Dataset Information

Diagnostic efficacy of targeted high-throughput sequencing for lower respiratory infection in preterm infants.

ABSTRACT:

Objective

To examine the pathogen diagnostic performance of targeted high-throughput next-gen sequencing (tNGS) in respiratory infectious diseases in preterm infants using dynamic follow-up.

Methods

Clinical samples of respiratory secretions were consecutively collected from 20 preterm infants weekly for 5 weeks, during which 10 developed bronchopulmonary dysplasia. Pathogen identification from these collected specimens was performed by both conventional cultivation and tNGS.

Results

We found that targeted next-generation sequencing shared a 90.9% full or partial consistency for lower respiratory pathogen detection with the traditional culture-based approach, and increased the detection rate by 105.9%. Moreover, most of the pathogens identified by tNGS were diminished in patients after treatment.

Conclusion

This study reveals the high sensitivity and performance of targeted high-throughput sequencing for respiratory infectious disease diagnosis and pathogen identification. The trial registry number is NCT03850457, and the trial URL is https://clinicaltrials.gov/ct2/show/NCT03850457.

SUBMITTER: Dai Y

PROVIDER: S-EPMC9730095 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Diagnostic efficacy of targeted high-throughput sequencing for lower respiratory infection in preterm infants.

Dai Yi Y Sheng Kai K Hu Lan L

American journal of translational research 20221115 11

<h4>Objective</h4>To examine the pathogen diagnostic performance of targeted high-throughput next-gen sequencing (tNGS) in respiratory infectious diseases in preterm infants using dynamic follow-up.<h4>Methods</h4>Clinical samples of respiratory secretions were consecutively collected from 20 preterm infants weekly for 5 weeks, during which 10 developed bronchopulmonary dysplasia. Pathogen identification from these collected specimens was performed by both conventional cultivation and tNGS.<h4>R ...[more]

PMID: 36505277

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Project description:IntroductionDiagnosis of pertussis is challenging especially in infants. Most low and middle-income countries (LMIC) lack resources for laboratory confirmation, relying largely on clinical diagnosis alone for both case management and surveillance. This necessitates robust clinical case definitions.ObjectivesThis study assesses the accuracy of clinical case definitions with and without lymphocytosis in diagnosing pertussis in children with severe lower respiratory tract infection (LRTI) in a LMIC setting.MethodsChildren hospitalized with severe LRTI in a South African hospital were prospectively enrolled and evaluated for pertussis using PCR on respiratory samples. Clinical signs and differential white cell counts were recorded. Sensitivity and specificity of pertussis clinical diagnosis using WHO and Global Pertussis Initiative (GPI) criteria; and with addition of lymphocytosis were assessed with PCR as the reference standard.Results458 children <10 years were enrolled. Bordetella pertussis infection was confirmed in 32 (7.0%). For WHO criteria, sensitivity was 78.1% (95% CI 60.7-89.2%) and specificity 15.5% (95% CI 12.4-19.3%); for GPI sensitivity was 34.4% (95% CI 20.1-52.1) and specificity 64.8% (95% CI 60.1-69.2%). Area under the curve (AUC) on receiver operating character (ROC) analysis was 0.58 (95% CI 0.46-0.70 for WHO criteria, and 0.72 (95% CI 0.56-0.88) for GPI with highest likelihood ratios of 5.33 and 4.42 respectively. Diagnostic accuracy was highest between five and seven days of symptoms for both criteria. Lymphocytosis had sensitivity of 31.3% (95% CI 17.5-49.3%) and specificity of 70.7% (95% CI 66.1-74.8%) and showed a marginal impact on improving clinical criteria.ConclusionClinical criteria lack accuracy for diagnosis and surveillance of pertussis. Non-outbreak settings should consider shorter durations in clinical criteria. New recommendations still fall short of what is required for a viable clinical screening test which means the need to improve access to laboratory diagnostic support remains crucial.

