Trudy Virginia Noller Murphy is an American pediatric infectious diseases physician, public health epidemiologist and vaccinologist. During the 1980s and 1990s, she conducted research at Southwestern Medical School in Dallas, Texas on three bacterial pathogens: Haemophilus influenzae type b (Hib),[1] Streptococcus pneumoniae (pneumococcus),[2] and methicillin-resistant Staphylococcus aureus (MRSA).[3] Murphy's studies advanced understanding of how these organisms spread within communities, particularly among children attending day care centers.[4][5][3][6] Her seminal work on Hib vaccines elucidated the effects of introduction of new Hib vaccines on both bacterial carriage[6] and control of invasive Hib disease.[7][8][9] Murphy subsequently joined the National Immunization Program at the Centers for Disease Control and Prevention (CDC). where she led multi-disciplinary teams in the Divisions of Epidemiology and Surveillance and The Viral Hepatitis Division. Among her most influential work at CDC was on Rotashield™,[10] which was a newly licensed vaccine designed to prevent severe diarrheal disease caused by rotavirus. Murphy and her colleagues uncovered that the vaccine increased the risk of acute bowel obstruction (intussusception).[10][11] This finding prompted suspension of the national recommendation to vaccinate children with Rotashield,[12] and led the manufacturer to withdraw the vaccine from the market.[13] For this work Murphy received the United States Department of Health and Human Services Secretary's Award for Distinguished Service in 2000,[14] and the publication describing this work[10] was recognized in 2002 by the Charles C. Shepard Science Award from the Centers for Disease Control and Prevention.[14]

Early life and education

Murphy was born in Oak Ridge, Tennessee, where her father, George Noller,[15] was employed by the Manhattan Project. She grew up in Berkeley, California, attended Berkeley High School, and graduated from the University of California Berkeley with a BA in Biological Sciences.[14] She earned her medical degree from the University of California Los Angeles and completed her post-graduate pediatric infectious disease work at the University of Texas Southwestern Medical School in Dallas, Texas, under the mentorship of George H. McCracken Jr. and John D. Nelson. Following her fellowship she became a member of the faculty Southwestern Medical School.

Research

Murphy is the author or co-author of around 100 publications in peer-reviewed academic journals[16] as well as numerous contributions in “Morbidity and Mortality Weekly Report”, published by the U.S. Centers for Disease Control and Prevention (CDC).  As a faculty member at Southwestern Medical School she established prospective, laboratory-based surveillance of severe bacterial diseases in residents of Dallas County, Texas.[1] In 1998, she joined CDC where her work focused on infectious disease epidemiology and vaccine policy. 

Haemophilus influenzae type b (Hib)

By the 1960s, Hib was recognized as an important cause of invasive bacterial disease in infants and children.[17] By the late 1970s, with increasing use of childcare outside the home, cases of Hib disease were being recognized with increasing frequency among infants and children attending child day care facilities.[18][19] Whether or not to give antimicrobial prophylaxis to day contacts of a case of Hib disease to prevent secondary cases was controversial.[20]  The reasons were that little was known about the extent of asymptomatic Hib infection among children attending child day care in the absence of cases of disease, or the risk of a secondary case of disease in contacts after exposure to a Hib case. Murphy and her colleagues obtained monthly pharyngeal cultures for Hib from children and their caretakers in a day care center in which no cases of Hib systemic disease had occurred.[4] Despite absence of exposure to a case, 71% of the toddler group and 48% of the preschool group became colonized by Hib at some time during the 18-month-study. These data showed that Hib could be widespread in a day care center without resulting in systemic disease.

Murphy and her colleagues also prospectively investigated cases of Hib disease among children attending day care in Dallas County, Texas, to determine the rate of subsequent disease among contacts exposed to a case.[9] During 60 days of follow-up after exposure, there was only a single case among 587 untreated classroom contacts, and no cases among 361 untreated contacts under two years of age, the age group considered to be at highest risk of disease.  This low risk indicated that antimicrobial prophylaxis may not be appropriate after the occurrence of a single case of Hib disease in a day-care facility, and that to avoid extensive potentially unnecessary exposure to antimicrobial agents, prophylaxis should be reserved for day care contacts exposed to two or more cases.

