Kinda Schepers

Université Libre de Bruxelles, Bruxelles, Brussels Capital, Belgium

Are you Kinda Schepers?

Claim your profile

Publications (20)106.85 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The screening and treatment of latent tuberculosis (TB) infection reduces the risk of progression to active disease and is currently recommended for HIV-infected patients. The aim of this study is to evaluate, in a low TB incidence setting, the potential contribution of an interferon-gamma release assay in response to the mycobacterial latency antigen Heparin-Binding Haemagglutinin (HBHA-IGRA), to the detection of Mycobacterium tuberculosis infection in HIV-infected patients. Treatment-naïve HIV-infected adults were recruited from 4 Brussels-based hospitals. Subjects underwent screening for latent TB using the HBHA-IGRA in parallel to a classical method consisting of medical history, chest X-ray, tuberculin skin test (TST) and QuantiFERON®-TB Gold In-Tube (QFT-GIT). Prospective clinical and biological follow-up ensued, with repeated testing with HBHA-IGRA. A group of HIV-infected patients with clinical suspicion of active TB was also recruited and tested with the HBHA-IGRA. Multiplex analysis was performed on the culture supernatants of this in-house assay to identify test read-outs alternative to interferon-gamma that could increase the sensitivity of the test. Among 48 candidates enrolled for screening, 9 were identified with latent TB by TST and/or QFT-GIT results. Four of these 9 patients and an additional 3 screened positive with the HBHA-IGRA. This in-house assay identified all the patients that were positive for the TST and showed the best concordance with the presence of a M. tuberculosis exposure risk. During follow-up (median 14 months) no case of active TB was reported and HBHA-IGRA results remained globally constant. Fourteen HIV-infected patients with clinical suspicion of active TB were recruited. Active TB was confirmed for 6 of them among which 3 were HBHA-IGRA positive, each with very high interferon-gamma concentrations. All patients for whom active TB was finally excluded, including 2 non-tubercular mycobacterial infections, had negative HBHA-IGRA results. Multiplex analysis confirmed interferon-gamma as the best read-out. The HBHA-IGRA appears complementary to the QuantiFERON®-TB Gold In-Tube for the screening of latent TB in HIV-infected patients. Large-scale studies are necessary to determine whether this combination offers sufficient sensitivity to dismiss TST, as suggested by our results. Furthermore, HBHA-IGRA may help in the diagnosis work-up of clinical suspicions of active TB.
    BMC Infectious Diseases 12/2015; 15(1):796. DOI:10.1186/s12879-015-0796-0 · 2.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A total of 120 bronchoalveolar lavage specimens from HIV and non-HIV immunocompromised patients, positive for Pneumocystis jirovecii by an "in house" real-time polymerase chain reaction (PCR), were evaluated by the Bio-Evolution Pneumocystis real-time PCR, a commercial quantitative assay. Patients were classified in 2 categories based on clinical and radiological findings: definite and unlikely Pneumocystis pneumonia (PCP). For the "in house" PCR, cycle threshold 34 was established as cut-off value to discriminate definite PCP from unlikely PCP with 65% and 85% of sensitivity and specificity, respectively. For the Bio-Evolution quantitative PCR, a cut-off value of 2.8×10(5)copies/mL was defined with 72% and 82% of sensitivity and specificity, respectively. Overlapped zones of results for definite and unlikely PCP were observed. Quantitative PCR is probably a useful tool for PCP diagnosis. However, for optimal management of PCP in non-HIV immunocompromised patients, operational thresholds should be assessed according to underlying diseases and other clinical and radiological parameters. Copyright © 2015. Published by Elsevier Inc.
