Containing antimicrobial resistance in rural Cambodia: a one-health multi-disciplinary intervention to improve village healthcare and farming practice

Antibiotic resistance has been termed the greatest menace of the current century by the World Health Organization. If appropriate measures to mitigate antibiotic resistance are not taken immediately, it is estimated that millions of people will die, in the near future due to complications arising out of inability to treat resistant infections and most of this burden will fall on the poor, underdeveloped part of the world.

The main drivers of antibiotic resistance are antibiotic use and antibiotic residues in the environment. Both generate resistant bacteria. Appropriate monitoring and mitigation of both is neglected in poorer countries due to inadequacy of awareness, infrastructure, economics, political will, socio-cultural dimensions and a myriad of other factors. Resistance knows no geographical or political boundaries; it spreads quickly all over the world. So, not only the poorer human beings from underdeveloped countries suffer, these countries also become 'hot spots' of resistance generation and spread.

Cambodia is the poorest country in the Greater Mekong Sub-Region and continues to recover from a prolonged civil war which saw its institutions and infrastructure destroyed, which resulted in the loss of most of its educated personnel. With support of international partners, Cambodia is rapidly developing; Cambodia was one of the countries, which achieved the millennium development goals in reducing infant and child mortality. The proposed provinces for the antibiotic resistance study and intervention are among the most remote and underserved both within the formal health and agricultural systems and rely for care on personnel who have minimal training for both care of patients and animals. When a person or animal becomes ill, medicines including antibiotics, often of dubious quality are bought from local pharmacies or market stalls and administered by the persons themselves. Human antibiotics are often given to animals and vice versa. Due to the deficit of trained health personnel, Cambodia has developed a cadre of village level healthcare workers, who have minimal training and little supervision to treat villagers or their sick animals. Little care is taken in disposing of antibiotics, which must be resulting in huge amount of residues in Cambodian environment.

The proposed project will investigate and map the current status of antibiotic use, antibiotic resistance and antibiotic residues in the target area and would examine the drivers for these in these remote areas, involving various stakeholders including human and animal healthcare providers and policy makers. We would involve the newly instituted laboratory and personnel in the Royal University of Agriculture and Veterinary Medicine as well as our partners, the Ministry of Health and the Ministry of Fisheries and Agriculture. We would also seek to evaluate the efficacy of a community dialogue intervention in improving the knowledge and understanding of use, handling and disposal of antibiotics to achieve appropriate antibiotic resistance management.

The study proposed is directly and primarily relevant to the development challenges of Cambodia. In particular, it addresses health and agriculture systems needs that have been identified by the Ministry of Health/communicable disease division (MoH/CDC) and Family Welfare (MOHFW) and Ministry of Agriculture, Forestry and Fisheries (MOAFF). Our CAmBR consortium has been formed after consultations by the Malaria Consortium (MC) Cambodia country office, and London/Leeds (by skype) with MOH/CDC and MOAFF. They have agreed to join the consortium for the development stage proposal, and possible full stage activity. The intervention will develop guides, training and monitoring meetings to improve the quality of the health services provided within the community facilities public and private in northern Cambodia to reduce antibiotic prescribing. The intervention will include working through agriculture extension workers, vets and farmers to reduce prescribing, and community dialogues to improve knowledge, attitude and practice of community members for improving the rational use of antibiotics. We will embed the intervention within the existing health and agriculture systems in order to maximise the potential for impact, replicability, sustainability and value for money.

The antibiotic over-use by health providers, farmers and community members is contributing to high rates of bacterial/ drug resistance. We propose to further build our partnership, involving the ministries of health, agriculture and Agricultural and Veterinary University in Cambodia and international partners. We propose to develop a 'one health' intervention focussed on behaviour change in village communities including:
i) farmers through agricultural extension workers,
ii) health centre and drug shop/ informal health providers,
iii) community members, through community dialogues

In the development phase will strengthen the partnership, learn how we may apply these interventions in the context, prioritise the outcomes and prepare a proposal to pilot and conduct a controlled intervention of the 'one health' intervention. The study will include assessing stool and environmental contamination and bacterial resistance.

The consortium includes partners with the knowledge and capacity to develop and deliver effective intervention in this context. The Cambodian ministries and Universities recognise this issue as a priority. Malaria Consortium has been active in Cambodia addressing malaria and anti-malarial drug resistance. Malaria Consortium and Leeds through the COMDIS research consortium have tested community dialogues and antibiotic use in Africa, and are testing this in Bangladesh. Leeds and China colleagues have shown an effective intervention to reduce rural primary care prescribing of antibiotics. Professor L of Karolinska is a world expert in environmental AMR.

The research will provide good evidence to shape the policy and practice to control antibiotic overuse in Cambodia and the SE Asian region. In the development phase we will research through record review and interviews what should be feasible intervention package. We will design and submit a proposal for the full stage. If funded we will do formative research including interviews with health workers, farmers/vets and the community and key informants from the ministries of health and agriculture. We will refine the intervention and pilot-evaluate the intervention. We then plan a controlled intervention (assessing the potential to do this as a village cluster randomised controlled trial). This will aim to assess the effectiveness of the multifaceted interventions on improving the rational use of antibiotics in rural Cambodia. The results will be disseminated nationally with the ministries of health and agriculture, and other stakeholders. We will support them to plan, budget and initiate scale up of the 'one health' intervention package.

This body of work will reinforce the policy of rational use of antibiotics; build the compelling and supportive climate for rational use of antibiotics; developing collaboration between the agricultural and health system and Universities in Cambodia and internationally. At the social level, the study will demonstrate how to change social norms on rational use of antibiotics. At the health and agricultural extension systems level, the study will contribute to reducing the antibiotic resistance and the burden of antibiotic resistant infections, and provide evidence for policy makers to reform the current antibiotic regulations and their implementation. The results will be disseminated internationally through peer reviewed publications and research/ policy briefs and presentations. It will contribute to further developing interventions and research that our consortia members and others are undertaking in other low-middle income countries.