PubMed Health⌕ Search

Biomedical subjects

F Portaels

Publications and source records attributed to F Portaels.

At least 19 recordsLinked to original sources

The local immune response in ulcerative lesions of Buruli disease.

Buruli disease (BU) is a progressive necrotic and ulcerative disease of the skin and subcutaneous tissue caused by Mycobacterium ulcerans. BU is considered the third most common mycobacterial disease after tuberculosis and leprosy. Three clinical stages of the cutaneous lesions have been described in BU: pre-ulcerative, ulcerative and healed lesions. In this study we used immunohistochemistry and automated morphometry to determine the percentage of macrophages and of CD4/CD8 lymphocytes and their expression of interferon (IFN)-gamma, interleukin (IL)-10, tumour necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta. Expression of these cytokines was correlated with the inflammatory response evaluated by histopathology. All the studied BU ulcerative cases showed extensive necrosis and chronic inflammation. The most important feature was the presence or absence of granulomas co-existing with a mixed pro-inflammatory/anti-inflammatory cytokine balance. When granulomas were present significantly higher expression of IFN-gamma was seen, whereas in ulcerative lesions without granulomas there was increased expression of IL-10 and significantly higher bacillary counts. These features correlated with the chronicity of the lesions; longer-lasting lesions showed granulomas. Thus, granulomas were absent from relatively early ulcerative lesions, which contained more bacilli and little IFN-gamma, suggesting that at this stage of the disease strong suppression of the protective cellular immune response facilitates proliferation of bacilli.

Adolescent↗

Evaluation of a rapid culture method for tuberculosis diagnosis: a Latin American multi-center study.

SETTINGS: Tuberculosis (TB) diagnostic laboratories in Latin America. OBJECTIVES: Evaluation of thin-layer agar (TLA) compared to Löwenstein-Jensen (LJ) culture for the diagnosis of TB. DESIGN: Phase II prospective study in six laboratories. Samples included sputum and extra-pulmonary specimens from patients with a clinical diagnosis of TB. Respiratory samples were decontaminated using NaOH/ NALC; all samples were centrifuged, stained with Ziehl-Neelsen for acid-fast bacilli (AFB), cultured on LJ and TLA and identified according to recommended procedures. Sensitivity and likelihood ratios (LR), growth detection time and contamination rate were calculated for both media. RESULTS: A total of 1118 clinical specimens were studied. Cultures detected Mycobacterium tuberculosis in all AFB-positive samples, whereas for AFB-negative specimens LJ detected 3.2% and TLA 4.4%. Sensitivity was 92.6% (95%CI 87.9-95.9) and 84.7% (95%CI 78.8-89.0) for TLA and LJ, respectively. Positive and negative LRs were similar. Contamination was 5.1% for TLA and 3.0% for LJ. Median time to detection of a positive culture was 11.5 days (95%CI 9.3-15.0) for TLA and 30.5 days (95%CI 26.9-39.0) for LJ (P < 0.0001). CONCLUSION: Difference in the characteristics of the participating laboratories, the disease prevalence and the number and type of specimens processed did not affect the overall performance of TLA as compared to LJ, supporting the robustness of the method and its feasibility in different laboratory settings.

Agar↗

Evaluation of the resazurin microtiter assay for rapid detection of ofloxacin resistance in M. tuberculosis.

OBJECTIVE: To evaluate the performance of the colorimetric resazurin microtiter assay (REMA) method for the detection of ofloxacin resistance. METHODS: A panel of 120 multidrug-resistant Mycobacterium tuberculosis strains was tested blindly by the REMA method and compared with the results obtained using the BACTEC 460 method. RESULT: A very good correlation was observed between the two methods. CONCLUSION: The REMA method is simple, rapid and can be an inexpensive alternative procedure for the rapid detection of anti-tuberculosis drug resistance in laboratories with limited resources.

Anti-Bacterial Agents↗

[Distribution of Mycobacterium ulcerans (Buruli ulcer) in the district of Lalo in Benin].

