Paediatric pneumonia remains a significant public health concern globally, and the risk factors for pneumonia and carriage vary across different populations. The accuracy of pneumococcal urinary antigen test (PUAT) remains unclear. We aimed to determine the prevalence of pneumococcal carriage, and the risk factors associated with pneumonia and carriage among children aged under 5 years in Peninsular Malaysia, and to evaluate the performance of the PUAT at detecting pneumococcal carriage. A total of 500 cases of pneumonia and 500 age-matched controls at three tertiary hospitals across three states in Peninsular Malaysia were recruited from October 2021 to August 2023. Nasopharyngeal swabs (NPS) were taken to test for Streptococcus pneumoniae (Spn) using culture and multiplex-PCR while urine samples were collected for PUAT with BinaxNOW®. Logistic regression analyses were fitted for paediatric pneumonia and pneumococcal carriage risk factors. The overall prevalence of nasopharyngeal pneumococcal carriage was 15.4% (n = 154) based on culture and optochin susceptibility, with identical rates observed among children with pneumonia and healthy controls. PUAT positivity was higher among pneumonia cases (11.8%, 59/500) than the controls (8.8%, 44/500) but was not statistically significant (p = 0.119). The carriage prevalence was significantly higher in the east coast (19.5%) compared to the central west coast (9.5%) (p < 0.001). Significant predictors of pneumonia were having siblings aged under 5 years (p = 0.002), pre-existing illness (p < 0.001), exposure to indoor smoking (p = 0.01), overcrowding (p = 0.012), underweight (p = 0.001) and obesity (p = 0.023). The predictors of pneumococcal carriage were recruiting sites and pneumococcal vaccination status. Compared to culture and PCR, the sensitivity and specificity of BinaxNOW® to detect Spn in urine were similar at about 31% and 93%, respectively. Pneumococcal carriage prevalence was similar in pneumonia cases and healthy controls, and the true burden of pneumococcal pneumonia in Malaysia remains unknown. Our findings identified risk factors for childhood pneumonia and pneumococcal carriage that are consistent with those reported elsewhere. The BinaxNOW® showed low sensitivity and moderate specificity indicating its limited utility as a standalone diagnostic tool for Spn detection in clinical settings. A focus should be made to recognise risk profiles to support early identification, timely intervention, and prevention strategies for respiratory infections in vulnerable paediatric populations. There is a need for continued Spn carriage surveillance and ongoing research to improve diagnostics to guide public health strategies for the prevention of pneumococcal infections.

BackgroundStreptococcus pneumoniae (the pneumococcus) is a leading cause of community-acquired pneumonia. Pneumococci are categorised into serotypes, based on the type of capsular polysaccharide produced, which has important implications for virulence, vaccine impact and global surveillance. Recently, we identified a novel serotype, which we named 33G, that is comprised of an O-acetylated hexasaccharide repeat unit. In this study, we report and describe variants of 33G, designated 33G-like, which we isolated from the nasopharynx of two adults hospitalised with pneumonia in Mongolia.MethodsSerological comparison of 33G and 33G-like pneumococci were conducted by Quellung serotyping. Genetic analysis of the capsular polysaccharide loci was performed using whole genome sequencing. Polysaccharide composition was determined using 1H nuclear magnetic resonance.ResultsBy Quellung serotyping, 33G pneumococci type as both 10B and 33B whereas 33G-like pneumococci type as both 10B and 33F. Genomic analysis of the capsular polysaccharide locus revealed 33G-like loci are identical to 33G, except for frameshift mutations in the wciG gene which encodes an acetyltransferase responsible for the O-acetylation of beta-galactofuranose (β-Galf) in the capsular polysaccharide repeat unit. We constructed an artificial 33G-like by deleting wciG in a 33G strain and confirmed this gene was responsible for the serological differences between 33G and 33G-like pneumococci. Lastly, 1H nuclear magnetic resonance confirmed the O-acetylation present in the 33G polysaccharide is absent in the 33G-like polysaccharide.ConclusionsHere, we have provided serological, genetic and biochemical evidence that the 33G-like capsule differs to 33G and all other pneumococcal serotypes, meeting the requirements to be designated as a new serotype, which we have named 33H.

