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Strep Throat Over and Over: How Frequent? How Real?

      Acute pharyngitis is one of the most common illnesses for which children visit pediatricians and other primary care physicians.
      • Armstrong GL
      • Pinner RW
      Outpatient visits for infectious diseases in the United States, 1980 through 1996.
      • Nash DR
      • Harman J
      • Wald ER
      • Kelleher KJ
      Antibiotic prescribing by primary care physicians for children with upper respiratory tract infections.
      Between 15% and 30% of pharyngitis episodes are reported to be associated with group A streptococcus (GAS)
      • Kaplan EL
      • Top Jr, FH
      • Dudding BA
      • Wannamaker LW
      Diagnosis of streptococcal pharyngitis: differentiation of active infection from the carrier state in the symptomatic child.
      ; some of these patients experience repetitive symptomatic bouts of sore throat associated with positive test results for GAS. In this issue of Mayo Clinic Proceedings, St. Sauver et al
      • St. Sauver JL
      • Weaver AL
      • Orvidas LJ
      • Jacobson RM
      • Jacobsen SJ
      Population-based prevalence of repeated group A β-hemolytic streptococcal pharyngitis episodes.
      used the database of the Rochester Epidemiology Project to estimate a population-based period prevalence of recurring GAS pharyngitis episodes for the years 1996 to 1998. Cases were defined as children between 4 and 15 years of age who experienced 3 or more episodes within a 1-year period. Episodes were defined as “evidence of a sore throat” accompanied by either a positive rapid antigen detection test result or a positive throat culture for GAS occurring at least 30 days after the most recent pharyngitis episode. The authors concluded that a relatively small proportion of children, approximately 1% overall and 2% between 4 and 6 years of age, experienced repeated GAS-related episodes of pharyngitis during the time interval reviewed.
      Even those low rates, however, may well be an overestimation. The methodology used, based solely on retrospective reviews of medical records and laboratory reports, has considerable limitations. The definition of an “episode” appears to be largely independent of clinical manifestations, which we believe were incompletely and therefore inadequately documented in the analyzed database. For example, in a random sample of 210 such episodes, the symptom of “sore throat” was recorded to be present in only 60% of patients. Similarly, other clinical findings often associated with streptococcal upper respiratory tract infection, such as pharyngeal erythema and tonsillar exudate, were documented as present in only approximately one third of cases. Temperature greater than 38°C was absent in two thirds of the 152 episodes for which temperature was recorded. Thus, one cannot be certain that many of these episodes would actually meet the accepted clinical profile (sudden onset, severe pain on swallowing, tonsillopharyngeal erythema, fever) usually associated with true acute GAS infection of the throat.
      • Bisno AL
      • Gerber MA
      • Gwaltney Jr, JM
      • Kaplan EL
      • Schwartz RH
      Practice guidelines for the diagnosis and management of group A streptococcal pharyngitis.
      • American Academy of Pediatrics
      Group A streptococcal infections.
      • Wannamaker LW
      Perplexity and precision in the diagnosis of streptococcal pharyngitis.
      A major issue that St. Sauver et al faced while performing these analyses was that of differentiating true GAS infection from episodes of chronic pharyngeal streptococcal carriage in patients with intercurrent viral infections. In prospective studies, this issue can be at least partially resolved by a number of methods, including serotyping/genotyping of recovered GAS isolates and determining the immune response to GAS extracellular antigens such as streptolysin O and streptococcal DNase B. Obviously, none of this information was available to the authors from their review of the medical records. They attempted to address this issue by identifying those episodes in which the signs and symptoms were more suggestive of viral rather than streptococcal infection, and such was the case in 21% of the reviewed records. The true figure may well be greater. For example, in one prospective study conducted a number of years ago, also in Minnesota, 57% of children with acute pharyngitis and positive GAS throat cultures failed to exhibit a diagnostic increase in antistreptolysin O or anti-DNase B,
      • Kaplan EL
      • Top Jr, FH
      • Dudding BA
      • Wannamaker LW
      Diagnosis of streptococcal pharyngitis: differentiation of active infection from the carrier state in the symptomatic child.
      suggesting that they might have been carriers rather than children experiencing acute streptococcal infection.
      While not completely solvable at the clinic level, one caveat from the American Academy of Pediatrics Redbook is worth remembering: “children with manifestations highly suggestive of viral infection, such as coryza, conjunctivitis, hoarseness, cough, anterior stomatitis, discrete ulcerative lesions, or diarrhea are unlikely to have GAS as the cause of their pharyngitis and generally should not be tested for GAS.”
      • American Academy of Pediatrics
      Group A streptococcal infections.
      A high proportion of children with positive cultures or rapid antigen detection test results in such instances are likely to be streptococcal carriers.
      • Kaplan EL
      The group A streptococcal upper respiratory tract carrier state: an enigma.
      Indeed, pharyngeal carriage rates of GAS in healthy children in schools and child-care centers may at times be 15% or even higher,
      • American Academy of Pediatrics
      Group A streptococcal infections.
      and carriage of a single GAS strain may persist for many months.

