07 August 2008
An outbreak of tularaemia occurred in Castilla y León in northwestern Spain between June and December 2007, as previously reported by Martín et al. . The scope of the present article is to describe in more detail, and update the results of, the outbreak investigation.
An increased incidence of cases diagnosed as “fever of unknown origin” was detected in late June 2007 by the Castilla y León Epidemiological Surveillance Network based on a series of notifications from a rural area in the province of Palencia and from Leon city. Subsequent epidemiological investigation confirmed a tularaemia outbreak.
After the initial cases were confirmed as tularaemia, the regional Epidemiology Service launched an active search for cases, both prospective and retrospective. Primary and specialised healthcare professionals were informed about the situation and asked to notify all suspected cases and to take clinical specimens for laboratory investigation.
Most collected samples were sent to the National Reference Laboratory in Madrid, where cases were confirmed by means of serological techniques (microagglutination and tube agglutination), culture or PCR.
All cases were first interviewed face-to-face by clinicians and then over the phone by epidemiologists. The questionnaire collected information about the patient, clinical symptoms and potential exposures associated with the risk of infection. Follow-up information on the conclusion of the treatment and disappearance of the symptoms were available for 73.5% of the cases.
The cases, as reported by clinicians, were classified by epidemiologists by means of the case definition and confirmation criteria agreed jointly with the National Epidemiological Surveillance Network and the European Centre for Disease Prevention and Control .
The clinical symptoms compatible with one of the different forms of tularaemia included:
• Ulceroglandular (cutaneous ulcer with regional lymphadenopathy),
• Glandular (regional lymphadenopathy with no ulcer),
• Oculoglandular (conjunctivitis with preauricular lymphadenopathy),
• Oropharyngeal (stomatitis or pharyngitis or tonsillitis and cervical lymphadenopathy),
• Intestinal (intestinal pain, vomiting, and diarrhoea),
• Pneumonic (primary pneumonic disease),
• Typhoidal (febrile illness without early localising signs and symptoms).
The laboratory criteria for diagnosis included:
• Isolation of Francisella tularensis from a clinical specimen,
• Detection of F. tularensis genome by PCR,
• Demonstration of a specific antibody response in paired serum samples.
Classification of confirmed case: a clinically compatible case confirmed by laboratory diagnosis.
Additional criteria for cases associated with the outbreak included: a person resident in Castilla y León who between mid-May and December 2007 met the above criteria.
A total of 507 cases were laboratory-confirmed, of these 91.5% using serological techniques (microagglutination and tube agglutination), 5% by culture and 3.5% by PCR. F. tularensis holarctica was identified as the agent causing the outbreak.
The outbreak was focused in the northwest quadrant of Castilla y León (in five of the nine provinces) and has not spread to either neighbouring areas of Castilla y León or other Spanish regions.
Figure 1. Confirmed cases of tularaemia by week of onset of symptoms, outbreak in Castilla y León, Spain, 2007 (n=507)
Cases were reported with the onset of symptoms between week 20 (earliest 15 May) and week 52 (latest 31 December) of 2007.
Ninety percent of cases occurred from week 25 (starting 18 June) to week 43 (starting 22 October) of 2007, with a peak (59.5% of the cases) between weeks 26 and 33 (24 June – 18 August) (Figure 1).
The majority of cases (80.1%) were male. Patients aged 41 to 70 years accounted for 69.2% of cases, although all age groups were affected (Figure 2).
Figure 2. Age distribution of confirmed cases of tularaemia, outbreak in Castilla y León, Spain, 2007 (n=507)
The most frequent clinical form reported was the typhoidal one (59.0%), followed by the ulceroglandular, glandular and pneumonic forms (14.6%, 12.6% and 7.9%, respectively) (Table 1).
Table 1. Clinical form of tularaemia reported in confirmed cases identified in the outbreak in Castilla y León, Spain, 2007 (n=507)
The majority of cases (71.1%) were treated by general practitioners, 25.0% were hospitalised, while the remaining 3.9% attended specialist out-patient facilities.
Ciprofloxacin (750 mg every 12 hours) and doxycicline (100 mg every 12 hours) for 10 to 14 days were the most frequently used antibiotics, although other fluoroquinolones and tetracyclines were also administered.
