Andrea Rachow

Deutsches Zentrum für Infektionsforschung DZIF, Brunswyck, Lower Saxony, Germany

Are you Andrea Rachow?

Claim your profile

Publications (27)232.22 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: The diagnosis of paediatric tuberculosis (TB) remains difficult in resource-poor settings. OBJECTIVE: To evaluate induced sputum collection and examination using microscopy, culture and Xpert® MTB/RIF assay for the diagnosis of pulmonary TB (PTB) in a Tanzanian hospital vs. PTB diagnosis using clinical scoring tools alone. METHODS: We conducted a cross-sectional study from October 2013 to April 2014 at our hospital in northwestern Tanzania. Children presumed to have TB were assessed using four TB score charts and sputum examination. Sputum samples were analyzed using fluorescence microscopy, solid culture and Xpert. The number of cases microbiologically confirmed was compared to the number of TB cases suspected based on TB score charts. RESULTS: A total of 192 patients were enrolled. Sputum specimens were successfully obtained in 187 (97.4%) patients without any major complications. Ten (5.2%) children were confirmed to have PTB by sputum examination. More than half (50-90%) of the confirmed cases were not detected by score charts alone. CONCLUSION: Sputum induction is both safe and feasible in a severely resource-limited hospital, and can lead to microbiological PTB diagnosis that would not be detected by clinical criteria alone.
    No preview · Article · Feb 2016
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Setting: Tanzania is a high-burden country for tuberculosis (TB), and prisoners are a high-risk group that should be screened actively, as recommended by the World Health Organization. Screening algorithms, starting with chest X-rays (CXRs), can detect asymptomatic cases, but depend on experienced readers, who are scarce in the penitentiary setting. Recent studies with patients seeking health care for TB-related symptoms showed good diagnostic performance of the computer software CAD4TB. Objective: To assess the potential of computer-assisted screening using CAD4TB in a predominantly asymptomatic prison population. Design: Cross-sectional study. Results: CAD4TB and seven health care professionals reading CXRs in local tuberculosis wards evaluated a set of 511 CXRs from the Ukonga prison in Dar es Salaam. Performance was compared using a radiological reference. Two readers performed significantly better than CAD4TB, three were comparable, and two performed significantly worse (area under the curve 0.75 in receiver operating characteristics analysis). On a superset of 1321 CXRs, CAD4TB successfully interpreted >99%, with a predictably short time to detection, while 160 (12.2%) reports were delayed by over 24 h with conventional CXR reading. Conclusion: CAD4TB reliably evaluates CXRs from a mostly asymptomatic prison population, with a diagnostic performance inferior to that of expert readers but comparable to local readers.
    Full-text · Article · Dec 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Setting: Tuberculosis (TB) is one of the major health problems in prisons. Objective: This study was done to assess the prevalence and determinants of active tuberculosis in Ethiopian prisons. Design: A cross-sectional study was conducted from January 2013 to December 2013 in 13 zonal prisons. All incarcerated inmates underwent TB symptom screening according to WHO criteria. From identified TB-suspects two sputum samples were analyzed using smear microscopy and solid culture. A standardized questionnaire assessing TB risk factors was completed for each TB suspect. Results: 765 (4.9%) TB suspects were identified among 15,495 inmates. 51 suspects were already on anti-TB treatment (6.67%) and 20 (2.8%) new culture-confirmed TB cases were identified in the study, resulting in an overall TB prevalence of 458.1/100,000 (95%CI: 350-560/100,000). Risk factors for active TB were alcohol consumption, contact with a TB case before incarceration and no window in prison cell. HIV prevalence was not different between TB suspects and active TB cases. Further, the TB burden in prisons increased with advancing distance from the capital Addis Ababa. Conclusions: The overall TB prevalence in Ethiopian prisons was high and extremely variable among different prisons. TB risk factors related to conditions of prison facilities and the impact of implemented TB control measures need to be further studied in order to improve TB control among inmates.
