Haemophilus Flashcards
Haemophilus
- Haemophilus are among the smallest of bacteria. The curved ends of the short (1.0 to 1.5 μm) bacilli make many appear nearly round; hence the term coccobacilli.
- The cell wall has a structure similar to that of other gram-negative bacteria. The most virulent strains of H influenzae have a polysaccharide capsule, but other species of Haemophilus are not encapsulated.
- The cultivation of Haemophilus species requires the use of culture media enriched with blood or blood products (Greek haema, blood, and philos, loving) for optimal growth. This requirement is attributable to the need for exogenous hematin (X factor) and/or nicotinamide adenine dinucleotide (V factor). These growth factors are both present in erythrocytes.
- In culture media, optimal concentrations are not available unless the red blood cells are lysed by gentle heat (chocolate agar) or added separately as a supplement. Although erythrocytes are the only convenient source of hematin, sufficient amounts of NAD may be provided by some other bacteria and yeasts. This is responsible for the “satellite phenomenon,” in which colonies of Haemophilus have been observed to grow only in the vicinity of a colony of Staphylococcus aureus.
- The several species of Haemophilus are defined by their requirement for hematin and/or NAD, CO2 dependence, and other cultural characteristics. Species of Haemophilus other than H influenzae have the same general biology described below for the nonencapsulated strains of H influenzae.
H. influenzae Organism
•Haemophilus that meet the species requirements for H influenzae may or may not have a capsule.
- Those that do are divided into six serotypes (a to f) based on the capsular polysaccharide antigen. The type b capsule is made up of a polymer of ribose, ribitol, and phosphate, called polyribitol phosphate (PRP).
- These surface polysaccharides are strongly associated with virulence, particularly H influenzae type b (Hib).
- The surface of H influenzae includes pili and an outer membrane similar to the structure of other Gram-negative bacteria.
- The outer membrane includes proteins (HMW1, HMW2) and lipooligosaccharides (LOS).
- The nonencapsulated, and thus nontypable, H influenzae (NTHi) can be classified by a number of typing schemes based on outer membrane proteins and other factors.
- H influenzae produces no known exotoxins.
H. influenzae Epidemiology
- H influenzae is a strictly human pathogen and has no known animal or environmental sources. It can be found in the nasopharyngeal microbiota of 20% to 80% of healthy persons, depending on age, season, and other factors.
- Spread is by respiratory droplets, as with streptococci.
H. influenzae Pathogenesis
- For unknown reasons, H influenzae strains in the microbiota of the nasopharynx occasionally invade deeper tissues.
- Bacteremia then leads to spread to the central nervous system and metastatic infections at distant sites such as bones and joints.
- These events seem to take place within a short period (less than 3 days) after an encounter with a new virulent strain. Systemic spread is typical only for capsulated H influenzae strains, and over 90% of invasive strains are type b
- Attachment to respiratory epithelial cells is mediated by pili and outer membrane proteins.
- H. influenzae can invade between the cells of the respiratory epithelium, and for a time reside between, and below, them.
- Once past the mucosal barrier, the antiphagocytic capsule confers resistance to C3b deposition in the same manner as it does with other encapsulated bacteria.
- LOS may provide an antiphagocytic effect by binding host components like sialic acid.
H. influenzae Localized Disease
•The NTHi produce disease under circumstances in which they are entrapped at a luminal site adjacent to the resident respiratory microbiota such as the middle ear, sinuses, or bronchi.
-This is usually associated with some compromise of normal clearing mechanisms, caused by a viral infection or structural damage.
- Consistent with their relative prevalence in the respiratory tract, NTHi account for more than 90% of localized HD influenzae disease, particularly otitis media, sinusitis, and exacerbations of chronic bronchitis.
- NTHi attach to bronchial epithelial cells and laminin using pili, OMPs and other proteins.
H. influenzae Immunity
- Immunity to Hib infections has long been associated with the presence of anti-PRP antibodies, which are bactericidal in the presence of complement.
- The infant is usually protected by passively acquired maternal antibody for the first few months of life.
- Thereafter, actively acquired antibody increases with age; it is present in the serum of most children by 10 years of age.
- The peak incidence of Hib infections in unimmunized populations occurs at 6 to 18 months of age, when serum antibody is least likely to be present.
