Paediatric hospital visit with laboratory-confirmed influenza improved family members' influenza vaccination.

OBJECTIVES: Vaccination is the primary intervention to prevent influenza infection, yet vaccine uptake remains low among children and other at-risk patients. The aim of the study is to investigate the impact of a paediatric hospital visit with laboratory-confirmed influenza on the influenza vaccination behaviour of participants and their family members in the subsequent influenza season. METHODS: This study compared the influenza vaccination coverage for participants < 18 years of age with a clinical suspicion of influenza in 2017-2018 during a hospital visit, in two subsequent influenza seasons. Data was retrieved from the hospital electronic medical record and a follow-up questionnaire (2018-2019) to ascertain the common reason(s) that families did not vaccinate their children the following year (2018-2019). The children were distributed into positive- (antigen and/or PCR) and negative-influenza groups. RESULTS: A total of 133 children were enrolled in our study. Participants' mean age was 4.6 years and 74 (55.6%) were males. Overall, 47 (35.3%) had confirmed influenza virus. A significant increase in influenza immunization was found among both positive- and negative-influenza participants between 2017-2018 and 2018-2019 (6.4% vs. 27.7%, p < 0.001; 8.1% vs. 29.1%, p < 0.001, respectively), as well as among family members of positive-influenza participants - siblings and parents (6.4% vs. 19.6%, p = 0.003; 0% vs. 17%, p < 0.001, respectively). Common reasons for failure to vaccinate included doubt in vaccine effectiveness, unlikely to get "flu", busy, and side effects. CONCLUSIONS: Our findings suggest that a paediatric hospital visit with laboratory-confirmed influenza increases vaccine uptake among families. Future studies should aim to evaluate evidence-based interventions to improve influenza vaccine uptake among children.

Multidomain Cognitive Impairment in Children With Pseudotumor Cerebri Syndrome.

BACKGROUND: Although prompt and suitable treatment of pseudotumor cerebri syndrome (PTCS) leads to an excellent prognosis and can prevent optic nerve atrophy, adults show long-lasting neurocognitive deficits even with prompt treatment. The purpose of our study was to evaluate cognitive outcomes in pediatric patients with PTCS. METHODS: We performed a prospective study on children diagnosed with PTCS and a healthy control group. Children with pre-existing neurological conditions or psychiatric drug use were excluded. Both groups underwent a neurocognitive evaluation, using the NeuroTrax computerized battery of tests. The PTCS group were tested 3 months after the initial diagnosis. RESULTS: We evaluated 82 children (49 females [60%], 6.5-16 years old, mean age 13.3), including 26 diagnosed with idiopathic PTC and 56 controls. Global cognitive score (P < 0.001), verbal memory (P < 0.001), executive function (P < 0.001), attention (P< 0.003), and information processing speed (P < 0.004) were all significantly lower in the PTCS group. No differences were found between children currently being treated and those whose symptoms had resolved and treatment was stopped. CONCLUSIONS: Children with PTCS experience comprehensive cognitive decline that persists after the resolution of the symptoms and treatment.

Evaluation of Israeli healthcare workers knowledge and attitudes toward the COVID-19 vaccine.

OBJECTIVES: Healthcare workers (HCWs) are considered an important target group for the COVID-19 vaccines. The current study assesses the knowledge and attitudes of Israeli HCWs regarding COVID-19 immunization, and how various occupational and demographic factors may underlie COVID-related knowledge and attitudes differences. METHODS: Following a pre-test to validate measures, a cross-sectional online anonymous survey was distributed to HCWs using a snowball sampling method. RESULTS: The survey was completed by 714 participants (mean age 39.9; range 18-74; 447 female), 52% doctors, 32% nurses, and the remainder by paramedical staff. Of the respondents, 553 (77.4%) answered the question are you in favor of getting the COVID-19 vaccine, 105 (14.7%) were not sure, and 56 (7.8%) were not in favor. Doctors had higher odds of agreement as compared to both nurses (p < .025) and paramedical staff (p < .001). Multivariate logistic regression analysis revealed that increased age (OR: 1.075; 95% CI: 1.04-1.11, p < .001), profession (physician vs. nurse; OR: 2.73; 95% CI: 1.32-5.65; p < .007), and getting the current influenza vaccine (OR: 4.96; 95% CI: 2.47-9.95) were significant predictors of agreement. CONCLUSIONS: A high level of HCWs knowledge and in favor attitudes were observed. Yet negative attitudes were also noted, particularly among nurses, paramedical staff, and young employees.

