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Other Haemophilus Species and Aggregatibacter Species
Of the Haemophilus species, H. influenzae causes by far the most human disease. Several other members of this genus, however, cause clinical illness. These include H. influenzae biogroup aegyptius , H. ducreyi, H. parainfluenzae, H. pittmaniae, H. sputorum, H. haemolyticus, H. parahaemolyticus, and the ill-defined species H. paraphrohaemolyticus . Three former Haemophilus species known to cause human disease have been reclassified into the genus Aggregatibacter. The former H. aphrophilus and H. paraphrophilus are now the single species Aggregatibacter aphrophilus , and H. segnis now is Aggregatibacter segnis . , Reclassification is based on phenotypic properties and molecular analyses (16S rRNA analysis and DNA-DNA hybridization studies). The Aggregatibacter appellation refers to a members’ “rod-shaped bacteria that aggregate with others” and aptly describes their tendency to adhere to test tube walls (see also Chapter 181 ).
The genus Haemophilus is classified in the family Pasteurellaceae. Members of this genus are small, pleomorphic, facultatively anaerobic, gram-negative coccobacilli. Haemophilus species can be distinguished based on the need for X factor (hemin) or V factor (nicotinamide) for in vitro growth, their ability to lyse horse erythrocytes, and production of catalase ( Table 173.1 ). Except for H. ducreyi , all Haemophilus species ferment glucose. H. ducreyi grows optimally at 33°C, whereas other species grow optimally at 35°C–37°C. In general, Haemophilus species grow best in a humid environment enriched with 5%–10% carbon dioxide. Both A. aphrophilus and A. segnis are small gram-negative bacilli that do not require X factor, have variable dependence on V factor, and ferment glucose.
TABLE 173.1
Some Differential Characteristics of Haemophilus Species
| Growth Factor Requirement | Hemolysis | Catalase | CO 2 Enhances Growth | ||
|---|---|---|---|---|---|
| X | V | ||||
| Haemophilus SPP | |||||
| H. influenzae | + | + | − | + | − |
| H. aegyptius | + | + | − | + | − |
| H. parainfluenzae | − | + | − | D | − |
| H. ducreyi | + | − | − | − | + |
| H. haemolyticus | + | + | + | + | − |
| H. parahaemolyticus | − | + | + | + | − |
| Aggregatibacter SPP | |||||
| A. aphrophilus a | − | D | − | − | + |
| A. segnis b | − | + | − | D | D |
D, differences are encountered; V, nicotinamide; X, hemin.
Haemophilus Influenzae Biogroup Aegyptius
The Koch-Weeks bacillus, originally observed in Egyptian children with conjunctivitis by Koch in 1883 and further characterized by Weeks in 1886, was designated Haemophilus aegyptius in 1950. Controversy over whether H. aegyptius merited classification as a separate species from H. influenzae, already extant at that time, persisted. Although there are phenotypic and pathogenetic differences between H. aegyptius and H. influenzae , no single characteristic unequivocally distinguishes the two organisms, and DNA hybridization studies indicate high relatedness. , Although it has been proposed to assign as a practical the designation of H. aegyptius as a separate species, continued uncertainty has led the Kochs-Weeks bacillus to continue to be considered as a distinct subgroup of H. influenzae biotype III, maintaining the appellation H. influenzae biogroup aegyptius. ,
In the US, H. influenzae biogroup aegyptius has been a cause of seasonal acute conjunctivitis in southern states during warmer months. Studies performed in Texas and Georgia found this organism to be the leading cause of acute purulent conjunctivitis among children in the 1930s to 1950s. Some studies have suggested that the eye gnat ( Hippelates pusio ) might serve as a transmission vector (hence the lay term, “gnat sore eyes”), although the gnat’s role has not been proved.
H. influenzae biogroup aegyptius also can cause severe infection, Brazilian purpuric fever (BPF). The first known cases of BPF occurred in 1984 in rural Brazil when 10 children died from a rapidly progressive illness characterized by fever, abdominal pain, vomiting, purpura, and vascular collapse. Epidemiologic investigations noted a strong association with the recent history of purulent conjunctivitis. When another outbreak occurred in Brazil in 1986, the etiology of BPF was established. H. influenzae biogroup aegyptius was isolated from 9 blood cultures and 1 hemorrhagic cerebrospinal fluid culture from 10 clinically affected children.
The age range of reported cases of BPF is 3 months to 10 years, with the peak incidence between 1 and 4 years. About 90% of patients have a recent history of conjunctivitis, and about 70% of identified cases have been fatal. , In Brazil, epidemic and sporadic cases have been reported from the states of São Paulo, Paraná, and Mato Grosso. Single cases of BPF with bloodstream infection due to H. influenzae biogroup aegyptius have been reported from Australia and the US. Molecular studies demonstrated that isolates were unique clones. , Extensive analyses, including examination of protein profiles, ribotyping, plasmid restriction patterns, seroagglutination, and multilocus sequencing, indicate that the isolates causing BPF in Brazil belong to a single clone that is distinct from other strains of H. influenzae biogroup aegyptius in Brazil and other countries.
Interestingly, there were no reports of BPF from the mid-1990s until 2007, when 7 suspected cases of BPF occurred in children in Anajas, Brazil, including 5 deaths within 24 hours. Speculation about the apparent “disappearance” of this illness includes the natural history of a bacterial species, under-recognition or underreporting of the disease (given clinical similarity to meningococcemia), and potential rapid acquisition of immunity in a previously nonimmune population. No explanation completely accounts for the unusual disease pattern, and investigations into the pathogenesis of BPF continue.
Potential virulence factors of BPF strains include lipo-oligosaccharides, capsular polysaccharides, pilus proteins, immunoglobulin A proteases, membrane-associated proteins, and extracellular proteins BPF strains express both pilus and nonpilus adhesins that presumably facilitate mucosal colonization. Compared with non-BPF strains, BPF strains resist lysis after incubation with normal adult human serum and are cytotoxic for microvascular endothelial cells. Additionally, BPF strains produce an extracellular hemagglutinating protein purported to be responsible for the hemorrhagic manifestations of BPF. Horizontal transfer of virulent genes from Neisseria meningitidis to H. influenzae recently has been described, and this type of genetic acquisition also may play a role in the pathogenic potential of H. influenzae biogroup aegyptius. Whole-genome sequencing has identified distinct multilocus sequence typing (MLST) profiles for the BPF-associated strains (ST65) and a strain causing only conjunctivitis (ST72). These distinctions assist in defining epidemiology and virulence factors.
Early systemic antibiotic therapy can improve clinical outcomes in patients with BPF. Appropriate therapeutic options include ampicillin, chloramphenicol, cefotaxime, or ceftriaxone; most isolates of the BPF clone are resistant to trimethoprim-sulfamethoxazole. In a randomized trial of children with H. influenzae biogroup aegyptius conjunctivitis, systemic therapy with rifampin (20 mg/kg orally once daily for 4 days) eradicated the organism in all 12 treated children compared with only 7 of 16 children treated with topical chloramphenicol 0.5%. This finding has led to speculation that oral rifampin might prevent the development of BPF.
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