PubMed Health⌕ Search

Biomedical subjects

D van Soolingen

Publications and source records attributed to D van Soolingen.

At least 19 recordsLinked to original sources

Public health impact of isoniazid-resistant Mycobacterium tuberculosis strains with a mutation at amino-acid position 315 of katG: a decade of experience in The Netherlands.

A previous limited study demonstrated that Mycobacterium tuberculosis isolates with a mutation at amino-acid position 315 of katG (Delta315) exhibited high-level resistance to isoniazid and were more frequently resistant to streptomycin. In the present study, isoniazid-resistant M. tuberculosis isolates from 8,332 patients in The Netherlands (1993-2002) were screened for the Delta315 mutation. Isoniazid resistance was found in 592 (7%) isolates, of which 323 (55%) carried Delta315. IS6110 restriction fragment length polymorphism analysis showed that Delta315 isolates occurred in clusters, suggesting recent transmission, at the same frequency as isoniazid-susceptible isolates. In contrast, other isoniazid-resistant isolates clustered significantly less frequently. Delta315 isolates were high-level isoniazid-resistant, streptomycin-resistant and multidrug-resistant significantly more often, and may have a greater impact on public health, than other isoniazid-resistant isolates.

Adolescent↗

[An outbreak of multiresistant tuberculosis from Eastern Europe in the Netherlands].

Infectious multiresistant pulmonary tuberculosis was diagnosed in a 24-year-old woman from an Eastern European country who resided in the Netherlands illegally. Her chest X-ray showed extensive cavitating lesions in both lungs. The patient was infectious for a long time and contact investigation revealed 2 other cases of multiresistant tuberculosis, her boyfriend aged 39 and his father, aged 58 years. Transmission from the index case was confirmed by DNA fingerprinting. Seven contacts had a latent tuberculosis infection. All 3 tuberculosis patients were successfully treated, while a number of the infected contacts received preventive treatment. Multiresistant tuberculosis is on the rise in Eastern Europe. It is a serious disease with a high mortality rate despite treatment and has considerable social implications. This outbreak emphasises the necessity of maintaining an efficient tuberculosis control network in low incidence countries, such as the Netherlands. This is the first time an outbreak of multiresistant tuberculosis of this magnitude is described in the Netherlands.

Adult↗

Efficient differentiation of Mycobacterium tuberculosis strains of the W-Beijing family from Russia using highly polymorphic VNTR loci.

The W-Beijing family is a widespread Mycobacterium tuberculosis clonal lineage that frequently causes epidemic outbreaks. This family is genetically homogeneous and conserved, so ETR-VNTR (exact tandem repeat-variable number of tandem repeats) typing is insufficient for strain differentiation, due to a common ETR-A to E profile (42435). This leads to the false clustering in molecular epidemiological studies, especially in the regions of predominance of the W-Beijing family. In this study, we searched for VNTR loci with a high evolutionary rate of polymorphism in the W-Beijing genome. Here we further evaluated VNTR typing on a set of 99 Mycobacterium tuberculosis clinical isolates and reference strains. These isolates were characterized and classified into several genotype families based on three ETR loci (A, C, E) and eight additional loci [previously described as QUB (Queen's University Belfast) or MIRU (Mycobacterial Interspersed Repetitive Units) or Mtubs]. Ninety-nine strains were divided into 74 VNTR-types, 51 isolates of the W-Beijing family identified by IS6110 RFLP-typing (the restriction fragment length polymorphism-typing) and/or spoligotyping were subdivided into 30 VNTR-types. HGDI (the Hunter-Gaston discriminatory index) for all studied loci was close to that of IS6110 RFLP typing, a "gold standard" method for subtyping M. tuberculosis complex strains. The QUB 26 and QUB 18 loci located in the PPE genes were highly polymorphic and more discriminative than other loci (HGDI is 0.8). Statistically significant increase of tandem repeats number in loci ETR-A, -E, QUB 26, QUB 18, QUB 11B, Mtub21 was revealed in the W-Beijing group compared to genetically divergent non-W-Beijing strains. Thirty-six isolates were subjected to IS6110 RFLP typing. The congruence between results of the IS6110 RFLP typing and 11-loci VNTR typing was estimated on 23 isolates of the W-Beijing family. These isolates were subdivided into 9 IS6110-RFLP types and 13 VNTR types. The poor profiles correlation (0.767) reflects the differences in the rate and type of evolution between genome regions targeted by IS6110-RFLP and VNTR typing. VNTR typing in proposed format is powerful tool for discrimination of M. tuberculosis strains with different level of genetic relationship.