The yield of CSF molecular testing in febrile neonates.

We retrospectively examined the yield of a cerebrospinal fluid (CSF) multiplex real-time PCR assay of febrile young infants undergoing a full sepsis work-up. Eighty infants were included in the study: Forty-nine (61%) neonates and 31 (39%) 29-90 day-old patients were included in the study. A viral pathogen was detected in 59% (47/80) of the samples, human enterovirus in 53% (42/80) and Human parechovirus in 6% (5/80). The CSF of nearly half of the subjects with CNS infection was without pleocytosis; all CSF cultures were negative. Multiplex PCR CSF testing enhances the diagnosis of pathogen-specific viral CNS infection among febrile young infants.

Cat Scratch Disease Presenting as Fever of Unknown Origin Is a Unique Clinical Syndrome.

BACKGROUND: Fever of unknown origin (FUO) is a rare manifestation of cat scratch disease (CSD). Data regarding CSD-associated FUO (CSD-FUO), particularly in adults, are limited. We aimed to study disease manifestations and long-term clinical outcome. METHODS: A national CSD surveillance study has been conducted in Israel since 1991. Data are obtained using questionnaires, review of medical records, and telephone interviews. FUO was defined as fever of ≥14 days without an identifiable cause. CSD-FUO patients were identified in the 2004-2017 CSD national registry. Follow-up included outpatient clinic visits and telephone/e-mail surveys. RESULTS: The study included 66 CSD-FUO patients. Median age was 35.5 years (range, 3-88). Median fever duration was 4 weeks (range, 2-9). Relapsing fever pattern was reported in 52% of patients, weight loss in 57%, and night sweats in 48%. Involvement of ≥1 organs occurred in 59% of patients; hepatosplenic space-occupying lesions (35%), abdominal/mediastinal lymphadenopathy (20%), ocular disease (18%), and multifocal osteomyelitis (6%) were the most common. Malignancy, particularly lymphoma, was the initial radiological interpretation in 21% of patients; 32% underwent invasive diagnostic procedures. Of the 59 patients available for follow-up (median duration, 31 weeks; range, 4-445), 95% had complete recovery; 3 patients remained with ocular sequelae. CONCLUSION: This is the first attempt to characterize CSD-FUO as a unique syndrome that may be severe and debilitating and often mimics malignancy. Relapsing fever is a common clinical phenotype. Multiorgan involvement is common. Recovery was complete in all patients except in those with ocular disease.

A Retrospective Study of the Impact of Pneumococcal Conjugate Vaccine-13 Immunization in a Northern Israel Hospital.

BACKGROUND: The introduction of pneumococcal conjugate vaccine-13 (PCV-13) has reduced the burden of invasive pneumococcal disease. OBJECTIVES: To characterize true positive blood cultures of children who presented to our hospital following implementation of the PCV-13 vaccine. METHODS: A retrospective study was conducted on positive blood cultures of children presenting with fever from 2010-2017. Subjects were divided into two age groups: a younger group 3-36 months and an older group 3-18 years. Patients were classified as either having or not having a focus of infection at the time of their bacteremia. Pneumococcal isolates were typed at Israel's Streptococcal Reference Laboratory. RESULTS: The samples included 94 true positive blood cultures. Focal infection with concomitant bacteremia was more common than bacteremia without a focus both overall: 67/94 (71%) vs. 27/94 (28.7%), P <0.001 as well as in the two groups: 32/48 (66%) vs. 16/48 (33%), P = 0.02 in the younger group and 35/46 (76%) vs. 11/46 (24%), P = 0.001 in the older group. Streptococcus pneumoniae was the most common pathogen overall, 27/94 (29%), and in the younger group, 21/48 (44%), but rare in the older group, 6/46 (13%). In the latter, Brucella species predominated, 12/46 (26%), along with Staphylococcus aureus 12/46 (26%). CONCLUSIONS: Our findings are consistent with other studies reporting decreased pneumococcal bacteremia, bacteremia primarily accompanying focal infection, and changing etiological agents among PCV-13-vaccinated children. Brucella species was prominent in older children with osteoarticular infections. Ongoing surveillance is warranted to better understand the implications of PCV-13.

