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1.
PLoS One ; 17(5): e0268749, 2022.
Article in English | MEDLINE | ID: covidwho-1933289

ABSTRACT

Local information is needed to guide targeted interventions for respiratory infections such as tuberculosis (TB). Case notification rates (CNRs) are readily available, but systematically underestimate true disease burden in neighbourhoods with high diagnostic access barriers. We explored a novel approach, adjusting CNRs for under-notification (P:N ratio) using neighbourhood-level predictors of TB prevalence-to-notification ratios. We analysed data from 1) a citywide routine TB surveillance system including geolocation, confirmatory mycobacteriology, and clinical and demographic characteristics of all registering TB patients in Blantyre, Malawi during 2015-19, and 2) an adult TB prevalence survey done in 2019. In the prevalence survey, consenting adults from randomly selected households in 72 neighbourhoods had symptom-plus-chest X-ray screening, confirmed with sputum smear microscopy, Xpert MTB/Rif and culture. Bayesian multilevel models were used to estimate adjusted neighbourhood prevalence-to-notification ratios, based on summarised posterior draws from fitted adult bacteriologically-confirmed TB CNRs and prevalence. From 2015-19, adult bacteriologically-confirmed CNRs were 131 (479/371,834), 134 (539/415,226), 114 (519/463,707), 56 (283/517,860) and 46 (258/578,377) per 100,000 adults per annum, and 2019 bacteriologically-confirmed prevalence was 215 (29/13,490) per 100,000 adults. Lower educational achievement by household head and neighbourhood distance to TB clinic was negatively associated with CNRs. The mean neighbourhood P:N ratio was 4.49 (95% credible interval [CrI]: 0.98-11.91), consistent with underdiagnosis of TB, and was most pronounced in informal peri-urban neighbourhoods. Here we have demonstrated a method for the identification of neighbourhoods with high levels of under-diagnosis of TB without the requirement for a prevalence survey; this is important since prevalence surveys are expensive and logistically challenging. If confirmed, this approach may support more efficient and effective targeting of intensified TB and HIV case-finding interventions aiming to accelerate elimination of urban TB.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis , Adult , Bayes Theorem , Humans , Malawi/epidemiology , Mass Screening/methods , Prevalence , Sputum/microbiology , Tuberculosis/complications , Tuberculosis/diagnosis , Tuberculosis/epidemiology
2.
BMJ Open ; 12(6): e058195, 2022 06 16.
Article in English | MEDLINE | ID: covidwho-1909754

ABSTRACT

OBJECTIVES: Prevalence surveys remain the best way to assess the national tuberculosis (TB) burden in many countries. Challenges with using culture (the reference standard) for TB diagnosis in prevalence surveys have led to increasing use of molecular tests (Xpert assays), but discordance between these two tests has created problems for deciding which individuals have TB. We aimed to design an accurate diagnostic algorithm for TB prevalence surveys (TBPS) that limits the use of culture. DESIGN: TBPS in four communities, conducted during 2019. SETTING: Three Zambian communities and one South-African community included in the TBPS of the Tuberculosis Reduction through Expanded Anti-retroviral Treatment and Screening study. PARTICIPANTS: Randomly sampled individuals aged ≥15 years. Among those who screened positive on chest X-ray or symptoms, two sputum samples were collected for field Xpert-Ultra testing and a third for laboratory liquid-culture testing. Clinicians reviewed screening and test results; in Zambia, participants with Mycobacterium tuberculosis-positive results were followed up 6-13 months later. Among 10 984 participants, 2092 screened positive, 1852 provided two samples for Xpert-Ultra testing, and 1009 had valid culture results. OUTCOMES: Culture and Xpert-Ultra test results. RESULTS: Among 946 culture-negative individuals, 917 were Xpert-negative, 12 Xpert-trace-positive and 17 Xpert-positive (grade very low, low, medium or high), with Xpert categorised as the highest grade of the two sample results. Among 63 culture-positive individuals, 8 were Xpert-negative, 9 Xpert-trace-positive and 46 Xpert-positive. Counting trace-positive results as positive, the sensitivity of Xpert-Ultra compared with culture was 87% (95% CI 76% to 94%) using two samples compared with 76% (95% CI 64% to 86%) using one. Specificity was 97% when trace-positive results were counted as positive and 98% when trace-positive results were counted as negative. Most Xpert-Ultra-positive/culture-negative discordance was among individuals whose Xpert-positive results were trace-positive or very low grade or they reported previous TB treatment. Among individuals with both Xpert-Ultra results grade low or above, the positive-predictive-value was 90% (27/30); 3/30 were plausibly false-negative culture results. CONCLUSION: Using Xpert-Ultra as the primary diagnostic test in TBPS, with culture only for confirmatory testing, would identify a high proportion of TB cases while massively reducing survey culture requirements. TRIAL REGISTRATION NUMBER: NCT03739736.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Tuberculosis , Humans , Mycobacterium tuberculosis/genetics , Prevalence , Sensitivity and Specificity , South Africa/epidemiology , Sputum/microbiology , Tuberculosis/diagnosis , Tuberculosis/epidemiology , Tuberculosis, Pulmonary/diagnosis , Zambia/epidemiology
3.
Braz J Microbiol ; 53(2): 633-639, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1872828

