson, 1941) are also susceptible to infection, but as wild rodents do not act as host for the tick vector, they are unlikely to play a role in the epidemiology of the disease.

Systems Affected

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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

Distribution

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Heartwater only occurs where its tick vectors, Amblyomma, are present. Countries where heartwater has been conclusively diagnosed are listed in the table. The improvement of molecular diagnosis allows confirmation of the presence of E. ruminantium in different countries. In South Africa, Plessis and Kümm (1971) isolated E. ruminantium, named the Kümm strain, from a Hyalomma tick removed from an eland in a non-heartwater endemic area where A. hebraeum ticks are not present.

According to Camus et al. (1996), after examining various reports and veterinary literature since 1930, heartwater does not occur in Guinea, Sierra Leone, Togo, Saudi Arabia and Yemen, even though there is at least one efficient vector present in these countries and it occurs in the neighbouring countries. However, three cases were reported in Oman in 2018 (El-Neweshy et al., 2019). A nervous condition and lesions very reminiscent to those of heartwater have been described in cattle in Cuba (Figueroa and Sutherland, 1968; Figueroa et al., 1970; Figueroa and Sutherland, 1972) and in French Guiana (Sapin, 1981). However, until now, no report or confirmation of a heartwater clinical case has been made in both countries. Although no African vectors have been found in these countries, a potential vector, Amblyomma cajennense, does occur there (Camus et al., 1996). In the Caribbean regions, only Guadeloupe and Antigua are infected with heartwater whereas Amblyomma variegatum is present in several islands of the lesser Antilles at lower level of infestation.

Therefore, all countries where known Amblyomma vectors are parasites of livestock, or where neighbouring countries are infected, are at risk from the disease. These include the countries listed above, most of the Caribbean islands and the American continent. Quite surprisingly, heartwater has never been observed in Asia from where most ruminants originated, and despite the fact that many Amblyomma spp. ticks occur there.

According to African Union-Interafrican Bureau for Animal Resources (2011), heartwater is present in Africa south of the Sahara and the islands of the Comoros, Zanzibar, Madagascar, Sao Tomé, Réunion and Mauritius. Many ruminants, including some antelope species, are susceptible.

For current information on disease incidence, see OIE's World Animal Health Information System (OIE-WAHIS).

Distribution Table

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The distribution in this summary table is based on all the information available. When several references are cited, they may give conflicting information on the status. Further details may be available for individual references in the Distribution Table Details section which can be selected by going to Generate Report.

Last updated: 10 Dec 2021
Continent/Country/Region Distribution Last Reported Origin First Reported Invasive Reference Notes

Africa

AlgeriaAbsent, No presence record(s)Jul-Dec-2019
AngolaAbsentJul-Dec-2018
BeninAbsentJan-Jun-2019
BotswanaPresentJul-Dec-2018
Burkina FasoPresentJul-Dec-2019
BurundiPresent, LocalizedJul-Dec-2018
Cabo VerdeAbsent, No presence record(s)Jul-Dec-2019
CameroonPresent
Central African RepublicAbsentJul-Dec-2019
ChadAbsentJul-Dec-2019
ComorosPresentJan-Jun-2018
Congo, Republic of theAbsentJan-Jun-2019
Côte d'IvoirePresent
DjiboutiAbsentJul-Dec-2019
EgyptAbsent, No presence record(s)Jul-Dec-2019
EritreaAbsentJul-Dec-2019
EswatiniPresentJul-Dec-2019
EthiopiaAbsentJul-Dec-2018
GabonPresent
GambiaPresentJul-Dec-2018
GhanaPresentJan-Jun-2019
KenyaPresent, LocalizedJul-Dec-2019
LesothoPresentJan-Jun-2020
LiberiaAbsentJul-Dec-2018
LibyaAbsent, No presence record(s)
MadagascarPresentJan-Jun-2019
MalawiAbsentJul-Dec-2018
MauritaniaAbsent, No presence record(s)Jul-Dec-2018
MauritiusAbsentJul-Dec-2019
MozambiquePresentJul-Dec-2019
NamibiaAbsentJul-Dec-2019
NigerAbsentJul-Dec-2019
NigeriaAbsentJul-Dec-2019
RéunionPresentJul-Dec-2019
RwandaAbsentJul-Dec-2018
Saint HelenaAbsent, No presence record(s)Jan-Jun-2019
São Tomé and PríncipePresentCAB Abstracts Data Mining
SenegalPresentJul-Dec-2019
SeychellesAbsent, No presence record(s)Jul-Dec-2018
SomaliaPresent, LocalizedJul-Dec-2020
South AfricaPresentJul-Dec-2019
SudanPresentJul-Dec-2019
TanzaniaPresentJul-Dec-2019
-Zanzibar IslandPresent
TogoPresentJul-Dec-2019
TunisiaAbsent, No presence record(s)Jul-Dec-2019
ZambiaPresentJul-Dec-2018
ZimbabwePresentJul-Dec-2019