    Diagnostic Microbiology and Infectious Disease 03/2015; 82(2). DOI:10.1016/j.diagmicrobio.2015.03.006 · 2.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The search for novel vaccines against tuberculosis (TB) would benefit from in-depths knowledge of the human immune responses to Mycobacterium tuberculosis (Mtb) infection. Here, we characterised in a low TB incidence country, the immune responses to a new candidate vaccine antigen against TB, the heparin-binding haemagglutinin (HBHA), in young children in contact with an active TB case (aTB). Children with no history of BCG vaccination were compared to those vaccinated at birth to compare the initial immune responses to HBHA with secondary immune responses. Fifty-eight children with aTB and 76 with latent TB infection (LTBI) were included and they were compared to 90 non-infected children. Whereas Mtb-infected children globally secreted more interferon-gamma (IFN-γ) in response to HBHA compared to the non-infected children, these IFN-γ concentrations were higher in previously BCG-vaccinated compared to non-vaccinated children. The IFN-γ concentrations were similar in LTBI and aTB children, but appeared to differ qualitatively. Whereas the IFN-γ secretion induced by native methylated and recombinant non-methylated HBHA were well correlated for aTB, this was not the case for LTBI children. Thus, Mtb-infected young children develop IFN-γ responses to HBHA that are enhanced by prior BCG vaccination, indicating BCG-induced priming, thereby supporting a prime-boost strategy for HBHA-based vaccines. The qualitative differences between aTB and LTBI in their HBHA-induced IFN-γ responses may perhaps be exploited for diagnostic purposes.
    Vaccine 01/2015; 33(8). DOI:10.1016/j.vaccine.2014.12.011 · 3.49 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Herpes simplex virus is the most common cause of severe sporadic encephalitis. We report a case of herpes simplex type 1-encephalitis in a 50-year-old woman receiving anti-tumor necrosis factor-α monoclonal antibodies adalimumab. Although she was an acyclovir naïve patient, a mixed viral population (wild-type and acyclovir-resistant bearing a thymidine-kinase mutation) was identified in the cerebrospinal fluid. The virus in cerebrospinal fluid evolved and a second thymidine-kinase mutant virus emerged. Combined foscavir and acyclovir treatment resolved the herpes simplex encephalitis. To our knowledge, this is the first report of acyclovir-resistant herpes simplex encephalitis in a patient treated with adalimumab.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 10/2013; 59(1). DOI:10.1016/j.jcv.2013.10.025 · 3.47 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background:Diagnosis of childhood active tuberculosis (aTB) or latent Mycobacterium tuberculosis (Mtb) infection (LTBI) remains a challenge, and replacement of tuberculin skin tests (TST) by commercialized interferon-gamma release assays (IGRA) is not currently recommended.Methods:266 children between 1 month and 15 years of age, 214 being at risk of recent Mtb infection and 51 being included as controls, were prospectively enrolled. According results of clinical evaluation, TST, chest X-Ray and microbiology, children were classified as non-infected, LTBI or aTB. Long-incubation time PPD-, ESAT-6-, and CFP-10-IGRA were performed and evaluated for their accuracy to correctly classify the children.Results:Whereas both TST and PPD-IGRA were suboptimal to detect aTB, combining CFP-10-IGRA with TST or with PPD-IGRA allowed us to detect all the children with aTB, with 96% specificity for children who were positive for CFP-10-IGRA. Moreover, combination of CFP-10- and PPD-IGRA also detected 96% of children classified as LTBI, but a strong IFN-γ response to CFP-10 (>500 pg/ml) was highly suggestive of aTB at least among children less than 3 years old.Conclusions:Long-incubation time CFP-10- and PPD-IGRA should help the clinicians to identify quickly aTB or LTBI in young children.
