Rapid diagnosis of
Lassa fever is desirable for the timely therapeutic intervention and implementation of strict quarantine procedures both in West Africa field hospitals where the disease is endemic and at international crossroads. An
enzyme-linked
immunosorbent assay (ELISA) to measure Lassa virus
antigens in viremic sera was developed in which experimentally infected monkeys were used as a model for the human disease. In this test, Lassa virus
antigens in test sera were captured in wells of microtiter plates by monkey anti-Lassa virus
immunoglobulin. Guinea pig anti-Lassa virus
immunoglobulin was then added, and binding of specific
immunoglobulin was quantitated by the addition of rabbit anti-guinea pig
immunoglobulin followed by
alkaline phosphatase-labeled anti-rabbit
immunoglobulin. This test detected
viremia titers as low as 2.1 log10 PFU/ml in experimentally infected monkey sera, a titer often exceeded in patients with
Lassa fever. Inactivation of infectious virus by
beta-propiolactone or gamma-irradiation did not diminish reactivity.
Antigen-ELISA concentrations increased with infectivity for the first 10 days after
infection but then declined while infectivity titers remained high, suggesting that the presence of humoral antibody in viremic sera diminishes the sensitivity of the
antigen ELISA. Lassa virus-specific
immunoglobulin M (
IgM) titers measured in an
IgM capture ELISA were detectable within 10 days of
infection and peaked after 36 days but remained detectable for 1.5 years. The Lassa virus-specific
IgG ELISA response was slightly delayed, peaking on day 73 but declining only slightly thereafter. These studies in a realistic primate model suggest that the
antigen detection ELISA or the
IgM capture ELISA described, in which
beta-propiolactone-inactivated sera are used, should be useful for the rapid diagnosis of human
Lassa fever.