Gert van der Hoek
In Memoriam - Editor, Senior Moderator
May , 2010
Executive summary
A risk assessment was carried out on a request from the European Commission to assess questions on Q fever
and its transmission through blood, the health impact of chronic Q fever and the risks for pregnant women.
With
reference to the ongoing outbreak in the Netherlands, ECDC was also asked to address the question of crossborder
spread and the need for better surveillance systems. The risk assessment was performed according to the
principles of evidence-based methodologies, by defining search terms for each question, inclusion and exclusion
criteria for identified studies and assessing the quality of the evidence.
A review of the best available evidence was
presented to, and discussed with, an expert panel with representatives from the Netherlands, France, Germany,
the UK and the United States. The work has been undertaken simultaneously, and in coordination with, a risk
assessment on Q fever from the European Food Safety Authority.
Acute Q fever is typically a mild, self-limiting, flu-like disease, but it sometimes presents with pneumonia,
hepatitis and other symptoms. It can usually be successfully treated with a two-week course of doxycycline.
Coxiella burnetii is an obligate intracellular bacterium that can be transmitted through blood and tissues. The
risk of such a transmission is low, and there is only one documented case in the literature.
During an outbreak,
the endemic area should be defined and safety precautions should be considered, such as active surveillance
among blood and tissue recipients, screening of donors, and screening of blood and tissue products. For travellers
returning from the area within the duration of the incubation period and with asymptomatic bacteraemia (five to
seven weeks), deferral from blood donation may be considered until the end of this period. An antibiotic course
could be considered for blood recipients at particularly high risk, such as patients with heart valve defects.
Donors
who have had an acute Q fever infection should be deferred from giving blood for two years following the date of
confirmed cure from acute infection. The benefits of implementation of such measures must be carefully
considered against the negative impacts they could have on blood supply in the area. A strategy for risk
communication should be developed.
Chronic Q fever is a serious complication of an acute Q fever infection that develops in some 2% of acute
symptomatic cases, and the fatality rate may vary from 5% to 50%. Chronic Q fever causes endocarditis in risk
groups like people with previous heart valve disease, a prosthetic valve or vascular graft. Patients with cancer or
those who are immunosuppressed are also at a higher risk. Chronic Q fever must be treated for at least one year,
in some cases for the lifetime with more than one antibiotic. Surgical replacement of damaged heart valves might
be needed.
Effective detection of, and treatment for, acute Q fever is the best strategy for avoiding chronic cases.
Three
possible strategies are described: (1) awareness raising among healthcare staff and the public to address the risk
groups; (2) active follow-up with serology for known risk groups to detect and treat an acute Q fever infection
early; or (3) refer all known acute Q fever patients to echocardiography for active case finding and follow-up.
There is a need to initiate good prospective cohort studies and controlled trials (when ethically feasible) to obtain
more robust evidence on how to prevent and inhibit outbreaks of Q fever in the public health field, and on how to
diagnose and treat acute and chronic disease at the clinical level.
Evidence on Q fever in pregnancy is very limited and comes mainly from observations and research in domestic
and experimental animals, seroprevalence studies, case reports, and one case series including 53 pregnant women
over a 15-year period.
The risk for pregnant women of severe Q fever outcomes compared with the risk for the
general (female) population cannot be quantified based on currently available evidence. Several cases of Coxiella
burnetii infection during pregnancy resulting in adverse pregnancy outcomes have been reported. In some of the
cases Coxiella burnetii was found in the placenta and in fetal tissue. Coxiella has also been identified in human
breast milk but no case of transmission to the breastfed child has been validated.
There is some indication that long-term antibiotic therapy with cotrimoxazole has the potential to prevent severe
pregnancy outcomes, but the evidence is based on a case series without randomisation and without controlling for
potential biases. As long as no further evidence from high quality treatment studies is available, pregnant women
with diagnosed Q fever infection should be treated with antibiotics throughout the remaining pregnancy. However,
the scientific basis for this recommendation is weak, and ECDC would strongly recommend that randomised
controlled trials are performed to obtain more reliable evidence.
Pregnant women should be advised not to visit farms in affected areas. ECDC does not recommend against
breastfeeding except in cases of chronic disease that need long-term treatment of the mother.
A formaline-inactivated whole-cell Q fever vaccine is produced and licensed in Australia. The vaccine is effective,
but pre-vaccination testing is necessary due to high reactogenicity in persons who have earlier been infected with
Coxiella burnetii, making the vaccine more suitable for defined risk groups than for general vaccination.
Available evidence suggests an effective range of airborne spread of Coxiella burnetii of less than 5 km. The risk
of airborne spread from the Netherlands is therefore limited to neighbouring countries (i.e. Germany, Belgium),
and to areas close to outbreak sources. Active surveillance or case finding for acute Q fever in possible risk groups
(i.e. pregnant women, patients with heart valve or vascular diseases) on a local level and for a defined period of
time is reported feasible and an efficient method for detecting acute infections. In areas adjacent to epidemic
settings (≤ 5 km from the source), awareness campaigns among healthcare providers should be initiated. If the
area also affects other Member States, the responsible public health authorities need to inform their cross-border
counterparts. Sharing of information between public health and veterinary authorities would facilitate an early
recognition of an outbreak. Further, the health and veterinary authorities at national and local levels should take
the neccessary action to stop an outbreak.
