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TicVac-U and the Prevention of Tick-borne Diseases in Uganda

Globally, tick-borne diseases pose a major threat to the livestock industry mainly because of the extensive distribution of ticks and the pathogens they transmit. Uganda suffers an aggregated annual loss (direct and indirect) of over US$1.1 billion in the fight against ticks and tick-borne diseases (TBDs). The economic losses are from increased tick control costs including the cost of acaricide use as well as its negative externalities, the cost of direct mortality of high-grade animals, and the loss of investment opportunities in the livestock sector arising from losses in milk and meat production due to ticks. Up to 90% of the most economically debilitating common cattle diseases in Uganda are caused by just three types of tick species – R. appendiculatus (Brown ear tick), R. decoloratus (blue tick) and A. variegatum (bont-legged tick).

Common tick-borne diseases in cattle in Uganda and their prevention (prophylaxis)

East Coast Fever

The most widely spread and economically significant of the tickborne livestock diseases in Uganda is East Coast fever (ECF). It is caused by the protozoan haemo-parasite Theileria parva, whose principal vector is R. appendiculatus (brown ear tick), the most widely distributed tick species in Uganda. The R. appendiculatus tick on its own contributes to almost 60% of losses in beef production and 48% of losses in milk production experienced by the livestock sector in Uganda.

East coast fever is enzootic and still endemic in 13 African countries across the East, Central and Southern Africa region including Kenya, Rwanda, Burundi, Tanzania, Malawi, Zimbabwe, Sudan and the DRC. 

Control and Prevention of East Coast Fever

The control of East Coast Fever depends on 2 strategies, tick control and vaccination. Tick control of R. appendiculatus (brown ear tick) in Uganda has been attempted mostly through acaricides– pesticides that kill ticks.

Until the TicVac-U anti-tick vaccine breakthrough, no practical vaccine for East Coast Fever existed in Uganda. Only South Africa and Mozambique have managed to reduce the national impact of the disease through tick control using a 50-year-old infection and treatment technique. Unfortunately, it’s time-consuming to manufacture and costs 20 times more than other common livestock vaccines.

In the absence of a practical, low priced East Coast Fever vaccine, farmers in Uganda have long resorted to regularly dipping their cattle in acaricides, but this is labor-intensive, often requiring farmers to dip their cows more than once a week. This has led to the emergence of acaricide-resistant ticks, acaricide contamination of meat, milk and the environment, and other risks to human and animal health or other collateral effects on cattle.

“We’re struggling to control East Coast Fever in much of Africa. Acaricides are not working and ticks are becoming resistant. The lack of a practical vaccine has necessitated us to develop a thermostable vaccine that is practical, user-friendly and low-priced” Principal Investigator, Dr Margaret Saimo-Kahwa said.

“TicVac-U anti-tick candidate vaccine has already shown 86% efficacy against the R. appendiculatus tick, making it the first thermostable vaccine for East Coast Fever in Uganda,” Dr. Saimo-Kahwa noted.

Heartwater (Cowdriosis)

The second most economically significant tick-borne disease in Uganda (after East Coast fever) is Heartwater (also known as cowdriosis). Its causative pathogen is an obligate intracellular bacterium previously known as Cowdria ruminantium, whose principal vector in Uganda is Amblyomma variegatum (the bont-legged tick). 

Once infected with heartwater, the average incubation period in cattle is around 18 days with an onset of neurological symptoms including high fever. The disease burns the liver and lungs of the affected animals, making them move in circles before they finally die. 

Control and prevention of heartwater 

There is no effective vaccine for heartwater (cowdriosis) in Uganda outside the use of a 50-year-old infection and treatment technique developed in South Africa. Clinical trials are underway involving the use of the TicVac-U candidate vaccine as a tick control method to prevent infestation of cattle with heartwater by the Amblyomma variegatum.

The technique of using TicVac-U as a tick control method to eliminate the vectors that cause heartwater is not new. In heartwater-free countries such as South Africa, strategic tick control through the elimination of Amblyomma ticks via vaccination has remained the main approach that has led to enzootic stability. 

Evidence from other countries also shows that strategic tick control using an anti-tick vaccine to control tick numbers leads to a situation where natural infection of livestock occurs and high levels of immunity are maintained, achieving not just epidemiological stability concerning heartwater, but also other tick-borne diseases. Through the elimination of vector numbers, this approach has been demonstrated to be the most economical and practical option for eradicating most tickborne diseases in endemic regions.

Babesiosis (Redwater)

Last but not least, another economically significant tick-borne disease in Uganda is Bovine babesiosis (Redwater). Babesiosis, also known as redwater fever, is a cattle disease whose main causative agent in Uganda is a protozoan parasite known as Babesia bigemina. It is transmitted by the Rhipicephalus decoloratus tick vector (African blue tick), which is widely present in Uganda and other tropical regions.

Common symptoms of Babesiosis in cattle include fever, anaemia (via direct red blood cell injury), and red urine (due to intravascular hemolysis).

Control and Prevention of Babesiosis

There is no effective vaccine for Babesiosis in Uganda and the cattle disease overall continues to cause a serious burden to livestock farming not just in Africa but globally. This is in no small part due to the ability of Babesia parasites to evade the host’s immune response, hence causing acute and persistent infections in cattle.

