Michal Stein

Colchicine prophylaxis for frequent periodic fever, aphthous stomatitis, pharyngitis and adenitis episodes

Aim: To review our experience with colchicine for the prophylaxis of PFAPA (periodic fever, aphthous stomatitis, pharyngitis, adenitis).

Invasive Bacterial Infections in Relation to Influenza Outbreaks, 2006–2010

BACKGROUNDnWe aimed to define the excess morbidity associated with bloodstream infections (BSIs), imposed by pandemic H1N1 influenza during 2009-2010 (pH1N1/2009-2010) and seasonal influenza.nnnMETHODSnEight hospitals, accounting for 33% of hospitalizations in Israel, provided data on BSI during 2006-2010. The age-specific incidence of BSI due to Streptococcus pneumoniae, Staphylococcus aureus, and Streptococcus pyogenes was determined. BSI incidence rate ratios (IRRs) during seasonal and pH1N1 influenza seasons were assessed.nnnRESULTSnRegular influenza seasons were characterized by increased rates of S. pneumoniae BSI but with no increase in S. aureus and S. pyogenes BSI rates. The pH1N1/2009-2010 influenza outbreak was characterized by (1) higher rates of S. pneumoniae bacteremia among children but not among adults (IRRs for S. pneumoniae BSI among children aged 0-4 years during the summer and winter of 2009-2010 were 14.8 [95% confidence interval {CI}, 5-43.7] and 6.5 [95% CI, 3.6-11.8], compared with 2006-2009 summers and influenza-active winter weeks, respectively [P < .0001]), higher rates of S. aureus BSI in all age groups (IRRs during the summer and winter of 2009-2010 were 1.6 [95% CI, 1.4-1.9] and 1.5 [95% CI, 1.2-1.7], compared with 2006-2009 summers and influenza-active weeks, respectively [P < .0001]), higher rates of S. pyogenes BSI during 2009-2010 influenza season (IRR 2.7 [95% CI, 1.6-4.6] and 3.3 [95% CI, 1.9-5.8] during the summer and winter of 2009-2010, compared with 2006-2009 summers and influenza-active weeks, respectively [P < .0001]).nnnCONCLUSIONSnpH1N1 influenza seasons were characterized by marked increases in invasive S. aureus and S. pyogenes infections among children and adults, with the highest increase in S. pneumoniae BSI among children.

A host-protein based assay to differentiate between bacterial and viral infections in preschool children (OPPORTUNITY): a double-blind, multicentre, validation study.

BACKGROUNDnA physician is frequently unable to distinguish bacterial from viral infections. ImmunoXpert is a novel assay combining three proteins: tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma induced protein-10 (IP-10), and C-reactive protein (CRP). We aimed to externally validate the diagnostic accuracy of this assay in differentiating between bacterial and viral infections and to compare this test with commonly used biomarkers.nnnMETHODSnIn this prospective, double-blind, international, multicentre study, we recruited children aged 2-60 months with lower respiratory tract infection or clinical presentation of fever without source at four hospitals in the Netherlands and two hospitals in Israel. A panel of three experienced paediatricians adjudicated a reference standard diagnosis for all patients (ie, bacterial or viral infection) using all available clinical and laboratory information, including a 28-day follow-up assessment. The panel was masked to the assay results. We identified majority diagnosis when two of three panel members agreed on a diagnosis and unanimous diagnosis when all three panel members agreed on the diagnosis. We calculated the diagnostic performance (ie, sensitivity, specificity, positive predictive value, and negative predictive value) of the index test in differentiating between bacterial (index test positive) and viral (index test negative) infection by comparing the test classification with the reference standard outcome.nnnFINDINGSnBetween Oct 16, 2013 and March 1, 2015, we recruited 777 children, of whom 577 (mean age 21 months, 56% male) were assessed. The majority of the panel diagnosed 71 cases as bacterial infections and 435 as viral infections. In another 71 patients there was an inconclusive panel diagnosis. The assay distinguished bacterial from viral infections with a sensitivity of 86·7% (95% CI 75·8-93·1), a specificity of 91·1% (87·9-93·6), a positive predictive value of 60·5% (49·9-70·1), and a negative predictive value of 97·8% (95·6-98·9). In the more clear cases with unanimous panel diagnosis (n=354), sensitivity was 87·8% (74·5-94·7), specificity 93·0% (89·6-95·3), positive predictive value 62·1% (49·2-73·4), and negative predictive value 98·3% (96·1-99·3).nnnINTERPRETATIONnThis external validation study shows the diagnostic value of a three-host protein-based assay to differentiate between bacterial and viral infections in children with lower respiratory tract infection or fever without source. This diagnostic based on CRP, TRAIL, and IP-10 has the potential to reduce antibiotic misuse in young children.nnnFUNDINGnMeMed Diagnostics.