Bacterial Typing Techniques↗

Molecular epidemiology of Mycobacterium tuberculosis in China: a nationwide random survey in 2000.

OBJECTIVE: To determine the contribution of the Mycobacterium tuberculosis (TB) Beijing genotype to the population structure of M. tuberculosis complex in China. DESIGN: Genotypes of 441 mycobacterial isolates were determined by spoligotyping and IS6110 restriction fragment length polymorphism (RFLP). The isolates were from a nationwide random survey for the epidemiology of TB conducted in 2000, and the drug susceptibility patterns and epidemiological data were known. RESULT: A total of 408 samples contained M. tuberculosis as determined by spoligotyping. Of the M. tuberculosis strains, 64.9% (265/408) were of the Beijing genotype. Using the chi-squared test, no statistically significant differences were observed in the proportion of Beijing genotype TB in patients of different sex, age or living in different areas of the country, but a significant difference was observed with multidrug-resistant (MDR) TB: 77.8% (42/ 54) of MDR isolates were of the Beijing genotype vs. 60.2% (213/354) of the drug-susceptible isolates. In the multivariate logistic regression model, the Beijing genotype was significantly associated with region and not with MDR. CONCLUSION: The M. tuberculosis Beijing genotype has prevailed in China for at least five decades and is associated with region.

Adolescent↗

Analysis of genetic polymorphisms affecting the four phospholipase C (plc) genes in Mycobacterium tuberculosis complex clinical isolates.

The Mycobacterium tuberculosis genome contains four highly related genes which present significant similarity to Pseudomonas aeruginosa genes encoding phospholipase C enzymes. Three of these genes, plcA, plcB and plcC, are organized in tandem (locus plcABC). The fourth gene, plcD, is located in a different region. This study investigates variations in plcABC and plcD genes in clinical isolates of M. tuberculosis, Mycobacterium africanum and 'Mycobacterium canettii'. Genetic polymorphisms were examined by PCR, Southern blot hybridization, sequence analysis and RT-PCR. Seven M. tuberculosis isolates contain insertions of IS6110 elements within plcA, plcC or plcD. In 19 of 25 M. tuberculosis isolates examined, genomic deletions were identified, resulting in loss of parts of genes or complete genes from the plcABC and/or plcD loci. Partial plcD deletion was observed in one M. africanum isolate. In each case, deletions were associated with the presence of a copy of the IS6110 element and in all occurrences IS6110 was transposed in the same orientation. A mechanism of deletion resulting from homologous recombination of two copies of IS6110 was recognized in a group of genetically related M. tuberculosis isolates. Five M. tuberculosis isolates presented major polymorphisms in the plcABC and plcD regions, along with loss of expression competence that affected all four plc genes. Phospholipase C is a well-known bacterial virulence factor. The precise role of phospholipase C in the pathogenicity of M. tuberculosis is unknown, but considering the potential importance that the plc genes may have in the virulence of the tubercle bacillus, the study of isolates cultured from patients with active tuberculosis bearing genetic variations affecting these genes may provide insights into the significance of phospholipase C enzymes for tuberculosis pathogenicity.

Bacterial Proteins↗

Correlation of virulence, lung pathology, bacterial load and delayed type hypersensitivity responses after infection with different Mycobacterium tuberculosis genotypes in a BALB/c mouse model.

