Development of a Bacteriophage Product to Control Campylobacter Contamination in Kenya

Lead Research Organisation: University of Nottingham
Department Name: Sch of Biosciences

Abstract

Campylobacter is the leading bacterial cause of gastroenteritis worldwide, and recent data demonstrate that it is particularly detrimental for children under age two in developing countries. Globally, Kenya has the highest case fatality rate of campylobacteriosis, with 8.8% of infected people dying, mostly children - as compared with <0.1% in most industrialized countries. Given that antibiotic resistance rates for Campylobacter are increasing, alternative sustainable options are urgently needed. To address this public health issue, we have undertaken to develop bacteriophage (phage) products to decrease Campylobacter levels, specifically targeted for applications in Kenya. Phages are naturally occurring viruses that target and kill specific bacteria, and are active against both antibiotic-resistant and antibiotic-sensitive bacteria. They are easy to isolate from contaminated environments, and relatively inexpensive to produce, and form the basis of several commercial products targeting foodborne pathogens in North America.

Technical Summary

Kenya has the highest case fatality rate of campylobacteriosis, with 8.8% of infected people dying, mostly children. As in many other countries, poultry sources are the primary source of Campylobacter infection in Kenya, with studies demonstrating contamination in up to 77% of retail poultry samples in the capital city of Nairobi. The bacteria frequently reside in the intestinal tracts of chickens then spread to the surface of meat products during slaughter. Campylobacter-specific bacteriophage will be isolated in Kenya and characterised in preparation for their application against Campylobacter contaminating chicken meat in Kenya. While phages in North America are currently sold in liquid formats, a liquid phage product would be disadvantageous in Kenya due to the requirement for refrigeration and the bulk shipping and storing of liquid products is costly. A spray dried product will be developed that can incorporate a cocktail of phages for rehydration at the site of use. These studies will be undertaken in parallel with stakeholder engagement research.

Planned Impact

Health and Well-Being Impacts
In contrast to Western countries where Campylobacter typically only affects adults, in developing countries Campylobacter infection is primarily a disease of childhood. This is presumably due to the fact that good hygiene practices are less common in the food chain in developing countries, so children there are more readily exposed to Campylobacter bacteria and also develop natural immunity against the bacteria by the time they become adults. Given that Campylobacter is the leading bacterial causes of diarrhoea in children in developing countries, and Kenya has the highest Campylobacter-associated death rate worldwide, a future phage product has the potential to save many lives, as well as to significantly improve overall health. And while having fewer diarrheal episodes has obvious short-term benefits, the long-term impacts are typically more profound. Studies have shown that frequent diarrhoea episodes early in life correlate with decreased physical growth, impaired cognitive development, and diminished performance in school years. Campylobacter infection of immuno-compromised members of the population can lead to increased debilitation and the need for medical intervention, and Kenya has the fourth highest HIV epidemic. Thus, by applying Campylobacter-specific phages to poultry products in Kenya, we aim to decrease the frequency of diarrhoea and thereby improve the overall well-being and productivity of the population for years to come.
Economic Impacts
Decreasing the number of Campylobacter-associated diarrhoea episodes would reduce the working days lost and also mean that families in Kenya could spend less time and money obtaining medical treatments. The mortality and long term effects of Campylobacter infection of children represent a significant loss in potential for the country.
Industry Impacts
Poultry meat producers could benefit, since applying Campylobacter phages to retail meat could circumvent negative market impact as the sources of Campylobacter are likely to become evident as Kenya addresses the root causes of child mortality.
Not only is there any commercial Campylobacter phage product available anywhere in the world, to our knowledge ours would be the first commercial application of any phage product on the African continent. In addition, ours would be the first project globally to incorporate dry powder formulated phage technology for an application in the food industry. This technology would enable the phages to be shipped and stored for extended periods of time without refrigeration, which would open the phage field more broadly to applications in developing countries. For all of these reasons, Campylobacter phages would be a first-in-class product.
Public Policy Impacts
The project hopes to bring the use of phage as a specific and sustainable anti-bacterial treatment to the attention of policymakers in Kenya. There is a general need for alternative ways to control bacterial exposure and treat bacterial infection as antibiotic resistant rates soar in developing countries.
Academic Impacts
The project offers a critical opportunity for capacity building and knowledge exchange for the Kenyan groups and the opportunity of the UK scientists to exploit research outcomes in Africa. There is opportunity for a Kenyan post-doctoral researcher to travel to the UK and work in the research laboratories to gain experience and apply the knowledge in Kenya.

