Effect of Pneumococcal Conjugate Vaccine on Pneumonia Incidence Rates among Children 2-59 Months of Age, Mongolia, 2015-2021.

Starting in June 2016, the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced into the routine immunization program of Mongolia by using a 2+1 dosing schedule, phased by district. We used prospective hospital surveillance to evaluate the vaccine's effect on pneumonia incidence rates among children 2-59 months of age over a 6-year period. Of 17,607 children with pneumonia, overall adjusted incidence rate ratios showed decreased primary endpoint pneumonia, very severe pneumonia, and probable pneumococcal pneumonia until June 2021. Results excluding and including the COVID-19 pandemic period were similar. Pneumonia declined in 3 districts that introduced PCV13 with catch-up campaigns but not in the 1 district that did not. After PCV13 introduction, vaccine-type pneumococcal carriage prevalence decreased by 44% and nonvaccine-type carriage increased by 49%. After PCV13 introduction in Mongolia, the incidence of more specific pneumonia endpoints declined in children 2-59 months of age; additional benefits were conferred by catch-up campaigns.

Training physicians in India to interpret pediatric chest radiographs according to World Health Organization research methodology.

BACKGROUND: Chest radiography is the standard for diagnosing pediatric lower respiratory infections in low-income and middle-income countries. A method for interpreting pediatric chest radiographs for research endpoints was recently updated by the World Health Organization (WHO) Chest Radiography in Epidemiological Studies project. Research in India required training local physicians to interpret chest radiographs following the WHO method. OBJECTIVE: To describe the methodology for training Indian physicians and evaluate the training's effectiveness. MATERIALS AND METHODS: Twenty-nine physicians (15 radiologists and 14 pediatricians) from India were trained by two WHO Chest Radiography in Epidemiological Studies members over 3 days in May 2019. Training materials were adapted from WHO Chest Radiography in Epidemiological Studies resources. Participants followed WHO methodology to interpret 60 unique chest radiographs before and after the training. Participants needed to correctly classify ≥80% of radiographs for primary endpoint pneumonia on the post-training test to be certified to interpret research images. We analyzed participant performance on both examinations. RESULTS: Twenty-six of 29 participants (89.7%) completed both examinations. The average score increased by 9.6% (95% confidence interval [CI] 5.0-14.1%) between examinations (P<0.001). Participants correctly classifying ≥80% of images for primary endpoint pneumonia increased from 69.2% (18/26) on the pretraining to 92.3% (24/26) on the post-training examination (P=0.003). The mean scores of radiologists and pediatricians on the post-training examination were not statistically different (P=0.43). CONCLUSION: Our results demonstrate this training approach using revised WHO definitions and tools was successful, and that non-radiologists can learn to apply these methods as effectively as radiologists. Such capacity strengthening is important for enabling research to support national policy decision-making in these settings. We recommend future research incorporating WHO chest radiograph methodology to consider modelling trainings after this approach.

Standardized Interpretation of Chest Radiographs in Cases of Pediatric Pneumonia From the PERCH Study.

BACKGROUND.: Chest radiographs (CXRs) are a valuable diagnostic tool in epidemiologic studies of pneumonia. The World Health Organization (WHO) methodology for the interpretation of pediatric CXRs has not been evaluated beyond its intended application as an endpoint measure for bacterial vaccine trials. METHODS.: The Pneumonia Etiology Research for Child Health (PERCH) study enrolled children aged 1-59 months hospitalized with WHO-defined severe and very severe pneumonia from 7 low- and middle-income countries. An interpretation process categorized each CXR into 1 of 5 conclusions: consolidation, other infiltrate, both consolidation and other infiltrate, normal, or uninterpretable. Two members of a 14-person reading panel, who had undertaken training and standardization in CXR interpretation, interpreted each CXR. Two members of an arbitration panel provided additional independent reviews of CXRs with discordant interpretations at the primary reading, blinded to previous reports. Further discordance was resolved with consensus discussion. RESULTS.: A total of 4172 CXRs were obtained from 4232 cases. Observed agreement for detecting consolidation (with or without other infiltrate) between primary readers was 78% (κ = 0.50) and between arbitrators was 84% (κ = 0.61); agreement for primary readers and arbitrators across 5 conclusion categories was 43.5% (κ = 0.25) and 48.5% (κ = 0.32), respectively. Disagreement was most frequent between conclusions of other infiltrate and normal for both the reading panel and the arbitration panel (32% and 30% of discordant CXRs, respectively). CONCLUSIONS.: Agreement was similar to that of previous evaluations using the WHO methodology for detecting consolidation, but poor for other infiltrates despite attempts at a rigorous standardization process.

