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Search Results: 1 - 10 of 372131 matches for " Bouke C de Jong "
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Mycobacterium africanum—Review of an Important Cause of Human Tuberculosis in West Africa
Bouke C. de Jong ,Martin Antonio,Sebastien Gagneux
PLOS Neglected Tropical Diseases , 2010, DOI: 10.1371/journal.pntd.0000744
Abstract: Mycobacterium africanum consists of two phylogenetically distinct lineages within the Mycobacterium tuberculosis complex, known as M. africanum West African 1 and M. africanum West African 2. These lineages are restricted to West Africa, where they cause up to half of human pulmonary tuberculosis. In this review we discuss the definition of M. africanum, describe the prevalence and restricted geographical distribution of M. africanum West African 1 and 2, review the occurrence of M. africanum in animals, and summarize the phenotypic differences described thus far between M. africanum and M. tuberculosis sensu stricto.
Supervised learning for the automated transcription of spacer classification from spoligotype films
David J Jeffries, Neil Abernethy, Bouke C de Jong
BMC Bioinformatics , 2009, DOI: 10.1186/1471-2105-10-248
Abstract: Features extracted from each of the 1849 spots on a spoligo film were classified using two supervised learning algorithms. A graphical user interface allows manual editing of the classification, before export to a database. The application was tested on ten films of differing quality and the results of the best classifier were compared to expert manual classification, giving a median correct classification rate of 98.1% (inter quartile range: 97.1% to 99.2%), with an automated processing time of less than 1 minute per film.The software implementation offers considerable time savings over manual processing whilst allowing expert editing of the automated classification. The automatic upload of the classification to a database reduces the chances of transcription errors.Genotyping of M. tuberculosis complex isolates has enhanced TB control and contact tracing while providing valuable insights on tuberculosis transmission and pathogenesis [1]. Recently, strain differences were found to affect clinical presentation [2], and unravelling of the genes responsible for these phenotypic differences might lead to the identification of drug- and vaccine targets.Spacer oligonucleotide typing (spoligotype) analysis is the most user-friendly and commonly applied genotyping tool for M. tuberculosis isolates worldwide. Global spoligotype databases include 'fingerprints' from thousands of M. tuberculosis complex isolates from diverse regions [3]. Based on hybridization of the direct repeat region of M. tuberculosis [4], spoligotype analysis generates reproducible binary patterns of 43 spacers, which can readily be shared electronically. This 43 binary spacer format can be transcribed as a 15-digit code [5], although no international standardization has been established. While spoligotype analysis lacks the resolution of the 'gold standard' genotyping method IS6110 restriction fragment length polymorphism (RFLP) [6], it has several advantages compared with this technique: Firstly, it r
The First Phylogeographic Population Structure and Analysis of Transmission Dynamics of M. africanum West African 1— Combining Molecular Data from Benin, Nigeria and Sierra Leone
Florian Gehre, Martin Antonio, Frank Fa?hun, Mathieu Odoun, Cecile Uwizeye, Pim de Rijk, Bouke C. de Jong, Dissou Affolabi
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0077000
Abstract: Mycobacterium africanum is an important cause of tuberculosis (TB) in West Africa. So far, two lineages called M. africanum West African 1 (MAF1) and M. africanum West African 2 (MAF2) have been defined. Although several molecular studies on MAF2 have been conducted to date, little is known about MAF1. As MAF1 is mainly present in countries around the Gulf of Guinea we aimed to estimate its prevalence in Cotonou, the biggest city in Benin. Between 2005–06 we collected strains in Cotonou/Benin and genotyped them using spoligo- and 12-loci-MIRU-VNTR-typing. Analyzing 194 isolates, we found that 31% and 6% were MAF1 and MAF2, respectively. Therefore Benin is one of the countries with the highest prevalence (37%) of M. africanum in general and MAF1 in particular. Moreover, we combined our data from Benin with publicly available genotyping information from Nigeria and Sierra Leone, and determined the phylogeographic population structure and genotypic clustering of MAF1. Within the MAF1 lineage, we identified an unexpected great genetic variability with the presence of at least 10 sub-lineages. Interestingly, 8 out of 10 of the discovered sub-lineages not only clustered genetically but also geographically. Besides showing a remarkable local restriction to certain regions in Benin and Nigeria, the sub-lineages differed dramatically in their capacity to transmit within the human host population. While identifying Benin as one of the countries with the highest overall prevalence of M. africanum, this study also contains the first detailed description of the transmission dynamics and phylogenetic composition of the MAF1 lineage.
