Julia Rhodes

Racial and Ethnic Differences in Asthma Diagnosis Among Children Who Wheeze

Background. Racial and ethnic disparities exist in reported childhood asthma prevalence, but it is unclear if disparities stem from true prevalence differences or a different likelihood of receiving a diagnosis from a health professional. Concern has been raised that asthma may be underdiagnosed, particularly among minority children who have more restricted access to high-quality health care. Objective. To examine racial/ethnic differences among currently symptomatic children in acquiring an asthma diagnosis to determine if relative underdiagnosis among minorities exists. Children for whom no symptoms were reported (a group that includes those with well-controlled symptoms) were excluded from the analysis. Methods. The 1999 National Health Interview Survey includes a nationally representative sample of children with reported wheezing symptoms. We included children 3 to 17 years old in the study and analyzed racial/ethnic differences in asthma diagnosis, controlling for young age, gender, parental education, single-parent household, central-city residence, region of residence, health insurance, having a usual place of care, and parent-reported severity of wheezing symptoms. Results. Among those reported to have wheezed in the past year (n = 946), 83% of Puerto Rican, 71% of non-Hispanic black, and 65% of Mexican children were diagnosed with asthma compared with 57% of non-Hispanic white children. Using non-Hispanic white children as the reference group, the approximate adjusted relative risk for physician diagnosis of asthma given wheezing in the past year was 1.43 (95% confidence interval [CI]: 1.04, 1.63) for Puerto Rican, 1.22 (95% CI: 1.03, 1.37) for non-Hispanic black, and 1.19 (95% CI: 0.94, 1.39) for Mexican children. Minority children were reported to have greater severity of wheezing symptoms. Even after accounting for this increased severity, children in racial and ethnic minority groups were as or more likely to have a reported asthma diagnosis than non-Hispanic white children. Conclusions. Our findings do not provide evidence for the hypothesis that symptomatic minority children are underdiagnosed with asthma compared with non-Hispanic white children. To the contrary, among currently symptomatic children, minority children were more likely to be diagnosed than non-Hispanic white children even after accounting for the higher wheezing severity among minority children.

Incidence of Pneumococcal Bacteremia Requiring Hospitalization in Rural Thailand

BACKGROUND Population-based estimates of the incidence of invasive pneumococcal disease are unavailable for Thailand and other countries in Southeast Asia. We estimated the incidence of pneumococcal bacteremia cases requiring hospitalization in rural Thailand. METHODS Blood cultures were performed on samples from hospitalized patients in 2 rural provinces where active, population-based surveillance of community-acquired pneumonia is conducted. Blood cultures were performed at clinician discretion and were encouraged for all patients with suspected pneumonia and all children aged <5 years with suspected sepsis. Pneumococcal antigen testing was performed on positive blood culture specimens that failed to grow organisms on subculture. RESULTS From May 2005 through June 2007, 23,853 blood culture specimens were collected overall, and 7319 were collected from children aged <5 years, which represented 66% and 47% of target patients, respectively. A total of 72 culture-confirmed pneumococcal bacteremia cases requiring hospitalization were identified. An additional 44 patients had media from positive blood cultures that yielded no growth on subculture but that had positive results of pneumococcal antigen testing. Of the 116 confirmed cases of bacteremia, 27 (23%) occurred in children aged <5 years; of these, 9 (33%) were confirmed by antigen testing only. The incidence of pneumococcal bacteremia cases requiring hospitalization among children aged <5 years had a range of 10.6-28.9 cases per 100,000 persons (incidence range if cases detected by antigen are excluded, 7.5-14.0 cases per 100,000 persons). CONCLUSIONS Invasive pneumococcal disease is more common than was previously suspected in Thailand, even on the basis of estimates limited to hospitalized cases of bacteremia. These estimates, which are close to estimates of the incidence of hospitalized cases of pneumococcal bacteremia in the United States before introduction of pneumococcal conjugate vaccine, provide important data to guide public health care policy and to inform discussions about vaccine introduction in Thailand and the rest of Southeast Asia.