BackgroundPopulations affected by humanitarian crises likely experience high burdens of pneumococcal disease. Streptococcus pneumoniae carriage estimates are essential to understand pneumococcal transmission dynamics and the potential impact of pneumococcal conjugate vaccines (PCV). Over 100 million people are forcibly displaced worldwide, yet here we present only the second pneumococcal carriage estimates for a displaced population.MethodsIn October 2019, we conducted a cross-sectional survey among internally displaced people (IDP) living in Digaale, a permanent IDP camp in Somaliland where PCV has not been implemented. We collected nasopharyngeal swab samples from 453 residents which were assessed for presence of pneumococci and serotyped using DNA microarray.ResultsWe found that pneumococcal carriage prevalence was 36% (95%CI 31–40) in all ages, and 70% (95%CI 64–76) in children under 5. The three most common serotypes were vaccine serotypes 6B, 19F, and 23F. We estimated that the serotypes included in the 10-valent PNEUMOSIL vaccine were carried by 41% (95%CI 33–49) of all pneumococcal carriers and extrapolated that they caused 52% (95%CI 35–70) of invasive pneumococcal disease. We found some evidence that pneumococcal carriage was associated with recent respiratory symptoms, the total number of physical contacts made, and with malnutrition in children under 5. Through linking with a nested contact survey we projected that pneumococcal exposure of children under 2 was predominantly due to contact with children aged 2–5 (39%; 95%CI 31–48) and 6–14 (25%; 95%CI 17–34).ConclusionsThese findings suggest considerable potential for direct and indirect protection against pneumococcal disease in Digaale through PCV use in children and potentially adolescents.

BackgroundMost Canadians receive their care in community hospitals, yet most clinical research is conducted in academic hospitals. This study aims to compare patients with community acquired pneumonia (CAP) treated in academic and community hospitals with respect to their demographics, clinical characteristics, treatments and outcomes.MethodsThis nested observational cohort substudy of the Community Acquired Pneumonia: Toward InnoVAtive Treatment (CAPTIVATE) trial included 1,329 hospitalized adults with CAP recruited between March 1st, 2018 and September 31st, 2023 from 15 Canadian hospitals. Unadjusted and adjusted analyses for age, sex and co-morbidities using logistic, Cox and censored quantile regressions were conducted.ResultsPatients in community hospitals were older (mean [SD] 75.0 [15.7] years vs. 68.3 [16.2] years; p < 0.001), were more likely to be female (49.7% vs. 41.0%, p = 0.002), and had more comorbidities (75.9% vs. 64.8%, p < 0.001). More patients in community hospitals received corticosteroids (49.2% vs. 37.4%, p < 0.001). Community hospital patients had a higher likelihood of developing acute respiratory distress syndrome (OR 3.13, 95% CI: 1.87, 5.24, p = < 0.001), and acute cardiac injury (OR 2.53, 95% CI: 1.33, 4.83, p = 0.005). In unadjusted and adjusted analyses, 28-day mortality difference did not meet statistical significance (OR 1.43, 95% CI: 0.98, 20.7, p = 0.062 and OR 1.23, 95% CI: 0.81, 1.87, p = 0.332, respective).ConclusionPatients with CAP in Canadian community and academic hospitals differed with respect to their age, clinical characteristics, treatments and outcomes, emphasizing the importance of including more community hospitals in clinical research studies to ensure the generalizability of results.

BackgroundBacterial pneumonia is among the leading causes of morbidity and mortality worldwide. The extensive misuse and overuse of antibiotics observed during the Corona Virus Disease 2019 (COVID-19) pandemic may have changed the patterns of pathogens causing bacterial pneumonia and their antibiotic susceptibility profiles. This study was designed to establish the prevalence of culture-confirmed bacterial pneumonia and describe their antimicrobial susceptibility profile in adult patients who presented with signs and symptoms of lower respiratory tract infections (LRTIs) during the COVID-19 pandemic.MethodologyThis hospital-based cross-sectional study was conducted from July 2021 to July 2022 at a zonal referral hospital and two district hospitals in Mwanza, Tanzania. Demographic and clinical data were collected using a standardized questionnaire. Sputum samples were processed by conventional culture followed by the identification of isolates and antibiotic susceptibility testing. Descriptive data analysis was performed using STATA version 15.0.ResultsA total of 286 patients with a median age of 40 (IQR 29–60) years were enrolled in the study. More than half of the patients enrolled were females (52.4%, n = 150). The overall prevalence of bacterial pneumonia was 34.3% (n = 98). The majority of the bacterial pathogens isolated were Gram-negative bacteria (GNB) (61.2%, 60/98), with a predominance of Klebsiella spp., 38.8% (38/98), followed by Streptococcus pyogenes (21.4%, 21/98). Multi drug resistant (MDR) bacteria were detected in 72/98 (73.5%) of the isolates. The proportions of GNB-resistant strains were 60.0% (36/60) for ciprofloxacin, 60% (36/60) for amoxicillin, 60% (36/60) for amoxicillin, 68.3% (41/60) for trimethoprim-sulfamethoxazole and 58.3% (35/60) for ceftriaxone.ConclusionOne-third of the patients with signs and symptoms of LRTIs had laboratory-confirmed bacterial pneumonia with a predominance of Gram negative MDR bacteria. This calls for continuous antimicrobial resistance (AMR) surveillance and antimicrobial stewardship programs in the study setting and other settings in developing countries as important strategies for tackling AMR.