Production of TNF-α, IL-12(p40) and IL-17 Can Discriminate between Active TB Disease and Latent Infection in a West African Cohort
Jayne S. Sutherland,Bouke C. de Jong,David J. Jeffries,Ifedayo M. Adetifa,Martin O. C. Ota
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0012365
Abstract: Mycobacterium tuberculosis (MTb) infects approximately 2 billion people world-wide resulting in almost 2 million deaths per year. Determining biomarkers that distinguish different stages of tuberculosis (TB) infection and disease will provide tools for more effective diagnosis and ultimately aid in the development of new vaccine candidates. The current diagnostic kits utilising production of IFN-γ in response to TB antigens can detect MTb infection but are unable to distinguish between infection and disease. The aim of this study was to assess if the use of a longer term assay and the analysis of multiple cytokines would enhance diagnosis of active TB in a TB-endemic population.
Relatively low primary drug resistant tuberculosis in southwestern Ethiopia
Gemeda Abebe, Ketema Abdissa, Alemseged Abdissa, Ludwig Apers, Mulualem Agonafir, Bouke C de-Jong, Robert Colebunders
BMC Research Notes , 2012, DOI: 10.1186/1756-0500-5-225
Abstract: A health institution based cross sectional study was conducted from November 2010 to September 2011. Any newly diagnosed smear positive TB patient 18?years and above was included in the study. Demographic and related data were collected by trained personnel using a pretested structured questionnaire. Mycobacterial drug susceptibility testing (DST) to the first line drugs isoniazid (INH), rifampicin (RIF), ethambutol (EMB) and streptomycin (STM) was performed on cultures using the indirect proportion method. M. tuberculosis complex (MTBC) was identified with the Capilia TB-Neo test.136 patients were enrolled in the study. Resistance to at least one drug was identified in 18.4%. The highest prevalence of resistance to any drug was identified against INH (13.2%) followed by STM (8.1%). There was no statistically significant difference in the proportion of any resistance by sex, age, HIV status and history of being imprisoned. The highest mono resistance was observed against INH (7.4%). Mono resistance to streptomycin was associated with HIV infection (crude OR 15.63, 95%CI: 1.31, 187). Multidrug-resistance TB (MDR-TB) was observed in two patients (1.5%).Resistance to at least one drug was 18.4% (INH-13.2% and STM-8.1%). STM resistance was associated with HIV positivity. There was relatively low prevalence of MDR-TB yet INH resistance was common around Jimma. The capacity of laboratories for TB culture and DST should be strengthened, in order to correctly manage TB patients and avoid amplification of drug resistance.TB is the world’s leading curable cause of infectious diseases mortality, with a disproportionate burden of the disease falling on low and middle income countries. In 2010, there were an estimated 8.8 million incident cases of TB globally. Most of the estimated number of cases occurred in Asia (59%) and Africa (26%) [1]. While most TB cases are in Asia, in Africa the incidence rates are highest, driven by high rates of HIV and malnutrition [2].One of the aim
Immunogenicity of antigens from the TbD1 region present in M. africanum and missing from "modern" M. tuberculosis: a cross- sectional study
Bouke C de Jong, Abdulrahman Hammond, Jacob K Otu, Martin Antonio, Richard A Adegbola, Martin O Ota
BMC Infectious Diseases , 2010, DOI: 10.1186/1471-2334-10-11
Abstract: We assessed the immunogenicity of the TbD1 region, present in M. africanum and absent from "modern" M. tuberculosis, in an ELISPOT assay using cells from confirmed M. africanum or M. tuberculosis infected TB patients without HIV infection in the Gambia.Antigens from the TbD1 region induced IFNγ responses in only 35% patients and did not discriminate between patients infected with M. africanum vs. M. tuberculosis, while PPD induced universally high responses.Further studies will need to assess other antigens unique to M. africanum that may induce discriminatory immune responses.An estimated third of the world's population is latently (asymptomatically) infected