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F Portaels

Publications and source records attributed to F Portaels.

At least 55 records · Page 3Linked to original sources

Directly observed treatment, short-course strategy and multidrug-resistant tuberculosis: are any modifications required?

Multidrug-resistant tuberculosis (MDRTB) should be defined as tuberculosis with resistance to at least isoniazid and rifampicin because these drugs are the cornerstone of short-course chemotherapy, and combined isoniazid and rifampicin resistance requires prolonged treatment with second-line agents. Short-course chemotherapy is a key ingredient in the tuberculosis control strategy known as directly observed treatment, short-course (DOTS). For populations in which multidrug-resistant tuberculosis is endemic, the outcome of the standard short-course chemotherapy regimen remains uncertain. Unacceptable failure rates have been reported and resistance to additional agents may be induced. As a consequence there have been calls for well-functioning DOTS programmes to provide additional services in areas with high rates of multidrug-resistant tuberculosis. These "DOTS-plus for MDRTB programmes" may need to modify all five elements of the DOTS strategy: the treatment may need to be individualized rather than standardized; laboratory services may need to provide facilities for on-site culture and antibiotic susceptibility testing; reliable supplies of a wide range of expensive second-line agents would have to be supplied; operational studies would be required to determine the indications for and format of the expanded programmes; financial and technical support from international organizations and Western governments would be needed in addition to that obtained from local governments.

Antitubercular Agents↗

Bleach sedimentation method for increased sensitivity of sputum smear microscopy: does it work?

SETTING: A non-governmental organisation (NGO) supported tuberculosis control programme in Bangladesh with good smear microscopy. OBJECTIVE: To verify whether bleach sedimentation method increases the sensitivity of sputum smear microscopy for acid-fast bacilli (AFB), and if so, how. DESIGN: Duplicate smears from successive routine specimens, peripheral centres examining direct smears, and blind examination of bleach sediment smears at central laboratories. RESULTS: When all 3,287 sputum samples were examined in duplicate and the International Union Against Tuberculosis and Lung Disease cut-off for positivity was applied, more positives were not found by bleach sedimentation. Using the much lower American Thoracic Society (ATS) threshold, the percentage positives rose slightly from 15.5% for direct smear to 16.6% after bleach. The gain was more evident when suspect examinations only were taken into consideration, as bleach missed many positives identified by direct follow-up smear. When patients rather than individual smears were counted, more suspects were detected by bleach (10% gain on average), but with considerable variation between the centres (range 6-16%). To arrive at this gain, the ATS cut-off was used, with corrections for false results. Under routine conditions, however, this threshold is too low in view of possible transfer of AFB. CONCLUSIONS: Bleach sedimentation can increase the diagnostic yield, but only to a minor extent if all other factors have been optimised already; it is not a panacea. Precautions against false negatives as well as false positives should be taken, and the additional workload is not negligible.

Bacteriological Techniques↗

Detection of rifampicin resistance in Mycobacterium tuberculosis isolates from diverse countries by a commercial line probe assay as an initial indicator of multidrug resistance.

The line probe assay (LiPA), a rapid molecular method for detecting rifampicin resistance (RMPr) in Mycobacterium tuberculosis, correctly identified all 145 rifampicin-sensitive (RMPs) and 262 (98.5%) of 266 RMPr strains among 411 isolates collected from diverse countries. If used as a marker of multidrug-resistant tuberculosis (MDR-TB), detection of RMPr by LiPA would have detected 236 of the 240 MDR strains in this study but would have wrongly suggested the presence of MDR in 26 RMP-monoresistant isolates (sensitivity 98.3%, specificity 84.8%). Hence, the reliability of using LiPA (or any other rapid RMPr-detection method) as a surrogate marker of MDR-TB largely depends on the prevalence of RMP-monoresistance in the study population. This approach must therefore be validated in each local situation.

Africa↗

Pulmonary tuberculosis in prisons of the ex-USSR state Georgia: results of a nation-wide prevalence survey among sentenced inmates.

SETTING: The penitentiary system of the ex-USSR state of Georgia. OBJECTIVES: To measure the prevalence of active pulmonary tuberculosis and drug-resistant disease among prisoners. To identify factors associated with active tuberculosis and multidrug resistance (MDR). DESIGN: A comprehensive multiphasic screening survey for tuberculosis. RESULTS: The prevalence of smear- or culture-positive tuberculosis was 5995 per 100,000 prisoners (n = 448 cases among 7473 inmates). Of all the strains, 215 (77.9%) were resistant to at least one drug and 37 (13.0%) were MDR. Independent risk markers associated smear- or culture-positive tuberculosis with included prison stay of 2 years or more, body mass index <20 kg/m2, accommodation in a large size prison, previous anti-tuberculosis treatment, cough of 2 weeks or more and loss of appetite. Risk markers associated with MDR were a prison stay of less than 2 years and being over 25 years of age. CONCLUSIONS: In Georgia, the excess risk for tuberculosis among prisoners is unprecedented, suggesting that prisons represent a significant reservoir of tuberculosis. Only a comprehensive strategy for tuberculosis control in prisons, including prison reform, control of anti-tuberculosis drugs, and prompt and efficient diagnosis and treatment of patients can have an impact on the tuberculosis burden in the prison system.