    Clinical and vaccine Immunology: CVI 10/2013; DOI:10.1128/CVI.00525-13 · 2.37 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Deep dermatophytosis is a severe and sometimes life-threatening fungal infection caused by dermatophytes. It is characterized by extensive dermal and subcutaneous tissue invasion and by frequent dissemination to the lymph nodes and, occasionally, the central nervous system. The condition is different from common superficial dermatophyte infection and has been reported in patients with no known immunodeficiency. Patients are mostly from North African, consanguineous, multiplex families, which strongly suggests a mendelian genetic cause. Methods We studied the clinical features of deep dermatophytosis in 17 patients with no known immunodeficiency from eight unrelated Tunisian, Algerian, and Moroccan families. Because CARD9 (caspase recruitment domain-containing protein 9) deficiency has been reported in an Iranian family with invasive fungal infections, we also sequenced CARD9 in the patients. Results Four patients died, at 28, 29, 37, and 39 years of age, with clinically active deep dermatophytosis. No other severe infections, fungal or otherwise, were reported in the surviving patients, who ranged in age from 37 to 75 years. The 15 Algerian and Tunisian patients, from seven unrelated families, had a homozygous Q289X CARD9 allele, due to a founder effect. The 2 Moroccan siblings were homozygous for the R101C CARD9 allele. Both alleles are rare deleterious variants. The familial segregation of these alleles was consistent with autosomal recessive inheritance and complete clinical penetrance. Conclusions All the patients with deep dermatophytosis had autosomal recessive CARD9 deficiency. Deep dermatophytosis appears to be an important clinical manifestation of CARD9 deficiency. (Funded by Agence Nationale pour la Recherche and others.).
    New England Journal of Medicine 10/2013; DOI:10.1056/NEJMoa1208487 · 54.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mycobacterium tilburgii rarely causes disseminated disease. We describe a case of M. tilburgii infection in an otherwise healthy 33-year-old woman, who was found to carry bi-allelic mutations of the gene encoding the β1 chain of the IL-12 receptor.
    Journal of Clinical Immunology 10/2013; 33(8). DOI:10.1007/s10875-013-9941-y · 2.65 Impact Factor
  • J-P Van Vooren, K Schepers
    [Show abstract] [Hide abstract]
    ABSTRACT: Rapid identification using bacteriological methods and adequate treatment of active tuberculosis cases are the most important objective of any tuberculosis activity but, in order to eliminate the disease, another important component of tuberculosis control is to reduce the vast reservoir of latent tuberculosis infections. Tuberculin skin test and interferon-gamma release assays are designed to identify immune response against mycobacterial antigens. Both tests are accurate to detect latent but not active forms of tuberculosis. Interferon-gamma release assays have higher specificity than tuberculin skin testing in BCG-vaccinated populations particularly if BCG was administered after 1 year of age. Both tests perform poorly to predict risk for progression to active tuberculosis. Screening should therefore be limited to situations with a clear likelihood of transmission after contact, taking account of the infectiousness of the index case and the intensity of exposure, or to those with a great probability of developing tuberculosis: young children and immunocompromised persons.
    Revue medicale de Bruxelles 09/2013; 34(4):301-5.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Most individuals infected with Mycobacterium tuberculosis develop latent tuberculosis infection (LTBI). Some may progress to active disease and would benefit from preventive treatment yet no means currently exists to predict who will reactivate. Here, we provide an approach to stratify LTBI based on IFN-γ responses to two antigens, the recombinant Early-Secreted Antigen Target-6 (rESAT-6) and the latency antigen Heparin-Binding Haemagglutinin (HBHA). We retrospectively analyzed results from in-house IFN-γ-release assays with HBHA (HBHA-IGRA) and rESAT-6 (rESAT-6-IGRA) performed during a 12-year period on serial blood samples (3 to 9) collected from 23 LTBI subjects in a low-TB incidence country. Both the kinetics of the absolute IFN-γ concentrations secreted in response to each antigen and the dynamics of HBHA/rESAT-6-induced IFN-γ concentrations ratios were examined. This analysis allowed the identification among the LTBI subjects of three major groups. Group A featured stable HBHA and rESAT-6-IGRA profiles with an HBHA/rESAT-6 ratio persistently higher than 1, and with high HBHA- and usually negative rESAT-6-IGRA responses throughout the study. Group B had changing HBHA/rESAT-6 ratios fluctuating from 0.0001 to 10,000, with both HBHA and rESAT-6 responses varying over time at least once during the follow-up. Group C was characterized by a progressive disappearance of all responses. By combining the measures of IFN-γ concentrations secreted in response to an early and a latency antigens, LTBI subjects can be stratified into different risk groups. We propose that disappearing responses indicate cure, that persistent responses to HBHA with HBHA/rESAT-6 ratios ≥ 1 represent stable LTBI subjects, whereas subjects with ratios varying from >1 to <1 should be closely monitored as they may represent the highest-risk group, as illustrated by a case report, and should therefore be prioritized for preventive treatment.
