KIT D816V and JAK2 V617F Point Mutations Are Recurrently Found In Suspected Hypereosinophilic Syndrome

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4100-4100
Author(s):  
Juliana Popa ◽  
Philipp Erben ◽  
Georgia Metzgeroth ◽  
Georg Bolz ◽  
Martin C Mueller ◽  
...  
Keyword(s):  
Clinical Features ◽  
Hypereosinophilic Syndrome ◽  
Point Mutations ◽  
Jak2 V617f ◽  
Molecular Testing ◽  
Rt Pcr ◽  
Serum Tryptase ◽  
Molecular Abnormalities ◽  
Number Of Patients ◽  
Kit D816v

Abstract Abstract 4100 In some patients with suspected hypereosinophilic syndrome (HES), clonality of eosinophils may be proven by identification of an acquired chromosome or molecular abnormality leading to the diagnosis of chronic eosinophilic leukemia (CEL). The most common molecular aberrations are fusion genes with involvement of PDGFRA, e.g. FIP1L1-PDGFRA (FP), or PDGFRB, e.g. ETV6-PDGFRB. Molecular testing for FP by RT-PCR or FISH is nowadays performed early in the diagnostic work-up of suspected non-reactive eosinophilia. However, eosinophilia is also present at variable frequency in patients with systemic mastocytosis (SM) and other subtypes of myeloproliferative neoplasms (MPN). Recurrent molecular markers for those entities are KIT D816V (80-90% positivity in SM) and JAK2 V617F (60-70% positivity in MPN). We therefore sought to evaluate the relative frequency of FP (by RT-PCR), KIT D816V (by D-HPLC plus direct sequencing) and JAK2 V617F (by ARMS-PCR) in 300 samples from patients with suspected HES/CEL and to correlate molecular findings with clinical features. Molecular abnormalities were identified in 42 (14%) cases; 22 (7.3%) were positive for FP, 14 (4.6%) for KIT D816V and 6 (2.0%) for JAK2 V617F, respectively. Most baseline clinical characteristics, e.g. leukocytes, absolute and relative number of eosinophils, hemoglobin, platelets or splenomegaly, were not different between the three entities. Significant differences were found regarding age, gender, serum tryptase levels and course of disease. FP positive patients were significantly younger (p<0.001) and exclusively male while a female prepoderance was observed for KIT and JAK2 mutated patients. Significantly elevated serum tryptase levels (normal value <11.4μ g/l) were found in all cases of FP and KIT D816V positive patients. However, serum tryptase levels >50μ g/l were almost exclusively seen in KIT D816V positive SM patients. Aggressive SM (ASM) was diagnosed in 6 of 14 (43%) KIT D816V positive patients due to characteristic bone marrow morphology and the presence of diverse C-findings (e.g. anemia <10g/dl, n=2, and/or thrombocytopenia <100×109/μ l, n=7). Frequent additional clinical features included lymphadenopathy (n=9) and urticaria pigmentosa (n=6). Two ASM patients died within first year of diagnosis while 21 (95%) FP positive CEL patients are in complete molecular remission on imatinib after a median treatment time of 28 months (range 8–149). We conclude that the serum tryptase level is an important diagnostic and prognostic marker in eosinophilia. We suggest that FP negative HES patients should be screened for KIT D816V and JAK2 V617F point mutations, both of which are potentially targetable by small molecule inhibitors. FIP1L1-PDGFRA KIT D816V JAK2 V617F Number of patients 22 (7.3%) 14 (4.6%) 6 (2.0%) Age (median, years) 4418–73 6342–81 7269–87 Gender (m/f) 22/0 6/8 4/6 Leukocytes (median, range, ×109/l) 13.57.2–85.6 10.06.8–124.0 26.812.7–61.1 Eosinophil (median, range, ×109/l) 6.51.4–34.8 2.21.2–100.0 10.03.2–16.5 Eosinophils (%) 469–74 246–81 378–61 Hemoglobin (median, range, g/dl) 12.67.1–15.8 11.77.9–15.7 13.511.4–16.2 Platelets (median, range, ×109/l) 16034–375 11215–945 17434–364 Splenomegaly 14/14 (100%) 13/13 (100%) 4/4 (100%) Serum tryptase >50μ g/l 1/13 (8%) 8/9 (88%) not done >100μ g/l 0/13 (-) 7/7 (100%) not done Disclosures: Erben: Novartis: Honoraria, Research Funding.

