The Novel C-Tb Skin Test for LTBI

Total Page：16

File Type：pdf, Size：1020Kb

The novel C-Tb skin test for LTBI Peter Andersen VP vaccine R/D Statens Serum Institut Copenhagen, Denmark 1 CTHE-TB C-Tb SKINTEST C-Tb combines the simplicity and low cost of the skin test with the diagnostic accuracy of the IGRA tests PPD ESAT-6 CFP-10 ESAT-6 CFP-10 2 C-TBTb IS Mtb-SPECIFIC C-Tb & IGRAs are both based on purified ESAT-6 and CFP-10 PPD C-Tb ESAT-6 CFP-10 Mtb BCG & non-tuberculous mycobacteria 3 C-Tb IN CLINICAL DEVELOPMENT Phase I Phase I Phase II Phase III 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 Phase III results TESAT trials TESEC-01 TESEC-02 TESEC-03 TESEC-06 Reporting (rdESAT-6) ID of TESEC-04 TESEC-05 commercial Toxicology partner incl. embryo- fetal toxicity TESEC-07 Partnership SEVEN CLINICAL TRIALS 3,109 participants 723 children 867 HIV-infected Lillebaek et al, Tuberculosis 2009; Arend et al, Tuberculosis 2008; Aggerbeck et al, PlosOne 2013; Hoff et al, ERJ 2016 4 C-TB CUT-OFF P P D C -T b 1 0 0 1 0 0 9 0 9 0 8 0 8 0 7 0 7 0 ROC curve analysis n 6 0 n 6 0 o o i ) i ) t t a m a m r 5 0 r 5 0 m u m u ( ( d d n n I 4 0 I 4 0 3 0 3 0 Optimal cut-off: ≥ 5mm 2 0 2 0 1 0 1 0 5 5 0 0 s s s l t l ts o n o n tr e r i t ie n t n t o a a c p o c p G B B T G C C T B B BCG controls N=153 (all HIV-) TB patients N=241 (146 HIV- and 95 HIV+) Aggerbeck et al, PlosOne 2013; Hoff et al, ERJ 2016 5 UNIVERSAL CUT-OFF OBVIATE CONFLICTING TST GUIDELINES Cut-off for PPD-TST depends on: Local guidelines Introduces risk of bias and BCG* vaccination status uncertainty of infection status Clinical context incl. HIV infection and age 0 5 10 15 mm *Bacillus Calmette-Guérin, tuberculosis vaccine 6 CONCLUSIONS & RESULTS FROM PHASE 3 • C-Tb test results correlate with exposure to M. tuberculosis • C-Tb and QFT have similar positivity rates • C-Tb is only impacted by HIV-infection with low CD4 counts (<100 cells/uL) • C-Tb induration size is impacted by young age on a level with PPD • C-Tb deliver IGRA like performance in the field friendly skin test format using a universal 5mm cut off 7.

Copy Link

Recommended publications

No. 24, 2002 Respiratory Syncytial Virus (RSV) Is Table 1
EPI• NEWS NATIONAL SURVEILLANCE OF COMMUNICABLE DISEASES Editor: Susanne Samuelsson Dept. of Epidemiology Tel.: +45 3268 3268 • Fax: +45 3268 3874 Statens Serum Institut • 5 Artillerivej • DK 2300 Copenhagen S www.ssi.dk • [email protected] • ISSN: 1396-4796 RESPIRATORY SYNCYTIAL VIRUS No. 24, 2002 Respiratory syncytial virus (RSV) is Table 1. No. of specimens positive tions collected by nasal suction or the most common cause of acute lo- for respiratory syncytial virus (RSV) swab can be used, but this method is wer respiratory tract infections in by age, M/F ratio and incidence per less sensitive. RSV is detected in cli- small children. RSV is a single- 105, 1998-2000 nical microbiological departments by strained RNA virus, belonging to the immunofluorescence, ELISA and Age M/F Incidence pneumovirus genus of the Paramyxo- 5 PCR. Quick tests (20 minutes) are a viridae family. The virus is divided (yrs) No.ratio per 10 little less sensitive. into two types, A and B, each of <1 3782 1.4 1892.6 which has several subtypes. 1 1336 1.3 659.1 Treatment 2 337 1.4 162.6 There is no sure and efficient treat- Occurrence 3-4 114 1.1 27.1 ment for RSV infection. Ribavirin has RSV was isolated for the first time 5-9 30 1.0 3.0 been used for the treatment of child- from American children with lower ren at risk of severe course of the in- 10-19 13 1.6 0.7 respiratory tract infections in 1957. fection, particularly in United States, A total of 90% of all children have 20-29 16 1.7 0.7 but serious questions have been rai- had one, and 50% have had two RSV 30-39 13 0.3 0.5 sed about the effect.
