Haemophilus influenzae – Habitat, Morphology, Pathogenesis, Treatment

What is Haemophilus influenzae?

• Haemophilus influenzae is a Gram-negative, non-motile, coccobacillary bacterium belonging to the family Pasteurellaceae. It is facultatively anaerobic and capnophilic, thriving best in environments with elevated carbon dioxide levels. The bacterium grows optimally at temperatures between 35 and 37 °C, making the human body an ideal host. It was first described in 1893 by Richard Pfeiffer during an influenza pandemic, mistakenly believed to be the causative agent of influenza, leading to its name.
• This pathogen is an important cause of a range of localized and invasive infections, particularly in young children and immunocompromised individuals. It is associated with respiratory tract infections such as pneumonia and bronchitis and systemic conditions like meningitis, epiglottitis, cellulitis, and septic arthritis. The bacterium is classified into encapsulated and non-encapsulated forms. Encapsulated strains are further divided into serotypes labeled ‘a’ through ‘f’ based on their polysaccharide capsule, with serotype b (H. influenzae type b or Hib) historically causing the most severe diseases in infants and children, such as meningitis, often leading to complications like deafness or cognitive impairment.
• The advent of the Hib conjugate vaccine in the 1980s has significantly reduced the incidence of infections caused by type b strains, particularly in developed nations. However, non-encapsulated strains, also known as non-typeable H. influenzae (NTHi), have emerged as the primary cause of illnesses such as otitis media, sinusitis, and pneumonia, especially in vaccinated individuals.
• Transmission of H. influenzae occurs via inhalation of respiratory droplets or through direct contact with secretions from infected individuals. Effective treatment often involves antibiotics; however, many strains exhibit resistance to penicillin-based drugs. In mild cases, combinations like amoxicillin with clavulanic acid are employed.
• A notable milestone in scientific history is that H. influenzae was the first organism to have its entire genome sequenced, marking a significant advancement in microbiology and genomics.

Scientific classification of H. influenzae Infection

Domain:	Bacteria
Phylum:	Pseudomonadota
Class:	Gammaproteobacteria
Order:	Pasteurellales
Family:	Pasteurellaceae
Genus:	Haemophilus
Species:	H. influenzae

Geographical Distribution and Habitat of H. influenzae Infection

The geographical spread of H. influenzae and its habitat are both shaped by factors like vaccination coverage and population immunity.

Geographical Distribution

• Before the Hib Vaccine:
  • H. influenzae type b (Hib) was a major cause of infections in children across the globe.
  • The incidence of invasive Hib diseases was high in young children, leading to significant morbidity and mortality.
• Post-Hib Vaccine Era:
  • With the introduction of the Hib vaccine, the incidence of invasive Hib infections has drastically reduced worldwide.
  • In developing countries, where vaccination programs are still expanding, the frequency of Hib infections has decreased to only 2–3 cases per 100,000 children under five years old.
• Current Trends:
  • Despite the success of the vaccine, Hib infections still occur in nonimmune children due to incomplete vaccination or inadequate immune responses.
  • The elderly are now more likely to experience Hib infections, as they may have lower immunity or no prior exposure to the vaccine.
  • In regions with successful vaccination campaigns, other encapsulated bacteria and nonencapsulated H. influenzae strains have been emerging as causes of disease.

Habitat

• Strictly Human Pathogen:
  • H. influenzae is a pathogen that exclusively infects humans. It does not naturally inhabit animals or other species.
• Nonencapsulated Strains:
  • These strains are common commensals of the human nasopharyngeal and oropharyngeal mucosa.
  • Nearly all children become colonized by nonencapsulated H. influenzae strains within their first few months of life.
• Encapsulated Strains (Hib):
  • H. influenzae serotype b (Hib) is much less common in the upper respiratory tract.
  • If it is found, it is typically present in only a small percentage of children (1–5%).