    Full-text · Article · Dec 2015 · PLoS ONE
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The commercially available urine LAM strip test, a point-of-care tuberculosis (TB) assay, requires evaluation in a primary care setting where it is most needed. There is currently inadequate data to guide implementation in TB and HIV-endemic settings. Adult HIV-infected outpatients with suspected pulmonary TB able to self-expectorate sputum from four primary clinics in South Africa, Zambia and Tanzania underwent diagnostic evaluation [sputum smear microscopy, Xpert-MTB/RIF, and culture (reference standard)] as part of a prospective parent study. Urine LAM testing (grade-2 cut-point) was performed on archived samples. Performance characteristics of LAM alone or in combination with sputum-based diagnostics were evaluated. Potential impact on 2 and 6-month morbidity (TBscore), patient dropout rates, and prognosis (death/ loss to follow-up) were evaluated. Among 583 participants with suspected TB that were HIV-infected or refused testing, the overall LAM sensitivity (95 % CI; n/N) and in the CD4 ≤ 100 cells/mm(3) sub-group was 22.7 % (16.6-28.7; 41/181) and 30.4 % (17.1-43.7; 14/46), respectively. Overall specificity was 93.0 % (90.5-95.6; 361/388). Amongst culture-positive TB cases, adjunctive LAM testing did not improve the sensitivity of either sputum Xpert-MTB/RIF [78.2 % (69.8-86.7; 72/92) versus 76.1 % (67.4-84.8; 70/92), p = 0.7] or smear-microscopy [56.2 % (45.9-66.5; 50/89) versus 43.8 % (33.5-54.1; 39/89), p = 0.1). Clinic-based LAM, as an adjunct to either smear microscopy or Xpert MTB/RIF same-day testing, would neither have decreased patient dropout, nor increased same-day treatment initiation in this clinical setting where same-day chest radiography was available. LAM positivity was associated with 6-month lost-to-follow-up/death (AOR 4.4; p = 0.002) but not TBscore (at baseline or change in TBscore 2-months post-treatment) (p = 0.17). In African HIV-TB co-infected outpatients able to self-expectorate sputum LAM had limited sensitivity even at low CD4 counts, and offered no significant incremental diagnostic yield over Xpert-MTB/RIF or smear microscopy. In primary care clinics with chest radiography and where empiric TB treatment is common, LAM seems unlikely to improve rates of same-day treatment initiation and patient dropout, however, the ability of LAM to identify patients at high risk of death or lost-to-follow-up may offer important prognostic value.
    Full-text · Article · Dec 2015 · BMC Infectious Diseases

  • No preview · Article · Sep 2015 · Tropical Medicine & International Health
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The successful cure of tuberculosis (TB) is dependent on adherence to treatment. Various factors influence adherence, however, few are easily modifiable. There are limited data regarding correlates of psychological distress and their association with non-adherence to anti-TB treatment. In a trial of a new TB test, we measured psychological distress (K-10 score), TB-related health literacy, and morbidity (TBscore), prior to diagnosis in 1502 patients with symptoms of pulmonary TB recruited from clinics in Cape Town (n = 419), Harare (n = 400), Lusaka (n = 400), Durban (n = 200), and Mbeya (n = 83). Socioeconomic, demographic, and alcohol usage-related data were captured. Patients initiated on treatment had their DOTS cards reviewed at two-and six-months. 22 %(95 % CI: 20 %, 25 %) of patients had severe psychological distress (K-10 ≥ 30). In a multivariable linear regression model, increased K-10 score was independently associated with previous TB [estimate (95 % CI) 0.98(0.09-1.87); p = 0.0304], increased TBscore [1(0.80, 1.20); p <0.0001], and heavy alcohol use [3.08(1.26, 4.91); p = 0.0010], whereas male gender was protective [-1.47(-2.28, -0.62); p = 0.0007]. 26 % (95 % CI: 21 %, 32 %) of 261 patients with culture-confirmed TB were non-adherent. In a multivariable logistic regression model for non-adherence, reduced TBscore [OR (95 % CI) 0.639 (0.497, 0.797); p = 0.0001], health literacy score [0.798(0.696, 0.906); p = 0.0008], and increased K-10 [1.082(1.033, 1.137); p = 0.0012], and heavy alcohol usage [14.83(2.083, 122.9); p = 0.0002], were independently associated. Culture-positive patients with a K-10 score ≥ 30 were more-likely to be non-adherent (OR = 2.290(1.033-5.126); p = 0.0416]. Severe psychological distress is frequent amongst TB patients in Southern Africa. Targeted interventions to alleviate psychological distress, alcohol use, and improve health literacy in newly-diagnosed TB patients could reduce non-adherence to treatment.
