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BACKGROUND: Screening for opisthorchiasis, a parasitic worm infection affecting many millions of people in Southeast Asia, has traditionally relied on faecal egg examination such as the formalin-ethyl acetate concentration technique (FECT) and Kato-Katz method. Although the urinary enzyme-linked immunosorbent assay (ELISA) has been used more recently, we developed a urinary antigen-based rapid diagnostic test (RDT) to simplify diagnosis and as a point-of-care testing (POCT) and field applications for surveillance and control of opisthorchiasis. METHODS: A urinary Opisthorchis viverrini (OV)-RDT was developed using immunochromatographic methodology with a specific monoclonal antibody against OV. The diagnostic performance of the urinary OV-RDT was compared to that of quantitative faecal FECT and urinary antigen ELISA (n = 493). Cross-reactivities of urinary OV-RDT with other helminthiases coexisted with O. viverrini were determined (n = 96). A field trial in the application of urinary OV-RDT was compared with urinary antigen ELISA at baseline screening and assessment of drug treatment outcomes in opisthorchiasis (n = 1629). The McNemar chi-square, Kruskal-Wallis and Cohen's kappa coefficient (κ-value) tests were used for statistical analyses. RESULTS: Urinary OV-RDT had sensitivity of 94.2% and specificity of 93.2%, compared to faecal FECT. Urinary OV-RDT had high diagnostic agreement (Kappa = 0.842-0.874, P < 0.001) and quantitative correlation with urinary antigen ELISA (Kruskal-Wallis tests = 316.2, P < 0.0001) and faecal FECT (Kruskal-Wallis tests = 362.3, P < 0.0001). The positive rates by OV-RDT, ELISA and FECT were 48.9%, 52.5% and 49.3%, respectively. Cross-reactions of urinary OV-RDT with other helminthiases were few (2%). Field trials of urinary OV-RDT yielded comparable prevalence of O. viverrini between urinary OV-RDT (53.2%) and urinary antigen ELISA (54.0%). OV screening showed high diagnostic agreement (kappa > 0.8, P < 0.0001) between urinary OV-RDT and urinary antigen ELISA. The cure rates of opisthorchiasis at 1 month post-praziquantel treatment determined by urinary OV-RDT (86.6%) and urinary antigen ELISA (80.5%) were similar (P > 0.05). CONCLUSIONS: The urinary OV-RDT test has high potential as a new tool for screening and evaluating treatment outcomes in opisthorchiasis. The ease of sample collection and simplicity of urinary OV-RDT may facilitate mass screening, control and elimination of opisthorchiasis, thereby contributing to a reduction in the disease burden in Southeast Asia.
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Opistorquíase , Opisthorchis , Animais , Humanos , Opistorquíase/diagnóstico , Opistorquíase/tratamento farmacológico , Opistorquíase/epidemiologia , Testes de Diagnóstico Rápido , Sensibilidade e Especificidade , Praziquantel/uso terapêutico , Tailândia/epidemiologiaRESUMO
Greece introduced a 13-valent pneumococcal conjugate vaccine (PCV13) into the infant national immunization program in 2010 (3 + 1 schedule until June 2019). Since 2015, PCV13 has been recommended for adults aged 19-64 years with comorbidities and adults ≥65 years sequentially with 23-valent pneumococcal polysaccharide vaccine (PPSV23). We examined pneumococcal serotype distribution among Greek adults aged ≥19 years hospitalized with community-acquired pneumonia (CAP) during November 2017-April 2019. This was an interim analysis of EGNATIA, a prospective study of adult hospitalized CAP in the cities of Ioannina and Kavala. Pneumococcus was identified using cultures, BinaxNow®, serotype-specific urinary antigen detection assays (UAD-1/2). Our analysis included overall 482 hospitalized CAP patients (mean age: 70.5 years; 56.4% male). 53.53% of patients belonged to the highest pneumonia severity index (PSI) classes (IV-V). Pneumococcus was detected in 65 (13.5%) patients, with more than half (57%) of cases detected only by UAD. Approximately two-thirds of pneumococcal CAP occurred in those aged ≥65 years (n = 40, 8.3% of CAP). More than half of pneumococcal CAP (n = 35, 53.8%) was caused by PCV13 serotypes. Most frequently detected PCV13 serotypes were 3, 19A, 23F, collectively accounting for 83% of PCV13 vaccine-type (VT) CAP and 6% of all-cause CAP. Overall, 82.9% of PCV13 VT CAP occurred among persons with an indication (age/risk-based) for PCV13 vaccination. Even with a mature PCV13 childhood immunization program, a persistent burden of PCV13 VT CAP exists in Greek adults. Strategies to increase PCV13 (and higher-valency PCVs, when licensed) coverage in adults should be implemented to reduce the disease burden.