Preliminary report from the World Health Organisation Chest Radiography in Epidemiological Studies project.

Childhood pneumonia is among the leading infectious causes of mortality in children younger than 5 years of age globally. Streptococcus pneumoniae (pneumococcus) is the leading infectious cause of childhood bacterial pneumonia. The diagnosis of childhood pneumonia remains a critical epidemiological task for monitoring vaccine and treatment program effectiveness. The chest radiograph remains the most readily available and common imaging modality to assess childhood pneumonia. In 1997, the World Health Organization Radiology Working Group was established to provide a consensus method for the standardized definition for the interpretation of pediatric frontal chest radiographs, for use in bacterial vaccine efficacy trials in children. The definition was not designed for use in individual patient clinical management because of its emphasis on specificity at the expense of sensitivity. These definitions and endpoint conclusions were published in 2001 and an analysis of observer variation for these conclusions using a reference library of chest radiographs was published in 2005. In response to the technical needs identified through subsequent meetings, the World Health Organization Chest Radiography in Epidemiological Studies (CRES) project was initiated and is designed to be a continuation of the World Health Organization Radiology Working Group. The aims of the World Health Organization CRES project are to clarify the definitions used in the World Health Organization defined standardized interpretation of pediatric chest radiographs in bacterial vaccine impact and pneumonia epidemiological studies, reinforce the focus on reproducible chest radiograph readings, provide training and support with World Health Organization defined standardized interpretation of chest radiographs and develop guidelines and tools for investigators and site staff to assist in obtaining high-quality chest radiographs.

Impact of childhood 13-valent pneumococcal conjugate vaccine introduction on adult pneumonia hospitalisations in Mongolia: a time series analysis.

Background: Few studies have assessed the potential indirect effects of childhood pneumococcal conjugate vaccine (PCV) programs on the adult pneumonia burden in resource-limited settings. We evaluated the impact of childhood PCV13 immunisation on adult all-cause pneumonia following a phased program introduction from 2016. Methods: We conducted a time-series analysis to assess changes in pneumonia hospitalisation incidence at four district hospitals in Mongolia. Adults (≥18 years) that met the clinical case definition for all-cause pneumonia were enrolled. A negative binomial mixed-effects model was used to assess the impact of PCV13 introduction on monthly counts of pneumonia admissions from January 2015-February 2022. We also performed a restricted analysis excluding the COVID-19 pandemic period. All models were stratified by age and assessed separately. Additional analyses assessed the robustness of our findings. Findings: The average annual incidence of all-cause pneumonia hospitalisation was highest in adults 65+ years (62.81 per 10,000 population) and declined with decreasing age. After adjusting for the COVID-19 pandemic period, we found that rates of pneumonia hospitalisation remained largely unchanged over time. We did not observe a reduction in pneumonia hospitalisation in any age group. Results from restricted and sensitivity analyses were comparable to the primary results, finding limited evidence of a reduced pneumonia burden. Interpretation: We did not find evidence of indirect protection against all-cause pneumonia in adults following childhood PCV13 introduction. Direct pneumococcal vaccination and other interventions should be considered to reduce burden of pneumonia among older adults. Funding: Pfizer clinical research collaboration agreement (contract number: WI236621).

Epidemiology of pneumonia in the pre-pneumococcal conjugate vaccine era in children 2-59 months of age, in Ulaanbaatar, Mongolia, 2015-2016.