In the mid-1980s, a plain (unconjugated) Hib polysaccharide vaccine (called PRP) was licensed by the U.S. Food and Drug Administration (FDA) and recommended for children ages 18 to 72 months. There was controversy about the efficacy of this vaccine[21] and, subsequently, it was replaced by second-generation Hib vaccines in which the polysaccharide was conjugated to protein carriers.  The first Hib conjugate vaccine used diphtheria toxoid as the carrier protein, was called PRP-D[22] and was also recommended for the age group 18 to 72 months.[23] Murphy and her colleagues were one of the first to document the decline of Hib disease after introduction of PRP-D vaccine in the U.S.[8] Unexpectedly, they observed both in the age group being vaccinated and in children less than 18 months of age who at the time were not being vaccinated against Hib. In previous studies, plain polysaccharide vaccines against other encapsulated pathogens (pneumococci and meningococci) protected against invasive disease but did decrease disease in the unvaccinated population or prevent asymptomatic infection of the nasopharynx.[24][25] Murphy's observations of a decrease in Hib disease among unvaccinated children <18 months of age after introduction of PRP-D in older children, suggested that vaccination might confer indirect protection on developing disease in unvaccinated children by decreasing transmission of the organism in the population (so-called "herd immunity", now called “community protection”).  

To investigate the effect of Hib vaccination on asymptomatic Hib colonization, Murphy obtained pharyngeal cultures in children attending a day care center and analyzed acquisition of carriage in relation to previous Hib vaccination.[6] Among children exposed to a child with a positive Hib culture, those who had been previously vaccinated with a conjugate vaccine (>90% PRP-D) were much less likely to become Hib carriers than those who were unvaccinated, or who had been vaccinated with unconjugated PRP vaccine. Overall, PRP-D vaccination in this study was 81% effective in preventing Hib colonization, whereas unconjugated PRP vaccination conferred no significant protection against colonization.  These results provided an explanation for the decline in the incidence of Hib disease in unvaccinated children in the general population, namely by decreasing transmission of Hib from vaccinated children to unvaccinated children.  This study and others by Murphy et al. documented how protein-conjugate Hib vaccines resulted in dramatic declines in serious Hib infections in the population.[26]

Neisseria meningitidis, Streptococcus pneumoniae and methicillin resistant Staphylococcus aureus (MRSA)

Murphy subsequently expanded the county-wide surveillance system in Dallas County to include other severe infections by encapsulated bacteria and Staphylococcal infection. The results underscored the importance of development of new vaccines for prevention of N. meningitidis (meningococcal)[27] and S. pneumoniae (pneumococcal) infections.[2][28] She also identified rare strains of S. pneumoniae that caused a form of kidney failure called hemolytic uremic syndrome.[29] Her studies of MRSA in the community and in day care centers[3] were the first to document community spread of MRSA among children in two day care centers.

Research informing national vaccine recommendations

Rotavirus was a leading cause of severe gastroenteritis among infants and young children.[30] In August 1998, the U.S. Food and Drug Administration (FDA) approved the first rotavirus vaccine for use in infants. The vaccine, called Rotashield™ (Wyeth Lederle Vaccines and Pediatrics] was a live attenuated virus. Within months after introduction, cases of an uncommon form of bowel obstruction (intussusception) were reported in infants who had been given the vaccine, which prompted the CDC to initiate a multi-state public health emergency investigation. Led by Murphy, the investigation found that infants given a first dose of the vaccine were at ~22-fold higher risk of intussusception from 3 to 14 days after vaccination compared to unvaccinated infants.[10] These results were central to suspension of the national recommendation to use Rotashield™, and led the manufacturer to withdraw the vaccine from the market,[13] which paved the way for the development of safer rotavirus vaccines.[31]

Research for the Advisory Committee on Immunization Practices (ACIP)

At the CDC (1998-2014), Murphy led multi-disciplinary teams that performed critical research and analysis used for updating and creating new ACIP vaccine policy. She also led ACIP working groups that drafted national recommendations for prevention of infectious diseases, including Hib;[32] whooping cough (Bordetella pertussis);[33][34] tetanus;[35] hepatitis B;[36] and hepatitis A[37][38] virus infections.

