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] [7] and control of invasive Hib disease. [8] [9] [10] 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™, [11] [12] 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). [13] [11] [14] This finding prompted suspension of the national recommendation to vaccinate children with Rotashield, [13] [15] and led the manufacturer to withdraw the vaccine from the market. [13] [16] For this work Murphy received the United States Department of Health and Human Services Secretary's Award for Distinguished Service in 2000, [17] and the publication describing this work [11] was recognized in 2002 by the Charles C. Shepard Science Award from the Centers for Disease Control and Prevention. [17]
Murphy was born in Oak Ridge, Tennessee, where her father, George Noller, [18] 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. [17] 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 at Southwestern Medical School. [17]
Murphy is the author or co-author of around 100 publications in peer-reviewed academic journals [19] as well as numerous contributions in “Morbidity and Mortality Weekly Report”, [19] 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.
By the 1960s, Hib was recognized as an important cause of invasive bacterial disease in infants and children. [20] 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. [21] [22] Whether or not to give antimicrobial prophylaxis to day contacts of a case of Hib disease to prevent secondary cases was controversial. [23] [24] The reasons were that little was known about the extent of asymptomatic Hib colonization 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] [25] 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.
In the 1980s, Murphy, collaborating with Dr Dan M Granoff at Washington University School of Medicine in St. Louis, and Dr. Michael Osterholm, at the Minnesota Department of Health, developed prospective active surveillance of Hib disease in Dallas County TX and the State of Minnesota. [26] In one study, Murphy and her colleagues 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. [10] 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. [23]
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 [27] and, subsequently, it was replaced by second-generation Hib vaccines in which the polysaccharide was conjugated to protein carriers. [28] The first Hib conjugate vaccine used diphtheria toxoid as the carrier protein, was called PRP-D [29] and was also recommended for the age group 18 to 72 months. [30] 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. [9] Unexpectedly, they observed a decrease in disease in both 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. [31] [32] 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 Hib conjugate vaccine were much less likely to become Hib carriers than those who were unvaccinated, or who had been vaccinated with unconjugated PRP vaccine. Overall, Hib conjugate vaccination in this study was 81% effective in preventing Hib colonization, whereas unconjugated PRP vaccination conferred no significant protection against colonization. These results were unexpected [33] and 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. [33] 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. [28] [34] [35]
Murphy subsequently expanded the county-wide surveillance system in Dallas County to include other severe infections by encapsulated bacteria and cases hospitalized with Staphylococcal infection. The results underscored the importance of development of new vaccines for prevention of N. meningitidis (meningococcal) [36] and S. pneumoniae (pneumococcal) infections. [2] [37] She also identified rare strains of S. pneumoniae that caused a form of kidney failure called hemolytic uremic syndrome. [38] 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.
Rotavirus was a leading cause of severe gastroenteritis among infants and young children. [39] 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. [40] 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. [11] These results were central to suspension of the national recommendation to use Rotashield™, and led the manufacturer to withdraw the vaccine from the market, [40] [16] which paved the way for the development of safer rotavirus vaccines. [41] [12]
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; [42] whooping cough (Bordetella pertussis); [43] [44] tetanus; [45] hepatitis B; [46] and hepatitis A [47] [48] virus infections.
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. [17] 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) [49] and by Dynavax (Heplisav, hepatitis B.