Incidence and Etiology of Acute Lower Respiratory Tract Infections in Hospitalized Children Younger Than 5 Years in Rural Thailand

Background: Pneumonia remains a leading cause of under-five morbidity and mortality globally. Comprehensive incidence, epidemiologic and etiologic data are needed to update prevention and control strategies. Methods: We conducted active, population-based surveillance for hospitalized cases of acute lower respiratory tract infections (ALRI) among children <5 years of age in rural Thailand. ALRI cases were systematically sampled for an etiology study that tested nasopharyngeal specimens by polymerase chain reaction; children without ALRI were enrolled as controls from outpatient clinics. Results: We identified 28,543 hospitalized ALRI cases from 2005 to 2010. Among the 49% with chest radiographs, 63% had findings consistent with pneumonia as identified by 2 study radiologists. The hospitalized ALRI incidence rate was 5772 per 100,000 child-years (95% confidence interval: 5707, 5837) and was higher in boys versus girls (incidence rate ratio 1.38, 95% confidence interval: 1.35–1.41) and in children 6–23 months of age versus other age groups (incidence rate ratio 1.76, 95% confidence interval: 1.69–1.84). Viruses most commonly detected in ALRI cases were respiratory syncytial virus (19.5%), rhinoviruses (18.7%), bocavirus (12.8%) and influenza viruses (8%). Compared with controls, ALRI cases were more likely to test positive for respiratory syncytial virus, influenza, adenovirus, human metapneumovirus and parainfluenza viruses 1 and 3 (P ⩽ 0.01 for all). Bloodstream infections, most commonly Streptococcus pneumoniae and nontyphoidal Salmonella, accounted for 1.8% of cases. Conclusions: Our findings underscore the high burden of hospitalization for ALRI and the importance of viral pathogens among children in Thailand. Interventions targeting viral pathogens coupled with improved diagnostic approaches, especially for bacteria, are critical for better understanding of ALRI etiology, prevention and control.

Pneumococcal antigen testing of blood culture broth to enhance the detection of Streptococcus pneumoniae bacteremia.

The purpose of this investigation was to enhance the detection of pneumococcal bacteremia cases using the Binax NOW® immunochromatographic test (ICT) on blood culture broth as part of surveillance in two rural Thailand provinces. Blood cultures were collected as clinically indicated from hospitalized patients. ICT was performed on broth from culture bottles flagged as positive by BactT/ALERT® (alarm-positive) but which failed to grow organisms on subculture. During the period May 2005–June 2007, ICT was positive on 43 (24%) of 182 alarm-positive blood cultures with no growth on subculture. Compared to pneumococcal bacteremia cases confirmed by culture, cases detected only by ICT had a longer median time from culture collection to incubation and a longer median time from alarm positivity to subculture, and were more likely to be from patients pretreated with antibiotics. In a subsequent surveillance period (July 2007–December 2009), ICT continued to detect additional pneumococcal cases, but in a lower proportion of samples (7 of 221, 3.2%). Recently, as part of a separate study, ICT applied to uninoculated blood culture broth produced weak-positive results, mandating caution if testing broth from patient blood cultures. The antigen testing of blood culture broth appears to enhance the detection of pneumococcal bacteremia, but a controlled evaluation is needed.

Density of Upper Respiratory Colonization With Streptococcus pneumoniae and Its Role in the Diagnosis of Pneumococcal Pneumonia Among Children Aged <5 Years in the PERCH Study

Upper airway pneumococcal colonization density among children hospitalized with World Health Organization–defined pneumonia was associated with microbiologically confirmed pneumococcal pneumonia (MCPP). The optimal colonization density threshold for discriminating MCPP from non-MCPP was ≥7 log10 copies/mL (sensitivity, 64.3%, specificity, 92.2%).