Asia

AfghanistanAbsent, No presence record(s)Jul-Dec-2019
ArmeniaAbsentJul-Dec-2019
AzerbaijanAbsentJul-Dec-2019
BahrainAbsent, No presence record(s)Jul-Dec-2020
BangladeshAbsent, No presence record(s)Jan-Jun-2020
BhutanAbsent, No presence record(s)Jan-Jun-2020
BruneiAbsent, No presence record(s)Jul-Dec-2019
ChinaAbsent, No presence record(s)
GeorgiaAbsent, No presence record(s)Jul-Dec-2019
IndiaAbsent, No presence record(s)Jan-Jun-2019
IndonesiaAbsent, No presence record(s)
IraqAbsent, No presence record(s)Jul-Dec-2019
IsraelAbsent, No presence record(s)Jul-Dec-2020
JordanAbsent, No presence record(s)Jul-Dec-2018
KazakhstanAbsent, No presence record(s)Jul-Dec-2019
KuwaitAbsentJan-Jun-2019
KyrgyzstanAbsentJan-Jun-2019
LaosAbsentJan-Jun-2019
LebanonAbsent, No presence record(s)
MalaysiaAbsent, No presence record(s)Jan-Jun-2019
-Peninsular MalaysiaAbsent, No presence record(s)
-SabahAbsent, No presence record(s)
-SarawakAbsent, No presence record(s)
MaldivesAbsent, No presence record(s)Jan-Jun-2019
MongoliaAbsent, No presence record(s)Jan-Jun-2019
MyanmarAbsentJul-Dec-2019
NepalAbsent, No presence record(s)Jul-Dec-2019
North KoreaAbsent, No presence record(s)
OmanPresent
PakistanAbsent, No presence record(s)
PalestineAbsentJul-Dec-2019
PhilippinesAbsent, No presence record(s)Jul-Dec-2019
Saudi ArabiaAbsentJan-Jun-2020
SingaporeAbsent, No presence record(s)Jul-Dec-2019
South KoreaAbsent, No presence record(s)Jul-Dec-2019
Sri LankaAbsent, No presence record(s)Jul-Dec-2018
SyriaAbsentJul-Dec-2019
TaiwanAbsent, No presence record(s)Jul-Dec-2019
TajikistanAbsentJan-Jun-2019
ThailandAbsentJan-Jun-2020
TurkmenistanAbsentJan-Jun-2019
United Arab EmiratesAbsent, No presence record(s)Jul-Dec-2020
UzbekistanAbsent, No presence record(s)Jul-Dec-2019
VietnamAbsentJul-Dec-2019

Europe

AlbaniaAbsent, No presence record(s)Jul-Dec-2019
AndorraAbsent, No presence record(s)Jul-Dec-2019
BelarusAbsent, No presence record(s)Jul-Dec-2019
BelgiumAbsentJul-Dec-2019
Bosnia and HerzegovinaAbsent, No presence record(s)Jul-Dec-2019
BulgariaAbsent, No presence record(s)Jan-Jun-2019
CroatiaAbsent, No presence record(s)Jul-Dec-2019
CyprusAbsent, No presence record(s)Jul-Dec-2019
CzechiaAbsent, No presence record(s)Jul-Dec-2019
DenmarkAbsent, No presence record(s)Jan-Jun-2019
EstoniaAbsent, No presence record(s)Jul-Dec-2019
Faroe IslandsAbsent, No presence record(s)Jul-Dec-2018
FinlandAbsent, No presence record(s)Jul-Dec-2019
FranceAbsentJul-Dec-2019
GermanyAbsent, No presence record(s)Jul-Dec-2019
GreeceAbsent, No presence record(s)Jan-Jun-2018
HungaryAbsent, No presence record(s)Jul-Dec-2019
IcelandAbsent, No presence record(s)Jul-Dec-2019
IrelandAbsent, No presence record(s)Jul-Dec-2019
Isle of ManAbsent, No presence record(s)
ItalyAbsent, No presence record(s)Jul-Dec-2020
JerseyAbsent, No presence record(s)
LatviaAbsent, No presence record(s)Jul-Dec-2020
LiechtensteinAbsentJul-Dec-2019
LithuaniaAbsent, No presence record(s)Jul-Dec-2019
LuxembourgAbsent, No presence record(s)
MaltaAbsent, No presence record(s)Jan-Jun-2019
MoldovaAbsent, No presence record(s)Jan-Jun-2020
MontenegroAbsent, No presence record(s)Jul-Dec-2019
NetherlandsAbsent, No presence record(s)Jul-Dec-2019
North MacedoniaAbsent, No presence record(s)Jul-Dec-2019
NorwayAbsent, No presence record(s)Jul-Dec-2019
PolandAbsent, No presence record(s)Jan-Jun-2019
PortugalAbsentJul-Dec-2019
RomaniaAbsent, No presence record(s)Jul-Dec-2018
RussiaAbsent, No presence record(s)Jan-Jun-2020
San MarinoAbsent, No presence record(s)Jan-Jun-2019
SerbiaAbsent, No presence record(s)Jul-Dec-2019
Serbia and MontenegroAbsent, No presence record(s)
SlovakiaAbsentJul-Dec-2020
SloveniaAbsent, No presence record(s)Jul-Dec-2018
SpainAbsent, No presence record(s)Jul-Dec-2020
SwedenAbsent, No presence record(s)Jul-Dec-2020
SwitzerlandAbsent, No presence record(s)Jul-Dec-2020
UkraineAbsent, No presence record(s)Jul-Dec-2020
United KingdomAbsent, No presence record(s)Jul-Dec-2019
-Northern IrelandAbsent, No presence record(s)

North America

Antigua and BarbudaPresent
BahamasAbsent, No presence record(s)Jul-Dec-2018
BarbadosAbsent, No presence record(s)Jul-Dec-2020
BelizeAbsent, No presence record(s)Jul-Dec-2019
BermudaAbsent, No presence record(s)
British Virgin IslandsAbsent, No presence record(s)
CanadaAbsent, No presence record(s)Jul-Dec-2019
Cayman IslandsAbsentJan-Jun-2019
Costa RicaAbsent, No presence record(s)Jul-Dec-2019
CubaAbsent, No presence record(s)Jan-Jun-2019
CuraçaoAbsent, No presence record(s)Jan-Jun-2019
DominicaAbsent, No presence record(s)
Dominican RepublicAbsent, No presence record(s)Jan-Jun-2019
El SalvadorAbsent, No presence record(s)Jul-Dec-2019
GreenlandAbsent, No presence record(s)Jul-Dec-2018
GuadeloupePresentJul-Dec-2019
GuatemalaAbsent, No presence record(s)Jan-Jun-2019
HaitiAbsent, No presence record(s)Jul-Dec-2019
HondurasAbsent, No presence record(s)Jul-Dec-2018
JamaicaAbsent, No presence record(s)Jul-Dec-2018
MartiniqueAbsentJul-Dec-2019
MexicoAbsent, No presence record(s)Jul-Dec-2019
NicaraguaAbsent, No presence record(s)Jul-Dec-2019
PanamaAbsent, No presence record(s)Jan-Jun-2019
Saint Kitts and NevisPresentCAB Abstracts Data Mining
Saint LuciaAbsent, No presence record(s)Jul-Dec-2018
Saint Vincent and the GrenadinesAbsentJan-Jun-2019
Trinidad and TobagoAbsent, No presence record(s)Jan-Jun-2018
United StatesAbsent, No presence record(s)Jul-Dec-2019

