Project Number: 9278430 Project Title: Method Development for Fungi in Occupational Diseases Division: DART Project Officer (PO): Millie P. Schafer PO Degree: Ph.D. PO Area of Expertise (scientific discipline): Molecular Biology Project Start Date: 10/1/1997 Project End Date: 9/30/2002 Total Budget over the Project Period: $ 53,847 Goal/Sub-Goal: Exposure Assessment Research Challenge/Issue: Approximately 120,000 poultry farm workers are at increased risk for mycotic respiratory diseases (Olson, AAOHN 1996). Inhalation of spore-containing dust often contaminated with bird or bat droppings is the primary cause of these diseases. The efficacy of various technologies and methods for preventing these infections has not been adequately evaluated. Fast, inexpensive, specific fungal analytical methods would permit the detection of these fungi in soil and bird and bat droppings. The utility of various disinfectants could then be evaluated as well as environmental control measures such as dust suppression methods. NIOSH has received numerous inquiries and has been actively engaged in Health Hazard Evaluations pertaining to worker concerns involving Histoplasma capsulatum, Cryptococcus neoformans, Blastomyces dermatitidis, and Coccidioides immitis associated with bat and bird droppings or contaminated soil in various occupational settings. The extent of occupational risk in these work environments is unknown as no fast, specific, sensitive, relatively inexpensive analytical methods are available for the detection of these particular fungal pathogens. Activities: The main goal of this project is to develop a sampling and analytical method for disease-causing fungi, a major hazard in construction and agricultural occupations. The project utilizes state-ofthe-art molecular bioanalytical techniques in order to identify pathogenic fungi in the workplace. This approach would permit the screening of potential environmental hazardous sites for the presence of these disease-causing fungi. Disinfection procedures could then be used to kill the fungi thereby minimizing occupational exposure as well as exposure to others living nearby. Development of fungal DNA analytical methods, such as the polymerase chain reaction (PCR), would overcome the difficulties stated above. Limits of detection and the feasibility of quantification will be determined. Development of a DNA analytical method which may permit rapid simultaneous screening for the four fungi without culturing would also be undertaken. In-house collaborators include DSHEFS and DBBS. Real world samples which tested positive via the traditional indirect mouse inoculum assay have been located (1999).The method (H. Capsulatum) has been compared with other methods in a field test. Results are not final yet. A technical journal article is planned. Outputs:
A DNA analytical method, the polymerase chain reaction (PCR), has been developed to specifically detect Histoplasma capsulatum and has been used in some Health Hazard Evaluations. An international patent is in the process of being filed on the method. The related publication is: Direct Detection of Histoplasma Capsulatum in Soil Suspensions by Two-Stage PCR - T. M., Reid and M. P. Schafer [1999] MOL CELL PROBE 13 (4): 269-273 AUG 1999. [cited 11 times] A fact sheet entitled "Histoplasmosis" and a document entitled "Histoplasmosis: Work Practices and Personal Protective Equipment Selection for Workers at Risk of Exposure to Histoplasma Capsulatum" were co-authored with Steve Lenhardt, DSHEFS and Rana Hajjeh, NCID. Histoplasmosis: Protecting Workers at Risk - S. W. Lenhart, M. P. Schafer, M. Singal and R. A. Hajjeh [1997] DHHS (NIOSH) Publication No. 97-146. A task contract was awarded to Aerotech Laboratories, Inc. to continue validation studies of the NIOSH Histoplasma capsulatum PCR method and to determine the optimal recovery of histo DNA from various environmental matrices. Real world samples will be tested for the presence of Histoplasma capsulatum. Chapter J in NMAM; 'Sampling and Characterization of Bioaerosols', Jensen PA, Schafer, MP, 31pp. [1998] in NIOSH Manual of Analytical Methods (NMAM®), 4th ed. DHHS (NIOSH) Publication 94-113 (August, 1994), 1st Supplement Publication 96-135, 2nd Supplement Publication 98-119, 3rd Supplement 2003-154, Schlecht, P.C. & O'Connor, P.F. (pfo1@cdc.gov), Eds. Presentations: A poster presentation on "Direct Detection of Histoplasma capsulatum in Contaminated Soil by 2-stage PCR" by Tom Reid, DBBS and Millie Schafer, DPSE will be presented at the American Society of Microbiology in May 1997. Schafer, M.P. Guidelines for Prevention of Histoplasmosis in the Cleanup of Bird Droppings and Bat Guano. MidAtlantic Environmental Resource Center, October 1997 (invited). Lenhart, S.W. and Schafer, M.P. Removal of 60 tons of manure from a building: Protecting workers at risk. American industrial Hygiene Conference & Exposition (AIHCE), May 1998. Patent: A joint patent application between Reid and Schafer has been filed on the novel H. capsulatum PCR method. An Issue Notification involving the U.S. Patent Application for the “Rapid and Sensitive Method for Detecting Histoplasma capsulatum” was received. The patent issued on October 22, 2002 as U.S. Patent No. 6,469,156.
