Haemophilus influenzae
Encyclopedia
Haemophilus influenzae, formerly called Pfeiffer's bacillus or Bacillus influenzae, Gram-negative
, rod-shaped
bacterium first described in 1892 by Richard Pfeiffer
during an influenza
pandemic
. A member of the Pasteurellaceae
family, it is generally aerobic
, but can grow as a facultative anaerobe. H. influenzae was mistakenly considered to be the cause of influenza
until 1933, when the viral etiology
of the flu became apparent. Still, H. influenzae is responsible for a wide range of clinical diseases.
H. influenzae was the first free-living organism to have its entire genome sequenced. The sequencing project was completed and published in 1995.
of H. influenzae infections is not completely understood, although the presence of the capsule in encapsulated type b (Hib), a serotype causing conditions such as epiglottitis
, is known to be a major factor in virulence. Their capsule allows them to resist phagocytosis and complement-mediated lysis
in the nonimmune host. The unencapsulated strains are almost always less invasive; they can, however, produce an inflammatory response in humans, which can lead to many symptoms. Vaccination with Hib conjugate vaccine
is effective in preventing Hib infection. Several vaccines are now available for routine use against Hib, but vaccines are not yet available against NTHi.
Naturally-acquired disease caused by H. influenzae seems to occur in humans only. In infants and young children, H. influenzae type b (Hib) causes bacteremia
, pneumonia
, and acute bacterial meningitis
. On occasion, it causes cellulitis
, osteomyelitis
, epiglottitis
, and infectious arthritis. Due to routine use of the Hib conjugate vaccine in the U.S. since 1990, the incidence of invasive Hib disease has decreased to 1.3/100,000 in children. However, Hib remains a major cause of lower respiratory tract infections in infants and children in developing countries where the vaccine is not widely used. Unencapsulated H. influenzae causes ear infections (otitis media
), eye infections (conjunctivitis
), and sinusitis
in children, and is associated with pneumonia
.
, with added X
(hemin) & V
(NAD) factors at 37°C in a CO2-enriched incubator. Blood agar growth is only achieved as a satellite phenomenon around other bacteria. Colonies of H. influenzae appear as convex, smooth, pale, grey or transparent colonies. Gram-stained and microscopic observation of a specimen of H. influenzae will show Gram-negative, coccobacilli, with no specific arrangement. The cultured organism can be further characterized using catalase
and oxidase
tests, both of which should be positive. Further serological testing is necessary to distinguish the capsular polysaccharide and differentiate between H. influenzae b and nonencapsulated species.
Although highly specific, bacterial culture of H. influenzae lacks in sensitivity. Use of antibiotics prior to sample collection greatly reduces the isolation rate by killing the bacteria before identification is possible. Beyond this, H. influenzae is a finicky bacterium to culture, and any modification of culture procedures can greatly reduce isolation rates. Poor quality of laboratories in developing countries has resulted in poor isolation rates of H. influenzae.
H. influenzae will grow in the hemolytic zone of Staphylococcus aureus on blood agar plates; the hemolysis of cells by S. aureus releases nutrients vital to its growth. H. influenzae will not grow outside the hemolytic zone of S. aureus due to the lack of nutrients in these areas. Fildes agar is best for isolation. In Levinthal medium capsulated strains show distinctive iridescence.
(PCR) assays have been proven to be more sensitive than either LAT or culture tests, and highly specific. However, PCR assays have not yet become routine in clinical settings. Countercurrent immunoelectrophoresis has been shown to be an effective research diagnostic method, but has been largely supplanted by PCR.
can be found in the upper respiratory system of humans. In an in vitro study of competition, S. pneumoniae always overpowered H. influenzae by attacking it with hydrogen peroxide
and stripping off the surface molecules H. influenzae needs for survival.
When both bacteria are placed together into a nasal cavity, within 2 weeks, only H. influenzae survives. When either is placed separately into a nasal cavity, each one survives. Upon examining the upper respiratory tissue from mice exposed to both bacteria species, an extraordinarily large number of neutrophils (immune cells) was found. In mice exposed to only one bacterium, the cells were not present.
Lab tests showed neutrophils exposed to dead H. influenzae were more aggressive in attacking S. pneumoniae than unexposed neutrophils. Exposure to dead H. influenzae had no effect on live H. influenzae.
Two scenarios may be responsible for this response:
It is unclear why H. influenzae is not affected by the immune response.
In severe cases, cefotaxime
and ceftriaxone
delivered directly into the bloodstream are the elected antibiotics, and, for the less severe cases, an association of ampicillin
and sulbactam
, cephalosporins of the second and third generation, or fluoroquinolones are preferred. (Fluoroquinolone-resistant Haemophilus influenzae has been observed.)