Publications

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Description Chickens are a common foodborne and cross-contamination source for the dissemination of Campylobacter-associated disease in Kenya as they are in many countries around the world. Chickens reared in Kenya and consumed in Kenya are reared on small holdings, often by women. These are consumed either by the family or sold to supplement family income. Chicken meat attracts a premium price in Kenya. Female ownership of small livestock in rural agricultural settings is not uncommon in developing countries. Therefore to administer the product the anti-Campylobacter bacteriophage product will require local engagement and compliance. Although the slaughter of chickens for retail is controlled by regional veterinarians (meat inspectors) the conditions are quite variable and frequently sub-optimal for the application of bacteriophage on to carcass. Alternatively the administration of the bacteriophage in water could be effective as chickens are kept in lairage and slaughtered to order. This will require the availability of cheap long shelf-life bacteriophage products that are in development in the project.
Exploitation Route Bacteriophage may be used in drinking water for chickens in lairage pre-slaughter in Kenya. To achieve this phase diagram have been developed and used to predict the long-term ambient storage stability of spray dried products under different processing conditions. Long-term ambient storage stability is particularly important for distribution to developing countries where access to refrigeration facilities needed for biologics in liquid formulation are not always available. Although we have successfully produced a long shelf life products for Campylobacter phages using spray-dry and lyophilization technologies the approaches and learnings are of value to the low cost preparation of other bacteriophage preparations and biologics to be transported worldwide.
Based on interviews with Kenyan poultry farmers would put their trust in the product if it had a Diamond Mark of Quality from the Kenya Bureau of Standards. There was a strong preference indicated for a powder formulation that could be given to poultry orally (either in water or food). These messages need to be the focus of further engagement activities with government stakeholders.
Sectors Agriculture, Food and Drink,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

URL https://www.phagesforglobalhealth.org/
 
Description Interactions with farmers, butchers and retailers to provide information on phage and other sustainable farming practices applicable in rural East Africa that do not rely on antibiotics.
First Year Of Impact 2018
Sector Agriculture, Food and Drink
Impact Types Cultural,Societal

 
Title Phage lyophilization 
Description We have designed a systematic lyophilization method to produce freezedried bacteriophage suitable for transport, enabling phage therapy candidates to be screened and propagated in the pursuit of the international development of sustainable phage products to reduce the global disease burdens. 
Type Of Material Technology assay or reagent 
Year Produced 2020 
Provided To Others? Yes  
Impact Researchers asking for details to enable methods to be developed for bacteriophages for inter-laboratory transport. 
 
Title Phage spray dry technology 
Description Spray drying can be used to produce dry powder that has improved thermal stability relative to liquid dosage forms, which compared to other alternatives s is a low-cost process. Dry powders have less weight and volume compared to liquid, which can reduce transportation costs and storage space requirements. 
Type Of Material Technology assay or reagent 
Year Produced 2019 
Provided To Others? Yes  
Impact Interest from phage companies on how to utilise the findings. 
 
Description Extending phage applications to Africa 
Organisation Kampala International University in Uganda
Country Uganda 
Sector Academic/University 
PI Contribution Providing technology and adapting methods for local use.
Collaborator Contribution Partners have attended technology dissemination meetings in Africa and begun the task of isolating phage from local sources.
Impact Multidisciplinary with public health, agricultural and social science interactions.
Start Year 2017
 
Description Extending phage applications to Africa 
Organisation Makerere University
Department School of Public Health
Country Uganda 
Sector Academic/University 
PI Contribution Providing technology and adapting methods for local use.
Collaborator Contribution Partners have attended technology dissemination meetings in Africa and begun the task of isolating phage from local sources.
Impact Multidisciplinary with public health, agricultural and social science interactions.
Start Year 2017
 
Description Extending phage applications to Africa 
Organisation Sokoine University of Agriculture
Country Tanzania, United Republic of 
Sector Academic/University 
PI Contribution Providing technology and adapting methods for local use.
Collaborator Contribution Partners have attended technology dissemination meetings in Africa and begun the task of isolating phage from local sources.
Impact Multidisciplinary with public health, agricultural and social science interactions.
Start Year 2017
 
Description Phage Laboratory Workshop in East Africa: Measuring Impacts 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Two-week, hands-on laboratory training course we teach scientists in developing countries how to isolate and characterize phages in their own regions.
July 2017: East Africa Workshop (Uganda)
June 2018: East Africa Workshop (Kenya)
July 2019: West Africa Workshop (Ghana)
Year(s) Of Engagement Activity 2017,2018,2019
URL https://www.phagesforglobalhealth.org/workshops