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Biomedical subjects

A Van Deun

Publications and source records attributed to A Van Deun.

At least 19 recordsLinked to original sources
PubMed2006

Rifampicin mono-resistant Mycobacterium tuberculosis in Bujumbura, Burundi: results of a drug resistance survey.

SETTING: Bujumbura, Burundi. OBJECTIVES: To determine resistance levels of Mycobacterium tuberculosis (TB) to the main anti-tuberculosis drugs after 11 years of a DOTS programme using a WHO-recommended partially intermittent 6-month rifampicin (RMP) first-line regimen and fixed-dose drug combinations (FDCs). DESIGN: Drug susceptibility testing of systematic samples of M. tuberculosis isolated from newly registered sputum smear-positive cases in the capital during a 15-month period (2002-2003). RESULTS: Of 496 strains from new cases, 16.1% showed resistance to any drug, 6.3% to isoniazid (INH), 2.0% to RMP (1.4% multidrug-resistant TB [MDR-TB]), 13.3% to streptomycin and 1.6% to ethambutol. Among 69 strains from previously treated cases, the prevalence of resistance was 30%, 19%, 15% (12% MDR-TB strains), 25% and 6%, respectively. CONCLUSION: Levels of drug resistance in Bujumbura are higher than average for Africa, despite long-term use of the DOTS strategy with FDCs and a ban on sales of TB drugs. Most worrying is the appearance of MDR-TB and RMP-resistant, INH-susceptible strains in new cases. Although a survey cannot prove that high HIV prevalence, elevated levels of resistance to some other drugs and irregular intake allowed acquisition of drug resistance, the effectiveness and safety of 6-month regimens with (partially) intermittent RMP throughout under such conditions should be investigated.

Adolescent↗
PubMed2006

Not all microscopes are equal.

A functional microscope is the most important and most expensive piece of equipment required for smear microscopy. Global Fund monies have provided a unique opportunity to equip laboratories in low-resource countries, but these funds must be spent wisely. Cheap microscopes are superficially appealing. However, higher-quality microscopes generally have better optics and last longer. International agencies should consider establishing a purchasing service to assist countries in their microscope procurement. Such a system would provide quality assurance and increased purchasing power.

Humans↗
PubMed2006

Early and rapid microscopy-based diagnosis of true treatment failure and MDR-TB.

SETTING: Damien Foundation tuberculosis (TB) control project in Bangladesh. OBJECTIVE: Early diagnosis of true TB treatment failure and multidrug resistance (MDR) for more efficient DOTS-Plus. DESIGN: Prospective comparison of performance on smear-positive sputum of fluorescein diacetate (FDA) vital staining vs. culture, and of slide drug susceptibility testing (slide DST) vs. the Löwenstein-Jensen (LJ) proportion method. RESULTS: FDA reached 92% positive and 97% negative predictive value directly on fresh sputum, but only 94% and 62%, respectively, on transported smears. Accuracy on washed cetylpyridinium chloride transported sputum was similar to that on fresh sputum. Slide DST on fresh smear-positive sputum failed less often than LJ DST, with 96% accurate results for rifampicin and MDR-TB diagnosis. Good results were obtained for isoniazid (90% accuracy), but not for ethambutol or streptomycin. CONCLUSIONS: We can confirm that FDA staining allows rapid screening for viable acid-fast bacilli and true treatment failure in delayed smear converters or smear-defined failures, while slide DST assures fast and accurate confirmation of MDR-TB in selected populations. The tests can be applied safely in resource-poor settings. Their successive use could be an efficient strategy for screening and an early start on standardised regimens of DOTS-Plus candidates.

Antitubercular Agents↗
PubMed2006

Extension of the intensive phase reduces unfavourable outcomes with the 8-month thioacetazone regimen.

