Journal Article > ResearchFull Text
PLOS One. 2015 December 15; Volume 10 (Issue 12); e0144656.; DOI:10.1371/journal.pone.0144656
Ardizzoni E, Fajardo E, Saranchuk P, Casenghi M, Page AL, et al.
PLOS One. 2015 December 15; Volume 10 (Issue 12); e0144656.; DOI:10.1371/journal.pone.0144656
BACKGROUND
The Xpert® MTB/RIF (Xpert) is an automated molecular test for simultaneous detection of tuberculosis (TB) and rifampicin resistance, recommended by the World Health Organization as the preferred diagnostic method for individuals presumed to have multi-drug resistant TB (MDR-TB) or HIV-associated TB. We describe the performance of Xpert and key lessons learned during two years of implementation under routine conditions in 33 projects located in 18 countries supported by Médecins Sans Frontières across varied geographic, epidemiological and clinical settings.
METHODS
Xpert was used following three strategies: the first being as the initial test, with microscopy in parallel, for all presumptive TB cases; the second being only for patients at risk of MDR-TB, or with HIV- associated TB, or presumptive paediatric TB; and the third being as the initial test for these high-risk patients plus as an add-on test to microscopy in others. Routine laboratory data were collected, using laboratory registers. Qualitative data such as logistic aspects, human resources, and tool acceptance were collected using a questionnaire.
FINDINGS
In total, 52,863 samples underwent Xpert testing from April 2011 to December 2012. The average MTB detection rate was 18.5%, 22.3%, and 11.6% for the three different strategies respectively. Analysis of the results on samples tested in parallel showed that using Xpert as add-on test to microscopy would have increased laboratory TB confirmation by 49.7%, versus 42.3% for Xpert replacing microscopy. The main limitation of the test was the high rate of inconclusive results, which correlated with factors such as defective modules, cartridge version (G3 vs. G4) and staff experience. Operational and logistical hurdles included infrastructure renovation, basic computer training, regular instrument troubleshooting and maintenance, all of which required substantial and continuous support.
CONCLUSION
The implementation of Xpert was feasible and significantly increased TB detection compared to microscopy, despite the high rate of inconclusive results. Xpert implementation was accompanied by considerable operational and logistical challenges. To further decentralize diagnosis, simpler, low-cost TB technologies well-suited to low-resource settings are still urgently needed.
The Xpert® MTB/RIF (Xpert) is an automated molecular test for simultaneous detection of tuberculosis (TB) and rifampicin resistance, recommended by the World Health Organization as the preferred diagnostic method for individuals presumed to have multi-drug resistant TB (MDR-TB) or HIV-associated TB. We describe the performance of Xpert and key lessons learned during two years of implementation under routine conditions in 33 projects located in 18 countries supported by Médecins Sans Frontières across varied geographic, epidemiological and clinical settings.
METHODS
Xpert was used following three strategies: the first being as the initial test, with microscopy in parallel, for all presumptive TB cases; the second being only for patients at risk of MDR-TB, or with HIV- associated TB, or presumptive paediatric TB; and the third being as the initial test for these high-risk patients plus as an add-on test to microscopy in others. Routine laboratory data were collected, using laboratory registers. Qualitative data such as logistic aspects, human resources, and tool acceptance were collected using a questionnaire.
FINDINGS
In total, 52,863 samples underwent Xpert testing from April 2011 to December 2012. The average MTB detection rate was 18.5%, 22.3%, and 11.6% for the three different strategies respectively. Analysis of the results on samples tested in parallel showed that using Xpert as add-on test to microscopy would have increased laboratory TB confirmation by 49.7%, versus 42.3% for Xpert replacing microscopy. The main limitation of the test was the high rate of inconclusive results, which correlated with factors such as defective modules, cartridge version (G3 vs. G4) and staff experience. Operational and logistical hurdles included infrastructure renovation, basic computer training, regular instrument troubleshooting and maintenance, all of which required substantial and continuous support.
CONCLUSION
The implementation of Xpert was feasible and significantly increased TB detection compared to microscopy, despite the high rate of inconclusive results. Xpert implementation was accompanied by considerable operational and logistical challenges. To further decentralize diagnosis, simpler, low-cost TB technologies well-suited to low-resource settings are still urgently needed.