Standardization of Clinical Assessment and Sample Collection Across All PERCH Study Sites

Abstract Background. Variable adherence to standardized case definitions, clinical procedures, specimen collection techniques, and laboratory methods has complicated the interpretation of previous multicenter pneumonia etiology studies. To circumvent these problems, a program of clinical standardization was embedded in the Pneumonia Etiology Research for Child Health (PERCH) study. Methods. Between March 2011 and August 2013, standardized training on the PERCH case definition, clinical procedures, and collection of laboratory specimens was delivered to 331 clinical staff at 9 study sites in 7 countries (The Gambia, Kenya, Mali, South Africa, Zambia, Thailand, and Bangladesh), through 32 on-site courses and a training website. Staff competency was assessed throughout 24 months of enrollment with multiple-choice question (MCQ) examinations, a video quiz, and checklist evaluations of practical skills. Results. MCQ evaluation was confined to 158 clinical staff members who enrolled PERCH cases and controls, with scores obtained for >86% of eligible staff at each time-point. Median scores after baseline training were ≥80%, and improved by 10 percentage points with refresher training, with no significant intersite differences. Percentage agreement with the clinical trainer on the presence or absence of clinical signs on video clips was high (≥89%), with interobserver concordance being substantial to high (AC1 statistic, 0.62–0.82) for 5 of 6 signs assessed. Staff attained median scores of >90% in checklist evaluations of practical skills. Conclusions. Satisfactory clinical standardization was achieved within and across all PERCH sites, providing reassurance that any etiological or clinical differences observed across the study sites are true differences, and not attributable to differences in application of the clinical case definition, interpretation of clinical signs, or in techniques used for clinical measurements or specimen collection.

Is Higher Viral Load in the Upper Respiratory Tract Associated With Severe Pneumonia? Findings From the PERCH Study

Abstract Background. The etiologic inference of identifying a pathogen in the upper respiratory tract (URT) of children with pneumonia is unclear. To determine if viral load could provide evidence of causality of pneumonia, we compared viral load in the URT of children with World Health Organization–defined severe and very severe pneumonia and age-matched community controls. Methods. In the 9 developing country sites, nasopharyngeal/oropharyngeal swabs from children with and without pneumonia were tested using quantitative real-time polymerase chain reaction for 17 viruses. The association of viral load with case status was evaluated using logistic regression. Receiver operating characteristic (ROC) curves were constructed to determine optimal discriminatory viral load cutoffs. Viral load density distributions were plotted. Results. The mean viral load was higher in cases than controls for 7 viruses. However, there was substantial overlap in viral load distribution of cases and controls for all viruses. ROC curves to determine the optimal viral load cutoff produced an area under the curve of <0.80 for all viruses, suggesting poor to fair discrimination between cases and controls. Fatal and very severe pneumonia cases did not have higher viral load than less severe cases for most viruses. Conclusions. Although we found higher viral loads among pneumonia cases than controls for some viruses, the utility in using viral load of URT specimens to define viral pneumonia was equivocal. Our analysis was limited by lack of a gold standard for viral pneumonia.

Microscopic Analysis and Quality Assessment of Induced Sputum From Children With Pneumonia in the PERCH Study

Abstract Background. It is standard practice for laboratories to assess the cellular quality of expectorated sputum specimens to check that they originated from the lower respiratory tract. The presence of low numbers of squamous epithelial cells (SECs) and high numbers of polymorphonuclear (PMN) cells are regarded as indicative of a lower respiratory tract specimen. However, these quality ratings have never been evaluated for induced sputum specimens from children with suspected pneumonia. Methods. We evaluated induced sputum Gram stain smears and cultures from hospitalized children aged 1–59 months enrolled in a large study of community-acquired pneumonia. We hypothesized that a specimen representative of the lower respiratory tract will contain smaller quantities of oropharyngeal flora and be more likely to have a predominance of potential pathogens compared to a specimen containing mainly saliva. The prevalence of potential pathogens cultured from induced sputum specimens and quantity of oropharyngeal flora were compared for different quantities of SECs and PMNs. Results. Of 3772 induced sputum specimens, 2608 (69%) had <10 SECs per low-power field (LPF) and 2350 (62%) had >25 PMNs per LPF, measures traditionally associated with specimens from the lower respiratory tract in adults. Using isolation of low quantities of oropharyngeal flora and higher prevalence of potential pathogens as markers of higher quality, <10 SECs per LPF (but not >25 PMNs per LPF) was the microscopic variable most associated with high quality of induced sputum. Conclusions. Quantity of SECs may be a useful quality measure of induced sputum from young children with pneumonia.

