Scrub typhus is a bacterial infection causing febrile illness in many tropical and subtropical countries in East, South East and South Asia. Countries where scrub typhus occurs include India, China, Bangladesh, Pakistan, Indonesia, Vietnam, Thailand, Japan and Australia. The bacterium (Orienta tsutsugamushi) is transmitted by the larvae of mites during blood-feeding. Scrub typhus can lead to severe complications including lung failure, kidney failure and brain infection. Scrub typhus appears to be very common in affected regions, accounting for up to a third of all fever cases in some settings. Nevertheless, little is known with respect to the transmission of scrub typhus. Scrub typhus is one of the most neglected tropical infections in terms of research, clinical management and prevention. We do not know how many cases develop fever after infection and how many cases with fever develop complications. We further do not know how scrub typhus infection is transmitted in the community and what role rodents play in attracting mite larvae. This study is the first large scale cohort study specifically designed to gain a fundamental understanding of scrub typhus epidemiology in a region that is highly affected by the disease. While the main emphasis of this study is on scrub typhus as the most important infection, we will study two less common infections caused by very similar bacteria called Rickettsia: flea-borne murine typhus and tick-borne spotted fever. The study will be conducted in South India (Tamil Nadu) and follows up 40,000 people living in affected villages. Participants will be followed up at 2 monthly intervals to ask for the occurrence of fever in the past 2 months. We will take blood samples of all identified fever cases and test for the three infections (scrub typhus, murine typhus and spotted fever). They will be asked to proactively come to study clinics in the case of any fever or subfebrile temperature. In these ongoing fever cases we will do additional blood tests including polymerase chain reaction to understand the genetic variety of Orienta tsutsugamushi. Participants will be asked questionnaires regarding living conditions, socio-economic data and occupational factors. We will use satellite images and GPS data to study the geographical risk factors for scrub typhus and Rickettsia infections. We will catch rodents (the main carriers of infected mite larvae) at different locations in the study area and explore whether there is a relationship between the number of infected mite larvae on rodents and the occurrence of human cases in the neighbourhood. The data collected in this study will be used to estimate the incidence of scrub typhus and severe scrub typhus in the community. We will calculate household and spatial risk factors for scrub typhus and the economic impact of scrub typhus in the community. While expected case numbers for murine typhus and spotted fever may be lower, we aim at estimating most of these same parameters for these two infections as well alongside scrub typhus. The data from this study will help doctors to decide on treatment approaches and public health services to decide on intervention efforts. The immunological data will help vaccine developers to understand better how scrub typhus infection confers immunity. Data on rodents and mites will help inform disease control policies. Data on murine typhus and spotted fever will provide a basic understanding of the epidemiology of these rarely studied infections.