Strain-specific virulence phenotypes of Streptococcus pneumoniae assessed using the Chinchilla laniger model of otitis media.

BACKGROUND: Streptococcus pneumoniae [Sp] infection is associated with local and systemic disease. Our current understanding of the differential contributions of genetic strain variation, serotype, and host response to disease phenotype is incomplete. Using the chinchilla model of otitis media [OM] we investigated the disease phenotype generated by the laboratory strain TIGR4 and each of thirteen clinical strains (BS68-75, BS290, BS291, BS293, BS436 and BS437); eleven of the thirteen strains have been genomically sequenced. METHODOLOGY/PRINCIPAL FINDINGS: For each strain 100 colony forming units were injected bilaterally into the tympanic bullae of 6 young adult chinchillas under general anesthesia. All animals were examined daily for local and systemic disease by a blinded observer. Pneumatic otoscopy was used to evaluate local disease, and behavioral assessments served as the measure of systemic disease. Virulence scoring was performed using a 4-point scale to assess four clinical parameters [severity and rapidity of local disease onset; and severity and rapidity of systemic disease onset] during a 10-day evaluation period. Highly significant variation was observed among the strains in their ability to cause disease and moribundity. CONCLUSIONS/SIGNIFICANCE: As expected, there was a significant correlation between the rapidity of systemic disease onset and severity of systemic disease; however, there was little correlation between the severity of otoscopic changes and severity of systemic disease. Importantly, it was observed that different strains of the same serotype produced as broad an array of disease phenotypes as did strains of different serotypes. We attribute these phenotypic differences among the strains to the high degree of genomic plasticity that we have previously documented.

Virulence phenotypes of low-passage clinical isolates of nontypeable Haemophilus influenzae assessed using the chinchilla laniger model of otitis media.

BACKGROUND: The nontypeable Haemophilus influenzae (NTHi) are associated with a spectrum of respiratory mucosal infections including: acute otitis media (AOM); chronic otitis media with effusion (COME); otorrhea; locally invasive diseases such as mastoiditis; as well as a range of systemic disease states, suggesting a wide range of virulence phenotypes. Genomic studies have demonstrated that each clinical strain contains a unique genic distribution from a population-based supragenome, the distributed genome hypothesis. These diverse clinical and genotypic findings suggest that each NTHi strain possesses a unique set of virulence factors that contributes to the course of the disease. RESULTS: The local and systemic virulence patterns of ten genomically characterized low-passage clinical NTHi strains (PittAA - PittJJ) obtained from children with COME or otorrhea were stratified using the chinchilla model of otitis media (OM). Each isolate was used to bilaterally inoculate six animals and thereafter clinical assessments were carried out daily for 8 days by blinded observers. There was no statistical difference in the time it took for any of the 10 NTHi strains to induce otologic (local) disease with respect to any or all of the other strains, however the differences in time to maximal local disease and the severity of local disease were both significant between the strains. Parameters of systemic disease indicated that the strains were not all equivalent: time to development of the systemic disease, maximal systemic scores and mortality were all statistically different among the strains. PittGG induced 100% mortality while PittBB, PittCC, and PittEE produced no mortality. Overall Pitt GG, PittII, and Pitt FF produced the most rapid and most severe local and systemic disease. A post hoc determination of the clinical origins of the 10 NTHi strains revealed that these three strains were of otorrheic origin, whereas the other 7 were from patients with COME. CONCLUSION: Collectively these data suggest that the chinchilla OM model is useful for discriminating between otorrheic and COME NTHi strains as to their disease-producing potential in humans, and combined with whole genome analyses, point the way towards identifying classes of virulence genes.

Outpatient treatment suite: a safe and cost-effective venue to perform myringotomy and tubes placement in children.

CONTEXT: Otitis media (OM) is the most common reason that a child undergoes a general anesthetic, with the total costs of treating this disease exceeding five billion dollars annually. Concerns regarding the development of antibiotic-resistant organisms in response to medical treatment for OM have fueled the demand for surgical intervention. However, reimbursements are decreasing. Non-traditional settings for children requiring bilateral myringotomy and tube (BMT) placement for ear disease have the potential to offer the same degree of patient safety and improved efficiency but at lower cost. OBJECTIVE: To develop a non-traditional setting for BMT surgery that is safe, cost effective, and well received by patients, families and staff. DESIGN: Prospective design of an outpatient treatment suite (OTS) for BMT placement; prospective evaluation of safety and family satisfaction; analysis of costs. SETTING: A 778 bed US urban area level one trauma center and teaching hospital, with a 2160 ft(2) electro-convulsive therapy suite that was underutilized and non-revenue generating on Tuesdays and Thursdays. PARTICIPANTS: A design task force of health care providers, administrators and operations personnel; 794 healthy children between the ages of 6 months to 16 years requiring BMT surgery; 100 families of patients. MAIN OUTCOME MEASURES: Financial comparison was made between the traditional operating room (OR) setting, the outpatient surgery center (SC) and the OTS comparing overhead and indirect costs to run each site. A prospective survey was conducted of 100 consecutive patients undergoing surgery between November 2000 and June 2001. The survey was conducted at the 2 weeks postoperative check and was composed of 18 questions divided into five sections, with a 5-point rating scheme, with one being very poor, and five being very good. RESULTS: Designing a new treatment venue was successful because of teamwork and a willingness to think creatively. The OTS was found to be far more cost-effective than both the main OR and SC for BMTs. The contribution to margin for the SC was US$ 280 per case and for the main OR was US$ 2130 per case. By operating on 794 patients in OTS, the hospital was able to generate additional contribution to margin of US$ 197,100 when compared to the cost of performing these cases in the SC and US$ 1,499,500 when compared to performing all cases in the main OR. No adverse consequences were noted. Patient/Family satisfaction was also rated very high, with an overall rating of 4.85 and markedly reduced time in hospital. CONCLUSION: Operating rooms (ORs) today are busier than in years past, but revenues barely meet or in some cases fall below expenses due to insurers' decreased reimbursement. This innovative approach to BMT placement has been shown to be safe and results in excellent family satisfaction, with a substantial contribution to margin. As over one million BMT cases are performed annually in the US, adoption of this approach nationally has the potential to markedly reduce the treatment costs of this common disease.