Adult↗

What is the meaning of repeated isolation of Mycobacterium africanum?

Mycobacterium africanum is a member of the tuberculosis complex, together with M. tuberculosis and M. bovis. Its morphological growth is quite different from that of M tuberculosis. It is a causative agent of the same tuberculosis disease, and its precise identification seems important only for epidemiological purposes. We report here the repetitive isolation of 17 M. africanum strains (among 321 TB complex strains) during a national primary resistance survey in C te d'Ivoire in 1995. All of the M. africanum strains were isolated in four regions located in the same geographical area. They showed biochemical heterogeneity yielding three patterns, none of which was specific to one region. Molecular analysis by RFLP for 14 strains showed identical patterns for four strains, two by two, and a clustering of 62-77% homology for eight of the 14 strains (57%). This report confirms that M. africanum is less frequent than M. tuberculosis. Its repeated isolation may reflect inter-human transmission. Biochemical similarities between strains may not always be associated with a common geographical origin.

Africa South of the Sahara↗

[Buruli ulcer: risk of bone involvement! Apropos of 33 cases observed in Benin].

Skin lesions are the best known manifestations of Mycobacterium ulcerans infection. However osteomyelitis is not uncommon with incidences as high as 14 p. 100 having been reported. The literature contains little specific data on bone lesions. This report describes a series of 33 patients presenting bacteriologically and/or histologically confirmed osteomyelitis induced by Mycobacterium ulcerans. In 64 p. 100 of cases, bone involvement occurred within the first year of the disease. In 70 p. 100 of cases, the site of involvement was on extremities. The median number of sites per patient was two (range, 1 to 5) and the number of bones was not correlated with the duration of disease. Overall, 41 p. 100 of bone sites occurred locally beneath skin lesions and 59 p. 100 were distant metastases. Osteomyelitis was associated with other germs in only 16 p. 100 of cases and superinfection was not a prerequisite for development of bone involvement. Clinical manifestations were usually low-grade with non-inflammatory, slightly painful local mass. The patient's general health status was unaffected in 79 p. 100. Histological examination allowed identification of the type of bone lesions induced by Mycobacterium ulcerans. For the first time, bone biopsy specimens were cultured. Based on bacteriological and histological findings, several postulations can be made about underlying pathophysiological mechanisms. The role of Buruli toxin is dealt with in the discussion.

Adolescent↗

Growth and cytotoxic activity by Mycobacterium ulcerans in protein-free media.

The pathogenic slow-growing Mycobacterium ulcerans has, until now, been cultured in liquid media containing albumin. Here, we report the first description of use of Sauton medium and modified Reid medium, two protein-free media, in which M. ulcerans was able to grow and produce its toxin, a major virulence factor of this environmental organism which causes a skin disease commonly called Buruli ulcer. These results suggest that Sauton and modified Reid may be useful for certain fields of M. ulcerans research requiring protein-free growth conditions.

Bacterial Toxins↗

Simple procedure for drug susceptibility testing of Mycobacterium tuberculosis using a commercial colorimetic assay.

The aim of this study was to evaluate a simple method using a commercial colorimetric assay (Alamar Blue Oxidation-Reduction Indicator; Accumed, USA) in a microtiter format for testing the susceptibility of 94 strains of Mycobacterium tuberculosis to isoniazid, rifampicin, ethambutol and streptomycin. The method makes use of one critical concentration of each drug, and the results are available within 8-10 days. Overall, 97.1% agreement with the proportion method was obtained. Full agreement was obtained for isoniazid and rifampicin. The method is simple to perform, permits visual reading of results, and is practicable for laboratories with limited resources.

Antibiotics, Antitubercular↗

Blood and charcoal added to acidified agar media promote the growth of Mycobacterium genavense.