Leadership

The Pediatric Infectious Diseases Society (PIDS) promotes the health of children through prevention and control of infectious diseases worldwide. Murphy's leadership in the organization includes election as Council Member at Large (now known as the board of directors) for 2000–2004, and election as a member of the Nominations and Awards Committee from 2007 to 2009.[14] She also was chair of the Training Programs Committee, a member of the Membership Committee, and served as the PIDS Liaison to both the Infectious Diseases Society of America (IDSA) Adult Infectious Disease Training Programs Committee, and the IDSA Public Health Committee.

Murphy served as the CDC representative for the FDA National Vaccine and Related Advisory Committee (NVRBAC) on licensure application of vaccines by Sanofi Pasteur (Pentacel, DTaP-IPV-Hib) (2007) and by Dynavax (Heplisav, hepatitis B [39]

Murphy served as the CDC representative and subject matter expert to the WHO Consultation on Preventing Perinatal Hepatitis B Transmission, (2010) and Optimizing Hepatitis B vaccination Schedules (2014-2015).[40]

Awards and honors

For her work uncovering the risk of Rotashield vaccine causing acute bowel obstruction in infants, Murphy received the United States Department of Health and Human Services Secretary's Award for Distinguished Service in 2000.[14]

Murphy and her team on Rotashield vaccine was also recognized by the Charles Shepard Science Award presented by the CDC for the best manuscript on original research published in a reputable, peer-reviewed journal[41] (i.e., Murphy et al., New England Journal of Medicine 2001.[10]