Oceania

AustraliaAbsent, No presence record(s)Jul-Dec-2019
Cook IslandsAbsent, No presence record(s)Jan-Jun-2019
Federated States of MicronesiaAbsent, No presence record(s)Jan-Jun-2019
FijiAbsent, No presence record(s)Jan-Jun-2019
French PolynesiaAbsent, No presence record(s)Jan-Jun-2019
KiribatiAbsent, No presence record(s)Jan-Jun-2018
Marshall IslandsAbsent, No presence record(s)Jan-Jun-2019
New CaledoniaAbsent, No presence record(s)Jul-Dec-2019
New ZealandAbsent, No presence record(s)Jul-Dec-2019
PalauAbsent, No presence record(s)Jul-Dec-2020
SamoaAbsent, No presence record(s)Jan-Jun-2019
Timor-LesteAbsent, No presence record(s)Jul-Dec-2018
TongaAbsentJul-Dec-2019
VanuatuAbsent, No presence record(s)Jan-Jun-2019

South America

ArgentinaAbsentJul-Dec-2019
BoliviaAbsent, No presence record(s)Jan-Jun-2019
BrazilAbsent, No presence record(s)Jul-Dec-2019
ChileAbsent, No presence record(s)Jan-Jun-2019
ColombiaAbsent, No presence record(s)Jul-Dec-2019
EcuadorAbsent, No presence record(s)Jul-Dec-2019
Falkland IslandsAbsent, No presence record(s)Jul-Dec-2019
French GuianaAbsent, No presence record(s)Jul-Dec-2019
GuyanaAbsent, No presence record(s)Jul-Dec-2018
ParaguayAbsent, No presence record(s)Jul-Dec-2019
PeruAbsent, No presence record(s)Jan-Jun-2019
SurinameAbsent, No presence record(s)Jan-Jun-2019
UruguayAbsent, No presence record(s)Jul-Dec-2019
VenezuelaAbsent, No presence record(s)Jan-Jun-2019

Pathology

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Macroscopic pathology

Lesions in cattle, sheep and goats are similar, although quite variable in extent and some changes are more common in certain species than in others. Effusion of body cavities, (hydropericardium, hydrothorax, and, in some cases a degree of ascites) 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 L 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 choroid 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).

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 fibrinous choroiditis 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.

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.

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 microscopy 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, b).

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.

Diagnosis

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Clinical Diagnosis

Infected domestic ruminants exhibit a wide range of clinical signs varying from a peracute to mild (clinically inapparent) form. The incubation period in naturally infected cattle ranges from 9 to 29 days (average 18 days) and that of sheep and goats 7-35 days (average 14 days). Peracutely affected animals die within a few hours after the initial fever, either with or without any clinical signs (Alexander, 1931; Neitz, 1968; Uilenberg, 1983).

Acute heartwater is the most common form of the disease in endemic areas. Fever of 40°C in bovine or higher for sheep and goats (40.5°C), which usually persists for 3-6 days and is followed by a drop of 1°C or more shortly before death. Animals gradually show inappetence and eventually stop feeding. Cessation of rumination and difficult breathing follows. Petechiae are visible on the mucous membranes of the conjunctiva (mainly cattle). During the latter stage of acute heartwater, the majority of animals manifest nervous symptoms ranging from a mild incoordination to pronounced convulsions (Alexander, 1931). They are hypersensitive when handled or startled. The gait of affected animals becomes progressively more unsteady, whereas some animals show hypermetria, especially of the forelegs (mainly cattle). They eventually become prostrate, assume a position of lateral recumbency and show intermittent leg-paddling, chewing movements, opisthotonus, licking of the lips and nystagmus. A large amount of froth is usually present at the mouth and nostrils. Diarrhoea is occasionally seen in cattle, sheep and goats.

Less severe cases (subacute and mild) occur with clinical signs ranging from slightly less intense than the acute form to little or no signs at all.

Differential Diagnosis

Numerous conditions causing nervous symptoms or acute death must be differentiated from heartwater. Diseases such as rabies, cerebral babesiosis/theileriosis, bacterial meningitis/encephalitis, numerous plant, pesticide and heavy metal poisonings show similar symptoms (Bezuidenhout et al., 1994).

Laboratory Diagnosis

The confirmation of a diagnosis based on clinical signs and postmortem lesions requires the demonstration of the organisms in the cytoplasm of endothelial cells of blood vessels. The easiest, most efficient and quickest way of doing this is to visualize them in stained smears of the brain (Purchase, 1945) although they may also be found in histological sections such as the brain and kidneys. The examination of brain biopsies in live animals for the confirmation of a diagnosis of heartwater is useful in experimental animals, but is not practical under field conditions (Synge, 1978; Camus and Barré, 1982; Amstel, 1987). Smears should be air-dried before staining, and stains such as Giemsa or the CAM’s Quick stain give the best results.