ABSTRACT

Tuberculosis (TB) and COVID-19 affect the lungs and are transmitted mainly by aerosols or particles of saliva from infected persons. Clinical similarities between diseases can affect correct diagnosis. Individuals belonging to the population deprived of liberty (PDL) are at increased risk of contagion due to precarious sanitary conditions and overcrowded environments. A variety of specimens may be suitable for the diagnosis of COVID-19, using molecular diagnostic techniques; however, there is little data on the analysis of sputum samples with the Xpert Xpress SARS-CoV-2® for the diagnosis of COVID-19, especially in this population group. The present study reports a case of TB and COVID-19 co-infection detected in sputum from an individual belonging to the PDL. For the detection, it used the GeneXpert platform (Cepheid, USA). Mycobacterium tuberculosis complex (MTC) was detected using the Xpert MTB/RIF Ultra® cartridge and SARS-CoV-2 was detected using the Xpert Xpress SARS-CoV-2® cartridge. The genes IS6110 and IS1081 were detected within 80 min indicating the presence of MTC, with no mutations related to resistance to rifampicin. The SARS-CoV-2 E and N2 genes were detected within 45 min. The result was confirmed by RT-qPCR with detection of E, N, and RdRP/S genes in the sputum and nasopharyngeal (NP) specimens. Rapid diagnoses that allow the identification and differentiation of such diseases are important for adequate epidemiological surveillance, isolation of infected individuals, and interruption of the transmission chain. Using the GeneXpert platform, specimens can be tested as soon as they are received, without the need for prior preparation. The US Food and Drug Administration has issued emergency authorization for the use of the Cepheid Xpert Xpress SARS-CoV-2 for the rapid detection of SARS-CoV-2 using specimens from a NP or nasal wash/aspirate. The case presented here gains an innovation with the use of the sputum to COVID-19 diagnosis.


Subject(s)
COVID-19 , Coinfection , Mycobacterium tuberculosis , Tuberculosis , COVID-19/diagnosis , COVID-19 Testing , Coinfection/diagnosis , Humans , Molecular Diagnostic Techniques/methods , Mycobacterium tuberculosis/genetics , Rifampin , SARS-CoV-2/genetics , Sensitivity and Specificity , Sputum/microbiology , Tuberculosis/diagnosis , Tuberculosis/microbiology
4.
BMJ Glob Health ; 7(2)2022 02.
Article in English | MEDLINE | ID: covidwho-1685569

ABSTRACT

INTRODUCTION: Active case finding (ACF) of individuals with tuberculosis (TB) is a key intervention to find the 30% of people missed every year. However, ACF requires screening large numbers of individuals who have a low probability of positive results, typically <5%, which makes using the recommended molecular tests expensive. METHODS: We conducted two ACF surveys (in 2020 and 2021) in high TB burden areas of Lao PDR. Participants were screened for TB symptoms and received a chest X-ray. Sputum samples of four consecutive individuals were pooled and tested with Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF) (Xpert-MTB/RIF) (2020) or Xpert-Ultra (2021). The agreement of the individual and pooled samples was compared and the reasons for discrepant results and potential cartridge savings were assessed. RESULTS: Each survey included 436 participants, which were tested in 109 pools. In the Xpert-MTB/RIF survey, 25 (sensitivity 89%, 95% CI 72.8% to 96.3%) of 28 pools containing MTB-positive samples tested positive and 81 pools containing only MTB-negative samples tested negative (specificity 100%, 95% CI 95.5% to 100%). In the Xpert-Ultra survey, all 32 (sensitivity 100%, 95% CI 89.3% to 100%) pools containing MTB-positive samples tested positive and all 77 (specificity 100%, 95% CI 95.3% to 100%) containing only MTB-negative samples tested negative. Pooling with Xpert-MTB/RIF and Xpert-Ultra saved 52% and 46% (227/436 and 199/436, respectively) of cartridge costs alone. CONCLUSION: Testing single and pooled specimens had a high level of agreement, with complete concordance when using Xpert-Ultra. Pooling samples could generate significant cartridge savings during ACF campaigns.