scholarly journals Molecular Features and Clinical Outcomes of Extramedullary Plasmacytomas

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 398-398
Author(s):  
Rie Nakamoto-Matsubara ◽  
Valentina Nardi ◽  
Cristina Panaroni ◽  
Keertik Fulzele ◽  
Tomoaki Mori ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Chromosome 1 ◽  
Molecular Testing ◽  
Fish Analysis ◽  
Braf Mutations ◽  
Kras Mutations ◽  
Molecular Abnormalities ◽  
Molecular Features ◽  
Number Of Patients

Abstract The treatment of multiple myeloma (MM) continues to evolve with new drugs, resulting in dramatically improved outcomes. Despite these advances, MM remains an incurable disease, with Extraosseous/Extramedullary disease (EMD) playing a major role in the development of relapsed refractory disease. EMD is defined by the development of plasma cell neoplasms that arise in tissues other than bones. EMD can present at diagnosis or develop during the disease course of MM. Sometimes EMD can be solitary without bone marrow (BM) involvement. Determining the molecular underpinnings of EMD are critical to advance the care of such patients. A few reports suggest a possible role of Ras mutations in the intramedullary to extramedullary transition in a limited number of patients. Therefore, the molecular biology of developing EMD has not yet been clearly defined. We sought to identify molecular features of EMD and associated these with clinical outcomes. We analyzed samples from 443 MM patients who presented to Massachusetts General Hospital between 2013 and 2021. All patients voluntarily signed informed consent approved by the institutional review board for SNaPshot (molecular) testing. BM aspirate, biopsy and EMD tumor specimens underwent pathological analysis as well as FISH testing. The diagnosis of EMD was determined by either CT, PET-CT or MRI done as part of their clinical course. In some cases, EMD was confirmed by biopsy. Although there were some cases of EMD adjacent to bones, we strictly defined EMD as non-adjacent to bones based on imaging. Nucleic acids were extracted from BM and EMD samples obtained from MM patients. Multiplexed mutational analysis was done with primers designed to cover 111 genes including genes known to be oncogenic. SNaPshot was done and the threshold for allele frequencies was determined as 8% based on our laboratory cut-offs. The median follow-up of the entire MM population was 63.7 months (range 1 to 408). Overall, 96 of 443 patients (21.6%) developed EMD as previously defined. Sixty-five out of 96 patients had biopsy confirmed EMD, while 31 patients were diagnosed by imaging only. SNaPshot molecular testing was performed on 30 EMD samples from the 65 patients who had biopsies. Interestingly, all EMD samples except for 1 had either NRAS, KRAS, or BRAF mutations. There were 14 EMD samples with NRAS mutations, 6 with KRAS mutations, 4 with BRAF mutations, and 1 with both KRAS and BRAF mutations. All BRAF mutations coexisted with other mutations, such as TP53, ATM, and ARID1A whereas some of the NRAS and KRAS mutations were observed alone. Next SNaPshot was analyzed for 8 paired BM and EMD samples. Three BM samples were negative for NRAS mutations while all EMD samples were positive. Patients with KRAS/NRAS/BRAF mutations who developed EMD had poorer prognosis than non-EMD patients with KRAS/NRAS/BRAF mutations. In patients with KRAS mutations, the median overall survival (OS) was 36.9 months (EMD) vs not reached (non-EMD) (p&lt;0.01); and BRAF mutations, the median OS was 58.5 months (EMD) vs 112.4 months(non-EMD) (p=0.194). In patients with NRAS mutations, the median OS was 94.5 months(EMD) vs 124.5 months (non-EMD) (p=0.11). Average time from diagnosis of MM to developing EMD in 68 patients with longitudinal follow up was 41.6 months and average time from developing EMD to death in 54 patients with longitudinal follow-up was 7.6 months. There were significant differences in BM FISH analysis in KRAS/NRAS/BRAF mutation harboring EMD vs non-EMD; Chromosome 1 abnormalities (79.2% vs 34.2%), TP53 deletion (41.7% vs 22.4%) and hyperdiploidy (37.5% vs 67.1%). Our data suggest that KRAS/NRAS/BRAF mutations may play an important role in the development of EMD. These and other associated molecular abnormalities portend a poorer prognosis and may provide novel therapeutic insights. Disclosures Nardi: Loxo Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees. Yee: Amgen: Consultancy; Bristol Myer Squibb: Consultancy; Adaptive: Consultancy; GSK: Consultancy; Janssen: Consultancy; Oncopeptides: Consultancy; Sanofi: Consultancy; Takeda: Consultancy; Karyopharm: Consultancy. Branagan: Adaptive Biotechnologies: Consultancy; BeiGene: Consultancy; CSL Behring: Consultancy; Karyopharm: Consultancy; Pharmacyclics: Consultancy; Sanofi Genzyme: Consultancy. O'Donnell: Onocopeptide: Consultancy; Karyopharm: Consultancy; Janssen: Consultancy; Bristol Myer Squibb: Consultancy; Adaptive: Consultancy; Takeda: Consultancy. Raje: Celgene, Amgen, Bluebird Bio, Janssen, Caribou, and BMS: Other.

