Comparison of two antigen detection techniques in a primate model of Haemophilus influenzae type b infection

Abstract

Rapid diagnosis of Haemophilus influenzae type b meningitis is possible using immunological tests for capsular antigen (polyribophosphate, PRP), such as countercurrent immunoelectrophoresis (CIE) and latex particle agglutination (LPA). The authors compared 2 tests in monkeys with evolving, serially quantitated H. influenzae type b bacteremia (n = 23) and meningitis (n = 21). In vitro, the LPA test was sensitive to 0.5 ng of PRP/ml of saline, and the CIE test was sensitive to 1.0 ng/ml; in serum, however, CIE detected 5.0 ng of PRP/ml, whereas the sensitivity of LPA was unchanged. LPA detected PRP earlier in the course of bacteremia (mean, 12 hr after onset; range, 4 to 36 hr) than did CIE (mean, 45 hr; range, 4 to 168 hr) (P < 0.01). A positive LPA test required ≥ 100 bacteria per ml of blood, whereas CIE required ≥ 1,000/ml. PRP accumulated with continuing blood stream infection, aiding detection of low-grade bacteremia. LPA detected antigen in cerebrospinal fluid (CSF) earlier in the course of meningitis and at a lower bacteria density than did CIE. Both methods detected antigen reliably with ≥ 1,000 bacteria per ml of CSF. A close correlation existed between CSF concentrations of capsular antigen and bacteria (r = 0.90, P < 0.001). The authors conclude that the LPA method permits earlier diagnosis of H. influenzae type b infection in part because of its greater sensitivity.