Characterization of chlamydial genital infection resulting from sexual transmission from male to female guinea pigs and determination of infectious dose

Abstract

A major problem in the study of chlamydial genital infections in animal models has been the use of varied doses of chlamydiae for infection in different laboratories. It is clearly desirable to use a dose which approximates that of natural sexual infection, but that dose to date has not been determined because of the inability of researchers to quantify chlamydiae in semen. Fortunately, sexual transmission of chlamydiae has been described for the guinea pig model of infection with the chlamydial agent of guinea pig inclusion conjunctivitis (GPIC). In this study, we undertook to determine the approximate infection dose in actual sexual transmission by comparing the kinetics of infection in female guinea pigs acquired via sexual contact to those of genital infections induced artificially with known quantities of chlamydiae. Groups of guinea pigs were infected intravaginally with 10(4), 10(3), 10(2), and 10(1) inclusion-forming units (IFU) of GPIC, and the kinetics of the infection were determined. Infection with 10(2) IFU produced infections with lower peak levels than those in animals receiving 10(4) or 10(3) IFU. Seventy percent of animals receiving 10(2) IFU became infected, while 100 and 79% of animals receiving 10(4) and 10(3) IFU, respectively, became infected. Animals receiving 10(2) IFU also had a longer incubation period. Of 19 animals that mated with infected males, 63.2% became infected, with an infection course which was not significantly different than that of the 10(2)-IFU-infected group. The data suggest that female guinea pigs received approximately 10(2) IFU by sexual transmission. Of interest was the observation that the guinea pigs infected by sexual transmission shed organisms for a significantly shorter time period than that of any group that was artificially infected. This result suggests that there may be factors associated with semen which passively transfer antimicrobial activity to the female or enhance the innate host response in the female. Immunization of females with an inactivated vaccine was also found to elicit a protective immune response against sexual challenge, demonstrating that the model can be used in the evaluation of possible vaccine candidates and/or methodologies. There is currently no other animal model available for any sexually transmitted disease in which the disease or the ability to prevent the disease may be studied in animals infected by the natural means.

FIG. 1.

Kinetics of genital infection in female guinea pigs infected intravaginally with various doses of chlamydiae or by sexual transmission. In order to facilitate statistical comparison of infection curves for different animals and different groups, the curves were normalized by reporting the data in relation to when infection was first detected; i.e., the first day of positive isolation was arbitrarily called day 3 of infection. The numbers in parentheses are the numbers of animals which became infected in each group. The average numbers of IFU are plotted. Animals that did not become infected were not included.

FIG. 2.

Effect of immunization with UV-inactivated elementary bodies upon artificial-challenge infection with various doses of chlamydiae in comparison to the effect after sexual transmission. The numbers in parentheses are the total numbers of guinea pigs per group. The P value represents the level of significance according to a chi-square analysis. The absence of a P value indicates that the differences between the groups were not significant.

FIG. 3.

Course of infection in immunized guinea pigs challenged with 10³ IFU. The numbers in parentheses are the total numbers of guinea pigs per group. Only guinea pigs which were isolation positive are included in this figure.

FIG. 4.

Course of infection in immunized guinea pigs challenged by sexual transmission. The numbers in parentheses are the total numbers of guinea pigs per group. Only results for guinea pigs which were isolation positive are included in this figure.