Subject(s)
Antibiotics, Antitubercular , Tuberculosis, Pulmonary , Tuberculosis , Antibiotics, Antitubercular/pharmacology , Antibiotics, Antitubercular/therapeutic use , Drug Resistance, Bacterial , Humans , Laos , Rifampin , Sensitivity and Specificity , Sputum/microbiology , Tuberculosis/diagnosis , Tuberculosis/drug therapy , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/epidemiology
5.
PLoS One ; 16(12): e0261849, 2021.
Article in English | MEDLINE | ID: covidwho-1623664

ABSTRACT

BACKGROUND: Tuberculosis (TB) and COVID-19 pandemics are both diseases of public health threat globally. Both diseases are caused by pathogens that infect mainly the respiratory system, and are involved in airborne transmission; they also share some clinical signs and symptoms. We, therefore, took advantage of collected sputum samples at the early stage of COVID-19 outbreak in Ghana to conduct differential diagnoses of long-standing endemic respiratory illness, particularly tuberculosis. METHODOLOGY: Sputum samples collected through the enhanced national surveys from suspected COVID-19 patients and contact tracing cases were analyzed for TB. The sputum samples were processed using Cepheid's GeneXpert MTB/RIF assay in pools of 4 samples to determine the presence of Mycobacterium tuberculosis complex. Positive pools were then decoupled and analyzed individually. Details of positive TB samples were forwarded to the NTP for appropriate case management. RESULTS: Seven-hundred and seventy-four sputum samples were analyzed for Mycobacterium tuberculosis in both suspected COVID-19 cases (679/774, 87.7%) and their contacts (95/774, 12.3%). A total of 111 (14.3%) were diagnosed with SARS CoV-2 infection and six (0.8%) out of the 774 individuals tested positive for pulmonary tuberculosis: five (83.3%) males and one female (16.7%). Drug susceptibility analysis identified 1 (16.7%) rifampicin-resistant tuberculosis case. Out of the six TB positive cases, 2 (33.3%) tested positive for COVID-19 indicating a coinfection. Stratifying by demography, three out of the six (50%) were from the Ayawaso West District. All positive cases received appropriate treatment at the respective sub-district according to the national guidelines. CONCLUSION: Our findings highlight the need for differential diagnosis among COVID-19 suspected cases and regular active TB surveillance in TB endemic settings.


Subject(s)
COVID-19/diagnosis , COVID-19/epidemiology , Coinfection/diagnosis , Coinfection/epidemiology , Mycobacterium tuberculosis/genetics , Pandemics/prevention & control , SARS-CoV-2/genetics , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/epidemiology , Antibiotics, Antitubercular/pharmacology , COVID-19/prevention & control , COVID-19/virology , Coinfection/virology , Diagnosis, Differential , Drug Resistance, Bacterial/drug effects , Female , Ghana/epidemiology , Humans , Male , Microbial Sensitivity Tests , Mycobacterium tuberculosis/drug effects , Rifampin/pharmacology , Sputum/microbiology , Tuberculosis, Pulmonary/microbiology
6.
PLoS One ; 16(12): e0261442, 2021.
Article in English | MEDLINE | ID: covidwho-1593549

ABSTRACT

A laboratory validation study was conducted to assess the equivalence of Xpert MTB/RIF Ultra testing on the GeneXpert System and the GeneXpert Omni System ('Omni') for tuberculosis and rifampicin resistance. High concordance of the two devices was demonstrated for well-characterized clinical samples as well as control materials, with controls tested on Omni at normal and challenging environmental conditions (i.e. 35°C, 90% relative humidity). Equivalence of the Cts for all probes was also shown. Equivalence was demonstrated for the Omni and GeneXpert devices for tuberculosis and rifampicin resistance detection for a diverse range of clinical specimens and environmental conditions.


Subject(s)
Antibiotics, Antitubercular/pharmacology , Mycobacterium tuberculosis/drug effects , Point-of-Care Testing , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Pulmonary/diagnosis , Bacterial Proteins/genetics , DNA-Directed RNA Polymerases/genetics , Drug Resistance, Multiple, Bacterial/genetics , Humans , Microbial Sensitivity Tests , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/isolation & purification , Rifampin/pharmacology , Sputum/microbiology , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Pulmonary/drug therapy
7.
Ann Clin Microbiol Antimicrob ; 20(1): 69, 2021 Sep 25.
Article in English | MEDLINE | ID: covidwho-1438275

