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PubMed2026

Application of metagenomic next-generation sequencing in children with pneumonia of unknown etiology.

OBJECTIVE: To investigate the pathogen spectrum and clinical application value of metagenomic next-generation sequencing (mNGS) in lower respiratory tract specimens from children with pneumonia of unknown etiology. METHODS: A retrospective analysis was conducted on children hospitalized in the intensive care unit (ICU) and respiratory department ward of Children's Hospital of Chongqing Medical University from January 2025 to December 2025. All enrolled cases presented negative results for conventional respiratory pathogen tests and received mNGS testing of lower respiratory tract specimens for etiological identification. The mNGS findings and clinical data of the included children were analyzed. RESULTS: A total of 92 children were enrolled, including 54 males and 38 females, with ages ranging from 2 months to 13 years and 8 months. Causative pathogens were detected in 77 cases (83.7%). The clinically adjudicated etiological diagnosis rates of bacteria, viruses, fungi and atypical pathogens were 75.0% (69/92), 37.0% (34/92), 13.0% (12/92) and 5.4% (5/92), respectively. Thirty-eight cases were complicated with polymicrobial infection, among which bacterial-viral infection was predominant, accounting for 23.1% (24/92). Children with immunocompromised conditions exhibited higher incidences of clinically adjudicated bacterial, fungal and polymicrobial infection than immunocompetent patients. The most common clinically confirmed causative pathogens in immunocompromised children were Streptococcus pneumoniae, human cytomegalovirus, Haemophilus influenzae, Stenotrophomonas maltophilia and Enterococcus faecalis. Treatment regimens were adjusted in 58 cases (63.0%) based on mNGS findings, switching to pathogen-targeted anti-infective therapy. CONCLUSION: For pediatric pneumonia with negative conventional etiological tests, mNGS of lower respiratory tract specimens significantly enhances pathogen detection rates, effectively identifies polymicrobial infection and opportunistic pathogens. Immune status serves as a critical stratification factor influencing pathogen spectrum and infection patterns, with immunocompromised children being more susceptible to opportunistic infections. Adjustment of anti-infective regimens based on mNGS results can effectively facilitate personalized anti-infective therapy.

Humans↗
PubMed1976

Virus antibody levels in IgA deficiency.

IgA-deficient blood donors and their age- and sex-matched controls were compared for the occurrence of complement-fixing antibodies in serum against several viruses. The level in the IgA-deficient persons was slightly higher against several respiratory pathogens (adenoviruses, type B influenza virus, parainfluenza virus, and respiratory syncytial virus) that give rise to localized infections, and against coxsackie B group of viruses. No corresponding difference was observed in mumps, varicella, and cytomegalovirus infections, where viraemia is a characteristic feature, or in Mycoplasma pneumoniae infection.

Adenoviruses, Human↗
PubMed1979

Distribution of hemolytic streptococci in respiratory specimens.

One hundred thirty-seven isolates of beta-hemolytic streptococci were recovered from 623 pharyngeal cultures. Twenty-nine percent of these were group A, 10% were group B, 31% were group C, 11% were group F, 12% were group G, and 7% could not be grouped. The significance of non-group A isolates in pharyngitis could not be evaluated in the absence of viral and serological studies. Hemolytic streptococci were recovered from 9% of 799 lower respiratory cultures. All except one were non-group A, and other potential respiratory pathogens were also present in these specimens. It is our impression that the presence of hemolytic streptococci in lower respiratory tract specimens usually represents pharnygeal contamination.

Adult↗
PubMed1978

Bronchopulmonary infection due to Branhamella catarrhalis: 11 cases assessed by transtracheal puncture.

