Optimal control strategies for rodent-borne zoonoses in Brazilian slum settlements One billion of the world's population lives in slum settlements, comprising 78% of the urban populations from the world's poorest countries.  Residents suffer an increased burden of a wide range of diseases. Many of these health problems involve zoonotic disease - infections circulating in wildlife or domesticated 'reservoir' hosts that can be transmitted to humans, where they can cause serious illness or mortality. Most of the infectious diseases that have emerged in humans recently are zoonotic (e.g. HIV-AIDS, Ebola). Most circulate naturally in wildlife, often rodent reservoirs. Hence, learning to control the spread of infection from rodent reservoirs to humans in urban slums, particularly in poor countries, is a challenge that must be addressed.    Leptospirosis is perhaps the most widespread zoonotic disease. Hosts are infected with bacteria, leptospires, which infect the kidneys of reservoir hosts and are shed with the urine. This is the ultimate source of infection for humans, though the main mode of transmission is contact with contaminated water or soil. Leptospirosis is a systemic disease in humans. Manifestations range from relatively mild to severe life-threatening forms for which case fatality may be >50%. Its burden falls mainly on the world's poorest people, traditionally rural-based subsistence farmers, but recently shifting from a rural to an urban setting. Our study will focus on leptospirosis, which is important in its own right, but the project is directly relevant to other zoonoses in slum settings, and to the health of these communities more generally. The work will be carried out in the urban slums (favelas) of the city of Salvador, Brazil. More than 12,000 cases of leptospirosis are reported in Brazil during urban epidemics each year of which around 12% are fatal.  Realistically, the threat from leptospirosis and similar diseases in impoverished urban slums will not be countered by technological or sophisticated measures. Rather, a global health priority, and an overarching aim of our program, is to develop the means of enabling agencies working locally to minimise the threat that these reservoirs of infection pose, using methodologies that can be applied effectively, cheaply, and without the need for a sophisticated infrastructure. To this end, we will determine the consequences of various management practices (controlling either rats or the environment) so that optimal interventions can be identified that reduce total rat population size, and hence the quantity of shed leptospires and the risk to humans, in the most cost-effective way.  We are in an arguably unique position to do this. We have a very broad multi-disciplinary team from medics to social scientists, combining expertise from the UK, Brazil and the USA, and we have strong links to local public health agencies. Hence, through our project, we will determine the efficacy (evidenced by a range of metrics) of a range of control strategies, guided by, and in collaboration with, local agencies.   The overall structure of our study will be a comparison of the range of sanitation-control measures currently being employed in different favelas across the municipality of Salvador. Following consultations locally, we have identified three categories that have been operational for at least the last twelve months, and that provide us with sufficient sites to support statistically valid comparisons. At each site, the following data will be collected: (i) rat abundance; (ii) the proportion of the rat populations carrying leptospires and other key pathogens (iii) concentrations of pathogenic leptospires in the environment; (iv) the proportion of the human population that have been infected with leptospires and these other key pathogens; (v) severe cases of leptospirosis reported in humans over the last 20 years; and (vi) attitudes of local residents to methods of sanitation control, especially in relation to effects on disease risk. The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world.