References

  1. ↑ Murphy, T. V.; Osterholm, M. T.; Pierson, L. M.; White, K. E.; Breedlove, J. A.; Seibert, G. B.; Kuritsky, J. N.; Granoff, D. M. (1987-02-01). "Prospective surveillance of Haemophilus influenzae type b disease in Dallas County, Texas, and in Minnesota". Pediatrics. 79 (2): 173–180. doi:10.1542/peds.79.2.173. ISSN 0031-4005. PMID 3492702. S2CID 25939698.
  2. 1 2 Pastor, P.; Medley, F.; Murphy, T. V. (1998-03-01). "Invasive pneumococcal disease in Dallas County, Texas: results from population-based surveillance in 1995". Clinical Infectious Diseases. 26 (3): 590–595. doi:10.1086/514589. ISSN 1058-4838. PMID 9524828.
  3. 1 2 3 Adcock, P. M.; Pastor, P.; Medley, F.; Patterson, J. E.; Murphy, T. V. (1998-08-01). "Methicillin-resistant Staphylococcus aureus in two child care centers". The Journal of Infectious Diseases. 178 (2): 577–580. doi:10.1086/517478. ISSN 0022-1899. PMID 9697748.
  4. 1 2 Murphy, T. V.; Granoff, D.; Chrane, D. F.; Olsen, K. D.; Barenkamp, S. J.; Dowell, S. F.; McCracken, G. H. (1985-05-01). "Pharyngeal colonization with Haemophilus influenzae type b in children in a day care center without invasive disease". The Journal of Pediatrics. 106 (5): 712–716. doi:10.1016/s0022-3476(85)80341-3. ISSN 0022-3476. PMID 3873532.
  5. ↑ Osterholm, M. T.; Kuritsky, J. N.; Murphy, T. V.; Mead, W. C. (1985-05-10). "Haemophilus influenzae type b in day care centers". JAMA. 253 (18): 2647–2648. doi:10.1001/jama.253.18.2647. ISSN 0098-7484. PMID 3872948.
  6. 1 2 3 Murphy, T. V.; Pastor, P.; Medley, F.; Osterholm, M. T.; Granoff, D. M. (1993-04-01). "Decreased Haemophilus colonization in children vaccinated with Haemophilus influenzae type b conjugate vaccine". The Journal of Pediatrics. 122 (4): 517–523. doi:10.1016/s0022-3476(05)83529-2. ISSN 0022-3476. PMID 8463894.
  7. ↑ Shapiro, E. D.; Murphy, T. V.; Wald, E. R.; Brady, C. A. (1988-09-09). "The protective efficacy of Haemophilus b polysaccharide vaccine". JAMA. 260 (10): 1419–1422. doi:10.1001/jama.1988.03410100109034. ISSN 0098-7484. PMID 3261349.
  8. 1 2 Murphy, T. V.; White, K. E.; Pastor, P.; Gabriel, L.; Medley, F.; Granoff, D. M.; Osterholm, M. T. (1993-01-13). "Declining incidence of Haemophilus influenzae type b disease since introduction of vaccination". JAMA. 269 (2): 246–248. doi:10.1001/jama.1993.03500020080036. ISSN 0098-7484. PMID 8417244.
  9. 1 2 Murphy, Trudy V.; Clements, Joe F.; Breedlove, Jeri A.; Hansen, Eric J.; Seibert, G. Burton (1987-01-01). "Risk of Subsequent Disease among Day-Care Contacts of Patients with Systemic Hemophilus Influenzae Type B Disease". New England Journal of Medicine. 316 (1): 5–10. doi:10.1056/NEJM198701013160102. ISSN 0028-4793. PMID 3491319.
  10. 1 2 3 4 5 Murphy, T. V.; Gargiullo, P. M.; Massoudi, M. S.; Nelson, D. B.; Jumaan, A. O.; Okoro, C. A.; Zanardi, L. R.; Setia, S.; Fair, E.; LeBaron, C. W.; Wharton, M.; Livengood, J. R.; Rotavirus Intussusception Investigation Team (2001-02-22). "Intussusception among infants given an oral rotavirus vaccine". The New England Journal of Medicine. 344 (8): 564–572. doi:10.1056/NEJM200102223440804. ISSN 0028-4793. PMID 11207352.
  11. ↑ Murphy, Trudy V.; Smith, Philip J.; Gargiullo, Paul M.; Schwartz, Benjamin (2003-04-15). "The first rotavirus vaccine and intussusception: epidemiological studies and policy decisions". The Journal of Infectious Diseases. 187 (8): 1309–1313. doi:10.1086/374420. ISSN 0022-1899. PMID 12696011. S2CID 27772541.
  12. ↑ Centers for Disease Control and Prevention (CDC) (2004-09-03). "Suspension of rotavirus vaccine after reports of intussusception--United States, 1999". MMWR. Morbidity and Mortality Weekly Report. 53 (34): 786–789. ISSN 1545-861X. PMID 15343145.
  13. 1 2 Delage, G. (2000-01-01). "Rotavirus vaccine withdrawal in the United states; the role of postmarketing surveillance". The Canadian Journal of Infectious Diseases. 11 (1): 10–12. doi:10.1155/2000/414396. ISSN 1180-2332. PMC 2094741. PMID 18159257.
