update on q fever epidemic in the netherlands and us public health response n.
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Update on Q Fever Epidemic in the Netherlands and US Public Health Response

Update on Q Fever Epidemic in the Netherlands and US Public Health Response

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Update on Q Fever Epidemic in the Netherlands and US Public Health Response

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  1. Update on Q Fever Epidemic in the Netherlands and US Public Health Response Hira Nakhasi, Ph.D.CBER/FDABlood Product Advisory Committee Meeting Rockville, MD, USA July 26, 2010

  2. Background-I- Causative agent • The causative agent of Q fever is a gram-negative coccobacillus Coxiella burnetii, anobligate intracellular bacterium that lives in macrophages. • ~40 species of ticks involved in Tx in animals. Tx to humans through ticks is rare • Q fever was first described in Australia in 1935 and since then cases have been reported worldwide including in the US. • C. burnetii is resistant to heat and drying, osmotic shock, UV and common disinfectants because of the presence of a spore-like stage. • The microorganisms exists in two antigenic forms: • Phase I- highly infectious; found in nature • Phase II- attenuated and avirulent. • Can be easily spread in humans through inhalation • As few as 10 organism of Cb in humans can be infectious • Bacteria are shed in milk, urine, and feces of infected animals, amniotic fluid, placenta during birthing, and contaminated wool.

  3. Background-II- Clinical outcome • On average,incubation period prior to development of clinical symptoms is ~14 days (7-28 days) • Approximately 60% of bactermic cases are asymptomatic • Infection may lead to acute or chronic disease • The clinical symptoms in acute cases are: • Often non-specific • Self-limiting flu like syndrome • Pneumonia • Hepatitis • Approximately 5% of infected individuals may develop chronic infection • More severe, CFR 15%; Endocarditis + chronic hepatitis • The Standard treatment is doxycycline (daily two doses of 100mg for 14-21 days) • Infection in children is milder and less symptomatic compared to adults • Farmers, veterinarians and animal handlers are at risk for infection

  4. Background-III- Transmission • Transmission can occur through: • Inhalation of aerosols or contaminated dusts from infected ruminants or their products • Ingestion of contaminated meat or unpasteurized milk • Direct contact with infected animals, contaminated materials (wool, straw, fertilizer and laundry) • Interdermal inoculation • Bone marrow transplantation • Transplacental route • Sexual (Cb DNA in semen) • Blood transfusion (one reported case in the US in 1977)

  5. Background-IV - Tests • There is no FDA licensed blood donor screening test for C. burnetii • In house developed IFA, complement fixation, microagglutination or ELISA are commonly used for diagnosis • In research setting PCR based tests and cultures are also used to detect C. burnetii.

  6. Q Fever Epidemiology in the US • Q fever first described in 1938 by Cox and Davis • Cases reported during World war II and in Gulf war among military personnel • < 200 cases reported in US/year • Q fever is considered enzootic in ruminants (sheep, goats, and cattle) throughout the country • Disease is believed to be substantially underreported because of its nonspecific presentation and the subsequent failure to suspect infection • Recent nation wide sero-survey in the US suggested ~3.1% seroprevelance among adults aged 20 years and older.

  7. Q Fever Epidemic in the Netherlands • In the past, about 17 cases/yr on average • 168 cases in 2007 • 1000 cases in 2008 • 2357 cases in 2009- 6 deaths • Considered a major public health problem • Pneumonia predominant clinical presentation • ~20% of cases admitted to hospital

  8. The origin of Q fever in NL: • 3 years of airborne spread of Coxiella burnetii spores from infected dairy goat farms • Close proximity of goat farms to human habitations • Factory farming- high density of goats • “Deep Litter” animal husbandary • Abortion “waves”

  9. Netherlands 2009:largest outbreak of Q fever ever(Prof. Hans L. Zaaijer, Sanquin - The Netherlands)

  10. Notified cases of Q fever in NL, 2007-2009(Prof. Hans L. Zaaijer, Sanquin - The Netherlands) !?

  11. Q fever and Dutch blood donors: • A retrospective sero-survey in 2009: • PCR testing of 1000 donations: • 6 reactive (weak signal, high Ct value) • 3/6 confirmed by serology in index-and F/U samples • 3/6 F/P PCR, sero-negative in F/U samples • 2/3 PCR + donations transfused • 1 recipient tested (IgG +++, IgM borderline 10 m after transfusion) • Possible /probable case of T-T Cb • Serological testing (IgM &IgG): • 545 (serial F/U) samples revealed 13% seroprevelance and a seroconversion rate of 2%. • Look back on 8 donors (notified their BB Q fever within 3 wk) • 1/8 PCR positive (recipient terminally ill, not tested) • 6 recipients of PCR negative donations • 2/6 IgG positive (1 diagnosed Q fever before Tx ; and another living in endemic area)

  12. Current Control Measures in the Netherlands • Mandatory animal vaccination • Culling of 10s of thousands of pregnant goats • Testing of milk tanks • Life time deferral with history of Q fever compared to 2 year deferral in rest of Europe • In 2010 started screening donations for Cb DNA in high incidence areas

  13. Q fever Status in the NL as of July 2010 • Measures instituted seem to have resulted in the control of Q fever epidemic • So far no outbreak reported • No wave of abortions occurred in the goat farms • Testing of donations from at risk areas, since March 15th 2010 for Coxiella DNA found no positives (0/3000) • According to Dutch Health Council “Q fever is not a threat to safety of blood” in the NL • Dutch Agriculture Ministry has lifted restriction on breeding and transporting milk goats and milk sheep

  14. US Public Health Concern- based on the epidemic in the NL for the last three years • Epidemic in the NL raised a public health concern as to whether there is risk of Coxiella burnetiitransmission through transfusion from US donors who travelled to the NL. • Visiting an affected farm is highly correlated with rate of infection

  15. US Public Health Response • Starting Jan 2010, monthly meetings held among the PHS agencies to monitor the epidemic in the NL • FDA and DHHS participated in a meeting organized by European Center for Diseases Prevention and Control (ECDC) on April 9, 2010 to take stock of the factors responsible for Q fever Epidemic in the NL • Based on Q fever risk models developed in the NL and France by ECDC, FDA and CDC determined there is low risk to blood safety from US travelers to NL (~6-15 imported cases/year) • No US sero surveys are needed at this time • If the circumstances warrant FDA will consider issuing guidance for donor deferral for travel to the NL

  16. US Public Health Response • CDC issued a Health Alert Network Notification (HAN) for “Potential for Q fever infection among Travelers returning from Iraq and the NL”. May 12, 2010. • Both AABB and DOD continue to enforce the Leishmania deferral policy for civilians and military personnel returning from Q fever endemic countries such as Iraq and Afghanistan • Given the current status of the Q fever epidemic in the NL, it is likely that the risk to US blood safety is low, however FDA will continue to monitor the situation.