This study aimed to determine the distribution of Buruli ulcer (BU) in Lalo, one of the endemic districts of the Couffo department in Bénin. A total of 752 BU patients were detected in this district with 160 active and 592 inactive cases. The overall prevalence of BU in this district is 86.6 per 10,000 inhabitants, varying from 0 to 249/10,000 between sub-districts. At village level the prevalence varies between 0 and 561 cases per 10,000 inhabitants. Our findings confirm the large variation of distribution of the disease at the village level in endemic area. Children under 15 years are frequently affected. We also found a significant association between age and location of Buruli lesions. Further epidemiological and environmental studies are needed to identify the reasons for the extraordinary variation in BU distribution between villages from the same sub-district, and to confirm if it is associated with temporal variations.

Adolescent↗

Multicenter study of MTT and resazurin assays for testing susceptibility to first-line anti-tuberculosis drugs.

OBJECTIVE: A multicentre evaluation was performed to assess two rapid low-cost methods, MTT (3-[4.5-dimethylthiazol-2-yl]-2.5-diphenyltetrazolium bromide) and resazurin assays, for testing the susceptibility of Mycobacterium tuberculosis to the first-line anti-tuberculosis drugs rifampicin (RMP), isoniazid (INH), ethambutol (EMB) and streptomycin (SM). METHODS: Thirty coded M. tuberculosis strains were sent to seven laboratories located in Latin America, representing six countries. Each site performed the colorimetric assays, MTT and resazurin, blind for the first-line drugs RMP, INH, EMB and SM. The minimum inhibitory concentration results obtained were compared to the conventional proportion method on Lowenstein-Jensen medium. RESULTS: After establishing the breakpoint concentrations, excellent results were obtained for RMP, INH and EMB, with levels of specificity and sensitivity of between 96% and 99%. CONCLUSION: MTT and resazurin assays are promising, accessible new alternative methods for middle- and low-resource countries that need low-cost methods to perform rapid susceptibility testing of M. tuberculosis to key anti-tuberculosis drugs.

Antitubercular Agents↗

Mycobacterium ulcerans disease: role of age and gender in incidence and morbidity.

During the 5-year period, 1997-2001, 1700 patients with a clinical diagnosis of Mycobacterium ulcerans disease [Buruli ulcer (BU)] were treated at the Centre Sanitaire et Nutritionnel Gbemoten, Zagnanado, Benin. The patients lived in the four regions of southern Benin: Atlantique, Mono, Oueme and Zou, with the largest number coming from the Zou Region where the centre is located. The median age of BU patients was 15 years (q1=7, q3=30). Lower limbs are involved 3.2 times more frequently than upper limbs in older patients and younger patients have the highest prevalence of multiple lesions. The latter are frequently associated with bone lesions. Specific detection rates for age and gender showed a distribution with maximum peaks in the 10-14 years group and among adults between 75 and 79 years. Over 59 years, males are more at risk of developing M. ulcerans disease than females. Children under 15 years represent the largest part of the BU disease burden and of the general population. The highest detection rates (per 100,000 population) were in the 75-79-year-old patients. The most likely explanation of this was reactivation of disease from a latent infection of M. ulcerans. Educational programmes should target especially these two groups of population at risk.

Adolescent↗

Mycobacterium bovis BCG vaccination as prophylaxis against Mycobacterium ulcerans osteomyelitis in Buruli ulcer disease.

