Meningococcal disease

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Meningococcal disease
Charlotte Cleverley-Bisman Meningicoccal Disease.jpg
Charlotte Cleverley-Bisman, one of the youngest survivors of the disease. The infected arms and legs had to be amputated later.
Specialty Infectious disease, critical care medicine
Symptoms Flu-like symptoms, stiff neck, altered mental status, seizures, purpura
Complications Gangrene leading to amputation, sepsis, brain damage, blindness, deafness
Prevention Meningococcal vaccine
Treatment Antibiotics
Prognosis 10–20% mortality generally. 10% mortality with treatment.

Meningococcal disease describes infections caused by the bacterium Neisseria meningitidis (also termed meningococcus). [1] It has a high mortality rate if untreated but is vaccine-preventable. [2] 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.

Contents

There are approximately 2,600 cases of bacterial meningitis per year in the United States, and on average 333,000 cases in developing countries. The case fatality rate ranges between 10 and 20 percent. [3] The incidence of endemic meningococcal disease during the last 13 years ranges from 1 to 5 per 100,000 in developed countries, and from 10 to 25 per 100,000 in developing countries. During epidemics the incidence of meningococcal disease approaches 100 per 100,000. Meningococcal vaccines have sharply reduced the incidence of the disease in developed countries.[ citation needed ]

The disease's pathogenesis is not fully understood. Neisseria meningitidis colonises a substantial proportion of the general population harmlessly, but in a very small percentage of individuals it can invade the bloodstream, affecting the entire body, most notably limbs and brain, causing serious illness. Over the past few years[ when? ], experts have made an intensive effort to understand specific aspects of meningococcal biology and host interactions; however, the development of improved treatments and effective vaccines is expected to depend on novel efforts by workers in many different fields. [4]

While meningococcal disease is not as contagious as the common cold (which is spread through casual contact), it can be transmitted through saliva and occasionally through close, prolonged general contact with an infected person.

Types

Meningococcemia

Meningococcemia, like many other gram-negative blood infections, can cause disseminated intravascular coagulation (DIC), which is the inappropriate clotting of blood within the vessels. DIC can cause ischemic tissue damage when upstream thrombi obstruct blood flow and hemorrhage because clotting factors are exhausted. Small bleeds into the skin cause the characteristic petechial rash, which appears with a star-like shape. This is due to the release of toxins into the blood that break down the walls of blood vessels. A rash can develop under the skin due to blood leakage that may leave red or brownish pinprick spots, [5] which can develop into purple bruising. Meningococcal rash can usually be confirmed by a glass test in which the rash does not fade away under pressure. [6]

Meningitis

Meningococcal meningitis is a form of bacterial meningitis. Meningitis is a disease caused by inflammation and irritation of the meninges, the membranes surrounding the brain and spinal cord. In meningococcal meningitis this is caused by the bacteria invading the cerebrospinal fluid and circulating through the central nervous system. Sub-Saharan Africa, the Americas, Western Europe, the UK, and Ireland still face many challenges combating this disease. [7]

Other types

As with any gram-negative bacterium, N. meningitidis can infect a variety of sites.[ citation needed ]

Meningococcal pneumonia can appear during influenza pandemics and in military camps. This is a multilobar, rapidly evolving pneumonia, sometimes associated with septic shock. With prompt treatment, the prognosis is excellent. [8] Pericarditis can appear, either as a septic pericarditis with grave prognosis or as a reactive pericarditis in the wake of meningitis or septicaemia.[ citation needed ]

Signs and symptoms

Meningitis

The patient with meningococcal meningitis typically presents with high fever, nuchal rigidity (stiff neck), Kernig's sign, severe headache, vomiting, purpura, photophobia, and sometimes chills, altered mental status, or seizures. Diarrhea or respiratory symptoms are less common. Petechiae are often also present, but do not always occur; their absence does not negate a diagnosis of meningococcal disease. Anyone with symptoms of meningococcal meningitis should receive intravenous antibiotics prior to the results of lumbar puncture being known, as delay in treatment can greatly worsen the prognosis.[ citation needed ]