Macrolide antibiotics (e.g., clarithromycin
) may be used in patients with a history of allergy to beta-lactam antibiotics. Macrolide resistance has also been observed.
recommends a pentavalent vaccine, combining vaccines against diphtheria
, tetanus
, pertussis
, hepatitis B and Hib. There is not yet sufficient evidence on how effective this pentavalent vaccine is in relation to the individual vaccines. Hib vaccines cost about seven times the total cost of vaccines against measles, polio, tuberculosis, diphtheria, tetanus, and pertussis. Consequently, whereas 92% of the populations of developed countries was vaccinated against Hib as of 2003, vaccination coverage was 42% for developing countries, and only 8% for least-developed countries.
genes, and 18 other RNA genes. The sequencing method used was whole-genome shotgun, which was completed and published in Science
in 1995 and conducted at The Institute for Genomic Research
.
Gram-negative
Gram-negative bacteria are bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color...
, rod-shaped
Bacillus (shape)
The word bacillus may be used to describe any rod-shaped bacterium, and such bacilli are found in many different taxonomic groups of bacteria. However, the name Bacillus, capitalized and italicized, refers to a specific genus of bacteria...
bacterium first described in 1892 by Richard Pfeiffer
Richard Friedrich Johannes Pfeiffer
Richard Friedrich Johannes Pfeiffer was a German physician and bacteriologist.Pfeiffer was born in Zduny, Province of Posen, and died in Bad Landeck....
during an influenza
Influenza
Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
pandemic
Pandemic
A pandemic is an epidemic of infectious disease that is spreading through human populations across a large region; for instance multiple continents, or even worldwide. A widespread endemic disease that is stable in terms of how many people are getting sick from it is not a pandemic...
. A member of the Pasteurellaceae
Pasteurellaceae
Pasteurellaceae comprise a large and diverse family of Gram-negative Proteobacteria with members ranging from important pathogens such as Haemophilus influenzae to commensals of the animal and human mucosa. Most members live as commensals on mucosal surfaces of birds and mammals, especially in the...
family, it is generally aerobic
Aerobic organism
An aerobic organism or aerobe is an organism that can survive and grow in an oxygenated environment.Faculitative anaerobes grow and survive in an oxygenated environment and so do aerotolerant anaerobes.-Glucose:...
, but can grow as a facultative anaerobe. H. influenzae was mistakenly considered to be the cause of influenza
Influenza
Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
until 1933, when the viral etiology
Etiology
Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....
of the flu became apparent. Still, H. influenzae is responsible for a wide range of clinical diseases.
H. influenzae was the first free-living organism to have its entire genome sequenced. The sequencing project was completed and published in 1995.
Serotypes
In 1930, two major categories of H. influenzae were defined: the unencapsulated strains and the encapsulated strains. Encapsulated strains were classified on the basis of their distinct capsular antigens. There are six generally recognized types of encapsulated H. influenzae: a, b, c, d, e, and f. Genetic diversity among unencapsulated strains is greater than within the encapsulated group. Unencapsulated strains are termed nontypable (NTHi) because they lack capsular serotypes; however, they can be classified by multilocus sequence typing. The pathogenesisPathogenesis
The pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent...
of H. influenzae infections is not completely understood, although the presence of the capsule in encapsulated type b (Hib), a serotype causing conditions such as epiglottitis
Epiglottitis
Epiglottitis is an inflammation of the epiglottis - the flap that sits at the base of the tongue, which keeps food from going into the trachea . Due to its place in the airway, swelling of this structure can interfere with breathing and constitutes a medical emergency...
, is known to be a major factor in virulence. Their capsule allows them to resist phagocytosis and complement-mediated lysis
Lysis
Lysis refers to the breaking down of a cell, often by viral, enzymic, or osmotic mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a "lysate"....
in the nonimmune host. The unencapsulated strains are almost always less invasive; they can, however, produce an inflammatory response in humans, which can lead to many symptoms. Vaccination with Hib conjugate vaccine
Hib vaccine
Haemophilus influenzae type B vaccine is a conjugate vaccine developed for the prevention of invasive disease caused by Haemophilus influenzae type b bacteria. The Centers for Disease Control and Prevention has recommended the use of the Hib vaccine. Due to routine use of the Hib vaccine in...
is effective in preventing Hib infection. Several vaccines are now available for routine use against Hib, but vaccines are not yet available against NTHi.