BACKGROUND: Respiratory diseases, including pneumonia, are the second largest cause of under-five mortality in Mongolia and the most common cause of childhood hospitalization. However information regarding the contribution of Streptococcus pneumoniae to pneumonia causation in Mongolia is limited. We aimed to describe the epidemiology of hospitalized children aged 2-59 months with pneumonia, enrolled into a surveillance program in the period prior to pneumococcal conjugate vaccine (PCV) introduction, in Mongolia. METHODS: An expanded pneumonia surveillance program enrolled children, who met the surveillance case definition, at participating hospitals, between April 2015 and May 2016. Cumulative incidence rates were calculated by district for all pneumonia endpoints using district specific denominators from the Mongolian Health Department census for 2016. Socio-economic and disease-associated factors were compared between districts using chi-squared tests. RESULTS: A total of 4318 eligible children with pneumonia were enrolled over the 14 month period. Overall the incidence for all-cause pneumonia in children aged 12-59 months was 31.8 per 1000 population; children aged 2-11 months had an almost four-fold higher incidence than children aged 12-59 months. Differences were found between districts with regards to housing type, fuel used for cooking, hospital admission practices and the proportions of severe and primary endpoint pneumonia. DISCUSSION: This study shows a high burden of pneumonia in children aged 2-59 months in Mongolia prior to PCV introduction. Rates differed somewhat by district and age group and were influenced by a number of socio-economic factors. It will be important to consider these differences and risk factors when assessing the impact of PCV introduction.

Economic evaluation of a clinical protocol for diagnosing emergency patients with suspected pulmonary embolism.

BACKGROUND: The objective of this paper is to estimate the amount of cost-savings to the Australian health care system from implementing an evidence-based clinical protocol for diagnosing emergency patients with suspected pulmonary embolism (PE) at the Emergency department of a Victorian public hospital with 50,000 presentations in 2001-2002. METHODS: A cost-minimisation study used the data collected in a controlled clinical trial of a clinical protocol for diagnosing patients with suspected PE. The number and type of diagnostic tests in a historic cohort of 185 randomly selected patients, who presented to the emergency department with suspected PE during an eight month period prior to the clinical trial (January 2002-August 2002) were compared with the number and type of diagnostic tests in 745 patients, who presented to the emergency department with suspected PE from November 2002 to August 2003. Current Medicare fees per test were used as unit costs to calculate the mean aggregated cost of diagnostic investigation per patient in both study groups. A t-test was used to estimate the statistical significance of the difference in the cost of resources used for diagnosing PE in the control and in the intervention group. RESULTS: The trial demonstrated that diagnosing PE using an evidence-based clinical protocol was as effective as the existing clinical practice. The clinical protocol offers the advantage of reducing the use of diagnostic imaging, resulting in an average cost savings of at least $59.30 per patient. CONCLUSION: Extrapolating the observed cost-savings of $59.30 per patient to the whole of Australia could potentially result in annual savings between $3.1 million to $3.7 million.

Reducing the use of diagnostic imaging in patients with suspected pulmonary embolism: validation of a risk assessment strategy.

OBJECTIVES: The aims of this study were to measure the: (i) effects of implementation of a new risk assessment strategy for patients with suspected pulmonary embolism (PE) on the use of imaging and D-dimer assay; (ii) negative predictive value for PE of a combination of low risk and negative D-dimer assay; and (iii) compliance of ED clinicians with the strategy. METHODS: A non-randomized clinical trial was conducted in the ED of a 720-bed teaching hospital between November 2002 and August 2003. Study subjects with suspected PE were compared with 191 randomly selected historical controls. The risk assessment strategy of Kline et al. was disseminated and implemented. RESULTS: The negative predictive value for PE was 99% (95% confidence interval [CI] = 97-100%) in 114 patients with low risk and negative D-dimer. There was a 21% absolute reduction in the rate of imaging following the implementation of the risk assessment strategy (56% vs 77%, P < 0.001). CONCLUSION: Low risk combined with a negative D-dimer result may allow exclusion of PE without imaging.

Rates of radiologically confirmed pneumonia as defined by the World Health Organization in Northern Territory Indigenous children.

OBJECTIVE: To determine the burden of hospitalised, radiologically confirmed pneumonia (World Health Organization protocol) in Northern Territory Indigenous children. DESIGN, SETTING AND PARTICIPANTS: Historical, observational study of all hospital admissions for any diagnosis of NT resident Indigenous children, aged between > or = 29 days and < 5 years, 1 April 1997 to 31 March 2005. INTERVENTION: All chest radiographs taken during these admissions, regardless of diagnosis, were assessed for pneumonia in accordance with the WHO protocol. MAIN OUTCOME MEASURE: The primary outcome was endpoint consolidation (dense fluffy consolidation [alveolar infiltrate] of a portion of a lobe or the entire lung) present on a chest radiograph within 3 days of hospitalisation. RESULTS: We analysed data on 24,115 hospitalised episodes of care for 9492 children and 13,683 chest radiographs. The average annual cumulative incidence of endpoint consolidation was 26.6 per 1000 population per year (95% CI, 25.3-27.9); 57.5 per 1000 per year in infants aged 1-11 months, 38.3 per 1000 per year in those aged 12-23 months, and 13.3 per 1000 per year in those aged 24-59 months. In all age groups, rates of endpoint consolidation in children in the arid southern region of NT were about twice that of children in the tropical northern region. CONCLUSION: The rates of severe pneumonia in hospitalised NT Indigenous children are among the highest reported in the world. Reducing this unacceptable burden of disease should be a national health priority.