    PLoS ONE 08/2012; 7(8):e43285. DOI:10.1371/journal.pone.0043285 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pancreatitis is a common complication of acquired immunodeficiency syndrome. The most common causes of acute pancreatitis in an HIV population are medication and opportunistic infections. We report the case of a young, untreated, HIV-infected female who presented with acute pancreatitis of unknown origin. Unique to this case are the autoimmune pancreatitis-like features on imaging studies associated with renal mass-like lesions and lymph node involvement as well as the favorable outcome using highly active antiretroviral therapy alone. In HIV-infected patients, acute pancreatitis may present on imaging studies as autoimmune pancreatitis. In patients with uncontrolled HIV infection and imaging studies suggestive of autoimmune pancreatitis, direct HIV-related inflammation should be considered after exclusion of all other causes of pancreatitis.
    JOP: Journal of the pancreas 09/2011; 12(5):477-81. DOI:10.6092/1590-8577/457
  • [Show abstract] [Hide abstract]
    ABSTRACT: Immunizations are extremely efficient in prevention of diseases with a lethal potential. Healthy adults, pregnant women and patients suffering from chronic diseases may have a different benefit from vaccine available in our country. Numerous health problems need to be addressed during a short consultation, relegating immunization to a position of secondary importance. This paper will address the issue of immunization in special circumstances such as: healthy adults, pregnant women, HIV-infected patients, patients with end-stage renal disease, patients with chronic liver diseases and solid organ transplant candidates and recipients.
    Revue medicale de Bruxelles 09/2011; 32(4):321-7.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Interleukin-12 receptor β1 (IL-12Rβ1) deficiency is the most common form of Mendelian susceptibility to mycobacterial disease (MSMD). We undertook an international survey of 141 patients from 102 kindreds in 30 countries. Among 102 probands, the first infection occurred at a mean age of 2.4 years. In 78 patients, this infection was caused by Bacille Calmette-Guérin (BCG; n = 65), environmental mycobacteria (EM; also known as atypical or nontuberculous mycobacteria) (n = 9) or Mycobacterium tuberculosis (n = 4). Twenty-two of the remaining 24 probands initially presented with nontyphoidal, extraintestinal salmonellosis. Twenty of the 29 genetically affected sibs displayed clinical signs (69%); however 8 remained asymptomatic (27%). Nine nongenotyped sibs with symptoms died. Recurrent BCG infection was diagnosed in 15 cases, recurrent EM in 3 cases, recurrent salmonellosis in 22 patients. Ninety of the 132 symptomatic patients had infections with a single microorganism. Multiple infections were diagnosed in 40 cases, with combined mycobacteriosis and salmonellosis in 36 individuals. BCG disease strongly protected against subsequent EM disease (p = 0.00008). Various other infectious diseases occurred, albeit each rarely, yet candidiasis was reported in 33 of the patients (23%). Ninety-nine patients (70%) survived, with a mean age at last follow-up visit of 12.7 years ± 9.8 years (range, 0.5-46.4 yr). IL-12Rβ1 deficiency is characterized by childhood-onset mycobacteriosis and salmonellosis, rare recurrences of mycobacterial disease, and more frequent recurrence of salmonellosis. The condition has higher clinical penetrance, broader susceptibility to infections, and less favorable outcome than previously thought.