Transtracheal punctures were performed in 193 miners of anthracosilicotic coal who presented with an acute exacerbation of chronic bronchitis. The transtracheal aspirates were bacteriologically positive in 104 patients. Branhamella catarrhalis was isolated in 15 patients; 10 of these responded to chemotherapy, as shown by the resolution of all symptoms and the disappearance of the organism on a repeat transtracheal puncture performed 48 hours after the end of treatment. One ampicillin-treated patient, whose bronchial secretions yielded a beta-lactamase-producing B catarrhalis, showed no improvement. But subsequent treatment with cefuroxime was followed by clinical and bacteriological recovery. B catarrhalis probably acted as an opportunistic respiratory pathogen in these patients, who were probably compromised hosts in view of their clinical history. B catarrhalis normally responds to the penicillins commonly used for respiratory infections, but if treatment fails a transtracheal puncture is essential to identify the strain and determine an appropriate antibiotic.

Ampicillin↗
PubMed1976

Rhinovirus and influenza type A infections as precipitants of asthma.

Specimens from 49 persons, 3 to 60 years of age, who were prone to attacks of apparently infectious asthma were cultured for viruses and bacteria during episodes of symptomatic respiratory infection from September 1972 to June 1973. Seventy-one of 128 episodes (55 per cent) of symptomatic respiratory infection occurred with asthma. Shedding of respiratory pathogens was associated with 43 of the 128 episodes, and 19 of the 43 etiologically defined episodes occurred with wheezing. Seven of 15 rhinovirus symptomatic respiratory infections were linked with asthma, as were 4 of 5 influenza type A (H3N2) and 2 of 3 respiratory syncytial virus infections. A total of 21 different rhinovirus serotypes have been identified from asthmatic patients during 2 years of study; 14 of these were associated with wheezing, indicating that the ability to cause asthma is not restricted to only a few types. Other viruses that were shed during wheezing-associated symptomatic respiratory infections included para-influenza type 3, adenovirus type 7, and 2 unidentified viruses. Although infectious asthma was not easily defined in adults and some older children, viruses that appeared to precipitate asthma were distributed among patients of widely differing ages.

Asthma↗
PubMed2025

Distinct Evolutionary Signatures of Human Parainfluenza Viruses 2 and 4 Reveal Host Antagonism Divergence and Phylogenetic Discordance.

Human parainfluenza virus 2 (HPIV-2) and human parainfluenza virus 4 (HPIV-4) are significant but underappreciated respiratory pathogens, particularly among high-risk populations including children, the elderly, and immunocompromised individuals. In this study, we sequenced 101 HPIV-2 and HPIV-4 genomes from respiratory samples collected in western Washington State and performed comprehensive evolutionary analyses using both new and publicly available sequences. Phylogenetic and phylodynamic analyses revealed that both HPIV-2 and HPIV-4 evolve at significantly faster rates compared to the mumps virus, a reference human orthorubulavirus. Notably, while HPIV-2 demonstrated the highest evolutionary rates in the surface glycoprotein HN, consistent with humoral immune-driven selection, the innate immune antagonist V/P gene evolved fastest in HPIV-4. We identified a hypervariable region within the HPIV-4V/P protein (residues 35 to 75), which structural modeling placed in a loop overlapping a known interferon antagonism domain in other paramyxovirus V proteins, though HPIV-4 is functionally incompetent in this activity. Expanded phylogenetic analysis across the Paramyxoviridae family uncovered a striking evolutionary discordance: while the HN glycoprotein and L polymerase of HPIV-4 and its 2 closest bat-derived viruses clustered within the Orthorubulavirus genus, their nucleoprotein (N), phosphoprotein (P), matrix (M), and fusion (F) proteins formed a distinct lineage outside the Rubulavirinae subfamily. Together, these findings highlight the distinct evolutionary trajectories of HPIV-2 and HPIV-4, raise hypotheses around complex Paramyxoviridae zoonotic events including recombination-like patterns, and demonstrate limitations of current L protein-based taxonomic classification schemes.

Humans↗
PubMed1979

Relationship of bacterial and viral infections to exacerbations of asthma.