Journal Article > ResearchFull Text
BMC Infect Dis. 2010 September 21; Volume 10 (Issue 1); DOI:10.1186/1471-2334-10-276
Hepple P, Nguele P, Greig J, Bonnet MMB, Sizaire V
BMC Infect Dis. 2010 September 21; Volume 10 (Issue 1); DOI:10.1186/1471-2334-10-276
ABSTRACT: BACKGROUND: Diagnostic options for pulmonary tuberculosis in resource-poor settings are commonly limited to smear microscopy. We investigated whether bleach concentration by sedimentation and sputum cytology analysis (SCA) increased the positivity rate of smear microscopy for smear-positive tuberculosis. METHODS: We did a prospective diagnostic study in a Medecins Sans Frontieres-supported hospital in Mindouli, Republic of Congo. Three sputum samples were obtained from 280 consecutive pulmonary tuberculosis suspects, and were processed according to WHO guidelines for direct smear microscopy. The remainder of each sputum sample was homogenised with 2.6% bleach, sedimented overnight, smeared, and examined blinded to the direct smear result for acid-fast bacilli (AFB). All direct smears were assessed for quality by SCA. If a patient produced fewer than three good-quality sputum samples, further samples were requested. Sediment smear examination was performed independently of SCA result on the corresponding direct smear. Positivity rates were compared using McNemar's test. RESULTS: Excluding SCA, 43.2% of all patients were diagnosed as positive on direct microscopy of up to three samples. 47.9% were diagnosed on sediment microscopy, with 48.2% being diagnosed on direct microscopy, sediment microscopy, or both. The positivity rate increased from 43.2% to 47.9% with a case definition of one positive smear ([greater than or equal to]1 AFB/100 high power fields) of three, and from 42.1% to 43.9% with two positive smears. SCA resulted in 87.9% of patients producing at least two good-quality sputum samples, with 75.7% producing three or more. Using a case definition of one positive smear, the incremental yield of bleach sedimentation was 14/121, or 11.6% (95% CI 6.5-18.6, p=0.001) and in combination with SCA was 15/121, or 12.4% (95% CI 7.1-19.6, p=0.002). Incremental yields with two positive smears were 5/118, or 4.2% (95% CI 1.4-9.6, p=0.062) and 7/118, or 5.9% (95% CI 2.4-11.8, p=0.016), respectively. CONCLUSIONS: The combination of bleach sedimentation and SCA resulted in significantly increased microscopy positivity rates with a case definition of either one or two positive smears. Implementation of bleach sedimentation led to a significant increase in the diagnosis of smear-positive patients. Implementation of SCA did not result in significantly increased diagnosis of tuberculosis, but did result in improved sample quality. Requesting extra sputum samples based on SCA results, combined with bleach sedimentation, could significantly increase the detection of smear-positive patients if routinely implemented in resource-limited settings where gold standard techniques are not available. We recommend that a pilot phase is undertaken before routine implementation to determine the impact in a particular context.
Journal Article > Short ReportFull Text
Int J Tuberc Lung Dis. 2011 March 1; Volume 15 (Issue 3); 405-407.
Hepple P, Novoa-Cain J, Cheruiyot C, Richter E, Ritmeijer KKD
Int J Tuberc Lung Dis. 2011 March 1; Volume 15 (Issue 3); 405-407.
Although sputum smear microscopy is the primary method for tuberculosis (TB) diagnosis in low-resource settings, it has low sensitivity. The World Health Organization recommends the use of liquid culture techniques for TB diagnosis and drug susceptibility testing in low- and middle-income countries. An evaluation of samples from southern Sudan found that culture was able to detect cases of active pulmonary TB and extra-pulmonary TB missed by conventional smear microscopy. However, the long delays involved in obtaining culture results meant that they were usually not clinically useful, and high rates of non-tuberculous mycobacteria isolation made interpretation of results difficult. Improvements in diagnostic capacity and rapid speciation facilities, either on-site or through a local reference laboratory, are crucial.
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 2010 May 1
Bonnet MMB, Tajahmady A, Hepple P, Ramsay AR, Githui W, et al.