BackgroundHaemophilus influenzae community-acquired pneumonia (CAP) is common, and it is equally common to Streptococcus pneumoniae in some settings. The purpose of this study was to provide additional data on patients affected by H. influenzae CAP and their outcomes.MethodsStreptococcus pneumoniae-caused CAP (111 cases) was compared to CAP with H. influenzae (53 cases). Patients were adults (≥ 18 years) from the prospective study “Etiology of community acquired pneumonia in Sweden” (ECAPS), which was established during the years 2016–2018.ResultsCases with H. influenzae CAP were significantly older compared to S. pneumoniae CAP (median 77 vs 70 years, p = 0.037) albeit similar comorbidities. Haemophilus influenzae was generally absent in the bloodstream compared to S. pneumoniae (18% vs 2%, p = 0.01) but clinical presentations were comparable. Only a minority of patients, 34% with H. influenzae and 41% with S. pneumoniae CAP had underlying lung disease.ConclusionIn the light of childhood immunization campaigns against S. pneumoniae and the increasing numbers of pneumococcal vaccinations among the elderly, coupled with an aging population, the incidence of CAP caused by H. influenzae may increase. Further research is needed to understand the impact of H. influenzae CAP and to a development of a vaccine against this emerging microbe.

BackgroundThere exists consistent empirical evidence in the literature pointing out ample heterogeneity in terms of the clinical evolution of patients with COVID-19. The identification of specific phenotypes underlying in the population might contribute towards a better understanding and characterization of the different courses of the disease. The aim of this study was to identify distinct clinical phenotypes among hospitalized patients with SARS-CoV-2 pneumonia using machine learning clustering, and to study their association with subsequent clinical outcomes as severity and mortality.MethodsMulticentric observational, prospective, longitudinal, cohort study conducted in four hospitals in Spain. We included adult patients admitted for in-hospital stay due to SARS-CoV-2 pneumonia. We collected a broad spectrum of variables to describe exhaustively each case: patient demographics, comorbidities, symptoms, physiological status, baseline examinations (blood analytics, arterial gas test), etc.For the development and internal validation of the clustering/phenotype models, the dataset was split into training and test sets (50% each). We proposed a sequence of machine learning stages: feature scaling, missing data imputation, reduction of data dimensionality via Kernel Principal Component Analysis (KPCA), and clustering with the k-means algorithm. The optimal cluster model parameters –including k, the number of phenotypes– were chosen automatically, by maximizing the average Silhouette score across the training set.ResultsWe enrolled 1548 patients, each of them characterized by 92 clinical attributes (d=109 features after variable encoding). Our clustering algorithm identified k=3 distinct phenotypes and 18 strongly informative variables: Phenotype A (788 cases [50.9% prevalence] – age∼57, Charlson comorbidity∼1, pneumonia CURB-65 score∼0 to 1, respiratory rate at admission∼18 min-1, FiO2∼21%, C-reactive protein CRP∼49.5 mg/dL [median within cluster]); phenotype B (620 cases [40.0%] – age∼75, Charlson∼5, CURB-65∼1 to 2, respiration∼20 min-1, FiO2∼21%, CRP∼101.5 mg/dL); and phenotype C (140 cases [9.0%] – age∼71, Charlson∼4, CURB-65∼0 to 2, respiration∼30 min-1, FiO2∼38%, CRP∼152.3 mg/dL). Hypothesis testing provided solid statistical evidence supporting an interaction between phenotype and each clinical outcome: severity and mortality. By computing their corresponding odds ratios, a clear trend was found for higher frequencies of unfavourable evolution in phenotype C with respect to B, as well as more unfavourable in phenotype B than in A.ConclusionA compound unsupervised clustering technique (including a fully-automated optimization of its internal parameters) revealed the existence of three distinct groups of patients – phenotypes. In turn, these showed strong associations with the clinical severity in the progression of pneumonia, and with mortality.