Fifty-one asthmatic patients were followed for up to 18 months. During this time 111 exacerbations of wheeze were recorded. Involvement by pathogenic respiratory bacteria and viruses was looked for directly by culture and indirectly by antibody studies. Proof of infection was found in only 12 (10.8%) of the 111 exacerbations. Only eight patients provided sputum samples. Potential bacterial pathogens were found in four. Viruses were isolated in four of 27 exacerbation specimens; significant rises in specific viral antibody titres occurred in three. Six patients developed precipitating antibody to respiratory bacteria over the study but only one in relation to an exacerbation. The study therefore indicated that the great majority of exacerbations of asthma in these patients were not due to respiratory tract infection.

Adult↗
PubMed1979

Are anaerobic pleuropulmonary infections uncommon or commonly undetected in Britain?

Despite marked and increasing awareness of the clinical significance of pathogenic anaerobes, the role of anaerobes in pleuropulmonary infections is still largely unrecognised in Britain. A considerable literature testifies that this is not so in America. The reasons for this paradox are explored. British anaerobic methodology is briefly reviewed, with special reference to the range of recognised respiratory pathogens and the anaerobes that can be cultured in simple anaerobic jars. The limitations of sampling and transport procedures are considered. Differences in approach are discussed. The technological problems of the isolation and culture of "difficult" pathogenic anaerobes have been largely solved at the laboratory level; effective approaches to sampling and transit of specimens require more positive consideration and the results might influence our choice of specific antimicrobial therapy. If these points are taken and an increased awareness of the role of the anaerobes in certain pathological conditions of the lower respiratory tract is generated, we might hope either to produce a meaningful parallel to the experience of our American colleagues--or to structure a more valid defence to explain our lack of experience of these infections in the lower respiratory tract.

Bacterial Infections↗
PubMed2026

Acute respiratory viral diseases in Amazonas, Brazil: epidemiological patterns and implications for health surveillance.

BACKGROUND: Acute respiratory viral diseases are a major public health challenge in the Brazilian Amazon, where ecological, logistical, and social factors shape patterns of transmission and response. METHODS: This study aimed to analyze the epidemiological patterns and temporal-spatial distribution of Influenza-like illness (ILI) and severe acute respiratory syndrome (SARS) in the state of Amazonas, Brazil, between 2015 and 2025, distinguishing SARS-CoV-2 and non-SARS-CoV-2 etiologies using data from OpenDataSUS. RESULTS: Incidence peaks occurred in early 2021 and 2022, with pronounced regional disparities. The highest burdens were concentrated in specific municipalities, with Manaus exhibiting an intermediate incidence and playing a central role in case notifications and healthcare provision. DISCUSSION: We describe the integration of surveillance systems, laboratory networks, and healthcare infrastructure, which enabled improvements in diagnosis, monitoring, and care. The region's response model, centered in Manaus, includes primary-to-tertiary care coordination, molecular diagnostics, telemedicine, and mobile health units for Indigenous and remote areas. Research efforts during the COVID-19 pandemic provided critical insights into therapeutic strategies, immunopathology, and long-term sequelae, while also highlighting persistent inequities and diagnostic gaps. Our findings underscore the co-circulation of multiple respiratory pathogens and the need for continued genomic and syndromic surveillance. Future strategies must address regional disparities, support decentralized diagnostics, and expand clinical research. Strengthening integrated health systems in the Brazilian Amazon is essential for timely, equitable responses to emerging respiratory threats.

Brazil↗
PubMed1977

Respiratory-tract colonization and a distinctive pneumonia syndrome in infants infected with Chlamydia trachomatis.

To learn if Chlamydia trachomatis causes in young infants a distinctive penumonia characterized by chronic, afebrile course, diffuse lung involvement and elevated serum immunoglobulins G and M, 47 black infants four to 24 weeks of age were examined for nasopharyngeal shedding of C. trachomatis and serum immunofluorescent antibody to lymphogranuloma venereum Type I. Nasopharyngeal C. trachomatis was found in 18 of 20 with the pneumonia syndrome, two of 15 with various other illnesses and 10 of 12 with inclusion conjunctivitis but without lower respiratory illness. Chlamydial antibody titers of infants with the pneumonia syndrome were significantly elevated (geometric mean-1, pneumonia vs. conjunctivitis = 24,833 vs. 1024 P less than 0.001). No other commonly recognized respiratory pathogens were consistently associated with the pneumonia syndrome. We believe these findings demonstrate an association between the distinctive pneumonia syndrome and C. trachomatis. This, in turn, is a particular facet of a more general event consisting of frequent colonization of the respiratory tract by C. trachomatis in natally acquired infection.

