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Tackling protozoan parasites of cattle in sub-Saharan Africa

Cattle are host to a plethora of infectious agents including viruses, bacteria, prions, and a range of parasites comprising worms, ectoparasites, and protozoa. Many cattle pathogens are closely related to pathogens of humans, including some that are zoonotic or with zoonotic potential.
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Cattle are host to a plethora of infectious agents including viruses, bacteria, prions, and a range of parasites comprising worms, ectoparasites, and protozoa. Many cattle pathogens are closely related to pathogens of humans, including some that are zoonotic or with zoonotic potential. Any infectious disease that causes loss of cattle life or decreased productivity (work, growth, or fertility) imposes an economic impact. This burden heavily and disproportionately affects low- and-middle-income countries and, in particular, smallholder farmers and pastoralists. Among the myriad of infectious agents of cattle in sub-Saharan Africa, there are a small selection of protozoan pathogens that collectively cost the region’s economy billions of US$ per annum. These are some of the biggest constraints to livestock production across sub-Saharan Africa, affecting food security and hindering socioeconomic development.

Tick and tsetse fly control are used to prevent against infections, as has been the case for many generations. Vector control is complex and comes with many limitations, including the following: (i) Tsetse- and tick-infected regions are vast; therefore, traps can only provide a local level of protection, which needs to be ongoing; (ii) ticks and related insects are a valuable source of nutrition to reptiles and birds and so large-scale insecticide use is not feasible; (iii) cattle plunge-dipping into toxic organophosphates or synthetic pyrethroids can cause significant illness to the farmer and the environment and is not a widely available control option; and (iv) the choice of insecticides used are key, due to selective toxicity and resistance.

Vaccination of cattle to prevent disease transmission is therefore considerably preferable to arthropod management. Although ECF and babesiosis are both preventable diseases through live cell vaccination, such vaccines require a cold chain from lab to cow, which is inappropriate for use in rural settings due to expense and logistics. Additionally, vaccination with Tparva is followed by antibiotic treatment in a simultaneous infection treatment immunisation model. These impracticalities mean that the vaccine is not widely used. A modern subunit, RNA or DNA vaccine, is urgently required.

The primary drug available to treat ECF is buparvaquone; this is over 30 years old and expensive to use, yet, to our knowledge, no new drugs are under development. Buparvaquone is also used to control Theileria annulata (causative agent of tropical theileriosis), and resistance due to mutations in the cytochrome b gene has been identified. The primary treatment for babesiosis is imidocarb. Concerns have been raised regarding use of imidocarb in livestock due to its passage into milk and retention in tissues that are then used as human food . Currently, AAT is primarily controlled by regular administration of prophylactic isometamidium chloride and therapeutic diminazene aceturate and homidium bromide/chloride. The latter is a mutagenic (possibly carcinogenic) DNA intercalating agent, which can be toxic at high doses. Benzoxaboroles have been identified as a potential new class of veterinary drugs against AAT with research and development underway.

Typically, human-infective parasites are subject to more experimental research than relatives that infect cattle. This research gap needs to be addressed if the effects of such pathogens on livestock are to be more effectively prevented. The cellular and infection biology of cattle-infecting parasites do vary from human-infective species and so cannot always be reliably inferred. For example, many apicomplexan parasites are motile and invade host cells using an apical complex, forming a pointed end to the cell. In contrast, Theileria parasites are nonmotile and do not reorient during host cell invasion. These differences are fundamental when designing subunit vaccines against cell surface proteins. Similarly, while the mutations that lead to diminazene aceturate resistance have been characterised in Tbrucei, the mode of resistance in Tcongolense and Tvivax is both distinct and unknown. However, many of the tools and techniques developed for human-infective pathogens can be adapted for use in animal pathogens.

While conscious of biological differences, advances in human-infective parasitology research can and should be exploited wherever possible to improve research capacity and knowledge of cattle parasites. For example, related parasite species often have similar capacity for genetic modification, so experimental protocols (i.e., transfection methodology) and resources (i.e., plasmids) developed in one species can be the starting point for developing methods for others. Similarly, the advancement of experimental techniques in one species (i.e., optimisation of cell fractionation methods for subcellular proteomics) may then facilitate the use of that technique in related organisms. Where novel biology is uncovered, the assessment of similar features (i.e., conserved protein function) in related species is less resource demanding than the original discovery. Finally, the development of treatments or prevention measures against human-infective species could have real impact on cattle diseases if they were studied or developed in parallel.

There is no doubt that veterinary important species continue to be understudied compared to their human-infective counterparts and that we cannot simply extrapolate data from one species to another. However, this is progressively being recognised as an important area of research and with the ability to draw on data and methodology from human-infective parasite species, the scientific community is well placed to start to close this gap.

MacGregor P, Nene V, Nisbet RER (2021) Tackling protozoan parasites of cattle in sub-Saharan Africa. PLoS Pathog 17(10): e1009955. https://doi.org/10.1371/journal.ppat.1009955


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