ABSTRACT

BACKGROUND: Coronavirus SARS-CoV-2 causes COVID-19 illness which can progress to severe pneumonia. Empiric antibacterials are often employed though frequency of bacterial coinfection superinfection is debated and concerns raised about selection of bacterial antimicrobial resistance. We evaluated sputum bacterial and fungal growth from 165 intubated COVID-19 pneumonia patients. Objectives were to determine frequency of culture positivity, risk factors for and outcomes of positive cultures, and timing of antimicrobial resistance development. METHODS: Retrospective reviews were conducted of COVID-19 pneumonia patients requiring intubation admitted to a 1058-bed four community hospital system on the east coast United States, March 1 to May 1, 2020. Length of stay (LOS) was expressed as mean (standard deviation); 95% confidence interval (95% CI) was computed for overall mortality rate using the exact binomial method, and overall mortality was compared across each level of a potential risk factor using a Chi-Square Test of Independence. All tests were two-sided, and significance level was set to 0.05. RESULTS: Average patient age was 68.7 years and LOS 19.9 days. Eighty-three patients (50.3% of total) originated from home, 10 from group homes (6.1% of total), and 72 from nursing facilities (43.6% of total). Mortality was 62.4%, highest for nursing home residents (80.6%). Findings from 253 sputum cultures overall did not suggest acute bacterial or fungal infection in 73 (45%) of 165 individuals sampled within 24 h of intubation. Cultures ≥ 1 week following intubation did grow potential pathogens in 72 (64.9%) of 111 cases with 70.8% consistent with late pneumonia and 29.2% suggesting colonization. Twelve (10.8% of total) of these late post-intubation cultures revealed worsened antimicrobial resistance predominantly in Pseudomonas, Enterobacter, or Staphylococcus aureus. CONCLUSIONS: In severe COVID-19 pneumonia, a radiographic ground glass interstitial pattern and lack of purulent sputum prior to/around the time of intubation correlated with no culture growth or recovery of normal oral flora ± yeast. Discontinuation of empiric antibacterials should be considered in these patients aided by other clinical findings, history of prior antimicrobials, laboratory testing, and overall clinical course. Continuing longterm hospitalisation and antibiotics are associated with sputum cultures reflective of hospital-acquired microbes and increasing antimicrobial resistance. TRIAL REGISTRATION: Not applicable as this was a retrospective chart review study without interventional arm.


Subject(s)
Bacteria/drug effects , Bacterial Infections/complications , COVID-19/therapy , Cross Infection/complications , Fungi/drug effects , Mycoses/complications , Pneumonia/therapy , Sputum/microbiology , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents , Anti-Infective Agents/pharmacology , Bacteria/genetics , Bacteria/isolation & purification , Bacterial Infections/drug therapy , Bacterial Infections/microbiology , COVID-19/complications , COVID-19/mortality , COVID-19/virology , Cross Infection/drug therapy , Cross Infection/microbiology , Drug Resistance, Bacterial , Drug Resistance, Multiple, Fungal , Female , Fungi/genetics , Fungi/isolation & purification , Hospitalization , Humans , Intubation , Length of Stay , Male , Middle Aged , Mycoses/microbiology , Pneumonia/complications , Pneumonia/mortality , Pneumonia/virology , Retrospective Studies , SARS-CoV-2/physiology
8.
PLoS One ; 16(9): e0257647, 2021.
Article in English | MEDLINE | ID: covidwho-1430547

ABSTRACT

INTRODUCTION: Despite the exalted status of sputum mycobacterial load for gauging pulmonary tuberculosis treatment and progress, Chest X-rays supplement valuable information for taking instantaneous therapeutic decisions, especially during the COVID-19 pandemic. Even though literature on individual parameters is overwhelming, few studies have explored the interaction between radiographic parameters denoting severity with mycobacterial burden signifying infectivity. By using a sophisticated approach of integrating Chest X-ray parameters with sputum mycobacterial characteristics, evaluated at all the three crucial time points of TB treatment namely pre-treatment, end of intensive phase and completion of treatment, utilizing the interactive Cox Proportional Hazards model, we aimed to precisely deduce predictors of unfavorable response to TB treatment. MATERIALS AND METHOD: We extracted de-identified data from well characterized clinical trial cohorts that recruited rifampicin-sensitive Pulmonary TB patients without any comorbidities, taking their first spell of anti-tuberculosis therapy under supervision and meticulous follow up for 24 months post treatment completion, to accurately predict TB outcomes. Radiographic data independently obtained, interpreted by two experienced pulmonologists was collated with demographic details and, sputum smear and culture grades of participants by an independent statistician and analyzed using the Cox Proportional Hazards model, to not only adjust for confounding factors including treatment effect, but also explore the interaction between radiological and bacteriological parameters for better therapeutic application. RESULTS: Of 667 TB patients with data available, cavitation, extent of involvement, lower zone involvement, smear and culture grade at baseline were significant parameters predisposing to an unfavorable TB treatment outcome in the univariate analysis. Reduction in radiological lesions in Chest X-ray by at least 50% at 2 months and 75% at the end of treatment helped in averting unfavorable responses. Smear and Culture conversion at the end of 2 months was highly significant as a predictor (p<0.001). In the multivariate analysis, the adjusted hazards ratios (HR) for an unfavorable response to TB therapy for extent of involvement, baseline cavitation and persistence (post treatment) were 1.21 (95% CI: 1.01-1.44), 1.73 (95% CI: 1.05-2.84) and 2.68 (95% CI: 1.4-5.12) respectively. A 3+ smear had an HR of 1.94 (95% CI: 0.81-4.64). Further probing into the interaction, among patients with 3+ and 2+ smears, HRs for cavitation were 3.26 (95% CI: 1.33-8.00) and 1.92 (95% CI: 0.80-4.60) while for >2 zones, were 3.05 (95% CI: 1.12-8.23) and 1.92 (95% CI: 0.72-5.08) respectively. Patients without cavitation, zonal involvement <2, and a smear grade less than 2+ had a better prognosis and constituted minimal disease. CONCLUSION: Baseline Cavitation, Opacities occupying >2 zones and 3+ smear grade individually and independently forecasted a poorer TB outcome. The interaction model revealed that Zonal involvement confined to 2 zones, without a cavity and smear grade up to 2+, constituting "minimal disease", had a better prognosis. Radiological clearance >50% along with smear conversion at the end of intensive phase of treatment, observed to be a reasonable alternative to culture conversion in predicting a successful outcome. These parameters may potentially take up key positions as stratification factors for future trials contemplating on shorter TB regimens.


