Diphtheria is an acute, bacterial disease caused by toxin-producing strains of Corynebacterium diphtheriae. The name of the disease is derived from the Greek diphthera, meaning ‘leather hide.’ The disease was described in the 5th century BCE by Hippocrates, and epidemics were described in the 6th century AD by Aetius. The bacterium was first observed in diphtheritic membranes by Edwin Klebs in 1883 and cultivated by Friedrich Löffler in 1884. Beginning in the early 1900s, prophylaxis was attempted with combinations of toxin and antitoxin. Diphtheria toxoid was developed in the early 1920s but was not widely used until the early 1930s. It was incorporated with tetanus toxoid and pertussis vaccine and became routinely used in the 1940s.

Quick facts

• Described by Hippocrates in 5th century BCE
• Epidemics described in 6th century
• Bacterium first observed in 1883 and cultivated in 1884
• Diphtheria toxoid developed in 1920s

Haemophilus influenzae is a bacterium that causes often-severe infections, particularly among infants. It was first described by Richard Pfeiffer in 1892. During an outbreak of influenza, he found H. influenzae in patients’ sputum and proposed a causal association between this bacterium and the clinical syndrome known as influenza. The organism was given the name Haemophilus by Charles-Edward Winslow, et al. in 1920. It was not until 1933 that it was established that influenza was caused by a virus and that H. influenzae was a cause of secondary infection.

In the 1930s, Margaret Pittman demonstrated that H. influenzae could be isolated in encapsulated (typeable) and unencapsulated (nontypeable) forms. She observed that virtually all isolates from cerebrospinal fluid (CSF) and blood were of the capsular type b.

Before the introduction of effective vaccines, H. influenzae type b (Hib) was the leading cause of bacterial meningitis and other invasive bacterial disease, primarily among children younger than age 5 years; approximately one in 200 children in this age group developed invasive Hib disease. Approximately two-thirds of all cases occurred among children younger than age 18 months.

A pure polysaccharide vaccine was licensed for use in the United States in 1985 and was used until 1988. The first Hib conjugate vaccine was licensed in 1987.

Quick facts

• Causes severe bacterial infection, particularly among infants
• During late 19th century believed to cause influenza
• Immunology and microbiology clarified in 1930s
• Leading cause of bacterial meningitis during prevaccine era

The first descriptions of hepatitis (epidemic jaundice) are generally attributed to Hippocrates. Outbreaks of jaundice, probably hepatitis A, were reported in the 17th and 18th centuries, particularly in association with military campaigns. Hepatitis A (formerly called “infectious hepatitis”) was first differentiated epidemiologically from hepatitis B, which has a longer incubation period, in the 1940s. Development of serologic tests allowed definitive diagnosis of hepatitis B. In the 1970s, identification of the virus and development of serologic tests helped differentiate hepatitis A from other types of non-B hepatitis.

In the prevaccine era, the primary methods used for preventing hepatitis A were hygienic measures and passive protection with immune globulin (IG). Hepatitis A (HepA) vaccines were first licensed for use in the United States in 1995. These vaccines provide long-term protection against hepatitis A virus (HAV) infection. The similarities between the epidemiology of hepatitis A and poliomyelitis suggest that widespread vaccination of appropriate susceptible populations with HepA vaccines can substantially lower disease incidence, eliminate virus transmission, and ultimately, eliminate HAV infection. Prior to 2004, hepatitis A was the most frequently reported type of hepatitis in the United States. From 1996, when the HepA vaccine was introduced, through 2011, hepatitis A cases decreased by over 95%, but re-emerged in 2016 in the United States due to widespread outbreaks among persons reporting drug use and homelessness. In response, CDC has been assisting multiple state and local health departments with hepatitis A outbreaks.