Intermediate Outcomes: Assistance was given in regard to an outbreak of histoplasmosis at a Texas zoo. Numerous animals died and a newly hired worker became ill. Future Directions: This project has continued under 9278456 [Bartley]. The issued patent is listed under 9278456. References: Olson DK, Bark SM., Health hazards affecting the animal confinement farm worker. AAOHN J. 1996 Apr; 44 (4):198-204.
Project Number: 927Z1NG Title: Prevention of Occupational Respiratory Disease in Agriculture Division: DRDS Project Officer: Greg Kullman, Paul Henneberger, and Teri Palermo Start Date: 10/1/2005 End Date: 9/1/2010 Total Budget: $299,000 Goal: Health Effects of Agriculture Exposures SubGoal: Respiratory Disease Target Audience: Pesticide manufacturers Pesticide applicators USDA - Cooperative Extension State Health Departments Medical providers / rural clinics Universities / agricultural health and safety research centers Agricultural Health Researchers Collaborators: NIOSH, The National Institute of Environmental Heatlh Sciences (NIEHS) The Environmental Protection Agency (EPA) The National Cancer Institute (NCI) University of Iowa Battelle The US Department of Agriculture, National Agricultural Surveillance System Stakeholders: Pesticide manufacturers Pesticide applicators Farmer applicators Agricultural / pesticide research centers State Health Departments NIOSH Agricultural Centers USDA - Agricultural Extension Challenge / Issue: Agriculture consistently ranks as one of the most hazardous industries in the United States. Over 3 million agricultural workers are at high risk for fatal and nonfatal injuries, noise-induced hearing loss, skin diseases, and certain cancers associated with chemical use and prolonged sun exposure. Agricultural workers are also at significant, increased risk for work related lung disease including organic dust toxic syndrome (ODTS), hypersensitivity pneumonitis, asthma, and other chronic obstructive airways diseases including chronic bronchitis The lack of adequate health surveillance data continues to be an important gap in targeting prevention. Historically, agricultural respiratory diseases have been largely attributed to organic dust exposures including bioaerososl.
Associations between pesticide exposures and respiratory disease in agriculture are largely unstudied. This project supports two research and surveillance efforts in agriculture for respiratory disease prevention: The Agricultural Health Study and a USDA, National Agricultural Surveillance survey. The lack of sources of good health surveillance date in agriculture has been a focus of the NIOSH Agricultural Steering Committee. This committee has recommended that additional resources be applied to health surveillance in agriculture including respiratory disease. This was one of the major recommendations from a NIOSH prioritization exercise conducted by the NIOSH Agricultural Steering Committee. The surveillance efforts in this project will target many different agricultural sectors nationally. No one specific sector or population is targeted. Some of the efforts involving pesticide exposures and respiratory disease focus on agriculture in the states of Iowa and North Carolina where the Agricultural Health Study is currently ongoing. Since this is a newer project, no major problems have emerged to date. The total budget to date is $229,000. The project includes approximately 1.15 FTEs Activity: This project will address the knowledge gaps regarding respiratory health outcomes in agriculture including asthma, hypersensitivity pneumonitis, chronic bronchitis, and agricultural respiratory exposures. To accomplish the goal, NIOSH partnered with two existing studies to gather respiratory health outcomes data – the Agricultural Health Study (AHS) and the US Department of Agriculture (USDA), National Agricultural Surveillance System (NASS). The staff involved in both of the existing studies has expertise in epidemiology, occupational medicine, environmental health, and biostatistics, while the NIOSH staff provides its own expertise in respiratory disease, agricultural health and safety, data analysis and information dissemination. The Agricultural Health Study (AHS) is one of the hallmark efforts currently underway on agricultural health in the United States. The study was initiated in 1993 by 3 lead organizations including: The National Cancer Institute (NCI), The National Institute of Environmental Health Scientists (NIEHS), and The US Environmental Protection Agency (EPA). The study uses a longitudinal cohort design and evaluates how lifestyle habits, genetic factors, and agricultural exposures at work and in the environment contribute to the risk of disease. Over 89,000 certified farmer pesticide applicators and their spouses from North Carolina and Iowa and licensed commercial pesticide applicators from Iowa are included in the study making it one of the largest agricultural health studies ever conducted in the United States. The AHS is now in the third round. Initial study efforts focused on pesticide exposures in the etiology of various cancers. However, more recent efforts have begun to address other health outcomes including kidney disease, nervous system disorders, reproductive effects, and respiratory disease. The project provides