[Show full text]
Curriculum Vitae Kåre Mølbak
Curriculum vitae Kåre Mølbak CURRICULUM VITAE, KÅRE MØLBAK Division of Infectious Disease Preparedness, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark Telephone +45 3268 3157 (office) + 45 2280 6076 (mobile) E-mail: [email protected] Born 24 September 1955 Education: M.D., 1985, from University of Copenhagen, Denmark DMSc: 'The Epidemiology of Diarrhoeal Diseases in Early Childhood. A review of community studies in Guinea-Bissau', 2000 Most recent employments: From 2017: Executive vice president, Statens Serum Institut From 2017: Professor, Faculty of Health and Medical Sciences, University of Copenhagen 2004-2016: Director, State Epidemiologist, Department of Infectious Disease Epidemiology, Statens Serum Institut 2003: Senior medical officer, Department of Epidemiology, Statens Serum Institut. 2001-2002: Guest researcher at Foodborne and Diarrheal Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA 1996-2003: Department specialist (zoonosis epidemiology) at the Department of Gastrointestinal Infection and the Department of Epidemiology Research, Statens Serum Institut. From 1999: Associate professor at the University of Copenhagen, Faculty of Health Sciences, adjuncted to the ph.d. study programme. Profile: After basic training in clinical infectious diseases, Kåre Mølbak held research positions in connection with the Bandim health research project in Guinea Bissau and at several departments at Statens Serum Institut. Additional international collaboration include work in Liberia, Vietnam, India, and Ghana. At the present position, he works as the head of the Division of Infectious Diseases Preparedness in Denmark which includes public health reference laboratories as well as surveillance and control activities. Particular areas of interest are control of infections, vaccines as well as the emerging problems of zoonotic infections and antibiotic resistant bacteria transferred from food animals to humans.
[Show full text]
Instruction for Use of Bcg Vaccine Ssi (For Intradermal Use Only)
INSTRUCTION FOR USE OF BCG VACCINE SSI (FOR INTRADERMAL USE ONLY) Description BCG Vaccine is a live freeze-dried vaccine, made from an attenuated strain of S T A T E N S S E Mycobacterium bovis (BCG), Danish Strain 1331. It R U M is used for the prevention of tuberculosis, I N S T I T U T but does not ensure complete immunity. The Vaccine fulfills the Requirements for dried BCG vaccine (Requirements for Biological Substances No. 11), formulated by the WHO Expert Committee on Biological Standardization. 5 Artillerivej DK-2300 Declaration Copenhagen S 1 ml of the reconstituted vaccine contains: Denmark Mycobacterium bovis (BCG) Danish 1331 0.75 mg Tel: +45 32 68 32 Sodium glutamate 3.75 mg 68 Magnesium 125 microgram Fax: +45 38 68 Dipottasium phosphate 125 microgram 32 68 L-asparagine monohydrate 1 mg Telex: 31316 Ferriammonium citrate 12,5 microgram Serum dk Glycerol (85%) 18.4 mg Citric acid monohydrate 0.5 mg Water for injection to 1 ml Produced in Denmark by Statens Serum Institut Administration FOR INTRADERMAL USE ONLY. Dose for children below one year: 0.05 ml of the reconstituted vaccine and for others 0.1 ml. Use a sterile syringe and a sterile fine short needle for each injection (25 G or 26 G x 10 mm). The skin should not be cleaned with antiseptic. Jet injectors should not be used. The injection should be made slowly into the upper layer of skin. Injections made too deeply increase the risk of abcess formation. The vaccine should be protected from light.
