Evaluation of the impact of childhood 13-valent pneumococcal conjugate vaccine introduction on adult pneumonia in Ulaanbaatar, Mongolia: study protocol for an observational study.

BACKGROUND: Community-acquired pneumonia is an important cause of morbidity and mortality in adults. Approximately one-third of pneumonia cases can be attributed to the pneumococcus. Pneumococcal conjugate vaccines (PCVs) protect against colonisation with vaccine-type serotypes. The resulting decrease in transmission of vaccine serotypes leads to large indirect effects. There are limited data from developing countries demonstrating the impact of childhood PCV immunisation on adult pneumonia. There are also insufficient data available on the burden and severity of all-cause pneumonia and respiratory syncytial virus (RSV) in adults from low resource countries. There is currently no recommendation for adult pneumococcal vaccination with either pneumococcal polysaccharide vaccine or PCVs in Mongolia. We describe the protocol developed to evaluate the association between childhood 13-valent PCV (PCV13) vaccination and trends in adult pneumonia. METHODS: PCV13 was introduced into the routine childhood immunisation schedule in Mongolia in a phased manner from 2016. In March 2019 we initiated active hospital-based surveillance for adult pneumonia, with the primary objective of evaluating trends in severe hospitalised clinical pneumonia incidence in adults 18 years and older in four districts of Ulaanbaatar. Secondary objectives include measuring the association between PCV13 introduction and trends in all clinically-defined pneumonia, radiologically-confirmed pneumonia, nasopharyngeal carriage of S. pneumoniae and pneumonia associated with RSV or influenza. Clinical questionnaires, nasopharyngeal swabs, urine samples and chest radiographs were collected from enrolled patients. Retrospective administrative and clinical data were collected for all respiratory disease-related admissions from January 2015 to February 2019. DISCUSSION: Establishing a robust adult surveillance system may be an important component of monitoring the indirect impact of PCVs within a country. Monitoring indirect impact of childhood PCV13 vaccination on adult pneumonia provides additional data on the full public health impact of the vaccine, which has implications for vaccine efficiency and cost-effectiveness. Adult surveillance in Mongolia will contribute to the limited evidence available on the burden of pneumococcal pneumonia among adults in low- and middle-income countries, particularly in the Asia-Pacific region. In addition, it is one of the few examples of implementing prospective, population-based pneumonia surveillance to evaluate the indirect impact of PCVs in a resource-limited setting.

Accuracy of High-Throughput Nanofluidic PCR-Based Pneumococcal Serotyping and Quantification Assays Using Sputum Samples for Diagnosing Vaccine Serotype Pneumococcal Pneumonia: Analyses by Composite Diagnostic Standards and Bayesian Latent Class Models.

The lack of reliable diagnostic tests for detecting vaccine serotype pneumococcal pneumonia (VTPP) remains a challenging issue in pneumococcal vaccine studies. This study assessed the performances of high-throughput nanofluidic PCR-based pneumococcal serotyping and quantification assay methods using sputum samples (the nanofluidic sputum quantitative PCR [Sp-qPCR] assay) to diagnose 13-valent pneumococcal conjugate VTPP compared with the performance of the serotype-specific urinary antigen detection (UAD) assay using urine samples. Adult pneumonia patients from Japan were enrolled in this study between September 2012 and August 2014. Sputum samples were subjected to the nanofluidic Sp-qPCR assay, quantitatively cultured, and serotyped by the Quellung reaction (SpQt). Urine samples were tested by the UAD method. The diagnostic performances of these tests were assessed using composite reference standards and Bayesian latent class models (BLCMs). Among 244 total patients, 27 (11.1%) tested positive with the UAD assay, while 16 (6.6%) and 34 (13.9%) tested positive with the SpQt and nanofluidic Sp-qPCR assays, respectively, with a cutoff value of ≥104 DNA copies/ml, which showed the maximum value of the Youden index. Using BLCMs, the estimated prevalence for VTPP was 12.9%, and the nanofluidic Sp-qPCR assay demonstrated the best performance (sensitivity, 90.2%; specificity, 96.9%), followed by UAD (sensitivity, 75.6%; specificity, 97.9%) and SpQt (sensitivity, 45.8%; specificity, 99.5%). However, when a higher cutoff value of ≥107 DNA copies/ml was applied, the performance of UAD became comparable to that of Sp-qPCR. The vaccine serotype-specific pneumococcal DNA load in sputum among UAD-positive patients was 3 logs higher than that among UAD-negative patients (P = 0.036). The nanofluidic Sp-qPCR assay may be accurate and useful for detecting VTPP among adults.

Six underlying health conditions strongly influence mortality based on pneumonia severity in an ageing population of Japan: a prospective cohort study.