      Kaplan EL, Kurlan R, Van Gheem A, Johnson DR. Two year persistence of group A streptococci (GAS) in the throat accompanied by falling streptococcal antibody titers: the upper respiratory tract carrier state confirmed and microbiologically/immunologically examined [abstract]. Presented at the Pediatric Academic Societies' Annual Meeting; San Francisco, Calif; April 29-May 2, 2006.

      Determining the presence or absence of GAS in the pharynx during asymptomatic intervals may be helpful to some extent in differentiating chronic carriage from acute streptococcal pharyngitis. We suspect that many of the children in the Rochester study with frequent recurrences (≥7 in 38 patients) may well have been in this category. In addition to chronic carriage, other possible explanations are noncompliance with the prescribed antimicrobial regimen; a new infection acquired from family, classroom, or community contacts; or true treatment failure, ie, a second episode of pharyngitis caused by the original infecting strain. However, the last-mentioned occurs rarely.
      Regardless of the exactitude of the period-prevalence estimate, we concur with the authors that the absolute number of children they found to be visiting primary care physicians repeatedly with GAS-positive sore throats is substantial at the population level. This represents not merely a conundrum for the epidemiologist but a management problem for the practitioner. Although not the focus of the article by St. Sauver et al, it is worth noting that suggestions to clinicians for dealing with such perplexing patients are spelled out in the Practice Guidelines of the Infectious Disease Society of America.
      • Bisno AL
      • Gerber MA
      • Gwaltney Jr, JM
      • Kaplan EL
      • Schwartz RH
      Practice guidelines for the diagnosis and management of group A streptococcal pharyngitis.
      Those guidelines also provide specific antibiotic regimens most likely to terminate carriage, in the event that this strategy (not routinely recommended) is required to help clarify the situation. The role of tonsillectomy is often discussed for children with frequent recurrent sore throats. This procedure may decrease the number of recurrences in some patients, but only for a limited time,
      • Paradise JL
      • Bluestone CD
      • Bachman RZ
      • et al.
      Efficacy of tonsillectomy for recurrent throat infection in severely affected children: results of parallel randomized and nonrandomized clinical trials.
      and it is recommended only in the most severe cases.
      • Paradise JL
      • Bluestone CD
      • Colborn DK
      • Bernard BS
      • Rockette HE
      • Kurs-Lasky M
      Tonsillectomy and adenotonsillectomy for recurrent throat infection in moderately affected children.
      The authors advocate further studies “to determine how best to reduce episodes and treatment costs in this group of children.” Although it is hard to question this laudable goal, we wonder whether the low overall period prevalence reported from this retrospective database in the defined population of Rochester and Olmsted County, Minnesota, justifies the effort and expense of such studies. Given the ubiquity of GAS, is a 1% period-prevalence rate of recurrent episodes near the irreducible minimum? Such efforts could be justifiable, however, in other populations with high rates of occurrence of nonsuppurative streptococcal sequelae or of invasive streptococcal diseases.
      Substantial current research is directed toward the development of a safe and effective vaccine to prevent GAS infections and their life-threatening suppurative and nonsuppurative sequelae.
      • Bisno AL
      • Rubin FA
      • Cleary PP
      • Dale JB
      Prospects for a group A streptococcal vaccine: rationale, feasibility, and obstacles—report of a National Institute of Allergy and Infectious Diseases workshop.
      There are a number of vaccine candidates, some of which have already been subjected to limited testing of safety and immunogenicity in human volunteers. Should these efforts be successful, this group of children with repetitive symptomatic cases of acute GAS-positive pharyngitis might well be among the most grateful of recipients, and such gratitude would surely be shared by their parents and physicians.

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