One of the most intriguing aspects of tuberculosis is that the outcome of an infection with M. tuberculosis (TB) is highly variable between individuals. The possibility of differences in virulence between M. tuberculosis strains or genotypes has only recently been studied. There is evidence of multifactorial genetic predisposition in humans that influences the susceptibility to tuberculosis. A better understanding of differences in virulence between M. tuberculosis genotypes could be important with regard to the efforts at TB control and the development of improved antituberculosis vaccines. Survival, lung pathology, bacterial load and delayed type hypersensitivity (DTH) responses of BALB/c mice after intratracheal infection with any of 19 different M. tuberculosis complex strains of 11 major genotype families were studied. The results indicate that among genetically different M. tuberculosis strains a very broad response was present with respect to virulence, pathology, bacterial load and DTH. 'Low'-responders were the H37Rv, Canetti, Beijing-1 strains, while Beijing-2,3, Africa-2 and Somalia-2 strains were 'high'-responders. A severe pathological response correlates with a high mortality and a high CFU counts in lungs, but poorly with the degree of the DTH response.

Animals↗

Pneumonia caused by Mycobacterium kansasii in a series of patients without recognised immune defect.

The clinical and epidemiological characteristics of 17 patients diagnosed with Mycobacterium kansasii pneumonia within a limited geographical region over a period of 10 years are described. An in-depth evaluation of the innate and adaptive immune systems was performed for five available patients. A comparison was made of the genetic fingerprint patterns of the isolates obtained by restriction fragment length polymorphism (RFLP) analysis, with the major polymorphic tandem repeat (MPTR) as a probe. Predisposing factors consisted of smoking, airway abnormalities, substance abuse, diabetes or poor general condition, but in two patients no risk factor was identified. In the five patients tested, no abnormalities or deficiencies were detected in the innate or adaptive type-1 immunity. All M. kansasii isolates had identical MPTR RFLP patterns, although no epidemiological connection could be established, and these were identical to those of clinical isolates from Australian patients. These data do not support the theory that defects in the innate or adaptive type-1 immunity have a role in the pathogenesis of invasive M. kansasii infections. The identical fingerprint patterns of the isolates suggested the existence of a virulent strain of M. kansasii.

Adult↗

Molecular characteristics and global spread of Mycobacterium tuberculosis with a western cape F11 genotype.

In order to fully understand the global tuberculosis (TB) epidemic it is important to investigate the population structure and dissemination of the causative agent that drives the epidemic. Mycobacterium tuberculosis strain family 11 (F11) genotype isolates (found in 21.4% of all infected patients) are at least as successful as the Beijing genotype family isolates (16.5%) in contributing to the TB problem in some Western Cape communities of South Africa. This study describes key molecular characteristics that define the F11 genotype. A data-mining approach coupled with additional molecular analysis showed that members of F11 can easily and uniquely be identified by PCR-based techniques such as spoligotyping and dot blot screening for a specific rrs491 polymorphism. Isolates of F11 not only are a major contributor to the TB epidemic in South Africa but also are present in four different continents and at least 25 other countries in the world. Careful study of dominant compared to rare strains should provide clues to their success and possibly provide new ideas for combating TB.

Genotype↗

Drug susceptibility of Mycobacterium tuberculosis in HIV-infected and -uninfected Ethiopians and its impact on outcome after 24 months of follow-up.

From a prospective cohort study on tuberculosis/human immunodeficiency virus (TB/HIV) interaction in Addis Ababa, Ethiopia, drug susceptibility results were available for 94 TB patients (46% HIV-infected). Resistance to one or more drug(s) was detected in 21 (22.3%) and multidrug resistance in five (5.3%) patients. Occurrence of resistance was not related to HIV status or outcome after 24 months of follow-up. However, among HIV-infected TB patients who died during follow-up, survival time in those with a resistant Mycobacterium tuberculosis strain was significantly shorter compared to those with a sensitive strain (6 vs. 13 months). Early detection of drug resistance and timely treatment change can therefore have a positive impact on survival in HIV-infected TB patients.