Diseases
Most strains of H. influenzae are opportunistic pathogens; that is, they usually live in their host without causing disease, but cause problems only when other factors (such as a viral infection or reduced immune function) create an opportunity.Naturally-acquired disease caused by H. influenzae seems to occur in humans only. In infants and young children, H. influenzae type b (Hib) causes bacteremia
Bacteremia
Bacteremia is the presence of bacteria in the blood. The blood is normally a sterile environment, so the detection of bacteria in the blood is always abnormal....
, pneumonia
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
, and acute bacterial meningitis
Meningitis
Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...
. On occasion, it causes cellulitis
Cellulitis
Cellulitis is a diffuse inflammation of connective tissue with severe inflammation of dermal and subcutaneous layers of the skin. Cellulitis can be caused by normal skin flora or by exogenous bacteria, and often occurs where the skin has previously been broken: cracks in the skin, cuts, blisters,...
, osteomyelitis
Osteomyelitis
Osteomyelitis simply means an infection of the bone or bone marrow...
, epiglottitis
Epiglottitis
Epiglottitis is an inflammation of the epiglottis - the flap that sits at the base of the tongue, which keeps food from going into the trachea . Due to its place in the airway, swelling of this structure can interfere with breathing and constitutes a medical emergency...
, and infectious arthritis. Due to routine use of the Hib conjugate vaccine in the U.S. since 1990, the incidence of invasive Hib disease has decreased to 1.3/100,000 in children. However, Hib remains a major cause of lower respiratory tract infections in infants and children in developing countries where the vaccine is not widely used. Unencapsulated H. influenzae causes ear infections (otitis media
Otitis media
Otitis media is inflammation of the middle ear, or a middle ear infection.It occurs in the area between the tympanic membrane and the inner ear, including a duct known as the eustachian tube. It is one of the two categories of ear inflammation that can underlie what is commonly called an earache,...
), eye infections (conjunctivitis
Conjunctivitis
Conjunctivitis refers to inflammation of the conjunctiva...
), and sinusitis
Sinusitis
Sinusitis is inflammation of the paranasal sinuses, which may be due to infection, allergy, or autoimmune issues. Most cases are due to a viral infection and resolve over the course of 10 days...
in children, and is associated with pneumonia
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
.
Diagnosis
Clinical diagnosis of H. influenzae is typically performed by bacterial culture or latex particle agglutinations. Diagnosis is considered confirmed when the organism is isolated from a sterile body site. In this respect, H. influenzae cultured from the nasopharyngeal cavity or sputum would not indicate H. influenzae disease, because these sites are colonized in disease-free individuals. However, H. influenzae isolated from cerebrospinal fluid or blood would indicate H. influenzae infection.Culture
Bacterial culture of H. influenzae is performed on agar plates, the preferable one being chocolate agarChocolate agar
Chocolate agar - is a non-selective, enriched growth medium. It is a variant of the blood agar plate. It contains red blood cells, which have been lysed by heating very slowly to 56 °C. Chocolate agar is used for growing fastidious respiratory bacteria, such as Haemophilus influenzae...
, with added X
Hemin
Hemin is an iron-containing porphyrin. More specifically, it is Protoporphyrin IX containing a ferric iron ion with a chloride ligand....
(hemin) & V
Nicotinamide adenine dinucleotide
Nicotinamide adenine dinucleotide, abbreviated NAD, is a coenzyme found in all living cells. The compound is a dinucleotide, since it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine base and the other nicotinamide.In metabolism, NAD is involved...
(NAD) factors at 37°C in a CO2-enriched incubator. Blood agar growth is only achieved as a satellite phenomenon around other bacteria. Colonies of H. influenzae appear as convex, smooth, pale, grey or transparent colonies. Gram-stained and microscopic observation of a specimen of H. influenzae will show Gram-negative, coccobacilli, with no specific arrangement. The cultured organism can be further characterized using catalase
Catalase
Catalase is a common enzyme found in nearly all living organisms that are exposed to oxygen, where it catalyzes the decomposition of hydrogen peroxide to water and oxygen...
and oxidase
Oxidase
An oxidase is any enzyme that catalyzes an oxidation-reduction reaction involving molecular oxygen as the electron acceptor. In these reactions, oxygen is reduced to water or hydrogen peroxide ....
tests, both of which should be positive. Further serological testing is necessary to distinguish the capsular polysaccharide and differentiate between H. influenzae b and nonencapsulated species.
Although highly specific, bacterial culture of H. influenzae lacks in sensitivity. Use of antibiotics prior to sample collection greatly reduces the isolation rate by killing the bacteria before identification is possible. Beyond this, H. influenzae is a finicky bacterium to culture, and any modification of culture procedures can greatly reduce isolation rates. Poor quality of laboratories in developing countries has resulted in poor isolation rates of H. influenzae.