scholarly journals Hypereosinophilic Syndrome of Undetermined Significance – Difficulties in Clinical and Therapeutic Approach

2018 ◽  
Vol 15 (4) ◽  
pp. 61-65
Author(s):  
Vlad Florin Anton ◽  
Polliana Mihaela Leru
Keyword(s):  
Systemic Mastocytosis ◽  
Hypereosinophilic Syndrome ◽  
Genetic Mutation ◽  
High Serum ◽  
Parasitic Infections ◽  
High Dose ◽  
Serum Tryptase ◽  
Major Criterion ◽  
Kit D816v

AbstractWe report a case of a 69-year-old woman who is followed since seven years for persistent blood hypereosinophilia up to 5100/mmc. She has been extensively investigated for other diseases known to induce hypereosinophilia, including allergies, parasitic infections and neoplasia. No end-organ dysfunction could be confirmed. We considered a possible primary hypereosinophilic syndrome (HES) and determined the genetic mutation FIP1L1-PDGFRA characteristic for HES, which was negative.Bone marrow showed reactive eosinophilia with no malignant cells and rare mast cells, less than 15 in aggregates, which is the major criterion for diagnosing mastocytosis. Knowing the association between HES and mastocytosis, we measured and found high serum tryptase levels and positive c-kit D816V genetic mutation, characteristic for systemic mastocytosis. The patient was closely monitored, with regular hematologic and clinical evaluation, mainly for cardiac and neurologic manifestations.A short trial of high dose corticotherapy induced remission of hypereosinophilia, but this could not be maintained with lower doses. The clinical outcome during follow-up period was rather good, except mild cognitive decline and atrial fibrillation.The reported case is illustrative for versatile presentation and difficulties in management of hypereosinophilia in clinical practice.

Molecular Characterization of the Idiopathic Hypereosinophilic Syndrome (HES) in 35 French Patients with Normal Conventional Cytogenetics.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2442-2442 ◽  
Author(s):  
Catherine Roche-Lestienne ◽  
Valerie Soenen-Cornu ◽  
Jean-Emmanuel Kahn ◽  
Jean-Luc Lai ◽  
Eric Hachulla ◽  
...  
Keyword(s):  
T Cell ◽  
Serum Level ◽  
Hypereosinophilic Syndrome ◽  
Elevated Serum ◽  
Fish Analysis ◽  
Rt Pcr ◽  
Serum Tryptase ◽  
High Occurrence ◽  
Molecular Features ◽  
T Cell Clone