Quick facts

• Descriptions of epidemic jaundice attributed to Hippocrates
• Differentiated from hepatitis B in 1940s
• Serologic tests developed in 1970s
• Vaccines first licensed in the U.S. in 1995

Viral hepatitis is a term commonly used for several diseases that are clinically similar but etiologically and epidemiologically distinct. Hepatitis A (formerly called “infectious hepatitis”) and hepatitis B (formerly called “serum hepatitis”) have been recognized as separate entities since the early 1940s and can be diagnosed with specific serologic tests. Hepatitis D, or Delta hepatitis, is an infection dependent on the hepatitis B virus (HBV). It may occur as a coinfection with acute HBV infection or as superinfection of an HBV carrier.

Epidemic jaundice was described by Hippocrates in the 5th century BCE. The first recorded cases of serum hepatitis are thought to be those that followed the administration of smallpox vaccine containing human lymph to shipyard workers in Germany in 1883. In the early and middle parts of the 20th century, serum hepatitis was repeatedly observed following the use of contaminated needles and syringes. The role of blood as a vehicle for virus transmission was further emphasized in 1943, when Paul Beeson described jaundice that had occurred in seven recipients of blood transfusions. Australia antigen, later called hepatitis B surface antigen (HBsAg), was first described in 1965, and the Dane particle (complete hepatitis B virion) was identified in 1970. Identification of serologic markers for HBV infection followed and helped to clarify the natural history of the disease. Ultimately, HBsAg, the surface protein of HBV, was manufactured in quantity and now comprises the immunogen in highly effective vaccines for prevention of HBV infection.

A plasma-derived Hepatitis B (HepB) vaccine was first licensed for use in the United States in 1981. The vaccine was safe and effective but was not well accepted, possibly because of unsubstantiated fears of transmission of live HBV and other blood-borne pathogens. Recombinant HepB vaccines replaced plasma-derived HepB vaccines beginning in 1986. Plasma-derived HepB vaccines are no longer used in the United States.

Quick facts

• Epidemic jaundice described by Hippocrates in 5th century BCE
• First recorded cases in 1883 following administration of smallpox vaccine containing human lymph
• Transmission via blood further emphasized in 1943
• HBsAg first described in 1965
• Plasma-derived HepB vaccine licensed in 1981 replaced in 1986 with recombinant HepB vaccines

Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. Although the majority of HPV infections are asymptomatic and resolve spontaneously, persistent infections can develop into anogenital warts, precancers, and cervical, anogenital, or oropharyngeal cancers in women and men. The relationship between cervical cancer and sexual behavior was suspected for more than 100 years and was established by epidemiologic studies in the 1960s. In the early 1980s, cervical cancer cells were shown to contain HPV DNA. Epidemiologic studies demonstrating a consistent association between HPV and cervical cancer were published in the 1990s; more recently, HPV has been identified as a cause of certain other mucosal cancers. A quadrivalent vaccine to prevent infection with four types of HPV was licensed for use in the United States in 2006, a bivalent vaccine was licensed in 2009, and a 9-valent vaccine was licensed in 2014.

Quick facts

• Small DNA virus
• More than 200 types have been identified
• Most HPV types infect the cutaneous epithelium and can cause common skin warts
• 40 types infect the mucosal epithelium

Influenza is an infectious viral illness. The name “influenza” originated in 15th century Italy, from an epidemic attributed to “influence of the stars.” The first documented pandemic, or worldwide epidemic, that clearly fits the description of influenza was in 1580. At least four pandemics of influenza occurred in the 19th century, three in the 20th century, and one thus far in the 21 century. The pandemic of “Spanish” influenza in 1918–1919 caused an estimated 21 million deaths worldwide.

Wilson Smith, Christopher Andrewes, and Patrick Laidlaw isolated influenza A virus in ferrets in 1933, and Thomas Francis Jr. isolated influenza B virus in 1936. Also in 1936, Macfarlane Burnet discovered that influenza virus could be grown in embryonated hens’ eggs. This led to the study of the virus’s characteristics and the development and use of inactivated vaccines in the late 1930s and 1940s. The protective efficacy of these inactivated vaccines was demonstrated in the 1950s. The first live, attenuated influenza vaccine was licensed in 2003. A non-live, recombinant influenza virus vaccine not requiring isolation or growth in hen’s eggs was licensed in 2013.

