Introduction
Haemophilus influenzae is a tiny Gram-negative coccobacillus that often colonizes the human respiratory system. There are two types of H. influenzae: encapsulated strains and unencapsulated strains. Encapsulated strains are categorized into six serotypes based on their capsular antigens (a, b, c, d, e, and f), but unencapsulated strains are nontypable since they lack the polysaccharide capsule and hence capsular antigens.
The Characteristics of Haemophilus Influenzae
Haemophilus influenzae has a thin peptidoglycan layer, so it doesn't retain the crystal violet dye during Gram staining. Instead, like all other Gram-negative bacteria, it stains pink with safranin dye. And because it's a coccobacillus, its form varies between spherical, like a coccus, and linear, like a bacillus. Haemophilus influenzae is non-motile, meaning it does not move, and facultative anaerobic, which means it can live in both aerobic and anaerobic conditions. It is also catalase and oxidase positive, which implies it makes both of these enzymes. Finally, chocolate agar may be used to cultivate Haemophilus influenzae because it includes critical nutrients that the bacteria requires to flourish, such as factor X, also known as hemin, and factor V, also known as nicotinamide adenine nucleotide. Another method is to cultivate it with Staphylococcus aureus colonies on blood agar, which supplies factor V through red blood cell hemolysis. On both blood agar and chocolate agar, Haemophilus influenzae forms convex, smooth, gray, or translucent colonies.
The Virulence Characteristics of Haemophilus Influenzae
Haemophilus influenzae possesses a number of virulence characteristics that behave like assault weapons, allowing it to target and damage host cells while evading the immune system. Initially, encapsulated strains of Haemophilus influenzae are protected by a polysaccharide layer known as a capsule. This capsule is now a prominent virulence factor for Haemophilus influenzae due to its antiphagocytic capacity, which shields the bacterium against phagocytosis by macrophages and neutrophils. This permits Haemophilus influenzae to survive and bind to epithelial cells in the airways.
The capsule also contains pili, which are hair-like extensions, as well as adhesion proteins like HMW1 and HMW2, which aid in the bacteria's attachment to host cells. Both encapsulated and unencapsulated strains contain an outer membrane composed of lipooligosaccharides, or LOS. LOS decreases mucociliary clearance, or the bronchi's self-clearing process, which ordinarily removes microorganisms from the respiratory system. LOS allows Haemophilus influenzae to colonize the respiratory tract. Furthermore, both encapsulated and unencapsulated strains produce IgA protease, a toxic protein that degrades Immunoglobulin A (IgA). IgA is an immune system protein present in nasopharyngeal mucosa secretions that ordinarily tags invading bacteria, allowing neutrophils to detect and eliminate them. So IgA protease eliminates the first barrier of mucosal protection!
Surprisingly, unencapsulated viruses have two additional abilities that enable them to avoid the immune system. First, these strains may modify the oligosaccharides on their outer membrane each time they infect a cell, a process known as phase variation. Because of phase fluctuation, the immune system is unable to recall the infecting strain, preventing it from mounting a rapid specific immune response against it when it encounters the strain again. Finally, unencapsulated bacteria can generate biofilms. A biofilm is essentially a coating of goop-like substance composed of exopolysaccharides, or EPS, in which Haemophilus influenzae bacteria reside and multiply. When comparing a biofilm to strawberry jam, the seeds are the bacteria and the remainder of the jam is the EPS. The bacteria in the biofilm evade the host's immune system and antibiotics.
Types of Infections Caused by Haemophilus Influenzae
Encapsulated strains tend to induce more invasive sickness due to their capsules. One method is to spread straight from the nasopharynx to the epiglottis, resulting in epiglottitis, or to the soft skin tissues of the face, causing cellulitis. Encapsulated strains can potentially pass past the nasopharyngeal epithelium and directly infect the blood capillaries, resulting in bacteremia. It can spread from the circulation to distant areas such as the meninges (meningitis), bones (osteomyelitis), or joints (septic arthritis).
Nonencapsulated strains of Haemophilus influenzae, on the other hand, are less invasive and typically cause mucosal infections by direct extension. For example, they may go up the eustachian tubes and into the middle ear, resulting in otitis media. If they spread to the paranasal sinuses, sinusitis develops. Finally, if they enter the respiratory tract, they can induce bronchitis (bronchial inflammation) or pneumonia (lung inflammation).
Nonencapsulated forms of Haemophilus influenzae now populate the nasopharynx of 40 to 80% of children and adults, whereas encapsulated strains, such as Hib, colonize just 3 to 5% of children aged 2 to 5 years. Haemophilus influenzae is mostly spread by respiratory droplets and secretions. Risk factors differ according to the infecting strain.
Haemophilus influenzae type b often causes sickness in youngsters and persons with spleen problems, as the spleen plays a crucial role in immunity against encapsulated bacteria. This category comprises persons who have had a splenectomy, which is the removal of the spleen, as well as those with sickle cell disease, who have functional asplenia, and people with malignancies or congenital deficits of complement components. Furthermore, persons with an acute viral illness, particularly with the influenza virus, are at danger of a potentially deadly bacterial superinfection with Haemophilus influenzae, even if their spleen is functioning normally.