An interim analysis of a prospective study in adults hospitalized with CAP in Greece.Serotype-specific urinary antigen detection assays were used to detect pneumococcus.A persistent burden of PCV13 vaccine-type CAP was observed in Greek adults.Improved PCV13 uptake and higher-valency PCVs may reduce the pneumococcal disease burden.
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Infecções Comunitárias Adquiridas , Infecções Pneumocócicas , Pneumonia Pneumocócica , Pneumonia , Adulto , Lactente , Humanos , Masculino , Criança , Idoso , Feminino , Sorogrupo , Grécia/epidemiologia , Estudos Prospectivos , Vacinas Pneumocócicas , Infecções Comunitárias Adquiridas/prevenção & controle , Streptococcus pneumoniae , Pneumonia/epidemiologia , Pneumonia/prevenção & controle , Infecções Pneumocócicas/prevenção & controle , Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/prevenção & controle , Vacinas ConjugadasRESUMO
Background: Infections with respiratory viruses [e.g. influenza and respiratory syncytial virus (RSV)] can increase the risk of severe pneumococcal infections. Likewise, pneumococcal coinfection is associated with poorer outcomes in viral respiratory infection. However, there are limited data describing the frequency of pneumococcus and SARS-CoV-2 coinfection and the role of coinfection in influencing COVID-19 severity. We, therefore, investigated the detection of pneumococcus in COVID-19 inpatients during the early pandemic period. Methods: The study included patients aged 18 years and older, admitted to the Yale-New Haven Hospital who were symptomatic for respiratory infection and tested positive for SARS-CoV-2 during March-August 2020. Patients were tested for pneumococcus through culture-enrichment of saliva followed by RT-qPCR (to identify carriage) and serotype-specific urine antigen detection (UAD) assays (to identify presumed lower respiratory tract pneumococcal disease). Results: Among 148 subjects, the median age was 65 years; 54.7% were male; 50.7% had an ICU stay; 64.9% received antibiotics; and 14.9% died while admitted. Pneumococcal carriage was detected in 3/96 (3.1%) individuals tested by saliva RT-qPCR. Additionally, pneumococcus was detected in 14/127 (11.0%) individuals tested by UAD, and more commonly in severe than moderate COVID-19 [OR: 2.20; 95% CI: (0.72, 7.48)]; however, the numbers were small with a high degree of uncertainty. None of the UAD-positive individuals died. Conclusions: Pneumococcal lower respiratory tract infection (LRTI), as detected by positive UAD, occurred in patients hospitalized with COVID-19. Moreover, pneumococcal LRTI was more common in those with more serious COVID-19 outcomes. Future studies should assess how pneumococcus and SARS-CoV-2 interact to influence COVID-19 severity in hospitalized patients.
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BACKGROUND: Streptococcus pneumoniae is a causative agent of community-acquired pneumonia (CAP). The 13-valent pneumococcal conjugate vaccine (PCV13) has significantly decreased the burden of PCV13-serotype pneumococcal disease; however, disease from nonvaccine serotypes remains substantial. A recent study documented the persistence of PCV13 serotypes among US adults hospitalized with radiographically confirmed CAP. The current analysis used a recently developed urinary antigen detection (UAD) assay (UAD2) to extend these results to additional serotypes included in an investigational PCV20 vaccine. METHODS: This prospective study enrolled adults aged ≥18 years hospitalized with radiographically confirmed CAP between October 2013 and September 2016. Presence of S pneumoniae was determined by blood and respiratory sample culture, BinaxNOW urine testing, and UAD. In addition to Quellung on cultured isolates when available, serotypes were identified from urine specimens using UAD1 for PCV13 serotypes and UAD2 for 7 PCV20-unique serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) and 4 additional serotypes (2, 9N, 17F, and 20). RESULTS: Among 12 055 subjects with radiographically confirmed CAP, 1482 were positive for S pneumoniae. PCV13- and PCV20-unique serotypes were associated with 37.7% (n = 559) and 27.0% (n = 400) of cases, respectively; 288 subjects were exclusively diagnosed as positive for S pneumoniae by UAD2. Demographic and clinical disease characteristics were similar between subjects with CAP caused by PCV13 and PCV20-unique serotypes. CONCLUSIONS: The current analysis using UAD2 identified a sizeable proportion of hospitalized adult CAP associated with PCV20-unique serotypes. PCV20 may therefore address the burden of CAP caused by the additional serotypes present in the vaccine.