Quick facts

• Viral illness
• First pandemic in 1580
• Estimated 21 million deaths worldwide in pandemic of 1918-1919
• Influenza A and B viruses isolated in the 1930s
• Inactivated vaccines first developed and used in the late 1930s and 1940s

Measles is an acute, viral, infectious disease. References to measles can be found from as early as the 7th century. The disease was described by the Persian physician Rhazes in the 10th century as “more to be dreaded than smallpox.”

In 1846, Peter Panum described the incubation period of measles and lifelong immunity after recovery from the disease. John Enders and Thomas Chalmers Peebles isolated the virus in human and monkey kidney tissue culture in 1954. The first live, attenuated vaccine (Edmonston B strain) was licensed for use in the United States in 1963. In 1971, a combined measles, mumps, and rubella (MMR) vaccine was licensed for use in the United States. In 2005, a combination measles, mumps, rubella, and varicella (MMRV) vaccine was licensed.

Before a vaccine was available, infection with measles virus was nearly universal during childhood, and more than 90% of persons were immune due to past infection by age 15 years. Measles is still a common and often fatal disease in developing countries. The World Health Organization estimates there were 142,300 deaths from measles globally in 2018. In the United States, there have been recent outbreaks; the largest occurring in 2019 primarily among people who were not vaccinated.

Quick facts

• Acute viral infectious disease
• First described in 7th century
• Vaccines first licensed include measles in 1963, MMR in 1971, and MMRV in 2005
• Infection nearly universal during childhood in prevaccine era
• Still common and often fatal in developing countries

Meningococcal disease is an acute, severe illness caused by the bacterium Neisseria meningitidis. A leading cause of bacterial meningitis and sepsis in the United States, N. meningitidis can also cause pneumonia and focal disease, such as septic arthritis. As of August 2020, five meningococcal vaccines are licensed and available in the United States: three quadrivalent (serogroups A, C, W, and Y) conjugate meningococcal vaccines and two recombinant serogroup B vaccines.

Quick facts

• A leading cause of bacterial meningitis and sepsis in U.S.
• As of August 2020, five meningococcal vaccines licensed in U.S.

Mumps is an acute viral illness. Parotitis and orchitis were described by Hippocrates in the 5th century BCE. In 1934, Claud Johnson and Ernest Goodpasture showed that mumps could be transmitted from infected patients to rhesus monkeys and demonstrated that mumps was caused by a filterable agent present in saliva. This agent was shown to be a virus in 1935. Mumps was one of the most common causes of aseptic meningitis and sensorineural hearing loss in childhood in the United States until the introduction of a vaccine in 1967. In 1971, mumps vaccine was licensed in the United States as a combined measles, mumps, and rubella (MMR) vaccine. In 2005, a combination measles, mumps, rubella, and varicella (MMRV) vaccine was licensed.

During World War I, only influenza and gonorrhea were more common than mumps as causes of hospitalization among soldiers. A successful 2-dose vaccination program in the United States led to a greater than 99% reduction in the number of mumps cases reported annually. However, starting in 2006, there has been an increase in mumps cases and outbreaks, particularly in close-contact settings, with many occurring among fully vaccinated persons.

Quick facts

• Acute viral illness
• Parotitis and orchitis described by Hippocrates in 5th century BCE
• Viral etiology described by Johnson and Goodpasture in 1934
• Before vaccine, one of the most common causes of aseptic meningitis and hearing loss among children and hospitalization among military
• Vaccination led to over 99% reduction in mumps cases

Pertussis, or whooping cough, is an acute infectious disease caused by the bacterium Bordetella pertussis. Outbreaks of pertussis were first described in the 16th century by Guillaume de Baillou. The organism was first isolated by Jules Bordet and Octave Gengou in 1906.

