Molecular detection and quantification of pertussis and correlation with clinical outcomes in children

DeVincenzo, John P.; Guyton, Cliff; Rea, Harrison; Elmore, Evan; Patel, Shivam; Wynn, Luke; Harrison, Lisa M.; Saleeby, Chadi M. El; Bagga, Bindiya

doi:10.1016/j.diagmicrobio.2012.12.015

Cited by 11 publications

(10 citation statements)

References 24 publications

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“…The median Ct value of cases varied by age, with patients under one year having the lowest Ct values. This is also concordant with other studies [ 23 , 24 ]. In particular, Nakamura et al .…”

Section: Discussionsupporting

confidence: 94%

“…The proportions of patients who, according to reportable disease data, reported the symptoms most indicative of pertussis were not significantly different between those with positive RT-PCR tests compared to those with indeterminate results. This was discordant with findings from other studies, in which lower Ct values were associated with the presence of symptoms [ 10 , 24 ]. For example, another study performed in Ontario a few years before ours found a significant correlation between the estimated probability of meeting clinical case definition and Ct value [ 13 , 27 ].…”

Section: Discussionsupporting

confidence: 78%

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Correlation of Real Time PCR Cycle Threshold Cut-Off with Bordetella pertussis Clinical Severity

et al. 2015

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Bordetella pertussis testing performed using real-time polymerase chain reaction (RT-PCR) is interpreted based on a cycle threshold (Ct) value. At Public Health Ontario Laboratories (PHOL), a Ct value <36 is reported as positive, and Ct values ≥36 and <40 are reported as indeterminate. PHOL reported indeterminate results to physicians and public health units until May 2012, after which these results were only reported to physicians. We investigated the association between Ct value and disease symptom and severity to examine the significance of indeterminate results clinically, epidemiologically and for public health reporting. B. pertussis positive and indeterminate RT-PCR results were linked to pertussis cases reported in the provincial Integrated Public Health Information System (iPHIS), using deterministic linkage. Patients with positive RT-PCR results had a lower median age of 10.8 years compared to 12.0 years for patients with indeterminate results (p = 0.24). Hospitalized patients had significantly lower Ct values than non-hospitalized patients (median Ct values of 20.7 vs. 31.6, p<0.001). The proportion of patients reporting the most indicative symptoms of pertussis did not differ between patients with positive vs. indeterminate RT-PCR results. Taking the most indicative symptoms of pertussis as the gold-standard, the positive predictive value of the RT-PCR test was 68.1%. RT-PCR test results should be interpreted in the context of the clinical symptoms, age, vaccination status, prevalence, and other factors. Further information on interpretation of indeterminate RT-PCR results may be needed, and the utility of reporting to public health practitioners should be re-evaluated.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 78%

Correlation of Real Time PCR Cycle Threshold Cut-Off with Bordetella pertussis Clinical Severity

et al. 2015

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“…Ct values significantly correlated with length of hospitalization and lymphocytosis (9). Our results follow the same trend.…”

Section: Cohort Studysupporting

confidence: 87%

“…In our study, the two groups were significantly different with regards to their clinical presentations and outcomes, possibly because our population consisted of children, who are usually more severely affected by pertussis than adults. DeVincenzo et al (9) also evaluated the relationship between PCR Ct value and pertussis severity. They showed that Abbreviations: CI, confidence interval; n, number; NA, not applicable; MPS, Modified Preziosi Scale; OR, odds ratio; PCR, polymerase chain reaction; RSS, Respiratory Severity Score; SD, standard deviation a All results reported as n (%) with the exception of length of cough (days) and lymphocytes, which are reported as a mean with standard deviation, and MPS and RSS severity score, which are reported as a mean b Statistically significant results (p<0.…”

Section: Discussionmentioning

confidence: 99%

Should equivocal Bordetella pertussis PCR results in children be reported to public health?