Morphology of Haemophilus influenzae

Haemophilus influenzae is a Gram-negative bacterium with distinct physical and structural characteristics. Its morphology plays a key role in its identification and pathogenicity.

• Size and Shape:
  The bacterium is small and pleomorphic, with a typical size of approximately 1 × 0.3 micrometers.
  In fresh cultures, it primarily appears as coccobacilli, while older cultures may exhibit elongated filamentous forms.
• Structural Features:
  H. influenzae is non-motile, meaning it lacks structures like flagella for movement.
  It is also non-spore-forming, distinguishing it from certain other bacterial species.
  The bacterium is non-acid-fast, indicating that it does not retain certain dyes during acid-fast staining procedures.
• Capsule Presence:
  Some strains of H. influenzae have a polysaccharide capsule, which is a key virulence factor.
  The capsule can be visualized using techniques such as India ink preparation or capsular swelling reaction with type-specific antiserum.

Culture and Biochemical Reactions of Haemophilus influenzae

Haemophilus influenzae is a fastidious bacterium with precise growth requirements and distinct biochemical properties that aid in its identification and study.

Growth Conditions and Culture Requirements

• Oxygen Requirements:
  H. influenzae is a facultative anaerobe, thriving better in environments with reduced oxygen or in anaerobic conditions.
  Growth improves in the presence of 5–10% carbon dioxide.
• Temperature Preferences:
  Optimal growth occurs between 35–37°C.
  It cannot grow at temperatures below 22°C.
• Growth Factors:
  The bacterium requires two specific growth factors—X factor and V factor—for survival and replication:
  • X Factor:
    • This is a heat-stable substance found in blood, identified as hemin or protoporphyrin IX.
    • It is essential for synthesizing iron-dependent bacterial enzymes like catalase, cytochrome oxidase, and peroxidase.
  • V Factor:
    • A heat-labile substance, V factor is NAD or NADP, required as a hydrogen acceptor during bacterial oxidation-reduction processes.
    • It can be destroyed at 120°C after 30 minutes.
    • V factor is synthesized by organisms like Staphylococcus aureus and some fungi.
• Preferred Culture Media:
  • Chocolate Agar:
    • Prepared by heating blood agar to 80–90°C to release the X and V factors from red blood cells.
    • Supports robust colony growth for H. influenzae.
  • Blood Agar with Satellitism:
    • Growth can occur in the presence of Staphylococcus aureus, which provides the V factor.
    • Colonies closer to the staphylococcal streak grow larger due to higher V factor availability, a phenomenon called satellitism.
  • Fildes’ Agar and Levinthal’s Agar:
    • These are transparent media made by processing blood with nutrient broth or peptic digests.
    • Best suited for primary isolation and yield distinct colony morphologies based on capsular presence.
• Colony Morphology:
  • Capsulated Strains:
    • Produce larger, high convex, mucoid colonies with an iridescent appearance on Levinthal’s agar.
    • Colonies range from 1–3 mm in diameter on media containing blood or V factors.
  • Non-Capsulated Strains:
    • Colonies are smaller, low convex, smooth, and transparent compared to capsulated forms.
  • On ordinary blood agar, growth is minimal due to the lack of freely available V factor, and there is no hemolysis.

Biochemical Reactions

• Enzymatic Activity:
  • Positive for catalase and oxidase enzymes, indicating metabolic activity involving oxygen.
• Fermentation:
  • Can ferment glucose and galactose.
  • Does not ferment lactose, sucrose, or mannitol.
• Nitrate Reduction:
  • Reduces nitrates to nitrites, a key biochemical characteristic used in differentiation.

Human Infections Caused by Haemophilus Species

Haemophilus species are known for their ability to cause various infections, ranging from localized to systemic. Each species exhibits distinct pathogenic potential, targeting specific tissues and systems.

