HEALTH MONITORING OF IMMUNODEFICIENT MICE

Transcription

1 HEALTH MONITORING OF IMMUNODEFICIENT MICE Charles River Laboratories currently maintains over 400 isolators at 2 locations to produce nude mice and other immunologically compromised mouse strains. These animals, while maintained under a more microbiologically controlled environment, are not axenic (free of all known organisms). Moreover, while they are initiated as defined flora animals (containing only a few well-defined organisms), our policy has been to continue operating individual isolators if an occasional mold, yeast, fungi or common nonpathogenic environmental bacterium is detected in the isolator. In assessing the health and bacteriologic profiles of the isolators, it is important to understand that each individual isolator functions similarly to a separate barrier production room, each containing between 30 and 75 cages. Depending upon the specifications for any given order, mice from multiple isolators may be required to fill that order, and different groups of isolators may fill repeat orders in subsequent weeks. Since each isolator may have a somewhat different profile in terms of additional organisms beyond the Charles River Altered Schaedler Flora (CRASF), the discrete bacterial profile may vary between subsequent groups of animals. Each isolator is swabbed for assessment of bacterial flora at least every four weeks. In addition, once every 13 weeks a randomized sampling of animals from one fourth of all of the isolators is collected and screened for viral pathogens, parasites, and gross pathologic lesions, as well as bacterial profiles of the respiratory and gastrointestinal tracts. Four animals are sampled from each isolator for this intensive screening process. Health monitoring reports are provided by Charles River Laboratories on our website( or in hard copy for customers preferring that format. These reports document the status of the composite of all the isolator colonies located on a given site. Given the large number of isolators maintained, screening all isolators on a more frequent basis, or taking larger numbers of samples/animals would greatly increase the cost of the animals, yet would not contribute commensurately to the health monitoring program. In the years we have produced immunodeficient animals in isolators for commercial sale, we have never detected a contamination from an organism on our VAFÒ profile list. Moreover, only on a very few occasions have we found an isolator contaminated with a coagulase positive Staphylococcus or b -hemolytic Streptococcus, which are of the most common concern to our customers. When that occurred, we have immediately recycled that isolator. The enclosed list of bacteria is categorized by the action that will be taken by Charles River Laboratories if the organisms are ever detected in an isolator. As can be seen from the chart, the first group of organisms would initiate an immediate notification of ALL customers that had received mice from any of the isolators in the facility. In keeping with our policy of open communication, all Charles River customers regardless of whether or not they received isolator-reared animals would also be notified. These organisms would be cause for immediate recycle of a standard barrier production room and would clearly result in cessation of shipment of any animals from affected isolators and their immediate recycle. The circumstances involving the contamination would be thoroughly investigated and reported. The second category of organisms would also result in immediate termination of the contaminated isolator. Customers receiving

2 animals from that isolator during the period since the last negative screening will be notified. The entire customer base would not be notified, nor will customers that did not receive mice from the contaminated isolator be routinely notified unless requested. If specific information is needed regarding the occurrence of the bacteria in this category, on a case by case basis, such information is available through the Charles River Technical Assistance Department. The remaining categories list organisms for which shipment would not be halted. In an effort to more closely approach CRASF associated status, Category III isolators would not be used as sources for new colony start ups. Clearly, management of a very large group of barrier production units such as isolators poses a difficult task both from a production and a health monitoring standpoint. We feel that it is important that our customers understand the conditions under which our immunodeficient animals are produced and how to interpret the health monitoring data we provide regarding these animals. In developing this production system, we have had to balance the level of risk to the health of the animals inherent in this production system with the amount, frequency and completeness of the information generated, as well as with the information our customers require or expect. We are committed to providing our customers with the information that they require to make animal health management decisions, and in this regard we would appreciate your comments on how we might cost effectively improve the present system. Should you require any additional information or have specific requests, please contact our Technical Assistance Department at or send an to comments@crl.com. Charles B. Clifford, DVM, PhD Director, Pathology and Technical Services

3 GUIDELINES FOR THE RECYCLING AND CUSTOMER NOTIFICATION OF PRODUCTION ISOLATORS FOR IMMUNODEFICIENT MICE Category/Action Organisms I. STOP SHIPMENT FROM ISOLATOR EDIM SEN CAR bacillus Immediate Recycle MCMV PVM Clostridium piliforme Notify All Customers ECUN MHV Corynebacterium kutscheri HANT MVM Mycoplasma pulmonis LDV GD-7 Bordetella bronchiseptica MPV REO-3 Citrobacter freundii 4280 Ectro Helicobacter hepaticus Internal Parasites MAD Salmonella spp. External Parasites K-Virus Streptobacillus moniliformis Poly LCMV II. STOP SHIPMENT Pneumocystis carinii Immediate Recycle b -hemolytic Strep. spp. Notify customers That received animals from the isolator Coagulase (+) Staph. spp. Corynebacterium bovis PROVIDE INFORMATION TO OTHER CUSTOMERS ON REQUEST Pasteurella pneumotropica Streptococcus pneumoniae Mycoplasma spp. Helicobacter bilis Helicobacter spp.