    Full-text · Article · Jul 2015 · BMC Infectious Diseases
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We evaluated the diagnostic performance of two tests based on the release of lipoarabinomannan (LAM) into the urine, the MTB-LAM-ELISA assay and the Determine TB-LAM-strip assay, in children with suspected tuberculosis (TB) in a high TB/HIV-prevalence setting.In a prospective study, 132 children with suspected active TB were assigned to diagnostic subgroups. Urine samples were subjected to testing by both assays to ascertain sensitivity and specificity. Host factors associated with positive LAM results were investigated and LAM excretion monitored after antituberculous treatment initiation.18 (13.6%) children had culture-confirmed pulmonary TB. The assays' sensitivity was higher in HIV-positive versus HIV-negative children: 70% (95% confidence interval 35-93%) versus 13% (0-53%) for MTB-LAM-ELISA and 50% (19-81%) versus 0% (0-37%) for Determine TB-LAM. In 35 (27%) children with excluded active TB, both assays showed a specificity of 97.1% (85-100%). Proteinuria and low body mass index were independently associated with LAM positivity. In most patients, LAM excretion declined to zero during or at conclusion of antituberculous treatment.HIV/TB co-infected children might benefit from LAM-based tests to aid early TB diagnosis and subsequent positive impact on morbidity and mortality. Using LAM as a rule-in and treatment-monitoring tool may also show further potential. Copyright ©ERS 2015.
    Full-text · Article · Jun 2015 · European Respiratory Journal
  • [Show abstract] [Hide abstract]
    ABSTRACT: It is well accepted that aging and HIV infection are associated with quantitative and functional changes of CMV-specific T cell responses. We studied here the expression of Mip-1β and the T cell maturation marker CD27 within CMVpp65-specific CD4+ and CD8+ T cells in relation to age, HIV and active Tuberculosis (TB) co-infection in a cohort of Tanzanian volunteers (≤16 years of age, n = 108 and ≥18 years, n = 79). Independent of HIV co-infection, IFNγ+ CMVpp65-specific CD4+ T cell frequencies increased with age. In adults, HIV co-infection further increased the frequencies of these cells. A high capacity for Mip-1β production together with a CD27low phenotype was characteristic for these cells in children and adults. Interestingly, in addition to HIV co-infection active TB disease was linked to further down regulation of CD27 and increased capacity of Mip-1β production in CMVpp65-specific CD4+ T cells. These phenotypic and functional changes of CMVpp65-specific CD4 T cells observed during HIV infection and active TB could be associated with increased CMV reactivation rates.
    No preview · Article · May 2015 · PLoS ONE
  • Source

    Full-text · Article · Feb 2015 · EBioMedicine
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: SQ109, an asymmetrical diamine, is a novel anti-TB drug candidate. This first study in patients was done to determine safety, tolerability, pharmacokinetics and bacteriological effect of different doses of SQ109 alone and in combination with rifampicin when administered over 14 days. Patients and methods: Smear-positive pulmonary TB patients were randomized into six groups of 15 to receive once-daily oral treatment with 75, 150 or 300 mg of SQ109, rifampicin (10 mg/kg body weight), rifampicin plus 150 mg of SQ109, or rifampicin plus 300 mg of SQ109 for 14 days. Patients were hospitalized for supervised treatment, regular clinical, biochemical and electrocardiographic safety assessments, pharmacokinetic profiling and daily overnight sputum collection. Results: SQ109 was safe and generally well tolerated. Mild to moderate dose-dependent gastrointestinal complaints were the most frequent adverse events. No relevant QT prolongation was noted. Maximum SQ109 plasma concentrations were lower than MICs. Exposure to SQ109 (AUC0-24) increased by drug accumulation upon repeated administration in the SQ109 monotherapy groups. Co-administration of SQ109 150 mg with rifampicin resulted in decreasing SQ109 exposures from day 1 to day 14. A higher (300 mg) dose of SQ109 largely outweighed the evolving inductive effect of rifampicin. The daily fall in log cfu/mL of sputum (95% CI) was 0.093 (0.126-0.059) with rifampicin, 0.133 (0.166-0.100) with rifampicin plus 150 mg of SQ109 and 0.089 (0.121-0.057) with rifampicin plus 300 mg of SQ109. Treatments with SQ109 alone showed no significant activity. Conclusions: SQ109 alone or with rifampicin was safe over 14 days. Upon co-administration with rifampicin, 300 mg of SQ109 yielded a higher exposure than the 150 mg dose. SQ109 did not appear to be active alone or to enhance the activity of rifampicin during the 14 days of treatment.
