The single recombinant M. tuberculosis protein DPPD provides enhanced performance of skin testing among HIV-infected tuberculosis patients.

Diagnostic testing for M. tuberculosis infection has advanced with QuantiFERON and GeneXpert, but simple cost-effective alternatives for widespread TB screening has remained elusive and purified protein derivative (PPD)-based tuberculin skin testing (TST) remains the most widely used method. PPD-based tests have reduced performance, however, in BCG vaccinees and in individuals with immune deficiencies. We compared the performance of skin testing with the recombinant DPPD protein against that of a standard PPD-based skin test. Our data indicates similar performance of DPPD and PPD (r2 = 0.7689) among HIV-negative, active TB patients, all of whom presented greater than 10 mm induration following administration. In contrast to results demonstrating that PPD induced indurations greater than 5 mm (i.e., the recommended threshold for positive results in this population) in only half (19 of 38) of the HIV positive TB patients, 89.5% (34 of 38) of these participants developed indurations greater than 5 mm when challenged with DPPD. Importantly, none of the patients that were positive following PPD administration were negative following DPPD administration, indicating markedly improved sensitivity of DPPD among HIV-infected individuals. Our data indicate that DPPD has superior performance in skin testing than the current TST standard.

Differences in evolution of children with non-severe acute lower respiratory tract infection with and without radiographically diagnosed pneumonia.

OBJECTIVE: To identify differences in the evolution of children with non-severe acute lower respiratory tract infection between those with and without radiographically diagnosed pneumonia. DESIGN: Prospective cohort study. SETTING: A public university pediatric hospital in Salvador, Northeast Brazil. PATIENTS: Children aged 2-59 months. METHODS: By active surveillance, the pneumonia cases were prospectively identified in a 2-year period. Each case was followed-up for changes in various clinical symptoms and signs. Demographic, clinical and radiographic data were recorded in standardized forms. Exclusion was due to antibiotic use in the previous 48 hours, signs of severe disease, refusal to give informed consent, underlying chronic illness, hospitalization in the previous 7 days or amoxicillin allergy. Chest X-ray (CXR) was later read by at least 2 independent pediatric radiologists. MAIN OUTCOME MEASURES: Radiographic diagnosed pneumonia based on agreed detection of pulmonary infiltrate or pleural effusion in 2 assessments. RESULTS: A total of 382 patients receiving amoxicillin were studied, of whom, 372 (97.4%) had concordant radiographic diagnosis which was pneumonia (52%), normal CXR (41%) and others (7%). By multivariate analysis, age (OR=1.03; 95% CI: 1.02-1.05), disease > 5 days (OR = 1.04; 95% CI: 1.001-1.08), reduced pulmonary expansion (OR = 3.3; 95% CI: 1.4-8.0), absence of wheezing (OR = 0.5; 95% CI: 0.3-0.9), crackles on admission (OR = 2.0; 95% CI: 1.2-3.5), inability to drink on day 1 (OR = 4.2; 95% CI: 1.05-17.3), consolidation percussion sign (OR = 7.0; 95% CI: 1.5-32.3), tachypnea (OR = 2.0; 95% CI: 1.09-3.6) and fever (OR = 3.6; 95% CI: 1.4-9.4) on day 2 were independently associated with pneumonia. The highest positive predictive value was at the 2nd day of evolution for tachypnea (71.0%) and fever (81.1%). CONCLUSION: Persistence of fever or tachypnea up to the second day of amoxicillin treatment is predictive of radiographically diagnosed pneumonia among children with non-severe lower respiratory tract diseases.

Characteristics of radiographically diagnosed pneumonia in under-5 children in Salvador, Brazil.

OBJECTIVE: To assess the association of demographic and clinical aspects with radiographically diagnosed pneumonia. DESIGN: By active surveillance, the admitted pneumonia cases by the pediatrician on duty were identified in a 2 year period. Demographic, clinical and radiographic data were registered into standardized forms. SETTING: A public university pediatric hospital in Salvador, Northeast Brazil. PATIENTS: Children <5 years-old. MAIN OUTCOME MEASURES: Radiographically diagnosed pneumonia based on detection of pulmonary infiltrate/ consolidation. RESULTS: 301 cases had the chest X-ray evaluated by a pediatric radiologist blinded to clinical information, among whom pulmonary infiltrate and consolidation were described in 161 (54%) and 119 (40%), respectively. Chest X-ray was read normal for 140 cases. Overall, the median age was 17 months (mean 20±14, range 12 days-59 months). Pulmonary infiltrate was less frequently described among patients aged under 1 year (41.3% vs 59.9%, P=0.002, OR [95% CI] = 0.47 [0.29-0.76]) and hyperinflation was significantly more frequent in this age group (27.9% vs 4.1%, P<0.001, OR [95% CI] = 9.14 [4.0-20.9]). By multiple logistic regression, fever on admission was independently associated with pulmonary infiltrate (OR [95% CI] = 1.68 [1.03-2.73]) or consolidation (1.79 [1.10-2.92]), wheezing was independently associated with absence of pulmonary infiltrate (0.53 [0.33-0.86]) or of consolidation (0.53 [0.33-0.87]). The positive likelihood ratio of fever on examination for pulmonary infiltrate and consolidation was 1.49 (95% CI:1.11-1.98) and 1.49 (95% CI: 1.14-1.94), respectively. CONCLUSION: Presence of fever enhanced 2.5 times the chance of children hospitalized with lower respiratory tract disease to have radiographically diagnosed pneumonia.

Additional markers to refine the World Health Organization algorithm for diagnosis of pneumonia.

INTRODUCTION: WHO guidelines for primary care of children with tachypnea indicate that all should receive antibiotics for presumed pneumonia. These guidelines have led to excessive antibiotic use. OBJECTIVE: To examine the value of history of previous respiratory distress, chest indrawing and fever, and response to bronchodilator(BD) to refine these guidelines. DESIGN: Prospective study. SETTING: Urban tertiary care hospital. SUBJECTS: Children, between the ages of 6 and 59 months, presenting with cough and tachypnea. METHODS: 182 children were enrolled. Each child had a chest X-ray that was read by two blinded, independent radiologists. Discordance between the two radiologists led to excluding 17 patients. The remaining 165 children were examined for fever and/or chest indrawing, and if they had a history of previous respiratory distress, challenge with a BD. The association of persistent tachypnea after BD and presence of pulmonary infiltrates was recorded. RESULTS: The median age was 22 months (mean 25.1 +- 14.5 mo) and 75.8% were aged greater than 1 year. There were 58.8% males. Previous respiratory distress occurred in 65.0% and 79.2% of children aged less than 1 year and 1 year, respectively. Pneumonia was radiologically diagnosed in 26/165 (15.8%). 2/40 (5 %) of children without a history of previous respiratory distress had pneumonia diagnosed. Of 125 children with history of previous respiratory distress, pneumonia was identified in 24 (19.2 %). Persistence of tachypnea after BD was associated with pulmonary infiltrate in 14/24 (58.3%), whereas, tachypnea persisted in 32/101 (31.7%) children without pulmonary infiltrates (P = 0.02). The negative predictive value of resolution of tachypnea was 87.3% (95% CI 77.5 93.4). BD non-response was most useful in children without fever and/or with chest indrawing to indicate pneumonia as the cause of the tachypnea. CONCLUSION: This study indicates that by adding the simple procedures of a history of previous respiratory distress, recording of fever and chest indrawing, and observing the response to bronchodilators, pneumonia can be reliably identified in children presenting with tachypnea and cough. It is probable that this approach to management of children with cough and tachypnea could reduce unnecessary use of antibiotics.