The indirect immunofluorescence test (IFA test) is not used anymore (Plessis and Malan, 1987a, b). Many attempts at developing a diagnostic serological test for heartwater have failed due to the high degree of cross-reaction occurring between antigens from different strains of Ehrlichia and antibodies against Cytoecetes phagocytophila [Anaplasma phagocytophilum], and some Ehrlichia spp. (Ehrlichia equi [Anaplasma phagocytophilum], E. canis, E. ovina and E. bovis [Anaplasma bovis]) (Logan et al., 1986; Camus, 1987; Holland et al., 1987; Plessis and Malan, 1987b). The IFA test is not reliable when testing field samples because of cross reactions with other Ehrlichia spp., but it is useful to use in experimental heartwater trials when heartwater free animals are vaccinated with an experimental developed vaccine to confirm infection (Latif et al., 2020).

To minimize the degree of cross-reaction, two ELISA were developed using recombinant MAP1. The first one is an indirect ELISA, ELISA MAP1-B using an immunogenic fraction of MAP1, the recombinant antigen MAP1-B (Vliet et al., 1995). The second one is a competitive ELISA using the MAP-1 gene cloned in baculovirus and monoclonal antibodies raised against MAP1 (Katz et al., 1997). Both tests improved the specificity but there is still some cross reactivity with E. canis and E. chaffeensis. Although, these two strains do not occur in South Africa.

Low seropositivity of cattle (even cattle that had previously been vaccinated) occurs in heartwater endemic areas. The detection of antibodies is possible 2 weeks after natural infection and lasts for a few months in naturally infected domestic ruminants. This period is shorter for bovines than for small ruminants. Serology as a diagnostic tool for detecting individual animals exposed specifically to E. ruminantium is unreliable. Serological analysis should be considered at herd level, taking into account the epidemiological environment, and should be complemented by molecular diagnosis.

Molecular Diagnosis

There have been significant improvements in the development of molecular tools for the diagnosis of heartwater and the genetic typing of the different strains of E. ruminantium. Two primers, AB128 and AB129, have been designed by Waghela et al. (1991) to target a fragment of a unique and specific region that consist of parts of two overlapping genes of the E. ruminantium genome, referred to as the pCS20 gene region. These primers amplify a 280 bp region of pCS20 which is revealed by a labelled pCS20 probe (Waghela et al., 1991; Peter et. al., 1995).

The PCR/hybridization allows increased sensitivity of the method with an experimental detection threshold of one to ten organisms per sample. However, the sensitivity of the PCR assay is lower and drops to 61% and 28% with tick samples containing 103 and 102 organisms, respectively (Peter et al., 2000). This method was replaced with the quantitative TaqMan probe (Steyn et al., 2008).

A nested PCR targeting the pCS20 fragment was developed using external primers AB128 and a new primer AB130 followed by a second amplification of the first PCR product using the primers AB128 and AB129 (Martinez et al., 2004). The detection limit (six organisms per sample) is similar to the PCR/hybridization method described above, but the nested PCR method is easier and less time consuming.

The diagnosis of heartwater based on examination of brain smears from dead ruminants is much less sensitive than by molecular diagnosis. As an example, in a comparison of methods, brain smear observations and pCS20 nested PCR on the same brain samples demonstrated improvement of the detection threshold with a percentage of heartwater positive cases after brain smears observations of 75% compare to 97% by pCS20 nested PCR (Adakal et al., 2010a). The main disadvantage with nested PCR is the higher contamination risk. The range of strain detection was increased by the use of primers including AB128, AB130 and AB129 and this method is used routinely for E. ruminantium detection in field samples, especially ticks (Molia et al., 2008; Adakal et al., 2009; 2010b). The pCS20 nested PCR is versatile and allows detection in organs from infected dead animals (lung and brain), blood from infected animals during hyperthermia, and ticks (fresh, frozen or preserved in 70% ethanol). Detection by nested PCR is possible in the blood of animals 1 or 2 days before hyperthermia and during the hyperthermia period but not in asymptomatic animals. PCR based methods appear to be more reliable in detecting infection in ticks. This could have epidemiological value in determining the E. ruminantium geographical distribution and prevalence in ticks.

Several quantitative real time PCRs have also been developed for the detection of E. ruminantium targeting map-1, map1-1 and pCS20 gene region (Postigo et al., 2002; Peixoto et al., 2005; Steyn et al., 2008). These methods allow the quantification of the pathogen with a similar sensitivity to the nested PCR. pCS20 real time PCR can be used for diagnosis due to its ability to detect different E. ruminantium strains. This assay is highly sensitive and could detect up to one copy of the organism in 70 min. It eliminates the use of nested PCR, is less laborious and safer and does not require the 32P-probe, as in the PCR/hybridization method. This method is useful for detection of E. ruminantium in diagnostic samples while the animal is still alive, from blood and ticks from the animal for epidemiology and genetic diversity studies (Steyn and Pretorius, 2020).

The genetic characterization and structure of E. ruminantium population at regional scale is essential in order to select potential vaccine strains. The genetic typing of strains was previously done using RFLP on the polymorphic gene map-1 after PCR amplification (Faburay et al., 2007b; Adakal et al., 2010a). Based on the genome analysis of two different strains, Gardel and Welgevonden (Collins et al., 2005), truncated and unique coding sequences specific of strains have been identified. This analysis allows the development of a differential strain-specific diagnosis using nested PCRs targeting six unique and four truncated CDS (Vachiéry et al., 2008b). New multi-locus methods adapted to E. ruminantium were validated such as multi-locus sequence typing (Adakal et al., 2009) and multi-locus variable number of tandem repeated sequence analysis (Pilet et al., 2012). These tools are used on field samples for molecular epidemiological studies.