4 III. CONTINUE SHIPMENT Coagulase (-) Staph. spp. Planned Recycle Non-b -hemolytic Strep. spp. DO NOT USE AS SOURCE OF BREED STOCK FOR NEW ISOLATORS Klebsiella spp. * Pseudomonas aeruginosa * NO NOTIFICATION OF CUSTOMERS Corynebacterium spp. (not C. bovis) PROVIDE INFORMATION TO CUSTOMERS ON REQUEST * - Shipping would be terminated immediately for these organisms IV. CONTINUE SHIPMENT Bacillus spp. No Recycle Fungi (molds and yeasts) No Other Actions All other non-pathogenic bacteria PROVIDE INFORMATION TO CUSTOMERS ON REQUEST

5 Division: KINGSTON Area: K95 Species: MICE Current 18 Month Report Date: 7/06/07 Pos/Tstd Pos/Tstd SEROLOGY SEND {ad} 0/008 0/0127 PVM {ad} 0/008 0/0127 MHV {ad} 0/008 0/0127 MVM {ad} 0/008 0/0127 MPV {ad} 0/008 0/0127 TMEV(GDVII) {ad} 0/008 0/0127 REO {ad} 0/008 0/0127 EDIM {ad} 0/008 0/0127 MPUL {ad} 0/008 0/0127 MAV {ae} 0/008 0/0032 POLY {ae} 0/008 0/0032 K {ae} 0/008 0/0032 MCMV {ae} 0/008 0/0032 MTLV {ae} 0/008 0/0030 LCMV {ae} 0/008 0/0032 HANT {ae} 0/008 0/0032 ECTRO {ae} 0/008 0/0032 ECUN {ae} 0/008 0/0032 CARB {ae} 0/008 0/0032 LDV {af} 0/008 0/0016 MNV {ad} 0/004 0/0020 MICROBIOLOGY B. bronchiseptica {be} 0/008 0/0039 C. rodentium {ae} 0/008 0/0040 C. kutscheri {ae} 0/008 0/0039 M. pulmonis {ae} 0/008 0/0039 Salmonella spp. {ae} 0/008 0/0039 S. moniliformis {af} 0/008 0/0016 H. hepaticus {ae} 0/008 0/0039 H. bilis {be} 0/008 0/0039 Helicobacter spp. {be} 0/008 0/0039 K. pneumoniae {ce} 1/016 1/0040 K. oxytoca {ce} 0/016 0/0040 P. multocida {ce} 0/006 0/0034 P. pneumotropica {ce} 0/006 0/0034 P. aeruginosa {ce} 0/016 0/0040 Staph. aureus {ce} 1/008 6/0039 S. pneumoniae {be} 0/008 0/0039 Beta Strep. Grp B {ce} 0/008 1/0039 Beta Strep. Grp G {ce} 0/008 0/0039 Beta Strep. spp. {ce} 0/008 0/0039 Tyzzer's Disease {ag} 0/016 0/0079 PATHOLOGY Gross Exam {eh} 0/016 0/0079 PARASITOLOGY Ectoparasites {ae} 0/008 0/0039 Helminths {ae} 0/008 0/0040 Giardia sp. {be} 0/008 0/0040 Spironucleus sp. {be} 0/008 0/0040 Other Protozoa {ce} 0/008 0/0040

6 Division: KINGSTON Area: K95 Species: MICE TESTING PROFILES DATE ANNUAL LDV SCREEN 3/06/07 COMPLETE HM 2/13/07 SEROLOGY (AP+) 4/10/07 SEROLOGY (TR) 6/05/07 STRAINS & STOCKS INBRED OUTBRED OTHER SPP. C57BL/6 CD-1 RATS REMARKS COLONY POLICY FOR POSITIVE RESULT: a = immediate termination; b = planned future recycle of the colony; c = no action. TESTING SCHEDULE: d = screened every four weeks; e = screened quarterly; f = screened annually. g = screened quarterly by clinical exam. h = results do not include incidental or strain related findings; significant findings would result in immediate termination of the colony. Data shown are representative of the colony; Please contact Technical Assistance at for more information on any positive findings appearing in this report as well as assistance in interpreting them.

