The pathogen discoverer – in search of novel and/or emerging tick-borne pathogens

Posted on November 01, 2017

 

Africa has one of the highest burdens of infectious diseases of humans and animals. Zoonotic diseases – those transmitted from domestic and wild animals to humans – annually cause 2,2 million deaths and 2,4 billion cases of human illness worldwide. Many of these are concentrated in low- or middle-income countries in Africa.

In many parts of South Africa wildlife, domestic animals and humans live in very close proximity to one another. Rural areas on the boundaries of the Kruger National Park (KNP) are a prime example of this interface. With 65% of all diseases being zoonotic and the incidence of zoonotic diseases on the increase, ensuring an optimum One Health system is essential. While most zoonotic diseases are manageable, it is important to know what diseases are prevalent or emerging in an area to ensure outbreaks do not occur. Diseases such as Ebola and avian flu show the devastating capabilities of zoonotic diseases and the importance of minimising risk.

The University of Pretoria has a strong research focus on ensuring a healthy One Health system, which makes programmes like the Mnisi Community Programme (MCP) essential to ensuring research is relevant and impactful. The MCP is a multidisciplinary platform for research, training and community engagement within the One Health philosophy. At the centre of the programme are the Mnisi community, its animals and the surrounding conservation areas.

Rodents abound in the Mnisi community. In a recent study, Amanda Berrian and colleagues (2016) gained insight into the levels of interaction between humans and animals, including rodents such as rats and mice. It was found that an overwhelming majority of the participants said that they see rodents in and around their homes almost daily. Apart from the aesthetical issues that come with having rodents in one's home, rodents pose a serious risk of transmitting pathogens, directly or indirectly. As such, rodents are considered important reservoir hosts for many tick-transmitted pathogens, and play a key role in the natural circulation of tick-borne viral, bacterial and parasitic infections.

Prof Marinda Oosthuizen is a pathogen discoverer, always on the lookout for novel and/or emerging tick-borne pathogens. Understanding what something is, why it is there and what it can do is her forte. In the past several years she has identified and molecularly characterised new tick-borne blood parasites of domestic and wild animals, including ones that threaten endangered and rare wildlife species. Some highlights include novel Babesia and Theileria species, which she identified as possible causes of mortality in various wildlife species, including sable antelope, roan, rhino, cheetah and giraffe. She aims to build on this by developing molecular diagnostic assays for detecting haemoparasites of veterinary importance.

Prof Oosthuizen says that she has a special interest in the role of rodents as a reservoir host of infection for humans and domestic animals, and the genetic diversity that exists within these rodent-borne zoonotic organisms. She further explains that a big problem in Africa is undifferentiated human febrile illness, which is among the most common symptoms that patients seeking medical care present with, and occurs at a high incidence in both urban and rural communities. However, it is frequently misdiagnosed, and understanding of aetiologies is still very limited. Fever is very often misclassified as malaria, leading to delays in appropriate treatment.

Recent research by Prof Lucille Blumberg and colleagues from the Centre for Emerging and Zoonotic Diseases at the South African National Institute for Communicable Diseases (NICD), suggests that, among others, rodent-borne zoonoses may be common aetiologies for febrile illness in the Mnisi community. This remains of concern, and Oosthuizen therefore turned her attention to rodents in the community in an effort to uncover the threats they might pose as reservoirs of tick-borne bacterial pathogens.

In this study, the research team*, which included collaborators from Washington State University (USA), Stellenbosch University, the NICD, as well as colleagues and postgraduate students from the University of Pretoria, engaged with the Mnisi community regarding the health risks rodents pose to them and their domestic animals. The community members were only too happy to participate and welcomed Prof Oosthuizen and her colleagues into their homes. Rodent traps were set in homes, rangelands and the adjacent Manyeleti Game Reserve. It was noted that in winter, the incidence of rodents in and around people's homes was much higher than in the warmer months – an indication of the seasonal availability of food in the wild. Once caught, specimens and ectoparasites (including ticks) were collected for later testing for a range of zoonotic pathogens. Ticks were also collected from the veld, and from the community's dogs and cattle.

One of the team's rodent traps

Discovering emerging, novel tick-borne bacterial pathogens is important so that people and animals receive the necessary treatment. Prof Oosthuizen begins her search for these pathogens by following a microbiome approach. The microbiome can be explained as the collection of microbes or microorganisms that inhabit a particular environment, creating a sort of mini-ecosystem. Results obtained from microbiome analysis are used to inform further testing with more specific molecular assays (such as real-time PCR assays), and results are confirmed by gene sequence analysis.

During one of the screening processes, the team discovered a blood-borne rickettsia that had not been reported in South Africa before. Anaplasma phagocytophilum is a tick-borne intracellular pathogen that causes granulocytic anaplasmosis in humans, dogs and horses, and tick-borne fever in ruminants. Reports of the zoonotic disease, human granulocytic anaplasmosis, occurring in Africa have been few. In South Africa there have been no official diagnoses of A phagocytophilum in humans. Studies in other parts of the world suggest that multiple strains of A phagocytophilum may be circulating among wild and domestic animals, and these strains may have differential host tropisms and pathogenicity. Furthermore, the degree to which genetic variation contributes to altered pathogenicity of different strains of A phagocytophilum is poorly understood. This is an area that Prof Oosthuizen is currently investigating, and her research will show how closely related the South African strains are to American and European human pathogenic strains. This will be critical for interpreting surveillance data and evaluating the risk to humans, and will contribute important baseline information for understanding the ecology of this emerging zoonotic pathogen.

Prof Oosthuizen says that this research project will undoubtedly expand our knowledge base of zoonotic tick-borne pathogens impacting human health in South Africa, and will enhance our understanding of the challenges faced by rural communities living at the interface. It will also provide valuable data for the development of diagnostic tests that can be implemented in rural communities, ensuring appropriate interventions and improving human health and well-being. Overall, this will be of value not only for South Africa, but also for other African countries.

Prof Oosthuizen continues on her quest to find novel and/or emerging tick-borne pathogens that can have detrimental effects on the One Health system. Playing her part in ensuring the health of people and animals is what motivates her research.

She is a trained microbiologist, focusing on molecular parasitology in the Faculty of Veterinary Science's Department of Veterinary Tropical Diseases Vector and Vector-borne Diseases Research Programme. She is an NRF C2 rated researcher and received the Researcher of the Year Award in the Faculty in 2011.

 

* Oosthuizen's research forms part of a collaborative project with Prof Kelly Brayton (Washington State University, Pullman, USA), Prof Lucille Blumberg (Centre for Emerging and Zoonotic Diseases, National Institute for Communicable Diseases), Prof Sonja Matthee (Stellenbosch University), colleagues from the University of Pretoria (Prof Armanda Bastos, Dr Nicola Collins, Prof Luis Neves, Dr Jacques van Rooyen and Ms Jeanette Wentzel), as well as postgraduate students from the University of Pretoria (Dr Agatha Kolo, PhD, and postdoctoral fellows Dr Mamohale Chaisi and Dr Cory Gall).

 

 

- Author Louise de Bruin

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