LABORATORY ACQUIRED INFECTIONS (LAI) INFECTIONS (LAI)

Karen B Byers, MS, RBP, CBSPBiosafety Managery g

Dana Farber Cancer Institute

60th Annual Biological Safety ConferenceOctober 13 - October 18 Albuquerque, New Mexico

3,230 Primary LAIs - data from 488references published 1979 2015 references published 1979-2015.

Symptomatic Asymptomatic TotalSymptomatic Asymptomatic Total

Bacteria 1212-1226 142 1354-1368

Rickettsia 205 269 474Rickettsia 205 269 474

Viruses 764-766 439 1203-1205

Parasites 170 4 174Parasites 170 4 174

Fungi 25-26 0 25

Total 2376-2392 854 3230-3246Total 2376 2392 854 3230 3246Byers, K and L. Harding. 2017. Laboratory Acquired Infections In Biological Safety, Principlesand Practices, 5th edition, D. Wooley and K.Byers, editors. ASM Press.

Limitations of Literature Survey that Limitations of Literature Survey that produced the data presented today -

Literat re search of p blished reports not a s r e■ Literature search of published reports, not a survey.■ International search, but for journals with English

abstract – found on PubMed or Google.g

WHY Do it?WHY Do it?■ Acknowledging that LAI occur fosters change■ Develop evidence-based prevention programsp p p g■ Provide examples for training programs

TOP TEN LAI Reported in Literature 1930 1979 1979 20151930-1979 1979-2015

Rank Agent # LAI

1 Brucella spp. 378

Rank Agent # LAI

1 Brucella spp 426

2 M. tuberculosis 255

3 Arboviruses 222

4 Salmonella spp. 212

2 Coxiella burnetti 280

3 Hepatitis B 268

4 Salmonella enterica Typhi 258 Sa o e a spp

5 Coxiella burnetii 205

6 Hantavirus 189

7 Hepatitis B virus 113

yp

5 Francisella tularensis 225

6 M. tuberculosis 194

7 Blastomyces dermatitidis 162 7 Hepatitis B virus 113

8 Shigella spp. 88

9 HIV 48

10 N i i idi 43

7 Blastomyces dermatitidis 162

8 VEE 146

9 Chlamydia psittacosis 116

10 N. meningitidis 43

TOTAL 1,753

10 Coccicioides immitis 93

TOTAL 2,168

Byers, K and L. Harding. 2017. Laboratory Acquired Infections In Biological Safety, Principles and Practices, 5th.ed.

LAI in Various Types Work[CATEG [CATEGLAI in Various Types Work

Site

[CATEGORY

NAME][PERC

[CATEGORY

NAME]LAISite

Clinical [CATEGORY

[PERCENTAG

E]

][PERCENTAG

E]

LAI

1008

Research

Industry

NAME][PERCENTAG

E]

[CATEGORY

NAME]

916

90

Teaching

Field

E]NAME][PERCENTAGE]276

18Field 18

Byers, K and L. Harding. 2017. Laboratory Acquired Infections In Biological Safety, Principles and Practices, 5th.ed.

Primary

Secondary(2y) & Tertiary (3y)Primary LAI (1y)Infected Lab worker

Bacteria Viruses Parasites

Secondary 12 19 2Secondary 12 19 2

Tertiary 3 7 -

Secondary LAI-1Y LAI transmitted Infection to someoneOutside workplaceOutside workplace

B K d L H di 2017 L b t A i d I f ti

Tertiary LAIInfection transmitted from 2y.

Byers, K and L. Harding. 2017. Laboratory Acquired InfectionsIn Biological Safety, Principles and Practices, 5th edition, D. Wooley and K.Byers, editors. ASM Press.

Bacterial: 2y & 3y Infections were to Bacterial: 2y & 3y Infections were to Close Contacts.

■ LAI with S sonnei in clinical laboratory; 2y transmission to grandchild; ■ LAI with S. sonnei in clinical laboratory; 2y transmission to grandchild; 3y to 3 family members. Reference (Ref) #1.

■ 4 secondary infections in children under age 4 whose parents were students in microbiology teaching laboratories in the US. Ref #2.

■ 2 incidents of sexual transmission of Brucella. Ref#3, 4. ■ Dinner prepared by microbiologist transmitted Salmonella to wife and

son. Ref. #5.■ Lactating mother transmitted Leptospira interrogans through breast

milk. Ref. #6.■ 2 secondary transmissions of Bordetella pertussis occurred. Ref. #7

Byers, K and L. Harding. 2017. Laboratory Acquired Infections IN Biological Safety, Principles and Practices,5th ed. D. Wooley and K.Byers, ed. ASM Press

2y Viral Infections were in Close ContactsContacts.■ Zika Virus – wife of entomologist returning from mosquito study in Senegal.