Antibodies, Bacterial↗
PubMed1978

Respiratory syncytial virus infection: admissions to hospital in industrial, urban, and rural areas. Report to the Medical Research Council Subcommittee on Respiratory Syncytial Virus Vaccines.

A collaborative study of 10 centres during the winters of 1973-4 and 1974-5 showed that respiratory syncytial virus (RSV) was the major cause of admission to hospital for respiratory disease in children under 5 years of age in industrial, urban, and rural communities. In all areas the distribution of clinical symptoms and their severity was similar, but the rate of admission in relation to population was over twice as high in industrial as in other areas. The maximum yearly admission rate occurred among infants aged 1 to 3 months: 24.5 per 1000 of that age group were admitted to hospital. Two methods of diagnosing RSV infection--virus isolation and immunofluorescence from postnasal aspirates--were compared, and the two methods were found to agree in 91% of cases. The results of this study confirmed the importance of RSV as a respiratory pathogen in young children. Further studies are needed to determine how the virus produces its effects and to develop preventive measures.

Age Factors↗
PubMed2026

Influenza A virus in Swiss pig herds with respiratory disease: Seasonality and age dependence.

Influenza A virus (IAV) is an important respiratory pathogen in pigs and poses a zoonotic risk to humans in close contact. While IAV epidemiology has been extensively studied in large-scale production systems, data from Switzerland - characterized by small herds and limited live pig imports - remain scarce. This exploratory nationwide cross-sectional study aimed to assess the association between herd-level IAV detection and reported respiratory disease in pig herds, and to explore associations with husbandry-, animal-, and human health-related factors. Between November 2023 and April 2025, 25 Swiss pig herds with caretaker-suspected respiratory symptoms were investigated. In each herd, five nasal swabs were collected and analyzed by quantitative PCR. Herd managers completed an interview, and clinical examinations were performed. Overall, 56 % (95 % CI: 37,1 - 73,3) of herds tested positive for IAV, comparable to reports from other European countries. The estimated intra-herd detection rate was 49,6 % (95 % CI: 31,2 - 68,0). Respiratory disease outbreaks associated with IAV detection showed indications of seasonal variation, with no positive herds identified during summer. Across age groups, pigs aged 11-14 weeks had a higher likelihood of IAV detection, with 15,79-fold increased odds (95 % CI: 1,50 - 860,4), although with considerable uncertainty. The interpretation is limited by the small sample size, heterogeneous data, and reliance on single time-point qPCR detection. The results suggest that IAV detection in clinically apparent respiratory outbreaks may follow seasonal patterns in Swiss pig herds. Weaners and newly introduced fattening pigs may play a role in such respiratory outbreaks and could represent relevant targets for IAV surveillance in Switzerland. Continued monitoring and the implemen tation of appropriate control measures remain important given the virus's zoonotic potential and impact on pig health.

Animals↗
PubMed1977

Known and newer manifestations by mycoplasma pneumoniae in adults.

Although M. pneumoniae is a well recognised respiratory pathogen both in children and in young adults, its infections have shown recently some pathomorphism and may also involve other organ systems. The paper reviews the various clinical syndromes in adults by M. pneumoniae, with particular emphasis on those more unusual and nevertheless seen by us. In this connection the possibility of pleural effusions (with a well defined cytology) associated or not with typical Mycoplasma pneumoniae and of chronic bronchopneumonias eventually evolving even in pulmonary fibrosis is stressed. Moreover, the development of M. pneumoniae respiratory infections during the course or hematological malignancies and their characteristics are described in some detail because of the relative rarity of this kind of infections in the above patients. Finally, some less frequently reported manifestations of M. pneumoniae infections, as hemolytic anemia, hepatitis and others are described and discussed.