SETTING: Damien Foundation tuberculosis (TB) control projects in Bangladesh. OBJECTIVE: To assess the effectiveness of a 1-month extension of the intensive phase for smear-positives at 2 months of an 8-month regimen with a continuation phase consisting of isoniazid (INH) and thioacetazone (Th). DESIGN: A prospective study of two cohorts of newly registered smear-positive cases, with extension of the intensive phase for the control cohort, but not for the study cohort. Culture and drug susceptibility testing (DST) of smear-defined failures and relapses and of random samples of new cases. RESULTS: Among 8230 study patients (86.7% 2-month conversion) and 7206 controls (83.4% conversion), smear-defined failure or relapse outcome was 3.0% for 2-month smear-negatives vs. 3.1% for 2-month smear-positives with extension (non-significant, NS), and 8.2% for 2-month smear-positives with no extension (P < 0.00001). Culture-confirmed failure and relapse reached 1.9% in 2-month smear-negatives and 1.6% (NS) in 2-month smear-positives with vs. 3.7% (P < 0.001) in 2-month smear-positives with no extension. The relative risk (RR) of non-extension in 2-month smear-positives was 2.4 (cultures) to 2.7 (smears). The same RR and borderline significance was found for non-extension of patients with pan-susceptible strains. CONCLUSIONS: Extension of the intensive phase considerably reduces failures and relapses with a weaker regimen in patients smear-positive at 2 months. Its effectiveness may vary with extent of initial drug resistance vs. power of the regimen.

Antitubercular Agents↗
PubMed2005

Performance of variations of carbolfuchsin staining of sputum smears for AFB under field conditions.

SETTING: A field project in Bangladesh. OBJECTIVE: To compare the effectiveness of commonly used carbolfuchsin staining variations. DESIGN: Routine hot Ziehl-Neelsen (ZN) 1% basic fuchsin staining for 15 min in 75 field clinics. Blind reading of duplicate smears stained by ZN 1% vs. 0.3% basic fuchsin applied for 5 min, or by ZN 1% 5 min vs. Kinyoun cold staining. Rechecking of discordant series. RESULTS: For comparable numbers of false positives, sensitivity was significantly lower with Kinyoun than with ZN 1% 5 min (85.6% vs. 93.0%, P < 0.001). Sensitivity with ZN 1% 5 min was not significantly higher than with 0.3% 5 min staining (89.9% vs. 86.5%). Routine examination using 1% 15 min ZN identified more positives than any of the study techniques. CONCLUSIONS: Kinyoun cold staining sensitivity was unsatisfactory in field clinics. The sensitivity of the WHO/IUATLD recommended 0.3% fuchsin for 5 min was not significantly different from the original 1% ZN for 5 min, but 1% 15 min hot staining might be superior. A reduced fuchsin concentration together with a short staining time may leave too narrow a margin for error. TB programmes using hot ZN with a concentrated stain or longer staining time should not be urged to change.

Bangladesh↗
PubMed2004

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↗
PubMed2004

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↗
PubMed2004

Scanty AFB smears: what's in a name?

SETTING: A tuberculosis control project in Bangladesh. OBJECTIVE: To document the frequency and diagnostic value of smears with scanty acid-fast bacilli (AFB) (IUATLD/WHO scale, < 10/100 high power fields), and to assess the appropriateness of the current positivity threshold. DESIGN: Analysis of databases of laboratory registers, patient records and the diagnostic yield of sputum collection strategies. RESULTS: Scanty smears constituted about 10% of suspect and almost 50% of follow-up smears. In suspect series, 10% of scanty 1-9/100 were not confirmed by another positive or scanty AFB sputum, compared to 7.5% of results at the current cut-off value of 10/100. Considering such results as positive by adopting a lower cut-off as low as the 1/100 used in the ATS scale added 1.5% false positives at the most. In return, the gain in confirmed positive cases was up to 10%, and that in positive results exceeded the incremental yield of the third diagnostic sputum. Significance of scanty follow-up smears at the end of the intensive phase was suggested by their association with treatment failure and unfavourable outcome overall. CONCLUSIONS: Scanty results (IUATLD/WHO scale) are not rare and should not be ignored. Adoption of a considerably lower positivity threshold would be appropriate in control programmes where basic conditions for reliable AFB microscopy, including regular quality assessment, are present.