Abstract HES, characterized by unexplained and persistent hypereosinophilia, is heterogeneous and comprises several entities including a myeloproliferative form where myeloid lineages are involved with interstitial chromosome 4q12 deletion leading to fusion between FIP1L1 and PDGFRA (F/P) genes, the latter acquiring increased tyrosine kinase activity, and a lymphocytic variant where hypereosinophilia is secondary to a primitive T lymphoid disorder demonstrated by the presence of a circulating T cell clone. Patients and methods: 35 HES patients diagnosed in 6 French centers and with normal karyotype by conventional cytogenetic analysis were included in this study. 9 patients had clinical or hematological features of myeloproliferative syndrome; 4 patients had recurrent diarrhea with intestinal eosinophilic infiltration. No patient had clinical or pathological features for systemic mastocytosis. At the time they were tested, any patient received imatinib. Patients were studied for clonality of T-cell-receptor gamma gene rearrangements, detection of F/P by FISH and/or RT-PCR, and screening for activating mutations in the juxtamembrane and TK regions of PDGFRA and PDGFRB genes. Relashionships between molecular features and IL5 and serum tryptase levels were analyzed. Results: We found a high occurrence of T-cell related HES (11 patients, 31%) and none of them had F/P deletion. 6 patients (17%) presented the F/P fusion by RT-PCR. In agreement with previous reports, we found a significantly elevated tryptase serum level in all of these F/P deleted patients (p= 0.006, Mann-Whitney test). Sequence of fusion transcripts in 6 F/P patients revealed breakpoints scattered between FIP1L1-exons 10 to 13, whereas breakpoints were restricted to exon 12 of PDGFRA. Clinical improvement and complete hematological remission under imatinib was observed in all 6 F/P patients at the end of the study. In the 29 patients without F/P, no activating mutation of PDGFRA/PDGFRB was detected, however one patient respond to imatinib. FISH analysis of the F/P was concordant with RT-PCR data, and previous May-Gründwald-Giemsa staining of slides suggested an heterogeneous eosinophilic population. Conclusion : We described here a high occurrence of T-cell related HES, fully representative since none of the patients has been recruited from dermatology clinics, and none of them had F/P deletion, suggesting that F/P deletion in HES may involved the myeloid lineage. No significant higher IL5 serum level was observed between T-cell associated HES patients and other case of HES in our study, but F/P and elevated serum tryptase level define a strongly overlapping group of HES patients. In our study, F/P deleted cells have been observed by FISH analyses in a part of the eosinophilic population. Extensive analysis of aberrant-T cells and of the nature of F/P affected cells could then improve the HES classification.

MPL Mutation Profile in JAK2 Mutation-Negative Patients with Myeloproliferative Neoplasms.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1891-1891
Author(s):  
Wanlong Ma ◽  
XI Zhang ◽  
Xiuqiang Wang ◽  
Zhong Zhang ◽  
Chen-Hsiung Yeh ◽  
...  
Keyword(s):  
Bone Marrow Cells ◽  
Conflicts Of Interest ◽  
Myeloproliferative Neoplasms ◽  
Point Mutations ◽  
Jak2 V617f ◽  
Jak2 Mutation ◽  
Hematopoietic Stem ◽  
Number Of Patients ◽  
Exon 11 ◽  
Exon 10