Meningococcemia

Symptoms of meningococcemia are, at least initially, similar to those of influenza. Typically, the first symptoms include fever, nausea, myalgia, headache, arthralgia, chills, diarrhea, stiff neck, and malaise. Later symptoms include septic shock, purpura, hypotension, cyanosis, petechiae, seizures, anxiety, and multiple organ dysfunction syndrome. Acute respiratory distress syndrome and altered mental status may also occur. The petechial rash appear with the 'star-like' shape. Meningococcal sepsis has a greater mortality rate than meningococcal meningitis, but the risk of neurologic sequelae is much lower.[ citation needed ]

Pathogenesis

Meningococcal disease causes life-threatening meningitis and sepsis conditions. In the case of meningitis, bacteria attack the lining between the brain and skull called the meninges. Infected fluid from the meninges then passes into the spinal cord, causing symptoms including stiff neck, fever and rashes. The meninges (and sometimes the brain itself) begin to swell, which affects the central nervous system.[ citation needed ]

Even with antibiotics, approximately 1 in 10 people who have meningococcal meningitis will die; however, about as many survivors of the disease lose a limb or their hearing, or experience permanent brain damage. [9] The sepsis type of infection is much more deadly, and results in a severe blood poisoning called meningococcal sepsis that affects the entire body. In this case, bacterial toxins rupture blood vessels and can rapidly shut down vital organs. Within hours, patient's health can change from seemingly good to mortally ill. [10] [ unreliable source? ]

The N. meningitidis bacterium is surrounded by a slimy outer coat that contains disease-causing endotoxin. While many bacteria produce endotoxin, the levels produced by meningococcal bacteria are 100 to 1,000 times greater (and accordingly more lethal) than normal. As the bacteria multiply and move through the bloodstream, it sheds concentrated amounts of toxin. The endotoxin directly affects the heart, reducing its ability to circulate blood, and also causes pressure on blood vessels throughout the body. As some blood vessels start to hemorrhage, major organs like the lungs and kidneys are damaged.[ citation needed ]

Patients with meningococcal disease are treated with a large dose of antibiotic. The systemic antibiotic flowing through the bloodstream rapidly kills the bacteria but, as the bacteria are killed, even more toxin is released. It takes up to several days for the toxin to be neutralized from the body by using continuous liquid treatment and antibiotic therapy. [10]

Prevention

The most effective method of prevention is a vaccine against N. meningitidis. Different countries have different strains of the bacteria and therefore use different vaccines. Twelve serogroups (strains) exist, with six having the potential to cause a major epidemic - A, B, C, X, Y and W135 are responsible for virtually all cases of the disease in humans. Vaccines are currently available against all six strains, including a newer vaccine against serogroup B. The first vaccine to prevent meningococcal serogroup B (meningitis B) disease was approved by the European Commission on 22 January 2013. [11]

Vaccines offer significant protection from three to five years (plain polysaccharide vaccine Menomune, Mencevax and NmVac-4) to more than eight years (conjugate vaccine Menactra). [12] [13]

Vaccinations

Children

Children 2–10 years of age who are at high risk for meningococcal disease such as certain chronic medical conditions and travel to or reside in countries with hyperendemic or epidemic meningococcal disease should receive primary immunization. Although safety and efficacy of the vaccine have not been established in children younger than 2 years of age and under outbreak control, the unconjugated vaccine can be considered. [14] [15] [16] [17]

Adolescents

Primary immunization against meningococcal disease with meningitis A, C, Y and W-135 vaccines is recommended for all young adolescents at 11–12 years of age and all unvaccinated older adolescents at 15 years of age. Although conjugate vaccines are the preferred meningococcal vaccine in adolescents 11 years of age or older, polysaccharide vaccines are an acceptable alternative if the conjugated vaccine is unavailable. [15] [16] [18]

Adults

Primary immunization with meningitis A, C, Y and W-135 vaccines is recommended for college students who plan to live in dormitories, although the risk for meningococcal disease for college students 18–24 years of age is similar to that of the general population of similar age. [9]

Routine primary immunization against meningococcal disease is recommended for most adults living in areas where meningococcal disease is endemic or who are planning to travel to such areas. Although conjugate vaccines are the preferred meningococcal vaccine in adults 55 years of age or younger, polysaccharide vaccines are an acceptable alternative for adults in this age group if the conjugated vaccine is unavailable. Since safety and efficacy of conjugate vaccines in adults older than 55 years of age have not been established to date, polysaccharide vaccines should be used for primary immunization in this group. [15] [16]

