Haemophilus influenzae : Clinical Features, Laboratory Diagnosis and Medical Management

Haemophilus influenzae : Clinical Features, Laboratory Diagnosis and Medical Management

Haemophilus influenzae is a gram-negative coccobacillus. It is generally aerobic but can grow as a facultative anaerobe. In vitro growth requires accessory growth factors, including “X” factor (hemin) and “V” factor (nicotinamide adenine dinucleotide [NAD]).

Chocolate agar media are used for isolation. H. influenzae will generally not grow on blood agar, which lacks NAD.

H. influenzae has encapsulated (typeable) and unencap­sulated nontypeable strains. The outermost structure of encapsulated H. influenzae is composed of polyribosyl-ribitol-phosphate (PRP), a polysaccharide that is responsible for virulence and immunity. Six antigenically and biochemically distinct capsular polysaccharide serotypes have been described; these are designated types a through f. There are currently no vaccines to prevent disease caused by non-b encapsulated or nontypeable strains. In the prevaccine era, type b organisms accounted for 95% of all strains that caused invasive disease.

Pathogenesis

The organism enters the body through the nasopharynx. Organisms colonize the nasopharynx and may remain only transiently or for several months in the absence of symptoms (asymptomatic carrier). In the prevaccine era, Hib could be isolated from the nasopharynx of 0.5%–3% of normal infants and children but was not common in adults. Nontypeable (unencapsulated) strains are also frequent inhabitants of the human respiratory tract.

In some persons, the organism causes an invasive infection. The exact mode of invasion to the bloodstream is unknown. Antecedent viral or mycoplasma infection of the upper respiratory tract may be a contributing factor. The bacteria spread in the bloodstream to distant sites in the body. Meninges are especially likely to be affected.

Incidence is strikingly age-dependent. In the prevaccine era, up to 60% of invasive disease occurred before age 12 months, with a peak occurrence among children 6–11 months of age. Passive protection of some infants is provided by transplacentally acquired maternal IgG antibodies and breastfeeding during the first 6 months of life. Children 60 months of age and older account for less than 10% of invasive disease. The presumed reason for this age distribution is the acquisition of immunity to Hib with increasing age.

Antibodies to Hib capsular polysaccharide are protective. The precise level of antibody required for protection against invasive disease is not clearly established. However, a titer of 1 μg/mL 3 weeks postvaccination correlated with protection in studies following vaccination with unconjugated purified polyribosyl-ribitol-phosphate (PRP) vaccine and suggested long-term protection from invasive disease.

Acquisition of both anticapsular and serum bactericidal antibody is inversely related to the age-specific incidence of Hib disease.

In the prevaccine era, most children acquired immunity by 5–6 years of age through asymptomatic infection by Hib bacteria. Since only a relatively small proportion of children carry Hib at any time, it has been postulated that exposure to organisms that share common antigenic structures with the capsule of Hib (so-called “cross-reacting organisms”) may also stimulate the development of anticapsular antibodies against Hib.

Natural exposure to Hib also induces antibodies to outer membrane proteins, lipopolysaccharides, and other antigens on the surface of the bacterium.

The genetic constitution of the host may also be important in susceptibility to infection with Hib. Risk for Hib disease has been associated with a number of genetic markers, but the mechanism of these associations is unknown. No single genetic relationship regulating susceptibility or immune responses to polysaccharide antigens has yet been convinc­ingly demonstrated.

Clinical Features

Invasive disease caused by H. influenzae type b can affect many organ systems. The most common types of invasive disease are meningitis, epiglottitis, pneumonia, arthritis, and cellulitis.

Meningitis is infection of the membranes covering the brain and spinal cord and is the most common clinical manifesta­tion of invasive Hib disease, accounting for 50%–65% of cases in the prevaccine era. Hallmarks of Hib meningitis are fever, decreased mental status, and stiff neck (these symptoms also occur with meningitis caused by other bacteria). Hearing impairment or other neurologic sequelae occur in 15%–30% of survivors. The case-fatality rate is 3%–6%, despite appropriate antimicrobial therapy.