Sensory processing patterns affect headache severity among adolescents with migraine.

OBJECTIVE: To evaluate the relationship between pain catastrophizing level, sensory processing patterns, and headache severity among adolescents with episodic migraine. BACKGROUND: Catastrophizing about pain is a critical variable in how we understand adjustment to pain and has a unique contribution in predicting pain intensity. Recent reports found that migraine is also related to enhanced sensory sensitivity. However, the relationship between pain severity, pain catastrophizing level and sensory sensitivity requires greater study especially among adolescents. METHODS: Participants were 92 adolescents aged 13-18 years, 40 with episodic migraine and 52 healthy controls. The migraine patients were prospectively recruited from outpatient pediatric neurology clinics. All participants completed the Adolescent/Adult Sensory Profile (AASP), and the Pain Catastrophizing Scale for children (PCS-ch). The migraine groups also completed the PedMIDAS, which measures Headache related disability. RESULTS: Adolescents with migraine had significantly lower tendency to seek sensory input than healthy controls. Elevated rumination and helplessness correlated with higher migraine pain severity. Tendency to avoid sensory input predicted the migraine related disability level. They also significantly higher pain catastrophizing level than healthy controls, as seen in enhanced rumination (p ≤ 0.001) and helplessness (p ≤ 0.05). CONCLUSIONS: Sensory processing difficulties are common among adolescents with episodic migraine. Sensory avoidance may be related to pain experience, and pain catastrophizing and disability level. TRIAL REGISTRATION: ISRCTN ISRCTN73824458. Registered 28 September 2014. retrospectively registered.

Antibiotic misuse in respiratory tract infections in children and adults-a prospective, multicentre study (TAILORED Treatment).

Respiratory tract infections (RTI) are more commonly caused by viral pathogens in children than in adults. Surprisingly, little is known about antibiotic use in children as compared to adults with RTI. This prospective study aimed to determine antibiotic misuse in children and adults with RTI, using an expert panel reference standard, in order to prioritise the target age population for antibiotic stewardship interventions. We recruited children and adults who presented at the emergency department or were hospitalised with clinical presentation of RTI in The Netherlands and Israel. A panel of three experienced physicians adjudicated a reference standard diagnosis (i.e. bacterial or viral infection) for all the patients using all available clinical and laboratory information, including a 28-day follow-up assessment. The cohort included 284 children and 232 adults with RTI (median age, 1.3 years and 64.5 years, respectively). The proportion of viral infections was larger in children than in adults (209(74%) versus 89(38%), p < 0.001). In case of viral RTI, antibiotics were prescribed (i.e. overuse) less frequently in children than in adults (77/209 (37%) versus 74/89 (83%), p < 0.001). One (1%) child and three (2%) adults with bacterial infection were not treated with antibiotics (i.e. underuse); all were mild cases. This international, prospective study confirms major antibiotic overuse in patients with RTI. Viral infection is more common in children, but antibiotic overuse is more frequent in adults with viral RTI. Together, these findings support the need for effective interventions to decrease antibiotic overuse in RTI patients of all ages.

A host-protein signature is superior to other biomarkers for differentiating between bacterial and viral disease in patients with respiratory infection and fever without source: a prospective observational study.

