OCCUPATIONAL HEALTH IMPLICATIONS: FROM LABORATORY TO FIELD
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1 OCCUPATIONAL HEALTH IMPLICATIONS: FROM LABORATORY TO FIELD USDA ARS 5 TH INTERNATIONAL BIOSAFETY & BIOCONTAINMENT SYMPOSIUM February 13 th, 2019 Lee Wugofski MD,MPH Deputy Medical Director, CHS, FOH
2 ASSESSING EXPOSURES IN THE FIELD Challenges Unknown Source Presence of zoonotic agent from a bite, splash or wound are typically unknown and based upon endemic and epizootic outbreaks, which can change over time Analyzing source may take time Exposure incident could be in remote environment, delaying access to immediate treatment 2
3 ASSESSING EXPOSURES IN THE FIELD Challenges cont d Caregivers may not be familiar with particular infectious agents in question Bedside Manner Factor Exposures can occur outside normal line of work 3
4 CLINICAL TESTING ISSUES Exposed workers can be symptom-free (depending upon the Agent) Timing of test may affect outcome If workforce over wide geographic area tests ordered must be standardized Low predictive value when prevalence of Agent is low Interpretation of results can be difficult 4
5 INTERPRETING TEST RESULTS Clinical information often lacking Isolated test result could be due to prior exposure Is there a baseline test? Paired sera? Serum banking? Many studies on exposed populations may not be generalizable 5
6 CLINICAL APPROACH TO ZOONOTICS Understand pathogenesis and pathophysiology Prevalence Infective routes of exposure Incubation Period Acute and chronic health effects Natural clinical course Special Circumstances 6
7 OCCUPATIONAL HEALTH CONCERNS Understand Work Environments Employee tasks (risk assessment) Are certain activities associated with higher risk of exposure? Personal Protective Equipment Appropriate and adequate? Access to Health Care Need for any immediate prophylaxis if required Depends upon Agent in question 7
8 APPROACH TO TWO AGENTS Lyme Disease Borrelia burgdorferi Q Fever Coxiella burnetti 8
9 LYME DISEASE Causative Agent Borrelia burgdorferi - spiral shaped bacteria Vector Eastern U.S. - Ixodes scapularis (deer tick) Western U.S. Ixodes pacificus Route of transmission Prolonged tick bite from an infected tick Most common vector-borne infection in US about 30,000 cases reported annually 9
10 VECTOR TRANSMISSION AND ANIMAL HOSTS Larvae and Nymphs feed primarily on rodents (white-footed mice: Peromyscus leucopus) infected nymph mouse infected larva Adults feed on larger mammals (deer) Important for Life Cycle of Tick, but not for spirochete Infected Nymph Infect Larva Mouse 10
11 TICK VECTORS Ixodes scapularis adult female, adult male, nymph, and larva (centimeter scale) Infected ticks in nymphal stage >> risk Feed mostly during late spring / early summer Highest tick infested areas in US (CT, NY) I. scapularis % nymphs infected 11
12 RISK OF INFECTION Density of Ticks in Particular Area Depends upon host population Presence of spirochete in tick Feeding habits of ticks I. pacificus prefers lizards than rodents Prolonged (36+ hour) feeding Patients age 2-88; 1:1 gender ratio May October: most in June and July 12
13 Lyme disease Confirmed cases by month of disease onset, United States,
14 14
15 LYME SEROLOGY SURVEILLANCE APHIS 2005 TO 2010 Over 1020 serologies In latter two Fiscal Years 34 ELISA positives (34/ %) Of 34 ELISA positives 3 positive Western Blot (3/34=8.8%; 3/395=0.8%) Year # Titers
16 LYME SEROLOGY - APHIS Western Blot Cases All from US Northeast Region One with prior history (+EM) and treated One with no history saw PMD and took 4 week oral antibiotic therapy Never had symptoms One with IgM WB only never developed IgG False Positive 16
17 LYME SEROLOGY TESTING PROGRAM COMPELLING QUESTIONS States Total States Total AK 1 MT 2 How much AL benefit 20 NC achieved? 30 AR 11 ND 11 AZ 3 NE 3 CA 77 NM 5 CO 23 NV 6 FL 50 OH 32 GA 21 OK 6 $58 per test Is program risk based? HI 1 OR 3 IA 3 PR 50 ID 2 SC 23 IL 14 TN 34 IN 14 TX 4 Who gets tested? When? How much KS spent 5 UTon tick bite 5 KY 32 VA 17 LA 2 WA 2 prevention MO activities? 9 WI 49 MS 12 WV 6 WY 3 State # Tested CT 10 DE 5 MA 22 MD 4 ME 71 MI 91 MN 41 NH 4 NJ 32 NY 127 PA 34 RI 4 VT 6 Total 451 States Total Other States
18 DISCRETE EXPOSED COHORT 18
19 INFORMAL STUDY OF TICK PRESENCE Date Range Embedded Ticks Repellant used Ticks found on body April - October %
20 CONCLUSION - Lyme Serology Surveillance APHIS Baseline ALL employees who s tasks place them in potential contact with ticks Annual testing for employees above working in endemically high risk areas Enhanced testing for ALB program Twice a year: July and November 20
21 Q FEVER 21
22 Q FEVER Mode of Transmission Inhalation from air contaminated from byproducts of infected animals Birth-products (highest concentration) Feces, urine and milk RARE Tick bites Ingestion of unpasteurized milk Human-to-human transmission 22
