Quantifying the transmission routes of gastroenteritis in Pakistan and developing targeted interventions

Gastroenteritis is an infection of the stomach and the intestine by harmful bacteria, and other similar microbes, such as viruses. It causes diarrhoea and dehydration, which can be easily complicated in areas of the world where clean water is in short supply. The disease is a major health problem in Pakistan, where it is estimated to be responsible for nearly 60,000 deaths annually. Indeed, in Pakistan, 38% of children under five years old have received treatment for diarrhoea at some point in their lives.

In this project, our project team of social scientists, microbiologists, engineers, epidemiologists, chemists and statisticians will combine to take a genuinely inter-disciplinary approach to understanding the various social, biological, chemical and technical factors affecting the spread of gastroenteritis through agriculture, sanitation, drinking water, food, and person-to-person contact. A significant effort will be made to understand the social attitudes to water, sanitation, hygiene and how those link to agriculture, food and the way communities live their lives. At the same time, the information obtained from studying those cultural issues will be used to help decide on a plan for sampling water and other environmental samples for chemical and biological measurements and experiments.

We will focus on some important bacteria and parasites associated with gastroenteritis. Tests will be developed that allow us to rapidly detect those target bacteria (Campylobacter and E.coli) and parasites (Cryptosporidium and Giardia) based on DNA sequencing technology. Among these, Campylobacter is particularly strongly associated with growth-stunting in children. We have recently developed new tests in the UK to allow for rapid detection of the bacteria associated with tuberculosis (bTB) in cows, and we will adapt that technology in Pakistan for gastroenteritis.

The development of such low-cost, easily portable, and reliable tests for rapid detection of harmful bacteria and parasites will be a groundbreaking development for disease surveillance and prevention.

As part of the project, we will also test the various transmission routes of those bacteria in causing gastroenteritis. To do this, we will set up experiments to, for example, explore the transmission of harmful bacteria from soil or water into leaf crops, root vegetables and fruit.

We will also involve a wide variety of social partners. We will use surveys and run facilitated workshops to meet the various people with a stake in clean water and food, good sanitation, and public health. This includes households, tenants and landlords; community leaders; politicians; local and central government; governmental agencies, including those responsible for environmental protection; academic partners in the local universities; water and wastewater companies; the farming community; medical personnel; public health experts and administrators; and a wide variety of NGOs and development agency representatives, including UNICEF.

The project will generate a large amount of information about the cultural issues affecting the transmission of harmful bacteria such as Campylobacter, as well as technical information on the means of infection. Importantly, useful tests will be developed to help significantly improve the ability of experts in Pakistan to monitor harmful bacteria and prevent infections. We also see important opportunities for transferring our knowledge and technology further afield to other low- and middle-income countries.

Gastroenteritis contributes to stunting and cognitive impairment in children, particularly following bacterial and parasitic infection. Transmission mechanisms, including food, e.g. vegetables and poultry, drinking water, and person-to-person contact, are intensified by social determinants, such as poverty and inequality. The health burden is particularly high in LMICs, such as Pakistan. Critically, it is in these countries that we know least about the importance of different transmission routes. Water Sanitation and Hygiene interventions have been disappointing. We believe that this can be improved by basing interventions on evidenced transmission pathways, and knowledge of the societal structures and behaviours that facilitate infection and are amenable to intervention.

We will combine social science, molecular biology and microbial ecology, bioinformatics, epidemiology, and environmental engineering, to quantify transmission routes for non-viral gastro-enteric pathogens at multiple locations in Pakistan and determine the social context influencing transmission.

Work packages include structured sampling for infection in patients and healthy people to quantify and characterise bacterial and parasitic pathogens selected for their impact on acute gastroenteritis and evidence linking them to enteric dysbiosis, growth and cognitive development (Shigella, E. coli, Campylobacter, Salmonella including Typhi, Cryptosporidium and Giardia). Domestic, environmental and food chain sampling will support tracking of sources and transmission. Complementary work will (i) seek to understand societal and cultural features relevant to gastrointestinal infection and control and (ii) evaluate approaches to agriculture and wastewater treatment to decrease pathogen burden in the environment and on food.

Findings from this work will inform identification and prioritisation of interventions and will be followed by an evaluation of the most promising feasible intervention.

Gastroenteritis is a major public health burden in Pakistan and this project will attempt to mitigate that. Furthermore, the information gained about non-viral gastroenteritis transmission in Pakistan and the molecular tools developed to do that will be transferrable to other low income countries where in general there is a high risk of gastroenteritis and its health sequelae. The substantial importance of these infections arises from both acute illness with associated social impact on education and economic productivity, and the longer-term effects. This is why we are targeting those non-viral infections with strong associations with growth faltering and intellectual impacts in children. Gains from reduction in these infections are therefore potentially substantial, as evidenced by the support we have received for this proposal from UNICEF.

By mapping out transmission routes accurately and quantitatively to inform control measures, we expect to allow more cost-effective interventions. This has the potential double-impact of making it more likely investment will flow to support more effective, evidence-based, and culturally-appropriate and acceptable approaches, as well as cost savings, by avoiding the implementation of ineffective interventions. To optimise our ability to achieve real impact, we plan to include both technical and sociological research to underpin the planning of interventions. Although we are working carefully to ensure that we identify and test the most effective intervention(s) in a way that is fully informed by the local context, we do also expect that our findings will have the scope for far wider impact. Firstly, we have chosen populations and settings that are not particularly unusual or unique so that many areas with similar contexts prevail widely elsewhere. Secondly, the general approach of identifying the contextual factors fully can be applied in other settings if we can demonstrate that it allows an efficient and effective intervention.

The project will impact - and we will explicitly monitor and assure - capacity development in Pakistan. The research programme will be structured in such a way that during the first half of the project, Pakistani researchers will visit the UK for training in molecular biology methods, bioinformatics and statistical analysis. Samples will be processed in the UK during this first phase to ensure quality-control based on established and well-performing protocols. During the second half of the project the entirety of the sample processing - and, crucially, the analyses - will be performed in Pakistan. Developing a cohort of junior researchers with the skills necessary to make a major public health impact in that country will thus be a lasting mark of this project. Using our contacts from a wide, collective network across a range of countries, we will additionally invite researchers from other LMICs to the UK training workshops. This will result in a similar impact for those countries but will also contribute to developing potential international links between the early-stage researchers who may, indeed, over the course of their own careers, face similar public health challenges. Our commitment to this is reflected in focussing a substantial proportion of funding for work in the field and to support travel for project staff to work at each other's institutions.

Finally, there is a major potential impact from raising the profile of the commercial pathogen surveillance opportunities in LMICs with companies such as Oxford Nanopore. Some funding is available in Pakistan but purchasing equipment and consumables required, or securing the long-term support to run, and maintain, equipment is challenging. Through our links with these companies, and invitations to UK workshops, we will demonstrate the inherent commercial opportunities to achieve more efficient technical support with consequent long-term benefits in health and medical research in Pakistan.