Bacterial and viral infections often present with similar symptoms. Etiologic misdiagnosis can alter the trajectory of patient care, including antibiotic overuse. A host-protein signature comprising tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and C-reactive protein (CRP) was validated recently for differentiating bacterial from viral disease. However, a focused head-to-head comparison of its diagnostic performance against other biomarker candidates for this indication was lacking in patients with respiratory infection and fever without source. We compared the signature to other biomarkers and prediction rules using specimens collected prospectively at two secondary medical centers from children and adults. Inclusion criteria included fever > 37.5 °C, symptom duration ≤ 12 days, and presentation with respiratory infection or fever without source. Comparator method was based on expert panel adjudication. Signature and biomarker cutoffs and prediction rules were predefined. Of 493 potentially eligible patients, 314 were assigned unanimous expert panel diagnosis and also had sufficient specimen volume. The resulting cohort comprised 175 (56%) viral and 139 (44%) bacterial infections. Signature sensitivity 93.5% (95% CI 89.1-97.9%), specificity 94.3% (95% CI 90.7-98.0%), or both were significantly higher (all p values < 0.01) than for CRP, procalcitonin, interleukin-6, human neutrophil lipocalin, white blood cell count, absolute neutrophil count, and prediction rules. Signature identified as viral 50/57 viral patients prescribed antibiotics, suggesting potential to reduce antibiotic overuse by 88%. The host-protein signature demonstrated superior diagnostic performance in differentiating viral from bacterial respiratory infections and fever without source. Future utility studies are warranted to validate potential to reduce antibiotic overuse.

Frequency of pediatric migraine with aura in a clinic-based sample.

OBJECTIVE: To assess the prevalence and risk factors for pediatric migraine with aura (MWA) among patients presenting to pediatric neurology clinics. BACKGROUND: Headache is a common complaint among children, and the prevalence of migraine is about 8%. Up to one third of adults with migraine report experiencing aura; however, the exact percentage in children is unknown. METHODS: Medical records of children presenting with headache to three pediatric neurology clinics in Haifa in the last 5 years were retrospectively reviewed. Inclusion criteria were a diagnosis of migraine headache at 5-18 years of age. RESULTS: Of 260 children (140 female) who had migraine, 26.2% experienced aura. MWA was more common among females compared to males (32.6% vs 18.9%, P < .01) and among older children (OR: 2.50, 95% CI: 1.20-5.20; P < .01). Among those who experienced aura, visual aura was more common in females than males (66.7% vs 33.3%, P < .04). Family history of migraine was strongly related to MWA (P < .02): the odds of MWA were 2.46 times greater in children who had a family history of migraine. (OR: 2.46, 95% CI: 1.08-5.62; P < .03). CONCLUSIONS: MWA is as common in children as in adults. Aura is more common in older children. Children who have MWA are more likely to have a family history of migraine.

Pediatric mixed headache -The relationship between migraine, tension-type headache and learning disabilities - in a clinic-based sample.

BACKGROUND: Headache is a common complaint among children. The most common primary headache syndromes in childhood are migraine and TTH. However many times they seem to overlap. The purpose of our study was to assess the relationship between pediatric migraine, tension-type headache (TTH) and learning disabilities. METHODS: Children presenting with headache to three pediatric neurology clinics in the last 5 years were assessed. Two hundred sixty-two children, 5-18 years of age, who met the criteria for migraine were included. RESULTS: Of 262 children (54 % female) who had migraine, 26.2 % had migraine with aura. 59 children (22.5 % of the full sample) reported also having headaches that met the criteria for episodic TTH/mixed headaches. Females were more than 2.8 times more likely to experience mixed headaches than males (OR: 2.81, 95 % CI: 1.43-5.54; p <.003). Multiple logistic regression analysis revealed that older age (p <0.02), family history of aura (p <.02), and (lack of) TTH (p <.003) were significant predictors of aura, whereas gender was not significant (p >0.20). Children who had migraine with aura were less likely to have mixed headaches than children who did not have aura (OR: 0.26, 95 % CI: 0.11-0.63; p <.003). Children with mixed headaches were 2.7 times more likely to have a learning disability than children with migraine alone. CONCLUSIONS: Episodic TTH and migraine without aura (mixed headaches) in children might be part of a continuum, which can explain the high incidence of their co-occurrence as opposed to migraine with aura. Children with mixed headaches have a higher incidence of learning disability compare to those with migraine alone.