Subject(s)
Mycobacterium tuberculosis/physiology , Rifampin/therapeutic use , Sputum/microbiology , Tuberculosis, Pulmonary/diagnostic imaging , Tuberculosis, Pulmonary/drug therapy , Adult , Female , Humans , Kaplan-Meier Estimate , Male , Multivariate Analysis , Proportional Hazards Models , Rifampin/pharmacology , Treatment Outcome , Tuberculosis, Pulmonary/microbiology , Young Adult
10.
Future Microbiol ; 16(11): 769-776, 2021 07.
Article in English | MEDLINE | ID: covidwho-1308246

ABSTRACT

The current study presents two patients who lived in a rural family with close contact and suffered from rapidly progressive pneumonia. Chest computed tomography images and lymphocytopenia indicated the possibility of COVID-19 infection, but antibody and nucleic acid tests excluded this possibility. Negative results were obtained from corresponding tests for pneumococcal, adenovirus, fungal and legionella infection. Metagenomics analysis and subsequent antibody tests confirmed mycoplasma pneumonia. After treating with moxifloxacin, both patients recovered well and left the hospital. In terms of complicated infectious disease, consideration of atypical pathogens and medical and epidemiological history were important for differential diagnosis of COVID-19; metagenomics analysis was useful to provide direct references for diagnosis.


Subject(s)
Moxifloxacin/therapeutic use , Pneumonia, Mycoplasma/diagnosis , Adolescent , Adult , COVID-19 , DNA, Bacterial , Diagnosis, Differential , Feces/microbiology , Female , Humans , Male , Metagenomics , Mycoplasma pneumoniae/genetics , Mycoplasma pneumoniae/isolation & purification , Pneumonia, Mycoplasma/drug therapy , Sputum/microbiology , Young Adult
11.
BMC Pulm Med ; 20(1): 233, 2020 Aug 31.
Article in English | MEDLINE | ID: covidwho-1257932

ABSTRACT

BACKGROUND: Lower respiratory tract infection (LRIs) is very common both in terms of community-acquired infection and hospital-acquired infection. Sputum and bronchoalveolar lavage fluid (BALF) are the most important specimens obtained from patients with LRI. The choice of antibiotic with which to treat LRI usually depends on the antimicrobial sensitivity of bacteria isolated from sputum and BALF. However, differences in the antimicrobial sensitivity of pathogens isolated from sputum and BALF have not been evaluated. METHODS: A retrospective study was conducted to analyze the differences between sputum and BALF samples in terms of pathogen isolation and antimicrobial sensitivity in hospitalized patients with LRI. RESULTS: Between 2013 and 2015, quality evaluation of sputum samples was not conducted before performing sputum culture; however, between 2016 and 2018, quality evaluation of sputum samples was conducted first, and only quality-assured samples were cultured. The numbers of sputum and BALF in 2013-2015 were 15,549 and 1671, while those in 2016-2018 were 12,055 and 3735, respectively. The results of pathogen culture showed that Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus, Hemophilus influenzae, Escherichia coli, Stenotrophomonas maltophilia, and Streptococcus pneumoniae were in the top ten pathogens isolated from sputum and BALF. An antimicrobial susceptibility test showed that the susceptibility of BALF isolates to most antibiotics was higher compared with the susceptibility of sputum isolates, especially after quality control of sputum samples (2016-2018). CONCLUSIONS: Our findings suggest that caution is needed in making therapeutic choices for patients with LRI when using antimicrobial sensitivity results from sputum isolates as opposed to BALF isolates.


Subject(s)
Bacterial Infections/microbiology , Bronchoalveolar Lavage Fluid/microbiology , Microbial Sensitivity Tests , Respiratory System/microbiology , Sputum/microbiology , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/epidemiology , China/epidemiology , Escherichia coli/drug effects , Escherichia coli/isolation & purification , Female , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/isolation & purification , Gram-Positive Bacteria/drug effects , Gram-Positive Bacteria/isolation & purification , Hospitals, Teaching , Humans , Male , Retrospective Studies , Staphylococcus aureus/isolation & purification
12.
BMC Infect Dis ; 21(1): 352, 2021 Apr 15.
Article in English | MEDLINE | ID: covidwho-1191295