[Show full text]
EPI-NEWS NATIONAL SURVEILLANCE of COMMUNICABLE DISEASES Editor: Peter Henrik Andersen Dept
EPI-NEWS NATIONAL SURVEILLANCE OF COMMUNICABLE DISEASES Editor: Peter Henrik Andersen Dept. of Epidemiology Tel.: +45 3268 3268 • Fax: +45 3268 3874 Statens Serum Institut • 5 Artillerivej • DK 2300 Copenhagen S www.ssi.dk • [email protected] • ISSN: 1396-4798 DANISH HEALTH RESEARCH IN GUINEA-BISSAU No. 34, 2006 In one of the world’s poorest years, the BHP has been the focus of yields 70% protection against countries, Guinea-Bissau in West 22 PhD theses, mainly Danish, and rotavirus diarrhoea, and 52% Africa, the Bandim Health Project nine doctoral dissertations. protection against reinfection during (BHP) has been engaged in epide- the first year following the initial miological research since 1978 Research focus areas infection. This high protection rate focussing on infection, vaccination Two-dose measles vaccination suggests that a rotavirus vaccine and the long-term effects of health strategy: would be an effective means to intervention. Infection with measles before the reduce the incidence of acute The BHP is a collaboration between WHO recommended vaccination age diarrhoea with dehydration and Statens Serum Institut and the at 9 months is a growing problem in associated deaths. Guinea-Bissau Ministry of Health. the developing countries. This is For further information on the BHP, Child mortality in Guinea-Bissau due, among others, to increasing please contact project secretary ranks among the highest worldwide: urbanisation and an increase in the Christina Rasmussen, [email protected]. > 200 per 1000 live born infants share of mothers who were them- (P. Valentiner-Branth, K. Mølbak, during the first three years of life. selves measles vaccinated at a young Dept.
[Show full text]
EPI-NEWS NATIONAL SURVEILLANCE of COMMUNICABLE DISEASES Editor: Peter Henrik Andersen Dept
EPI-NEWS NATIONAL SURVEILLANCE OF COMMUNICABLE DISEASES Editor: Peter Henrik Andersen Dept. of Epidemiology Tel.: +45 3268 3268 • Fax: +45 3268 3874 Statens Serum Institut • 5 Artillerivej • DK 2300 Copenhagen S www.ssi.dk • [email protected] • ISSN: 1396-4798 REVISION OF VACCINATION RECCOMENDATIONS FOR TRAVELS ABROAD No. 21/22, 2006 Since 1985, Statens Serum Institut has asplenia/no splenic function or known extended period of time (group 4). published an annual overview detail- complement defect. Furthermore, it is Vaccination of other groups may be ing vaccination recommendations for recommended to health care workers considered, for instance vaccination travellers going abroad. To ensure who will be stationed in densely of health care workers who will have continued and full national consensus populated refugee camps where the close contact with the local population on the Danish recommendations, SSI risk of a meningitis epidemic is non- for an extended period of time (group set up a working group of represen- neglible. Besides, vaccination is 4), if necessary preceded by a Man- tatives from a range of scientific recommended for the following toux test. Vaccination should be ad- societies in the spring of 2005. groups of travellers: ministered intradermally and should The working group’s participants - Pilgrims travelling to Mecca (ACY- be given 6-8 weeks before departure. include Mads Buhl and Eskild W135 vaccination is required) Petersen, Danish Society of Travel - Travellers (apart from group 1) Hepatitis A Medicine, Søren Thybo, Danish entering the African meningitis belt Vaccination is recommended to all (Sahel). The risk peaks during the dry travellers (including group 1) to areas Infectious Diseases Society, Jørgen season from December to July.