(Ref.#8.)

M thi h i 1 t itt d th h h d t b f ■ Macathine herpesvirus 1 –transmitted through shared tube of hydrocortisone cream. (Ref #9).

■ Marburg virus - pathologist who did autopsy on LAI. (Ref #10)

P li i i i T i i i i d hild f ff ■ Polio virus – vaccine strain. Transmission to immunized child of staff member involved in spill cleanup. (Ref.#11) (Note: an ABSA member states that the worker showered and was provided with a change of clothing)

■ SARS – 2 secondary 5 tertiary Inadequately inactivated samples removed ■ SARS 2 secondary, 5 tertiary. Inadequately inactivated samples removed from BSL3; 2: mother and nurse of student, 5 patients of nurse. (Ref. #12).

■ Titi monkey Adenovirus – 1 attending veterinary for sick monkeys became ill; also one household member. (Ref #13)

Byers, K and L. Harding. 2017. Laboratory Acquired Infections IN Biological Safety, Principles and Practices, 5th ed. D. Wooley and K.Byers, ed. ASM Press

Fatal LAIs-BacteriaFatal LAIs Bacteria

■ 13 fatalities due to N. meningitidis. (Refs # 14-20). ■ 4 aborted fetuses due to Brucella melitensis LAI. (Ref #21-

23). ■ 3 due to Salmonella ( 1 was a secondary infection-wife of ■ 3 due to Salmonella ( 1 was a secondary infection wife of

clinical microbiologist). (Ref # 24,25,26).■ 1 due to Y. pestis (autopsy of mountain lion in a garage

without precautions) (Ref #27)without precautions) (Ref #27)■ 1 due to attenuated Y. pestis KIMD27 (LAI had undiagnosed

hereditary hemochromatosis). (Ref #28)Byers, K and L. Harding. 2017. Laboratory Acquired Infections IN Biological Safety, Principles and Practices, 5th edition. D. Wooley and K.Byers, ed. ASM Press.

FATAL LAIs - VIRALFATAL LAIs VIRAL■ Macacine herpesvirus 1 (CHV-1, Monkey B)- 5 LAI. Ref list #29 -33.

■ Arboviruses – 3 (Ref# 34) ■ Arboviruses – 3 (Ref# 34)

■ Hantavirus 2 (refs # 35, 36)

■ Hepatitis B virus 1 LAI. (ref #37)

■ Hepatitis C virus 1 Ref. (ref #38)

■ Ebola virus 2 LAI* Ref # (ref #39, 40)

■ SARS Co-V (Ref #12)( )

■ 1 fetal abortion due to Parvovirus LAI. (Ref #41)

*H lth /l b t k i th 2014 Eb l id i b d t *Healthcare/laboratory workers in the 2014 Ebola epidemic succumbed to occupational infections, but exact data is not available.

DROPLET Transmission DROPLET Transmission 43 cases of LAI N. meningitidis in literature—

■ ONLY 1 microbiologist infected in each case ■ ONLY 1 microbiologist infected in each case

■ 41 worked on the open bench (catalase assays, made suspensions, etc.) 2 worked behind a plastic shield; 1 in a defective biosafety cabinet.

■ None were immunized.

Brucella exposure-HIGH Risk AerosolHIGH:1. Having direct personal exposure to Brucella

(sniffing bacterial cultures, direct skin contact, pipetting by mouth, inoculation, or spraying into the eyes, nose,or mouth.)

2. Performing work on the open bench (outside of BL3) with an open culture plate or being in close

i i h k ( b h proximity to such work (across an open bench top or within 5 feet)

3. Presence in the laboratory during any procedure B ll i l t th t ight lt i on a Brucella isolate that might result in

generation of aerosolized organisms and inhalational exposure (e.g. vortexing or catalasetesting)testing)

- MMWR 57(02) 39-42

Brucella Exposure-Low riskBrucella Exposure Low risk

LOW RISK

■ Present in the laboratory during workup and

RISK

■ Present in the laboratory during workup and identification of a Brucella isolate

■ From the time the culture is first isolated until all culture isolates are removed or destroyed from the laboratory.

■ Not meeting criteria (1 2 3) for high-risk■ Not meeting criteria (1,2,3) for high risk.

BSAT LAIsBSAT LAIs■ 2004-2010: 10,000 individuals with access to BSAT.

11 LAI no fatalities no secondar infections 8 research labs 3 ■ 11 LAI; no fatalities, no secondary infections. 8 research labs, 3 clinical labs.