ABSTRACT

BACKGROUND: Identifying the causes of community-acquired pneumonia (CAP) is challenging due to the disease's complex etiology and the limitations of traditional microbiological diagnostic methods. Recent advances in next generation sequencing (NGS)-based metagenomics allow pan-pathogen detection in a single assay, and may have significant advantages over culture-based techniques. RESULTS: We conducted a cohort study of 159 CAP patients to assess the diagnostic performance of a clinical metagenomics assay and its impact on clinical management and patient outcomes. When compared to other techniques, clinical metagenomics detected more pathogens in more CAP cases, and identified a substantial number of polymicrobial infections. Moreover, metagenomics results led to changes in or confirmation of clinical management in 35 of 59 cases; these 35 cases also had significantly improved patient outcomes. CONCLUSIONS: Clinical metagenomics could be a valuable tool for the diagnosis and treatment of CAP. TRIAL REGISTRATION: Trial registration number with the Chinese Clinical Trial Registry: ChiCTR2100043628 .


Subject(s)
Community-Acquired Infections/diagnosis , Metagenomics/methods , Pneumonia/diagnosis , Adult , Aged , Aged, 80 and over , Bronchoalveolar Lavage Fluid/microbiology , Cohort Studies , Community-Acquired Infections/microbiology , DNA, Bacterial/chemistry , DNA, Bacterial/metabolism , Female , High-Throughput Nucleotide Sequencing , Humans , Male , Middle Aged , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/isolation & purification , Pneumonia/microbiology , Sequence Analysis, DNA , Sputum/microbiology , Young Adult
13.
Indian J Tuberc ; 67(4S): S61-S68, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1125720

ABSTRACT

The laboratory plays an important role in diagnosing tuberculosis (TB) and the identification and drug sensitivity testing (DST) of Mycobacterium tuberculosis. With a timely diagnosis and treatment with appropriate anti-TB drugs, most people who develop TB can be cured and onward transmission of infection curtailed. For a long time, laboratories used only microscopy and conventional culture-based diagnosis, however these procedures are slow and may require 3-4 weeks to yield results. Given the increasing rate of drug resistance, it has been necessary to look for new and rapid diagnostic methods. Various molecular based diagnostic technologies became available in the beginning of early 90s, providing rapid detection, identification and DST of M. tuberculosis. Molecular technologies offer the greatest potential for laboratories because they have the highest sensitivity and specificity. The present article will review some of the new methodology that has been introduced in the clinical laboratory.


Subject(s)
Mycobacterium tuberculosis/isolation & purification , Tuberculosis, Pulmonary/diagnosis , Humans , Microscopy , Mycobacterium tuberculosis/genetics , Sputum/microbiology , Whole Genome Sequencing
14.
Emerg Infect Dis ; 27(3): 719-727, 2021 03.
Article in English | MEDLINE | ID: covidwho-1100025

ABSTRACT

GeneXpert-based testing with Xpert MTB/RIF or Ultra assays is essential for tuberculosis diagnosis. However, testing may be affected by cartridge and staff shortages. More efficient testing strategies could help, especially during the coronavirus disease pandemic. We searched the literature to systematically review whether GeneXpert-based testing of pooled sputum samples achieves sensitivity and specificity similar to testing individual samples; this method could potentially save time and preserve the limited supply of cartridges. From 6 publications, we found 2-sample pools using Xpert MTB/RIF had 87.5% and 96.0% sensitivity (average sensitivity 94%; 95% CI 89.0%-98.0%) (2 studies). Four-sample pools averaged 91% sensitivity with Xpert MTB/RIF (2 studies) and 98% with Ultra (2 studies); combining >4 samples resulted in lower sensitivity. Two studies reported that pooling achieved 99%-100% specificity and 27%-31% in cartridge savings. Our results show that pooling may improve efficiency of GeneXpert-based testing.


Subject(s)
COVID-19/epidemiology , Molecular Diagnostic Techniques , Mycobacterium tuberculosis/isolation & purification , Sputum/microbiology , Tuberculosis/diagnosis , Cost-Benefit Analysis , Humans , Mycobacterium tuberculosis/genetics , SARS-CoV-2 , Sensitivity and Specificity , Specimen Handling
15.
J Korean Med Sci ; 35(43): e388, 2020 Nov 09.
Article in English | MEDLINE | ID: covidwho-918114