In the 20th century, pertussis was one of the most common childhood diseases and a major cause of childhood mortality in the United States. Before the availability of pertussis vaccine in the 1940s, more than 200,000 cases of pertussis were reported annually. Since widespread use of the vaccine began, incidence has decreased more than 75% compared with the prevaccine era.

Pertussis remains a major health problem among children worldwide. Data from a recent modeling study suggest that more than 24 million new pertussis cases occurred globally among children younger than age 5 years in 2014 and caused an estimated 160,700 deaths.

Quick facts

• Acute infectious disease caused by Bordetella pertussis
• Outbreaks first described in 16th century
• Bordetella pertussis isolated in 1906
• More than 200,000 cases annually in the United States in prevaccine era

Streptococcus pneumoniae causes acute bacterial infections. The bacterium, also called pneumococcus, was first isolated by Louis Pasteur in 1881 from the saliva of a patient with rabies. The association between pneumococcus and lobar pneumonia was first described in 1883, but pneumococcal pneumonia was confused with other types of pneumonia until the development of the Gram stain in 1884. Between 1915 and 1945, the chemical structure and antigenicity of the pneumococcal capsular polysaccharide, its association with virulence, and the role of bacterial polysaccharides in human disease were described. More than 80 serotypes of pneumococci had been described by 1940.

Efforts to develop effective pneumococcal vaccines began as early as 1911. However, with the advent of penicillin in the 1940s, interest in pneumococcal vaccination declined until it was observed that many patients still died despite antibiotic treatment. By the late 1960s, efforts were again being made to develop a polyvalent pneumococcal vaccine. The first pneumococcal vaccine was licensed for use in the United States in 1977. The first conjugate pneumococcal vaccine was licensed in the United States in 2000.

Quick facts

• S. pneumoniae first isolated by Pasteur in 1881
• Confused with other types of pneumonia until discovery of Gram stain in 1884
• More than 80 serotypes described by 1940
• First pneumococcal vaccine licensed in U.S. in 1977; first conjugate pneumococcal vaccine in 2000

Descriptions of polio-like illnesses have been around since antiquity, including a funerary stele depicting a man with a withered leg leaning on a staff. Michael Underwood first described a debility of the lower extremities in children that was recognizable as poliomyelitis in England in 1789, but the disease was not observed in epidemics until the late 19th century. During the first half of the 20th century, developed countries in the Northern Hemisphere suffered epidemics each summer and fall that became increasingly severe. Polio infections peaked in the United States in 1952, with more than 21,000 paralytic cases. Following introduction of effective vaccines in 1955 (inactivated polio vaccine, IPV) and 1961 (oral poliovirus vaccine, OPV), polio incidence declined rapidly. The last case of wild poliovirus acquired in the United States was in 1979.

Quick facts

• First described by Michael Underwood in 1789
• Developed countries in Northern Hemisphere suffered increasingly severe epidemics in the first half of the 20th century
• More than 21,000 paralytic cases reported in the U.S. in 1952
• Last case of wild poliovirus acquired in the U.S. was 1979

On July 6, 1885, Louis Pasteur and his colleagues injected the first of 14 daily doses of rabbit spinal cord suspensions containing progressively inactivated rabies virus into 9-year-old Joseph Meister, who had been severely bitten by a rabid dog 2 days before. This was the beginning of the modern era of immunization, which had been presaged by Edward Jenner nearly 100 years earlier.

Pasteur's decision to treat the child followed 4 years of intensive research, culminating in the development of a vaccine capable of protecting experimentally challenged rabbits and dogs. His decision was difficult: "The child's death appeared inevitable. I decided not without acute and harrowing anxiety, as may be imagined, to apply to Joseph Meister the method which I had found consistently successful with dogs". The immunization was successful; and the Pasteur rabies immunization procedure was rapidly adopted throughout the world. By 1890, there were rabies treatment centers in Budapest, Madras, Algiers, Bandung, Florence, Sao Paulo, Warsaw, Shanghai, Tunis, Chicago, New York, and many other places throughout the world.

