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A 6-year-old boy is brought to the emergency department with increased work of breathing. His parents, who are at the bedside, recall that the patient developed a “stuffy nose” two days ago. This morning, he was noted to have a hoarse voice, drooling, and increased work of breathing. The patient was born full-term at home and has rarely seen a physician. Past medical history is otherwise noncontributory. Temperature is 39.4°C (103°F), pulse is 140/min, respirations are 32/min, and blood pressure is 90/50 mmHg. On physical examination, the patient is noted to be leaning forward with the neck hyperextended and chin thrust forward. The patient is drooling and has stridorous breathing. Radiographic imaging reveals the following finding:
Image reproduced from Radiopedia
Which of the following best describes the medication that would have been most effective in preventing this patient’s current symptoms?
Content Reviewers:Viviana Popa, MD
Haemophilus influenzae is a small Gram-negative coccobacillus which can normally colonize the human respiratory tract. There are two major categories of H. influenzae - encapsulated strains and unencapsulated strains.
Encapsulated strains are classified into six serotypes based on their capsular antigens - a, b, c, d, e and f, and unencapsulated strains are called nontypable, because they lack the polysaccharide capsule, and, consequently, capsular antigens.
Now, Haemophilus influenzae has a thin peptidoglycan layer, so it doesn’t retain the crystal violet dye during Gram staining. Instead, like any other Gram-negative bacteria, it stains pink with safranin dye.
And since it’s a coccobacillus, it’s shaped somewhere between round, like a coccus, and linear, like a bacillus. Haemophilus influenzae is non-motile, so it doesn’t move, and facultative anaerobic which means it can survive both in aerobic and anaerobic environments. It’s also catalase and oxidase positive which means it produces both these enzymes.
Finally, Haemophilus influenzae can be cultivated on chocolate agar, because this medium contains essential nutrients that Haemophilus influenzae needs to grow, like factor X, also called hemin, and factor V, also called nicotinamide adenine nucleotide.
On both blood agar and chocolate agar, Haemophilus influenzae grows into convex, smooth, gray or transparent colonies. Now, Haemophilus influenzae has a number of virulence factors, that are like assault weaponry that help it attack and destroy the host cells, and evade the immune system.
So first, encapsulated strains of Haemophilus influenzae are covered by a polysaccharide layer called a capsule. Now, this capsule is a major virulence factor for Haemophilus influenzae because of its antiphagocytic ability, meaning that it protects the bacteria against phagocytosis by macrophages or neutrophils.
This allows Haemophilus influenzae to escape destruction and attach to epithelial cells in the airways. Also, on the capsule, there are pili, which are hair-like extensions, and adhesion proteins such as HMW1 and HMW2 that help the bacteria attach to host cells.
Both encapsulated and unencapsulated strains have an outer membrane - which consist of lipooligosaccharides, or LOS.
LOS inhibits mucociliary clearance, or the self-clearing mechanism of the bronchi, that would normally sweep the bacteria out of the respiratory tract. With the help of LOS, Haemophilus influenzae can colonize the respiratory tract.
What is more, both encapsulated and unencapsulated strains make IgA protease, a toxic protein that destroys Immunoglobulin A, or IgA.
IgA is an immune system protein found in the nasopharyngeal mucosa secretions that normally opsonizes invading bacteria, meaning it tags them so neutrophils can recognize and destroy them. So IgA protease neutralizes the first line of mucosal defense!
Interestingly, unencapsulated strains have two other abilities that allow it to evade the immune system. First, these strains can change the oligosaccharides they express on their outer membrane each time they infect a cell, and this process is called phase variation.
Finally, unencapsulated strains have the ability to produce biofilms. A biofilm is basically a layer of goop-like material made of exopolysaccharides or EPS, within which Haemophilus influenzae bacteria live and reproduce.
Comparing a biofilm to strawberry jam, the seeds would be the bacteria and the rest of the jam would be the EPS. The bacteria in the biofilm hide from the host's immune system and antibiotics.
Ok, now, encapsulated strains tend to cause more invasive disease on account of their capsule. One way is to spread directly from the nasopharynx to the epiglottis, causing epiglottitis, or to the soft skin tissues in the face, causing cellulitis.
Now, nonencapsulated strains of Haemophilus influenzae colonize the nasopharynx of 40 to 80% of children and adults, whereas encapsulated strains, such as Hib, colonizes 3 to 5% of children aged 2 to 5 years.
Either way, Haemophilus influenzae is mostly transmitted via respiratory droplets and respiratory secretions. Risk factors vary depending on the infecting strain.