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused disruptions to healthcare systems and endangered the control and prevention of tuberculosis (TB). We investigated the nationwide effects of COVID-19 on the national Public-Private Mix (PPM) TB control project in Korea, using monitoring indicators from the Korean PPM monitoring database. METHODS: The Korean PPM monitoring database includes data from patients registered at PPM hospitals throughout the country. Data of six monitoring indicators for active TB cases updated between July 2019 and June 2020 were collected. The data of each cohort throughout the country and in Daegu-Gyeongbuk, Seoul Metropolitan Area, and Jeonnam-Jeonbuk were collated to provide nationwide data. The data were compared using the χ² test for trend to evaluate quarterly trends of each monitoring indicator at the national level and in the prespecified regions. RESULTS: Test coverages of sputum smear (P = 0.622) and culture (P = 0.815), drug susceptibility test (P = 0.750), and adherence rate to initial standard treatment (P = 0.901) at the national level were not significantly different during the study period. The rate of loss to follow-up among TB cases at the national level was not significantly different (P = 0.088); however, the treatment success rate among the smear-positive drug-susceptible pulmonary TB cohort at the national level significantly decreased, from 90.6% to 84.1% (P < 0.001). Treatment success rate in the Seoul metropolitan area also significantly decreased during the study period, from 89.4% to 84.5% (P = 0.006). CONCLUSION: Our study showed that initial TB management during the COVID-19 pandemic was properly administered under the PPM project in Korea. However, our study cannot confirm or conclude a decreased treatment success rate after the COVID-19 pandemic due to limited data.


Subject(s)
Coronavirus Infections/pathology , Pneumonia, Viral/pathology , Tuberculosis/prevention & control , Antitubercular Agents/therapeutic use , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/epidemiology , Databases, Factual , Delivery of Health Care , Drug Resistance, Microbial , Humans , Pandemics , Patient Compliance , Pneumonia, Viral/epidemiology , Republic of Korea/epidemiology , SARS-CoV-2 , Sputum/microbiology , Tuberculosis/diagnosis , Tuberculosis/drug therapy
16.
J Cyst Fibros ; 20(4): 699-701, 2021 07.
Article in English | MEDLINE | ID: covidwho-912332

ABSTRACT

The COVID19 pandemic has shifted the paradigm of how outpatient clinics are delivered within CF care, resulting in a significant reduction of patient visits to CF centres. One consequence of this has been a reduction in the number of sputa/cough swabs that patients submit for routine analysis. This report examines why it is important to maintain optimal sputum microbiology and explores (i). the microbiological efficiency of postal submission of sputum specimens from the community and (ii) the regulatory conditions that must be met through postal submission of respiratory specimens. Virtual clinics have now been established within CF care and it is incumbent on each speciality within the CF MDT to explore ways to nurture and support their individual contribution to the success of the virtual clinic. Within microbiology, adopting innovative approaches to sputum collection in the community and transportation via postal services will allow for continued microbiological vigilance thereby supporting patient safety.


Subject(s)
Cystic Fibrosis/microbiology , Sputum/microbiology , Telemedicine , Humans
17.
Clin Microbiol Infect ; 27(1): 61-66, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-808838

ABSTRACT

SCOPE: The Dutch Working Party on Antibiotic Policy constituted a multidisciplinary expert committee to provide evidence-based recommendation for the use of antibacterial therapy in hospitalized adults with a respiratory infection and suspected or proven 2019 Coronavirus disease (COVID-19). METHODS: We performed a literature search to answer four key questions. The committee graded the evidence and developed recommendations by using Grading of Recommendations Assessment, Development, and Evaluation methodology. QUESTIONS ADDRESSED BY THE GUIDELINE AND RECOMMENDATIONS: We assessed evidence on the risk of bacterial infections in hospitalized COVID-19 patients, the associated bacterial pathogens, how to diagnose bacterial infections and how to treat bacterial infections. Bacterial co-infection upon admission was reported in 3.5% of COVID-19 patients, while bacterial secondary infections during hospitalization occurred up to 15%. No or very low quality evidence was found to answer the other key clinical questions. Although the evidence base on bacterial infections in COVID-19 is currently limited, available evidence supports restrictive antibiotic use from an antibiotic stewardship perspective, especially upon admission. To support restrictive antibiotic use, maximum efforts should be undertaken to obtain sputum and blood culture samples as well as pneumococcal urinary antigen testing. We suggest to stop antibiotics in patients who started antibiotic treatment upon admission when representative cultures as well as urinary antigen tests show no signs of involvement of bacterial pathogens after 48 hours. For patients with secondary bacterial respiratory infection we recommend to follow other guideline recommendations on antibacterial treatment for patients with hospital-acquired and ventilator-associated pneumonia. An antibiotic treatment duration of five days in patients with COVID-19 and suspected bacterial respiratory infection is recommended upon improvement of signs, symptoms and inflammatory markers. Larger, prospective studies about the epidemiology of bacterial infections in COVID-19 are urgently needed to confirm our conclusions and ultimately prevent unnecessary antibiotic use during the COVID-19 pandemic.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , COVID-19/drug therapy , Opportunistic Infections/drug therapy , Pneumonia, Bacterial/drug therapy , SARS-CoV-2/pathogenicity , Bacterial Infections/diagnosis , Bacterial Infections/microbiology , Bacterial Typing Techniques , Bias , Blood Culture/methods , COVID-19/microbiology , COVID-19/virology , Coinfection , Evidence-Based Medicine , Humans , Opportunistic Infections/diagnosis , Opportunistic Infections/microbiology , Pneumonia, Bacterial/diagnosis , Pneumonia, Bacterial/microbiology , Sputum/microbiology
18.
Clin Microbiol Infect ; 27(1): 83-88, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-764421