[Show full text]
Epi-News 3/10
EPI-NEWS NATIONAL SURVEILLANCE OF COMMUNICABLE DISEASES Editor: Peter Henrik Andersen Dept. of Epidemiology Tel.: +45 3268 3268 • Fax: +45 3268 3874 Statens Serum Institut • 5 Artillerivej • DK 2300 Copenhagen S www.ssi.dk • [email protected] • ISSN: 1396-4798 No. 3, 2010 INCREASE IN THE NUMBER OF Figure 1. Notified cases of listeriosis per 105 per year, 2000-2009 LISTERIA CASES IN 2009 Incidence After remaining stable at 30-40 for a period of years, the number of noti- 2,0 fied listeriosis cases has increased 1,8 every year as from 2003, barring 2008, Figure 1. In 2009, a total of 97 1,6 cases were notified, i.e. 2-3 times the 1,4 previous level. 1,2 Listeriosis is a food-borne disease caused by infection with Listeria 1,0 monocytogenes. The bacterium oc- 0,8 curs in many types of raw and proc- 0,6 essed foods including vegetables, smoked foods, meat and diary pro- 0,4 ducts. The bacteria reproduce at 0,2 fridge temperature, but perish when 0,0 heated. 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 Listeriosis is typically seen in con- junction with sepsis with or without meningitis, while localised infections are rare. departments have forwarded the iso- children adopted from Ethiopia. The The condition primarily affects per- lated strains soon after bacteria 2009 increase shows that this issue sons above 60 years and immunode- growth, and it has therefore been remains relevant. When assessing ficient individuals. Risk factors in- possible to obtain timely typing re- the state of health of adopted Ethio- clude, among others: Cancer, hae- sults.
[Show full text]
Introduction and Transmission of SARS-Cov-2 B.1.1.7 in Denmark
medRxiv preprint doi: https://doi.org/10.1101/2021.06.04.21258333; this version posted June 7, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Introduction and transmission of SARS-CoV-2 B.1.1.7 in Denmark Thomas Y. Michaelsen1, Marc Bennedbæk2, Lasse E. Christiansen3, Mia S. F. Jørgensen4, Camilla H. Møller5, Emil A. Sørensen1, Simon Knutsson1, Jakob Brandt1, Thomas B. N. Jensen1, Clarisse 5 Chiche-Lapierre1, Emilio F. Collados1, Trine Sørensen1, Celine Petersen1, Vang Le-Quy6, Mantas Sereika1, Frederik T. Hansen1, Morten Rasmussen7, Jannik Fonager7, Søren M. Karst7, Rasmus L. Marvig8, Marc Stegger9, Raphael N. Sieber9, Robert Skov5, Rebecca Legarth4, Tyra G. Krause5, Anders Fomsgaard7, The Danish Covid-19 Genome Consortium (DCGC)10, Mads Albertsen1,* Affiliations: 10 1 Department of Chemistry and Bioscience, Aalborg University; Aalborg, Denmark. 2 Centre of Excellence for Health, Immunity and Infection (CHIP), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen; Copenhagen, Denmark. 3 Department of Applied Mathematics and Computer Science, Technical University of Denmark; Lyngby, Denmark. 15 4 Infectious Disease Epidemiology & Prevention, Statens Serum Institut; Copenhagen, Denmark. 5 Infectious Disease Preparedness, Statens Serum Institut; Copenhagen, Denmark. 6 Unit for Research Data Services (CLAAUDIA), Aalborg University; Aalborg, Denmark. 7 Department of Virus & Microbiological Special Diagnostics, Statens Serum Institut; 20 Copenhagen, Denmark. 8 Center for Genomic Medicine, Rigshospitalet; Copenhagen, Denmark 9 Department of Bacteria, Parasites and Fungi, Statens Serum Institut; Copenhagen, Denmark 10 https://www.covid19genomics.dk/about *Corresponding author.