Monitoring Select Agent Theft, Loss and Release Reports in the United S 2004 2010 A li d Bi f V l 17 I 4 2012States—2004–2010 Applied Biosafety Vol 17, Issue 4, 2012

2015 Annual Report on Federal Select Agent Program2015 Annual Report on Federal Select Agent Program

■ 199 potential exposure incidents resulting in monitoring

■ 0 LAI

https://www.selectagents.gov/annualreport2015.html

Case study example: Could a researcher in Case study example: Could a researcher in a hurry do this at your institution?

Follow SOP for filtering virus: remove capped needle from syringe, use syringe to draw up virus, filter. Then… because the syringe did not fit in the bottom of the tube… the needle was re-attached to draw the virus into the syringe. The needle had to be removed in order to replace the filter, and the researcher sustained a needlestick at that point.

The technician did self-testing; symptoms of dengue infection presented on day 9; the assay was positive on day 10.

Th th bli h d i i l ti th i id t d d d t The authors published images simulating the exposure incident, and recommended stronger language in the WHO advice on the use of needles.

After recovery, the technician was assigned to a different laboratory to prevent exposure to other serotypes of dengueserotypes of dengue.

https://aoemj.biomedcentral.com/articles/10.1186/s40557-016-0104-5

Lessons learned about PPE for Lessons learned about PPE for Field Studies Fatal infection of wildlife biologist in US National Park.

died 1 week after conducting necropsy in his garage of plague-infected mountain lion.

no PPE used.

Fatal infection of graduate student:

interview of 2 other students on the same project ambitious student interview of 2 other students on the same project –ambitious student collecting samples from wild rodents: many bites, no PPE, no handwashing, even before eating.

References:References:http://cid.oxfordjournals.org/content/49/3/e33.fullhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Am+J+Trop+Med+Hyg+76(3)+2997+438-442

National Park Service ResponseNational Park Service Response■ Biosafety guidelines

■ Survey of staff points out the need for PPE availability, portability, and f ibilit d fi ld ditifeasibility under field conditions.

■ Found staff that were trained by ■ Found staff that were trained by supervisor more likely to use PPE.

https://www.nps.gov/public_health/info/di/Field%20Guide%20NPS%20biologists.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/23778595

References References ■ 1) De Schrijver, KAL et.al. 2007.Tijdsch Geneeskd 63:686-690.

■ 2) Centers for Disease Control.2014. https://www.cdc.gov/salmonella/typhimurium-labs-06-14/index.html/

■ 3) Goosens H. et.al. 1983. Lancet 231:773

■ 4) Ruben B. et al. 1991. Lancet 337:14-15.

■ 5) Blaser,MJ.1981. J Clin Microbiol 3:855-858.

■ 6) Bolin CA, Koellner.P. 1988. J Infect Dis 158:246-247.

■ 7) US Department of Health and Human Services. 1999. BMBL.

■ 8) Foy BD et al. 2011. Emerg Infec Dis 17:880-882.

■ 9) Centers for Disease Control. 1987. MMWR 36:289-290, 295-296.

■ 10) Alibek,K. 1999. Biohazard. Dell Publishing of Random House, New York.

■ 11) Mulders, MN et al. 1997. J Infec Dis 176:517-624,

References■ 12) Heymann DL et al. Lancet 363: 1566-1568.

■ 13) Chen EC et al. 2011. PLoS Pathog 7:e1002155.

■ 14) Walker, D. Campbell, D. 1999. J Clin Pathol 52: 415-418.

■ 15) Boutet R et al. 2001. J Hosp Infect 49::282-284.

■ 16) Bremner, D. A. 1992. Aust Microbiol.13:: A106.■ 16) Bremner, D. A. 1992. Aust Microbiol.13:: A106.

■ 17) CDC. 1991. MMWR 40: 46-47, 55.

■ 18) Sheets, CD et al. 2014. MMWR 63: 770-772.

■ 19) Paradis JF Grimard D 1994. Can Commun Dis Rep 20: 12-14.

20) S j l 2005 J Cli Mi bi l 43 4811 4814 ■ 20) Sejvar et al. 2005. J Clin Microbiol 43: 4811-4814.

■ 21) Al_Aska, AK, Chagla, AH. 1989. J Hosp Infec 14: 69-71.

■ 22) Georghiou PR, Young, EJ. 1989. Lancet 337: 1543.

■ 23) Young, E.J. 1983. Rev. Infect Dis 5:821-842. Young E. J. 1991. Rev. Infect Dis 13: 359-372.

■ 24) 25) CDC.2011.http://www.cdc.gov/salmonella/typhimurium-laboratory/index.html

■ 25) Blaser, MJ et al. 1980. J. Infect Dis. 142: 934-938.

■ 26) Blaser MJ, Lofgren, JP. 1981. J Clin Microbiol. 13: 855-858. .

■ 28) Wong, D. et. al. 2009. Clin Infect Dis 49: e33-e38. 8) o g, et a 009 C ect s 9 e33 e38

■ 29) CDC. 2011. MMWR 60:201-205.

