AUTHOR=Thomas Richard , Davies Carwyn , Nunez Alejandro , Hibbs Stephen , Eastaugh Lin , Harding Sarah , Jordan Janine , Barnes Kay , Oyston Petra , Eley Steve 

TITLE=Particle-size dependent effects in the Balb/c murine model of inhalational melioidosis

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 2 - 2012

YEAR=2012

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2012.00101

DOI=10.3389/fcimb.2012.00101

ISSN=2235-2988

ABSTRACT=Deposition of Burkholderia pseudomallei within either the lungs or nasal passages of the Balb/c murine model resulted in different infection kinetics. The infection resulting from the inhalation of B. pseudomallei within a 12 um particle aerosol was prolonged compared to a 1 um particle aerosol with a mean time-to-death (MTD) of 73.8 ± 11.3 h and 174.7 ± 14.9 h respectively. Inhalation of B. pseudomallei within 1 um or 12 um particle aerosols resulted in a median lethal dose (MLD) of 4 and 12 cfu respectively. The 12 mm particle inhalational infection was characterised by involvement of the respiratory epithelium and inflammation of the neurological path leading from the olfactory epithelium to the olfactory bulb (100%), culminating in abscessation of the brain (33%). Initial involvement of the upper respiratory tract lymphoid tissues (nasal-associated lymphoid tissue and cervical lymph nodes) was observed in both the 1 and 12 um particle inhalational infections (80-85%). Necrotising alveolitis and bronchiolitis were evident in both inhalational infections however lung pathology was greater after inhalation of the 1 mm particle aerosol with pronounced involvement of the mediastinal lymph node (50%). Terminal disease was characterised by bacteraemia in both inhalational infections with dissemination to the spleen, liver, kidneys and thymus. Treatment with co-trimoxazole was more effective than treatment with doxycycline irrespective of the size of the particles inhaled. Doxycycline was more effective against the 12 um particle inhalational infection as evidenced by increased time to death. However, both treatment regimes exhibited significant relapse when therapy was discontinued with massive enlargement and abscessation of the lungs, spleen and cervical lymph nodes observed.