I.D. SCAN
Duration of Pertussis PCR positivity a Median of 58 Days
There is a median duration of 58 days for Bordetella pertussis PCR positivity, according to recent study findings published in the Journal of the Pediatric Infectious Diseases Society.
Bryan L. Stone, of the division of pediatric inpatient medicine, department of pediatrics at the University of Utah School of Medicine, and colleagues evaluated children younger than 18 years with positive B. pertussis PCR (index cases; n=14) and close contacts with at least 7 days of cough illness without a known etiology (associated cases; n=35). Participants provided nasopharyngeal samples for PCR testing at baseline, then weekly for 3 weeks, followed by testing monthly or every other month from symptom onset until samples were negative.
Fifty-one percent of associated cases were PCR-positive. Including negative baseline samples more than 21 days after symptom onset, 31 PCR-positive participants and three PCR-negative participants were included in analysis.Samples were positive from days 4 to 172 following symptom onset, and conversion to negative samples occurred between 22 and 207 days in PCR-positive participants.Out of 34 participants who provided 50 PCR samples, 34 received either erythromycin or azithromycin.
“B. pertussis PCR may remain positive in 50% of patients for >50 days after the onset of symptoms, despite antibiotic treatment and clinical improvement,” the researchers wrote. “Testing for B. pertussis by PCR when clinical suspicion of infection exists may be useful weeks after symptoms onset; respiratory illness testing strategies need to include consideration that persistent positive B. pertussis PCR results may confuse the diagnosis in nonpertussis infection.”
(Stone BL. J Pediatr Infect Dis Soc. 2014;doi:10.1093/jpids/pui004.)
Comment
Roger Baxter
I found this a helpful study, in both a clinical and research context. Clinically, we often wonder if a person with prolonged cough has pertussis, and this study is reassuring that, even after several weeks (when many patients present), the test can be useful. For research, we use the test as a marker of infection, and there has been concern that many people with pertussis might have a false negative test if they present late, leading to misclassification and diluting the vaccine effectiveness estimates. Once again, this is reassuring.I agree with the researchers’ conclusions that this makes repeat testing pretty useless, but in my experience patients rarely like to go through the nasopharyngeal test again, once they’ve had the pleasure of a 3-inch swab up their nose.
(Roger Baxter, MD; Co-Director of the Vaccine Study Center at Kaiser Permanente, Oakland, Calif, In Infectious Diseases in Children, 2014.)
Antibiotic Treatment of Pertussis - Are 7 Days Really Sufficient?
Short courses of antibiotic therapy are recommended for treatment of pertussis. We report two young unvaccinated infants with persistently positive B. pertussis by PCR from nasopharyngeal swabs despite 7 days of clarithromycin (15 mg/kg/d) therapy. In one patient, quantitative PCR was 7.02 (log GEq/ml) at onset of treatment, 6.26 at end of treatment and remained positive with 2.64 and 2.69 during and after a second 7-day-course, respectively. The generally believed assumption that contagiousness of pertussis is terminated after 5 days of antibiotic treatment should be challenged, at least in young infants.
(Dierig, Alexa, Beckmann, Christiane, et al. Pediatr Infect Dis J. 2014 Sep 22. [Epub ahead of print] doi: 10.1097/INF.0000000000000567)
C-Reactive Protein, Procalcitonin, and the Lab-Score for Detecting Serious Bacterial Infections in Febrile Children
C-reactive protein (CRP) and procalcitonin (PCT) are useful diagnostic tools to estimate the risk of serious bacterial infection (SBI) in febrile children at the emergency department (ED). The Lab-score combines these two biomarkers with urinalysis in an easy to use validated model. Kinetics of inflammatory markers suggests a differentiating role of duration of disease.
Aim: Appraisal of the diagnostic role of CRP and PCT in febrile children at risk of SBI, determining the differentiating value of duration of fever, and validating and updating the Lab-score.