Initial Effects of the National PCV7 Childhood Immunization Program on Adult Invasive Pneumococcal Disease in Israel

Background PCV7 was introduced as universal childhood vaccination in Israel in July 2009 and PCV13 in November 2010. Here we report data on adult invasive pneumococcal disease (IPD), two years post PCV7 implementation and before an expected effect of PCV13. Methods An ongoing nationwide active-surveillance (all 27 laboratories performing blood cultures in Israel), providing all blood & CSF S. pneumoniae isolates from persons >18 y was initiated in July 2009. Capture-recapture method assured reporting of >95% cases. All isolates were serotyped in one central laboratory. IPD outcome and medical history were recorded in 90%. Second year post PCV implementation is compared to the first year. Results During July 2009 to June 2011, 970 IPD cases were reported (annual incidence [/100,000] of 9.17 and 10.16 in the two consecutive years, respectively). Respective case fatality rates (CFRs) were 20% and 19.1%. Incidence of IPD and CFR increased with age and number of comorbidities. Incidence rate was significantly greater during the second winter, 7.79/100,000 vs. 6.14/100,000 in first winter, pu200a=u200a0.004, with a non-significant decrease during summer months (3.02 to 2.48/100,000). The proportion of IPD cases due to PCV7-serotypes decreased from 27.5% to 13.1% (first to second year) (p<0.001). Yet, non-PCV13-strains increased from 32.7% to 40.2% (pu200a=u200a0.017). The increase in non-PCV13-strains was highly significant in immunocompromised patients and to a lesser degree in non-immunocompromised at risk or in older patients (>64 y). Among younger/healthier patients serotype 5 was the major increasing serotype. Penicillin and ceftriaxone resistance decreased significantly in the second year. Conclusions While overall annual incidence of IPD did not change, the indirect effect of PCV7 vaccination was evident by the significant decrease in PCV7 serotypes across all age groups. Increase in non-VT13 strains was significant in immunocompromised patients. A longer follow-up is required to appreciate the full effect of infant vaccination on annual IPD.

Validation of a Novel Assay to Distinguish Bacterial and Viral Infections

A novel 3-protein host-assay’s diagnostic performance for distinguishing between bacterial and viral etiologies is validated in a double-blind, investigator-driven study in febrile children. BACKGROUND: Reliably distinguishing bacterial from viral infections is often challenging, leading to antibiotic misuse. A novel assay that integrates measurements of blood-borne host-proteins (tumor necrosis factor-related apoptosis-inducing ligand, interferon γ-induced protein-10, and C-reactive protein [CRP]) was developed to assist in differentiation between bacterial and viral disease. METHODS: We performed double-blind, multicenter assay evaluation using serum remnants collected at 5 pediatric emergency departments and 2 wards from children ≥3 months to ≤18 years without (n = 68) and with (n = 529) suspicion of acute infection. Infectious cohort inclusion criteria were fever ≥38°C and symptom duration ≤7 days. The reference standard diagnosis was based on predetermined criteria plus adjudication by experts blinded to assay results. Assay performers were blinded to the reference standard. Assay cutoffs were predefined. RESULTS: Of 529 potentially eligible patients with suspected acute infection, 100 did not fulfill infectious inclusion criteria and 68 had insufficient serum. The resulting cohort included 361 patients, with 239 viral, 68 bacterial, and 54 indeterminate reference standard diagnoses. The assay distinguished between bacterial and viral patients with 93.8% sensitivity (95% confidence interval: 87.8%–99.8%) and 89.8% specificity (85.6%–94.0%); 11.7% had an equivocal assay outcome. The assay outperformed CRP (cutoff 40 mg/L; sensitivity 88.2% [80.4%–96.1%], specificity 73.2% [67.6%–78.9%]) and procalcitonin testing (cutoff 0.5 ng/mL; sensitivity 63.1% [51.0%–75.1%], specificity 82.3% [77.1%–87.5%]). CONCLUSIONS: Double-blinded evaluation confirmed high assay performance in febrile children. Assay was significantly more accurate than CRP, procalcitonin, and routine laboratory parameters. Additional studies are warranted to support its potential to improve antimicrobial treatment decisions.