Mycobacterium ulcerans disease, or Buruli ulcer (BU), causes significant morbidity in West Africa. Clinically, the disease presents in the skin as either nonulcerative or ulcerative forms and often invades bones either subjacent to the skin lesion (contiguous osteomyelitis) or remote from the skin lesion (metastatic osteomyelitis). Osteomyelitis represents a severe form of the disease that often requires numerous surgical interventions, even amputations. Surgery is accepted as the present definitive treatment for BU. In the absence of an effective drug treatment, the need for the development of preventive and control strategies becomes paramount. No specific vaccine, however, is presently available for BU. Of 372 consecutive patients in Benin presenting with BU (confirmed by microbiological and histopathological analyses) whose Mycobacterium bovis BCG scar statuses were known, 196 children (<15 years old) and 108 adults had neonatal BCG vaccination scars. Of 196 children with BCG scars, 17 (8.7%) had osteomyelitis, while 7 of 28 children without BCG scars (25.0%) had osteomyelitis. Of 108 adults with BCG scars, 17 (15.7%) had osteomyelitis, while 14 of 40 adults without BCG scars (35.0%) had osteomyelitis. Our results show that effective BCG vaccination at birth provides significant protection against the development of M. ulcerans osteomyelitis in children and adults. Therefore, health authorities should give attention to the enhancement of neonatal BCG vaccination coverage in all countries of Africa where BU is endemic. Protection against severe forms of BU and childhood tuberculosis would likewise be improved by this intervention.

Adolescent↗

Drug resistance monitoring: combined rates may be the best indicator of programme performance.

SETTING: Greater Mymensingh District, Bangladesh. OBJECTIVES: To determine changes in prevalence of drug resistance of Mycobacterium tuberculosis under DOTS. DESIGN: Drug susceptibility testing of systematic samples of M. tuberculosis isolated from all sputum smear-positive cases newly registered in sentinel centres during 1995 and 2001. Continuous monitoring of retreatment registrations and resistance of strains from relapse and failure cases. RESULTS: Of 942 strains from the new cases in 2001, 10.8% showed resistance to any drug, 6.2% to isoniazid, 0.4% to rifampicin (all of them multidrug-resistant, MDR), 7.1% to streptomycin, and 1.0% to ethambutol. Corresponding rates for 99 strains from previously treated cases were 32%, 20%, 3%, 20% and 2%, respectively. Although most rates of resistance had decreased since 1995, increased streptomycin resistance was the only significant change when new and previously treated cases were considered separately. However, combined resistance for any drug, isoniazid, rifampicin and MDR had decreased significantly. CONCLUSION: As suggested by monitoring of resistance in failure and relapse cases and by routine programme reports, drug resistance had decreased. Combined resistance demonstrated changes between periodic surveys better than its subgroups, and may be a more reliable and comprehensive indicator. However, continuous monitoring of the pool of resistant retreatment cases is a more efficient strategy.

Antitubercular Agents↗

Results of a standardised regimen for multidrug-resistant tuberculosis in Bangladesh.

SETTING: Individualised regimens based on drug susceptibility test results, generally used to treat multidrug-resistant tuberculosis (MDR-TB), require often unavailable expertise and resources. OBJECTIVE: To evaluate a standardised regimen based on the susceptibility profiles of locally prevalent MDR-TB strains. DESIGN: The activities of a successful DOTS programme in Bangladesh were complemented by offering treatment with a standardised 21-month regimen to patients with laboratory-confirmed MDR-TB disease. The regimen contained kanamycin, ofloxacin, prothionamide, pyrazinamide, ethambutol, isoniazid and clofazimine. Clinical and bacteriological progress was monitored quarterly until treatment completion, then 6 monthly for 2 years. RESULTS: The status at the end of treatment of this cohort of 58 documented MDR-TB patients was as follows: eight (14%) deaths, seven (12%) defaults, three (5%) failures and 40 (69%) cures. One bacteriologically-confirmed relapse was recognised. Frequent and sometimes serious side effects proved to be the main problem, suggesting the need for a better tolerated but equally effective regimen. CONCLUSION: A standardised approach may provide a reasonable alternative to individualised treatment of MDR-TB in resource-poor settings. However, DOTS-plus programmes in resource-poor settings may confront significant difficulties in the enrolment, diagnosis and management of MDR-TB patients.

Adolescent↗

Social research as an intervention tool in tuberculosis control.

Our multidisciplinary project on TB control in the Free State, South Africa, is targeting two dimensions for intervention: firstly, patients, to facilitate compliance and improve quality of care; secondly, the health care system, to identify weaknesses that require remedying and best practices to promote better TB control. This communication illustrates how social scientists can contribute towards the implementation of interventions related to their research, thus influencing TB policy, programme planning and practice more directly.