Haemophilus influenzae nontypable most commonly causes sickness in children and those with immunocompromising diseases such as diabetes, cancer, or HIV infection. It is possible to develop postviral pneumonia following a viral infection. Other risk factors include having an underlying lung illness like chronic obstructive pulmonary disease or cystic fibrosis. In persons with chronic obstructive pulmonary disease, Haemophilus influenzae nontypable causes bronchopneumonia.
Symptoms and Diagnosis of Haemophilus Influenzae Infections
Symptoms are now disease-specific. First, consider infections caused by Haemophilus influenzae type B. Epiglottitis causes fever, painful throat, trouble speaking, and dyspnea. Meningitis causes fever, tiredness, irritability, vomiting, a painful neck, and impaired mental state, whereas cellulitis causes fever and a warm, sensitive region of erythema on the cheek or periorbital area. Bacteremia can cause fever, chills, hypotension, and tachycardia; septic arthritis can cause fever, pain, swelling, and tenderness of the afflicted joint; and osteomyelitis can cause fever, bone pain, and weakness.
Now consider illnesses produced by Haemophilus influenzae that are nontypable. Otitis media is associated with fever, ear discomfort, and otorrhea, which is discharge originating from the ear. Sinusitis symptoms include fever, pain around the afflicted sinus, and persistent, purulent nasal discharge. The symptoms of bronchopneumonia include fever, chills, chest discomfort, coughing, and shortness of breath. Finally, conjunctivitis causes redness, discomfort, and burning in the eye.
Diagnosis can be made by detecting Haemophilus influenzae in a culture of a biological sample such as blood, CSF, synovial fluid, pleural fluid, or fluid collected during sinus aspiration, tympanocentesis, tracheal or lung aspiration, bronchoscopy, or bronchoalveolar lavage. Serological techniques such as latex agglutination, enzyme immunoassay, and coagglutination can also be used to identify antibodies to Haemophilus influenzae. A laryngoscopy can be used to diagnose epiglottitis, which is characterized by a cherry red, swollen epiglottis, and an X-ray can reveal a thumbprint sign on the epiglottis. When bronchopneumonia is suspected, a chest X-ray is performed, which reveals ground-glass opacities, bronchial wall thickening, and confluent regions of consolidation.
Treatment and Prevention of Haemophilus Influenzae Infections
Ceftriaxone and chloramphenicol are now used to treat Haemophilus influenzae type B infections, particularly meningitis. Mucosal infections with nontypable Haemophilus influenzae, on the other hand, are treated initially with amoxicillin +/- clavulanate, followed by third and second-generation cephalosporins, macrolides, or fluoroquinolones as alternatives.
Finally, a vaccination for Haemophilus influenzae type B is suggested between the ages of 2 and 18 months. This vaccine has a type B capsular polysaccharide conjugated with a diphtheria toxoid component, and its usage has significantly reduced the incidence of Haemophilus influenzae meningitis. As a result, unimmunized children account for the vast majority of instances of Haemophilus influenzae meningitis. Finally, contacts of children with Haemophilus influenzae type B infections can be treated with chemoprophylaxis with rifampin.
Conclusion
Haemophilus influenzae is a non-motile Gram-negative coccobacillus that grows on chocolate agar with factors V and X, is facultatively anaerobic, and produces catalase and oxidases. There are two kinds of Haemophilus influenzae strains: encapsulated and unencapsulated. Both encapsulated and unencapsulated bacteria have an exterior membrane with LOS and release IgA protease, but only encapsulated strains have a capsule containing pilli and adhesion proteins. On the other hand, only non-encapsulated strains are capable of phase variation and biofilm development.
Notes:
Characteristics of Haemophilus influenzae:
- Tiny Gram-negative coccobacillus.
- Two types: encapsulated (six serotypes) and unencapsulated (nontypable).
- Thin peptidoglycan layer, stains pink with safranin dye.
- Coccobacillus shape, non-motile, facultative anaerobic.
- Catalase and oxidase positive.
- Grows on chocolate agar containing factors X and V.
Virulence Characteristics:
- Encapsulated strains protected by a capsule, resistant to phagocytosis.
- Capsule contains pili and adhesion proteins aiding in attachment.
- Outer membrane with lipooligosaccharides (LOS) reduces mucociliary clearance.
- Produces IgA protease, degrades Immunoglobulin A.
- Unencapsulated strains capable of phase variation and biofilm formation.
Infections Caused:
- Encapsulated strains: epiglottitis, cellulitis, bacteremia, meningitis, osteomyelitis, septic arthritis.
- Nonencapsulated strains: otitis media, sinusitis, bronchitis, pneumonia.
Epidemiology:
- Nonencapsulated strains prevalent in 40-80% of children and adults.
- Encapsulated strains (Hib) primarily affect young children and immunocompromised individuals.
Symptoms and Diagnosis:
- Disease-specific symptoms: fever, pain, inflammation depending on the site of infection.
- Diagnosis via culture of biological samples or serological techniques.
- Specific diagnostics for epiglottitis and bronchopneumonia through laryngoscopy and chest X-ray, respectively.
Treatment and Prevention:
- Ceftriaxone and chloramphenicol for type B infections.
- Amoxicillin +/- clavulanate, followed by cephalosporins, macrolides, or fluoroquinolones for nontypable strains.
- Vaccination recommended for Hib between 2 and 18 months, significantly reducing meningitis incidence.
- Contacts of infected children treated with rifampin as chemoprophylaxis.