Immunity

Protective immunity to E. ruminantium seems to be predominantly cell mediated. Transfer of immune T cells to naïve mice protect them against heartwater and knockout mice studies demonstrate the importance of memory T cells in protection (Plessis et al., 1991; Byrom et al., 2000). In vitro assays on peripheral blood mononuclear cells (PBMC) from vaccinated animals showed the IFNg mediated induction of both CD8+ and CD4+ T cells in response to total E. ruminantium antigens (Esteves et al., 2004). PBMC from immune animals vaccinated with live vaccine generated CD4+ T cell lines after MAP1 antigen stimulation which expressed IFNg, IFNa, TNFa (Mwangi et al., 2002). There have, however, been mixed results concerning the production of IFN-γ in vaccinated animals. Esteves et al. (2004) reported that in goats, IFN-γ could only be detected in the vaccinated animals after antigenic recall in vitro, while the control animals did not produce the cytokine. Other studies indicated that the production of IFN-γ is variable between immunized and control animals and cannot be used on its own as an indicator for host survival or to measure vaccine potency (Vachiéry, et al., 2006; Pretorius, et al., 2007; 2008). Immune transcriptome analyses showed that innate immune response pathway markers, including TLR2, TLR4, TLR9, NOD-like receptor and markers for the chemokine and cytokine receptor signalling pathways were up-regulated in sheep PBMC during E. ruminantium infection. These sheep were infested with Amblyomma ticks experimentally infected with the E. ruminantium Welgevonden strain and challenged with infected ticks (Nefefe et al., 2017).

List of Symptoms/Signs

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SignLife StagesType
Cardiovascular Signs / Muffled, decreased, heart sounds Sign
Cardiovascular Signs / Tachycardia, rapid pulse, high heart rate Sign
Cardiovascular Signs / Weak pulse, small pulse Sign
Digestive Signs / Abdominal distention Sign
Digestive Signs / Anorexia, loss or decreased appetite, not nursing, off feed Cattle and Buffaloes|All Stages; Sheep and Goats|All Stages Sign
Digestive Signs / Ascites, fluid abdomen Sign
Digestive Signs / Bloody stools, faeces, haematochezia Sign
Digestive Signs / Diarrhoea Cattle and Buffaloes|All Stages Sign
Digestive Signs / Excessive salivation, frothing at the mouth, ptyalism Sign
Digestive Signs / Grinding teeth, bruxism, odontoprisis Sign
Digestive Signs / Melena or occult blood in faeces, stools Cattle and Buffaloes|All Stages Sign
Digestive Signs / Mucous, mucoid stools, faeces Cattle and Buffaloes|All Stages Sign
Digestive Signs / Rumen hypomotility or atony, decreased rate, motility, strength Sign
Digestive Signs / Tongue protrusion Sign
General Signs / Ataxia, incoordination, staggering, falling Cattle and Buffaloes|All Stages Diagnosis
General Signs / Dysmetria, hypermetria, hypometria Sign
General Signs / Fever, pyrexia, hyperthermia Cattle and Buffaloes|All Stages; Sheep and Goats|All Stages Diagnosis
General Signs / Generalized weakness, paresis, paralysis Sign
General Signs / Head, face, ears, jaw weakness, droop, paresis, paralysis Sheep and Goats|All Stages Sign
General Signs / Hypothermia, low temperature Cattle and Buffaloes|All Stages Diagnosis
General Signs / Inability to stand, downer, prostration Sign
General Signs / Opisthotonus Cattle and Buffaloes|All Stages; Sheep and Goats|All Stages Diagnosis
General Signs / Reluctant to move, refusal to move Sign
General Signs / Sudden death, found dead Cattle and Buffaloes|All Stages; Sheep and Goats|All Stages Sign
General Signs / Tenesmus, straining, dyschezia Sheep and Goats|All Stages Sign
General Signs / Torticollis, twisted neck Sign
General Signs / Trembling, shivering, fasciculations, chilling Sign
General Signs / Underweight, poor condition, thin, emaciated, unthriftiness, ill thrift Sign
General Signs / Weight loss Sign
Musculoskeletal Signs / Spasms of the limbs, legs, foot, feet in birds Cattle and Buffaloes|All Stages; Sheep and Goats|All Stages Diagnosis
Nervous Signs / Abnormal anal, perineal, tail reflexes, increased or decreased Sheep and Goats|All Stages Sign
Nervous Signs / Abnormal behavior, aggression, changing habits Cattle and Buffaloes|Calf Sign
Nervous Signs / Abnormal forelimb reflexes, increased or decreased Cattle and Buffaloes|All Stages; Sheep and Goats|All Stages Diagnosis
Nervous Signs / Circling Sign
Nervous Signs / Coma, stupor Sign
Nervous Signs / Constant or increased vocalization Sheep and Goats|All Stages Sign
Nervous Signs / Dullness, depression, lethargy, depressed, lethargic, listless Sheep and Goats|Lamb Sign
Nervous Signs / Excitement, delirium, mania Cattle and Buffaloes|All Stages Diagnosis
Nervous Signs / Head pressing Cattle and Buffaloes|All Stages Sign
Nervous Signs / Head tilt Cattle and Buffaloes|All Stages; Sheep and Goats|All Stages Sign
Nervous Signs / Hyperesthesia, irritable, hyperactive Cattle and Buffaloes|All Stages; Sheep and Goats|All Stages Diagnosis
Nervous Signs / Propulsion, aimless wandering Cattle and Buffaloes|Calf Sign
Nervous Signs / Seizures or syncope, convulsions, fits, collapse Cattle and Buffaloes|All Stages; Sheep and Goats|All Stages Diagnosis
Nervous Signs / Tremor Sign
Ophthalmology Signs / Abnormal pupillary response to light Sign
Ophthalmology Signs / Blindness Sign
Ophthalmology Signs / Mydriasis, dilated pupil Sign
Ophthalmology Signs / Nystagmus Sheep and Goats|All Stages Sign
Reproductive Signs / Abortion or weak newborns, stillbirth Sign
Reproductive Signs / Agalactia, decreased, absent milk production Sign
Respiratory Signs / Abnormal lung or pleural sounds, rales, crackles, wheezes, friction rubs Sign
Respiratory Signs / Coughing, coughs Cattle and Buffaloes|All Stages; Sheep and Goats|All Stages Sign
Respiratory Signs / Decreased, muffled, lung sounds, absent respiratory sounds Sign
Respiratory Signs / Dull areas on percussion of chest, thorax Sign
Respiratory Signs / Dyspnea, difficult, open mouth breathing, grunt, gasping Cattle and Buffaloes|All Stages; Sheep and Goats|All Stages Sign
Respiratory Signs / Increased respiratory rate, polypnea, tachypnea, hyperpnea Cattle and Buffaloes|All Stages; Sheep and Goats|All Stages Sign
Respiratory Signs / Mucoid nasal discharge, serous, watery Sign
Respiratory Signs / Purulent nasal discharge Sign
Skin / Integumentary Signs / Rough hair coat, dull, standing on end Sign
Urinary Signs / Polyuria, increased urine output Sign