    No preview · Article · Jan 2015 · Journal of Antimicrobial Chemotherapy
  • [Show abstract] [Hide abstract]
    ABSTRACT: We evaluated the relationship between the degree of immunodeficiency indicated by the number of circulating CD4+ T-cells and Mycobacterium tuberculosis lineages identified by spoligotyping and mycobacterial interspersed repetitive units-variable number of tandem repeats genotyping in human immunodeficiency virus (HIV) infected individuals with pulmonary tuberculosis from Mbeya, Tanzania. Of M. tuberculosis strains from 129 patients, respectively 55 (42.6%) and 37 (28.7%) belonged to Latin American Mediterranean and Delhi/Central-Asian lineages, while 37 (28.7%) patients were infected with other strains. There was no difference in the distribution of M. tuberculosis lineages among patients with early or advanced stages of HIV infection (P = 0.785), indicating that the virulence of strains from these lineages may not be substantially different in vivo.
    No preview · Article · Jan 2015 · The International Journal of Tuberculosis and Lung Disease
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: The relationship between cfu and Mycobacterial Growth Indicator Tube (MGIT) time to positivity (TTP) is uncertain. We attempted to understand this relationship and create a mathematical model to relate these two methods of determining mycobacterial load. Methods: Sequential bacteriological load data from clinical trials determined by MGIT and cfu were collected and mathematical models derived. All model fittings were conducted in the R statistical software environment (version 3.0.2), using the lm and nls functions. Results: TTP showed a negative correlation with log10 cfu on all 14 days of the study. There was an increasing gradient of the regression line and y-intercept as treatment progressed. There was also a trend towards an increasing gradient with higher doses of rifampicin. Conclusions: These data suggest that there is a population of mycobacterial cells that are more numerous when detected in liquid than on solid medium. Increasing doses of rifampicin differentially kill this group of organisms. These findings support the idea that increased doses of rifampicin are more effective.
    No preview · Article · Oct 2014 · Journal of Antimicrobial Chemotherapy
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Following endorsement by the World Health Organisation, the Xpert MTB/RIF assay has been widely incorporated into algorithms for the diagnosis of adult tuberculosis (TB). However, data on its performance in children remain scarce. This prospective, multi-centre study evaluated the performance of Xpert MTB/RIF to diagnose pulmonary tuberculosis in children. Methods: Children older than eight weeks and younger than 16 years with suspected pulmonary tuberculosis were enrolled at three TB endemic settings in Tanzania and Uganda, and assigned to five well-defined case definition categories: culture-confirmed TB, highly probable TB, probable TB, not TB, or indeterminate. The diagnostic accuracy of Xpert MTB/RIF was assessed using culture-confirmed TB cases as reference standard. Results: In total, 451 children were enrolled. 37 (8%) had culture-confirmed TB, 48 (11%) highly probably TB and 62 probable TB (13%). The Xpert MTB/RIF assay had a sensitivity of 68% (95% CI, 50%-82%) and specificity of 100% (95% CI, 97%-100%); detecting 1.7 times more culture-confirmed cases than smear microscopy with a similar time to detection. Xpert MTB/RIF was positive in 2% (1/48) of highly probable and in 3% (2/62) of probable TB cases. Conclusions: Xpert MTB/RIF provided timely results with moderate sensitivity and excellent specificity compared to culture. Low yields in children with highly probable and probable TB remain problematic.