  14. 1 2 3 4 5 "PIDS Foundation News: Trudy Murphy (Donor) – Pediatric Infectious Diseases Society". pids.org. Retrieved 2023-08-15.
  15. ↑ "George Noller - Nuclear Museum". ahf.nuclearmuseum.org/. Retrieved 2023-08-17.
  16. ↑ "My Bibliography - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-08-15.
  17. ↑ McGowan, J. E.; Klein, J. O.; Bratton, L.; Barnes, M. W.; Finland, M. (1974-08-01). "Meningitis and Bacteremia due to Haemophilus influenzae: Occurrence and Mortality at Boston City Hospital in 12 Selected Years, 1935-1972". Journal of Infectious Diseases. 130 (2): 119–124. doi:10.1093/infdis/130.2.119. ISSN 0022-1899. PMID 4152256.
  18. ↑ Ginsburg, C. M.; McCracken, G. H.; Rae, S.; Parke, J. C. (1977-08-15). "Haemophilus influenzae type b disease. Incidence in a day-care center". JAMA. 238 (7): 604–607. doi:10.1001/jama.1977.03280070044021. ISSN 0098-7484. PMID 301947.
  19. ↑ Goodman, R. A.; Osterholm, M. T.; Granoff, D. M.; Pickering, L. K. (1984-07-01). "Infectious diseases and child day care". Pediatrics. 74 (1): 134–139. doi:10.1542/peds.74.1.134. ISSN 0031-4005. PMID 6330662. S2CID 46163574.
  20. ↑ Gilsdorf, Janet; Granoff, Dan; Murphy, Trudy; Osterholm, Michael (1984-11-01). "Guidelines for dealing with the guidelines: Rifampin prophylaxis for day care contacts of patients with serious Haemophilus influenzae type b infections". The Journal of Pediatrics. 105 (5): 761–763. doi:10.1016/S0022-3476(84)80298-X. PMID 6334148.
  21. ↑ Osterholm, M. T.; Rambeck, J. H.; White, K. E.; Jacobs, J. L.; Pierson, L. M.; Neaton, J. D.; Hedberg, C. W.; MacDonald, K. L.; Granoff, D. M. (1988-09-09). "Lack of efficacy of Haemophilus b polysaccharide vaccine in Minnesota". JAMA. 260 (10): 1423–1428. doi:10.1001/jama.1988.03410100113035. ISSN 0098-7484. PMID 3261350.
  22. ↑ Granoff, Dan M.; Boies, Eyla G.; Munson, Robert S. (1984-07-01). "Immunogenicity of Haemophilus influenzae type b polysaccharide—diphtheria toxoid conjugate vaccine in adults". The Journal of Pediatrics. 105 (1): 22–27. doi:10.1016/S0022-3476(84)80350-9. PMID 6610736.
  23. ↑ Weinberg, Geoffrey A.; Granoff, Dan M. (1988-10-01). "Polysaccharide-protein conjugate vaccines for the prevention of Haemophilus influenzae type b disease". The Journal of Pediatrics. 113 (4): 621–631. doi:10.1016/S0022-3476(88)80369-X. PMID 3050001.
  24. ↑ Hassan-King, M.K.A.; Wall, R.A.; Greenwood, B.M. (1988-01-01). "Meningococcal carriage, meningococcal disease and vaccination". Journal of Infection. 16 (1): 55–59. doi:10.1016/S0163-4453(88)96117-8. PMID 3130424.
  25. ↑ Herva, E.; Luotonen, J.; Timonen, M.; Sibakov, M.; Karma, P.; Mäkelä, P. H. (1980). "The effect of polyvalent pneumococcal polysaccharide vaccine on nasopharyngeal and nasal carriage of Streptococcus pneumoniae". Scandinavian Journal of Infectious Diseases. 12 (2): 97–100. doi:10.3109/inf.1980.12.issue-2.04. ISSN 0036-5548. PMID 6990475.
  26. ↑ Takala, AK (1994). Effect of Vaccination on Oropharyngeal Carriage, in, Development and clinical uses of Haemophilus b conjugate vaccines. New York: M Dekker. pp. 403–418.
  27. ↑ Pastor, P.; Medley, F. B.; Murphy, T. V. (2000-04-01). "Meningococcal disease in Dallas County, Texas: results of a six-year population-based study". The Pediatric Infectious Disease Journal. 19 (4): 324–328. doi:10.1097/00006454-200004000-00012. ISSN 0891-3668. PMID 10783023. S2CID 5752532.
  28. ↑ Pastor, Patricia; Medley, Francinne B.; Murphy, Trudy V. (2000-04-01). "Meningococcal disease in Dallas County, Texas: results of a six-year population-based study". The Pediatric Infectious Disease Journal. 19 (4): 324–328. doi:10.1097/00006454-200004000-00012. ISSN 0891-3668. PMID 10783023. S2CID 5752532.
  29. ↑ Coats, Mamie T.; Murphy, Trudy; Paton, James C.; Gray, Barry; Briles, David E. (2011-06-01). "Exposure of Thomsen-Friedenreich antigen in Streptococcus pneumoniae infection is dependent on pneumococcal neuraminidase A". Microbial Pathogenesis. 50 (6): 343–349. doi:10.1016/j.micpath.2011.02.010. ISSN 1096-1208. PMC 3088309. PMID 21377521.