Gastrointestinal Diseases↗
PubMed2026

[Genomic evolution and epidemiological patterns of respiratory syncytial virus and their implications for surveillance and early warning].

Respiratory syncytial virus (RSV) is an important respiratory pathogen in infants, young children and older adults. Based on global RSV genomic surveillance data, this review systematically summarizes the geographic distribution, seasonal epidemic patterns, and long-term evolutionary trends of RSV, with particular emphasis on the sustained circulation and evolutionary mechanisms of dominant genotypes such as ON1 in RSV-A and BA9 in RSV-B. Current evidence indicates that RSV transmission dynamics are tightly coupled with viral evolution. The G gene evolves relatively rapidly and contains multiple positively selected sites, suggesting an important role in immune escape and population adaptation. In recent years, changes in social behavior patterns and population immunity have further disrupted the seasonal rhythm of RSV and may have influenced the spread of dominant genotypes. Under routine respiratory infectious disease surveillance, strengthened genomic monitoring and integration of multi-source data are needed to improve early warning of abnormal RSV epidemics and variant-associated risks, thereby providing prospective evidence for protecting high-risk populations and informing public health decision-making.

Humans↗
PubMed2026

A standardized, genome-guided MLST scheme for Avibacterium paragallinarum: enhanced epidemiological typing and validation against existing methods.

Avibacterium paragallinarum, the causative agent of infectious coryza (IC), is an important respiratory pathogen of chickens with growing prevalence in commercial and backyard flocks. Current strain-typing methods, including classical serotyping and molecular approaches, such as ERIC-PCR or single-locus HPG2 typing, lack sufficient discriminatory power to investigate the epidemiology or population structure. To address this limitation, we developed a genome-guided multilocus sequence typing (MLST) scheme as a robust and portable tool for A. paragallinarum strain differentiation. Housekeeping genes were identified from 42 whole-genome sequences (WGS); 18 candidates were evaluated; and six were selected for the final MLST scheme. We used the scheme to differentiate 75 A. paragallinarum samples and compared its performance against classical HPG2-based typing, ad hoc core genome MLST (cgMLST), and the MLST scheme published by M. Guo, Y. Jin, H. Wang, X. Zhang, and Y. Wu (Vet Sci 11:208, 2024, https://doi.org/10.3390/vetsci11050208). The new MLST showed higher discriminatory power than HPG2 and outperformed Guo's scheme with higher discriminatory power, particularly for characterizing the samples originating from North and South America. It also showed strong concordance with cgMLST clustering while being more practical for routine use. Overall, the six-locus MLST identified 31 sequence types across 75 samples, revealing epidemiologically meaningful clustering at regional and national scales and capturing temporal persistence of lineages. All allele definitions and sequence types have been deposited in PubMLST, ensuring standardized nomenclature and global accessibility. This scheme represents a reproducible, cost-effective, and globally applicable tool that enhances outbreak investigation, surveillance, and population studies of A. paragallinarum, bridging the gap between low-resolution traditional methods and resource-intensive whole-genome sequencing.IMPORTANCEInfectious coryza (IC) caused by Avibacterium paragallinarum is a major respiratory disease of poultry that causes acute infection, reducing egg production and growth and resulting in significant economic losses in poultry production worldwide. Controlling IC depends on understanding how different strains spread and persist, yet current methods to differentiate strains are either unreliable or too costly for routine use. In this study, we developed a standardized multilocus sequence typing system that provides a simple, accurate, and globally accessible way to identify and compare strains of A. paragallinarum. This scheme identified important links between outbreaks at local and regional levels and showed that certain strains persisted over time. By making the scheme available through PubMLST, laboratories worldwide can use a common tool to track and investigate the pathogen. This accessible tool improves disease surveillance, supports outbreak investigations, and helps poultry producers and veterinarians respond more effectively to IC.