The basic "Pasteur Treatment," based on brain tissue vaccine with the addition of formaldehyde, is still used in many countries of the world where rabies is prevalent. This treatment still involves immunizations given daily for 14-21 days, and it still carries the same risk of neurologic sequelae as in Pasteur's day. In the United States and other developed countries, more potent, safer, but very expensive, cell culture-based rabies vaccines are combined with hyperimmune globulin for postexposure treatment. The efficacy of such regimens has been well proven.

Another era in vaccine development is now beginning--an era based on the practical application of recombinant-deoxyribonucleic acid (DNA) technology and other novel genetic manipulations of rabies and other viruses and microorganisms. These new technologies promise even more potent and safer vaccines, as well as lower costs, improved stability, and easier delivery throughout the world to people at risk.

In celebrating the Pasteur centennial, the preeminent role of vaccines in the control of infectious diseases is recognized; as Rene Dubos stated: "Even granted that the antirabies treatment had saved the lives of a few human beings, this would have been only meager return for so much effort . . . . It is on much broader issues that Pasteur's achievements must be judged. He had demonstrated the possibility of investigating by rigorous techniques the infectious diseases caused by invisible, noncultivable viruses; he had shown that their pathogenic potentialities could be modified by various laboratory artifices; he had established beyond doubt that a solid immunity could be brought about without endangering the life or health of the vaccinated person. Thanks to the rabies epic . . . immunization (has) become recognized as a general law of nature. Its importance for the welfare of man and animals is today commonplace, but only the future will reveal its full significance in the realm of human economy". Reported by Div of Viral Diseases, Center for Infectious Diseases, CDC.

Diarrheal disease has been recognized in humans since antiquity. Until the early 1970s, a bacterial, viral, or parasitic etiology of diarrheal disease in children could be detected in fewer than 30% of cases. In 1973, Ruth Bishop and colleagues observed a virus particle in the intestinal tissue of children with diarrhea by using electron micrography. This virus was subsequently called “rotavirus” because of its similarity in appearance to a wheel (rota is Latin for wheel). By 1980, rotavirus was recognized as the most common cause of severe gastroenteritis in infants and young children in the United States. In the prevaccine era, the majority of children were infected by age 5 years, and rotavirus was responsible for up to 500,000 deaths among children annually worldwide. A vaccine to prevent rotavirus gastroenteritis was first licensed in the United States in 1998 but was withdrawn in 1999 because of its association with intussusception, a type of bowel blockage when the bowel folds into itself like a telescope. Second-generation vaccines were licensed in the United States in 2006 and 2008.

Quick facts

• First identified as cause of diarrhea in 1973
• Most common cause of severe gastroenteritis in infants and children*
• Nearly universal infection by age 5 years*
• Responsible for up to 500,000 diarrheal deaths each year worldwide*

*Prevaccine era

The name rubella is derived from Latin, meaning “little red.” Rubella was initially considered to be a variant of measles or scarlet fever. It was not until 1814 that it was first described as a separate disease in the German medical literature, hence the common name “German measles.” In 1914, Alfred F. Hess postulated a viral etiology based on his work with monkeys. Following a widespread epidemic of rubella infection in 1940, Norman Gregg, an Australian ophthalmologist, reported in 1941 the occurrence of congenital cataracts among infants born following maternal rubella. This was the first published recognition of congenital rubella syndrome (CRS). Rubella virus was first isolated in 1962 by two independent groups, Paul D. Parkman and colleagues and Thomas H. Weller and Franklin A. Neva. The first rubella vaccines were licensed in 1969. In 1971, a combined measles, mumps, and rubella (MMR) vaccine was licensed for use in the United States. In 2005, a combination measles, mumps, rubella, and varicella (MMRV) vaccine was licensed.