Methods: In this prospective observational study previously healthy children with fever, 1 month to 16 years of age, attending the EDs of a university hospital and a teaching hospital (Rotterdam, the Netherlands) between 2009 and 2012 were included. Standardised information on clinical signs and symptoms, CRP, PCT, and urinalysis were collected prospectively. Logistic multivariable regression analysis was used to assess diagnostic performance. The original Lab-score included CRP, PCT, and urinalysis and the total score ranged 0 to 9 points.
Results: 1,084 children were included, median age was 1.6 years (IQR: 0.8-3.5), 170 children (16%) had SBI. CRP (ROC-area 0.77 (95% confidence interval (CI) 0.69 - 0.85)) and PCT (ROC-area 0.75 (95% CI 0.67 - 0.83)) were both strong predictors of SBI. Duration of fever had no added diagnostic value to CRP and PCT. The Lab-score performed well (ROC area 0.79, 95% CI 0.72-0.87), but thresholds values performed similar to often used cut-offs of single biomarkers. An updated Lab-score improved only moderately (ROC area 0.83 (95% CI 0.76 - 0.90)). PCT did not alter post-test probabilities for SBI substantially in patients with low (<20 mg/L) or elevated CRP (>=100 mg/L) levels (67% of population).
Conclusion: CRP and PCT were both strong predictors of SBI. The original and updated Lab-score performed well, but thresholds values lacked diagnostic value for ruling out SBI. Depending on clinical risk thresholds, diagnostic testing can be limited to CRP or PCT, rather than both, in many febrile children.
(Nijman, Ruud G.; Moll, Henriëtte A. Et al. Pediatr Infect Dis J 2014. [Epub ahead of print] doi: 10.1097/INF.0000000000000466)
Ceftriaxone Alone versus Ceftriaxone plus Macrolide in Hospitalized Community-acquired Pneumonia
Guidelines for management of community-acquired pneumonia recommend empiric therapy with a macrolide and beta-lactam when infection with Mycoplasma pneumoniae is a significant consideration. Evidence to support this recommendation is limited. We sought to determine the effectiveness of ceftriaxone alone compared with ceftriaxone combined with a macrolide with respect to length of stay and total hospital costs.
Methods:
We conducted a retrospective cohort study of children 1–17 years with pneumonia, using Poisson regression and propensity score analyses to assess associations between antibiotic and length of stay. Multivariable linear regression and propensity score analyses were used to assess log-treatment costs, adjusting for patient and hospital characteristics and initial tests and therapies.
Results:
A total of 4701 children received combination therapy and 8892 received ceftriaxone alone. Among children 1–4 years of age, adjusted models revealed no significant difference in length of stay, with significantly higher costs in the combination therapy group [cost ratio: 1.08 (95% confidence interval: 1.05–1.11)]. Among children 5–17 years of age, children receiving combination therapy had a shorter length of stay [relative risk: 0.95 (95% confidence interval: 0.92–0.98)], with no significant difference in costs [cost ratio: 1.01 (95% confidence interval: 0.98–1.04)].
Conclusions:
Combination therapy did not appear to benefit preschool children but was associated with higher costs. Among school-aged children, combination therapy was associated with a shorter length of stay without a significant impact on cost. Development of sensitive point-of-care diagnostic tests to identify children with M. pneumoniae infection may allow for more focused prescription of macrolides and enable comparative effectiveness studies of targeted provision of combination therapy.