  30. ↑ Centers for Disease Control and Prevention (CDC) (1998-11-20). "Laboratory-based surveillance for rotavirus--United States, July 1997-June 1998". MMWR. Morbidity and Mortality Weekly Report. 47 (45): 978–980. ISSN 0149-2195. PMID 9843356.
  31. ↑ Glass, Roger I.; Tate, Jacqueline E.; Jiang, Baoming; Parashar, Umesh (2021-09-30). "The Rotavirus Vaccine Story: From Discovery to the Eventual Control of Rotavirus Disease". The Journal of Infectious Diseases. 224 (12 Suppl 2): S331–S342. doi:10.1093/infdis/jiaa598. ISSN 1537-6613. PMC 8482027. PMID 34590142.
  32. ↑ Centers for Disease Control and Prevention (CDC) (2002-03-22). "Progress toward elimination of Haemophilus influenzae type b invasive disease among infants and children--United States, 1998-2000". MMWR. Morbidity and Mortality Weekly Report. 51 (11): 234–237. ISSN 0149-2195. PMID 11925021.
  33. ↑ Broder, Karen R.; Cortese, Margaret M.; Iskander, John K.; Kretsinger, Katrina; Slade, Barbara A.; Brown, Kristin H.; Mijalski, Christina M.; Tiwari, Tejpratap; Weston, Emily J.; Cohn, Amanda C.; Srivastava, Pamela U.; Moran, John S.; Schwartz, Benjamin; Murphy, Trudy V.; Advisory Committee on Immunization Practices (ACIP) (2006-03-24). "Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the Advisory Committee on Immunization Practices (ACIP)". MMWR. Recommendations and Reports. 55 (RR-3): 1–34. ISSN 1545-8601. PMID 16557217.
  34. ↑ Murphy, Trudy V.; Slade, Barbara A.; Broder, Karen R.; Kretsinger, Katrina; Tiwari, Tejpratap; Joyce, Patricia M.; Iskander, John K.; Brown, Kristin; Moran, John S.; Advisory Committee on Immunization Practices (ACIP) Centers for Disease Control and Prevention (CDC) (2008-05-30). "Prevention of pertussis, tetanus, and diphtheria among pregnant and postpartum women and their infants recommendations of the Advisory Committee on Immunization Practices (ACIP)". MMWR. Recommendations and Reports. 57 (RR-4): 1–51. ISSN 1545-8601. PMID 18509304.
  35. ↑ Pascual, F. Brian; McGinley, Emily L.; Zanardi, Lynn R.; Cortese, Margaret M.; Murphy, Trudy V. (2003-06-20). "Tetanus surveillance--United States, 1998--2000". Morbidity and Mortality Weekly Report. Surveillance Summaries. 52 (3): 1–8. ISSN 1546-0738. PMID 12825541.
  36. ↑ Schillie, Sarah; Murphy, Trudy V.; Sawyer, Mark; Ly, Kathleen; Hughes, Elizabeth; Jiles, Ruth; de Perio, Marie A.; Reilly, Meredith; Byrd, Kathy; Ward, John W.; Centers for Disease Control and Prevention (CDC) (2013-12-20). "CDC guidance for evaluating health-care personnel for hepatitis B virus protection and for administering postexposure management". MMWR. Recommendations and Reports. 62 (RR-10): 1–19. ISSN 1545-8601. PMID 24352112.
  37. ↑ Centers for Disease Control and Prevention (CDC); Advisory Committee on Immunization Practices (2009-09-18). "Updated recommendations from the Advisory Committee on Immunization Practices (ACIP) for use of hepatitis A vaccine in close contacts of newly arriving international adoptees". MMWR. Morbidity and Mortality Weekly Report. 58 (36): 1006–1007. ISSN 1545-861X. PMID 19763077.
  38. ↑ Murphy, Trudy V.; Denniston, Maxine M.; Hill, Holly A.; McDonald, Marian; Klevens, Monina R.; Elam-Evans, Laurie D.; Nelson, Noele P.; Iskander, John; Ward, John D. (2016-02-12). "Progress Toward Eliminating Hepatitis A Disease in the United States". MMWR Supplements. 65 (1): 29–41. doi:10.15585/mmwr.su6501a6. ISSN 2380-8942. PMID 26916458.
  39. ↑ http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/VaccinesandRelatedBiologicalProductsAdvisoryCommittee/UCM327696.pdf
  40. ↑ "Hepatitis B vaccines: WHO position paper". Wkly Epidemiol Rec. 92 (27): 369–92. July 17, 2012. PMID 28685564.
  41. ↑ "CDC - 2018 Shepard Science Awards - Advancing Excellence and Integrity of CDC Science - SPA - OADS". www.cdc.gov. 2022-01-03. Retrieved 2023-08-16.
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