Desjardins

Mousseau

Doyon-Plourde

et al. 2018

CCDR

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Introduction: Real-time polymerase chain reaction (PCR) is the preferred method for the diagnosis of pertussis. In Quebec, positive and equivocal results are reportable to public health; in contrast, in Ontario equivocal results are not reportable. Objective: To determine the clinical significance of equivocal, compared with positive results, in children with suspected pertussis. Methods: Retrospective cohort of consecutive patients seen at the Centre Hospitalier Universitaire Sainte-Justine in Montréal, Quebec, with suspected pertussis and tested with a bacterial multiplex PCR (including Bordetella pertussis) between 2015 and 2017. Medical records were reviewed using a standardized form. Univariate analyses (Student's t-test and chi-square test) and multivariable logistic regression were used to compare cases of positive and equivocal results. Results: Of the 1,526 multiplex PCR performed, 109 were positive and 24 equivocal. Both groups were similar in terms of demographics and disease severity assessments, but patients in the equivocal group had less paroxysmal cough (33.3% vs 79.8%, adjusted odds ratio [aOR] 0.11, 95% confidence interval [CI] 0.04-0.29) and whoop (0% vs 18.3%, p<0.001), lower lymphocyte counts (6.6 vs 11.9 x10 9 /L, p=0.008), were more likely to be diagnosed with a viral co-infection (16.7% vs 3.7%, aOR 5.62, 95% CI 1.17-27.54) and were less likely to receive a macrolide (25% vs 89%, aOR 0.04, 95% CI 0.01-0.11). When admitted, patients with equivocal results had a shorter average length of stay (3.3 vs 12.2 days, p=0.001). Conclusion: Although there were similarities in disease severity, children with suspected pertussis who had equivocal PCR results had significantly different clinical presentations compared with those with positive results. In the context of limited public health resources, these results may inform the decision whether or not equivocal results need to be reported to public health by laboratories.

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“…For assessment of the sensitivity of culture, various clinical case definitions are used, and sensitivities have been calculated for various patient and age groups, such as in outbreak settings (schools), vaccine efficacy trials (infants), or a population with sporadic cases (all age groups). The sensitivity of culture also depends on the bacterial load, as demonstrated by studies using semiquantitative PCRs (40,111,(262)(263)(264). It was found that the culture sensitivity decreased with increasing C q values (and hence a decreasing bacterial DNA presence) for real-time PCR (85,265).…”

Section: Factors That Influence the Sensitivity Of Diagnostic Methodsmentioning

confidence: 99%

Laboratory Diagnosis of Pertussis

2015

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SUMMARYThe introduction of vaccination in the 1950s significantly reduced the morbidity and mortality of pertussis. However, since the 1990s, a resurgence of pertussis has been observed in vaccinated populations, and a number of causes have been proposed for this phenomenon, including improved diagnostics, increased awareness, waning immunity, and pathogen adaptation. The resurgence of pertussis highlights the importance of standardized, sensitive, and specific laboratory diagnoses, the lack of which is responsible for the large differences in pertussis notifications between countries. Accurate laboratory diagnosis is also important for distinguishing between the several etiologic agents of pertussis-like diseases, which involve both viruses and bacteria. If pertussis is diagnosed in a timely manner, antibiotic treatment of the patient can mitigate the symptoms and prevent transmission. During an outbreak, timely diagnosis of pertussis allows prophylactic treatment of infants too young to be (fully) vaccinated, for whom pertussis is a severe, sometimes fatal disease. Finally, reliable diagnosis of pertussis is required to reveal trends in the (age-specific) disease incidence, which may point to changes in vaccine efficacy, waning immunity, and the emergence of vaccine-adapted strains. Here we review current approaches to the diagnosis of pertussis and discuss their limitations and strengths. In particular, we emphasize that the optimal diagnostic procedure depends on the stage of the disease, the age of the patient, and the vaccination status of the patient.

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Molecular detection and quantification of pertussis and correlation with clinical outcomes in children

Cited by 11 publications

References 24 publications

Correlation of Real Time PCR Cycle Threshold Cut-Off with Bordetella pertussis Clinical Severity

Correlation of Real Time PCR Cycle Threshold Cut-Off with Bordetella pertussis Clinical Severity

Should equivocal Bordetella pertussis PCR results in children be reported to public health?

Laboratory Diagnosis of Pertussis

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