The Decline of Pertussis-Specific Antibodies After Tetanus, Diphtheria, and Acellular Pertussis Immunization in Late Pregnancy.

We prospectively measured pertussis-specific antibodies 9-15 months after delivery in women immunized with tetanus, diphtheria, and acellular pertussis (Tdap) after the 20th week of their recent pregnancy. The Tdap-immunized women (n = 38) exhibited a decline in geometric mean concentrations between their peripartum and follow-up levels for immunoglobulin G to pertussis toxin (21.48 [95% confidence interval, 12.51-36.89] vs 11.72 [7.09-19.37] IU/mL];); filamentous hemagglutinin (185.95 [157.93-218.94] vs 140.33 IU/mL [113.46-173.57] IU/mL); and pertactin (171.52 [120.73-243.67] vs 83.74 [60.58-115.75] IU/mL) (all P < .001). For women immunized with Tdap during late pregnancy, pertussis-specific immunoglobulin G levels decreased significantly 9-15 months after delivery.

[PRIMARY HEADACHE IN CHILDREN AND ADOLESCENTS--DIAGNOSIS AND TREATMENT].

BACKGROUND: Primary headaches are one of the most common disorders of childhood, with migraine and tension type headaches (TTHs) being the most frequent ones. In spite of their prevalence, there is paucity of knowledge regarding the underlying pathophysiological mechanisms that cause headaches and regarding the unique aspects of headaches in children and adolescents. AIM: To review the literature and summarize the knowledge regarding clinical features, diagnosis and management of primary headache in children and adolescents, mainly migraine and TTH. RESULTS AND CONCLUSIONS: Most of our current knowledge regarding primary headaches in children and adolescents is driven from extrapolations from studies that were conducted with adult patients. Therefore, it needs to be validated for the different age groups. Migraines may be diagnosed effectively based on the 2nd edition of the International Classification of Headache Disorders (ICHD-II), however, TTH is diagnosed mainly by the absence of features found in other headache types. Treatment strategies for primary headaches vary according to patient's age, family structure, culture and beliefs, headache diagnosis, and based on the disability the headache imposes on the patient's daily living. It was shown that a multidisciplinary approach, that includes continuing counseling, education, and reassurance, in combination with pharmacological and non-pharmacological treatment, is an effective strategy for children and adolescents suffering from primary headaches. Further studies are needed to enrich our knowledge about the pathophysiological mechanisms that cause headaches in children and adolescents and to develop efficient strategies to alleviate their burden.

Intravenous fluids versus gastric-tube feeding in hospitalized infants with viral bronchiolitis: a randomized, prospective pilot study.

The American Academy of Pediatrics recommends intravenous fluids for infants with bronchiolitis who are unable to sustain oral feedings. Our randomized, prospective pilot study shows that gastric tube feeding (in 31 infants) is feasible and demonstrated comparable clinical outcomes with intravenous fluids (in 20 infants) among hospitalized infants ≤6 months of age with moderate bronchiolitis.

Beyond "safe sex"--can we fight adolescent pelvic inflammatory disease?