Medical staff

Health care people should receive routine immunization against meningococcal disease for laboratory personnel who are routinely exposed to isolates of N. meningitidis. Laboratory personnel and medical staff are at risk of exposure to N. meningitides or to patients with meningococcal disease. Hospital Infection Control Practices Advisory Committee (HICPAC) recommendations regarding immunization of health-care workers that routine vaccination of health-care personnel is recommended, Any individual 11–55 years of age who wishes to reduce their risk of meningococcal disease may receive meningitis A, C, Y and W-135 vaccines and those older than 55 years of age. Under certain circumstances if unvaccinated health-care personnel cannot get vaccinated and who have intensive contact with oropharyngeal secretions of infected patients and who do not use proper precautions should receive anti-infective prophylaxis against meningococcal infection (i.e., 2-day regimen of oral rifampicin or a single dose of IM ceftriaxone or a single dose of oral ciprofloxacin). [15] [19]

USA military recruits

Because the risk of meningococcal disease is increased among USA's military recruits, all military recruits routinely receive primary immunization against the disease. [15]

Travelers

Immunization against meningococcal disease is not a requirement for entry into any country, unlike yellow fever. Only Saudi Arabia requires that travelers to that country for the annual Hajj and Umrah pilgrimage have a certificate of vaccination against meningococcal disease, issued not more than 3 years and not less than 10 days before arrival in Saudi Arabia.[ citation needed ]

Travelers to or residents of areas where N. meningitidis is highly endemic or epidemic are at risk of exposure should receive primary immunization against meningococcal disease. [15] [16]

HIV-infected individuals

HIV-infected individuals are likely to be at increased risk for meningococcal disease; HIV-infected individuals who wish to reduce their risk of meningococcal disease may receive primary immunization against meningococcal disease. [19] Although efficacy of meningitis A, C, Y and W-135 vaccines have not been evaluated in HIV-infected individuals to date, HIV-infected individuals 11–55 years of age may receive primary immunization with the conjugated vaccine. [19] Vaccination against meningitis does not decrease CD4+ T-cell counts or increase viral load in HIV-infected individuals, and there has been no evidence that the vaccines adversely affect survival. [20] [21] [22]

Close contacts

Protective levels of anticapsular antibodies are not achieved until 7–14 days following administration of a meningococcal vaccine, vaccination cannot prevent early onset disease in these contacts and usually is not recommended following sporadic cases of invasive meningococcal disease. Unlike developed countries, in sub-Saharan Africa and other under developed countries, entire families live in a single room of a house. [23] [24]

Meningococcal infection is usually introduced into a household by an asymptomatic person. Carriage then spreads through the household, reaching infants usually after one or more other household members have been infected. Disease is most likely to occur in infants and young children who lack immunity to the strain of organism circulating and who subsequently acquire carriage of an invasive strain. [25]

Close contacts are defined as those persons who could have had intimate contact with the patient's oral secretions such as through kissing or sharing of food or drink. The importance of the carrier state in meningococcal disease is well known. In developed countries the disease transmission usually occurs in day care, schools and large gatherings where usually disease transmission could occur. Because the meningococcal organism is transmitted by respiratory droplets and is susceptible to drying, it has been postulated that close contact is necessary for transmission. Therefore, the disease transmission to other susceptible person cannot be prevented. Meningitis occurs sporadically throughout the year, and since the organism has no known reservoir outside of man, asymptomatic carriers are usually the source of transmission. [26]

Additionally, basic hygiene measures, such as handwashing and not sharing drinking cups, can reduce the incidence of infection by limiting exposure. When a case is confirmed, all close contacts with the infected person can be offered antibiotics to reduce the likelihood of the infection spreading to other people. However, rifampin-resistant strains have been reported and the indiscriminate use of antibiotics contributes to this problem. Chemoprophylaxis is commonly used to those close contacts who are at highest risk of carrying the pathogenic strains. Since vaccine duration is unknown, mass select vaccinations may be the most cost-effective means for controlling the transmission of the meningococcal disease, rather than mass routine vaccination schedules. [27] [ unreliable source? ] [28]

Chronic medical conditions

Persons with component deficiencies in the final common complement pathway (C3, C5-C9) are more susceptible to N. meningitidis infection than complement-satisfactory persons, [29] [30] [31] [32] [33] [34] [35] [ excessive citations ] and it was estimated that the risk of infection is 7000 times higher in such individuals. [30] In addition, complement component-deficient populations frequently experience frequent meningococcal disease [36] since their immune response to natural infection may be less complete than that of complement non-deficient persons. [29] [37]