Health Policy↗

[Traditional treatment for Buruli ulcer in Benin].

The purpose of this transversve qualitative study on traditional treatment for Buruli ulcer in Benin was to track the treatment itinerary of patients, the main phases of traditional treatment, cost and efficacy of such treatment, and the knowledge and skills of traditional practitioners. A total of 20 traditional practitioners, 35 patients treated by traditional therapy, and 35 patients treated by surgery were included. Findings showed that both traditional and surgical treatment was sought at a late stage. Reasons determining the type of treatment chosen included religion, access to adequate care facilities, constraints involved in surgical treatment, duration of hospitalization, and fear of scarring. The four main steps in traditional treatment were diagnosis, removal of necrotic tissue, wound care, and exorcism. The cost of traditional treatment was high not only in currency but also by payment in kind (eg., livestock and land). Although it is performed with patient consent, traditional treatment presents a number of risks. Information campaigns are necessary to inform populations about available treatments and the possible risks associated with each modality. Care centers must do more to lessen the constraints involved in surgical treatment both in terms of duration of hospitalization and cosmetic outcome.

Adolescent↗

Non-tuberculous mycobacteria: patterns of isolation. A multi-country retrospective survey.

OBJECTIVE: To collect data on non-tuberculous mycobacteria (NTM) isolated from clinical laboratories in different countries to establish: 1) whether the isolation of NTM was increasing, 2) which species were increasing, and 3) whether there was any pattern of geographical distribution. DESIGN: In 1996, the Working Group of the Bacteriology and Immunology Section of the International Union Against Tuberculosis and Lung Disease contacted 50 laboratories in different countries for the necessary information. RESULTS: The number of patients reported with NTM was 36099 from 14 countries. Mycobacterium avium complex, M. gordonae, M. xenopi, M. kansasii and M. fortuitum were the five species most frequently isolated. There was a significant upward trend for M. avium complex and M. xenopi. Pigmented mycobacteria predominated in Belgium, the Czech Republic and the Mediterranean coast of Spain. Non-chromogenic mycobacteria were found to be predominant in the area of the Atlantic coast of Brazil and in Turkey, the United Kingdom, Finland and Denmark. CONCLUSIONS: There was an increase in the number of NTM isolated from clinical samples of patients. Isolation of the most frequent species is constantly changing in most of the geographical areas, and newer species are emerging due to better diagnostic techniques to detect and identify NTM.

Brazil↗

Molecular epidemiology of drug-resistant Mycobacterium tuberculosis strains isolated from patients with pulmonary tuberculosis in Poland: a 1-year study.

OBJECTIVE: To characterise drug-resistant Mycobacterium tuberculosis strains isolated in Poland and to estimate the amount of recent transmission in the population. DESIGN: M. tuberculosis strains isolated from 251 patients with resistant pulmonary tuberculosis in Poland in 2000 were analysed by spoligotyping and IS6110 DNA fingerprinting. Part of the strains was also characterised by sequencing of the rpoB, katG and/or the regulatory region of the inhA gene. RESULTS: Using combined spoligotyping/IS6110-RFLP defined clusters, 29% of the strains were clustered, suggesting possible recent transmission. In some cases, transmission links among strains in clusters could be confirmed by epidemiological data and in addition, for most of the strains, by analysis of the mutations associated with resistance to rifampicin and/or isoniazid. Younger age, sex, immigration and history of previous treatment were not associated with clustering, whereas multidrug-resistant disease was more likely to cluster. Strains of the Beijing family could also be found in Poland, although with a much lower frequency than in the neighbouring countries. CONCLUSION: Transmission of drug-resistant M. tuberculosis strains was demonstrated, which might contribute to the emergence of drug-resistant tuberculosis in Poland.

Adolescent↗

Evaluation of a commercial line probe assay for identification of mycobacterium species from liquid and solid culture.

