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Differential effects of infection with a Babesia-like piroplasm, WA1, in inbred mice
M H Moro1, C S David, J M Magera
1Department of Experimental Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Abstract:
A newly identified intraerythrocytic Babesia-like organism, WA1, and its relatives were recently shown to be infectious for humans in the western United States. The purpose of the present study was to determine the susceptibilities of selected mouse genotypes to WA1 infection in an attempt to develop a murine model of the human disease. Several mouse strains were inoculated intraperitoneally with various passages of WA1-parasitized erythrocytes. Parasitemia was evaluated by blood smears and by PCR with blood samples collected at various intervals after inoculation. Hematologic parameters were monitored in blood samples at all intervals. C57BL/6 and C57BL/10 mice exhibited mortality rates of <10%. BALB/cJ, CBAJ, and 129/J mice had higher peak parasitemias than did C57BL mice, with mortality rates of 40, 50, and 50%, respectively. A/J, AKR/N, C3H, and DBA/1J mice also had higher peak parasitemia and mortality rates (>95%). An F1 cross of C57BL/6 (resistant) and C3H.RKK (susceptible) mice had a mortality rate similar to that of the resistant parental strain. Histopathology of BALB/cJ and C3H mice at 9 and 14 days after inoculation revealed erythrophagocytosis and deposition of an iron-negative pigment in multiple organs. Morbidly ill C3H mice at 14 days had severe pulmonary edema, hemoglobinuria, and glomerulonephritis.
Insights
Researchers investigated mouse susceptibility to the WA1 Babesia-like organism to model human disease. Susceptible mouse strains like A/J and C3H showed high mortality, aiding in understanding disease progression.
Area of Science:
- Veterinary Parasitology
- Infectious Diseases
- Mammalian Genetics
Background:
- A novel intraerythrocytic Babesia-like organism, designated WA1, has been identified as infectious to humans in the western United States.
- The development of a reliable animal model is crucial for studying human diseases caused by emerging pathogens.
Purpose of the Study:
- To establish a murine model for human WA1 infection by assessing the susceptibility of various mouse genotypes.
- To characterize the pathological outcomes and mortality rates associated with WA1 infection across different mouse strains.
Main Methods:
- Multiple mouse strains were inoculated intraperitoneally with different passages of WA1-infected erythrocytes.
- Parasitemia was quantified using peripheral blood smears and PCR analysis at regular intervals post-inoculation.
- Hematological parameters and histopathological changes, including organ pathology and pigment deposition, were evaluated.
Main Results:
- Significant variations in susceptibility and mortality were observed among mouse strains.
- Highly susceptible strains (A/J, AKR/N, C3H, DBA/1J) exhibited >95% mortality, while resistant strains (C57BL/6, C57BL/10) had <10% mortality.
- Pathological findings in susceptible mice included erythrophagocytosis, pigment deposition, pulmonary edema, hemoglobinuria, and glomerulonephritis.
Conclusions:
- Mouse genotype significantly influences susceptibility and outcome of WA1 infection, enabling the development of a relevant murine model.
- The observed pathology in susceptible mice mimics key aspects of severe human babesiosis.
- This model provides a valuable tool for investigating WA1 pathogenesis and evaluating potential therapeutic interventions.