Major Diseases and Pathogens

• Haemophilus influenzae:
  • Known for causing severe invasive diseases.
  • Meningitis: Often presents in young children, characterized by inflammation of the protective membranes around the brain and spinal cord.
  • Epiglottitis: Life-threatening condition where the epiglottis becomes inflamed, blocking the airway.
  • Cellulitis: Localized infection causing redness, swelling, and pain in the skin and soft tissues.
  • Pneumonia: Involves lung infection, resulting in fever, cough, and difficulty breathing.
  • Otitis Media: Middle ear infection leading to ear pain, fever, and hearing issues.
  • Bronchitis: Causes inflammation of the airways, leading to cough and sputum production.
  • Conjunctivitis: Pink eye, marked by redness, itching, and discharge from the eye.
• Haemophilus ducreyi:
  • The causative agent of chancroid, a sexually transmitted infection.
  • Presents as soft, painful sores on the genital area, often accompanied by swollen lymph nodes.
• Haemophilus aphrophilus:
  • Known to cause subacute endocarditis, which affects the heart valves.
  • Can lead to brain abscesses, often linked to oral infections or dental procedures.
  • Associated with pneumonia and sinusitis, resulting from respiratory infections.
• Haemophilus parainfluenzae:
  • A less common pathogen, but it can cause endocarditis, particularly in individuals with predisposing heart conditions.
  • Also involved in opportunistic infections, especially in immunocompromised patients.
• Haemophilus aegyptius:
  • The primary cause of conjunctivitis, characterized by inflammation, redness, and discharge from the eyes.
• Haemophilus haemolyticus:
  • Rarely pathogenic but can cause opportunistic infections, particularly in individuals with compromised immunity.
• Haemophilus parahaemolyticus:
  • Occasionally linked to opportunistic infections in vulnerable hosts.
• Haemophilus segnis:
  • Infrequently associated with human disease, but may act as an opportunistic pathogen in rare cases.

Cell Wall Structures and Antigenic Properties of Haemophilus Species

The cell wall of Haemophilus species, typical of Gram-negative bacteria, plays a critical role in its pathogenicity and immune interactions. It contains unique structures and antigens that define the organism’s behavior and immune response.

Key Components of the Cell Wall

• Lipopolysaccharides (LPS):
  • Found in the outer membrane of the cell wall.
  • Possess endotoxin activity, which contributes to the bacteria’s ability to cause inflammation and disease.
• Species- and Strain-Specific Outer Membrane Proteins (OMP):
  • These proteins vary significantly between strains and species, adding diversity to the bacterial surface.

Major Antigenic Features

1. Capsular Polysaccharide Antigen:
   • Found only in encapsulated strains of H. influenzae.
   • Composed of polysaccharides that determine the organism’s serotype.
   • Six serotypes (a, b, c, d, e, and f) are defined based on the structure of this antigen.
   • Type b Capsule (Hib):
     • Contains polyribosyl ribitol phosphate (PRP), a critical component for its virulence.
     • Before widespread Hib vaccination, this serotype caused over 95% of invasive infections.
     • PRP-based vaccines, including conjugate forms, generate protective antibodies (IgG, IgM, IgA) that are bactericidal and opsonic.
     • After the introduction of the Hib vaccine, infections caused by serotype b have declined, with serotypes c, f, and non-encapsulated strains emerging as more common causes of disease.
2. Outer Membrane Proteins (OMP):
   • Serve as antigens with high variability between strains.
   • Classified into 13 subtypes in serotype b (H. influenzae Hib).
   • Play roles in immune evasion and interaction with host tissues.
3. Lipooligosaccharide (LOS):
   • A structurally complex and antigenically diverse component.
   • Contributes to the bacterium’s immune resistance and pathogenicity.

Virulence Factors of Haemophilus Species

Haemophilus species rely on a range of virulence factors to establish infections, evade immune defenses, and persist within the host. These factors enhance their ability to colonize mucosal surfaces, resist immune responses, and cause invasive diseases.