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Infecções Pneumocócicas , Pneumonia Pneumocócica , Pneumonia , Adolescente , Adulto , Humanos , Vacinas Pneumocócicas , Pneumonia Pneumocócica/diagnóstico , Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/prevenção & controle , Estudos Prospectivos , Sorogrupo , Streptococcus pneumoniae , Vacinas ConjugadasRESUMO
Streptococcus pneumoniae infections continue to be an important cause of morbidity and mortality in low-and middle-income countries. Differentiating S. pneumoniae from viridans group streptococci is essential to ensure appropriate antibiotic therapy. Conventional microbial identification tests can often misidentify the two groups. We used a common pneumococcal urinary antigen test to identify S. pneumoniae that were misidentified by the VITEK 2. The performance of the test was similar to the pneumococcal latex agglutination test.
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Antígenos de Bactérias/urina , Infecções Pneumocócicas/diagnóstico , Kit de Reagentes para Diagnóstico , Streptococcus pneumoniae/isolamento & purificação , Antibacterianos/uso terapêutico , Antígenos de Bactérias/sangue , Técnicas Bacteriológicas , Humanos , Testes de Fixação do Látex , Infecções Pneumocócicas/tratamento farmacológico , Infecções Pneumocócicas/urina , Especificidade da Espécie , Streptococcus pneumoniae/imunologiaRESUMO
INTRODUCTION: Implementation of the 7-valent pneumococcal conjugate vaccine (PCV7) in infant vaccination programs has substantially reduced the burden of PCV7 serotypes also in adult community-acquired pneumonia (CAP). Currently, it is unclear, if this extensive herd protection effect can be extrapolated to the additional 6 serotypes included in the 13-valent pneumococcal conjugate vaccine (PCV13), which replaced PCV7 in Germany in 2010. OBJECTIVES: We investigated changing trends for PCV13 serotypes in adult CAP patients between three to seven years after implementation of PCV13 infant immunization in Germany. METHODS: Between December 2012 and January 2017, urine samples from German adult patients with radiologically confirmed CAP were prospectively collected by the multi-center cohort study CAPNETZ and analyzed by the serotype-specific multiplex urinary antigen detection assay (SSUAD) allowing for the detection of PCV13 serotypes. RESULTS: PCV13 serotypes were found in 59 of 796 (7.4%) patients with all-cause CAP, most prevalent was serotype 3 (30 of 59 patients, 50.8%). All patients with serotype 3-CAP were admitted to hospital and the majority required oxygen at admission (83.3% of patients with serotype 3-CAP versus 50.9% of patients with pneumococcal CAP by other serotypes, p = 0.005). Compared to SSUAD testing, conventional microbiological workup missed 27 of 30 (90.0%) serotype 3-CAP cases. We could not observe a time trend in the proportions of PCV13 serotypes and serotype 3 in all-cause CAP between 2013 and 2016 (OR trend per year 0.84, 95% CI 0.64-1.11 for PCV13 serotypes and OR trend per year 0.95, 95% CI 0.70-1.28 for serotype 3). CONCLUSIONS: Conventional methods underestimate serotype 3-CAP that can cause severe disease. Changes in overall PCV13 coverage were not detected during the years 2013 to 2016, mostly driven by a high proportion of serotype 3.
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Pneumonia Pneumocócica/microbiologia , Sorogrupo , Streptococcus pneumoniae/classificação , Idoso , Estudos de Coortes , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Vacinas Pneumocócicas , Pneumonia Pneumocócica/epidemiologia , Urinálise , Vacinas ConjugadasRESUMO
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.