Bacteriological Techniques↗
PubMed2004

Gender differences in tuberculosis: a prevalence survey done in Bangladesh.

SETTING: Bangladesh national tuberculosis control programme districts supported by the Damien Foundation (population 18 million). OBJECTIVE: To determine whether the observed gender difference is epidemiologically true or whether it is due to accessibility barriers for women. DESIGN: Two-stage random sampling population survey. People were interviewed by teams composed of one male and one female volunteer about the presence of symptoms suggestive of tuberculosis. One early morning sputum specimen of all thus identified tuberculosis suspects was examined by Ziehl-Neelsen technique. RESULTS: A total of 266189 people were surveyed, among whom 223 936 (84.1%) could be interviewed. This led to the identification of 7001 tuberculosis suspects (2406 females and 4595 males) and 64 confirmed TB cases (16 females and 48 males). The female/male ratio (0.33:1) of cases found during the survey was not higher than that observed through routine diagnosis (0.42:1). The routine case-notification rate of sputum-positive cases during 2000 was about twice the rate observed during the survey (44.3 vs. 24.0 per 100 000 population). CONCLUSIONS: The gender difference observed in routine tuberculosis diagnosis is real, and is not due to lesser accessibility of women to the health services. The routine notification rate compares favourably with the detection of previously unknown cases found during the survey.

Adolescent↗
PubMed2003

Systematic restaining of sputum smears for quality control is useful in Burundi.

SETTING: Routine tuberculosis control services in Burundi. OBJECTIVE: To determine whether systematic restaining of sputum smears for acid-fast bacilli (AFB) prior to rechecking quality assessment is necessary. DESIGN: Blinded rechecking of peripheral routine smears, including a second control of discordants, before and after restaining. RESULTS: Without restaining, 10/825 (1.2%) negative, and 59/189 (31.2%) positive results were declared false. After restaining, there were 34 (4.1%) false negatives and 13 (6.9%) false positives, both highly significant changes. Before restaining, quantification of positive smears was usually considered too high, while after restaining 41 out of 42 positives were found to have too low readings. CONCLUSIONS: Despite mild climatic conditions in Burundi, restaining all slides before rechecking revealed an unrecognised, widespread problem of false negatives, rather than false positives. This indicated the need for critical re-appraisal of the standard procedure using cold staining, rather than re-training, as would have been inferred from results without restaining. Systematic restaining of all slides prior to rechecking may be more widely needed in National Tuberculosis Programmes to cover all possible serious causes of error. Cold staining should be avoided in field programmes since its performance is easily affected by frequently encountered adverse factors.

Burundi↗
PubMed2002

Optimal tuberculosis case detection by direct sputum smear microscopy: how much better is more?

SETTING: A tuberculosis control project in Bangladesh. OBJECTIVE: To define the efficiency of numbers of microscopic fields screened and the sputum collection scheme used for diagnostic smear examination. DESIGN: Quality controllers noted cumulative numbers of acid-fast bacilli per 100 fields screened. The incremental diagnostic yield of different sputum sampling strategies was determined. Doubtful series were re-checked and/or further samples examined. RESULTS: Acid-fast bacilli were found in 99.6% of 1412 positive and in 79.3% of 576 scanty slides in the first 100 fields. Examination of a third specimen yielded a maximum of 2.7% positives incrementally. The most efficient strategy, using three morning specimens, yielded 94.2% positives on the first and 1.0% on the third sputum; although 10% of suspects did not return, only 1.5% of the positives were among them and more cases were confirmed and treated. The positive predictive value of a single positive or scanty smear was very high (99.2%). CONCLUSIONS: Reading more than 100 fields per smear or examining a third sputum has insufficient marginal returns to justify the workload. Examining morning samples only is more efficient, and their collection does not necessarily inconvenience patients. Treatment can be started on the basis of one positive smear. Provided that a well functioning system of smear-microscopy quality control is in place, we propose a strategy based on examination of two morning sputum samples for negative suspects, with the diagnosis based on a single positive result.