References- Fatalities from Viral LAIReferences Fatalities from Viral LAI■ 30) MWWR 36: 289-90, 295-6 MMWR 38: 453-4.

■ 31) MMWR 47: 1073-6, 1083.

■ 32) Davenport, 1994. Clin Infect Dis 19:33-41.

■ 33) R. Rebar, 1991. ABSA Newsletter, Dec.8.

■ 34) Subcommittee on Arbovirus Laboratory Safety of the American Committee on A th d B Vi 1990 A J T M d H 29 1359 1381Arthropod-Borne Viruses. 1990. Am J Trop Med Hyg 29:1359-1381.

■ 35) Israeli E. 2014. Harefuah 153:443-444, 499.

■ 36) Sinclair et. al. 2007. Am J Trop Med Hyg 76: 438-442.

■ 37) Jacobson, et al. 1985. J. Clin Microbiol. 21(4):468-9.

■ 38) Grist. J. Clin. Path. 38:721-725.

■ 39) ProMed mail archive #20040522.1337.

■ 40) LeGuenno 1995, Sci Am 273:56-64.

■ 41) Cohen, BJ. 1988. J Clin Pathol 1027-1028.

FOR MORE FOR MORE INFORMATION ON LAIINFORMATION ON LAI

LAI Database Resource LAI Database Resource

Open-access, searchable database of LAI published referencesOpen access, searchable database of LAI published references

Development description:

D. Gillum, P. Krishna, K. Byers. 2016. A Searchable Laboratory acquired Infection Database.Applied Biosafety 21:4.

A f 10/8/2017 258 f dd d As of 10/8/2017: 258 references added. Amazing volunteers!

Date(s) of LAI / exposure: 2008 07 31Location where LAI / exposure occurred:

Database entry – sample.

Date(s) of LAI / exposure: 2008-07-31Wisconsin, USA

Occupation(s) of affected personnel: University laboratory researcher

Age(s) of affected personnel: Unknown

Agent(s) involved: Brucella melitensisAgent(s) involved: Brucella melitensis

Biological Safety Level (BSL) for work being performed?:

Setting in which LAI / exposure occured:

University research laboratoryDevice or equipment involved: Goggles Procedure being performed: Removing safety goggles

How LAI / exposure occurred: Goggles had been removed for cleaning while the individual was working with the bacterium a few months before the illness began. The researcher had undulating fever, weakness, and arthralgia in back and ankle for 10 weeks. PPE worn at the time of LAI / exposure: Safety glasses Engineering controls used at the time of the LAI / exposure: UnknownEngineering controls used at the time of the LAI / exposure: UnknownFollow-up procedures taken: Laboratory procedures were reviewed, and recommendations were made to improve respiratory protection, disinfection, sharps management, training, and emergency planning. Baseline serum had been collected on all 12 lab members. Symptom surveillance was conducted for 24 weeks; Serological monitoring occurred at weeks 2,4, 6, and 24 weeks after the diagnosis. Symptom monitoring occurred weekly; there were no additional seroconversions in the other 11 researchers. occurred weekly; there were no additional seroconversions in the other 11 researchers.

Reference:R. M. Traxler, et.al. Review of Brucellosis Cases from Laboratory Exposures in the United States in 2008 to 2011 and Improved Strategies for Disease Prevention. J. Clin. Microbiol. 2013, 51(9):3132. DOI: 10.1128/JCM.00813-13.

Literature surveys to answer specific Literature surveys to answer specific questions- some open-access examples.

■ Kimman, T. et. al. 2008. Evidence-based biosafety: a review of the principles and effectiveness of microbiological containment measures http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2493080/pdf/0014-08 pdf08.pdf

■ Traxler et al. 2013. Review of brucellosis cases from laboratory exposures in the United States in 2008 to 2011 and improved strategies for disease prevention. g phttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3754678/pdf/zjm3132.pdf

■ Pedrosa, P.B, Cardosa, T.A. 2011. Viral infections in workers in hospital and research laboratory settings: a comparative review of infection modes and respective biosafety aspects. Int J Infect Dis. 2011 Jun;15(6):e366-76.

Recent Survey: Belgium 2007-2012Recent Survey: Belgium 2007 2012BELGIAN BIOSAFETY SERVER

Method: 2 anonymous, secure, online surveys Survey 1: biosafety, occupational health, prevention officers of 206 Institutions: 26 LAI 26 LAI Survey 2: 873 personnel from 26 relevant institutions surveyed. 68 LAI. Official occupational health records for workplace infections: 25.

Results: When insufficient detail was provided to determine whether both surveys referred to the same, or an additional LAI, this was reflected in the reported numbers. reported numbers.