Multilocus Sequence Typing↗
PubMed1975

The protean manifestations of Mycoplasma pneumoniae infection in adults.

Mycoplasma pneumoniae is a well recognized respiratory pathogen in children and young adults. In addition, M. pneumoniae infections may also involve other organ systems. Reviewed here are the various clinical syndromes in adults caused by this infectious agent, with emphasis on those which have recently been seen at The New York Hospital. Two previously unreported manifestations of M. pneumoniae infection, cranial nerve mononeuropathy and hepatitis, are described, and the laboratory methods for diagnosis are discussed.

Adolescent↗
PubMed1979

Diffuse pulmonary infiltrates in immunosuppressed patients. Prospective study of 80 cases.

Over a two year period, we studied prospectively 80 cases of diffuse pneumonia at Memorial Sloan-Kettering Cancer Center. In 72 per cent of these, the patient had leukemia or lymphoma. Diagnostic procedures consisted of extensive serologic testing for antibody to known respiratory pathogens, including the agent of Legionnaire's disease, and culturing of biopsy specimens for bacteria, viruses, mycoplasmas and fungi. Of 44 cases in which open lung biopsy was performed, a specific cause was found in 61.4 per cent: Pneumocystis carinii in 38.6 per cent, other infections in 9.1 per cent and tumor involvement in 13.7 per cent. There were nonspecific pulmonary changes in 38.6 per cent. Of the 56 cases in which biopsy, autopsy or both were performed, a specific diagnosis was made in 69.7 per cent: P. carinii infection in 37.5 per cent and other infections in 12.5 per cent. In cases in which neither biopsy nor autopsy was performed, a specific infection was diagnosed in 33 per cent; no specific diagnosis was made in the remainder. One patient in the entire group had a significant antibody titer for Legionnaire's disease. Although diagnostic in some cases, extensive serologic testing proved relatively unfruitful. Pneumocystosis was the most frequent diagnosis in this study. The cause of some cases remained obscure, even after lung biopsy.

Adolescent↗
PubMed2024

Human parainfluenza virus 3 vaccine candidates attenuated by codon-pair deoptimization are immunogenic and protective in hamsters.

Human parainfluenza virus type 3 (HPIV3) is a major pediatric respiratory pathogen lacking available vaccines or antiviral drugs. We generated live-attenuated HPIV3 vaccine candidates by codon-pair deoptimization (CPD). HPIV3 open reading frames (ORFs) encoding the nucleoprotein (N), phosphoprotein (P), matrix (M), fusion (F), hemagglutinin-neuraminidase (HN), and polymerase (L) were modified singly or in combination to generate 12 viruses designated Min-N, Min-P, Min-M, Min-FHN, Min-L, Min-NP, Min-NPM, Min-NPL, Min-PM, Min-PFHN, Min-MFHN, and Min-PMFHN. CPD of N or L severely reduced growth in vitro and was not further evaluated. CPD of P or M was associated with increased and decreased interferon (IFN) response in vitro, respectively, but had little effect on virus replication. In Vero cells, CPD of F and HN delayed virus replication, but final titers were comparable to wild-type (wt) HPIV3. In human lung epithelial A549 cells, CPD F and HN induced a stronger IFN response, viral titers were reduced 100-fold, and the expression of F and HN proteins was significantly reduced without affecting N or P or the relative packaging of proteins into virions. Following intranasal infection in hamsters, replication in the nasal turbinates and lungs tended to be the most reduced for viruses bearing CPD F and HN, with maximum reductions of approximately 10-fold. Despite decreased in vivo replication (and lower expression of CPD F and HN in vitro), all viruses induced titers of serum HPIV3-neutralizing antibodies similar to wt and provided complete protection against HPIV3 challenge. In summary, CPD of HPIV3 yielded promising vaccine candidates suitable for further development.

Animals↗