Haemophilus influenzae Infections

Dennis E. Amundson and Jennifer M. Radin

Haemophilus influenzae are small, pleomorphic, nonmotile oxidative-positive, Gram-negative rods that occur in both encapsulated and nonencapsulated forms. The encapsulated forms (types A–F), and particularly H. influenzae type B, have increased virulence and are associated with invasive disease (e.g., meningitis, bacteremia, epiglottitis, pneumonia, and septic arthritis), primarily in children younger than age 5. In contrast, the genetically diverse unencapsulated (nontypeable) strains of H. influenzae commonly cause mucosal diseases such as community- acquired pneumonia in adults, sinusitis in children and adults, otitis media in children, and bronchitis in patients with chronic lung disease. All strains of H. influenzae are fastidious, tend to be overgrown by other bacteria in culture, and require special growth factors (X [hemin] and V [nicotinamide adenine dinucleotide]) to grow aerobically. These factors can be supplied with chocolate or supplemented agars. The six capsular forms are identified and differentiated from the heterogeneous nontypeable H. influenzae strains by a variety of serotyping methodologies (e.g., latex particle slide agglutination, countercurrent immunoelectrophoresis).

A dramatic shift has occurred in the epidemiology of H. influenzae infections in developed countries since the early 1990s because of the universal implementation of H. influenzae type B vaccines in infancy. H. influenzae type B is now only a small burden with an estimated incidence of 0.05/100,000 population in the United States. In contrast, all of the H. influenzae subtypes together have an estimated incidence of 1.63 of every 100,000 population in the United States and a case fatality rate of 15.3%, with most of the burden coming from the nontypeable strains. Concurrently, there has been increasing global recognition of the importance of nontypeable H. influenzae strains as causative agents for respiratory tract infections and for invasive disease. Nontypable strains cause 59% of invasive disease in children and 61% in adults.

Humans are the only known hosts for H. influenzae. The organisms, predominately the nontypeable strains, colonize the nasopharynx throughout life, beginning in infancy and can be cultured from 3% to 88% of asymptomatic individuals, depending on the population sampled. Higher rates, increased susceptibility, and more prolonged duration of carriage are observed in those with underlying lung disease (e.g., cystic fibrosis, chronic obstructive pulmonary disease [COPD]) as well as in the relatively immunosuppressed (e.g., chronic renal failure, myeloma, alcoholism, and diabetes). Colonization can be a very dynamic process, with coinfection and strain turnover within days to weeks. Unlike the nontypeable strains, H. influenzae type B and other encapsulated strains colonize only a few percentage of healthy individuals. The rate of carriage of H. influenzae type B has substantially declined in countries using the H. influenzae type B vaccine.

Bacterial transmission occurs through respiratory droplets or contact with secretions and fomites. Increased transmission occurs in closed settings, such as households, child day care centers, and nursing homes. H. influenzae, primarily nontypeable strains, cause approximately 20% of all otitis media infections in children and 20% to 25% of all sinus infections in adults. In addition, nontypeable H. influenzae strains are second only to Streptococcus pneumoniae as the causative agents in community-acquired pneumonia (12%–28% of cases) and are the most common cause of exacerbations of COPD and bronchiectasis. Infection with H. influenzae in bronchiectasis is particularly interesting in that the eradication of one strain of the bacteria is quickly followed by reacquisition of another. Additionally, the degree of bacterial load in bronchiectasis is associated with evidence of inflammatory infiltration of the airways and increased airway injury. Risk factors for H. influenzae pneumonia include (1) antecedent viral respiratory tract infection (especially influenza A); (2) chronic lung disease (e.g., COPD or bron-chiectasis); (3) systemic diseases associated with immunosuppression (e.g., diabetes or cancer); (4) environmental exposures (e.g., exposure to smoke); and, in some cases, (5) strain-specific virulence factors.

The pathogenesis of disease is very different between encapsulated and unencapsulated strains. The encapsulated strains are better able to survive in the bloodstream because the polysaccharide capsules confer virulence, as in the case of the polyribosylribitol phosphate moieties of H. influenzae type B. H. influenzae type B invades the nasopharyngeal vascular space; the ensuing bacteremia can result in sepsis, meningitis, epiglottitis, and other deep-seated infections. Other encapsulated serotypes (especially a and f) can cause invasive disease, especially in the immunocompromised population and in a small minority of immunocompetent individuals.

Pathogenesis of disease for the unencapsulated strains is by contiguous spread from a colonized nasopharynx, resulting in localized upper and lower respiratory tract infections. The oligoliposaccharide of H. influenzae plays a major role in microbe adherence and colonization. Historically, unencapsulated strains of H. influenzae rarely caused tissue invasion. Recent reports from both developing and developed countries suggest they are becoming more prevalent as causes of both invasive disease and pneumonia in healthy children and adults.

Nontypeable H. influenzae are common causes of pneumonia in adults and resemble other pneumonias in clinical presentation. Radiographically, multilobar involvement often occurs with patchy or lobar distribution of infiltrates. As with other bacterial pneumonias, bacteremia, parapneumonic effusions, and empyema can occur. Blood cultures and culture of other accessible specimens (e.g., parapneumonic pleural effusion) should be done, although the yield from blood cultures for nontypeable strains is low. Gram stain and culture of tracheobronchial secretions can be difficult to interpret, given the frequent colonization of the respiratory tract by H. influenzae. The diagnosis is supported if a predominance of Gram-negative bacilli and polymorphonuclear leukocytes are seen in a Gram stain of expectorated sputum (or transtracheal or bronchoscopic specimens). H. influenzae, however, may not be evident as the cause of pneumonia, by either Gram stain or culture. Recent studies of real-time polymerase chain reaction (PCR) testing for Haemophilus influenzae suggest that it offers more sensitive and more specific results than other methods previously used. More invasive sampling (e.g., protected bronchial brush catheterization or needle aspiration of lung tissue) can increase the likelihood of a definitive diagnosis. These procedures, however, are not usually necessary in stable, immuno-competent individuals presenting with community-acquired pneumonia. Rather, most patients are treated with empiric antibiotic therapy that covers the more common causes of community-acquired pneumonia.

Nontypeable H. influenzae is also a common cause of acute bacterial exacerbation of COPD and bronchiectasis. Colonization with H. influenzae in “stable” COPD patients has been shown to increase total symptoms during exacerbations and to prolong the recovery of peak flow afterward. Additionally, bacteria isolated from patients with COPD subjected to molecular typing demonstrate that the acquisition of a new strain of H. influenzae

Only gold members can continue reading. Log In or Register to continue