    Full-text · Article · Oct 2014 · Journal of Infection
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background The diagnosis of paediatric tuberculosis is complicated by non-specific symptoms, difficult specimen collection, and the paucibacillary nature of the disease. We assessed the accuracy of a novel immunodiagnostic T-cell activation marker–tuberculosis (TAM-TB) assay in a proof-of-concept study to identify children with active tuberculosis. Methods Children with symptoms that suggested tuberculosis were prospectively recruited at the NIMR-Mbeya Medical Research Center in Mbeya, and the Ifakara Health Institute in Bagamoyo, Tanzania, between May 10, 2011, and Sept 4, 2012. Sputum and peripheral blood mononuclear cells were obtained for Mycobacterium tuberculosis culture and performance assessment of the TAM-TB assay. The children were assigned to standardised clinical case classifications based on microbiological and clinical findings. Findings Among 290 children screened, we selected a subgroup of 130 to ensure testing of at least 20 with culture-confirmed tuberculosis. 17 of 130 children were excluded because of inconclusive TAM-TB assay results. The TAM-TB assay enabled detection of 15 of 18 culture-confirmed cases (sensitivity 83·3%, 95% CI 58·6–96·4). Specificity was 96·8% (95% CI 89·0–99·6) in the cases that were classified as not tuberculosis (n=63), with little effect from latent tuberculosis infection. The TAM-TB assay identified five additional patients with highly probable or probable tuberculosis, in whom M tuberculosis was not isolated. The median time to diagnosis was 19·5 days (IQR 14-45) for culture. Interpretation The sputum-independent TAM-TB assay is a rapid and accurate blood test that has the potential to improve the diagnosis of active tuberculosis in children. Funding European and Developing Countries Clinical Trials Partnership, German Federal Ministry of Education and Research, and Swiss National Science Foundation.
    Full-text · Article · Oct 2014 · The Lancet Infectious Diseases
  • [Show abstract] [Hide abstract]
    ABSTRACT: We evaluated the use of the molecular bacterial load (MBL) assay, for measuring viable Mycobacterium tuberculosis in sputum, in comparison with solid agar and liquid culture. The MBL assay provides early information on the rate of decline in bacterial load and has technical advantages over culture in either form.
    No preview · Article · Jul 2014 · Journal of Clinical Microbiology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mbeya, Tanzania. To develop a new liquid culture method to detect Mycobacterium tuberculosis complex (MTC) in sputum using 2,3-diphenyl-5-thienyl-(2)-tetrazolium (STC), the nitrate reductase assay (NRA) and p-nitrobenzoic acid (PNB). Ninety-three sputum samples collected from 18 tuberculosis patients were decontaminated with N-acetyl-L-cysteine-sodium hydroxide using MGIT™ 960 and in STC-NRA cultures, both in the presence and in the absence of PNB, an inhibitor of MTC growth. The reduction of STC by colour change indicated mycobacterial growth; NRA was then performed to confirm MTC. STC-NRA culture was positive for acid-fast bacilli in 66/93 (71%) samples, of which 60/93 (64.5%) were identified as MTC-positive and 6/93 (6.5%) as indeterminate mycobacteria. MGIT indicated MTC in 59/93 (63.4%) cultures. Contamination was detected in 12/93 (13%) STC-NRA cultures vs. 29/93 (31.2%) MGIT cultures. The mean time to detection (TTD) of MTC using STC-NRA was 14 days and 7 days using MGIT. The STC-NRA method is sensitive for the detection of MTC in sputum. TTD increased with duration of anti-tuberculosis treatment, highlighting the value of this method in monitoring treatment success. The method is simple and inexpensive and, unlike MGIT, does not require technical equipment. The preliminary performance characteristics of the method should be further evaluated in larger studies.
    Full-text · Article · Dec 2013 · The International Journal of Tuberculosis and Lung Disease
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Lipoarabinomannan (LAM), a cell wall component of mycobacteria, can be detected in the urine of tuberculosis (TB) patients. Advantages of this diagnostic include the ease of sample collection and test methods. However, as with most new TB diagnostics, LAM tests have been evaluated in well-controlled laboratory settings and subsequently need assessment under real working conditions. Our experience showed that the diagnosis of TB using the detection of LAM in urine under field conditions is prone to false-positive results due to contamination. Dust and soil, but also stool, seemed to lead to increased OD values and thus false-positive results of the enzyme-linked immunosorbent assay (ELISA) for LAM; however, contamination with blood, as well as bacterial or fungal organisms, had no influence. The collection of urine for the detection of LAM should therefore follow strict collection criteria in order to avoid contamination.