Disease Course

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The pathogenesis of the disease is still poorly understood, but the following hypothesis has been proposed.

The Amblyomma tick spp. attaches firmly on the host skin with their relatively big mouth parts (hyposome) that penetrate the skin damaging the tissue and small blood vessels. To secure them firmly on the host, they excrete proteinaceous cement that helps secure the hyposome of the tick at the bite site (Anderson and Magnarelli, 2008). The cement fills the gaps between the host skin and the hyposome of the tick to prevent the blood leaking during feeding while the tick also excretes anticoagulant that prevents blood clotting (Thomas et al., 2016; Denisov et al., 2021).

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 in 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 (Jackson and Neitz, 1932; Prozesky and Plessis, 1985a). 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.

Epidemiology

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Factors relating to the tick vector, causative organism and vertebrate host are important in the epidemiology of heartwater. These include genetic diversity and 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; Jongejan, 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). 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 h 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 strains 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 recombination of the strains of heartwater. This leads to a new strain that can be more or less virulent.

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), South African buffalo and black wildebeest, as well as helmeted guinea fowl, leopard tortoise (Geochelone pardalis [Stigmochelys pardalis]), A. marmoreum 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).

Ehrlichia ruminantium strains have been isolated from ticks other than Amblyomma; the Kümm strain from Hyalomma tick in 1971, and the Omatjenne strain from a non-endemic area in 1990. The original Kümm strain has since been shown to contain two separate strains: Kümm 1 and Kümm 2 (Zweygarth et al., 2002). In an epidemiological study by Steyn and Pretorius (2020) using the pCS20 gene region sequence, it was shown that the Kumm 2 and Omatjenne strains cluster together with a new strain called Riverside. However, genome sequencing of these strains revealed that the Riverside strain differed from the other two strains (Liebenberg et al., 2020). Interestingly, the Kümm 1 strain clusters together with the West African strains (Steyn and Pretorius, 2020). The Omatjenne strain has since been detected in endemic and non-endemic areas in South Africa in cattle, sheep and goats. The Ehrlichia Omatjenne strain must not be confused with the Anaplasma Omatjenne strain that have the same origin (Namibia).

Genome sequencing:

The complete genome sequence of E. ruminantium, the South African Welgevonden strain, was published in 2005 (Collins et al., 2005). This was soon followed by the genome sequences of the daughter strain of Welgevonden maintained in Guadeloupe since 1988, and the Gardel strain from Guadeloupe (Frutos et al., 2006). As sequencing technologies have advanced, whole genome sequencing of more strains became attainable. Consequently, several complete and draft genomes became available more recently (Nakao et al., 2016; Liebenberg et al., 2020). Currently, 23 genome sequences are available on the microbial genome database at the National Center for Biotechnology Information (NCBI) (https://www.ncbi.nlm.nih.gov/), representing isolates from southern Africa, as well as West Africa.

Impact: Economic

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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 high as those due to babesiosis and anaplasmosis. However, there have been no definitive studies designed to quantify this importance. 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 higher 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. Heartwater is not a notifiable disease in South Africa. As result of cases being unreported, there is no official data recording the impact statistically, however, it does have a great impact on the economy.

Zoonoses and Food Safety

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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).

Disease Treatment

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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 tetracyclines are used at 10 mg/10 kg body weight dose rates. 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 and 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 during the time that they are protected by the drug. With fluctuating infection rates in ticks under different ecological conditions this approach may fail. This method can also lead to antibiotic resistance. Many farmers in the endemic regions of South Africa farming Angora goats use tetracycline on a daily basis to treat Angora goats that appear sick (Allsopp, 2009).

Prevention and Control

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Heartwater can be controlled by immunization of calves, lambs or kids (generally no treatment is necessary following the immunization), treatment of sick animals infected by ticks, and the strategic control of the number of bont ticks to which livestock are exposed.

Tick Control

Sustained intensive tick control measures may under certain conditions succeed in preventing outbreaks of heartwater, even in endemic areas. This, however, should be considered a temporary measure which is accompanied by risks of later outbreaks of the disease if control measures are relaxed. It is important to remember that, since E. ruminantium replicates in the gut and salivary glands of the tick, the infection is amplified so that a single tick can transmit the disease to a large ruminant. Strict tick control can succeed in non-epidemic areas, where the disease normally does not occur and bont ticks could be considered to be only temporary invaders.

In endemic areas, where the disease normally occurs and the tick vector is permanently established, control is more difficult to accomplish and also costly. The disease can only be controlled successfully if all the animals on the farm can be dipped regularly throughout the year and if there are no, or an absolute minimum, of game and birds on which ticks can feed to survive. Intensive dipping programmes (high frequency dipping) also carry a high risk in regards to the development of tick resistance to dipping compounds and this approach is challenging in extensive farming enterprises.

In marginal (transitional) areas where fields suitable for bont ticks changes to fields in which they cannot survive, control may be difficult. This is because the transitional fields very often consist of bushy gorges and valleys (where the bont tick may occur) that connect heartwater-free middle- or highveld with lower-lying bushveld where the disease occurs regularly. In cases like these the disease can be prevented by a combination of an intensive dipping programme, particularly at strategic times (October-November and March-April) and management aimed at avoiding the grazing of these danger areas.