Epiglottitis is an infection and swelling of the epiglottis, the tissue in the throat that covers and protects the larynx during swallowing. Epiglottitis may cause life-threatening airway obstruction.
Septic arthritis (joint infection), cellulitis (rapidly progressing skin infection which usually involves face, head, or neck), and pneumonia (which can be mild focal or severe empyema) are common manifestations of invasive disease. Osteomyelitis (bone infection) and pericarditis (infection of the sac covering the heart) are less common forms of invasive disease.

Otitis media and acute bronchitis due to H. influenzae are generally caused by nontypeable strains. Hib strains account for only 5%–10% of H. influenzae causing otitis media.

Non-type b encapsulated strains can cause invasive disease similar to type b infections. Nontypeable (unencapsulated) strains may cause invasive disease but are generally less virulent than encapsulated strains. Nontypeable strains are rare causes of serious infection among children but are a common cause of ear infections in children and bronchitis in adults.

Laboratory Diagnosis

A Gram stain of an infected body fluid may demonstrate small gram-negative coccobacilli suggestive of invasive Haemophilus disease. CSF, blood, pleural fluid, joint fluid and middle ear aspirates should be cultured on appropriate media. A positive culture for H. influenzae (Hi) establishes the diagnosis.

All isolates of H. influenzae should be serotyped. This is an extremely important laboratory procedure that should be performed on every isolate of H. influenzae, especially those obtained from children younger than 15 years of age. Two tests are available for serotyping Hi isolates: slide agglu­tination and serotype-specific real-time PCR. These tests determine whether an isolate is type b, which is the only type that is potentially vaccine preventable. Serotyping is usually done by either a state health department laboratory or a reference laboratory. State health departments with questions about serotyping should contact the CDC Meningitis and Vaccine-Preventable Diseases Branch Laboratory at 404-639-3158.

Detection of antigen or DNA may be used as an adjunct to culture, particularly in diagnosing H. influenzae infection in patients who have been partially treated with antimicrobial agents, in which case the organism may not be viable on culture. Slide agglutination is used to detect Hib capsular polysaccharide antigen in CSF, but a negative test does not exclude the diagnosis, and false-positive tests have been reported. Antigen testing of serum and urine is not recommended because of false positives. Furthermore, no slide agglutination assay is available to identify non-b Hi serotypes.

Serotype-specific real-time PCR is currently available to detect the specific target gene of eachH. influenzae serotype and can be used for detection of H. influenzae in blood, CSF, or other clinical specimens.

Medical Management

Hospitalization is generally required for invasive Hib disease. Antimicrobial therapy with an effective third-generation cephalosporin (cefotaxime or ceftriaxone), or chloramphenicol in combination with ampicillin should be begun immediately. The treatment course is usually 10 days. Ampicillin-resistant strains of Hib are now common throughout the United States. Children with life-threatening illness in which Hib may be the etiologic agent should not receive ampicillin alone as initial empiric therapy.

Epidemiology

Occurrence
Hib disease occurs worldwide.

Reservoir
Humans (asymptomatic carriers) are the only known reservoir. Hib does not survive in the environment on inanimate surfaces.

Transmission
The primary mode of Hib transmission is presumably by respiratory droplet spread, although firm evidence for this mechanism is lacking. Neonates can acquire infection by aspiration of amniotic fluid or contact with genital tract secretions during delivery.

Temporal Pattern
Several studies in the prevaccine era described a bimodal seasonal pattern in the United States, with one peak during September through December and a second peak during March through May. The reason for this bimodal pattern is not known.

Communicability
The contagious potential of invasive Hib disease is considered to be limited. However, certain circumstances, particularly close contact with a case-patient (e.g., household, child care, or institutional setting) can lead to outbreaks or direct secondary transmission of the disease.

Haemophilus influenzae : Clinical Features, Laboratory Diagnosis and Medical Management 2019-01-07T06:42:00-08:00 Rating: 4.5 Diposkan Oleh: David Maharoni