Recently however, important progress has been made by our scientists working on the anti-tick vaccine breakthrough which has managed to achieve efficacious control of this important tick-borne disease with significant potential to positively impact livestock health in affected regions of Africa.

In early trials aimed at controlling Bovine Babesiosis, the overall efficacy of the TicVac-U vaccine candidate against R. decoloratus was 53% (This is the African blue adult tick responsible for transmitting Babesiosis). 

As our scientists at the Anti-Tick Vaccine Development Initiative continue to make advances in the control of ticks and tickborne diseases in Uganda, the goal is to improve TicVac-U vaccine efficacy and turn it into the first thermostable babesiosis vaccine in Uganda and Africa.

Anaplasmosis

The last of the economically significant tick-borne diseases in Uganda is Bovine Anaplasmosis (Gall sickness). It is caused by Anaplasma marginale parasites whose principal vector in Uganda is also the R. decoloratus (African blue tick). Clinical signs of Gallsickness in cattle include fever, progressive anaemia (blood loss), weight loss, rumen stasis, constipation and icterus. 

Once infected with Anaplasma parasites, they penetrate the red blood cells and start multiplying. The average incubation period in cattle is around 21-28 days after tick bite transmission. Once the red blood cells are infected, anemia develops which can result in cattle losing up to 70% of their red blood cells, which only becomes noticeable once the animal has lost more than 40-50% of its red blood cells.

Control and Prevention of Anaplasmosis

The control of Anaplasmosis (gallsickness) depends on 2 strategies, tick control and vaccination. Tick control in Uganda has been attempted mostly through acaricide use but this has failed and has led to the emergence of acaricide-resistant ticks on top of acaricide contamination of meat, milk and the environment.

There is no effective vaccine for Anaplasmosis in Uganda. Unlike Babesiosis, blocking against the Anaplasma parasite isn’t possible so the disease is still endemic in many pastoral regions of Africa. What is advisable, based on evidence from other countries, is strategic tick control using an anti-tick vaccine to control tick numbers

This leads to a situation where natural infection of livestock occurs and high levels of immunity are maintained, achieving not just epidemiological stability concerning Anaplasmosis, but also other tick-borne diseases. This is the most economical and practical option for eradicating most tickborne diseases in endemic regions. 

Clinical trials are thus still ongoing involving the use of the TicVac-U candidate vaccine to help cattle develop immunity against Anaplasmosis as well as other tick-borne diseases, by increasing antibody levels to ensure immunity.

The use of vaccines in the control of tick-borne diseases

Vaccination is an attractive alternative for the control of tick infestations as it is a more environmentally friendly method. By targeting tick vectors, tick vaccines can control several tick-borne diseases simultaneously. Considering that vector-borne pathogens exploit tick proteins to establish an infection, targeting the pathogen in the vector by blocking transmission is an innovative and promising method for controlling vector-borne infections. 

Tick vaccines first became commercially accessible in the early 1990s. During this period, commercial vaccines TickGARD (in Australia) and Gavac (in Latin America) containing the recombinant Bm86 gut antigen were developed for cattle. In Mexico, Cuba and other Latin American countries, tick vaccines based on the Bm86 gut antigen have proven to be the most feasible tick control method offering a cost-effective yet environmentally friendly alternative to acaricides. These regions have seen the tick population decline by at least 80%; they have also experienced a decline in tick-borne diseases (TBDs), especially babesiosis and anaplasmosis, proving vaccines to be the most viable option. 

Earlier stall experiments by our scientists at COVAB in Uganda have also shown that Ra86-based vaccines stop the attachment of ticks by 60% (Saimo et al 2011).  In addition to blocking the growth of Theileria parva parasites in adult ticks, it also reduced the ability of nymphs to moult into adult ticks (Olds et al, 2012).  

Ra86-based anti-tick vaccines can therefore play a part in integrated pest management and control strategies for R. appendiculatus, R. decoloratus and Amblyomma ticks because the Ra86 protein is localized in the tick gut and is known as a concealed antigen from the host immune response during normal tick feeding.  

Vaccination doesn’t just stimulate effective and long-lasting immunity to infectious diseases in animals but it can also help protect consumers against zoonotic pathogens that pass from livestock to humans.

Conclusion

As more farmers in the country continue to adopt susceptible exotic cattle and their crossbreeds, the control of TBDs has become a matter of national economic importance. But in the absence of a practical, low-priced anti-tick vaccine, farmers in Uganda have resorted to dipping their cattle regularly in acaricides, often dipping their cows more than once a week. This has led to the emergence of acaricide-resistant ticks and other collateral effects.

While acaricides have been helpful, they have failed to control tick infestations and should only be used as part of an integrated tick management and control strategy that includes vaccination. The launch of TicVac-U will play a major role in the control and prevention of tick-borne diseases such as East Coast fever, babesiosis, anaplasmosis, and heartwater. These have continued to decimate cattle and pastoral herds in Uganda. Vaccination will boost the dairy and milk export industry by boosting productivity and solving the issue of acaricide residues in beef and milk products which have been a hindrance to the dairy and beef export industry. 

 

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Dec 26, 2021