Adult↗

[Research into new methods for diagnosing, treating and preventing tuberculosis].

Tuberculosis control requires improved diagnostics, drugs, and vaccines. Their development is facilitated by progress in immunology, molecular biology, and genomics. In addition to sputum smear and culture, amplification techniques can already be used to diagnose tuberculosis and antigen-detection tests for this purpose are being developed. Molecular typing and DNA microarrays provide new insights in the natural history and transmission of tuberculosis. In addition to established drugs such as rifampicin, isoniazid, pyrazinamide, and ethambutol, a limited number of new drugs have been discovered such as rifampicin derivates and fluorochinolones. Improved screening techniques and insights from genomics may lead to new drugs being discovered. Factors hampering the development and evaluation of new vaccines include problems with extrapolation from animal models, incomplete natural immunity, and limited knowledge about protective immunity. However, new candidate vaccines are being developed and will be tested on humans in the near future.

Animals↗

A marked difference in pathogenesis and immune response induced by different Mycobacterium tuberculosis genotypes.

In the last decade, an unprecedented genetic diversity has been disclosed among Mycobacterium tuberculosis strains found worldwide. However, well-conserved genotypes seem to prevail in areas with high incidence of tuberculosis. As this may be related to selective advantages, such as advanced mechanisms to circumvent [M. bovis Bacille Calmette-Guerin (BCG)-induced] host defence mechanisms, we investigated the influence of strain diversity on the course of experimental disease. Twelve M. tuberculosis strains, representing four major genotype families found worldwide today, and the laboratory strain H37Rv were each used to infect BALB/c mice by direct intratracheal injection. Compared with H37Rv, infections with Beijng strains were characterized by extensive pneumonia, early but ephemeral tumour necrosis factor-alpha (TNF-alpha) and inducible isoform of nitric oxide synthetase (iNOS) expression, and significantly higher earlier mortality. Conversely, Canetti strains induced limited pneumonia, sustained TNF-alpha and iNOS expression in lungs, and almost 100% survival. Strains of the Somali and the Haarlem genotype families displayed less homogeneous, intermediate rates of survival. Previous BCG vaccination protected less effectively against infection with Beijing strains than against the H37Rv strain. In conclusion, genetically different M. tuberculosis strains evoked markedly different immunopathological events. Bacteria with the Beijing genotype, highly prevalent in Asia and the former USSR, elicited a non-protective immune response in mice and were the most virulent. Future immunological research, particularly on candidate vaccines, should include a broad spectrum of M. tuberculosis genotypes rather than a few laboratory strains.

Animals↗

Exogenous re-infection as a cause of recurrent tuberculosis in a low-incidence area.

SETTING: Surveillance data from the National Tuberculosis Register for the period 1993-1997 complemented with DNA fingerprinting results of Mycobacterium tuberculosis isolates. OBJECTIVE: To estimate the proportion of disease attributable to recent re-infection among Dutch tuberculosis patients with reported tuberculosis infection or disease before 1981. DESIGN: Data from 1,547 Dutch patients diagnosed between 1994 and 1997 in the Netherlands were studied. Cases with reported tuberculosis infection or disease before 1981 were attributed to reactivation if their M. tuberculosis isolate was unclustered based on DNA fingerprinting or if they were the first case in a cluster, and to re-infection if they were clustered, but not as the first case. RESULTS: In total, 183 Dutch tuberculosis patients (12%) had reported tuberculosis infection or disease before 1981. Tuberculosis in 29 of these patients (16%) was attributed to recent re-infection. CONCLUSION: In this setting with a low tuberculosis incidence, approximately one in six new disease episodes among patients with previous tuberculosis infection or disease may be attributable to recent re-infection.

Adolescent↗

Drug resistance among failure and relapse cases of tuberculosis: is the standard re-treatment regimen adequate?