Pelvic inflammatory disease (PID) is a common disorder affecting sexually active adolescents. The Centers for Disease Control and Prevention (CDC) and European CDC report Chlamydia trachomatis as the most common sexually transmitted infection and one of the main etiological agents causing PID. C. trachomatis' and PID's high prevalence may be attributed to multiple factors including high-risk sexual behaviors, sensitive laboratory diagnostics (polymerase chain reaction), and the introduction of chlamydia screening programs. The pathogenesis of C. trachomatis infection is complex with recent data highlighting the role of toll-like receptor 2 and four in the mediation of the inflammatory cascade. The authors review the etiology of the disease, explore its pathogenesis, and discuss a variety of strategies that may be implemented to reduce the prevalence of C. trachomatis including: (a) behavioral risk reduction, (b) effective screening of asymptomatic females, (c) targeted male screening, (d) implementation of a sensitive, rapid, self-administered point-of-care testing, and (e) development of an effective vaccine.

Is it justified to include urine cultures in early (< 72 hours) neonatal sepsis evaluations of term and late preterm infants?

OBJECTIVE: Evaluate the need for urine culture in early neonatal sepsis workup of term and late preterm infants. STUDY DESIGN: Urine culture by suprapubic aspiration or catheter was included in early sepsis evaluations of 173 term and late preterm newborns (mean gestational age 38.6 ± 2.0 weeks) during a 6-month study period. A historic control group included 182 newborns (38.6 ± 2.9 weeks) who had sepsis evaluations without routine urine cultures a year earlier. RESULTS: Urine cultures were sampled in 106 (61%) of the study group, No significant differences were found between study and control groups in the rate of bacteremia (1.73% versus 2.2%) or urinary tract infection (UTI; 0.94% versus 1.1%), which was low. Early UTIs were not accompanied by bacteremia or structural anomalies and were associated with exacerbation of neonatal jaundice in two of three infants. CONCLUSIONS: There seems to be no justification for routine urine culture in early neonatal sepsis workup of term and late preterm infants, unless there are accompanying clinical symptoms, usually related to neonatal jaundice.

The cross- ethnic variations in the prevalence of headache and other somatic complaints among adolescents in Northern Israel.

BACKGROUND: Headache is the most common cause for chronic or recurrent pain in childhood and adolescence. Chronic pain may have a long-term effect on adolescents. It might contribute to functional limitations, such as poor school attendance, and it may adversely affect development of healthy social relationships. The aim of our study was to examine the cross- ethnic variation in the prevalence of headache in a non- clinical sample of adolescents in Northern Israel and to learn about its association to other somatic complaints. METHODS: A self-administered, anonymous questionnaire was presented to 2,088 tenth grade students attending 19 high-schools in Northern Israel (all the public high schools within two districts). Participants were Jews and Arabs, the latter including Muslim, Christians, and Druze, aged 15 to 16. Parental and student consent was obtained from all participants. The study was approved by the IRB of our institution. RESULTS: All 2088 questionnaires were returned although only 2019 were usable and analyzed. Arab adolescents comprised 55% (1117) of the analyzed sample and Jews 45% (902), 56% of participants were girls. Of the Arab participants, 18.6% reported having frequent headaches (girls 25.3%, boys 9.1%, P<0.0001) much less than their Jewish peers (P<0.0001) among whom 27.9% reported having frequent headaches (girls 35.6%, boys 19% P<0.0001). Other somatic complaints such as abdominal pain, palpitations, disordered sleep and fatigue were more frequent in adolescents (Jews and Arabs, girls and boys) who suffered from headaches than in their peers who did not report having headaches (P<0.0001), the same pattern observed in the Jewish and the Arab group. CONCLUSIONS: Headache is a frequent complaint among adolescents in Northern Israel. Jewish adolescents reported having headaches more frequently than their Arab peers. Those who suffered from frequent headaches also reported having significantly more other somatic complaints than adolescents without headaches. Girls had more somatic complaints then boys in the two ethnic groups.

Primary headaches, attention deficit disorder and learning disabilities in children and adolescents.