7 Division: WILMINGTON Area: 091 Species: MICE Current 18 Month Report Date: 7/11/07 Pos/Tstd Pos/Tstd SEROLOGY SEND 0/028 0/1161 PVM 0/028 0/1161 MHV 0/028 0/1161 MVM 0/028 0/1161 MPV 0/028 0/1161 TMEV(GDVII) 0/028 0/1160 REO 0/028 0/1161 EDIM 0/028 0/1160 MPUL 0/028 0/1161 MAV 0/028 0/1157 POLY 0/028 0/1157 K 0/028 0/1155 MCMV 0/028 0/1144 MTLV 0/028 0/1113 LCMV 0/028 0/1156 HANT 0/028 0/1157 ECTRO 0/028 0/1157 ECUN 0/028 0/1157 CARB 0/028 0/1155 LDV 0/028 0/1161 MNV 0/056 0/2295 MICROBIOLOGY B. bronchiseptica {a} 0/056 0/2315 C. rodentium 0/056 0/2291 C. kutscheri {a} 0/029 0/8748 C. bovis {a} 0/029 0/7077 M. pulmonis 0/056 0/2315 Salmonella spp. 0/056 0/2315 S. moniliformis 0/056 0/2315 H. hepaticus 0/002 0/1180 H. bilis 0/002 0/1180 Helicobacter spp. 0/002 0/1180 K. pneumoniae {a} 0/029 0/8748 K. oxytoca {a} 0/029 0/8748 P. pneumotropica {a} 0/029 0/8745 P. aeruginosa {a} 0/029 0/8748 Staph. aureus {a} 0/029 0/8752 S. pneumoniae {a} 0/029 0/8748 Beta Strep. spp. {a} 0/029 0/8748 Pneumocystis 0/002 0/1140 Tyzzer's Disease {c} 0/056 0/2295 PATHOLOGY Gross Exam {b} 0/056 0/2317 PARASITOLOGY Ectoparasites 0/056 0/2315 Helminths 0/056 0/2308 Enteric Protozoa 0/056 0/2311

8 Division: WILMINGTON Area: 091 Species: MICE TESTING PROFILES DATE ANNUAL HM 6/11/07 COMPLT HM W/SEROLOGY 6/27/07 ISOLATOR SWAB 7/03/07 SEROLOGY (TR) 4/23/07 STRAINS & STOCKS INBRED OUTBRED CB17 NU+ CB17SCID NU/NU NOD SCID REMARKS IMMUNODEFICIENT MICE All agents are screened quarterly. The policy for a positive result is to immediately recycle the isolator. a = additional bacteriology is done every four weeks by isolator swab. b = results do not include incidental or strain related findings; significant findings would result in immediate recycle of the isolator. Data shown are representative of the colony; Please contact Technical Assistance at for more information on any positive findings appearing in this report as well as assistance in interpreting them.

9 Division: RALEIGH Area: R10 Species: RATS Current 18 Month Report Date: 7/06/07 Pos/Tstd Pos/Tstd SEROLOGY SEND {ad} 0/008 0/0151 PVM {ad} 0/008 0/0143 SDAV {ad} 0/008 0/0151 KRV {ad} 0/008 0/0151 H-1 {ad} 0/008 0/0151 RPV {ad} 0/008 0/0151 RMV {ad} 0/008 0/0151 REO {ad} 0/008 0/0151 RTV {ae} 0/008 0/0055 MPUL {ae} 0/008 0/0151 LCMV {ae} 0/008 0/0055 HANT {ae} 0/008 0/0055 MAV {ae} 0/008 0/0055 ECUN {ae} 0/008 0/0055 CARB {ae} 0/008 0/0055 MICROBIOLOGY B. bronchiseptica {be} 0/008 0/0048 C. kutscheri {ae} 0/008 0/0048 M. pulmonis {ae} 0/008 0/0048 Salmonella spp. {ae} 0/008 0/0048 S. moniliformis {af} 0/008 0/0016 H. hepaticus {ae} 0/008 0/0048 H. bilis {be} 0/008 0/0048 Helicobacter spp. {be} 0/008 0/0048 K. pneumoniae {ce} 0/008 0/0048 K. oxytoca {ce} 1/008 2/0048 P. multocida {ce} 0/007 0/0033 P. pneumotropica {ce} 0/007 0/0037 P. aeruginosa {ce} 0/008 1/0048 Staph. aureus {ce} 6/008 21/0048 S. pneumoniae {be} 0/008 0/0048 Beta Strep. Grp B {ce} 1/008 8/0048 Beta Strep. Grp G {ce} 0/008 0/0048 Beta Strep. spp. {ce} 0/008 0/0048 Tyzzer's Disease {ag} 0/016 0/0096 PATHOLOGY Gross Exam {eh} 0/016 0/0096 PARASITOLOGY Ectoparasites {ae} 0/008 0/0048 Helminths {ae} 0/008 0/0048 Giardia sp. {be} 0/008 0/0048 Spironucleus sp. {be} 0/008 0/0048 Other Protozoa {ce} 0/008 0/0048

10 Division: RALEIGH Area: R10 Species: RATS TESTING PROFILES DATE COMPLETE HM 5/29/07 SEROLOGY (AP+) 4/05/07 SEROLOGY (TR) 5/30/07 STRAINS & STOCKS OUTBRED CD REMARKS COLONY POLICY FOR POSITIVE RESULT: a = immediate termination; b = planned future recycle of the colony; c = no action. TESTING SCHEDULE: d = screened every four weeks; e = screened quarterly; f = screened annually. g = screened quarterly by clincial exam. h = results do not include incidental or strain related findings; significant findings would result in immediate termination of the colony. Data shown are representative of the colony; Please contact Technical Assistance at for more information on any positive findings appearing in this report as well as assistance in interpreting them.