23 Q FEVER - CAUSE Coxiella burnetii Intracellular bacterium Enters body via lungs Less through mucous membranes, abrasions, GI tract Antigenic Phases Phase I - infectious phase Phase II - avirulent phase Animal reservoirs Common: Cattle, sheep, goats Less common: dogs, cats, wild rabbits, moose 23
24 MODE OF TRANSMISSION Aerosols After birth high concentration of particles Newborns, placenta, wool Particles are very resistant to environment for several weeks Can be spread by the wind Q Fever contracted without any direct contact with animals Within 10 miles in one study; 2 km in another 24
25 NATURAL HISTORY ACUTE Q FEVER Incubation Period: 2 to 3 weeks (up to 6 weeks) Fever median 10 days (5-57 days) if untreated; subsides within 72 hours of Rx Rash 5%-21% Symptoms can be abrupt or gradual in onset Infrequent Pericarditis, myocarditis, meningitis, cholecystitis Mortality < 2% 25
26 CHRONIC Q FEVER Occurs in < 5% infected Months, years or decades after acute infection Endocarditis; chronic hepatitis; osteomyelitis Highest Risk Valvular heart disease, aneurysm or vascular graft Immunocompromised Pregnancy Can occur after asymptomatic infection 26
27 DIAGNOSIS PCR of whole blood/serum Within 2 weeks of symptom onset and before Rx Fourfold increase Phase II IgG Ab paired acute/convalescent sera (3-6 wks apart) Single titer after acute clinical illness Chronic Q Fever Phase I IgG >= 1:1024 with identifiable infection (eg. Endocarditis) PCR/culture of affected tissue 27
28 TREATMENT ACUTE Q FEVER Most acute cases resolve spontaneously within 2-3 weeks WITHOUT treatment Doxycycline most effective within first 3 days of symptoms Not indicated in symptom-free individuals Except for those high-risk for chronic disease Thorough clinical assessment of risk for chronic infection Immunosuppressive conditions Heart valve and other vascular defects Pregnancy testing when appropriate 28
29 GROUPS AT RISK Occupations increased animal contact Veterinarians Slaughterhouse Workers Farmers Laboratory Workers Living in Rural area within 10 miles of farm which houses livestock Cattle, sheep, goats 29
30 SPECIAL CIRCUMSTANCES Women infected during child-bearing age Pregnancy test - to guide nature/duration of Rx Avoid pregnancy at least 1 month after Dx & Rx Pregnant Women Increased risk for miscarriage (1 st trimester infection) Pre-term delivery (2 nd trimester or later infection) Congenital malformations not reported Infection during pregnancy requires antibiotic treatment (consult Infectious Disease specialist) Infection prior to pregnancy does not First trimester infections associated with > risk of chronic Q Fever 30
31 OCCUPATIONAL EXPOSURE Outbreaks reported Slaughterhouse workers Farms Animal Research Facilities (majority of reported cases in US pregnant ewes) Military Units Hospitals and Diagnostic Labs (rarely) 31
32 FOH SURVEILLANCE - APHIS Veterinarians and Animal Health Technicians Obtaining Q Fever titers since titers (1563 employees) obtained since 1/1/ tests (427 employees) were positive at ANY titer of Phase II IgG 27.3% all employees tested 333 tests (143 employees) were positive 1:128 for Phase II IgG 9.1% all employees tested 32
33 Q FEVER APHIS PERSONNEL Distribution of Phase II IgG Titers 1:128 or greater 33
34 WHERE TO GO FROM HERE? Elements for Surveillance Program Baseline titers Evaluation of any evidence of past infection for risk of chronic Q Fever Monitor individuals at high risk for chronic Q Fever Women of childbearing age particularly require education Baseline negative individuals High vs. low risk chronic Q Fever Identify high risk practices??? 34
35 TAKE HOME POINTS Infection frequently symptom-free When symptomatic, FEVER is key Pneumonia can be seen, as well as hepatitis Other clinical conditions RARE (meningitis, pericarditis, etc.) Chronic infection is uncommon but SERIOUS Risk of chronic infection Heart valve anomalies Artificial valves, Vascular grafts Immunocompromised individuals Pregnancy 35
36 TAKE HOME POINTS (CONTINUED) Education of Employees and Clinicians Training and Periodic Refreshers Factsheet for employees Information Card for Providers Periodic Health Assessments Focus on high risk of Chronic Q Fever Pregnancy Valvular heart disease; graft Immunocompromised Interpreting Your Q Fever Serology Tests Diagnosis of Q Fever typically cannot be done with a blood test alone. It requires evidence of clinical findings such as a pertinent history that includes onset of symptoms, types of symptoms, risk factors for complications and exam findings. The blood test is just ONE PIECE OF EVIDENCE, which taken in context of the whole picture, provides guidance to making wise decisions. Given that, what CAN this blood test tell me? Presumably you