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

D W Scheifele, R S Daum, V P Syriopoulou, G R Siber, A L Smith
1979 Infection and Immunity  
Rapid diagnosis of Haemophilus influenza type b meningitis is possible using immunological tests for capsular antigen (polyribophosphate, PRP), such as countercurrent immunoelectrophoresis (CIE) and latex particle agglutination (LPA). We compared two tests in monkeys with evolving, serially quantitated H. influenza 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,
more » ... 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 h after onset; range, 4 to 36 h) than did CIE (mean, 45 h; range, 4 to 168 h) (P < 0.01). A positive LPA test required 2100 bacteria per ml of blood, whereas CIE required 21,000/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). We conclude that the LPA method permits earlier diagnosis of H. influenzae type b infection in part because of its greater sensitivity. The recent development of rapid immunological tests for bacterial capsular antigens has added an important new dimension to diagnostic microbiology (7, 14) . The most commonly used methods are countercurrent immunoelectrophoresis (CIE) (9, 10, 13, 19) and antibody-coated latex particle agglutination (LPA) (14, 15, 22) ; both are rapid, simple, and inexpensive. The frequency with which capsular antigen has been detected in clinical trials has varied considerably, depending upon the bacterial species, methods and antiserum used, and site of infection. It has been difficult to describe test sensitivity in functional terms, i.e., the density or duration of infection required to produce a positive test. Such characterization is possible using animal models of infection, such as infant monkeys infected with Haemophilus influenza type t Present address: Infectious Diseases Laboratory, Children's Hospital, Vancouver, British Columbia, Canada V5X-1X2. t Present address:
doi:10.1128/iai.26.3.827-831.1979 fatcat:z3mdl4acijerbjoxksiuym4yk4