False Negative Reactions↗
PubMed2001

Evaluation of tuberculosis control by periodic or routine susceptibility testing in previously treated cases.

SETTING: A national tuberculosis control programme (NTP) disposing of baseline drug resistance rates and using 2EHRZ/6TH in the treatment of new cases. OBJECTIVE: To estimate the extent of drug resistance created by the NTP. DESIGN: Resistance rates in 2EHRZ/6TH failure and relapse cases were compared to baseline, and resistance profiles of repeat isolates were checked. Numbers of observed resistant failures were compared to numbers expected due to pre-existing resistance. Trends of resistance in combined new and previously treated cases were extrapolated. RESULTS: High drug resistance rates were observed. Changes in resistance to streptomycin, the virtual absence of documented acquired resistance and a close match of observed with expected resistant failures all indicated accumulation of primary drug resistance as the main mechanism. Resistance in relapse/failure cases showed a significantly declining trend, and estimated combined drug resistance decreased rapidly. CONCLUSIONS: Drug resistance in previously treated cases seems to consist of passed-on primary rather than true acquired resistance. A one-time survey is thus confusing, but continuous routine testing may constitute the best drug resistance monitoring method. Cases previously treated with short-course chemotherapy may show drug resistance much more frequently than generally assumed, and all should receive a re-treatment regimen. The 2EHRZ/6TH regimen proved very safe under field conditions, causing no 'amplification' towards multidrug resistance and almost no acquired isoniazid resistance. Implementation of this regimen, together with a standardised re-treatment regimen, seemed to rapidly reduce isoniazid as well as multidrug resistance levels, despite the fact that directly observed treatment was not strictly applied.

Antitubercular Agents↗
PubMed2000

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↗
PubMed2000

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↗
PubMed1999

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↗
PubMed1999

Reproducibility of sputum smear examination for acid-fast bacilli: practical problems met during cross-checking.

SETTING: A TB control programme in Bangladesh with proficiency testing of sputum smears for acid-fast bacilli (AFB) using cross-checking of routine smears. OBJECTIVE: To document factors that may adversely affect repeatability of the AFB smear, and which should be taken into account for interpretation of cross-checking. DESIGN: A number of simple experiments falling within the scope of small routine laboratories in a developing country. RESULTS: Fuchsin staining is not stable, fading quickly in direct sunlight and combinations of high temperature and humidity. Diffuse daylight, immersion oil or xylene did not have the same effect. Contamination of smears by saprophytic mycobacteria may occur during staining or rinsing, with contaminants becoming visible only after restaining and cross-checking. Finally, AFB may be dislodged from smears during soaking in xylene or restaining, especially if the smears are made from thin, liquefied sputum. CONCLUSIONS: These possible interfering factors should be taken into account when organizing proficiency testing and interpreting its results.

Bangladesh↗
PubMed1998

Limitations and requirements for quality control of sputum smear microscopy for acid-fast bacilli.

Sputum microscopy for acid-fast bacilli (AFB) is considered to be the most appropriate method for case-finding in a tuberculosis (TB) control programme. It is usually carried out by general technicians, often after minimal training. Quality control of their results therefore seems indispensable. The methods advocated for quality control are reviewed. Controls by culture leave too much uncertainty because of big differences in technical characteristics of the methods. Sets of smears sent out by a central laboratory can only be used to assess capability. Rechecking routine smears allows daily performance to be appraised and may be a strong motivation, but feasibility may be a problem. Based on our experience, we describe the technical requirements for cross-checking of routine smears. Counter-checking slides with discordant results is crucial for accurate assessments. A sample size should strike a balance between statistical accuracy and the man-power needed. Indicators for evaluation are proposed that allow discrimination of error gradings, to be used in a phased manner with priority at first being given to false negatives and false positives that pass the threshold for clinical decision-making. Estimates of critical values with suggestions about their interpretation are placed in the context of supervising TB laboratories.

Bacteriological Techniques↗