( Leyenaar, JoAnna K, Shieh, Meng-Shiou, et al. Pediatr Infect Dis J 2014; 33: 387-392)
Antioxidants: Potential antiviral agents for JE virus infection
Japanese encephalitis (JE) is prevalent throughout eastern and southern Asia and the Pacific Rim. It is caused by the JE virus (JEV), which belongs to the family Flaviviridae. Despite the importance of JE, little is known about its pathogenesis. The role of oxidative stress in the pathogenesis of viral infections has led to increased interest in its role in JEV infections. This review focuses mainly on the role of oxidative stress in the pathogenesis of JEV infection and the antiviral effect of antioxidant agents in inhibiting JEV production. First, this review summarizes the pathogenesis of JE. The pathological changes include neuronal death, astrocyte activation, and microglial proliferation. Second, the relationship between oxidative stress and JEV infection is explored. JEV infection induces the generation of oxidants and exhausts the supply of antioxidants, which activates specific signaling pathways. Finally, the therapeutic efficacy of a variety of antioxidants as antiviral agents, including minocycline, arctigenin, fenofibrate, and curcumin, was studied. In conclusion, antioxidants are likely to be developed into antiviral agents for the treatment of JE.
(Yu Zhang et al. In International J Infect Dis. 2014; 24: 30-36)
Performance of QuantiFERON-TB Gold versus TSTs in foreign-born children
Centers for Disease Control and Prevention requirements for pre-immigration tuberculosis (TB) screening of children 2-14 years old permit a tuberculin skin test (TST) or an interferon-gamma release assay (IGRA). Few data are available on the performance of IGRAs versus TSTs in foreign-born children.
Methods: We compared the performance of TST and QuantiFERON-TB Gold In-Tube (QFT) in children 2-14 years old applying to immigrate to the United States from Mexico, the Philippines, and Vietnam, using diagnosis of TB in immigrating family members as a measure of potential exposure.
Results: We enrolled 2,520 children: 664 (26%) were TST+ and 142 (5.6%) were QFT+. One hundred eleven (4.4%) were TST+/QFT+, 553 (21.9%) were TST+/QFT-, and 31 (1.2%) were TST-/QFT+. Agreement between tests was poor ([kappa]=0.20). While positive results of both tests were significantly associated with older age (RR TST+, 1.64; 95% CI, 1.36-1.97; RR QFT+, 3.05; 95% CI, 1.72-5.38) and with the presence of TB in at least one immigrating family member (RR TST+, 1.40; 95% CI, 1.12-1.75; RR QFT+ 2.24; 95% CI, 1.18-4.28), QFT+ results were more strongly associated with both predictive variables.
Conclusions: The findings support the preferential use of QFT over TST for pre-immigration screening of foreign-born children 2 years of age and older and lend support to the preferential use of IGRAs in testing foreign-born children for latent TB infection.
(Howley, Meredith M., Painter, John A. Et al. Pediatric Infectious Disease Journal: doi: 10.1097/INF.0000000000000494)
New drug combination shortens and improves TB treatment
A new drug cocktail may represent a huge step forward in treating tuberculosis. In a first study, which involved 200 patients in Tanzania and Bangladesh, the drug combination achieved very good results, reported Mel Spigelman, president of the "TB Alliance", at the International Aids Conference in Melbourne (Australia).
Tuberculosis is one of the main secondary diseases among HIV-infected patients. Approximately two billion people are carriers of the pathogen, but only a fraction of them actually develops the disease. However, TB is the cause of death in 20 percent of Aids patients.
The new treatment method is called PaMZ and includes the drugs PA-824, moxifloxacin and pyrazinamide. The drug combination is able to reduce the duration of treatment from two years to four months. In the study, the costs decreased by 90 percent and the cure rate increased from 50 to 90 percent, explained Spigelman. HIV patients tolerated the medications very well.
During the course of this year, it is planned to test the treatment in a large-scale study involving 1,500 participants in 15 countries. If it proved effective, this would constitute the first new TB treatment option for the past 50 years, said Spigelman.
How effective are Gastric Aspirates for Diagnosing Tuberculosis in Children?