Int J Tuberc Lung Dis. 2010 May 1
SETTING: Bleach sedimentation is a method used to increase the diagnostic yield of sputum microscopy for countries with a high prevalence of human immunodeficiency virus (HIV) infection and limited resources. OBJECTIVES: To compare the relative cost-effectiveness of different microscopy approaches in diagnosing tuberculosis (TB) in Kenya. METHODS: An analytical decision tree model including cost and effectiveness measures of 10 combinations of direct (D) and overnight bleach (B) sedimentation microscopy was constructed. Data were drawn from the evaluation of the bleach sedimentation method on two specimens (first on the spot [1] and second morning [2]) from 644 TB suspects in a peripheral health clinic. Incremental cost per smear-positive detected case was measured. Costs included human resources and materials using a micro-costing evaluation. RESULTS: All bleach-based microscopy approaches detected significantly more cases (between 23.3% for B1 and 25.9% for B1+B2) than the conventional D1+D2 approach (21.0%). Cost per tested case ranged between respectively euro 2.7 and euro 4.5 for B1 and B1+D2+B2. B1 and B1+B2 were the most cost-effective approaches. D1+B2 and D1+B1 were good alternatives to avoid using approaches exclusively based on bleach sedimentation microscopy. CONCLUSIONS: Among several effective microscopy approaches used, including sodium hypochlorite sedimentation, only some resulted in a limited increase in the laboratory workload and would be most suitable for programmatic implementation.
Journal Article > ReviewFull Text
Int J Tuberc Lung Dis. 2012 March 7; Volume 16 (Issue 5); 579-588.; DOI:10.5588/ijtld.11.0617
Hepple P, Ford NP, McNerney R
Int J Tuberc Lung Dis. 2012 March 7; Volume 16 (Issue 5); 579-588.; DOI:10.5588/ijtld.11.0617
BACKGROUND
Resource-limited settings rely on sputum examination using microscopy to diagnose tuberculosis (TB); however, the sensitivity of the test is poor and case detection rates are low. Sputum induction is proposed as a way to improve sample collection and enhance test sensitivity.
OBJECTIVE
To undertake a systematic review of studies comparing microscopy and culture sensitivity in induced sputum samples.
METHODS
We ran duplicate searches of databases (up to August 2011) and searchable websites of major human immunodeficiency virus (HIV) and TB conferences (up to November 2010) to identify studies comparing the performance of microscopy compared to culture on induced sputum samples, with culture as the reference standard.
RESULTS
A total of 23 studies met our inclusion criteria. The overall success of the induction was high, ranging from 76.4% (95%CI 68.5–83.2) to 100% (95%CI 98.5–100), while adverse events associated with sputum induction were infrequent and mild. The sensitivity of microscopy compared to culture ranged from 0% to 100%; only eight studies reported on the species of mycobacterium isolated in culture. Yield was generally higher for sputum induction compared to nasopharyngeal aspiration and gastric lavage, and compared equally well to bronchoalveolar lavage and physiotherapy.
DISCUSSION
Sputum induction increases TB case detection and is useful for people who are negative on spontaneous smear microscopy or unable to expectorate spontaneously. It is well-tolerated by children and adults, irrespective of HIV status, and can be used where culture is not available. The use of induced sputum samples with molecular tests, such as Xpert® MTB/RIF, warrants further investigation.
Resource-limited settings rely on sputum examination using microscopy to diagnose tuberculosis (TB); however, the sensitivity of the test is poor and case detection rates are low. Sputum induction is proposed as a way to improve sample collection and enhance test sensitivity.
OBJECTIVE
To undertake a systematic review of studies comparing microscopy and culture sensitivity in induced sputum samples.
METHODS
We ran duplicate searches of databases (up to August 2011) and searchable websites of major human immunodeficiency virus (HIV) and TB conferences (up to November 2010) to identify studies comparing the performance of microscopy compared to culture on induced sputum samples, with culture as the reference standard.
RESULTS
A total of 23 studies met our inclusion criteria. The overall success of the induction was high, ranging from 76.4% (95%CI 68.5–83.2) to 100% (95%CI 98.5–100), while adverse events associated with sputum induction were infrequent and mild. The sensitivity of microscopy compared to culture ranged from 0% to 100%; only eight studies reported on the species of mycobacterium isolated in culture. Yield was generally higher for sputum induction compared to nasopharyngeal aspiration and gastric lavage, and compared equally well to bronchoalveolar lavage and physiotherapy.
DISCUSSION
Sputum induction increases TB case detection and is useful for people who are negative on spontaneous smear microscopy or unable to expectorate spontaneously. It is well-tolerated by children and adults, irrespective of HIV status, and can be used where culture is not available. The use of induced sputum samples with molecular tests, such as Xpert® MTB/RIF, warrants further investigation.