Characterization of veterinary and community acquired MRSA: determinants, transmissibility and virulence

Traditionally, meticillin-resistant Staphylococcus aureus (MRSA) has been
considered as a hospital associated pathogen. Since approximately 10 years,
MRSA has expanded its territory to the community causing severe infections in
previously healthy persons all over the world. Although community-acquired MRSA
(CA-MRSA) infections are usually mild, they may also be severe, and can result
in hospitalisation and even death. In The Netherlands there is an increasing
number of individuals who are identified as carriers of MRSA that do not belong
to known risk groups, indicating a new source outside of the hospital. To
define preventive interventions in the community and to improve the control
measures in hospitals and nursing homes more knowledge is needed on the
reservoirs and transmission routes in the general population.
Furthermore, in 2003 a new clone of MRSA was observed in The Netherlands that
is related to an extensive reservoir in pigs and cattle. A survey among pigs at
slaughterhouses showed that 40% of all pigs were colonized with MRSA. This
clone is characterized by being non-typable by the typing method that is used
at the Dutch national reference laboratory at the RIVM and therefore is named
non-typable MRSA (NT-MRSA). By the end of 2007, 30% of all new MRSA strains in
The Netherlands were NT-MRSA.
At present it is unclear whether NT-MRSA is easily transmissible from human to
human. Considering the extensive reservoir in animals and people who work with
these animals, there are at present relatively few cases of NT-MRSA in people
who are not directly related to farming. If NT-MRSA is hardly transmissible
from human to human this would limit the public health impact and the control
measures in health care facilities could probably be less stringent.

The objective of this study is to identify determinants, to determine the
transmissibility and to determine the burden of disease of NT-MRSA and CA-MRSA
carriage compared to other typeable MRSA strains in the community.

Members of the VGV and newly found MRSA patients who are colonized with T-MRSA
will be asked to take a nasal and throat swab and return these by mail to a
central laboratory. All included subjects will be visited by the investigator
or a research nurse. The eligibility is checked and written informed consent is
obtained from all the household members. A questionnaire is taken to collect
demographic data and information on risk factors for MRSA
infection/colonization. Subsequently, a specimen for culture from both anterior
nares, the throat and skin lesions if applicable from all household members
will be obtained.
All subjects and their household members will be followed for the occurrence of
medical events during one year. This includes the development of infections
with MRSA, antibiotic use and other significant medical events. The sampling
will be repeated after 4, 8 and 12 months. The material and instructions for
sampling at 4 and 8 months will be delivered at the intake visit together with
a short questionnaire. Participants will be asked to take samples from nares
and throat and sent them together with the questionnaire to the central
laboratory. At 12 months the investigator or the research nurse will visit the
participants again and will take microbiological samples from nose and throat
and a final medical questionnaire.

Participation in the study does not take much time and there are no invasive
procedures. Altogether, nose and throat swab samples will be taken four times
from all subjects and their household members and will be send to the Amphia
Hospital Breda, Laboratory for Microbiology and Infection Control for
identification of MRSA. Taking nose and throat swabs should not be considered
to be much discomfort to the subjects.
Also, all samples will be typed using three different typing methods.
Amplified-fragment length polymorphism (AFLP) analysis will be performed at the
VUmc. Multi-locus variable-number tandem-repeat analysis (MLVA) and the spa
typing will be performed at the RIVM. Furthermore, during the one year
follow-up period questionnaires are taken four times, which are four short
questionnaires each period. At the beginning and at the end of the study two
extensive questionnaires will be taken. There will be no physical or
physiological discomfort, no site visits and no physical examinations or other
tests associated with participation. Therefore, participation in the study will
not involve any substantial risk for the included subjects and the
investigators will not interfere with treatment.