BACKGROUND: Mortality prediction of pneumonia by severity scores in patients with multiple underlying health conditions has not fully been investigated. This prospective cohort study is to identify mortality-associated underlying health conditions and to analyse their influence on severity-based pneumonia mortality prediction. METHODS: Adult patients with community-acquired pneumonia or healthcare-associated pneumonia (HCAP) who visited four community hospitals between September 2011 and January 2013 were enrolled. Candidate underlying health conditions, including demographic and clinical characteristics, were incorporated into the logistic regression models, along with CURB (confusion, elevated urea nitrogen, tachypnoea, and hypotension) score as a measure of disease severity. The areas under the receiver operating characteristic curves (AUROC) of the predictive index based on significant underlying health conditions was compared to that of CURB65 (CURB and age ≥ 65) score or Pneumonia severity index (PSI). Mortality association between disease severity and the number of underlying health conditions was analysed. RESULTS: In total 1772 patients were eligible for analysis, of which 140 (7.9%) died within 30 days. Six underlying health conditions were independently associated: home care (adjusted odds ratio, 5.84; 95% confidence interval, CI, 2.28-14.99), recent hospitalization (2.21; 1.36-3.60), age ≥ 85 years (2.15; 1.08-4.28), low body mass index (1.99, 1.25-3.16), neoplastic disease (1.82; 1.17-2.85), and male gender (1.78; 1.16-2.75). The predictive index based on these conditions alone had a significantly or marginally higher AUROC than that based on CURB65 score (0.78 vs 0.66, p = 0.02) or PSI (0.78 vs 0.71, p = 0.05), respectively. Compared to this index, the AUROC of the total score consisting of six underlying health conditions and CURB score (range 0-10) did not improve mortality predictions (p = 0.3). In patients with one or less underlying health conditions, the mortality was discretely associated with severe pneumonia (CURB65 ≥ 3) (risk ratio: 7.24, 95%CI: 3.08-25.13), whereas in patients with 2 or more underlying health conditions, the mortality association with severe pneumonia was not detected (risk ratio: 1.53, 95% CI: 0.94-2.50). CONCLUSIONS: Mortality prediction based on pneumonia severity scores is highly influenced by the accumulating number of underlying health conditions in an ageing society. The validation using a different cohort is necessary to generalise the conclusion.

A Study on the Etiology and Clinical Manifestations of Community-Acquired Pneumonia in Adults in Western India.

BACKGROUND:  Community-acquired pneumonia (CAP) is an acute lung infection affecting the alveoli in individuals who have not had recent exposure to healthcare settings. It is characterized by newly detected pulmonary infiltration on a chest X-ray or computed tomography scan, accompanied by at least two of the following symptoms: a new or worsening cough, shortness of breath, increased sputum production, fever or hypothermia, pleuritic chest pain, hypoxia, confusion, or an abnormal WBC count (either leukopenia or leukocytosis). It is a major contributor to global mortality and morbidity, especially in elderly populations. This study aims to investigate the etiology of CAP in our region and analyze the clinical characteristics of patients diagnosed with CAP. METHODOLOGY:  This prospective, hospital-based study was conducted at Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, a 2,011-bed multispecialty hospital. The study included 100 patients over 18 years old, diagnosed with CAP, and hospitalized between January 2023 and January 2024. All patients underwent a thorough clinical assessment, and sputum cultures were collected on the day of admission. Patients under 18 years old, those who had been hospitalized within the preceding two weeks, individuals with pneumonia caused by tuberculosis or aspiration pneumonia, patients with compromised immune systems, and pregnant women were excluded. RESULTS:  The study included 100 patients with a mean age of 53.13 years (±18.31). The most common age group was 59-68 years, which included 25 (25%) cases, followed by the 69-78 year age group with 18 (18%) cases and the 18-28 year age group with 15 (15%) cases. The majority were male, with 61 (61%) cases. Common symptoms included fever in 78 cases (78%), chest pain in 69 cases (69%), dyspnea in 65 cases (65%), and cough in 51 cases (51%). Sputum cultures showed growth in 65 cases (65%), with Klebsiella pneumoniae being the most prevalent pathogen in 28 cases (43%), followed by Streptococcus pneumoniae in 18 cases (28%). Together, these two pathogens accounted for 46 out of 65 positive samples (70%). CONCLUSIONS:  This study highlights the clinical profile and rising etiology of K. pneumoniae in CAP in adults in Western India, particularly in the elderly. These findings underscore the need for periodic updates on CAP etiology to inform empirical treatment strategies effectively. Future research should use advanced diagnostics and diverse samples to refine CAP management, with continuous monitoring to update treatment protocols.

Epidemiology of pneumonia in hospitalized adults ≥18 years old in four districts of Ulaanbaatar, Mongolia, 2015-2019.