Ten different agar media were tested for the in vitro growth of Mycobacterium genavense in primary cultures and in subcultures from BACTEC vials. These agar media were based on Middlebrook 7H9, 7H10 and 7H11, and supplemented with additives: mycobactin J, yeast extract, charcoal, or defibrinated sheep blood. Some media were acidified with phosphoric acid to a final pH of 6.2 +/- 0.2. Fourteen M. genavense strains from nude mouse organs as well as one decontaminated clinical specimen (from a bird) were tested. The optimal medium for primary cultures of M. genavense was Middlebrook 7H11 acidified to pH 6.2 +/- 0.2 and supplemented with charcoal and sheep blood: on this medium, all strains produced colonies within 6-12 weeks of incubation in numbers approaching the number of bacilli inoculated. It was also the only medium to support the growth of the decontaminated clinical specimen. Added blood and charcoal appeared not as essential for subcultures as for primary cultures. Three media supported the growth of all strains within 1 month incubation: they were acidified, and were supplemented with yeast extract or pancreatic digest of casein, and with either blood or charcoal.

AIDS-Related Opportunistic Infections↗

Relationship between pyrazinamide resistance, loss of pyrazinamidase activity, and mutations in the pncA locus in multidrug-resistant clinical isolates of Mycobacterium tuberculosis.

Sixty-two Mycobacterium tuberculosis isolates were tested for pyrazinamidase activity, and their pyrazinamide susceptibility was determined by the radiometric method. Sequencing of pncA genes in the 23 resistant strains revealed mutations in 16 pyrazinamidase-negative strains, 11 of which had not been previously described. Six isolates containing wild-type pncA might possess alternative resistance mechanisms.

Amidohydrolases↗

Comparison of two PCRs for detection of Mycobacterium ulcerans.

Two nested PCRs for the detection of Mycobacterium ulcerans were compared by using a collection of 65 clinical specimens. The first method amplifies the gene coding for 16S rRNA, and the second method amplifies a repetitive DNA sequence. The sensitivities of bacterioscopy, culture, 16S rRNA gene PCR, and repetitive-sequence PCR were 29, 34, 80, and 85%, respectively. Compared to the 16S rRNA gene PCR, the repetitive-sequence PCR was faster, easier to perform, and less expensive.

Bacteriological Techniques↗

Drug susceptibility of Mycobacterium tuberculosis in a rural area of Bangladesh and its relevance to the national treatment regimens.

SETTING: Greater Mymensingh District, a rural area of Bangladesh, at the start of the National Tuberculosis Programme (NTP). OBJECTIVES: To determine the prevalence of initial and acquired drug resistance of Mycobacterium tuberculosis, and to assess the appropriateness of the NTP's standard regimens. DESIGN: Sampling of pre-treatment sputum from all newly registered smear-positive cases in five centres covering the area. Culture and susceptibility testing in a supra-national reference laboratory. RESULTS: Initial resistance to isoniazid (H) was 5.4%, and to rifampicin (R) 0.5%. Acquired H and R resistance were 25.9% and 7.4%, respectively. Multidrug resistance (MDR) was observed in one new case only and in 5.6% of previously treated patients. Changing the present NTP indication for retreatment regimen to one month of previous H intake would increase coverage of H-resistant cases from 52% to 89%, adding 6% to drug costs. CONCLUSION: The prevalence of drug resistance is surprisingly low in Bangladesh, but could rise with improving economic conditions. The NTP regimens for smear-positive cases are appropriate, all the more so since the human immunodeficiency virus is virtually absent. Indications for the retreatment regimen should be extended to include all patients treated for at least one month with any drug. The NTP regimen for smear-negative cases runs the risk of leading to MDR under present field conditions.

Adolescent↗

Evaluation of Mycobacteria Growth Indicator Tube (MGIT) for drug susceptibility testing of Mycobacterium tuberculosis.

SETTING: Mycobacteria Supranational Reference Laboratory. OBJECTIVE: To evaluate the Mycobacteria Growth Indicator Tube (MGIT) method for drug susceptibility testing of Mycobacterium tuberculosis. DESIGN: One hundred and one clinical strains of M. tuberculosis were evaluated for their susceptibilities to isoniazid (INH), rifampicin (RIF), ethambutol (EMB) and streptomycin (SM) by MGIT and by the proportion method on Löwenstein-Jensen (L-J) medium. The concentrations of drugs in MGIT were: 0.1, 1.0, 3.5 and 0.8 microg/ml for INH, RIF, EMB and SM, respectively. RESULTS: The results for individual drugs showed a good correlation: the specificity was 100% for INH, RIF and EMB and 92% for SM; the sensitivity was 100%, 94.6%, 96.1% and 89.7% for INH, RIF, EMB and SM, respectively, and the accuracy values 1.0, 0.98, 0.99 and 0.91. CONCLUSION: The MGIT system appears to be a reliable and simple non-radiometric method for the drug susceptibility testing of M. tuberculosis.