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). [50] [ citation needed ]
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. [17]
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 [51] (i.e., Murphy et al., New England Journal of Medicine 2001. [11]
The DPT vaccine or DTP vaccine is a class of combination vaccines against three infectious diseases in humans: diphtheria, pertussis, and tetanus (lockjaw). The vaccine components include diphtheria and tetanus toxoids, and either killed whole cells of the bacterium that causes pertussis or pertussis antigens. The term toxoid refers to vaccines which use an inactivated toxin produced by the pathogen which they are targeted against to generate an immune response. In this way, the toxoid vaccine generates an immune response which is targeted against the toxin which is produced by the pathogen and causes disease, rather than a vaccine which is targeted against the pathogen itself. The whole cells or antigens will be depicted as either "DTwP" or "DTaP", where the lower-case "w" indicates whole-cell inactivated pertussis and the lower-case "a" stands for "acellular". In comparison to alternative vaccine types, such as live attenuated vaccines, the DTP vaccine does not contain any live pathogen, but rather uses inactivated toxoid to generate an immune response; therefore, there is not a risk of use in populations that are immune compromised since there is not any known risk of causing the disease itself. As a result, the DTP vaccine is considered a safe vaccine to use in anyone and it generates a much more targeted immune response specific for the pathogen of interest.
Haemophilus influenzae is a Gram-negative, non-motile, coccobacillary, facultatively anaerobic, capnophilic pathogenic bacterium of the family Pasteurellaceae. The bacteria are mesophilic and grow best at temperatures between 35 and 37 °C.
Epiglottitis is the inflammation of the epiglottis—the flap at the base of the tongue that prevents food entering the trachea (windpipe). Symptoms are usually rapid in onset and include trouble swallowing which can result in drooling, changes to the voice, fever, and an increased breathing rate. As the epiglottis is in the upper airway, swelling can interfere with breathing. People may lean forward in an effort to open the airway. As the condition worsens, stridor and bluish skin may occur.
A conjugate vaccine is a type of subunit vaccine which combines a weak antigen with a strong antigen as a carrier so that the immune system has a stronger response to the weak antigen.
The Vaccine Adverse Event Reporting System (VAERS) is a United States program for vaccine safety, co-managed by the U.S. Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA). VAERS is a postmarketing surveillance program, collecting information about adverse events that occur after administration of vaccines to ascertain whether the risk–benefit ratio is high enough to justify continued use of any particular vaccine.
The schedule for childhood immunizations in the United States is published by the Centers for Disease Control and Prevention (CDC). The vaccination schedule is broken down by age: birth to six years of age, seven to eighteen, and adults nineteen and older. Childhood immunizations are key in preventing diseases with epidemic potential.
Meningococcal disease describes infections caused by the bacterium Neisseria meningitidis. It has a high mortality rate if untreated but is vaccine-preventable. While best known as a cause of meningitis, it can also result in sepsis, which is an even more damaging and dangerous condition. Meningitis and meningococcemia are major causes of illness, death, and disability in both developed and under-developed countries.
Neal A. Halsey is an American pediatrician, with sub-specialty training in infectious diseases, international health and epidemiology. Halsey is a professor emeritus of international health and director emeritus of the Institute for Vaccine Safety at the Johns Hopkins Bloomberg School of Public Health, in Baltimore, Maryland. He had a joint appointment in the Department of Pediatrics at the Johns Hopkins School of Medicine and serves as co-director of the Center for Disease Studies and Control in Guatemala.
Hepatitis B vaccine is a vaccine that prevents hepatitis B. The first dose is recommended within 24 hours of birth with either two or three more doses given after that. This includes those with poor immune function such as from HIV/AIDS and those born premature. It is also recommended that health-care workers be vaccinated. In healthy people, routine immunization results in more than 95% of people being protected.
The Haemophilus influenzae type B vaccine, also known as Hib vaccine, is a vaccine used to prevent Haemophilus influenzae type b (Hib) infection. In countries that include it as a routine vaccine, rates of severe Hib infections have decreased more than 90%. It has therefore resulted in a decrease in the rate of meningitis, pneumonia, and epiglottitis.
The rotavirus vaccine is a vaccine used to protect against rotavirus infections, which are the leading cause of severe diarrhea among young children. The vaccines prevent 15–34% of severe diarrhea in the developing world and 37–96% of the risk of death among young children due to severe diarrhea. Immunizing babies decreases rates of disease among older people and those who have not been immunized.