    Medicine 11/2010; 89(6):381-402. DOI:10.1097/MD.0b013e3181fdd832 · 4.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Tuberculosis (TB) remains a major cause of mortality. A better understanding of the immune responses to mycobacterial antigens may be helpful to develop improved vaccines and diagnostics. The mycobacterial antigen heparin-binding hemagglutinin (HBHA) induces strong IFN-γ responses by circulating lymphocytes from subjects latently infected with Mycobacterium tuberculosis, and low responses associated with CD4(+) regulatory T (Treg) cells in patients with TB. Here, we investigated HBHA-specific IFN-γ responses at the site of the TB disease. Bronchoalveolar lavages, pleural fluids, and blood were prospectively collected from 61 patients with a possible diagnosis of pulmonary or pleural TB. HBHA-specific IFN-γ production was analyzed by flow cytometry and ELISA. The suppressive effect of pleural Treg cells was investigated by depletion experiments. The percentages of HBHA-induced IFN-γ(+) alveolar and pleural lymphocytes were higher for pulmonary (P < 0.0001) and for pleural (P < 0.01) TB than for non-TB controls. Local CD4(+) and CD8(+) T cells produced the HBHA-specific IFN-γ. This local secretion was not suppressed by Treg lymphocytes, contrasting with previously reported data on circulating lymphocytes. Patients with TB display differential effector and regulatory T-cell responses to HBHA in local and circulating lymphocytes with a predominant effector CD4(+) and CD8(+) response locally, compared with a predominant Treg response among circulating lymphocytes. These findings may be helpful for the design of new vaccines against TB, and the detection of HBHA-specific T cells at the site of the infection may be a promising tool for the rapid diagnosis of active TB.
    American Journal of Respiratory and Critical Care Medicine 09/2010; 182(6):848-54. DOI:10.1164/rccm.201001-0083OC · 11.99 Impact Factor
  • J P Van Vooren, K Schepers, M Wanlin
    [Show abstract] [Hide abstract]
    ABSTRACT: Tuberculosis (TB) is a global health problem driven by poverty, HIV infection, etc. In Europe, the problem of multidrug resistance (i.e., resistance to at least rifampin and isoniazid) (MR) develops. The cases come essentially from the former U.S.S.R. In Belgium, the incidence of tuberculosis continues to decline to 9.4/100,000 inhabitants in 2008. The percentage of MR germs is 2.8%. The distribution of cases is not uniform across the country. The incidence is much higher among people recently coming from high prevalence countries than among the Belgian native. The pulmonary forms of TB are more contagious and more common. The clinical signs are frequently non specific. The diagnosis is often mentioned up after performing a chest Xray and must always be confirmed by microbiological examination and culture of several sputum or other respiratory specimens. It is very important to identify the germ, M. tuberculosis complex and to test its sensitivity to anti-TB agents. Standard treatment consists of 4 drugs: isoniazid, rifampin, ethambutol and pyrazinamide for 2 months followed by rifampin and isoniazid for at least 4 additional months. In suspected cases of MR, 5 drugs are prescribed at the outset. Treatment and duration will be adjusted according to the results of susceptibility testing. The potential toxicities of second-line drugs should be well known by the physicians. Compliance of the patient is essential. Screening in the entourage is part of the therapeutic process.
    Revue medicale de Bruxelles 09/2010; 31(4):260-6.