The performance of a commercial line probe assay (LiPA) (Inno-LiPA Mycobacteria; Innogenetics, Belgium) for the detection and identification of Mycobacterium species from liquid and solid culture was evaluated at five routine clinical laboratories. The LiPA method is based on the reverse hybridization principle, in which the mycobacterial 16S-23S ribosomal RNA (rRNA) spacer region is amplified by polymerase chain reaction (PCR). Amplicons are subsequently hybridized with oligonucleotide probes arranged on a membrane strip and detected by a colorimetric system. The test detects the presence of Mycobacterium species and specifically identifies Mycobacterium tuberculosis complex, Mycobacterium kansasii, Mycobacterium xenopi, Mycobacterium gordonae, Mycobacterium avium complex, Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium scrofulaceum, and Mycobacterium chelonae - Mycobacterium abscessus complex. The results of LiPA were compared with the results obtained using traditional biochemical and molecular tests (DNA probe-based techniques, PCR restriction enzyme analysis of the 65 kDa heat-shock protein gene, and sequencing of the 16S rDNA). A total of 669 isolates, 642 of which were identified as Mycobacterium species and 27 as non- Mycobacterium species, were tested by LiPA. After analysis of 14 initially discordant results and exclusion of one isolate, concordant results were obtained for 636 of 641 Mycobacterium isolates (99.2% accuracy). All Mycobacterium species reacted with the MYC ( Mycobacterium species) probe (100% sensitivity), and all non- Mycobacterium species were identified as such (100% specificity).

Bacterial Typing Techniques↗

Prophylactic effect of mycobacterium bovis BCG vaccination against osteomyelitis in children with Mycobacterium ulcerans disease (Buruli Ulcer).

Mycobacterium ulcerans disease, or Buruli ulcer (BU), causes significant morbidity in West Africa. In 233 consecutive, laboratory-confirmed samples from BU patients in Benin whose Mycobacterium bovis BCG scar status was known, 130 children (<15 years old) and 75 adults had a neonatal BCG vaccination scar. Of 130 children with BCG scars, 10 (7.7%) had osteomyelitis, while 3 of 9 children without BCG scars (33.3%) had osteomyelitis. Our observations support the conclusion that having a BCG vaccination scar provides significant protection against M. ulcerans osteomyelitis in children with BU disease.

BCG Vaccine↗

Characterization of an unusual Mycobacterium: a possible missing link between Mycobacterium marinum and Mycobacterium ulcerans.

In an attempt to characterize an unusual mycobacterial isolate from a 44-year-old patient living in France, we applied phenotypic characterizations and various previously described molecular methods for the taxonomic classification of mycobacteria. The results of the investigations were compared to those obtained in a previous study with a set of temporally and geographically diverse Mycobacterium ulcerans (n = 29) and Mycobacterium marinum (n = 29) isolates (K. Chemlal, G. Huys, P.-A. Fonteyne, V. Vincent, A. G. Lopez, L. Rigouts, J. Swings, W. M. Meyers, and F. Portaels, J. Clin. Microbiol. 39:3272-3278, 2001). The isolate, designated ITM 00-1026 (IPP 2000-372), is closely related to M. marinum according to its phenotypic properties, lipid pattern, and partial 16S rRNA sequence. Moreover, fingerprinting by amplified fragment length polymorphism (AFLP) analysis unequivocally classified this strain as a member of the species M. marinum, although it lacked two species-specific AFLP marker bands. However, PCR and restriction fragment length polymorphism analysis based on M. ulcerans-specific insertion sequence IS2404 showed the presence of this element in a low copy number in isolate ITM 00-1026. In conclusion, the designation of this isolate as a transitional species further supports the recent claim by Stinear et al. (T. Stinear, G. Jenkin, P. D. Johnson, and J. K. Davies, J. Bacteriol. 182:6322-6330, 2000) that M. ulcerans represents a relatively recent phylogenetic derivative of M. marinum resulting from the systematic acquisition of foreign DNA fragments.

Adult↗