Strategic Tick Control

This method of control prevents ticks from becoming a nuisance to the animals, but allows sufficient numbers to maintain the animal’s immunity through regular re-infection. This approach is recommended in the vast majority of the heartwater endemic areas of southern Africa. In this approach, animals become naturally infected by tick exposure, or are immunized with the infected Ball3 Blood and treatment method, and their immunity is maintained by regular re-infection through the tick at intervals not exceeding 6-9 months. A dipping compound is applied once in 2 weeks or in some cases every week in South Africa.

In the Caribbean Amblyomma program, the acaricide treatment of ruminants with a dorsal mid-line pour-on solution containing the pyrethroid flumethrin has been practiced with a frequency of two treatments per month for 2 years with an initial objective of eradication of the ticks. This method diminished the tick population in several islands and eliminated the tick from four of them. An integrated tick control strategy taking into account the recent data on the heterogeneous drop off rhythm of Amblyomma variegatum nymphs has been proposed to reduce pasture infestation by adult ticks (Stachurski and Adakal, 2010). Mathematical models of Amblyomma population dynamics based on biotic and abiotic parameters are being developed with an objective of developing maps of habitat suitability and should allow testing of different control strategies.

Immunization and Vaccines

A number of different vaccination methods are used:

The only commercial vaccine strategy available is the infection and treated method (Merwe, 1987) that consists of the blood of sheep infected with live virulent E. ruminantium organisms (Ball3-strain) used as the vaccine. This vaccine is used on a large scale in South Africa and to a very limited extent in other African countries. Limitations are that the live Ball3 strain does not protect against all the strains in the field (Steyn and Pretorius, 2020), is expensive to produce, requires liquid nitrogen storage and needs to be injected intravenously into the jugular vein (Merwe, 1987). In the method, the animals infected with the Ball3 strain (vaccine) must be monitored daily for rise in temperature and clinical signs. When the temperature preferably increases for 2-3 days above 40.5°C (sheep and goats) and 39-40°C (cattle), the animals are treated with tetracycline. This method provides the animal with time to build immunity. If treatment is given too early, no protective immunity will develop. If treatment is given too late, the animal could die due to heartwater. Vaccination with the Ball3 strain will complement natural tick infection of young animals and also ensure immunity in those animals which escape natural infection.

Other experimental vaccines are being developed or registered such as inactivated, attenuated, recombinant and multi-epitope DNA vaccines. These are not yet commercially available.

Inactivated vaccines use the entire killed bacteria emulsified in the oily adjuvant ISA50. Inactivated vaccines have several advantages as they contain killed bacteria and their storage conditions are compatible with field use (-20°C or refrigerated). Two injections are necessary every second month and animals should be protected from tick infestation during at least these 2 months. This vaccine has been tested both in experimental and field conditions and its efficacy demonstrated (Martinez et al., 1994; Mahan et al., 1995; 1998a; 2001; Adakal et al., 2010b). The lack of vaccine efficiency has been attributed to the diversity of strains within a restricted area. An inactivated vaccine that included a second local strain improved significantly the protection in a field trial in Burkina Faso (Adakal et al., 2010b). Additionally, improvement of the production of E. ruminantium antigen at industrial scale and reduction in the minimal efficient dose of vaccine (35 µg) provides the opportunity to produce this vaccine at low cost (0.11 euros per dose) (Marcelino et al., 2006; 2007; Vachiéry et al., 2006). As soon as regional isolates are available (in culture), it becomes possible to produce an inactivated vaccine that includes a cocktail of regional strains. The major challenge remains the choice of strains which could protect against other circulating strains. The choice will depend on genetic characteristics and markers which are not yet defined.

The in vitro attenuated vaccine: Senegal, Welgevonden and Gardel strains were attenuated by successive in vitro passages and demonstrated their efficiency in experimental conditions (Jongejan, 1991; Zweygarth et al., 2005; 2008; Faburay et al., 2007b). Senegal attenuated vaccine confers good protection against homologous strains but poor protection against heterologous strains. Welgevonden attenuated vaccine in South Africa confers 100% protection in controlled conditions against homologous and four different strains but is not yet tested in field conditions (Latif et al., 2020). The main disadvantage of attenuated vaccines is the possible reversion to virulence. Moreover, as any live vaccine, it requires liquid nitrogen storage.

The DNA prime-recombinant protein boost vaccine (Pretorius et al., 2008) elicited a protective response against homologous experimental challenge. However, it did not give satisfactory results during field tick challenge. Moreover, simple intramuscular immunization is not sufficient to induce protection and the use of a biolistic particle delivery system (Gene gun) is necessary for the DNA injection. This is not suitable for large vaccination campaigns. One polymorphic gene has been identified as an efficient component of a recombinant vaccine against heartwater using prime/boost method (Pretorius et al., 2010). However, as this gene is polymorphic, a recombinant vaccine should include almost three different genotypes.

A recently developed multi-epitope DNA vaccine induced 60% protection against an experimental tick challenge when using both intramuscular (IM) and Gene gun inoculations together (provisional patent pending).

For any kind of vaccine, live, inactivated, attenuated or recombinant vaccines, the main problem is the presence of numerous strains in the field with high genetic diversity and the choice of vaccine strain genotype depends on the region.