Full report: http://ecdc.europa.eu/en/publications/Publications/1005_TER_Risk_Assessment_Qfever.pdf
Executive summary
A risk assessment was carried out on a request from the European Commission to assess questions on Q fever
and its transmission through blood, the health impact of chronic Q fever and the risks for pregnant women.
With
reference to the ongoing outbreak in the Netherlands, ECDC was also asked to address the question of crossborder
spread and the need for better surveillance systems. The risk assessment was performed according to the
principles of evidence-based methodologies, by defining search terms for each question, inclusion and exclusion
criteria for identified studies and assessing the quality of the evidence.
A review of the best available evidence was
presented to, and discussed with, an expert panel with representatives from the Netherlands, France, Germany,
the UK and the United States. The work has been undertaken simultaneously, and in coordination with, a risk
assessment on Q fever from the European Food Safety Authority.
Acute Q fever is typically a mild, self-limiting, flu-like disease, but it sometimes presents with pneumonia,
hepatitis and other symptoms. It can usually be successfully treated with a two-week course of doxycycline.
Coxiella burnetii is an obligate intracellular bacterium that can be transmitted through blood and tissues. The
risk of such a transmission is low, and there is only one documented case in the literature.
During an outbreak,
the endemic area should be defined and safety precautions should be considered, such as active surveillance
among blood and tissue recipients, screening of donors, and screening of blood and tissue products. For travellers
returning from the area within the duration of the incubation period and with asymptomatic bacteraemia (five to
seven weeks), deferral from blood donation may be considered until the end of this period. An antibiotic course
could be considered for blood recipients at particularly high risk, such as patients with heart valve defects.
Donors
who have had an acute Q fever infection should be deferred from giving blood for two years following the date of
confirmed cure from acute infection. The benefits of implementation of such measures must be carefully
considered against the negative impacts they could have on blood supply in the area. A strategy for risk
communication should be developed.
Chronic Q fever is a serious complication of an acute Q fever infection that develops in some 2% of acute
symptomatic cases, and the fatality rate may vary from 5% to 50%. Chronic Q fever causes endocarditis in risk
groups like people with previous heart valve disease, a prosthetic valve or vascular graft. Patients with cancer or
those who are immunosuppressed are also at a higher risk. Chronic Q fever must be treated for at least one year,
in some cases for the lifetime with more than one antibiotic. Surgical replacement of damaged heart valves might
be needed.
Effective detection of, and treatment for, acute Q fever is the best strategy for avoiding chronic cases.
Three
possible strategies are described: (1) awareness raising among healthcare staff and the public to address the risk
groups; (2) active follow-up with serology for known risk groups to detect and treat an acute Q fever infection
early; or (3) refer all known acute Q fever patients to echocardiography for active case finding and follow-up.
There is a need to initiate good prospective cohort studies and controlled trials (when ethically feasible) to obtain
more robust evidence on how to prevent and inhibit outbreaks of Q fever in the public health field, and on how to
diagnose and treat acute and chronic disease at the clinical level.
Evidence on Q fever in pregnancy is very limited and comes mainly from observations and research in domestic
and experimental animals, seroprevalence studies, case reports, and one case series including 53 pregnant women
over a 15-year period.
The risk for pregnant women of severe Q fever outcomes compared with the risk for the
general (female) population cannot be quantified based on currently available evidence. Several cases of Coxiella
burnetii infection during pregnancy resulting in adverse pregnancy outcomes have been reported. In some of the
cases Coxiella burnetii was found in the placenta and in fetal tissue. Coxiella has also been identified in human
breast milk but no case of transmission to the breastfed child has been validated.
There is some indication that long-term antibiotic therapy with cotrimoxazole has the potential to prevent severe
pregnancy outcomes, but the evidence is based on a case series without randomisation and without controlling for
potential biases. As long as no further evidence from high quality treatment studies is available, pregnant women
with diagnosed Q fever infection should be treated with antibiotics throughout the remaining pregnancy. However,
the scientific basis for this recommendation is weak, and ECDC would strongly recommend that randomised
controlled trials are performed to obtain more reliable evidence.
Pregnant women should be advised not to visit farms in affected areas. ECDC does not recommend against
breastfeeding except in cases of chronic disease that need long-term treatment of the mother.
A formaline-inactivated whole-cell Q fever vaccine is produced and licensed in Australia. The vaccine is effective,
but pre-vaccination testing is necessary due to high reactogenicity in persons who have earlier been infected with
Coxiella burnetii, making the vaccine more suitable for defined risk groups than for general vaccination.
Available evidence suggests an effective range of airborne spread of Coxiella burnetii of less than 5 km. The risk
of airborne spread from the Netherlands is therefore limited to neighbouring countries (i.e. Germany, Belgium),
and to areas close to outbreak sources. Active surveillance or case finding for acute Q fever in possible risk groups
(i.e. pregnant women, patients with heart valve or vascular diseases) on a local level and for a defined period of
time is reported feasible and an efficient method for detecting acute infections. In areas adjacent to epidemic
settings (≤ 5 km from the source), awareness campaigns among healthcare providers should be initiated. If the
area also affects other Member States, the responsible public health authorities need to inform their cross-border
counterparts. Sharing of information between public health and veterinary authorities would facilitate an early
recognition of an outbreak. Further, the health and veterinary authorities at national and local levels should take
the neccessary action to stop an outbreak.
Full report: http://ecdc.europa.eu/en/publications/Publications/1005_TER_Risk_Assessment_Qfever.pdf