Key Virulence Factors and Their Functions

• Capsular Polysaccharide (PRP):
  • Found in encapsulated strains, particularly in H. influenzae type b (Hib).
  • The capsule contains polyribosyl ribitol phosphate (PRP), making it antiphagocytic and resistant to immune cell attack.
  • Loss of the capsule directly reduces virulence, demonstrating its critical role in disease causation.
  • Protective antibodies against the capsule enhance bacterial clearance through phagocytosis and complement activation.
  • These antibodies can arise naturally during infection, through vaccination with PRP-based vaccines, or via maternal transfer to newborns.
  • Individuals lacking anti-PRP antibodies or complement proteins face a higher risk of invasive conditions like meningitis or epiglottitis.
• Lipid A Component of Lipopolysaccharide (LPS):
  • Contributes to inflammation, particularly in meningitis, by triggering a strong immune response.
  • Experimental studies have linked it to inflammatory damage in host tissues.
• IgA1 Protease:
  • Produced by both encapsulated and nonencapsulated strains.
  • Specifically targets and cleaves the heavy chain of IgA1, a crucial antibody in mucosal immunity.
  • This breakdown disrupts mucosal defenses and facilitates bacterial colonization on epithelial surfaces.
• Pili:
  • Specialized structures that promote adhesion to epithelial cells.
  • Essential for the initial stages of colonization, enabling the bacteria to establish infection sites.

Pathogenesis of H. influenzae Infection

H. influenzae infections occur through a series of well-defined steps involving colonization, immune evasion, and systemic spread. These processes vary based on whether the strain is encapsulated or noncapsulated, affecting the severity and type of disease.

Key Steps in Pathogenesis

• Entry into the Host:
  • Infection begins through the respiratory route.
  • The bacteria colonize the oropharynx or nasopharynx, using pili and nonpilous adhesins to adhere to epithelial cells.
• Disruption of Respiratory Defenses:
  • Lipid A, a component of lipopolysaccharide (LPS), disrupts ciliary activity in the respiratory mucosa.
  • This impairment allows the bacteria to invade deeper tissues and damage mucosal surfaces.
  • A high bacterial load or coexisting viral infections can enhance mucosal invasion.
• Bacteremia and Immune Clearance:
  • Once the bacteria breach the mucosa, they enter the bloodstream.
  • Immune factors, including anti-PRP antibodies, complement proteins, and phagocytes, play a crucial role in clearing the bacteria.
  • In individuals lacking adequate anti-PRP antibodies, the bacteria multiply rapidly, leading to high-grade bacteremia.
• Dissemination to Distant Sites:
  • Persistent bacteremia allows the bacteria to spread to the meninges, subcutaneous tissues, joints, pleura, and pericardium.
  • Hib meningitis often follows bacteremia and is rarely caused by direct extension from local infections like sinusitis or otitis media.
  • The duration and intensity of bacteremia determine central nervous system (CNS) invasion, typically occurring through the choroid plexus.
• CNS Infection and Meningitis:
  • Meningitis develops from inflammation, cerebrospinal fluid (CSF) pressure elevation, and edema.
  • Brain parenchymal invasion is rare, with the primary effects localized to the meninges.
• Pathogenesis in Noncapsulated Strains:
  • Noncapsulated strains, also called nontypable H. influenzae (NTHi), colonize up to 80% of individuals.
  • These strains spread by direct extension from colonized sites rather than through the bloodstream.
  • Common outcomes include sinusitis from sinus invasion, otitis media via the Eustachian tube, and lower respiratory tract infections like bronchitis or pneumonia.

Clinical Syndromes of H. influenzae Infection

Infections caused by H. influenzae vary significantly depending on whether the strain is encapsulated or nonencapsulated. Both types can lead to severe clinical outcomes, but the infections associated with encapsulated strains tend to be more serious.

