Kinetics of Bartonella birtlesii infection in experimentally infected mice and pathogenic effect on reproductive functions

Abstract

The kinetics of infection and the pathogenic effects on the reproductive function of laboratory mice infected with Bartonella birtlesii recovered from an Apodemus species are described. B. birtlesii infection, as determined by bacteremia, occurred in BALB/c mice inoculated intravenously. Inoculation with a low-dose inoculum (1.5 x 10(3) CFU) induced bacteremia in only 75% of the mice compared to all of the mice inoculated with higher doses (> or =1.5 x 10(4)). Mice became bacteremic for at least 5 weeks (range, 5 to 8 weeks) with a peak ranging from 2 x 10(3) to 10(5) CFU/ml of blood. The bacteremia level was significantly higher in virgin females than in males but the duration of bacteremia was similar. In mice infected before pregnancy (n = 20), fetal loss was evaluated by enumerating resorption and fetal death on day 18 of gestation. The fetal death and resorption percentage of infected mice was 36.3% versus 14.5% for controls (P < 0.0001). Fetal suffering was evaluated by weighing viable fetuses. The weight of viable fetuses was significantly lower for infected mice than for uninfected mice (P < 0.0002). Transplacental transmission of Bartonella was demonstrated since 76% of the fetal resorptions tested was culture positive for B. birtlesii. The histopathological analysis of the placentas of infected mice showed vascular lesions in the maternal placenta, which could explain the reproductive disorders observed. BALB/c mice appeared to be a useful model for studying Bartonella infection. This study provides the first evidence of reproductive disorders in mice experimentally infected with a Bartonella strain originating from a wild rodent.

FIG. 1

B. birtlesii bacteremia kinetics in BALB/c mice after i.v. infection. Mice (n = 8 per group) were infected with 3 × 10⁴ (A) or 3 × 10⁵ (B) CFU of B. birtlesii. No bacteremia was detected at day 0. Data are expressed as the mean ± the SE for each dot.

FIG. 2

Kinetics of bacteremia in male and virgin female BALB/c mice after i.v. infection with 2.5 × 10⁵ CFU of B. birtlesii. No bacteremia was detected at day 0. Data (obtained from eight mice) are expressed as the mean ± the SE.

FIG. 3

Histopathological findings. The lesions are seen in the vessels of the endometrium. The muscular wall (M) is thickened, due to an eosinophilic deposit suggestive of fibrinoid necrosis. Neutrophils (N) are present in large numbers in the lumen (L) of the vessels and are seen infiltrating the vessel wall. Magnification, × 800.