ABSTRACT
RATIONALE: Streptococcus pneumoniae is the leading cause of community-acquired pneumonia and infectious death in adults worldwide. A non-human primate model is needed to study the molecular mechanisms that underlie the development of severe pneumonia, identify diagnostic tools, explore potential therapeutic targets, and test clinical interventions during pneumococcal pneumonia. OBJECTIVE: To develop a non-human primate model of pneumococcal pneumonia. METHODS: Seven adult baboons (Papio cynocephalus) were surgically tethered to a continuous monitoring system that recorded heart rate, temperature, and electrocardiography. Animals were inoculated with 109 colony-forming units of S. pneumoniae using bronchoscopy. Three baboons were rescued with intravenous ampicillin therapy. Pneumonia was diagnosed using lung ultrasonography and ex vivo confirmation by histopathology and immunodetection of pneumococcal capsule. Organ failure, using serum biomarkers and quantification of bacteremia, was assessed daily. RESULTS: Challenged animals developed signs and symptoms of pneumonia 4 days after infection. Infection was characterized by the presence of cough, tachypnea, dyspnea, tachycardia and fever. All animals developed leukocytosis and bacteremia 24 hours after infection. A severe inflammatory reaction was detected by elevation of serum cytokines, including Interleukin (IL)1Ra, IL-6, and IL-8, after infection. Lung ultrasonography precisely detected the lobes with pneumonia that were later confirmed by pathological analysis. Lung pathology positively correlated with disease severity. Antimicrobial therapy rapidly reversed symptomology and reduced serum cytokines. CONCLUSIONS: We have developed a novel animal model for severe pneumococcal pneumonia that mimics the clinical presentation, inflammatory response, and infection kinetics seen in humans. This is a novel model to test vaccines and treatments, measure biomarkers to diagnose pneumonia, and predict outcomes.
Subject(s)
Pneumonia, Pneumococcal/microbiology , Streptococcus pneumoniae , Animals , Biomarkers , Biopsy , Cytokines/metabolism , Disease Models, Animal , Hemodynamics , Inflammation Mediators/metabolism , Lung/diagnostic imaging , Lung/microbiology , Lung/pathology , Papio , Phenotype , Pneumonia, Pneumococcal/diagnosis , Primates , Severity of Illness Index , Streptococcus pneumoniae/classification , UltrasonographySubject(s)
Esophagitis/virology , Frail Elderly , Herpes Simplex/complications , Acyclovir/analogs & derivatives , Acyclovir/therapeutic use , Aged, 80 and over , Antiviral Agents/therapeutic use , Esophagitis/diagnosis , Esophagitis/drug therapy , Female , Herpes Simplex/diagnosis , Herpes Simplex/drug therapy , Humans , Valacyclovir , Valine/analogs & derivatives , Valine/therapeutic useABSTRACT
BACKGROUND: Symptoms of sleep apnea are markedly increased in children exposed to smoke from biomass fuels and are reduced by kitchen stoves that improve indoor biomass pollution. However, the impact of adherence to the use of improved stoves has not been critically examined. METHODS: Sleep-related symptom questionnaires were obtained from children <15 years of age in 56 families residing in the communities of Lliupapuquio, Andahuaylas province in Peru before and 2 years after installation of less-polluting Inkawasi cooking stoves. RESULTS: 82 children with lifetime exposures to indoor fuel pollution were included. When compared to those alternating between both types of stoves or those using traditional stoves only, those children who exclusively used Inkawasi cooking stoves showed significant improvements in sleep and respiratory related symptoms, but some minor albeit significant improvements occurred when both stoves were concomitantly used. CONCLUSIONS: Improvements in respiratory and sleep-related symptoms associated with elevated indoor biomass pollution occur only following implementation and exclusive utilization of improved kitchen stoves.