H. influenzae will grow in the hemolytic zone of Staphylococcus aureus on blood agar plates; the hemolysis of cells by S. aureus releases nutrients vital to its growth. H. influenzae will not grow outside the hemolytic zone of S. aureus due to the lack of nutrients in these areas. Fildes agar is best for isolation. In Levinthal medium capsulated strains show distinctive iridescence.
Latex particle agglutination
The latex particle agglutination test (LAT) is a more sensitive method to detect H. influenzae than culture. Because the method relies on antigen rather than viable bacteria, the results are not disrupted by prior antibiotic use. It also has the added benefit of being much quicker than culture methods. However, antibiotic sensitivity is not possible with LAT, so a parallel culture is necessary.Molecular methods
Polymerase chain reactionPolymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....
(PCR) assays have been proven to be more sensitive than either LAT or culture tests, and highly specific. However, PCR assays have not yet become routine in clinical settings. Countercurrent immunoelectrophoresis has been shown to be an effective research diagnostic method, but has been largely supplanted by PCR.
Interaction with Streptococcus pneumoniae
Both H. influenzae and S. pneumoniaeStreptococcus pneumoniae
Streptococcus pneumoniae, or pneumococcus, is Gram-positive, alpha-hemolytic, aerotolerant anaerobic member of the genus Streptococcus. A significant human pathogenic bacterium, S...
can be found in the upper respiratory system of humans. In an in vitro study of competition, S. pneumoniae always overpowered H. influenzae by attacking it with hydrogen peroxide
Hydrogen peroxide
Hydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...
and stripping off the surface molecules H. influenzae needs for survival.
When both bacteria are placed together into a nasal cavity, within 2 weeks, only H. influenzae survives. When either is placed separately into a nasal cavity, each one survives. Upon examining the upper respiratory tissue from mice exposed to both bacteria species, an extraordinarily large number of neutrophils (immune cells) was found. In mice exposed to only one bacterium, the cells were not present.
Lab tests showed neutrophils exposed to dead H. influenzae were more aggressive in attacking S. pneumoniae than unexposed neutrophils. Exposure to dead H. influenzae had no effect on live H. influenzae.
Two scenarios may be responsible for this response:
- When H. influenzae is attacked by S. pneumoniae, it signals the immune system to attack the S. pneumoniae
- The combination of the two species triggers an immune system response that is not set off by either species individually.
It is unclear why H. influenzae is not affected by the immune response.
Treatment
Haemophilus influenzae produces beta-lactamases, and it is also able to modify its penicillin-binding proteins, so it has gained resistance to the penicillin family of antibiotics.In severe cases, cefotaxime
Cefotaxime
Cefotaxime is a third-generation cephalosporin antibiotic. Like other third-generation cephalosporins, it has broad spectrum activity against Gram positive and Gram negative bacteria...
and ceftriaxone
Ceftriaxone
Ceftriaxone is a third-generation cephalosporin antibiotic. Like other third-generation cephalosporins, it has broad spectrum activity against Gram-positive and Gram-negative bacteria. In most cases, it is considered to be equivalent to cefotaxime in terms of safety and efficacy...
delivered directly into the bloodstream are the elected antibiotics, and, for the less severe cases, an association of ampicillin
Ampicillin
Ampicillin is a beta-lactam antibiotic that has been used extensively to treat bacterial infections since 1961. Until the introduction of ampicillin by the British company Beecham, penicillin therapies had only been effective against Gram-positive organisms such as staphylococci and streptococci...
and sulbactam
Sulbactam
Sulbactam is a molecule that is given in combination with beta-lactam antibiotics to inhibit beta-lactamase, an enzyme produced by bacteria that destroys the antibiotics...
, cephalosporins of the second and third generation, or fluoroquinolones are preferred. (Fluoroquinolone-resistant Haemophilus influenzae has been observed.)
Macrolide antibiotics (e.g., clarithromycin
Clarithromycin
Clarithromycin is a macrolide antibiotic used to treat pharyngitis, tonsillitis, acute maxillary sinusitis, acute bacterial exacerbation of chronic bronchitis, pneumonia , skin and skin structure infections...
) may be used in patients with a history of allergy to beta-lactam antibiotics. Macrolide resistance has also been observed.
Prevention
Effective vaccines for Haemophilus influenzae have been available since the early 1990s, so it is preventable. The World Health OrganizationWorld Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
recommends a pentavalent vaccine, combining vaccines against diphtheria
Diphtheria
Diphtheria is an upper respiratory tract illness caused by Corynebacterium diphtheriae, a facultative anaerobic, Gram-positive bacterium. It is characterized by sore throat, low fever, and an adherent membrane on the tonsils, pharynx, and/or nasal cavity...