support for the respiratory disease portions of the study during the third round of the AHS including questionnaire administration. The Division will also provide consultation on respiratory disease study aspects including data analysis, poster presentation and journal manuscript planning. This large cohort provides a unique opportunity to apply division resources for the study of respiratory health outcomes in agriculture including asthma, hypersensitivity pneumonitis, and chronic bronchitis with the study of both prevalent and incident disease patterns as well as risk factors related to pesticide and non-pesticide exposures. This project also provides for collaboration with NIOSH / DSR on a National survey completed through contract with the US Department of Agriculture (USDA), National Agricultural Surveillance System (NASS). The USDA NASS has established the expertise and rapport for collecting survey data from agricultural populations. DRDS will add a respiratory health and exposure component to the larger agricultural health and safety survey funded through NIOSH / DSR. The respiratory focus will be on asthma and respiratory exposures. The survey will target 25,000 farm operators nationally stratified by geography and commodity providing a large, representative sample. This project promotes intermural and extramural collaboration in two exiting surveys which have been well received within the agricultural community. Results from these efforts will be shared with our partners nationally and applied to better direct exposure reduction and respiratory disease prevention efforts in agriculture. Study outcomes may also identify new research needs or be used to initiate new research studies addressing pesticide exposure and respiratory disease in agriculture. The work on this project will be completed over a 5 year time period. The total project budget to date is $229,000. This involves largely funds to two existing contractors to support respieatory questionnaire administration for the third round of the Agricultural Health Study. This funding also included: 1) travel to meet with collaborators at NIEHS, NCI, and EPA 2) Pilot testing or respiratory questionnaire questions 3) Support for an Association of Schools of Public Health Fellow, stationed at NIEHS, in Research Triangle Park, NC, to contribute to data analysis and report writing. Current NIOSH FTEs include approximately 1.15. DRDS, in collaboration with the NIEHS and NCI, will supporting the costs for the administration of respiratory questionnaire aspects for the 3rd round of the Agricultural Health Study. We will collaborate in presenting study findings and in the development of new research efforts. DRDS will also collaborate with DSR and DSHEFS in the analysis of respiratory questionnaire data from the National questionnaire survey currently being administered by the US Department of Agriculture, National Agricultural Statistical Service (NASS). Most of the research on agricultural pesticides to date has been focused on systemic toxicity and cancer outcomes. These research and surveillance efforts are novel in
addressing potential associations between agricultural pesticide exposures and respiratory disease – an area that has not been well studied. Preliminary findings from our collaborative research on the Agricultural Health Study are showing some previously unrecognized (and unreported in the agricultural health literature) associations between pesticide exposures and respiratory health outcomes including chronic brohchitis, hypersensitivity pneumonitis, and asthma. Results from these efforts will be applied to better direct exposure reduction and respiratory disease prevention in agriculture. The identification of new risk factors (pesticide expsoures) for these respiratory diseases in agriculture will help guide prevention efforts. Study outcomes may also identify new research needs or be used to initiate new research studies addressing pesticide exposure and respiratory disease in agriculture. Regarding our collaborative efforts with the NIOSH/DSR, administration of the NASS questionnaire is currently underway and results are not available at this time. Outputs: Presentations: Valcin M, Henneberger PK, Kullman GJ, Umbach DM, London SJ, Alavanja MCR, Sandler DP, Hoppin JA. Risk Factors for Chronic Bronchitis Among Non-Smoking Farm Women in the Agricultural Health Study. 2nd North American Congress of Epidemiology, 2006 Society for Epidemiologic Research, Seattle, Washington, June 21 – 24, 2006. Hoppin JA, Umbach DM, London SJ, Henneberger PK, Kullman GJ, Alavanja MCR. Sandler DP. Pesticide Exposure and Allergic and Non-Allergic Asthma in the Agricultural Health Study. 2nd North American Congress of Epidemiology, 2006 Society for Epidemiologic Research, Seattle, Washington, June 21 – 24, 2006. Journal manuscripts: Hoppin JA, Umbach DM, Henneberger PK, Kullman GJ, London SJ, Alavanja MCR. Sandler DP. Agricultural factors associated with Farmers Lung among Farm Residents in the Agricultural Health Study, submitted to OEM. Valcin M, Henneberger PK, Kullman GJ, Umbach DM, London SJ, Alavanja MCR, Sandler DP, Hoppin JA. Chronic Bronchitis Among Non-Smoking Farm Women in the Agricultural Health Study. Submitted to European Respiratory Journal. Intermediate Outcomes: The preliminary findings from these research efforts have moved researchers at NIOSH, NIEHS, and NCI to action in developing a new case control study addressing pesticide exposure, diesel exposure, and occupational asthma in agriculture. This new study proposal was based on the preliminary results from research efforts on the AHS. End Outcomes:
None to date