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Men are more than 7 times more likely to develop amebic liver abscess or amebic dysentery caused by Entamoeba histolytica than women. Because the complement system could play a key role in controlling amebiasis, we determined whether serum from men and women differ in the ability to kill amebic trophozoites. We found that serum from women was significantly more effective in killing E. histolytica trophozoites than serum from men, and this killing was complement dependent. Our results provide a possible explanation for the differential susceptibility of men and women to amebic liver abscess and amebic colitis.

Serology is a critical component in the diagnosis of amebic liver abscess. However, in areas endemic for amebiasis there is a high background level of seropositivity for amebiasis (owing to previous infection with Entamoeba histolytica), which may complicate the interpretation of a positive serologic test result. Recently, we reported that serologic tests based on recombinant E. histolytica antigens might offer improved diagnosis of current invasive amebiasis because they apparently differentiated active infection from past exposure to the parasite. To confirm this finding, we have performed a longitudinal study on 20 patients with amebic liver abscess by examining their seroreactivity over time with recombinant versions of two major E. histolytica proteins, the serine rich E. histolytica protein (SREHP), and the 170-kD subunit of the galactose-specific adhesin. We found that more than 50% of the patients examined had become seronegative by one or both recombinant tests within 180 days of their diagnosis of amebic liver abscess. In the case of the recombinant SREHP-based tests, 12 patients had become seronegative 90 days after presentation. In contrast, all patients remained seropositive by a standard conventional test, an indirect hemagglutination test, at more than six months after presentation. Our study shows that patients lose seroreactivity with the recombinant SREHP or 170-kD antigen-based tests more rapidly than with a conventional serologic test; this may make them useful for the serologic diagnosis of amebiasis in endemic areas.

The serine-rich Entamoeba histolytica protein (SREHP) has been shown to be a protective antigen in animal models of amebic liver abscess when delivered by either parenteral or oral routes of immunization, and antibodies to SREHP can prevent amebic liver abscess in severe combined immunodeficient mice. To identify B cell epitopes of the SREHP molecule that could serve as the basis for a peptide-based vaccine, we synthesized overlapping peptides spanning the amino acid sequence of SREHP, and looked at the reactivity of serum samples from five individuals with amebic liver abscess to the overlapping peptides. We found that most of the epitopes recognized by serum samples from patients with amebic liver abscess map to the hydrophilic dodecapeptide or octapeptide repeats of SREHP, but there was no universal epitope recognized by all five serum samples. In addition, we show that synthetic peptides that include the epitopes of SREHP recognized in the mapping study are immunogenic in animals and can generate antibodies that recognize SREHP.

We have used serum from patients with amebic liver abscess to investigate the role of antibody in the prevention of invasive amebiasis using the severe combined immunodeficient (SCID) mouse model of Entamoeba histolytica infection. The SCID mice were passively immunized with serum or purified antibody from patients with amebic liver abscess 24 hr prior to the direct intrahepatic challenge with 10(6) virulent E. histolytica trophozoites. This treatment reduced the mean abscess size in these animals from 24.5% to 3.5% (P < 0.0001). These results demonstrate that human anti-amebic antibodies are capable of exerting a protective effect in an animal model of amebic liver abscess formation.