Antitubercular Agents↗

Inadequacy of the current WHO re-treatment regimen in a central Siberian prison: treatment failure and MDR-TB.

Multidrug-resistant tuberculosis (MDR-TB) threatens the progress of global control efforts. Prisons represent a high risk setting for development and transmission of MDR-TB. In a Siberian TB referral prison (Kemerovo region), the treatment failure rate is 35% (June 1996-March 1997), despite implementation of a strict DOTS program and use of the World Health Organization Category 2 re-treatment regimen for all new cases. Among 164 patients (December 1997-March 1998), initial resistance to isoniazid and rifampin is 22.6%. Such a rate is a warning call to reconsider prison control strategies, and importantly, to address the treatment regimens necessary to combat an institutional epidemic of MDR-TB.

Antitubercular Agents↗

Addressing multidrug-resistant tuberculosis in penitentiary hospitals and in the general population of the former Soviet Union.

High rates of tuberculosis, including multidrug-resistant tuberculosis (MDR-TB), have been reported from the former Soviet Union. Our laboratory has supported operational studies in jails in Baku, Azerbaijan, and Mariinsk, Siberia. Combining the results from these two penal systems, the rates of MDR-TB among 'newly enrolled' and 'non-responding' cases were 24.6% and 92.1%, respectively. Restriction fragment length polymorphism (RFLP) studies strongly suggest transmission of MDR-TB between prisoners. In Mariinsk, the high rates of MDR-TB have been associated with failure rates of 23%-50% among smear-positive cases receiving fully-supervised standard short-course treatment. There are no coherent guidelines for TB control programmes confronted by high pre-existing levels of MDR-TB but who have only limited laboratory, clinical, pharmaceutical and financial resources. A 'DOTS plus' strategy has been advocated in which an established TB control programme is complemented by facilities to treat MDR-TB patients. However, the exact format of these programmes remains unresolved. Further research is required to describe the natural history of MDR-TB infection, to determine the failure rate of (and the additional resistance induced by) standard short-course treatment when MDR-TB is prevalent, to decide whether standardised or individualised second-line regimens can be employed, and to define the laboratory facilities required by a 'DOTS plus' programme.

Communicable Disease Control↗

Drug resistant tuberculosis in prisons in Azerbaijan: case study.

OBJECTIVES: To document the existence of drug resistance in a tuberculosis treatment programme that adheres strictly to the DOTS principles (directly observed treatment, short course) and to determine the extent of drug resistance in a prison setting in one of the republics of the former Soviet Union. DESIGN: Case study. SETTING: Central Penitentiary Hospital in Baku, the referral centre for tuberculosis patients from all prisons in Azerbaijan. SUBJECTS: Prisoners with tuberculosis: 28 selected patients not responding clinically or bacteriologically to the standard treatment (group 1) and 38 consecutive patients at admission to the programme (group 2). MAIN OUTCOME MEASURES: Drug resistance of Mycobacterium tuberculosis strains grown from sputum. RESULTS: All the non-responding patients (group 1) had strains resistant to at least one drug. 25 (89%) of the non-responding patients and nine (24%) of the consecutive patients had M tuberculosis strains resistant to both rifampicin and isoniazid. A further 17 patients in group 2 had strains resistant to one or more first line drugs. CONCLUSIONS: Drug resistant M tuberculosis strains are common in prisons in Azerbaijan. Tuberculosis problems tend to be worse in prisons, but prisoners and former prisoners may have an important role in the transmission of tuberculosis, particularly of drug resistant forms, in the community. National programmes to control tuberculosis will have to take into account and address the problems in prisons to ensure their success.

Antibiotics, Antitubercular↗

Mycobacterium ulcerans infection in a child from Angola: diagnosis by direct detection and culture.

Buruli ulcer, caused by Mycobacterium ulcerans, is a chronic ulcerative skin disease, found predominantly in central and west Africa and Australia. A boy of 2.5 years of age from Angola was admitted to our hospital with severe kwashiokor and a large ulcer with undermined edges on the left side of the thorax. Further examination revealed anaemia, hypoproteinaemia, bacterial superinfection of the ulcer and intestinal parasites. Histological analysis showed acid-fast bacilli and histopathological changes typical of Buruli ulcer. M. ulcerans was detected by PCR and culture. The patient was treated by surgical excision of diseased skin, followed by split-skin grafting. He also received antibiotic therapy (ciprofloxacin, clarithromycin, rifabutin, and dapsone). After six months, the child was discharged from hospital in good condition. This is the first published case of Buruli ulcer from Angola.

Angola↗