Abstract Abstract 1891 Poster Board I-914 Myeloproliferative neoplasms (MPNs) are multipotent hematopoietic stem cell neoplasms characterized by excess production of various blood cells. Mutations in the thrombopoietin receptor gene (MPL) have been reported in JAK2 V617F-negative patients with MPNs. We evaluated the prevalence of MPL mutations relative to those of JAK2 mutations at V617 or in exons 12 through 15 in a large number of patients with suspected MPNs. A total of 2790 patients with suspected MPNs referred to our institution were first screened for JAK2 V617F and exon 12–15 mutations. Patients with no JAK2 mutations detected were then tested for MPL mutations in exons 10 and 11 by means of a sensitive MPL reverse-transcription-PCR-based assay with direct bidirectional sequencing. All JAK2 and MPL mutation assays were performed on plasma RNA, rather than DNA isolated from blood or bone marrow cells. Of the 2790 patients, 529 (18.96%) had a V617F mutation; 12 (0.43%) had small insertion/deletions in exon 12; and 7 (0.25%) had other JAK2 mutations, including point mutations in exons 13–15 and an exon 14 splice mutation. MPL mutations were identified in 66 of the 2242 (2.94%) JAK2 mutation-negative patients (2.37% of all tested patients). W515L was the dominant MPL mutant detected in 46 patients (70%) including two patients with homozygous W515L mutation. The other W515 variants (W515K, W515R, W515S, W515G, W515A, W515*) comprised 16% (N=11) of the MPL mutations. The remaining MPL mutations (n =9, 14%) were detected at other locations in exon 10 and 11. Two of these were novel exon 10 deletion/insertion mutations and two were unreported exon 11 point mutations. The exon 10 T496-A497ALVI (4AA) homozygous insertion was detected in one patient with a confirmed diagnosis of idiopathic myelofibrosis and the W515-P518 del/ins (KT) mutation was detected in another patient with unspecified MPN. The two novel MPL exon 11 point mutations were D545G and D545N. The S505N mutation (n=2) and V507I (n=1), R514K (n=1), and A519V (n=1) were also detected. Furthermore, three unreported silent polymorphisms/mutations (T496, L543, and D534) were detected. In conclusion, our results demonstrate that for every 100 V617F mutations detected in patients with MPNs, there are 2.3 JAK2 exon 12 mutations, 1.3 JAK2 exon 13–15 mutations, and 12.5 MPL mutations. Thus, MPL mutation detection should be performed on all JAK2 V617F-negative patients with suspected MPNs. In addition, our findings indicate that >20% of MPL mutations would have been missed if only W515L and W515K were analyzed; thus, sequencing of both exon 10 and 11 may be beneficial. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Rapid PCR Influenza Testing Decreases Inappropriate Empiric Antibiotic Use

2020 ◽  
Vol 41 (S1) ◽  
pp. s366-s366
Author(s):  
Avnish Sandhu ◽  
Jordan Polistico ◽  
Ashwin Ganesan ◽  
Erin Goldman ◽  
Jennifer LeRose ◽  
...  
Keyword(s):  
Antibacterial Agents ◽  
Clinical Decision Making ◽  
Medical Center ◽  
Tertiary Care ◽  
Group Versus ◽  
Molecular Testing ◽  
Care Hospital ◽  
Rt Pcr ◽  
Influenza Like Illness ◽  
Number Of Patients

Background: The clinical picture of influenza-like illness can mimic bacterial pneumonia, and empiric treatment is often initiated with antibacterial agents. Molecular testing such as polymerase chain reaction (PCR) is often used to diagnose influenza. However, traditional PCR tests have a slow turnaround time and cannot deliver results soon enough to influence the clinical decision making. The Detroit Medical Center (DMC) implemented the Xpert Flu test for all patients presenting with influenza-like illness (ILI). We evaluated antibacterial use after implementation of rapid influenza PCR Xpert Flu. Methods: We conducted a retrospective study comparing all pediatric and adult patients tested using traditional RT PCR during the 2017–2018 flu season to patients tested using the rapid influenza Xpert Flu during the 2018–2019 flu season in a tertiary-care hospital in Detroit, Michigan. These patients were further divided into 3 groups: not admitted (NA), admitted to acute-care floor (ACF), or admitted to intensive care unit (ICU). The groups were then compared with respect to percentage of antibacterial use after traditional RT PCR versus rapid influenza Xpert Flu testing during their hospital visit for ILI. The χ2 test was used for statistical analyses. Results: In total, 20,923 patients presented with influenza-like illness during the study period: 26% (n = 5,569) had the rapid influenza Xpert Flu and 73.4% (n= 15,354) had traditional RT PCR. For a comparison of the number of patients in 3 groups (NA, ACF, and ICU) and type of influenza PCR performed among these patients, please refer to Table 1. When comparing antibacterial use in the NA group, the proportions of patients who received antibacterial agents in the traditional RT PCR group versus the rapid influenza Xpert Flu group were 24.4% (n = 695) versus 3.9% (n = 450), respectively (P < .0001). In the ACF group, the proportions of patients who received antibacterial agents in the traditional RT PCR group versus the rapid influenza Xpert Flu group was 62.3% (n = 1,406) versus 27.7% (n = 994), respectively (P < .001). In the ICU group, the proportions of patients who received antibacterials in the traditional RT PCR group versus the rapid influenza Xpert Flu group were 80.3% (n = 382) versus 38.3% (n = 204), respectively (P < .0001). Conclusions: With rising antimicrobial resistance and increasing influenza morbidity and mortality, rapid diagnostics not only can help diagnose influenza faster but also can reduce inappropriate antimicrobial use.Funding: NoneDisclosures: None