Inherited properdin deficiency also is related, with an increased risk of contracting meningococcal disease. [29] [37] Persons with functional or anatomic asplenia may not efficiently clear encapsulated Neisseria meningitidis from the bloodstream [29] [37] Persons with other conditions associated with immunosuppression also may be at increased risk of developing meningococcal disease. [38] [39]

Antibiotics

An updated 2013 Cochrane review investigated the effectiveness of different antibiotics for prophylaxis against meningococcal disease and eradication of N. meningitidis particularly in people at risk of being carriers. The systematic review included 24 studies with 6,885 participants. During follow up no cases of meningococcal disease were reported and thus true antibiotic preventative measures could not be directly assessed. However, the data suggested that rifampin, ceftriaxone, ciprofloxacin and penicillin were equally effective for the eradication of N. meningitidis in potential carriers, although rifampin was associated with resistance to the antibiotic following treatment. Eighteen studies provided data on side effects and reported they were minimal but included nausea, abdominal pain, dizziness and pain at injection site. [40]

Disease outbreak control

Meningitis A, C, Y and W-135 vaccines can be used for large-scale vaccination programs when an outbreak of meningococcal disease occurs in Africa and other regions of the world. Whenever sporadic or cluster cases or outbreaks of meningococcal disease occur in the US, chemoprophylaxis is the principal means of preventing secondary cases in household and other close contacts of individuals with invasive disease. Meningitis A, C, Y and W-135 vaccines rarely may be used as an adjunct to chemoprophylaxis,1 but only in situations where there is an ongoing risk of exposure (e.g., when cluster cases or outbreaks occur) and when a serogroup contained in the vaccine is involved. [15]

It is important that clinicians promptly report all cases of suspected or confirmed meningococcal disease to local public health authorities and that the serogroup of the meningococcal strain involved be identified. The effectiveness of mass vaccination programs depends on early and accurate recognition of outbreaks. When a suspected outbreak of meningococcal disease occurs, public health authorities will then determine whether mass vaccinations (with or without mass chemoprophylaxis) is indicated and delineate the target population to be vaccinated based on risk assessment. [15] [16]

Treatment

Charlotte Cleverley-Bisman, who had all four limbs partially amputated aged seven months due to meningococcal disease. Charlotte Cleverley-Bisman.jpg
Charlotte Cleverley-Bisman, who had all four limbs partially amputated aged seven months due to meningococcal disease.

When meningococcal disease is suspected, treatment must be started immediately and should not be delayed while waiting for investigations. Treatment in primary care usually involves prompt intramuscular administration of benzylpenicillin, and then an urgent transfer to hospital (hopefully, an academic level I medical center, or at least a hospital with round the clock neurological care, ideally with neurological intensive and critical care units) for further care. Once in the hospital, the antibiotics of choice are usually IV broad spectrum 3rd generation cephalosporins, e.g., cefotaxime or ceftriaxone. Benzylpenicillin and chloramphenicol are also effective. Supportive measures include IV fluids, oxygen, inotropic support, e.g., dopamine or dobutamine and management of raised intracranial pressure. Steroid therapy may help in some adult patients, but is unlikely to affect long term outcomes.[ citation needed ]

There is some debate on which antibiotic is most effective at treating the illness. A systematic review compared two antibiotics. There was one trial: an open label (not blinded) non-inferiority trial of 510 people comparing two different types of antibiotics; ceftriaxone (in which there were 14 deaths out of 247), and chloramphenicol (12 deaths out of 256). There were no reported side effects. Both antibiotics were considered equally effective. Antibiotic choice should be based on local antibiotic resistance information. [42]

Prognosis

Complications

Complications following meningococcal disease can be divided into early and late groups. Early complications include: raised intracranial pressure, disseminated intravascular coagulation, seizures, circulatory collapse and organ failure. Later complications are: deafness, blindness, lasting neurological deficits, reduced IQ, and gangrene leading to amputations.[ citation needed ]

Epidemiology

Africa

The distribution of meningococcal meningitis in the African meningitis belt Meningococcal Meningitis Range.svg
The distribution of meningococcal meningitis in the African meningitis belt