Infections Caused by Encapsulated H. influenzae

• Meningitis:
  • The most serious condition caused by H. influenzae, especially in children between 2 months and 2 years of age.
  • Symptoms include fever, altered mental state, headache, and photophobia (more common in older children).
  • Without treatment, the mortality rate exceeds 90%.
  • Rare in adults.
• Epiglottitis:
  • A life-threatening condition, primarily seen in children aged 3–18 months post-vaccine era.
  • Characterized by severe cellulitis and obstructive laryngeal edema, making it a medical emergency.
• Cellulitis:
  • Commonly affects children, especially in the buccal and periorbital regions.
  • Symptoms include fever, induration, and tenderness, particularly around the head and neck.
  • Most often seen in the buccal and preseptal areas.
• Septic Arthritis:
  • Seen in children, involving large joints like the knee, ankle, hip, or elbow.
  • In adults, it can be monoarticular or polyarticular, affecting multiple joints.
• Pneumonia:
  • More common in infants, presenting similarly to other bacterial pneumonia infections.
  • Difficult to distinguish clinically from other types of pneumonia.
• Suppurative Lesions:
  • H. influenzae can cause severe, pus-filled infections like epiglottitis, pericarditis, and septic arthritis.
  • Less common but still serious conditions include endophthalmitis, cervical adenitis, osteomyelitis, and endocarditis.

Infections Caused by Nonencapsulated H. influenzae

• Upper and Lower Respiratory Tract Infections:
  • Noncapsulated strains are opportunistic pathogens, most commonly affecting the respiratory system.
  • These strains are significant contributors to conditions like otitis media, bronchitis, pneumonia, and conjunctivitis.
• Otitis Media:
  • One of the most common infections caused by nonencapsulated H. influenzae, often seen alongside Streptococcus pneumoniae.
  • A major cause of ear infections in children.
• Conjunctivitis:
  • Nonencapsulated H. influenzae is the second most common cause of conjunctivitis in older children, after S. pneumoniae.
• Community-Acquired Pneumonia:
  • H. influenzae is a leading cause of pneumonia in adults, contributing to many cases of bacterial pneumonia in the community setting.

Reservoir, Source, and Transmission of H. influenzae Infection

The spread of H. influenzae depends largely on human carriers and certain transmission routes.

Reservoir of Infection

• Humans as the Primary Reservoir:
  • Humans are the sole reservoir for H. influenzae infections.
  • Infected individuals, particularly those with H. influenzae colonizing their respiratory tract, play a crucial role in spreading the bacteria.

Source of Infection

• Nasopharyngeal Mucosal Secretion:
  • The most common source of infection is the nasopharyngeal mucosal secretions of infected individuals.
  • These secretions contain high concentrations of the bacteria, which can be transmitted to others.

Transmission Routes

• Inhalation of Respiratory Droplets:
  • The bacteria are primarily spread through inhaling droplets from respiratory tract secretions.
  • Close contact with an infected person can also facilitate this type of transmission.
• Direct Contact:
  • H. influenzae can also be transmitted via direct contact with surfaces contaminated by respiratory droplets.
• Transmission to Neonates:
  • For newborns, the bacteria can be transmitted during delivery through the maternal genital tract.
  • Certain strains of nonencapsulated H. influenzae, particularly biotype 4, can colonize the genital tract and cause invasive diseases in neonates.

Biotyping of H. influenzae

Biotyping is a way to classify H. influenzae based on its biochemical properties.

• Biochemical Reactions Used for Biotyping
  • Indole Production: Measures the bacterium’s ability to produce indole.
  • Urease Activity: Tests for the ability to break down urea.
  • Ornithine Decarboxylase Activity: Determines if the bacteria can decarboxylate ornithine.
• Biotype Classification
  • H. influenzae is divided into eight biotypes based on these biochemical reactions.
  • Most clinical isolates of H. influenzae fall under biotypes I–III.
  • The most well-known and clinically significant strain, type b H. influenzae (Hib), is classified under biotype I.