Patients’ responses to the prescribed antibiotic treatment were favourable in most cases, with only a few complications and no fatal cases reported. The most frequently observed complications were: asthenia (8 cases), suppurative adenopathies (7 cases), persistent arthralgias (6 cases), persistent adenopathies (4 cases) and allergic reaction to prescribed treatment (2 cases).
Information on possible exposures revealed that 34.9% of cases were farm workers or people whose jobs involve contact with gardens or natural environments (e.g. gardeners, rangers or reserves and lakes maintenance staff). Contact with rodents (24.3%) or domestic animals such as dogs or cats (19.7%), handling crayfish (13.2%) or frequent walks through the countryside (11.8%) were reported in a significant number of cases. Other possible infection routes reported were recent arthropod bites (10.9%), contact with livestock (9.5%) or with manure, straw or alfalfa hay (4.9%), or having handled and/or skinned hares (6.5%). Patients could indicate more than one possible exposure and these are neither exclusive nor exhaustive (Table 2).
Table 2. Potential exposures associated with the risk of tularaemia infection reported by cases in the outbreak in Castilla y León, Spain, 2007 (n=507)
The first known tularaemia outbreak in Castilla y León, with 534 reported cases, took place in 1997 [4,5,7]. Another, smaller one, with 13 cases, occurred in 2004 . Several sporadic cases were also notified in the interim. The prevailing modes of transmission for these earlier outbreaks were contact with leporids in 1997 [4,5,7] and crayfish in 2004 .
In the 2007outbreak, the most frequent clinical presentation of the disease, the typhoidal form, together with the potential risk factors indicated by cases suggest two different means of transmission responsible for the outbreak: mainly by inhaling the bacteria, a pattern seen in just over half the cases (pneumonic and probably many of the typhoid forms), and, secondly, through direct contact, with local manifestations of the disease (ulceroglandular and ganglionar forms).
At the time of the outbreak, harvesting and related farm works were being conducted, which may have caused aerosols capable of transporting the bacterium. Unusual climatic and environmental circumstances (mild winter and dry spring) might have contributed to this outbreak, together with the significant diversity of illness reservoirs and infection sources that usually take part in transmission (leporids, sheep, rodents, canids and haematophagus vectors). All these factors have probably aided the proliferation of Francisella tularensis, a bacterium that can survive for long periods in water, mud and animal carcasses.
Different studies are being conducted in order to improve our knowledge of this outbreak and its causes: a) a spatial analysis to evaluate the possible correlation with either environmental or animal factors; b) a case-control study to identify the potential risk factors associated with infection sources and modes of transmission; and c) a seroprevalence study of F. tularensis in asymptomatic people in the case-control study area. A collection of cases’ sera was created to allow further investigation.
1. Martin C, Gallardo MT, Mateos L, Vian E, Garcia MJ, Ramos J, et al. Outbreak of tularaemia in Castilla y León, Spain. Euro Surveill. 2007;12(45):pii=3302. Available from: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=3302
2. Dirección General de Salud Pública. Manual de Notificación: Sistema de Enfermedades de Declaración Obligatoria. 1a edición. Junta de Castilla y León. Consejería de Sanidad. Valladolid, 2007.
3. Commission Decision of 17 July 2003 amending Decision No 2119/98/EC of the European Parliament and of the Council and Decision 2000/96/EC as regards communicable diseases listed in those decisions and amending Decision 2002/253/EC as regards the case definitions for communicable diseases (notified under document number C(2003) 2301. Official Journal of the European Union. Volume 46. 23 July 2003.
4. De Mateo S, Ruiz Coisin C. Outbreak of tularaemia in Castilla y León, Spain. Euro Surveill. 1998;2(4):pii=1268. Available from: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=1268
5. Instituto de Salud Carlos III. Centro Nacional de Epidemiología. Brote de tularemia en Castilla y León. Boletín Epidemiológico Semanal. 1997; 5: 249-52.
6. Boletín Epidemiológico de Castilla y León - Año 2005 - Volumen 21.
7. Andrés Puertas C, Mateos Baruque ML, Burón Lobo I, González Megido MJ, Rebollo Cuadrado C, Sangrador Arenas LA. [Epidemic outbreak of tularemia in Palencia][in Spanish] Rev Clin Esp. 1999;199(11):711-5.