New Haemophilus influenzae pathogen may be emerging

SALT LAKE CITY — While Haemophilus influenzae type b (Hib) has been nearly eliminated as a major cause of serious disease in children, other serotypes, especially H. influenzae type a, may have acquired virulence traits and may be emerging as disease-causing pathogens.

A recent report in Pediatrics described 5 cases of H. influenzae type a, 2 of which “were strikingly reminiscent of disease caused by Hib,” said the report. In 2 other cases, infections were similar to Hib infections, but different enough to suggest that 2 distinct clones of H. influenzae type a may be circulating concurrently.

Case reports

In December 1998, a previously healthy 6-month-old girl presented to her doctor with lethargy, irritability and poor oral intake for 1 day, following episodes of altered consciousness and peripheral cyanosis. Upon admission to the hospital, her blood pressure was 40/20 mm Hg, pulse was 210 beats/min and her tympanic temperature was 39.4° C; there was purpura present on the nose, ear and legs, and petechiae on her face and trunk. Medical history revealed that she had received 3 doses of Hib conjugate vaccine.

The infant required intubation and mechanical ventilation with fluid support and was given intravenous cefotaxime (Claforan, Aventis), vancomycin and gentamicin. Laboratory testing revealed a white blood count (WBC) of 4,900/mm³, hematocrit 27.5% and a platelet count of 35,000/mm³. Cultures of the cerebrospinal fluid (CSF) and blood grew H. influenzae type a.

Treatment was further complicated by renal failure, purpura fulminans and subdural empyema; soft-tissue necrosis ultimately required the amputation of 2 toes, said the report.

The second patient, a 1-year-old girl, was admitted to the hospital in June 1999 with a 3-day history of vomiting, fever, irritability, diarrhea and seizures. The infant also had received 3 doses of Hib conjugate vaccine.

An initial exam of the 1-year-old showed that she was toxic appearing and minimally responsive. CSF was cloudy; the WBC was 1,660/mm³, red blood count 70/mm³, glucose 34 mg/dl and protein levels were 300 mg/ml. Cultures of the CSF and blood grew H. influenzae serotype a.

The second patient’s hospitalization was complicated by aseptic necrosis of the right femoral head and prolonged fever. Following 4 weeks of treatment with cefotaxime, she was discharged with evidence of reduced hearing and regression of fine and gross motor skills.

Epidemiology and infectivity

There had been no reported cases of invasive disease caused by H. influenzae type a in Utah between 1991 and 1998. However, between November 1998 and October 1999, there were 4 reported cases in children ranging from 6-13 months of age. All cases displayed bacteremia and meningitis, and 3 had prolonged fever, subdural empyema and aseptic necrosis of the hip – common markers for Hib. A review of laboratory records for the same period revealed a fifth patient who grew H. influenzae type a on pure culture.

Previously reported cases of H. influenzae type a occurred exclusively in patients older than 5 years.

Serotype a strains isolated from 3 of the patients demonstrated the IS1016-bexA deletion that has been described in invasive type a and type b strains. DNA sequencing, assisted by primers specific to IS1016 and bexA, amplified a 362 base-pair sequence that confirmed the finding.

Three H. influenzae type a strains with the IS1016-bexA deletion may have recombined with a circulating Hib strain because Haemophilus strains are transformable. Most virulent Hib strains contain a 1,198 base-pair sequence that removes a portion of IS1016 and bexA, promoting gene amplification, resulting in an increase in the production of capsules and increasing the virulence of Hib. The areas where IS1016 and bexA are usually found are surrounded by transposable elements, further suggesting the possibility of a recombinant H. influenzae type a strain.

The 2 other patients lacked the IS1016-bexA deletion, but nevertheless suffered invasive disease due to H. influenzae type a, the report stated.

For more information:

• Adderson E, Byington C, Spencer L, et al. Invasive serotype a Haemophilus influenzae infections with a virulence genotype resembling Haemophilus influenzae type b: emerging pathogen in the vaccine era? Pediatrics. 2001;108(1):e18.