Microbiology & infectious diseases

Gram negative bacteria

Haemophilus influenzae



Last author update: 1 October 2024
Last staff update: 1 October 2024

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PubMed Search: Haemophilus influenzae

Megan Amerson-Brown, M.L.S., Ph.D.
Cite this page: Amerson-Brown M. Haemophilus influenzae. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/microbiologyhinfluenzae.html. Accessed December 25th, 2024.
Definition / general
  • Haemophilus influenzae is a fastidious, opportunistic pathogen of the respiratory tract that can cause invasive infections in susceptible populations
  • Primary diagnostic techniques include culture and species differentiation based on growth requirements of hemin (factor X) and NAD+ (factor V)
    • Gram negative, coccobacilli shaped bacteria
    • Taxonomy (Database (Oxford) 2020;2020:baaa062)
      • Kingdom: bacteria
      • Phylum: Pseudomonadota
      • Class: Gammaproteobacteria
      • Order: Pasteurellales
      • Family: Pasteurellaceae
      • Genus: Haemophilus
    • 13 species (Database (Oxford) 2020;2020:baaa062)
      • H. influenzae (primary clinical pathogen) belongs to the genus Haemophilus
      • Other species include H. aegyptius, H. ducreyi, H. felis, H. haemoglobinophilus, H. haemolyticus, H. parainfluenzae, H. paracuniculus, H. parahaemolyticus, H. paraphrohaemolyticus, H. pittamaniae, H. piscium, H. sputorum (commensal flora and rare clinical pathogens)
Essential features
Epidemiology
  • Children < 5 years old (Pediatr Infect Dis J 2021;40:1028)
    • Serious Hib infection most common in this age group
    • Carriage > 50%
  • Elderly patients with invasive disease have a higher fatality rate than children
  • Immunocompromised persons (including stem cell transplant and malignancy) (Pediatr Infect Dis J 2021;40:1028)
    • Persons with cystic fibrosis
    • Sickle cell disease
    • Asplenia
    • Complement deficiency
    • Nontypeable Haemophilus influenzae (NTHi) most common
Sites
Pathophysiology
  • Normal oropharyngeal flora (BMC Microbiol 2015;15:6)
  • Transmitted by respiratory droplets via coughing or sneezing
  • Virulence factors (J Med Microbiol 2022;71, Schaechter: Encyclopedia of Microbiology, 3rd Edition, 2009)
    • Protein H, Haemophilus surface fibrils (Hsf) and pili aid in adhesion (Infect Immun 2000;68:3362)
    • Polyribosyl ribitol phosphate (PRP) capsule is antiphagocytic and helps to evade the host's neutrophil response
    • IgA proteases help with evasion of host immune response
    • Lipooligosaccharide outer membrane proteins P1, P2, P5 (endotoxin activity)
    • Outer membrane protein engages toll-like receptor 2 (TLR2)
    • Sialyltransferases and galactosyltransferases (helps evade host immune response)
    • Genetic phase variation (helps evade host immune system) (Folia Med 2012;54:19)
  • Capsule containing strains can penetrate the epithelium and capillary endothelium
  • Spread from mucosa via lymphatic drainage or damaged mucosa
  • Invasive infections
    • Pneumonia
    • Meningitis, which may result in brain damage or hearing loss
    • Joint infections
    • Sepsis
  • Noninvasive infections
    • Mucosal infections
    • Exacerbation of underlying respiratory disease
Clinical features
Diagnosis
Laboratory
Case reports
Treatment
Clinical images

Contributed by Megan Amerson-Brown, M.L.S., Ph.D. and Julia Hankins, Ph.D.
H. influenzae on chocolate agar

H. influenzae on chocolate agar

Haemophilus ID quad plate

Haemophilus ID quad plate

H. infuenzae in a BAL culture

H. infuenzae in a BAL culture

Sinus culture growing H. influenzae

Sinus culture growing H. influenzae

Microscopic (histologic) description
  • Tiny Gram negative coccobacilli
  • Tiny Gram negative rods
Microscopic (histologic) images

Contributed by Megan Amerson-Brown, M.L.S., Ph.D.
H. influenzae Gram stain

H. influenzae Gram stain

bronchoalveolar lavage (BAL) direct Gram stain

BAL direct Gram stain

Sinus wash direct Gram stain

Sinus wash direct Gram stain

Gram stain from CSF culture

Gram stain from CSF culture

Peripheral smear description
  • Tiny Gram negative coccobacilli
  • Tiny Gram negative rods
Peripheral smear images

Contributed by Megan Amerson-Brown, M.L.S., Ph.D.
H. influenzae in blood culture

H. influenzae in blood culture

Board review style question #1

A 1 year old child presents to the emergency department with fever, lethargy and positive Kernig sign. A Gram stain of the cerebrospinal fluid (CSF) revealed Gram stain morphology as shown in the figure that only grew on chocolate agar. Which of the following is the most likely causative agent?

  1. Escherichia coli
  2. Haemophilus influenzae
  3. Neisseria gonorrhoeae
  4. Neisseria meningitidis
Board review style answer #1
B. Haemophilus influenzae. H. influenzae is the only Gram negative coccobacillus organism listed. Answer A is incorrect because Escherichia coli has Gram negative rods. Answers C and D are incorrect because Neisseria meningitidis and N. gonorrhoeae are both Gram negative diplococci. In addition, E. coli, N. meningitidis and N. gonorrhoeae can all grow on blood agar.

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Reference: Haemophilus influenzae
Board review style question #2
A 65 year old smoker presents to the emergency department with a persistent cough, purulent sputum and fever for > 1 week. Chest Xray reveals a right lower lobe consolidation. The microbiology laboratory reports abundant H. influenzae from the sputum culture. What does H. influenzae require for growth?

  1. Hemin and NAD+
  2. Only V factor
  3. Only X factor
  4. Red cells and NAD+
Board review style answer #2
A. Hemin and NAD+. H. influenzae requires both the presence of hemin (X factor) and NAD+ (V factor) for growth. Answers B and C are incorrect because only 1 of the 2 necessary factors are listed. Answer D is incorrect because while red cells contain both hemin and NAD+, these nutrients are only available to the bacteria if the red cells are lysed.

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Reference: Haemophilus influenzae
Board review style question #3
An unvaccinated 8 month old presents to urgent care with fever, otitis media, congestion and purulent nasal discharge. The Gram stain from the sinus wash shows 4+ Gram negative coccobacilli. The patient is discharged on amoxicillin clavulanate. 2 weeks later, the patient is admitted for symptoms of meningitis in which the cerebrospinal fluid grew H. influenzae. Which virulence factor of H. influenzae is primarily responsible for the invasive nature of this child’s disease?

  1. Capsular polysaccharide
  2. IgA protease
  3. Lipopolysaccharide (LPS)
  4. Pili
Board review style answer #3
A. Capsular polysaccharide. The capsular polysaccharide prevents phagocytosis and allows the organism to cross the epithelial and endothelial barriers and become invasive. Cerebrospinal fluid infection is an invasive infection. Answer B is incorrect because IgA protease leaves IgA to allow for successful colonization. Answer C is incorrect because lipopolysaccharide triggers the inflammatory process. Answer D is incorrect because pili aids in attachment to mucosal epithelia.

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Reference: Haemophilus influenzae
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