The importance of meningitis disease is as significant in Africa as HIV, TB and malaria. Cases of meningococcemia leading to severe meningoencephalitis are common among young children and the elderly. Deaths occurring in less than 24 hours are more likely during the disease epidemic seasons in Africa and Sub-Saharan Africa is hit by meningitis disease outbreaks throughout the epidemic season. It may be that climate change [43] contributes significantly the spread of the disease in Benin, Burkina Faso, Cameroon, the Central African Republic, Chad, Côte d'Ivoire, the Democratic Republic of the Congo, Ethiopia, Ghana, Mali, Niger, Nigeria and Togo. This is an area of Africa where the disease is endemic: meningitis is "silently" present, and there are always a few cases. When the number of cases passes five per population of 100,000 in one week, teams are on alert. Epidemic levels are reached when there have been 100 cases per 100,000 populations over several weeks. [44]

Further complicating efforts to halt the spread of meningitis in Africa is the fact that extremely dry, dusty weather conditions which characterize Niger and Burkina Faso from December to June favor the development of epidemics. Overcrowded villages are breeding grounds for bacterial transmission and lead to a high prevalence of respiratory tract infections, which leave the body more susceptible to infection, encouraging the spread of meningitis. IRIN Africa news has been providing the number of deaths for each country since 1995, [45] [46] [47] [48] and a mass vaccination campaign following a community outbreak of meningococcal disease in Florida was done by the CDC. [49]

Florida

As of June 2022, there is an ongoing outbreak of the disease in Florida. [50] The CDC has identified 26 cases of the disease. [51] Seven deaths have been attributed to the disease. [50]

History and etymology

From the Greek meninx (membrane) + kokkos (berry), meningococcal disease was first described by Gaspard Vieusseux during an outbreak in Geneva in 1805. In 1884, Italian pathologists Ettore Marchiafava and Angelo Celli described intracellular micrococci in cerebrospinal fluid, and in 1887, Anton Wiechselbaum identified the meningococcus (designated as Diplococcus intracellularis meningitidis) in cerebrospinal fluid and established the connection between the organism and epidemic meningitis. [52]

See also

Related Research Articles

<i>Neisseria</i> Genus of bacteria

Neisseria is a large genus of bacteria that colonize the mucosal surfaces of many animals. Of the 11 species that colonize humans, only two are pathogens, N. meningitidis and N. gonorrhoeae.

Asplenia refers to the absence of normal spleen function and is associated with some serious infection risks. Hyposplenism is used to describe reduced ('hypo-') splenic functioning, but not as severely affected as with asplenism.

MeNZB was a vaccine against a specific strain of group B meningococcus, used to control an epidemic of meningococcal disease in New Zealand. Most people are able to carry the meningococcus bacteria safely with no ill effects. However, meningococcal disease can cause meningitis and sepsis, resulting in brain damage, failure of various organs, severe skin and soft-tissue damage, and death.

<span class="mw-page-title-main">Conjugate vaccine</span> Type of vaccine

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.

<span class="mw-page-title-main">Pneumococcal polysaccharide vaccine</span> Pneumonia vaccine

Pneumococcal polysaccharide vaccine, sold under the brand name Pneumovax 23, is a pneumococcal vaccine that is used for the prevention of pneumococcal disease caused by the 23 serotypes of Streptococcus pneumoniae contained in the vaccine as capsular polysaccharides. It is given by intramuscular or subcutaneous injection.

<i>Neisseria meningitidis</i> Species of bacterium that can cause meningitis

Neisseria meningitidis, often referred to as the meningococcus, is a Gram-negative bacterium that can cause meningitis and other forms of meningococcal disease such as meningococcemia, a life-threatening sepsis. The bacterium is referred to as a coccus because it is round, and more specifically a diplococcus because of its tendency to form pairs.

The Advisory Committee on Immunization Practices (ACIP) is a committee within the United States Centers for Disease Control and Prevention (CDC) that provides advice and guidance on effective control of vaccine-preventable diseases in the U.S. civilian population. The ACIP develops written recommendations for routine administration of vaccines to the pediatric and adult populations, along with vaccination schedules regarding appropriate timing, dosage, and contraindications of vaccines. ACIP statements are official federal recommendations for the use of vaccines and immune globulins in the U.S., and are published by the CDC.

