Tularemia Outbreaks in Sweden | CDC EID

EID Journal Home > Volume 15, Number 12–December 2009

Volume 15, Number 12–December 2009
Research
Landscape Epidemiology of Tularemia Outbreaks in Sweden
Kerstin Svensson, Erik Bäck, Henrik Eliasson, Lennart Berglund, Malin Granberg, Linda Karlsson, Pär Larsson, Mats Forsman, and Anders Johansson
Author affiliations: Swedish Defense Research Agency, Umeå, Sweden (K. Svensson, M. Granberg, L. Karlsson, P. Larsson, M. Forsman, A. Johansson); Umeå University, Umeå (K. Svensson, A. Johansson); Örebro University Hospital, Örebro, Sweden (E. Bäck, H. Eliasson); Ljusdal Healthcare Centre, Ljusdal, Sweden (L. Berglund); and Umeå University Hospital, Umeå (A. Johansson)

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Abstract
Summer outbreaks of tularemia that occurred from 1995 through 2005 in 2 locations in Sweden affected 441 persons. We performed an epidemiologic investigation of these outbreaks using a novel strategy, involving high-resolution genotyping of Francisella tularensis isolates obtained from 136 patients (using 18 genetic markers developed from 6 F. tularensis genome sequences) and interviews with the patients. Strong spatial associations were found between F. tularensis subpopulations and the places of disease transmission; infection by some subpopulations occurred within areas as small as 2 km2, indicating unidentified environmental point sources of tularemia. In both locations, disease clusters were associated with recreational areas beside water, and genetic subpopulations were present throughout the tularemia season and persisted over years. High-resolution genotyping in combination with patients' statements about geographic places of disease transmission provided valuable indications of likely sources of infection and the causal genotypes during these tularemia outbreaks.

Traditional objectives of investigations of infectious disease outbreaks are to identify ways to control ongoing outbreaks and to prevent future outbreaks. However, a paucity of epidemiologic and ecologic knowledge hampers the investigation of tularemia outbreaks caused by the intracellular bacterium Francisella tularensis, although it is one of the most virulent pathogens known. The Centers for Disease Control and Prevention lists this pathogen as one of the most potentially dangerous bioterrorism bacteria (1). Little is known about natural reservoirs of tularemia, F. tularensis transmission mechanisms to humans, and factors influencing the often irregular pattern of outbreaks. Because tularemia is a zoonosis and little ecologic information exists about the causal organism, its prevention and control may require the development of novel outbreak investigation strategies.

In nature, F. tularensis is associated with an extremely wide range of hosts and arthropod vectors; a recent review listed 304 susceptible species (2). Transmission to humans may occur through a number of routes; skin inoculation by blood-feeding arthropod vectors is one of the most common routes (3). The infectious dose can be as low as 10 bacterial cells (4). Human tularemia naturally occurs only in biotopes in the Northern Hemisphere. We describe an investigation of a large number of F. tularensis isolates from humans. Patients were infected mainly from mosquito bites and had an influenza-like illness, a primary skin ulcer, and enlargement of lymph nodes, the ulceroglandular form of tularemia (5,6). Tularemia is endemic in Sweden, with seasonal outbreaks and a patchy geographic distribution. The number of infected humans ranged from 27 to 698 per year from 1998 through 2007 in a population of ≈9.1 million (annual incidence rate 0.30–7.78/100,000 persons) (7). For comparison, 20–64 humans were reported with tularemia from 2000 through 2006 in the tularemia-endemic US states of Arkansas and Missouri, from a population of ≈8.3 million (annual incidence rate 0.23–0.76/100,000 persons) (8). F. tularensis subsp. holarctica causes tularemia all over the Northern Hemisphere. This is a severe febrile disease but does not generally result in death. A more virulent variety, F. tularensis subsp. tularensis, exists in North America. It was associated with a human mortality rate of 5%–15% before the advent of effective antimicrobial drug treatments (4). F. tularensis has a clonal genetic structure, a property that should facilitate tracking the spread of tularemia by genotyping (9,10).

We demonstrate a strategy to enhance epidemiologic investigations of tularemia by combining geographic data collected from patient interviews and high-resolution genotyping of F. tularensis subsp. holarctica isolates recovered from tularemia patients. We found that geographic distributions of specific F. tularensis subsp. holarctica subpopulations were highly localized during outbreaks (infections by some genotypes were restricted to areas as small as 2 km2), indicating distinct point sources of infection.

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