The Effect of Antibiotic Exposure and Specimen Volume on the Detection of Bacterial Pathogens in Children With Pneumonia

Abstract Background. Antibiotic exposure and specimen volume are known to affect pathogen detection by culture. Here we assess their effects on bacterial pathogen detection by both culture and polymerase chain reaction (PCR) in children. Methods. PERCH (Pneumonia Etiology Research for Child Health) is a case-control study of pneumonia in children aged 1–59 months investigating pathogens in blood, nasopharyngeal/oropharyngeal (NP/OP) swabs, and induced sputum by culture and PCR. Antibiotic exposure was ascertained by serum bioassay, and for cases, by a record of antibiotic treatment prior to specimen collection. Inoculated blood culture bottles were weighed to estimate volume. Results. Antibiotic exposure ranged by specimen type from 43.5% to 81.7% in 4223 cases and was detected in 2.3% of 4863 controls. Antibiotics were associated with a 45% reduction in blood culture yield and approximately 20% reduction in yield from induced sputum culture. Reduction in yield of Streptococcus pneumoniae from NP culture was approximately 30% in cases and approximately 32% in controls. Several bacteria had significant but marginal reductions (by 5%–7%) in detection by PCR in NP/OP swabs from both cases and controls, with the exception of S. pneumoniae in exposed controls, which was detected 25% less frequently compared to nonexposed controls. Bacterial detection in induced sputum by PCR decreased 7% for exposed compared to nonexposed cases. For every additional 1 mL of blood culture specimen collected, microbial yield increased 0.51% (95% confidence interval, 0.47%–0.54%), from 2% when volume was ≤1 mL to approximately 6% for ≥3 mL. Conclusions. Antibiotic exposure and blood culture volume affect detection of bacterial pathogens in children with pneumonia and should be accounted for in studies of etiology and in clinical management.

Pneumococcal Bacteremia Requiring Hospitalization in Rural Thailand: An Update on Incidence, Clinical Characteristics, Serotype Distribution, and Antimicrobial Susceptibility, 2005–2010

Background Streptococcus pneumoniae is an important cause of morbidity and mortality in Southeast Asia, but regional data is limited. Updated burden estimates are critical as pneumococcal conjugate vaccine (PCV) is highly effective, but not yet included in the Expanded Program on Immunization of Thailand or neighboring countries. Methods We implemented automated blood culture systems in two rural Thailand provinces as part of population-based surveillance for bacteremia. Blood cultures were collected from hospitalized patients as clinically indicated. Results From May 2005– March 2010, 196 cases of pneumococcal bacteremia were confirmed in hospitalized patients. Of these, 57% had clinical pneumonia, 20% required mechanical ventilation, and 23% (n = 46) died. Antibiotic use before blood culture was confirmed in 25% of those with blood culture. Annual incidence of hospitalized pneumococcal bacteremia was 3.6 per 100,000 person-years; rates were higher among children aged <5 years at 11.7 and adults ≥65 years at 14.2, and highest among infants <1 year at 33.8. The median monthly case count was higher during December–March compared to the rest of the year 6.0 vs. 1.0 (p<0.001). The most common serotypes were 23F (16%) and 14 (14%); 61% (74% in patients <5 years) were serotypes in the 10-valent PCV (PCV 10) and 82% (92% in <5 years) in PCV 13. All isolates were sensitive to penicillin, but non-susceptibility was high for co-trimoxazole (57%), erythromycin (30%), and clindamycin (20%). Conclusions We demonstrated a high pneumococcal bacteremia burden, yet underestimated incidence because we captured only hospitalized cases, and because pre-culture antibiotics were frequently used. Our findings together with prior research indicate that PCV would likely have high serotype coverage in Thailand. These findings will complement ongoing cost effectiveness analyses and support vaccine policy evaluation in Thailand and the region.