against the M protein component of GAS is to identify epitopes that will induce the production of protective antibodies against as many different M types as possible while at the same time ensuring that the antibodies raised against these epitopes will not react with human tissues. It is also important to have a vaccine strategy that will elicit mucosal immunity, as that is likely to be important in protecting against this respiratory tract pathogen. The most advanced GAS candidate vaccine is 26-valent, targeting small N-terminal peptides on the M protein. Based on an epidemiologic survey of invasive GAS disease, it should cover ~80% of those isolates. In phase 1 and 2 trials, the vaccine was found to be safe and to have good immunogenicity. A phase 3 trial is needed to judge efficacy. However, with the ever expanding repertoire of emm types in GAS, the individual M protein approach is likely flawed. Identification of antigens that are shared across emm types and can induce protective immunity without producing molecular mimicry is the holy grail of GAS vaccinology.
REFERENCES
1. Ebell MH, Smith MA, Barry HC, Ives K, Carey M. 2000. The rational clinical examination. Does this patient have strep throat? JAMA 284:2912–2918.
2. ESCMID Sore Throat Guideline Group, Pelucchi C, Grigoryan L, Galeone C, Esposito S, Huovinen P, Little P, Verheij T. 2012. Guideline for the management of acute sore throat. Clin Microbiol Infect 18(Suppl 1):1–28.
3. O’Loughlin RE, Roberson A, Cieslak PR, Lynfield R, Gershman K, Craig A, Albanese BA, Farley MM, Barrett NL, Spina NL, Beall B, Harrison LH, Reingold A, Van Beneden C; Active Bacterial Core Surveillance Team. 2007. The epidemiology of invasive group A streptococcal infection and potential vaccine implications: United States, 2000–2004. Clin Infect Dis 45:853–862.
4. Seppälä H, Klaukka T, Vuopio-Varkila J, Muotiala A, Helenius H, Lager K, Huovinen P; Finnish Study Group for Antimicrobial Resistance. 1997. The effect of changes in the consumption of macrolide antibiotics on erythromycin resistance in group A streptococci in Finland. N Engl J Med 337:441–446.
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CASE 8
The patient was a 64-year-old retired postal worker with a medical history of extensive facial reconstruction for squamous cell carcinoma of the head and neck. He had a 30-year history of smoking. The patient presented with progressive shortness of breath, a persistent, productive cough, purulent sputum, and fever to 39.0°C 2 days prior to admission.
On physical examination he had a temperature of 37.3°C, respiratory rate of 18 per minute, pulse rate of 103 beats/min, blood pressure of 154/107 mm Hg, and pO2 of 92 mm Hg. Chest auscultation revealed coarse breath sounds at the left lower base with bibasilar fine crackles. He was found to have a left lower lobe infiltrate on chest radiograph. His admission white blood cell count was 10,600/μl with 70% neutrophils, and his hemoglobin was 9.4 g/dl. Sputum Gram stain at admission revealed >25 polymorphonuclear cells and >25 squamous epithelial cells per low-power field. Because of the high numbers of squamous epithelial cells, the specimen was not processed further. Two blood cultures obtained at admission were positive for the organism seen in Fig. 8.1. The Gram stain from the blood culture bottle is shown in Fig. 8.2.
The patient was admitted to the hospital and treated with ceftriaxone intravenously. Upon defervescence, he was discharged on a regimen of oral azithromycin based on the organism’s identification and antimicrobial susceptibility results. Of note: this was the patient’s third episode of this illness in the past month. Isolates from all three episodes belonged to the same serotype, type 23.
1 1. What disease process was ongoing in this patient? What clinical prediction rules could be applied to this patient in determining whether he should be hospitalized? Why do you think the decision was made to hospitalize him?
2 2. What organism was causing this individual’s infection?
3 3. What other patient populations are at risk for infection with this organism?
4 4. Two different virulence factors produced by the organism infecting this patient are important in disease pathogenesis. What are they, and what role do they have in the pathogenicity of this organism?
5 5. What strategies are available to prevent infections with this organism? Why are preventive strategies becoming of greater importance with this organism?
6 6. How do you explain the patient’s having repeated episodes of infection with the same serotype of this organism? There are at least two and possibly more explanations.
CASE 8 CASE DISCUSSION
1. Based on his physical findings of productive cough with purulent sputum, shortness of breath, fever, and bibasilar fine crackles on chest auscultation in the left lower lung, coupled with left lower lobe infiltrates on radiographic imaging, this patient had a lower respiratory tract infection most consistent with bacterial pneumonia. Because this patient was at home at the time of disease onset, he would be considered to have community-acquired pneumonia.
Two clinical prediction models are widely used to determine if patients with community-acquired pneumonia should be admitted to the hospital. Having metrics for this purpose is valuable because patients do not wish to be hospitalized. There are several reasons for this: they get better faster at home; they are not exposed to nosocomial risks, including infections; and it is more cost-efficient. These two models allow for a rational approach to this process. The pneumonia prediction rule is a scoring system based on demographics; coexisting conditions; and physical, laboratory, and radiographic findings. Because of its complexity, it is more of a research tool with limited practical application. The second system is CRB-65, a modification of CURB-65. CRB-65 is simple to use, as it has four criteria that can be easily determined: C, presence or absence of confusion; R, respiratory rate of >30 per minute; B, low systolic (≤90 mm Hg) or diastolic (≤60 mm Hg) blood pressure; and age >65 years. Patients are ranked on a scale of 0 to 4; those with a score of 3 or 4 are judged to have severe disease, with frequent admission to the intensive care unit and 30-day mortality of >40%. This patient had a CRB-65 score of 0. Patients with that score are usually not admitted to the hospital, as their 30-day mortality is 0%. However, CRB-65 is a simple system that does not take into account certain complexities in this patient. This patient was immunocompromised due to his history of head and neck carcinoma. He also had a long-term smoking history, which put him at increased risk for respiratory infections. Finally, he had previous episodes of respiratory infection, which