Gastric aspirate (GA) cultures positive for Mycobacterium tuberculosis were found in 7% of 285 patients who underwent GA. Positive GA cultures were associated with disseminated disease and intrathoracic lymphadenopathy, but not isolated airspace or pleural disease. Nontuberculous mycobacterial species isolated from GA in twelve patients did not reflect the pathogens causing disease in three children and were not associated with clinical disease in any patient. (Kordy, Faisal Richardson, Susan E. et al. Pediatr Infect Dis J. 2014. [Epub ahead of print] doi: 10.1097/INF.0000000000000498)
Papaya extract to treat dengue: A novel therapeutic option?
Dengue is a viral disease that today affects a vast number of people in over 125 countries and is responsible for a sizable number of deaths. In the absence of an effective antiviral drug to treat the disease, various treatments are being investigated. Studies have indicated that the juice of the leaves of the Carica papaya plant from the family Caricaceae could help to increase the platelet levels in these patients. This review describes some of the published studies on this topic. The search was done independently by the two authors using PubMed, Google and the library database and included relevant articles of the last 10 years. A total of 7 studies were included in this review, which were one animal study, one case report, three case series and two randomized controlled trials. Although many of the studies and case reports published in literature lack adequate information, some of the studies do raise the possibility that this treatment could be an important option in the future. Further large-scale studies could establish the usefulness or ineffectiveness of this natural product in the treatment of dengue.
(Sarala N, Paknikar SS. Ann Med Health Sci Res. 2014; 4: 320-324).
Potential novel biomarker identified for bacterial pneumonia
In the June 15th 2014 issue of Clinical Infectious Diseases, Huang and colleagues identified and validated a novel biomarker called Lipocalin-2 (Lpc-2) that may help distinguish children with severe bacterial pneumonia or bacteremia from those with non-bacterial illnesses (Huang H. Clin Infect Dis. 2014; 58: 1707-1715.). Plasma samples from Gambian infants and children aged 2 to 59 months were obtained and underwent mass spectrometry. When samples from healthy patients, patients with non-severe pneumonia, and patients with severe pneumonia were compared, eight proteins were identified that incrementally increased from healthy controls to patients with severe pneumonia. Lpc-2, a protein known to be expressed in neutrophils, which functions to sequester iron and thus limit bacterial growth, was among these proteins. They determined that elevated Lpc-2 levels had a sensitivity and specificity of approximately 70% in predicting severe disease and a sensitivity of 70% and specificity of 94% in predicting likely bacterial pneumonia. When used with clinical criteria, this marker increased diagnostic specificity for severe pneumonia to 82%.
Though this study has several limitations, I applaud the authors in their efforts to identify objective markers of bacterial infection. Among bacterial infections, pneumonia presents unique challenges in diagnosis in that there is no absolute “gold standard” clinical, laboratory or radiographic finding, often leaving the clinician uncertain about need for antibiotic therapy.
Many overlapping clinical syndromes, including bronchitis, bronchiolitis and upper respiratory infection may cause many of the same signs as bacterial pneumonia. Laboratory criteria, including white blood cell count and C-reactive protein, are non-specific. Finally, chest X-ray findings of atelectasis, chronic lung disease, pulmonary edema and viral pneumonia can be indistinguishable from bacterial pneumonia.
In the developing world, as pointed out by the authors, use of these biomarkers could (with more study) result in development of point-of-care testing to identify those children who require referral and/or antibiotic therapy, and thus better allocate scarce resources. Here in the United States, we also face a resource allocation issue in treating respiratory infections, though ours is more likely due to antibiotic over prescription. Among children admitted to US children’s hospitals, antibiotic therapy for pneumonia accounts for more antibiotic days than any other condition. In US intensive care units, suspected lower respiratory tract infection is the most common reason for antibiotic use. If specific markers can be developed that allow identification of those children with bacterial who will benefit from antibiotic therapy, we can likely save a great deal of unnecessary antibiotic exposure. This and other biomarkers warrant further investigation.
(http://www.healio.com/pediatrics/blogs/katie-chiotos/potential-novel-biomarker-identified-for-bacterial-pneumonia#)