ETHICOBOTS 2 - One Health Research for Impact

Ethiopia is the second most populous sub Saharan African country. It is also a predominantly agrarian country struggling to emerge from extreme poverty through an ambitious national growth and transformation plan, aiming to achieve middle income status by 2025. Livestock contributes to a high proportion of national income and is a pillars of economic development. Traditional extensive farming systems are being supplemented and replaced with intensive farming, in the case of dairy production using imported Holstein-Friesian crosses to meet high demand for dairy products in the rapidly growing urban population. Bovine tuberculosis (bTB) is endemic in Ethiopia and the prevalence is high in the emerging intensive dairy population, but currently low in local Zebu cattle. Periurban expansion of dairy farms has created hotspots of TB infection and there are no statutory controls in Ethiopia. Consequently, the potential for spread of bTB through trade is an emerging risk.

Our ongoing ZELS research in Ethiopia, Ethiopian Control of Bovine Tuberculosis Strategies (ETHICOBOTS) aims to provide a scientific understanding for the development of sustainable control strategies for bTB in Ethiopia, to reduce the high rate of bTB and its zoonotic transfer in the expanding dairy sector, especially to more disadvantaged population sectors. This Supplementary proposal 'ETHICOBOTS 2 - One Health with Impact' focusses on ensuring maximal impact of the research undertaken to date. It will improve the scientific base established in ETHICOBOTS and will provide clear, evidence-based tools to tackle the high burden of bTB in different sectors of the dairy industry and any zoonotic transmission. We will deliver this work through three specific work-packages, addressing critical evidence gaps to maximise impact:

- Develop a pathway for the Elimination of bovine TB infection from a sub-set of national herds, working closely with the Ministry of Agriculture and Livestock to clear Government farms of bTB. These farms will provide a clear local exemplar of how disease control based surveillance programmes can be successfully implemented. This will generate additional data on disease control and explore the prevalence of anergy, or test-insensitivity, in bovine TB infected cattle.

- Explore new tools to communicate disease control to farmers. We will work with innovators in this field who have established new ways to communicate with farmers in other parts of Africa and in a collaboration with Farmerline, we will test their methods in Ethiopian dairies.

- Address the major evidence gap regarding the cause of tuberculous disease in humans at high risk of exposure to infected cattle. Working with patients and health care facilities in areas with a high prevalence of bTB infection in cattle, we will markedly improve the diagnostic rate in TB patients by improving culture methods and by using modern molecular test to identify the causative disease agent (M. tuberculosis and M. bovis) in a range of samples, including testing for dual infections

The results will provide practical and effective bTB control strategies, targeted at the disease and its zoonotic transmission to humans. Delivering impact through close collaboration with key government and industry stakeholders, we aim to prevent further geographic spread of the disease and to minimise the risks of further transmission to national zebu herd, to protect the livelihood of poor farmers. The project will be carried out with the active participation of the relevant government units and local communities in the field to maximize the likelihood of implementation of results into policy and practice.

Working within the One Health framework established in the ETHICOBOTS (Ethiopian Control of Bovine Tuberculosis Strategies) Programme, we will deliver multidisciplinary research conducted by our Ethiopian partner organisations, supported from the UK, that will:

Determine rates of anergy (unresponsiveness of infected animals in immunological tests) in Ethiopian dairy cattle held in larger, well managed herds. This has been described to be caused by progressive disease, or alternatively, skin test desensitisation can also occur when cattle are repeatedly skin tested. Having determined this, we will use models to estimate true prevalence in these herds and use the data deliver optimal elimination of disease in these large, centrally managed herds.

We will work closely with owners of medium and small scale dairy farms, developing focus groups and community support groups to deliver improved control. We will use innovative mobile communication approaches to share disease control and biosecurity information, to aid controls in these individually owned herds. We will then use the mobile platforms developed above to provide farmers with other information that will help them improve profitability and hence health.

Working with patients and health care facilities in areas with a high prevalence of bTB infection in cattle, we will markedly improve the diagnostic rate in TB patients. We will achieve this by improving culture (enhancing the specimen cold chain and further improving media, including MGIT) and by using established RT-PCR assays, including on mixed cultures as well as actual clinical samples, to identify the causative disease agent (M. tuberculosis complex and M. bovis) in culture negative samples and in some culture positive samples, to check for mixed infections.

Impact Summary
This supplementary programme (ETHICOBOTS 2 - One Health Research for Impact) will address specific scientific research gaps to ensure maximal impact of the research from the research undertaken in ETHICOBOTS. The Ethiopian dairy industry is a major emerging livestock system, concentrated around growing urban centres. This industry depends on 'exotic', imported Holstein-Friesian (HF) cattle and their crosses with local Zebu cattle. These animals suffer a high prevalence of Mycobacterium bovis infection, the cause of bovine tuberculosis (bTB), >40% in infected herds. We hypothesise that the poor workers in this industry and their families are at particular risk of zoonotic exposure and transmission.

The traditional Zebu industry is not heavily infected with M. bovis, the increasing cross breeding of Zebu animals with HF cattle runs the risk of the infection spreading into more extensive, lower value traditional farms, typically managed in smallholdings. In common with most countries in sub-Saharan Africa, there are no control programmes for bTB. Furthermore, given that 90% or more of dairy products are sold direct to consumers, unpasteurised, there is a risk, as the dairy industry emerges further in peri-urban areas, of widespread zoonotic transmission of M. bovis in here - and also if any significant spread to the traditional husbandry systems occurs. It is vital that the disease be controlled before it spreads more to Zebus.

During the past 4 years the multi-disciplinary ETHICOBOTS project has generated significant scientific results/outputs and that will now be considered in year 5 when we will explore and propose bTB control strategies for Ethiopia. During the cause of this project, several research gaps and new concepts have been identified that could boost the outcomes of the original aims of ETHICOBOTS. This proposal (ETHICOBOTS 2) focuses on subjects that we believe will have the largest impact on bTB control, both short-term and long-term.

The outputs of ETHICOBOTS-2, involving senior scientists from both Ethiopian and UK government research institutes, will feed directly into policy making in both countries, as well as to key international agencies. This work is of direct relevance for other emerging dairy industries in LMICs, especially in sub-Saharan Africa, as well as for the UK industry. The desire to eradicate bovine TB from the National herd is the Eradication Strategies for England and Wales. Therefore work as proposed here to assess diagnostic tests that could unmask cryptic infection, i.e. animals that escape detection by the tuberculin skin test is relevant as leaving such animals in herds would at least prolong the eradication process.

Stakeholder meetings on bovine TB arranged by ETHICOBOTS have had a direct impact; the Ethiopian government is now planning for bTB control, initially by testing animals on their own Government farms. Here, we will further strengthen our interaction with the Government, including with a workshop early in the programme to engage between government, veterinary, medical, industry and farming stakeholders, to ensure that all key issues are being considered and covered.

Through our interaction in the field with individual farmers, farm-workers, community health workers and vets, we will develop targeted information about bTB with the aim of changing attitudes and practices relating to animal husbandry, consumption practices, and health seeking behaviour, in order to reduce the zoonotic impact on the health and economic burden of low-income farm workers and their families.

In all, the impact of the research will be to improve bTB control in Ethiopia and thus lead to significantly better human and animal health that will eventually translate itself into a significant input to accelerated economic development in Ethiopia and in other regions with emerging dairy systems.