have no symptoms, so keep in mind that we are looking for BASELINE status. Most tests will return completely negative. For some of you the tests will show evidence of a reaction. If the response is high enough in titer (to be explained further down) it probably represents that at some time in your life you were infected, but there s no infection now. For those with a low titer, this could just mean background noise from the difficult technical nature of the test. In EITHER CASE, we want to repeat the test, to make sure there is no significant change in the result. Why repeat the test? A fourfold rise in antibody titers over a 3 to 6 week period is presumptive evidence of acute infection. This helps us differentiate between the noise of low titer, versus catching the disease early. While one would expect symptoms such as fever, in some individuals no symptoms are apparent. If a fourfold increase in titer occurs, you should go to your doctor for further evaluation and treatment as deemed necessary. When is a titer considered significant? The CDC considers a titer of 1:128 or greater to be significant. Anything less than 1:128 should be considered inconclusive, even though the commercial lab reports positive. Language in the letters from FOH will reflect this as weakly reactive and any reference to positive will be dropped. Weakly positive may have been mentioned in earlier letters, but this is confusing and will no longer be used. Any titer at 1:128 or greater will be regarded as positive, however as noted above one cannot make a diagnosis based upon lab results alone. This usually involves the Phase II IgG component. Occasionally other components in the testing panel, Phase I IgG, Phase I IgM and/or Phase II IgM will show a reaction, but usually in conjunction with a Phase II IgG result. I have a titer of 1:256 (Phase II IgG only) and it has remained stable what should I do? This is consistent with past infection. If you have no symptoms you do not have to take any action. You should make your doctor aware of this finding during your next routine visit to have that documented in your medical history. If you have a history of congenital heart disease (eg. hole in heart or leaky valve ), vascular graft, or immunocompromised state, there is a risk of developing chronic Q Fever and they may wish to monitor you periodically. You should discuss with them what measures need to be taken if any. I have a titer of 1:64 (Phase II IgG only) and it has remained stable what should I do? No action is necessary for you at this point. 36
37 HEALTH ALERT CARD West Nile Virus West Nile Virus This employee of Plum Island Animal Disease Center (PIADC) is working with animals and/or tissue-fluid specimens from animals infected with the West Nile virus, a flavivirus which has been recently linked to human cases of encephalitis in the New York area. Unless the employee reports a breakdown in laboratory safety procedures, or if there has been an accidental exposure to the infected material, infection with the West Nile virus should not be a serious clinical consideration. Symptoms of West Nile Virus Infection Influenza-like illness with abrupt onset of moderate to high fever, headache, sore throat, conjunctivitis, myalgias/arthralgias, retrobulbar pain, lymphadenopathy, anorexia, nausea, abdominal pain, diarrhea and respiratory symptoms. In approximately 50% of cases, a maculopapular or roseolar rash occurs, spreading from the trunk to the extremities and head. In < 15% of cases, acute aseptic meningitis or encephalitis can occur. Anterior myelitis, hepatosplenomegaly, hepatitis, pancreatitis and myocarditis may also occur. Recovery is complete with no sequelae. Fatalities are unusual in persons younger than 50. There have been 18 documented cases of laboratory acquired infection, before current biosafety procedures had been introduced, and none of these cases resulted in mortality. Lab Findings M ild leukocytosis, slightly elevated ESR. When CNS is involved, the CSF is clear, with elevated protein and pleocytosis. Other findings dependent upon complications of infection (ie. hepatitis, pancreatitis, myocarditis, etc.) Infection Control Precautions Universal precautions. West Nile virus should be treated as a bloodborne pathogen, sim ilar to hepatitis B. Treatment Measures There are no antiviral agents known to be effective against West Nile Virus. Treatment is supportive care. If employee is to be hospitalized, please contact appropriate personnel listed below immediately. If employee has been seen and discharged from the Emergency Room or Doctor's Office, please notify the appropriate individuals below within 24 hours. Who to Contact PIADC Safety Office PIADC Duty Officer PIADC Medical Review Officer
38
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