[Show full text]
ERADICATION of POLIO - and THEN WHAT ? No
EPI-NEWS NATIONAL SURVEILLANCE OF COMMUNICABLE DISEASES Editor: Tove Rønne Statens Serum Institut - 5 Artillerivej - 2300 Copenhagen S - Denmark Tel.: +45 3268 3268 - Fax: +45 3268 3868 - E-mail: [email protected] - Website: www.ssi.dk ISSN: 1396-4798 ERADICATION OF POLIO - AND THEN WHAT ? No. 10, 2000 At a recent WHO meeting the status Fig. 1. Known or probable wild poliovirus transmission, 1988 and 1998 of the world-wide polio eradication Source: WHO campaign was reviewed and future polio vaccine needs discussed. In the course of the campaign the number 1988 of reported cases of paralytic polio has fallen from 35,000 in 1988 to 6200 in 1998 (Fig. 1). A provisional figure for 1999 is of 5300 cases. Because of inadequate surveillance and reporting in several countries, it is estimated that the true number of paralytic cases is higher - about 15,000 cases for 1999. The number of more or less asymptomatic poliovirus infections is over 100 times greater again. Thus, more than one million infectious cases are still occurring per annum. 1998 Stopping oral polio vaccination It is considered doubtful whether pa- ralytic polio will be eliminated in the year 2000, which has been the aim of the eradication campaign. An optimistic estimate is that the dis- ease will be eliminated by the year 2001 or shortly thereafter. Up to now, the Sabin live oral polio vaccine (OPV) has been the decisive factor in the world-wide campaign. The que- stions are now arising of when and how the use of OPV can be stopped. Known or probable wild poliovirus transmission This cannot be expected to happen before the year 2005, and 2010 or 2015 is regarded as a more realistic estimate.
[Show full text]
VACCINES Early and Late Protection from TB
RESEARCH HIGHLIGHTS VACCINES Early and late protection from TB The BCG vaccine (which is the only In the early stage of TB infection approved vaccine against tuberculosis (<4 weeks after exposure), the (TB)) and other TB vaccines that bacterial load in the lungs of are currently in clinical trials are H56‑vaccinated mice was similar designed to protect against infection to that of mice vaccinated with the by incorporating antigens that are BCG vaccine. However, in the later expressed early in the disease process. stage of infection (24 weeks after However, they do not prevent the exposure), H56‑vaccinated mice establishment of latent persistent had significantly lower numbers infection or reactivation of clinical of bacilli compared to BCG- disease, which is a major unmet need vaccinated mice. Moreover, H56 for infected patients and for reducing was an effective booster to BCG, further transmission. with H56‑vaccinated mice having Reporting in Nature Medicine, significantly lower bacterial loads Aagaard and colleagues show that a 24 weeks after infection compared to vaccine comprising antigens that are mice vaccinated with BCG alone. expressed in the early and late stages Importantly, in two mouse models of TB combated late-stage infection of latent TB, H56 provided significant in both pre- and post-exposure protection against reactivation of mouse models. the disease. Detailed examination The vaccine (termed H56) showed that H56 promoted the comprises a fusion protein generation in the lungs of antigen- (Ag85B–ESAT6 (a 6 kDa early specific, polyfunctional CD4+ T cells secretory antigenic target)–Rv2660c) expressing interferon-γ, interleukin‑2 and a cationic adjuvant (CAF01).
[Show full text]
Mink-Cluster-5-Short-Report AFO2
1 Working paper on SARS-CoV-2 spike mutations arising in Danish mink, their 2 spread to humans and neutralization data. 3 4 SARS-CoV-2 spike mutations arising in Danish mink and their spread to 5 humans 6 7 PRELIMINARY AUTHOR LIST: Senior scientist Ria Lassaunière1§, senior scientist Jannik Fonager1§, 8 Senior scientist Morten Rasmussen1, Anders Frische1, Senior Scientist Charlotta Polacek Strandh1, 9 Senior scientist veterinarian Thomas Bruun Rasmussen, Chief veterinarian Anette Bøtner, and Chief 10 Virologist Anders Fomsgaard1* 11 12 1Department of Virus and Microbiological Special Diagnostic, Statens Serum Institut, 5 Artillerivej, 13 DK-2300 Copenhagen S, DENMARK 14 § equal contribution 15 *Corresponding author: MD, DMSc, Professor infectious diseases, Chief of Virus Research & 16 Development Laboratory at SSI, Anders Fomsgaard; E-mail: [email protected] 17 18 Keywords: Sars-CoV-2, COVID-19, mink, cluster 5 Page 1 of 7 19 Background 20 Despite control measures, SARS-CoV-2 continued to spread among mink farms across northern 21 Denmark, with more than 200 farms infected by November 2020. SARS-CoV-2 genome sequences 22 obtained from infected mink and humans living on the farms provided evidence of SARS-CoV-2 spread 23 between mink and human in zoonotic events. This study investigates the amino acid changes in the 24 spike surface glycoprotein that appeared during this outbreak and their effect on the antigenicity of 25 the SARS-CoV-2 virus. 26 Spike mutations 27 Within the infected mink, the SARS-CoV-2 virus mutated, giving rise to several amino acid changes in 28 the spike protein. The first was a tyrosine to phenylalanine at amino acid 453 (Y453F), a mutation that 29 also appeared during the Dutch mink farm outbreaks.