PurposeTo design a randomized clinical trial to assess the efficacy and safety of favipiravir in patients with COVID-19 disease with pneumonia.MethodsA randomized, double blind, placebo-controlled clinical trial of favipiravir in patients with COVID-19 pneumonia was conducted in three Spanish sites. Randomization 1:1 to favipiravir or placebo (in both groups added to the Standard of Care) was performed to treat the patients with COVID-19 pneumonia. The primary endpoint was “time to clinical improvement,” measured as an improvement for ≥ two categories on a 7-point WHO ordinal scale in an up to 28 days' time frame.ResultsForty-four patients were randomized (23 in the favipiravir group and 21 in the placebo group). The median time to clinical improvement was not different between the favipiravir and the placebo arms (10 days for both groups) and none of the secondary endpoints showed significant differences between arms.The proportion of adverse events (both serious and non-serious) was statistically different between the favipiravir group (68.29%) and the placebo group (31.7%) (p = 0.019), but there was insufficient statistical evidence to correlate the degree of severity of the events with the treatment group.ConclusionsFavipiravir administered for ten days to patients with COVID-19 and pneumonia did not improve outcomes compared with placebo. Although this is an underpowered negative study, efficacy results align with other randomized trials. However, in the present study, the non-serious adverse events were more frequent in the favipiravir group.

BackgroundPneumococcal community-acquired pneumonia (P-CAP) is a major cause of morbidity and hospitalization. Several host genetics factors influencing risk of pneumococcal disease have been identified, with less information about its association with P-CAP. The aim of the study was to assess the influence of single nucleotide polymorphisms (SNP) within key genes involved in the innate immune response on the susceptibility to P-CAP and to study whether these polymorphic variants were associated with the severity and outcome of the episodes in a cohort of adult Caucasian patients.MethodsSeventeen SNPs from 7 genes (IL-R1, IL-4, IL-10, IL-12B, NFKBIA, NFKBIE, NFKBIZ) were analyzed. For susceptibility, a case-control study including a cohort of 57 adult with P-CAP, and 280 ethnically matched controls was performed. Genetic influence on clinical severity and outcome was evaluated in a prospective observational study including all consecutive adult P-CAP patients from November 2015 to May 2017.ResultsThe NFKBIA polymorphism rs696 and a haplotype combination were associated with susceptibility to P-CAP (OR = 0.62, p = 0.005 and OR = 0.63, p = 0.008, respectively). The SNP IL4 rs2227284 was associated with severe P-CAP (OR = 2.17, p = 0.04). IL-R1 (rs3917267) and IL-10 (rs3024509) variants were related with respiratory failure (OR = 3.31, p = 0.001 and OR = 0.18, p = 0.003, respectively) as well as several haplotype combinations in NFKBIA, NFKBIZ, IL-R1 and IL-10 (p = 0,02, p = 0,01, p = 0,001, p = 0,03, respectively). CURB-65 values were associated with the IL-10 rs3024509 variant (beta = − 0.4, p = 0.04), and with haplotype combinations of NFKBIZ and IL-10 (p = 0.05, p = 0.04, respectively). Genetic variants in IL-10 (rs3024509) and in IL-12B (rs730691) were associated with PSI values (beta = − 0.54, p = 0.01, and beta = − 0.28, p = 0.04, respectively), as were allelic combinations in IL-R1 (p = 0.02) and IL-10 (p = 0.01). Finally, several polymorphisms in the IL-R1 gene (rs13020778, rs2160227, & rs3917267) were associated with the time elapsed until clinical stability (beta = − 0.83, p = 0.03; beta = − 1, p = 0.02 and beta = 1.07, p = 0.008, respectively).ConclusionsA genetic variant in NFKBIA was associated with susceptibility to P-CAP in adult Caucasian patients and genetic variants from key cytokines of the innate immune response (Il-4, IL-10, IL-R1 and IL-12B) and NF-κB inhibitors were associated with different phenotypes of severe P-CAP. If validated, these SNPs may help to identify people at risk of P-CAP or severe P-CAP on which preventive measures could be applied.