Feasibility of Qualitative Testing of BCR-ABL and JAK2 V617F in Suspected Myeloproliperative Neoplasm (MPN) Using RT-PCR Reversed Dot Blot Hybridization (RT-PCR RDB)

2019 ◽  
Vol 19 (4) ◽  
pp. 220-227
Author(s):  
Najmiatul Masykura ◽  
Ummu Habibah ◽  
Siti Fatimah Selasih ◽  
Soegiarto Gani ◽  
Cosphiadi Irawan ◽  
...  
Keyword(s):  
Blot Hybridization ◽  
Jak2 V617f ◽  
Rt Pcr ◽  
Dot Blot ◽  
Dot Blot Hybridization

scholarly journals Screening, Diagnostic and Prognostic Tests for COVID-19: A Comprehensive Review

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 561
Author(s):  
Mariana Ulinici ◽  
Serghei Covantev ◽  
James Wingfield-Digby ◽  
Apostolos Beloukas ◽  
Alexander G. Mathioudakis ◽  
...  
Keyword(s):  
Point Of Care ◽  
Standard Test ◽  
Current Evidence ◽  
Molecular Testing ◽  
Rt Pcr ◽  
Diagnostic Screening ◽  
Comprehensive Review ◽  
Prognostic Tests ◽  
Polymerase Chain ◽  
Antigen Testing

While molecular testing with real-time polymerase chain reaction (RT-PCR) remains the gold-standard test for COVID-19 diagnosis and screening, more rapid or affordable molecular and antigen testing options have been developed. More affordable, point-of-care antigen testing, despite being less sensitive compared to molecular assays, might be preferable for wider screening initiatives. Simple laboratory, imaging and clinical parameters could facilitate prognostication and triage. This comprehensive review summarises current evidence on the diagnostic, screening and prognostic tests for COVID-19.

scholarly journals SARS-CoV-2 in peritoneal swabs from asymptomatic patients undergoing emergency abdominal surgery

2021 ◽  
Vol 2021 (4) ◽  
Author(s):  
Jasim AlAradi ◽  
Rawan A Rahman AlHarmi ◽  
Mariam AlKooheji ◽  
Sayed Ali Almahari ◽  
Mohamed Abdulla Isa ◽  
...  
Keyword(s):  
Peritoneal Fluid ◽  
Case Series ◽  
Rapid Test ◽  
Nasopharyngeal Swab ◽  
Rt Pcr ◽  
Protective Measures ◽  
The Public ◽  
Asymptomatic Patients ◽  
Number Of Patients ◽  
Viral Transfer