OBJECTIVE: To determine acquired drug resistance among failure and relapse cases after treatment of new smear-positive tuberculosis. METHODS: A cohort of 2901 patients with new smear-positive tuberculosis was enrolled in Vietnam. Sputum samples were stored at enrolment. Upon failure or relapse, another sputum sample was collected. Both were cultured and underwent drug susceptibility testing and restriction fragment length polymorphism (RFLP) typing. RESULTS: Of 40 failure cases, 17 had multidrug resistance (MDR) at enrolment. At failure, 15 of the 23 (65%) patients without primary MDR had acquired MDR. Of 39 relapse cases and 143 controls, none had primary MDR. CONCLUSION: Primary drug resistance was a strong risk factor for failure and relapse and for acquiring further resistance. As 80% of failure cases had MDR, the standard re-treatment regimen appears inadequate for failure cases in this control programme with a very high cure rate among new cases.

Adolescent↗

Tuberculosis contact investigation and DNA fingerprint surveillance in The Netherlands: 6 years' experience with nation-wide cluster feedback and cluster monitoring.

SETTING: The Netherlands, 1995-2000. OBJECTIVES: To describe the contribution of 6 years of nationwide DNA fingerprint surveillance to tuberculosis control in general and to conventional contact investigations in particular. DESIGN: All Mycobacterium tuberculosis cultures are subjected to standardised IS6110-based RFLP typing, and clustered cases are systematically reported to the regional TB services involved (cluster feedback). Standardised questionnaires are used to collect information on contact investigations and epidemiological links (epi links) at regional level. Revision of the questionnaires for the period 1997-2000 allows comparison of epi linking before and after cluster feedback. RESULTS: Among 2206 clustered cases, 462 (21%) epi links were expected before the RFLP result, whereas an additional 540 (24%) epi links were established after cluster feedback. Epi links based on documented exposure increased by 35%, from 357 to 550 (P < 0.001). Only 1% of contact investigations were extended, however, and relatively few additional persons with active or latent tuberculosis were diagnosed. Reasons for the limited impact on contact investigation outcome were 1) contact took place 1-7 years previously (51%), 2) documented contact involved a subsequent case in the cluster (21%), 3) casual contact (15.5%) and 4) different region (9%). Five per cent of epi links established by contact investigation were contradicted by RFLP data. Epi links were more frequently documented in Dutch (41%) than non-Dutch cases (19%, OR 3.0; 95%CI 1.41-1.91). Cluster monitoring permitted: 1) identification of transmission chains that could not be detected by contact investigations, 2) development and evaluation of targeted interventions, and 3) identification of professional failures and poor programme performance. CONCLUSIONS: RFLP surveillance forms the bridge between conventional contact investigation and other forms of targeted active case finding. Combining both complementary strategies in a comprehensive approach to systematic outbreak monitoring and management allows countries in the elimination phase of the disease to better target and evaluate TB control interventions.

Cluster Analysis↗

A new evolutionary scenario for the Mycobacterium tuberculosis complex.

The distribution of 20 variable regions resulting from insertion-deletion events in the genomes of the tubercle bacilli has been evaluated in a total of 100 strains of Mycobacterium tuberculosis, Mycobacterium africanum, Mycobacterium canettii, Mycobacterium microti, and Mycobacterium bovis. This approach showed that the majority of these polymorphisms did not occur independently in the different strains of the M. tuberculosis complex but, rather, resulted from ancient, irreversible genetic events in common progenitor strains. Based on the presence or absence of an M. tuberculosis specific deletion (TbD1), M. tuberculosis strains can be divided into ancestral and "modern" strains, the latter comprising representatives of major epidemics like the Beijing, Haarlem, and African M. tuberculosis clusters. Furthermore, successive loss of DNA, reflected by region of difference 9 and other subsequent deletions, was identified for an evolutionary lineage represented by M. africanum, M. microti, and M. bovis that diverged from the progenitor of the present M. tuberculosis strains before TbD1 occurred. These findings contradict the often-presented hypothesis that M. tuberculosis, the etiological agent of human tuberculosis evolved from M. bovis, the agent of bovine disease. M. canettii and ancestral M. tuberculosis strains lack none of these deleted regions, and, therefore, seem to be direct descendants of tubercle bacilli that existed before the M. africanum-->M. bovis lineage separated from the M. tuberculosis lineage. This observation suggests that the common ancestor of the tubercle bacilli resembled M. tuberculosis or M. canettii and could well have been a human pathogen already.