, tetanus
Tetanus
Tetanus is a medical condition characterized by a prolonged contraction of skeletal muscle fibers. The primary symptoms are caused by tetanospasmin, a neurotoxin produced by the Gram-positive, rod-shaped, obligate anaerobic bacterium Clostridium tetani...
, pertussis
Pertussis
Pertussis, also known as whooping cough , is a highly contagious bacterial disease caused by Bordetella pertussis. Symptoms are initially mild, and then develop into severe coughing fits, which produce the namesake high-pitched "whoop" sound in infected babies and children when they inhale air...
, hepatitis B and Hib. There is not yet sufficient evidence on how effective this pentavalent vaccine is in relation to the individual vaccines. Hib vaccines cost about seven times the total cost of vaccines against measles, polio, tuberculosis, diphtheria, tetanus, and pertussis. Consequently, whereas 92% of the populations of developed countries was vaccinated against Hib as of 2003, vaccination coverage was 42% for developing countries, and only 8% for least-developed countries.
Sequencing
H. influenzae was the first free-living organism to have its entire genome sequenced. Completed by Craig Venter and his team, Haemophilus was chosen because one of the project leaders, Nobel laureate Hamilton Smith, had been working on it for decades and was able to provide high-quality DNA libraries. The genome consists of 1,830,140 base pairs of DNA in a single circular chromosome that contains 1740 protein-coding genes, 58 transfer RNATransfer RNA
Transfer RNA is an adaptor molecule composed of RNA, typically 73 to 93 nucleotides in length, that is used in biology to bridge the three-letter genetic code in messenger RNA with the twenty-letter code of amino acids in proteins. The role of tRNA as an adaptor is best understood by...
genes, and 18 other RNA genes. The sequencing method used was whole-genome shotgun, which was completed and published in Science
Science (journal)
Science is the academic journal of the American Association for the Advancement of Science and is one of the world's top scientific journals....
in 1995 and conducted at The Institute for Genomic Research
The Institute for Genomic Research
The Institute for Genomic Research was a non-profit genomics research institute founded in 1992 by Craig Venter in Rockville, Maryland, United States. It is now a part of the J. Craig Venter Institute.-History:...
.
See also
- PasteurellaceaePasteurellaceaePasteurellaceae comprise a large and diverse family of Gram-negative Proteobacteria with members ranging from important pathogens such as Haemophilus influenzae to commensals of the animal and human mucosa. Most members live as commensals on mucosal surfaces of birds and mammals, especially in the...
- Maurice HillemanMaurice HillemanMaurice Ralph Hilleman was an American microbiologist who specialized in vaccinology and developed over three dozen vaccines, more than any other scientist...
- Hattie AlexanderHattie AlexanderHattie Elizabeth Alexander was an American pediatrician and microbiologist...
- Hib vaccineHib vaccineHaemophilus influenzae type B vaccine is a conjugate vaccine developed for the prevention of invasive disease caused by Haemophilus influenzae type b bacteria. The Centers for Disease Control and Prevention has recommended the use of the Hib vaccine. Due to routine use of the Hib vaccine in...
- Haemophilus influenzae cellulitisHaemophilus influenzae cellulitisHaemophilus influenzae cellulitis is a cutaneous condition characterized by a distinctive bluish or purplish-red cellulitis of the face.- References :...
- Haemophilus meningitisHaemophilus meningitisHaemophilus meningitis is a type of bacterial meningitis associated with Haemophilus influenzae infections.Vaccination can reduce incidence. Rates are still high in areas with limited levels of vaccination....
External links
- Hib information on the World Health OrganizationWorld Health OrganizationThe World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
(WHO) site. - Fact sheet on the Centers for Disease Control and PreventionCenters for Disease Control and PreventionThe Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
(CDC) site. - Hib Initiative - from Johns Hopkins UniversityJohns Hopkins UniversityThe Johns Hopkins University, commonly referred to as Johns Hopkins, JHU, or simply Hopkins, is a private research university based in Baltimore, Maryland, United States...
, London School of Hygiene & Tropical MedicineLondon School of Hygiene & Tropical MedicineThe London School of Hygiene & Tropical Medicine is a constituent college of the federal University of London, specialising in public health and tropical medicine...
, CDCCenters for Disease Control and PreventionThe Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
& WHOWorld Health OrganizationThe World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health... - November 2nd: World Pneumonia Day Website