Laboratory Diagnosis of H. influenzae

Diagnosing H. influenzae infection involves multiple methods, depending on the specimen type and the clinical presentation.

• Specimens Collected for Diagnosis
  • Cerebrospinal fluid (CSF): Preferred for diagnosing meningitis. Typically, 1-2 mL of CSF is collected for testing.
    • In meningitis, CSF shows pleocytosis (4000–5000 WBC/mL), with neutrophil predominance.
    • CSF glucose levels drop, and protein levels rise.
  • Blood: Commonly used for cultures to diagnose conditions like cellulitis, epiglottitis, arthritis, or pneumonia caused by H. influenzae.
  • Other Specimens: Depending on the infection site, specimens such as throat swabs, pus, and aspirates from joints, ears, and sinuses are collected.
  • Collection Conditions: All specimens should be gathered under strict aseptic conditions in sterile containers.
    • H. influenzae is sensitive to cold, so specimens should be kept at 37°C, not refrigerated, during transport.
    • Immediate transport to the laboratory is crucial for optimal isolation of the pathogen.
• Microscopic Examination
  • A Gram stain of CSF from untreated meningitis cases typically reveals small, Gram-negative coccobacilli in over 80% of samples.
  • Gram-staining can also be useful for quickly diagnosing H. influenzae in lower respiratory tract infections and arthritis.
• Culture Methods
  • CSF Culture: A positive culture confirms H. influenzae infection in meningitis cases.
    • On chocolate agar or Levinthal’s agar, H. influenzae forms smooth, opaque colonies (1–2 mm) after 24 hours of incubation.
  • Blood Culture: Especially important for diagnosing epiglottitis and pneumonia, where 70–80% of epiglottitis cases show positive blood cultures.
  • Satellite Growth: On blood agar, H. influenzae can also be identified by its ability to grow in satellite formation around colonies of other bacteria, like Staphylococcus aureus.
• Bacterial Identification
  • H. influenzae colonies can be identified by:
    • Their typical colony morphology: 1–2 mm smooth, opaque colonies on chocolate agar.
    • Satellitism: Demonstrating the organism’s need for X and V factors.
    • Biochemical Properties: Specific tests for biochemical reactions help identify the bacteria (outlined in Box 38-1).
• Serotyping
  • Encapsulated Strains: Can be typed using methods such as:
    • Agglutination reaction
    • Quellung reaction (using type-specific antisera).
    • Coagglutination
    • ELISA
    • DNA probe hybridization: This method targets the capsular antigen coding region.
  • Nontypable Strains: Non-capsulated strains cannot be typed and are referred to as nontypable.
• Antigen Detection
  • Several tests are used to detect H. influenzae polysaccharide antigens in body fluids:
    • Latex agglutination (LAT)
    • Co-agglutination (Co-A)
    • Counter-current immunoelectrophoresis (CIEP)
    • ELISA.

Treatment of H. influenzae Infection

Treating H. influenzae infections primarily involves the use of antibiotics. However, the choice of antibiotic depends on the specific infection and the strain of H. influenzae.

• First-Line Antibiotics for Serious Infections
  • Cefotaxime and Ceftriaxone are the go-to drugs for treating H. influenzae type b (Hib) meningitis.
  • These antibiotics are given parenterally (by injection or IV) for 7–14 days and are highly effective for uncomplicated meningitis cases.
• Other Antibiotics Effective Against H. influenzae
  • H. influenzae is generally susceptible to:
    • Sulfonamides
    • Chloramphenicol
    • Ciprofloxacin
    • Ampicillin
    • Cefotaxime and Ceftazidime
  • However, penicillins work well for nonencapsulated strains causing mucosal infections.
• Resistance Considerations
  • A significant proportion (25–50%) of H. influenzae isolates produce beta-lactamase, an enzyme that makes them resistant to beta-lactam antibiotics like penicillin.
  • For these resistant strains, beta-lactamase-resistant antibiotics are required, including:
    • Trimethoprim–sulfamethoxazole
    • Cefuroxime axetil
    • Cefixime
    • Clarithromycin
    • Azithromycin
    • Ciprofloxacin
  • These antibiotics are typically prescribed for 10 days to treat otitis media and at least 14 days for sinusitis.

