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Experimental infection by Haemophilus influenzae type b in inbred mice
S Sifontes1, J F Infante, V Capo
1Center of Chemical Bioactives, Las Villas, Cuba.
Abstract:
The epidemiological situation of bacterial meningitis is increasing dramatically. There is no doubt that the lack of proper animal models has hampered the achievement of effective prophylactic and therapeutic means. We report the characterization of the experimental disease caused by Haemophilus influenzae type b (Hib) in mice, taking into account its importance as an etiological agent of such a type of meningitis. The high resistance of C57BL/6, CBA/ J and BALB/cJ mice to Hib infection was proven. LD50 of Hib using trypsin or iron dextran as virulence enhancement factors (VEF), both being similar and more than 1000 times lower than that without any VEF, were determined. Lesions of CNS compatible with meningitis were found in about one third of specimens. Hair bristling, conjunctivitis, diarrhea, depression and prostration were the most characteristic symptoms. The proportion of animals which die is highest on the first day, lower on the second and almost zero after 48 h of infection. Water and food intake was higher in control than in infected animals; nevertheless, there were no differences in body weight increase among the mice after 5 days post-infection. Microorganisms were isolated from CSF and blood after 6 h of infection and positive results remained according to the size of the inoculum. Despite the acuteness of the experimental disease, antibiotic treatment with internationally recommended drugs was shown to be effective. Similar results were achieved when hyperimmune serum vs. Hib was applied.
Insights
Developing an effective Haemophilus influenzae type b (Hib) mouse model is crucial for combating rising bacterial meningitis. This study characterizes Hib infection in mice, demonstrating treatment efficacy.
Area of Science:
- Infectious Diseases
- Microbiology
- Animal Models
Background:
- Bacterial meningitis, particularly Haemophilus influenzae type b (Hib), presents a growing global health challenge.
- Effective prophylactic and therapeutic strategies are hindered by the lack of suitable animal models for studying Hib meningitis.
- Understanding Hib pathogenesis in a relevant model is essential for developing new treatments.
Purpose of the Study:
- To characterize an experimental model of bacterial meningitis caused by Haemophilus influenzae type b (Hib) in mice.
- To evaluate the efficacy of antibiotic treatment and hyperimmune serum against Hib infection in this model.
Main Methods:
- Infection of C57BL/6, CBA/J, and BALB/cJ mice with Haemophilus influenzae type b (Hib).
- Determination of lethal dose 50 (LD50) with and without virulence enhancement factors (VEF) like trypsin or iron dextran.
- Clinical observation, necropsy, and microbiological analysis of cerebrospinal fluid (CSF) and blood.
Main Results:
- C57BL/6, CBA/J, and BALB/cJ mice exhibited high resistance to Hib infection.
- Virulence enhancement factors significantly reduced LD50, enabling model establishment.
- Clinical signs included hair bristling, conjunctivitis, diarrhea, depression, and prostration, with mortality peaking within 48 hours.
- Hib was isolated from CSF and blood post-infection.
- Antibiotic treatment and hyperimmune serum demonstrated effectiveness against experimental Hib meningitis.
Conclusions:
- The characterized mouse model provides a valuable tool for studying Haemophilus influenzae type b meningitis.
- The study confirms the effectiveness of standard antibiotic treatments and hyperimmune serum against Hib infection.
- This research paves the way for further development of interventions against bacterial meningitis.