<span class="mw-page-title-main">Pneumococcal vaccine</span> Vaccine to prevent infection by the bacteria Stretococcus pneumoniae

Pneumococcal vaccines are vaccines against the bacterium Streptococcus pneumoniae. Their use can prevent some cases of pneumonia, meningitis, and sepsis. There are two types of pneumococcal vaccines: conjugate vaccines and polysaccharide vaccines. They are given by injection either into a muscle or just under the skin.

<span class="mw-page-title-main">Hib vaccine</span> Haemophilus influenzae type B vaccine

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.

Pneumococcal infection is an infection caused by the bacterium Streptococcus pneumoniae.

NmVac4-A/C/Y/W-135 is the commercial name of the polysaccharide vaccine against the bacterium that causes meningococcal meningitis. The product, by JN-International Medical Corporation, is designed and formulated to be used in developing countries for protecting populations during meningitis disease epidemics.

<span class="mw-page-title-main">Jeeri R. Reddy</span>

Jeeri Reddy an American biologist who became an entrepreneur, developing new generation preventive and therapeutic vaccines. He has been an active leader in the field of the biopharmaceutical industry, commercializing diagnostics and vaccines through JN-International Medical Corporation. He is the scientific director and president of the corporation that created the world's first serological rapid tests for Tuberculosis to facilitate acid-fast bacilli microscopy for the identification of smear-positive and negative cases. Prevention of mother-to-child transmission of HIV was achieved in South East Asia by the use of rapid tests developed by Reddy in 1999. Reddy through his Corporation donated $173,050 worth of Rapid Diagnostic Tests (RDTs) for malaria in Zambia and actively participated in the prevention of child deaths due to Malaria infections. Reddy was personally invited by the president, George W. Bush, and First Lady Laura Bush to the White House for Malaria Awareness Day sponsored by US President Malaria Initiative (PMI) on Wednesday, April 25, 2007.

<span class="mw-page-title-main">Meningitis</span> Inflammation of the membranes around the brain and spinal cord

Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, intense headache, vomiting and neck stiffness and occasionally photophobia.

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.

<span class="mw-page-title-main">African meningitis belt</span> Region of Africa with high rate of incidence of meningitis

The African meningitis belt is a region in sub-Saharan Africa where the rate of incidence of meningitis is very high. It extends from Senegal to Ethiopia, and the primary cause of meningitis in the belt is Neisseria meningitidis.

MenAfriVac is a vaccine developed for use in sub-Saharan Africa for children and adults between 9 months and 29 years of age against meningococcal bacterium Neisseria meningitidis group A. The vaccine costs less than US$0.50 per dose.

Sir Andrew John Pollard is the Ashall Professor of Infection & Immunity at the University of Oxford and a Fellow of St Cross College, Oxford. He is an Honorary Consultant Paediatrician at John Radcliffe Hospital and the Director of the Oxford Vaccine Group. He is the Chief Investigator on the University of Oxford COVID-19 Vaccine trials and has led research on vaccines for many life-threatening infectious diseases including typhoid fever, Neisseria meningitidis, Haemophilus influenzae type b, streptococcus pneumoniae, pertussis, influenza, rabies, and Ebola.

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), Streptococcus pneumoniae (pneumococcus), and methicillin-resistant Staphylococcus aureus (MRSA). Murphy's studies advanced understanding of how these organisms spread within communities, particularly among children attending day care centers. Her seminal work on Hib vaccines elucidated the effects of introduction of new Hib vaccines on both bacterial carriage and control of invasive Hib disease. 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™, 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). This finding prompted suspension of the national recommendation to vaccinate children with Rotashield, and led the manufacturer to withdraw the vaccine from the market. For this work Murphy received the United States Department of Health and Human Services Secretary's Award for Distinguished Service in 2000, and the publication describing this work was recognized in 2002 by the Charles C. Shepard Science Award from the Centers for Disease Control and Prevention.

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.

Penbraya is a pentavalent conjugate vaccine developed by Pfizer for the prevention of invasive meningococcal disease in people 10 through 25 years of age. Invasive meningococcal disease, caused by the bacterium Neisseria meningitidis, can lead to serious conditions such as meningitis and septicemia. Penbraya is approved for use by the US Food and Drug Administration (FDA). Penbraya is the first pentavalent vaccine that provides coverage against the five most common serogroups causing meningococcal disease.

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