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Development, Validation, and Cost Effectiveness of Clinical Prediction Rules for Group A Beta Hemolytic Streptococcal Pharyngitis In Children From Lower and Upper Middle Income Countries


Background: An estimated 3% of untreated group A beta hemolytic streptococcal (GABHS) pharyngitis can lead to rheumatic fever (RF), resulting in rheumatic heart disease (RHD) and other serious nonsuppurative sequelae of infection. Prevalence of disease is disproportionate with the greatest burden among children and adolescents of developing countries; an estimated 95% of RF and 79% of RHD cases are from low income countries. Accurate diagnosis and prompt antibiotic treatment of GABHS pharyngitis is a simple and effective strategy for primary prevention of RF and RHD. Accurate diagnosis is difficult without laboratory testing due to similarities in signs and symptoms with other causes of pharyngitis.

Due to financial constraints, laboratory capabilities are often limited, forcing many physicians in low and middle income countries (LMICs) to either prescribe antibiotics indiscriminately or rely on clinical prediction rules (CPRs). CPRs provide a practical alternative for diagnosis in the absence of laboratory testing. However, few CPRs have been derived specifically for LMICs. Studies have shown that CPRs can be cost effective in hospital settings, but few have been conducted for children from LMICs.

Methods: Children 2-12 years of age presenting with complaint of sore throat were enrolled in four urban university pediatric outpatient clinics from September 2001 to August 2005 in Rio de Janeiro, Brazil, Cairo, Egypt; Riga Latvia and Zagreb, Croatia. The diagnostic component of the study (Chapters 4-5) consisted of generating CPRs for the 1,993 children enrolled in the study. It also consisted of external validation of a) published CPRs from the literature, and b) study developed CPRs. The cost effectiveness analysis component of the study (Chapter 6) assessed the cost effectiveness of the CPR developed for Egypt versus five alternative diagnostic and management strategies.

Summary: The dissertation consists of findings from three papers (Chapters 4-6). In paper 1 (Chapter 4), five different CPRs were developed for use in Egypt, Brazil, Latvia, Croatia, and the combined study population. In paper 2 (Chapter 5), external validation of published and study CPRs suggested country specific CPRs were better in the population for which they were developed. In paper 3 (Chapter 6), Culture Only was the most cost effective strategy at baseline estimates; however, the Egypt CRP was cost effective when sensitivity and specificity were at or above 88%.

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