Coxiella burnetii Infection of a Bovine Jugular Vein Conduit in a Child

We report a case of an 11-year-old girl with Coxiella burnetii infection of a bovine jugular vein conduit which is an extremely rare manifestation of Q fever. The role of surgery in the management of C. burnetii endovascular infection and the use of serology are discussed.

Invasive pneumococcal disease (IPD) in HIV infected patients in Israel since the introduction of pneumococcal conjugated vaccines (PCV): Analysis of a nationwide surveillance study, 2009–2014

ABSTRACT Study aim: to assess the incidence, risk factors and outcome of invasive pneumococcal disease (IPD) among the Israeli HIV population. A matched case-control study nested in a nationwide, prospective, population-based, cohort of adult IPD was performed. In addition, the HIV-IPD patients were compared to the general adult HIV population in Israel. Study period: from the introduction of PCV into the national immunization program (NIP) in July 2009 to June 2014. Each HIV patient within the IPD cohort was matched to 4 non-HIV controls. Serotyping was performed by a central laboratory using the Quellung reaction. Thirty-five IPD episodes in 33 HIV patients were identified, with a median annual incidence of 128/100,000 HIV+ persons compared to 5.1/100,000 in the age-matched, non-HIV population. Compared to the general HIV population, HIV-IPD patients practiced intravenous drug use more frequently and originated from a country with generalized epidemic (OGE), mainly non-citizens lacking medical insurance. The proportion of men who have sex with men (MSM) was lower than in the general HIV population. Pneumonia was the most common clinical presentation (81%), while meningitis occurred in only one patient. Outcomes were similar to those of the IPD non-HIV population. Nineteen serotypes were identified, of which only 42% were covered by PCV13 vaccine. By 2014, none of the HIV-IPD cases belonged to serotypes covered by PCV13. In conclusion, most HIV IPD cases were from marginalized populations with poor access to health services. A decrease in IPD cases covered by PCV 13 was observed.

A novel host-protein assay outperforms routine parameters for distinguishing between bacterial and viral lower respiratory tract infections

Bacterial and viral lower respiratory tract infections (LRTIs) are often clinically indistinguishable, leading to antibiotic overuse. We compared the diagnostic accuracy of a new assay that combines 3 host-biomarkers (TRAIL, IP-10, CRP) with parameters in routine use to distinguish bacterial from viral LRTIs. Study cohort included 184 potentially eligible pediatric and adult patients. Reference standard diagnosis was based on adjudication by an expert panel following comprehensive clinical and laboratory investigation (including respiratory PCRs). Experts were blinded to assay results and assay performers were blinded to reference standard outcomes. Evaluated cohort included 88 bacterial and 36 viral patients (23 did not fulfill inclusion criteria; 37 had indeterminate reference standard outcome). Assay distinguished bacterial from viral LRTI patients with sensitivity of 0.93±0.06 and specificity of 0.91±0.09, outperforming routine parameters, including WBC, CRP and chest x-ray signs. These findings support the assays potential to help clinicians avoid missing bacterial LRTIs or overusing antibiotics.

Learning across borders: Advocacy of pediatricians in public health response during a recent wild poliovirus transmission in Israel.

srael has been certified as polio-free by the World Health Organization, and since 2005, its routine immunization schedule consists of inactivated poliovirus vaccine (IPV) only. At the end of May 2013, the Israeli Ministry of Health has confirmed the reintroduction of wild-type poliovirus 1 into the country. Documented ongoing human-to-human transmission necessitated a thorough risk assessment followed by a supplemental immunization activity (SIA) campaign using bivalent oral polio vaccine (bOPV). The unusual situation in which ongoing poliovirus transmission was picked up through an early warning system of sewage monitoring without active polio cases, brought about significant challenges in risk communication.

Automating a new host-protein assay for differentiating bacterial from viral infection to reduce operator hands-on time

Distinguishing bacterial from viral infections is often challenging, leading to antibiotic misuse, and detrimental ramifications for the patient, the healthcare system and society. A novel ELISA-based assay that integrates the circulating levels of three host-response proteins (TRAIL, IP-10 and CRP) was developed to assist in differentiation between bacterial and viral etiologies. We developed a new protocol for measuring the host-based assay biomarkers using an automated ELISA workstation. The automated protocol was validated and was able to reduce technician hands-on time by 76%, while maintaining high analytical performance. Following automation, the assay has been incorporated into the routine workflow at a pediatric department, and is performed daily on admitted and emergency department patients. The automation protocol reduces the overall burden on the hospital laboratory performing the assay. This benefit has potential to promote adoption of the host-based assay, facilitating timely triage of febrile patients and prudent use of antibiotics.