with M. tuberculosis, of whom 5-10% will progress to TB disease in their lifetime, with higher rates of progression in immune compromised people [1]. Latent infection can be diagnosed with the tuberculin skin test, or more recently with interferon gamma release assays using M. tuberculosis specific antigens ESAT-6 and CFP-10 [2]. These antigens are present in members of the M. tuberculosis complex, except for the vaccine strain M. bovis BCG [3], M. microti and the Dassie bacillus.Recent data suggest that M. africanum has a relatively large reservoir of latent infection that supports the 38% prevalence of active disease despite a lower rate of progression.Better characterization of the immune responses leading either to containment or progression of latent TB infection to disease by M. africanum or M. tuberculosis requires diagnosis of these organisms at the latent stage of infection. During latent TB infection, the bacterial load is estimated to be low, and the location of the persistent bacteria is unknown. Molecular genotyping methods rely on the isolation of bacterial DNA, which is currently not possible from patients with latent TB infection. Nevertheless, the persistent bacteria induce an immune response that can be assessed in the periphery [1].The TbD1 region is present in M. africanum but absent in "mo
Acquired Resistance of Mycobacterium tuberculosis to Bedaquiline
Koen Andries, Cristina Villellas, Nele Coeck, Kim Thys, Tom Gevers, Luc Vranckx, Nacer Lounis, Bouke C. de Jong, Anil Koul
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0102135
Abstract: Bedaquiline (BDQ), an ATP synthase inhibitor, is the first drug to be approved for treatment of multi-drug resistant tuberculosis in decades. In vitro resistance to BDQ was previously shown to be due to target-based mutations. Here we report that non-target based resistance to BDQ, and cross-resistance to clofazimine (CFZ), is due to mutations in Rv0678, a transcriptional repressor of the genes encoding the MmpS5-MmpL5 efflux pump. Efflux-based resistance was identified in paired isolates from patients treated with BDQ, as well as in mice, in which it was confirmed to decrease bactericidal efficacy. The efflux inhibitors verapamil and reserpine decreased the minimum inhibitory concentrations of BDQ and CFZ in vitro, but verapamil failed to increase the bactericidal effect of BDQ in mice and was unable to reverse efflux-based resistance in vivo. Cross-resistance between BDQ and CFZ may have important clinical implications.
Immune Reconstitution Inflammatory Syndrome and the Influence of T Regulatory Cells: A Cohort Study in the Gambia
Irfan Zaidi, Kevin Peterson, David Jeffries, Hilton Whittle, Thushan de Silva, Sarah Rowland-Jones, Assan Jaye, Bouke C. de Jong
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0039213
Abstract: Objective The factors associated with the development of immune reconstitution inflammatory syndrome in HIV patients commencing antiretroviral therapy have not been fully elucidated. Using a longitudinal study design, this study addressed whether alteration in the levels of T regulatory cells contributed to the development of IRIS in a West African cohort of HIV-1 and HIV-2 patients. Seventy-one HIV infected patients were prospectively recruited to the study and followed up for six months. The patients were categorized as IRIS or non-IRIS cases following published clinical guidelines. The levels of T regulatory cells were measured using flow cytometry at baseline and all follow-up visits. Baseline cytokine levels of IL-2, IL-6, IFN-γ, TNF-α, MIP-1β, IL-1, IL-12, IL-13, and IL-10 were measured in all patients. Results Twenty eight percent of patients (20/71) developed IRIS and were predominantly infected with HIV-1. Patients developing IRIS had lower nadir CD4 T cells at baseline (p = 0.03) and greater CD4 T cell reconstitution (p = 0.01) at six months post-ART. However, the development of IRIS was not influenced by the levels of T regulatory cells. Similarly, baseline cytokine levels did not predict the onset of IRIS. Conclusion The development of IRIS was not associated with differences in levels of T regulatory cells or baseline pro-inflammatory cytokines.