[Show full text]
OUTBREAK of TUBERCULOSIS No
EPI-NEWS NATIONAL SURVEILLANCE OF COMMUNICABLE DISEASES Editor: Tove Rønne Statens Serum Institut - 5 Artillerivej - 2300 Copenhagen S - Denmark Tel.: +45 3268 3268 - Fax: +45 3268 3868 www.ssi.dk - [email protected] - ISSN: 1396-4798 OUTBREAK OF TUBERCULOSIS No. 1-2, 2001 Investigation of a case of tuberculo- desinfected by washing all horizon- bacteria shows the same DNA re- sis (TB) in a young Danish national tal surfaces, bunks and cupboards striction fragment length pattern, serviceman has so far revealed two with a chlorinated compound. Mat- also called “DNA fingerprint”, further cases of TB. 14 of 37 persons tresses, curtains and cleaning rags Fig. 1, the patients are usually mem- examined at the barracks were Man- were destroyed. bers of the same chain of infection. toux positive, which is unusual for On the other hand, if the fingerprints Danish conditions. Comment are different, it is most unlikely that TB is still a serious disease. Although the patients belong to the same chain Tuberculosis in Næstved Barracks only a few hundred persons per year of infection. In August 2000 open pulmonary TB are infected by TB in Denmark , it is Fig. 1. Identical M. tuberculosis was diagnosed in a national service- important to consider this diagnosis DNA pattern from patients A and B man at the South Zealand military in patients with prolonged cough or installations at Næstved. Initial di- unexplained tiredness. 164 agnosis was by chest x-ray, followed (F. Juhl, Næstved Central Hosp., 176 171 182 200 by the observation of massive num- O. Mygind, MOH, Storstrøm County) 206 bers of acid-fast bacilli on sputum 268 microscopy.
[Show full text]
Escaping the Plato's Cave of Latent Tuberculosis Testing
EDITORIAL | TUBERCULOSIS Escaping the Plato’s cave of latent tuberculosis testing: a path for developers of predictive tests for risk of tuberculosis Morten Ruhwald1 and Roland Diel 2,3 Affiliations: 1Center for Vaccine Research, Statens Serum Institut, Copenhagen, Denmark. 2Institute for Epidemiology, University Medical Hospital Schleswig-Holstein, Kiel, Germany. 3Lung Clinic Grosshansdorf, Airway Disease Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany. Correspondence: Morten Ruhwald, Center for Vaccine Research, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, Denmark. E-mail: [email protected] @ERSpublications The End TB Strategy calls for renewed focus on latent TB, which requires development of more predictive tests. KIK et al. provide a framework for the clinical development of such tests, an ambition that calls for joint efforts by researchers and funders. http://ow.ly/O3tm30m95dy Cite this article as: Ruhwald M, Diel R. Escaping the Plato’s cave of latent tuberculosis testing: a path for developers of predictive tests for risk of tuberculosis. Eur Respir J 2018; 52: 1801616 [https://doi.org/ 10.1183/13993003.01616-2018]. The End TB Strategy and current state of play Tuberculosis (TB) is one of the leading causes of morbidity and death, disproportionately impacting the low- and middle-income countries, where 94% of TB cases occur. Every year, TB causes more than a million deaths and the World Bank estimates the epidemic will rob the world’s poorest countries of US$1–3 trillion over the next decade, causing a loss of productivity of up to 4–7% of some countries’ gross domestic product. Particularly troubling for the prospects of global prosperity, 75% of TB cases arise during people’s most productive years, between the ages of 15 and 54, stifling human development on a large scale.
[Show full text]