  • [Show abstract] [Hide abstract]
    ABSTRACT: In countries where the incidence of tuberculosis is low, perinatal tuberculosis is seldom diagnosed. With increasing numbers of human immunodeficiency virus-infected people and increasing immigrant population from high tuberculosis incidence countries, one might expect perinatal tuberculosis to become more frequent. Early recognition of newborns at risk for perinatal tuberculosis infection is of utmost importance to prevent disease by chemoprophylaxis. We describe a case of latent perinatal tuberculosis infection in a newborn infected from a mother with extrapulmonary primary tuberculosis. Tuberculin skin test was negative, and latent tuberculosis infection was eventually diagnosed by specific immunological tests. We discuss the difficulties in diagnosis of recent tuberculosis infection in neonates and infants, and the risk factors for vertical transmission of tuberculosis, which need to be taken into account in considering the need for chemoprophylaxis in the newborn. Although perinatal TB infection is a rare condition and diagnosis is difficult due to poor diagnostic testing in pregnancy and newborns, a high index of suspicion is needed to limit the diagnostic delay and to avoid progression to perinatal TB disease.
    European Journal of Pediatrics 09/2010; 169(9):1155-8. DOI:10.1007/s00431-010-1177-8 · 1.98 Impact Factor
  • Clinical Immunology 01/2009; 131. DOI:10.1016/j.clim.2009.03.413 · 3.99 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The detection of latent tuberculosis infection (LTBI) is a major component of tuberculosis (TB) control strategies. In addition to the tuberculosis skin test (TST), novel blood tests, based on in vitro release of IFN-gamma in response to Mycobacterium tuberculosis-specific antigens ESAT-6 and CFP-10 (IGRAs), are used for TB diagnosis. However, neither IGRAs nor the TST can separate acute TB from LTBI, and there is concern that responses in IGRAs may decline with time after infection. We have therefore evaluated the potential of the novel antigen heparin-binding hemagglutinin (HBHA) for in vitro detection of LTBI. HBHA was compared to purified protein derivative (PPD) and ESAT-6 in IGRAs on lymphocytes drawn from 205 individuals living in Belgium, a country with low TB prevalence, where BCG vaccination is not routinely used. Among these subjects, 89 had active TB, 65 had LTBI, based on well-standardized TST reactions and 51 were negative controls. HBHA was significantly more sensitive than ESAT-6 and more specific than PPD for the detection of LTBI. PPD-based tests yielded 90.00% sensitivity and 70.00% specificity for the detection of LTBI, whereas the sensitivity and specificity for the ESAT-6-based tests were 40.74% and 90.91%, and those for the HBHA-based tests were 92.06% and 93.88%, respectively. The QuantiFERON-TB Gold In-Tube (QFT-IT) test applied on 20 LTBI subjects yielded 50% sensitivity. The HBHA IGRA was not influenced by prior BCG vaccination, and, in contrast to the QFT-IT test, remote (>2 years) infections were detected as well as recent (<2 years) infections by the HBHA-specific test. The use of ESAT-6- and CFP-10-based IGRAs may underestimate the incidence of LTBI, whereas the use of HBHA may combine the operational advantages of IGRAs with high sensitivity and specificity for latent infection.
    PLoS ONE 02/2007; 2(10):e926. DOI:10.1371/journal.pone.0000926 · 3.53 Impact Factor
  • PLoS ONE 01/2007; 2(10). DOI:10.1371/journal.pone.0000926.t002 · 3.53 Impact Factor
  • K Schepers, J P Van Vooren, T Simonart
    International Journal of Dermatology 09/2006; 45(8):994-5. DOI:10.1111/j.1365-4632.2006.02945.x · 1.23 Impact Factor
  • T. Simonart, K. Schepers, J. Van Vooren
    Annales de Dermatologie et de Vénéréologie 10/2005; 132:277-277. DOI:10.1016/S0151-9638(05)80067-5 · 0.67 Impact Factor

Publication Stats

232 Citations
106.85 Total Impact Points


  • 2007–2015
    • Université Libre de Bruxelles
      • Laboratory of Vaccinology and Mucosal Immunity] (LoVMI)
      Bruxelles, Brussels Capital, Belgium
  • 2006
    • University Hospital Brussels
      Bruxelles, Brussels Capital Region, Belgium