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Vachiéry, N., Jeffery, H., Pegram, R., Aprelon, R., Pinarello, V., Kandassamy, R.L.Y., Raliniaina, M., Molia, S., Savage, H., Alexander, R., Frebling, M., Martinez, D., Lefrançois, T., 2008a. Amblyomma variegatum ticks and heartwater on three Caribbean Islands: tick infection and Ehrlichia ruminantium genetic diversity in bovine herds. Annals of the New York Academy of Sciences, 1149:191-195. DOI: 10.1196/annals.1428.081

Vachiéry, N., Lefrançois, T., Esteves, I., Molia, S., Sheikboudou, C., Kandassamy, Y., Martinez, D., 2006. Optimisation of the inactivated vaccine dose against heartwater and in vitro quantification of Ehrlichia ruminantium challenge material. Vaccine, 24(22):4747-4756. DOI: 10.1016/j.vaccine.2006.03.031

Vachiery, N., Maganga, G., Lefrançois, T., Kandassamy, Y., Stachurski, F., Adakal, H., Ferraz, C., Morgat, A., Bensaid, A., Coissac, E., Boyer, F., Demaille, J., Viari, A., Martinez, D., Frutos, R., 2008b. Differential strain-specific diagnosis of the heartwater agent: Ehrlichia ruminantium. Infection, Genetics and Evolution, 8(4):459-466. DOI: 10.1016/j.meegid.2007.06.001

Vaerenbergh, R.V., 1960. Deswcription clinique d'un cas de heartwater chez un bovin a Yamgambi. Considerations sur la l'incidence de cette maladie dans la pathologie locale. Annales de Médecine Vétérinaire, 104(4):200-207.

Valadao, F.G., 1969. Occurrence of hyperacute heartwater in Mozambique and the problem of premunition against this disease. Veterinary Bulletin, 39:696.

Villiers, E.P. de, Brayton, K.A., Zweygarth, E., Allsopp, B.A., 2000. Genome size and genetic map of Cowdria ruminantium. Microbiology (Reading), 146(10):2627-2634.

Vliet, A.H.M. van, Zeijst, B.A.M. van der, Camus, E., Mahan, S.M., Martinez, D., Jongejan, F., 1995. Use of a specific immunogenic region on the Cowdria ruminantium MAP1 protein in a serological assay. Journal of Clinical Microbiology, 33(9):2405-2410.

Waal, D.T. de, Matthee, O., Jongejan, F., 2000. Evaluation of the MAP1b ELISA for the diagnosis of heartwater in South Africa. Annals of the New York Academy of Sciences, 916:622-627. DOI: 10.1111/j.1749-6632.2000.tb05348.x

Waghela, S.D., Rurangirwa, F.R., Mahan, S.M., Yunker, C.E., Crawford, T.B., Barbet, A.F., Burridge, M.J., 1991. A cloned DNA probe identifies Cowdria ruminantium in Amblyomma variegatum ticks. Journal of Clinical Microbiology, 29(11):2571-2577.

Walker, D.H., Dumler, J.S., 1996. Emergence of the Ehrlichias as human health problems. Emerging Infectious Diseases, 2(1):18-29.

Webb, J., 1877. Report of the Cattle Diseases Commission of the Cape of Good Hope. Cape Town, South Africa: Saul Solomon & Co. Appendix. 108.

Wilson, D.D., Richard, R.D., 1984. Interception of a vector of heartwater, Amblyomma hebraeum Koch (Acari: Ixodidae) on black rhinoceroses imported into the United States. In: Proceedings, Eighty-eighth Annual Meeting of the United States Animal Health Association, The Hyatt Regency Fort Worth Hotel, Fort Worth, Texas, October 21-26, 1984. Richmond, Virginia, USA: United States Animal Health Association. 303-311.

Young, E., Basson, P.A., 1973. Heartwater in the eland. Journal of the South African Veterinary Association, 44(2):185-186.

Zweygarth, E., Josemans, A.I., Steyn, H.C., 2008. Experimental use of the attenuated Ehrlichia ruminantium (Welgevonden) vaccine in Merino sheep and Angora goats. Vaccine, 26(Supplement 6):G34-G39. DOI: 10.1016/j.vaccine.2008.09.068

Zweygarth, E., Josemans, A.I., Strijp, M. F. van, Lopez-Rebollar, L., Kleef, M. van, Allsopp, B.A., 2005. An attenuated Ehrlichia ruminantium (Welgevonden stock) vaccine protects small ruminants against virulent heartwater challenge. Vaccine, 23(14):1695-1702. DOI: 10.1016/j.vaccine.2004.09.030

Zweygarth, E., Josemans, A.I., Strijp, M.F. van, Heerden, H. van, Allsopp, M.T.E.P., Allsopp, B.A., 2002. The Kumm isolate of Ehrlichia ruminantium: in vitro isolation, propagation and characterization. Onderstepoort Journal of Veterinary Research, 69(2):147-153.

Zweygarth, E., Josemans, A.J., Strijp, M.F. van, 2000. In vitro initiation and propagation of Kumm stock of Cowdria ruminantium. In: Proceedings of the 15th meeting of the American Society of Rickettsiology. Florida, USA. 45.

Distribution References

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Links to Websites

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CFSPH: Animal Disease Informationhttp://www.cfsph.iastate.edu/DiseaseInfo/index.php"Animal Disease Information" provides links to various information sources, including fact sheets and images, on over 150 animal diseases of international significance.
OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animalshttps://www.oie.int/en/what-we-do/standards/codes-and-manuals/terrestrial-manual-online-access/The Manual of Diagnostic Tests and Vaccines for Terrestrial Animals (Terrestrial Manual) aims to facilitate international trade in animals and animal products and to contribute to the improvement of animal health services world-wide. The principal target readership is laboratories carrying out veterinary diagnostic tests and surveillance, plus vaccine manufacturers and regulatory authorities in Member Countries. The objective is to provide internationally agreed diagnostic laboratory methods and requirements for the production and control of vaccines and other biological products.
OIE Technical Disease Cardshttps://www.oie.int/en/document/heartwater/An updated compilation of 33 technical disease cards, containing summary information, mainly directed to a specialised scientific audience, including 32 OIE-listed priority diseases. USDA-APHIS (USA) are also credited with contributing to the maintenance of the cards.

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