Yasmin Jahan

Outbreak of Hepatitis E in Urban Bangladesh Resulting in Maternal and Perinatal Mortality

A large outbreak of hepatitis E occurred in urban Bangladesh during 2008–2009, resulting in increased maternal and neonatal mortality in the affected community. Case-patients who took paracetamol during their illness were more likely to die than other case-patients.

Safety of Induced Sputum Collection in Children Hospitalized With Severe or Very Severe Pneumonia

Abstract Background. Induced sputum (IS) may provide diagnostic information about the etiology of pneumonia. The safety of this procedure across a heterogeneous population with severe pneumonia in low- and middle-income countries has not been described. Methods. IS specimens were obtained as part a 7-country study of the etiology of severe and very severe pneumonia in hospitalized children <5 years of age. Rigorous clinical monitoring was done before, during, and after the procedure to record oxygen requirement, oxygen saturation, respiratory rate, consciousness level, and other evidence of clinical deterioration. Criteria for IS contraindications were predefined and serious adverse events (SAEs) were reported to ethics committees and a central safety monitor. Results. A total of 4653 IS procedures were done among 3802 children. Thirteen SAEs were reported in relation to collection of IS, or 0.34% of children with at least 1 IS specimen collected (95% confidence interval, 0.15%–0.53%). A drop in oxygen saturation that required supplemental oxygen was the most common SAE. One child died after feeding was reinitiated 2 hours after undergoing sputum induction; this death was categorized as “possibly related” to the procedure. Conclusions. The overall frequency of SAEs was very low, and the nature of most SAEs was manageable, demonstrating a low-risk safety profile for IS collection even among severely ill children in low-income-country settings. Healthcare providers should monitor oxygen saturation and requirements during and after IS collection, and assess patients prior to reinitiating feeding after the IS procedure, to ensure patient safety.

Chest Radiograph Findings in Childhood Pneumonia Cases From the Multisite PERCH Study

Summary In the Pneumonia Etiology Research for Child Health study, abnormal chest radiographs (CXRs) in cases were associated with hypoxemia, crackles, tachypnea, and fever. Overall, 54% of CXRs were abnormal (site range, 35%–64%). Consolidation on CXR was associated with an increased risk of mortality.

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.

Arsenic exposure is associated with pediatric pneumonia in rural Bangladesh: a case control study.

BackgroundPneumonia is the leading cause of death for children under 5 years of age globally, making research on modifiable risk factors for childhood pneumonia important for reducing this disease burden. Millions of children globally are exposed to elevated levels of arsenic in drinking water. However, there is limited data on the association between arsenic exposure and respiratory infections, particularly among pediatric populations.MethodsThis case control study of 153 pneumonia cases and 296 controls 28xa0days to 59xa0months of age in rural Bangladesh is the first to assess whether arsenic exposure is a risk factor for pneumonia in a pediatric population. Cases had physician diagnosed World Health Organization defined severe or very severe pneumonia. Urine collected during hospitalization (hospital admission time point) and 30xa0days later (convalescent time point) from cases and a single specimen from community controls was tested for urinary arsenic by graphite furnace atomic absorption.ResultsThe odds for pneumonia was nearly double for children with urinary arsenic concentrations higher than the first quartile (≥6xa0μg/L) at the hospital admission time point (Odd Ratio (OR):1.88 (95xa0% Confidence Interval (CI): 1.01, 3.53)), after adjustment for urinary creatinine, weight for height, breastfeeding, paternal education, age, and number of people in the household. This was consistent with findings at the convalescent time point where the adjusted OR for children with urinary arsenic concentrations greater than the first quartile (≥6xa0μg/L) was 2.32 (95xa0% CI: 1.33, 4.02).ConclusionWe observed a nearly two times higher odds of pneumonia for children with creatinine adjusted urinary arsenic concentrations greater than the first quartile (≥6xa0μg/L) at the hospital admission time point. This novel finding suggests that low to moderate arsenic exposure may be a risk factor for pneumonia in children under 5 years of age.

Limited Utility of Polymerase Chain Reaction in Induced Sputum Specimens for Determining the Causes of Childhood Pneumonia in Resource-Poor Settings: Findings From the Pneumonia Etiology Research for Child Health (PERCH) Study

Summary Among children with chest radiograph–confirmed pneumonia, polymerase chain reaction demonstrated relatively few additional pathogens in induced sputum specimens compared with nasopharyngeal/oropharyngeal specimens.