Project description:BackgroundRespiratory syncytial virus (RSV) prophylaxis using palivizumab effectively reduces RSV-associated morbidity in preterm infants. In Korea, national insurance coverage for palivizumab was implemented in October 2016 for moderate-to-late preterm (MLPT) infants born during the RSV season (October-March) who have older siblings. However, no large-scale studies have investigated the changes in the incidence and risk of severe acute lower respiratory infections (ALRIs) after insurance coverage implementation for MLPT infants.MethodsThis large-scale retrospective cohort study used data from the Korean National Health Insurance Service between October 2013 and December 2019. MLPT infants (32 0/7-35 6/7 weeks of gestation) with older siblings were stratified into pre-insurance period (PIP; October 2013-September 2016) and insurance period (IP; October 2016-March 2019) groups based on the date of birth with respect to initial insurance palivizumab implementation. Severe ALRI outcomes (hospitalization, respiratory support, and intensive care unit admission) were evaluated up to 1 year of age using multivariable logistic regression models.ResultsOf the 11,722 MLPT infants included in the study, 6,716 and 5,006 infants were included in the IP and PIP groups, respectively. The incidences of ALRI-hospitalization and ALRI-respiratory support were significantly lower in the IP group than that in PIP group (24.0% vs. 26.0% and 3.1% vs. 4.0%, respectively). Additionally, ALRI-respiratory support risk was significantly lower in the IP group (adjusted odds ratio 0.771, 95% confidence interval 0.626-0.949, P = 0.014) than that in the PIP group. Among infants born during the RSV season, the risk of ALRI-hospitalization and ALRI-respiratory support were significantly lower in the IP group than that in the PIP group. However, no significant differences were observed between the IP and PIP groups for infants born during the non-RSV season.ConclusionThe risks of severe ALRI outcomes decreased in Korea following the 2016 insurance implementation of palivizumab prophylaxis for MLPT infants born during the RSV season with older siblings.

Project description:BackgroundTo evaluate the clinical utility of targeted next-generation sequencing (tNGS) for pathogen detection of pediatric acute lower respiratory tract infections (ALRTIs), with a particular focus on the use of throat swab samples.MethodsIn this diagnostic accuracy study involving 132 children, throat swabs and bronchoalveolar lavage fluid (BALF) samples were collected and analyzed by tNGS, and the results were compared with those obtained from conventional diagnostic methods. The impact of prior antibiotic use on the detection rate of tNGS was evaluated, the consistency between throat swabs and BALF was assessed, and the economic cost and invasiveness of the sampling methods were examined.ResultsThis study enrolled 132 children, of whom 79 (60%) were boys and 53 (40%) were girls. Ninety-two (70%) of the patients had fever, and 128 (97%) had a cough. The detection rates of bacteria, viruses, and atypical pathogens in BALF samples by tNGS were 89.5% (n = 68), 98.2% (n = 108), and 77.8% (n = 63), respectively. Compared to traditional detection methods, tNGS showed significantly higher detection rates for bacteria and viruses (P < 0.001), but there was no statistically significant difference in the detection of atypical pathogens (P = 0.59). The use of antibiotics had no significant effect on bacterial detection by tNGS (P = 0.237). Using BALF-tNGS as the "gold standard," the sensitivities of tNGS of throat swabs for detecting bacteria, viruses, and atypical pathogens were 95.83%, 88.16%, and 92.06%, respectively, with specificities of 55.95%, 83.93%, and 100%. In the analysis of economic costs and invasiveness, the cost of throat swab sampling was significantly lower than that of BALF sampling, and the associated pain score and complication rate were significantly lower (P < 0.05).ConclusionstNGS with throat swabs offers higher sensitivity and specificity than traditional methods for diagnosing pediatric ALRTIs. As such, it offers a less invasive, more cost-effective alternative to BALF sampling.

Dataset Information

Diagnostic efficacy of targeted high-throughput sequencing for lower respiratory infection in preterm infants.

Objective

Methods

Results

Conclusion

Publications

Diagnostic efficacy of targeted high-throughput sequencing for lower respiratory infection in preterm infants.

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