ABSTRACT

OBJECTIVES: To describe the burden, epidemiology and outcomes of co-infections and superinfections occurring in hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS: We performed an observational cohort study of all consecutive patients admitted for ≥48 hours to the Hospital Clinic of Barcelona for COVID-19 (28 February to 22 April 2020) who were discharged or dead. We describe demographic, epidemiologic, laboratory and microbiologic results, as well as outcome data retrieved from electronic health records. RESULTS: Of a total of 989 consecutive patients with COVID-19, 72 (7.2%) had 88 other microbiologically confirmed infections: 74 were bacterial, seven fungal and seven viral. Community-acquired co-infection at COVID-19 diagnosis was uncommon (31/989, 3.1%) and mainly caused by Streptococcus pneumoniae and Staphylococcus aureus. A total of 51 hospital-acquired bacterial superinfections, mostly caused by Pseudomonas aeruginosa and Escherichia coli, were diagnosed in 43 patients (4.7%), with a mean (SD) time from hospital admission to superinfection diagnosis of 10.6 (6.6) days. Overall mortality was 9.8% (97/989). Patients with community-acquired co-infections and hospital-acquired superinfections had worse outcomes. CONCLUSIONS: Co-infection at COVID-19 diagnosis is uncommon. Few patients developed superinfections during hospitalization. These findings are different compared to those of other viral pandemics. As it relates to hospitalized patients with COVID-19, such findings could prove essential in defining the role of empiric antimicrobial therapy or stewardship strategies.


Subject(s)
Bacterial Infections/epidemiology , COVID-19/epidemiology , Cross Infection/epidemiology , Mycoses/epidemiology , SARS-CoV-2/pathogenicity , Superinfection/epidemiology , Virus Diseases/epidemiology , Aged , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/microbiology , Bacterial Infections/mortality , Bacterial Infections/therapy , Bacterial Typing Techniques , Blood Culture/methods , COVID-19/mortality , COVID-19/therapy , COVID-19/virology , Coinfection , Community-Acquired Infections , Cross Infection/microbiology , Cross Infection/mortality , Cross Infection/therapy , Female , Hospitalization , Hospitals , Humans , Incidence , Male , Middle Aged , Mycoses/microbiology , Mycoses/mortality , Mycoses/therapy , Retrospective Studies , Spain/epidemiology , Sputum/microbiology , Superinfection/mortality , Superinfection/therapy , Superinfection/virology , Survival Analysis , Virus Diseases/mortality , Virus Diseases/therapy , Virus Diseases/virology
19.
J Mycol Med ; 30(4): 101039, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-723228

ABSTRACT

As aspergillosis is a well-known complication of severe influenza, we suggest that SARS-CoV-2 might be a risk factor for invasive aspergillosis (IA). We report the case of an 87 year-old woman, with no history of immune deficit, admitted in our emergency room for severe respiratory distress. Coronavirus disease 2019 (COVID-19) diagnosis was confirmed by a SARS-CoV-2 reverse transcriptase polymerase chain reaction (PCR) on nasal swab. On day 14, pulmonary examination deteriorated with haemoptysis and a major increase of inflammatory response. A computed tomography (CT) scan revealed nodules highly suggestive of IA. Aspergillus antigen was found highly positive in sputum and blood, as was Aspergillusspp PCR on serum. Sputum cultures remained negative for Aspergillus. This patient died rapidly from severe respiratory failure, despite the addition of voriconazole. Considering SARS-CoV-2 acute respiratory distress syndrome (ARDS) as an acquired immunodeficiency, we report here a new case of "probable" IA based on clinical and biological arguments, in accordance with the last consensus definition of invasive fungal disease. On a routine basis, we have detected 30% of aspergillosis carriage (positive culture and antigen in tracheal secretions) in critically ill patients with COVID-19 in our centre. Further studies will have to determine whether sputum or tracheal secretions should be systematically screened for fungal investigations in intensive care unit (ICU) COVID-19 patients to early diagnose and treat aspergillosis.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , Invasive Pulmonary Aspergillosis/complications , Pneumonia, Viral/diagnosis , Aged, 80 and over , Antigens, Fungal/analysis , Antigens, Fungal/blood , Aspergillus/genetics , Aspergillus/immunology , Aspergillus/isolation & purification , Betacoronavirus/enzymology , Betacoronavirus/genetics , COVID-19 , Coronavirus Infections/complications , Fatal Outcome , Female , Humans , Invasive Pulmonary Aspergillosis/diagnosis , Nasal Mucosa/virology , Pandemics , Pneumonia, Viral/complications , Respiratory Distress Syndrome/etiology , Reverse Transcriptase Polymerase Chain Reaction , Risk Factors , SARS-CoV-2 , Sputum/microbiology
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