Persistent renal cortical scintigram defects in children 2 years after urinary tract infection.

BACKGROUND: Renal cortical scintigraphic studies challenge the role of vesicoureteric reflux in renal scar development, emphasizing instead the part played by acute pyelonephritis. OBJECTIVE: To determine the prevalence of renal cortical defects in a child cohort 2 years after the child's first diagnosed urinary tract infection and to analyze the relationship of these defects with acute illness variables, primary vesicoureteric reflux and recurrent infections. MATERIALS AND METHODS: In a prospective cohort study, 193 children younger than 5 years with their first proven urinary tract infection underwent renal sonography, voiding cystourethrogram, and renal cortical scintigraphy within 15 days of diagnosis. Two years later, 150 of the 193 children, or 77.7%, had a further renal cortical scintigram, including 75, or 86.2%, of the 87 children who had acute scintigraphic defects. The relationship of cortical defects to age, gender, pre-treatment symptom duration, hospitalization, presence and grade of vesicoureteric reflux, and recurrent urinary tract infections was evaluated. RESULTS: Overall, 20 of the 150 (13.3%; 95% confidence interval (CI) 8.3, 19.8) children had persistent defects 2 years after infection. This included 20 of 75 (26.7%; 95% CI 17.1, 38.1) with initially abnormal scintigrams. No new defects were detected. Although acute defects were more common in the young, those with persistent defects were older (median ages 16.4 vs. 6.8 months, P=0.004) than those with transient abnormalities. After adjustment for age, persistent defects were no longer associated with gender and were not predicted by acute illness variables, primary vesicoureteric reflux or recurrent infections. CONCLUSIONS: Renal cortical scintigraphic defects persisted in approximately one-quarter of young children after their first proven urinary tract infection. The associated clinical features, however, failed to predict scar formation. It is possible that some of the scintigraphic defects preceded the infection by arising from either previously undiagnosed acute pyelonephritis or from underlying congenital dysplasia. The etiology of scars may be best addressed by determining whether prevention of urinary tract infections from birth avoids post-natal scar acquisition or extension.

Time course of transient cortical scintigraphic defects associated with acute pyelonephritis.

BACKGROUND: Acute pyelonephritis is distinguished from renal scarring using repeat cortical scintigraphy. The defects of acute pyelonephritis resolve, while those of scars persist. OBJECTIVE: To determine the duration of reversible cortical defects following acute pyelonephritis and the time interval required to differentiate infection from scars. MATERIALS AND METHODS: An observational prospective study of 193 children (386 kidneys) aged less than 5 years following their first proven urinary tract infection (UTI). Renal cortical scintigraphic defects were detected in 112 (29%) kidneys within 15 days of diagnosis. Of these, 95 underwent repeat renal cortical scans 2 years after the UTI, including 50 with additional scans performed within 2-6 months of infection. RESULTS: Of the 50 kidneys undergoing a second renal cortical scan within 2-6 months of the first UTI, 22 (44%) had persistent defects. A third scan was performed on 17 (77%) kidneys after 2 years, by which time defects had resolved in another 8 (47%) kidneys. The predictive value of defects detected within 2-6 months of UTI representing scars is 53% (95% CI 28, 77). Overall, nine (18%) kidneys with initial renal cortical abnormalities had permanent defects. In the 45 kidneys undergoing a second cortical scan more than 6 months after the UTI, 11 (24%) had persistent defects. None of the 95 kidneys undergoing serial scans developed new or larger defects. CONCLUSIONS: Renal scars may not be reliably diagnosed by cortical scintigraphy performed within 6 months of UTI because the inflammatory lesions may not have fully resolved.