Background: Community-acquired pneumonia is a leading cause of morbidity and mortality among children and adults worldwide. Adult pneumonia surveillance remains limited in many low- and middle-income settings, resulting in the disease burden being largely unknown. Methods: A retrospective cohort study was conducted by reviewing medical charts for respiratory admissions at four district hospitals in Ulaanbaatar during January 2015-February 2019. Characteristics of community-acquired pneumonia cases were summarized by disease severity and age. To explore factors associated with severe pneumonia, we ran univariable and age-adjusted logistic regression models. Incidence rates were calculated using population denominators. Results: In total, 4290 respiratory admissions met the case definition for clinical pneumonia, including 430 admissions of severe pneumonia. The highest proportion of severe pneumonia admissions occurred in adults >65 years (37.4%). After adjusting for age, there were increased odds of severe pneumonia in males (adjusted odds ratio [aOR]: 1.63; 95% confidence interval [CI]: 1.33-2.00) and those with ≥1 underlying medical condition (aOR: 1.46; 95% CI: 1.14-1.87). The incidence of hospitalized pneumonia in adults ≥18 years increased from 13.49 (95% CI: 12.58-14.44) in 2015 to 17.65 (95% CI: 16.63-18.71) in 2018 per 10,000 population. The incidence of severe pneumonia was highest in adults >65 years, ranging from 9.29 (95% CI: 6.17-13.43) in 2015 to 12.69 (95% CI: 9.22-17.04) in 2018 per 10,000 population. Interpretations: Vaccination and other strategies to reduce the risk of pneumonia, particularly among older adults and those with underlying medical conditions, should be prioritized. Funding: Pfizer clinical research collaboration agreement (contract number: WI236621).

Epidemiology and Characteristics of Respiratory Syncytial Virus Pneumonia in Critically Ill Adults.

Background: Severe respiratory syncytial virus (RSV)-associated pneumonia in adults has rarely been addressed. We investigated the burden and clinical characteristics of severe RSV-associated pneumonia in critically ill adult patients. Methods: We analyzed a prospective cohort of 2865 adults with severe pneumonia who were admitted to the intensive care unit in a 2700-bed tertiary care hospital from 2010 to 2019. The epidemiology, characteristics, and outcomes of 92 cases of severe RSV-associated pneumonia and 163 cases of severe influenza virus (IFV)-associated pneumonia were compared. Results: Of 1589 cases of severe community-acquired pneumonia, the incidence of RSV-associated pneumonia was less than half that of IFV-associated pneumonia (3.4% vs 8.1%). However, among 1276 cases of severe hospital-acquired pneumonia (HAP), there were slightly more cases of RSV-associated than IFV-associated pneumonia (3.8% vs 3.5%). During the 9 epidemic seasons, RSV-A (5 seasons) and RSV-B (4 seasons) predominated alternately. Structural lung disease, diabetes mellitus, and malignancy were common underlying diseases in both groups. Immunocompromise (57.6% vs 34.4%; P < .001) and hospital acquisition (47.8% vs 23.9%; P < .001) were significantly more common in the RSV group. Coinfection with Streptococcus pneumoniae (3.3% vs 9.8%; P = .08) and methicillin-susceptible Staphylococcus aureus (1.1% vs 6.8%; P = .06) tended to be less frequent in the RSV group. The 90-day mortality was high in both groups (39.1% vs 40.5%; P = .89). Conclusions: RSV infection was associated with substantial morbidity and mortality in critically ill adult patients, similar to IFV. The relatively higher incidence of RSV in severe HAP suggests that the transmissibility of RSV can exceed that of IFV in a hospital setting.

Definitive and Indeterminate Pseudomonas aeruginosa Infection in Adults with Community-acquired Pneumonia: A Prospective Observational Study.

Rationale: Pneumonia due to Pseudomonas aeruginosa (PA) is associated with high mortality and requires antipseudomonal treatment. Because PA can colonize the respiratory tract, the diagnosis of pathogenic PA involvement is challenging. Objectives: To determine the prevalence of definitive and indeterminate PA infection in community-acquired pneumonia, to describe the clinical and microbiological profiles, and to estimate the burden of unnecessary antipseudomonal drug prescriptions. Methods: We prospectively enrolled 2,701 patients with community-acquired pneumonia. Using stringent criteria for diagnosing PA pneumonia, we generated the following three groups: 1) definitive PA, 2) indeterminate PA, and 3) non-PA pneumonia. Results: The prevalence of definitive PA pneumonia was 0.9% (n = 25), and that of indeterminate PA pneumonia was 4.9% (n = 131). Considerable clinical differences were observed among the groups. Patients with definitive PA pneumonia were more likely to have a history of tuberculosis and chronic obstructive pulmonary disease/bronchiectasis and had a higher 30-day mortality (28%) than patients with non-PA pneumonia. Patients with indeterminate PA pneumonia were more likely to have comorbidities than patients with non-PA pneumonia. More than half of the patients with indeterminate PA and 25% of the patients with non-PA pneumonia were treated with an antipseudomonal drug. No patients with definitive PA pneumonia had multidrug resistance. Conclusions: In this population, the prevalence of community-acquired pneumonia due to PA was low. The clinical features and 30-day mortality rates of patients with indeterminate PA pneumonia were different from those of patients with definitive PA pneumonia. Most of the prescribed antipseudomonal drugs for patients with community-acquired pneumonia were potentially unnecessary.