- This inverse relationship between infection and serum antibody is similar to that for N meningitidis.
- The major difference is that substantial immune protection is provided by antibody directed against a single type (Hib) rather than the multiple immunotypes of other encapsulated bacteria such as N meningitidis and S pneumoniae.
•Thus, systemic H influenzae infections (meningitis, epiglottitis, cellulitis) have always been rare in adults.
H. influenzae Meningitis
- Hib meningitis follows the same pattern as other causes of acute purulent bacterial meningitis.
- Meningitis is often preceded by signs and symptoms of an upper respiratory infection, such as pharyngitis, sinusitis, or otitis media.
-Whether these represent a predisposing viral infection or early invasion by the organism is not known.
- Just as often, meningitis is preceded by vague malaise, lethargy, irritability, and fever.
- Mortality is 3% to 6% despite appropriate therapy, and roughly one third of all survivors have significant neurologic sequelae.
H. influenzae Acute Epiglottitis
•Acute epiglottitis is a dramatic infection in which the inflamed epiglottis and surrounding tissues obstruct the airway.
-Hib is one of a number of causes.
- The onset is sudden, with fever, sore throat, hoarseness, an often muffled cough, and rapid progression to severe prostration within 24 hours.
- Affected children have air hunger, inspiratory stridor, and retraction of the soft parts of the chest with each inspiration.
- The hallmark of the disease is an inflamed, swollen, cherry-red epiglottis that protrudes into the airway.
H. influenzae Cellulitis and Arthritis
- A tender, reddish-blue swelling in the cheek or periorbital areas is the usual presentation of Hib cellulitis.
- Fever and a moderately toxic state are usually present, and the infection may follow an upper respiratory infection or otitis media.
- Joint infection begins with fever, irritability, and local signs of inflammation, often in a single large joint.
- Bacteremia is often present in both cellulitis and arthritis.
H. influenzae Other Infections
- H influenzae is an important cause of conjunctivitis, otitis media, and acute and chronic sinusitis.
- It is also one of several common respiratory organisms that can cause and exacerbate chronic bronchitis.
- Most of these infections are caused by NTHi strains and remain localized without bacteremia.
- Disease may be acute or chronic, depending on the anatomic site and underlying pathology
H. influenzae Diagnosis
- The combination of clinical findings and a typical Gram smear is usually sufficient to make a presumptive diagnosis of Haemophilus infection.
- The diagnosis must be confirmed by isolation of the organism from the site of infection or from the blood.
- Blood cultures are particularly useful in systemic H influenzae infections because it is often difficult to obtain an adequate specimen directly from the site of infection other than the CSF.
H. influenzae Treatment
- All forms of H influenzae disease were effectively treated with ampicillin until the 1970s, when resistance in a pattern similar to that of Neisseria gonorrhoeae emerged.
- The major mechanism is production of a β-lactamase identical with that found in Escherichia coli.
-The frequency of βlactamase–producing strains varies between 5% and 50% in different geographic areas.
- Ampicillin-resistant strains due to alterations in the transpeptidase binding site also occur, but are less common.
- Current practice is to start empiric therapy with a third-generation cephalosporin (eg, ceftriaxone, cefotaxime), which can be changed to ampicillin if susceptibility tests indicate that the infecting strain is susceptible.
H. influenzae Prevention
• PRP–protein conjugate vaccines were recommended for universal immunization in children beginning at 2 months of age in 1990.
H. ducreyi
•H. ducreyi causes chancroid, a common cause of genital ulcer in Africa, Southeast Asia, India, and Latin America.
- The typical lesion is a tender papule on the genitalia that develops into a painful ulcer with sharp margins.
- The lack of induration around the ulcer has caused the primary lesion to be called “soft chancre” to distinguish it from the primary syphilitic chancre, which is typically indurated and painless.
•The presence of open genital sores due to H ducreyi greatly enhances the risk of transmission of HIV either by providing a portal of entry or by the recruitment of CD4+ cells to the site.
H. ducreyi Diagnosis
•The laboratory diagnosis of H ducreyi infection is difficult. Although the organism grows on chocolate agar, it does so slowly, and other organisms in the genital flora are apt to over-grow the plates. Incorporating antibiotics (usually vancomycin) in the agar overcomes this problem, but few laboratories have this medium on hand.