Quick facts

• Initially thought to be variant of measles or scarlet fever
• First described as distinct disease in German literature in 1814 (hence “German measles”)
• Congenital rubella syndrome (CRS) first described 1941
• Rubella virus isolated in 1962

Tetanus is an acute, often fatal, disease caused by an exotoxin produced by the bacterium Clostridium tetani. It is characterized by generalized rigidity and convulsive spasms of skeletal muscles. The muscle stiffness usually begins in the jaw (lockjaw) and neck and then becomes generalized.

Although records from antiquity (5th century BCE) contain clinical descriptions of tetanus, it was in 1884 when tetanus was first produced in animals by injecting them with pus from a fatal human tetanus case. During the same year, tetanus was produced in animals by injecting them with samples of soil. In 1889, Kitasato Shibasaburo isolated the organism from a human, showed that it produced disease when injected into animals, and reported that the toxin could be neutralized by specific antibodies. In 1897, Edmond Nocard demonstrated the protective effect of passively transferred antitoxin, and passive immunization in humans was used for treatment and prophylaxis during World War I. A method for inactivating tetanus toxin with formaldehyde was developed in the early 1920s. This led to the development of tetanus toxoid in 1924. It was first widely used during World War II.

Quick facts

• Caused by exotoxin produced by bacterium Clostridium tetani
• Characterized by generalized rigidity and convulsive spasms
• First produced in animals in 1884
• Organism isolated in 1889
• Tetanus toxoid developed in 1924 and widely used during World War II

Varicella is an acute infectious disease caused by varicella-zoster virus (VZV). Primary varicella infection (chickenpox) was not reliably distinguished from smallpox until the end of the 19th century. In 1875, Rudolf Steiner demonstrated that chickenpox was caused by an infectious agent by inoculating volunteers with the vesicular fluid from a patient with acute varicella. In 1954, Thomas Weller used cell culture to isolate VZV from vesicular fluid of patients with varicella or zoster. A live, attenuated varicella vaccine was developed in Japan in the 1970s. The vaccine virus was developed from virus isolated by Michiaki Takahashi from vesicular fluid from an otherwise healthy child with varicella disease. Varicella vaccine was licensed for general use in Japan and Korea in 1988, and in the United States in 1995 for persons age 12 months or older. In 2005, a combination measles, mumps, rubella, and varicella (MMRV) vaccine was licensed in the United States for persons age 12 months through 12 years.

Quick facts

• Acute infectious disease caused by varicella-zoster virus (VZV)
• Distinguished from smallpox at the end of the 19th century
• Live, attenuated varicella vaccine developed in 1970s
• Varicella and MMRV vaccines licensed for use in the U.S. in 1995 and 2005, respectively

Herpes zoster, also known as zoster, or shingles, is caused by the reactivation of varicella-zoster virus (VZV). The term “herpes zoster” was first used by encyclopedist Celsus in c. 25 BCE to c. 50 AD. Clinical observations of the relationship between varicella and herpes zoster were made in 1888 by James von Bokay, when children who never had varicella (chickenpox) developed varicella after contact with a person with herpes zoster (shingles). In 1954, Thomas Weller used cell culture to isolate VZV from vesicular fluid of patients with varicella or zoster. However, it was not until 1965 that Edgar Hope-Simpson hypothesized that herpes zoster was due to the reactivation of latent VZV. The first vaccine to reduce the risk of herpes zoster was licensed in the United States in 2006.

Quick facts

• Caused by reactivation of varicella-zoster virus (VZV)
• Observed relationship between varicella and herpes zoster in 1888
• Hypothesis formed in 1965 that herpes zoster was due to reactivation of latent VZV
• First vaccine to reduce risk of herpes zoster licensed in the U.S. in 2006