Deciphering the Growth Behaviour of Mycobacterium africanum
Florian Gehre ,Jacob Otu,Kathryn DeRiemer,Paola Florez de Sessions,Martin L. Hibberd,Wim Mulders,Tumani Corrah,Bouke C. de Jong,Martin Antonio
PLOS Neglected Tropical Diseases , 2013, DOI: 10.1371/journal.pntd.0002220
Abstract: Background Human tuberculosis (TB) in West Africa is not only caused by M. tuberculosis but also by bacteria of the two lineages of M. africanum. For instance, in The Gambia, 40% of TB is due to infections with M. africanum West African 2. This bacterial lineage is associated with HIV infection, reduced ESAT-6 immunogenicity and slower progression to active disease. Although these characteristics suggest an attenuated phenotype of M. africanum, no underlying mechanism has been described. From the first descriptions of M. africanum in the literature in 1969, the time to a positive culture of M. africanum on solid medium was known to be longer than the time to a positive culture of M. tuberculosis. However, the delayed growth of M. africanum, which may correlate with the less virulent phenotype in the human host, has not previously been studied in detail. Methodology/Principal Findings We compared the growth rates of M. tuberculosis and M. africanum isolates from The Gambia in two liquid culture systems. M. africanum grows significantly slower than M. tuberculosis, not only when grown directly from sputa, but also in growth experiments under defined laboratory conditions. We also sequenced four M. africanum isolates and compared their whole genomes with the published M. tuberculosis H37Rv genome. M. africanum strains have several non-synonymous SNPs or frameshift mutations in genes that were previously associated with growth-attenuation. M. africanum strains also have a higher mutation frequency in genes crucial for transport of sulphur, ions and lipids/fatty acids across the cell membrane into the bacterial cell. Surprisingly, 5 of 7 operons, recently described as essential for intracellular survival of H37Rv in the host macrophage, showed at least one non-synonymously mutated gene in M. africanum. Conclusions/Significance The altered growth behaviour of M. africanum might indicate a different survival strategy within host cells.
Factors associated with mortality in patients with drug-susceptible pulmonary tuberculosis
Payam Nahid, Leah G Jarlsberg, Irina Rudoy, Bouke C de Jong, Alon Unger, L Masae Kawamura, Dennis H Osmond, Philip C Hopewell, Charles L Daley
BMC Infectious Diseases , 2011, DOI: 10.1186/1471-2334-11-1
Abstract: Retrospective chart review of patients with drug-susceptible tuberculosis reported to the San Francisco Tuberculosis Control Program from 1990-2001.Of 565 patients meeting eligibility criteria, 37 (6.6%) died during the study period. Of 37 deaths, 12 (32.4%) had tuberculosis listed as a contributing factor. In multivariate analysis controlling for follow-up time, four characteristics were independently associated with mortality: HIV co-infection (HR = 2.57, p = 0.02), older age at tuberculosis diagnosis (HR = 1.52 per 10 years, p = 0.001); initial sputum smear positive for acid fast bacilli (HR = 3.07, p = 0.004); and experiencing an interruption in tuberculosis therapy (HR = 3.15, p = 0.002). The association between treatment interruption and risk of death was due to non-adherence during the intensive phase of treatment (HR = 3.20, p = 0.001). The median duration of treatment interruption did not differ significantly in either intensive or continuation phases between those who died and survived (23 versus 18 days, and 37 versus 29 days, respectively). No deaths were directly attributed to adverse drug reactions.In addition to advanced age, HIV and characteristics of advanced tuberculosis, experiencing an interruption in anti-tuberculosis therapy, primarily due to non-adherence, was also independently associated with increased risk of death. Improving adherence early during treatment for tuberculosis may both improve tuberculosis outcomes as well as decrease mortality.Tuberculosis is a leading cause of death worldwide. According to the World Health Organization (WHO) over 1.7 million people with tuberculosis died in 2008 [1]. Advanced age, male gender, delays in diagnosis and treatment, drug resistance, and co-morbid conditions including HIV co-infection, diabetes, renal disease and COPD, have been associated with increased risk of death in patients with active tuberculosis [2-8]. A substantial proportion of deaths occur during tuberculosis treatment despite patient
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