John Bennett Robbins was a senior investigator at the National Institutes of Health (NIH), best known for his contribution to the development of the vaccine against bacterial meningitis Hib)) with his colleague Rachel Schneerson. He conducted research on the Bethesda, Maryland campus of the NIH from 1970 until his retirement at the age of 80 in 2012. During his tenure, he worked in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the Food and Drug Administration’s biologics laboratories on location.
Meningococcal vaccine refers to any vaccine used to prevent infection by Neisseria meningitidis. Different versions are effective against some or all of the following types of meningococcus: A, B, C, W-135, and Y. The vaccines are between 85 and 100% effective for at least two years. They result in a decrease in meningitis and sepsis among populations where they are widely used. They are given either by injection into a muscle or just under the skin.
Haemophilus meningitis is a form of bacterial meningitis caused by the Haemophilus influenzae bacteria. It is usually associated with Haemophilus influenzae type b. Meningitis involves the inflammation of the protective membranes that cover the brain and spinal cord. Haemophilus meningitis is characterized by symptoms including fever, nausea, sensitivity to light, headaches, stiff neck, anorexia, and seizures. Haemophilus meningitis can be deadly, but antibiotics are effective in treating the infection, especially when cases are caught early enough that the inflammation has not done a great deal of damage. Before the introduction of the Hib vaccine in 1985, Haemophilus meningitis was the leading cause of bacterial meningitis in children under the age of five. However, since the creation of the Hib vaccine, only two in every 100,000 children contract this type of meningitis. Five to ten percent of cases can be fatal, although the average mortality rate in developing nations is seventeen percent, mostly due to lack of access to vaccination as well as lack of access to medical care needed to combat the meningitis.
Tetanus vaccine, also known as tetanus toxoid (TT), is a toxoid vaccine used to prevent tetanus. During childhood, five doses are recommended, with a sixth given during adolescence.
DPT-Hib vaccine is a combination vaccine whose generic name is diphtheria and tetanus toxoids and whole-cell pertussis vaccine adsorbed with Hib conjugate vaccine, sometimes abbreviated to DPT-Hib. It protects against the infectious diseases diphtheria, tetanus, pertussis, and Haemophilus influenzae type B.
Haemophilus B and hepatitis B vaccine is a combination vaccine whose generic name is Haemophilus b conjugate and hepatitis B recombinant vaccine. It protects against the infectious diseases Haemophilus influenzae type B and hepatitis B.
A hexavalent vaccine, or 6-in-1 vaccine, is a combination vaccine with six individual vaccines conjugated into one, intended to protect people from multiple diseases. The term usually refers to the children's vaccine that protects against diphtheria, tetanus, pertussis, poliomyelitis, haemophilus B, and hepatitis B, which is used in more than 90 countries around the world including in Europe, Canada, Australia, Jordan, and New Zealand.
Janet Gilsdorf is an American pediatric infectious diseases physician, scientist, and writer at the University of Michigan. Her research has focused on the pathogenic, molecular, and epidemiologic features of the bacterium Haemophilus influenzae. She served as the Director of the Division of Pediatric Infectious Diseases in the University of Michigan Health System from 1989 to 2012 and Co-Director of the Center for Molecular and Clinical Epidemiology of Infectious Diseases at the School of Public Health at the University of Michigan from 2000 – 2015. In addition to her scientific publications, she is also the author of two novels, one memoir, one non-fiction book, and a number of medically-oriented essays.
Dan M. Granoff is an infectious disease physician-scientist who was named the 2014 Maurice Hilleman/Merck Laureate by the American Society for Microbiology for outstanding contributions to vaccine discovery and development. Beginning in 2011, Granoff held the Clorox Foundation Endowed Chair and was director of the Center of Immunobiology and Vaccine Development at Children's Hospital Oakland Research Institute. His work increased understanding of basic mechanisms of human immunity to encapsulated bacteria, and furthered development of vaccines against Haemophilus influenzae type B (Hib) and Neisseria meningitidis.