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Microfluídica , Vacinas Pneumocócicas/isolamento & purificação , Pneumonia Pneumocócica/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real/normas , Sorotipagem/métodos , Escarro/microbiologia , Streptococcus pneumoniae/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Bactérias/urina , Teorema de Bayes , Feminino , Humanos , Japão/epidemiologia , Análise de Classes Latentes , Masculino , Pessoa de Meia-Idade , Vacinas Pneumocócicas/genética , Pneumonia Pneumocócica/epidemiologia , Prevalência , Estudos Prospectivos , Sensibilidade e Especificidade , Sorotipagem/normas , Escarro/química , Streptococcus pneumoniae/genética , Adulto JovemRESUMO
BACKGROUND: A novel, rapid and noninvasive test (ODK0501, RAPIRUN(®)Streptococcus pneumoniae) uses polyclonal antibodies to detect C polysaccharide of S. pneumoniae derived from sputum samples using an immunochromatographic assay. We evaluated its usefulness in Japanese patients with pneumonia who exhibited positive urinary antigen tests for S. pneumoniae (BinaxNOW(®)S. pneumoniae). PATIENTS AND METHODS: Forty adult patients with pneumonia treated between May 2011 and August 2013 were enrolled. Bacterial cultures, Gram staining and ODK0501 assays of sputum as well as urinary antigen tests for S. pneumoniae using urine samples obtained from the same patients were performed upon admission, the fourth day after starting antimicrobial treatment and at the end of the antimicrobial treatment. RESULTS: Twenty-seven of the 40 patients were positive for ODK0501, while a negative result for ODK0501 was associated with low-quality sputum samples according to the Geckler classification of sputum. The sensitivity and specificity of the ODK0501 assay in the 40 patients were 90.9% and 61.1%, respectively, based on the culture results. The results obtained with this kit were more favorable than those observed on Gram staining. The ODK0501 assay also showed a rapid reaction to the disappearance of S. pneumoniae in the sputum samples, while approximately 80% of the patients exhibited persistent positive results on the urinary antigen detection tests at the end of treatment. CONCLUSIONS: The ODK0501 test is a noninvasive, rapid and accurate tool for diagnosing respiratory infections caused by S. pneumoniae, although good quality sputum must be obtained prior to adequate treatment with antibiotics.
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Antígenos de Bactérias/análise , Cromatografia de Afinidade/métodos , Pneumonia Bacteriana/diagnóstico , Infecções Respiratórias/diagnóstico , Escarro/microbiologia , Streptococcus pneumoniae/imunologia , Idoso , Idoso de 80 Anos ou mais , Líquido da Lavagem Broncoalveolar/microbiologia , Feminino , Violeta Genciana , Humanos , Masculino , Pessoa de Meia-Idade , Fenazinas , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/urina , Infecções Respiratórias/microbiologia , Infecções Respiratórias/urina , Urina/microbiologiaRESUMO
BACKGROUND: Streptococcus pneumoniae causes a substantial proportion of community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) in the United States. Limited data are available regarding the pneumococcal serotypes causing CAP and HCAP. METHODS: Adults aged ≥ 50 years presenting to participating US hospitals with radiographically confirmed pneumonia between February 2010 and September 2011 were screened for inclusion. S. pneumoniae was identified using microbiological cultures, BinaxNOW® S. pneumoniae assay, or urine antigen detection (UAD) assay capable of detecting 13-valent pneumococcal conjugate vaccine (PCV13)-associated serotypes. RESULTS: Among 710 subjects enrolled, the median age was 65.4 years; 54.2% of subjects were male, 22.4% of radiographically confirmed pneumonia cases were considered HCAP, and 96.6% of subjects were hospitalized. S. pneumoniae was detected in 98 subjects (13.8%) by any test, and PCV13-associated serotype(s) were identified by UAD in 78 (11.0%). Serotype 19A was most prevalent, followed by 7F/A, 3, and 5. Serotypes associated with 7-valent pneumococcal conjugate vaccine (PCV7) accounted for 25% of UAD-positive isolates. CONCLUSIONS: Pneumococcal serotypes causing noninvasive pneumonia in adults may differ significantly from those causing invasive disease, with PCV7-associated serotypes overrepresented. Serotype 5, rarely seen in contemporary surveillance of invasive disease in the United States, substantially contributed to the observed cases of S. pneumoniae-positive CAP or HCAP.