BACKGROUND: Primary headaches and Learning difficulties are both common in the pediatric population. The goal of our study was to assess the prevalence of learning disabilities and attention deficit disorder in children and adolescents with migraine and tension type headaches. METHODS: Retrospective review of medical records of children and adolescents who presented with headache to the outpatient pediatric neurology clinics of Bnai-Zion Medical Center and Meyer Children's Hospital, Haifa, during the years 2009-2010. Demographics, Headache type, attention deficit disorder (ADHD), learning disabilities and academic achievements were assessed. RESULTS: 243 patients met the inclusion criteria and were assessed: 135 (55.6%) females and 108 (44.4%) males. 44% were diagnosed with migraine (35.8% of the males, 64.2% of the females, p = 0.04), 47.7% were diagnosed with tension type headache (50.4% of the males, 49.6% of the females). Among patients presenting with headache for the first time, 24% were formerly diagnosed with learning disabilities and 28% were diagnosed with attention deficit disorder (ADHD). ADHD was more prevalent among patients with tension type headache when compared with patients with migraine (36.5% vs. 19.8%, p = 0.006). Poor to average school academic performance was more prevalent among children with tension type headache, whereas good to excellent academic performance was more prevalent among those with migraine. CONCLUSIONS: Learning disabilities and ADHD are more common in children and adolescents who are referred for neurological assessment due to primary headaches than is described in the general pediatric population. There is an association between headache diagnosis and school achievements.

[Genital ulcers--what's new?].

The most common infectious causes of genital ulcers are herpes simplex virus and syphilis. However, mixed infections can occur and genital ulcer may increase the risk of acquiring human immunodeficiency virus. Although the history and physical examination can narrow the differential diagnosis, there is a need for initial routine laboratory testing for the most common pathogens that includes: for syphilis: serologic screening and dark field examination of the lesion; for herpes simplex virus: serology, vial culture and/or polymerase chain reaction. Human immunodeficiency testing is mandatory. Recently, some clinical laboratories adapted the reverse screening algorithm for syphilis (initial treponemal test, and, if positive, followed by non-treponemal test) that may potentially lead to overtreatment. Early and prompt therapy may decrease the risk of transmission of the infectious agent to others. This article reviews the infectious pathogens causing genital ulcers, their unique clinical manifestation, diagnosis and treatment.

Diagnostic Accuracy of a Real-Time Host-Protein Test for Infection.

OBJECTIVE: Determining infection etiology can be difficult because viral and bacterial diseases often manifest similarly. A host protein test that computationally integrates the circulating levels of TNF-related apoptosis-induced ligand, interferon γ-induced protein-10, and C-reactive protein to differentiate between bacterial and viral infection (called MMBV) demonstrated high performance in multiple prospective clinical validation studies. Here, MMBV's diagnostic accuracy is evaluated in febrile children for whom physicians were uncertain about etiology when applied at the physician's discretion. METHODS: Patients aged 3 months to 18 years were retrospectively recruited (NCT03075111; SPIRIT study; 2014-2017). Emergency department physician's etiological suspicion and certainty level were recorded in a questionnaire at blood-draw. MMBV results are based on predefined score thresholds: viral/non-bacterial etiology (0 ≤ score <35), equivocal (35 ≤ score ≤65), and bacterial or coinfection (65 < score ≤100). Reference standard etiology (bacterial/viral/indeterminate) was adjudicated by 3 independent experts based on all available patient data. Experts were blinded to MMBV. MMBV and physician's etiological suspicion were assessed against the reference standard. RESULTS: Of 3003 potentially eligible patients, the physicians were uncertain about infection etiology for 736 of the cases assigned a reference standard (128 bacterial, 608 viral). MMBV performed with sensitivity 89.7% (96/107; 95% confidence interval 82.4-94.3) and specificity 92.6% (498/538; 95% confidence interval 90.0-94.5), significantly outperforming physician's etiological suspicion (sensitivity 49/74 = 66.2%, specificity 265/368 = 72.0%; P < .0001). MMBV equivocal rate was 12.4% (91/736). CONCLUSIONS: MMBV was more accurate in determining etiology compared with physician's suspicion and had high sensitivity and specificity according to the reference standard.