Prevention and Control of H. influenzae

Preventing and controlling H. influenzae infections hinges on vaccines, antibiotics, and measures to reduce bacterial spread.

• Vaccination
  • The Hib conjugate vaccine is the cornerstone of preventing invasive H. influenzae type b (Hib) disease.
  • This vaccine has significantly lowered the incidence of Hib diseases, like meningitis and pneumonia, by reducing pharyngeal colonization.
  • The Hib conjugate vaccine works by stimulating the immune system to produce protective antibodies.
  • The vaccine is not effective against non-typable H. influenzae strains, which are responsible for other types of infections.
  • Initially, the Hib vaccine was an unconjugated polysaccharide vaccine made from purified PRP (polyribosylribitol phosphate) capsular polysaccharide.
    • However, it was ineffective because it produced a weak immune response, especially in infants.
  • The development of the conjugate vaccine, where PRP is linked to a protein, led to a more effective and broader protection, especially for infants and young children.
• Chemoprophylaxis
  • Rifampin is used for chemoprophylaxis, particularly for high-risk groups like children under 2 years old.
  • Chemoprophylaxis is aimed at reducing Hib colonization in settings like households or daycare centers where an infected person has been identified.
  • This measure is especially important to prevent the spread of disease among children who are at higher risk due to close contact with infected individuals.

Other Haemophilus Species

Beyond H. influenzae, several other Haemophilus species contribute to various infections. These species exhibit distinct characteristics and grow under different conditions.

• Haemophilus ducreyi
  • H. ducreyi is the main cause of chancroid, a sexually transmitted infection leading to painful genital ulcers.
  • It’s most commonly seen in men, while women often remain asymptomatic.
  • This bacterium requires X factor but not V factor for growth. It is biochemically inert and grows poorly on most media.
  • Colonies are small (0.5 mm) on chocolate agar after 72 hours of incubation in the presence of CO2.
  • Chancroid lesions often present after 5-7 days as erythematous papules that ulcerate.
  • The infection can also cause inguinal lymphadenopathy.
  • Sulfonamides and tetracycline are typically used for treatment.
• Haemophilus aphrophilus
  • This species resides as a commensal in the mouth and throat.
  • It grows on chocolate agar as yellowish, convex colonies around 1.5 mm in diameter after 24 hours in a CO2-rich environment.
  • H. aphrophilus can spread to the bloodstream, leading to subacute endocarditis, especially in those with previous heart valve infections.
  • It can also cause brain abscesses, pneumonia, and sinusitis.
• Haemophilus parainfluenzae
  • An opportunistic pathogen, H. parainfluenzae can be found in the upper respiratory tract.
  • It may cause endocarditis, conjunctivitis, and bronchopulmonary infections.
  • On chocolate agar, the colonies are opaque and yellowish-white, larger than those of H. influenzae.
  • It requires only the V factor and ferments sucrose but not D-xylose.
• Haemophilus aegyptius
  • Known as the Koch–Weeks bacillus, H. aegyptius causes highly contagious acute conjunctivitis.
  • It was first observed by Koch in 1883 and cultured by Weeks in 1887.
  • Although it resembles H. influenzae, it requires more exact nutritional conditions.
  • It does not ferment xylose and is not found as a commensal in the nasopharynx of healthy individuals.
• Haemophilus haemolyticus
  • Found as a commensal in the upper respiratory tract, H. haemolyticus is generally nonpathogenic.
  • It produces hemolytic colonies on blood agar, which may resemble hemolytic streptococci.
  • It requires both X and V factors for growth.