Abstract This is a case series of five patients with acute abdomen requiring surgery who tested positive for coronavirus disease 2019 (COVID-19) and were asymptomatic, with the purpose of detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in peritoneal fluid. Nasopharyngeal swab was done as a prerequisite for admission or prior to admission as part of random testing. Two methods of viral testing were employed: Xpert® Xpress SARS-CoV-2 (rapid test) and real-time reverse transcription polymerase chain reaction (RT-PCR). Either or both tests were done, with the former performed for patients requiring surgery immediately. Surgery was performed within 24–36 h from admission. Peritoneal fluid swabs were obtained for the detection of SARS-CoV-2 using RT-PCR test. Swabs were immediately placed in viral transfer media and delivered to the public health laboratory in an ice bag. SARS-CoV-2 was not detected in peritoneal swabs. Due to the limited number of patients, further studies are required; yet, protective measures should still be taken by surgeons when dealing with COVID-19 cases.

scholarly journals EXPERIENCE WITH USING RAPID MOLECULAR TESTING IN DIAGNOSING PULMONARY AND EXTRA-PULMONARY PEDIATRIC TUBERCULOSIS IN A NON-ENDEMIC SETTING - A RETROSPECTIVE CASE SERIES

2018 ◽  
Vol 23 (suppl_1) ◽  
pp. e44-e45 ◽  
Author(s):  
Hana Mijovic ◽  
Yossef Al-Nasser ◽  
Ghada Al-Rawahi ◽  
Ashley Roberts
Keyword(s):  
Case Series ◽  
Pericardial Fluid ◽  
Diagnosis And Treatment ◽  
Molecular Testing ◽  
Retrospective Case ◽  
Detection Rates ◽  
Endemic Setting ◽  
Number Of Patients ◽  
Small Patient Population ◽  
Extra Pulmonary

Abstract BACKGROUND Tuberculosis (TB) is a rare but potentially devastating infection among Canadian children. Accurate diagnosis and initiation of treatment are limited in part by the fact that it takes 2–6 weeks for culture results to be confirmed. Xpert MTB/RIF (Xpert) is a rapid, automated molecular assay that has been validated for diagnosing pulmonary but not extra-pulmonary TB in children. OBJECTIVES This was a retrospective study of children investigated for active TB at our facility in order to: 1.Outline demographic characteristics and describe clinical presentations of children diagnosed with active TB. 2.Compare performance of molecular testing (Xpert) to stain and Mycobacterium tuberculosis culture on pulmonary and extra-pulmonary specimens. DESIGN/METHODS We conducted a retrospective chart review of all paediatric patients investigated for active TB at our facility with stain, culture and molecular (Xpert) testing between January 2015 and August 2017. Due to a small number of patients, our data analysis was limited to narrative summary and descriptive statistics. RESULTS A total of 10 children were diagnosed with active TB, including 3 cases of pulmonary, 4 extra-pulmonary and 3 disseminated disease. Age range at diagnosis was 2 months to 16 years, with 3 children younger than 1 year. Most children contracted TB while travelling to and/or being exposed to an index case from endemic areas, including East Asia/Western Pacific (5), South Asia (2) and Africa (1). All children were HIV negative. Time from symptom onset to TB diagnosis and treatment ranged from approximately 4 days to 5 months. Multi-drug resistant TB was confirmed in 1 child. Sadly, 1 child passed away from TB related complications. AFB stain was positive on at least one specimen in 4/10 cases, cultures were positive in 8/10 and molecular testing (Xpert) in 7/10 cases. Time to positive cultures ranged from 10 to 35 days, with an average of 19 days. All cases positive on Xpert were also culture positive. Xpert test diagnosed TB in 5/6 of extra-pulmonary specimens submitted, including pericardial fluid, lymph node tissues and cerebrospinal fluid. CONCLUSION Many paediatric TB patients at our facility are children who have traveled to/have contacts from TB endemic regions, emphasizing the need for obtaining thorough exposure and travel history. Culture and molecular testing demonstrated similar TB detection rates, albeit based on a small patient population. While cultures remain the most reliable diagnostic method, molecular testing may facilitate rapid diagnosis and treatment of pulmonary and extra-pulmonary paediatric TB in a non-endemic setting.

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