Base Sequence↗

Predominace of a novel Mycobacterium tuberculosis genotype in the Delhi region of India.

Using IS 6110 -restriction fragment length polymorphism (RFLP) and spoligotyping, genetic variations of 83 Mycobacterium tuberculosis strains isolated from tuberculosis patients from two wards in a hospital in Delhi and a rural chest clinic near Delhi were analysed. The vast majority of the isolates (75%) were closely related and this novel genogroup was designated the 'Delhi type'. Both drug-sensitive and drug-resistant strains were found among strains of this genogroup. A minority of the strains harboured a single IS 6110 copy and only one strain belonged to the Beijing genotype, a genotype that is predominant in other parts of Asia. A comparison of the RFLP and spoligotype with existing data suggests that the predominance of Delhi genogroup is geographically limited to the Indian subcontinent and perhaps to specific regions in India. Despite the high prevalence of the M. tuberculosis strains of the Delhi type, the strains could easily be discriminated due to polymorphisms in the IS 6110 patterns. Future studies may disclose the genetic characteristics of strains belonging to the Delhi genotype, analogous to the recently observed virulence among the Beijing genogroup.

Adolescent↗

Improvement of differentiation and interpretability of spoligotyping for Mycobacterium tuberculosis complex isolates by introduction of new spacer oligonucleotides.

The direct repeat (DR) region in Mycobacterium tuberculosis complex strains is composed of multiple well-conserved 36-bp DRs interspersed with nonrepetitive DNA spacer sequences of similar size. Clinical isolates show extensive polymorphism in this DR region, and this has led to the development of a 43-spacer reversed line blot methodology: spoligotyping. Although this method has contributed significantly to the molecular epidemiology of tuberculosis in the last decade, the discriminatory power and the readability of this method were not found to be optimal. In order to improve the discriminatory power, the usefulness of 43 redesigned oligonucleotides and the usefulness of 51 new spacer oligonucleotides were evaluated. For 314 M. tuberculosis complex strains isolated in the central part of The Netherlands over a 5-year period, 264 different IS6110 RFLP types could be distinguished, and 160 different spoligotype patterns were identified by traditional spoligotyping. After the introduction of 51 new spacer oligonucleotides, 14 additional spoligotypes were recognized. This enabled us to split 11 clusters of isolates identified by the traditional spoligotyping. Furthermore, on the basis of the new spacer oligonucleotides a dichotomy was found among the Beijing genotype isolates. Among 76 Mycobacterium bovis strains, 20 patterns were found by traditional spoligotyping and 30 patterns were found by novel probe spoligotyping, respectively. Nine M. bovis subsp. caprae isolates yielded six patterns by traditional spoligotyping and eight patterns by novel probe spoligotyping. A part of the redesigned oligonucleotides slightly improved the reading of spoligotype patterns. The reproducibility of spoligotyping, based on internal control probes, invariably yielded a high score; only 4 (1%) of the 314 patient isolates gave discrepant results. Analysis of a set of 31 duplicate M. tuberculosis complex strains demonstrated a 10% error rate for the identification of blinded duplicate samples. In a redundancy analysis, 40 essential spacer oligonucleotides of the 94-spacer sequences were selected, yielding the same number of spoligotype patterns. We propose to leave the traditional commercialized first-generation membrane for spoligotyping unchanged for current applications and to introduce a second-generation spoligotyping membrane whenever extended discrimination is required, e.g., for low-copy-number IS6110 strains or for phylogenetic studies of Beijing genotype strains.

Animals↗