    Full-text · Article · Nov 2013 · Scandinavian Journal of Infectious Diseases
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background The Xpert MTB/RIF test for tuberculosis is being rolled out in many countries, but evidence is lacking regarding its implementation outside laboratories, ability to inform same-day treatment decisions at the point of care, and clinical eff ect on tuberculosis-related morbidity. We aimed to assess the feasibility, accuracy, and clinical eff ect of point-of-care Xpert MTB/RIF testing at primary-care health-care facilities in southern Africa. Methods In this pragmatic, randomised, parallel-group, multicentre trial, we recruited adults with symptoms suggestive of active tuberculosis from fi ve primary-care health-care facilities in South Africa, Zimbabwe, Zambia, and Tanzania. Eligible patients were randomly assigned using pregenerated tables to nurse-performed Xpert MTB/RIF at the clinic or sputum smear microscopy. Participants with a negative test result were empirically managed according to local WHO-compliant guidelines. Our primary outcome was tuberculosis-related morbidity (measured with the TBscore and Karnofsky performance score [KPS]) in culture-positive patients who had begun anti-tuberculosis treatment, measured at 2 months and 6 months after randomisation, analysed by intention to treat. This trial is registered with Clinicaltrials. gov, number NCT01554384. Findings Between April 12, 2011, and March 30, 2012, we randomly assigned 758 patients to smear microscopy (182 culture positive) and 744 to Xpert MTB/RIF (185 culture positive). Median TBscore in culture-positive patients did not diff er between groups at 2 months (2 [IQR 0–3] in the smear microscopy group vs 2 [0·25–3] in the MTB/RIF group; p=0·85) or 6 months (1 [0–3] vs 1 [0–3]; p=0·35), nor did median KPS at 2 months (80 [70–90] vs 90 [80–90]; p=0·23) or 6 months (100 [90–100] vs 100 [90–100]; p=0·85). Point-of-care MTB/RIF had higher sensitivity than microscopy (154 [83%] of 185 vs 91 [50%] of 182; p=0·0001) but similar specifi city (517 [95%] 544 vs 540 [96%] of 560; p=0·25), and had similar sensitivity to laboratory-based MTB/RIF (292 [83%] of 351; p=0·99) but higher specifi city (952 [92%] of 1037; p=0·0173). 34 (5%) of 744 tests with point-of-care MTB/RIF and 82 (6%) of 1411 with laboratory-based MTB/RIF failed (p=0·22). Compared with the microscopy group, more patients in the MTB/RIF group had a same-day diagnosis (178 [24%] of 744 vs 99 [13%] of 758; p<0·0001) and same-day treatment initiation (168 [23%] of 744 vs 115 [15%] of 758; p=0·0002). Although, by end of the study, more culture-positive patients in the MTB/RIF group were on treatment due to reduced dropout (15 [8%] of 185 in the MTB/RIF group did not receive treatment vs 28 [15%] of 182 in the microscopy group; p=0·0302), the proportions of all patients on treatment in each group by day 56 were similar (320 [43%] of 744 in the MTB/RIF group vs 317 [42%] of 758 in the microscopy group; p=0·6408). Interpretation Xpert MTB/RIF can be accurately administered by a nurse in primary-care clinics, resulting in more patients starting same-day treatment, more culture-positive patients starting therapy, and a shorter time to treatment. However, the benefi ts did not translate into lower tuberculosis-related morbidity, partly because of high levels of empirical-evidence-based treatment in smear-negative patients.
    Full-text · Article · Oct 2013 · The Lancet
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: An accurate biomarker is urgently needed to monitor the response to treatment in patients with pulmonary tuberculosis. The Xpert MTB/RIF assay is a commercially available real-time PCR that can be used to detect Mycobacterium-tuberculosis-specific DNA sequences in sputum samples. We therefore evaluated this assay with serial sputum samples obtained over 26 weeks from patients undergoing treatment for tuberculosis. We analysed sputum samples from 221 patients with smear-positive tuberculosis enrolled at two sites (Cape Town, South Africa, and Mbeya, Tanzania) of a multicentre randomised clinical trial REMoxTB of antituberculosis treatment on a weekly basis (weeks 0 to 8), then at weeks 12, 17, 22, and 26 after treatment initiation. The Xpert MTB/RIF results over time were compared with the results of standard smear microscopy and culture methods. We obtained and analysed 2741 sputum samples from 221 patients. The reduction in positivity rates with Xpert MTB/RIF were slower than those with the standard methods. At week 8, positive results were obtained for 62 (29%) of 212 sputum samples with smear microscopy, 46 (26%) of 175 with solid culture (Löwenstein-Jensen medium), 77 (42%) of 183 with liquid culture (Bactec MGIT960 system), and 174 (84%) of 207 with Xpert MTB/RIF; at 26 weeks, positive results were obtained for ten (5%) of 199, four (3%) of 157, seven (4%) of 169, and 22 (27%) of 83 sputum samples, respectively. The reduction in detection of quantitative M tuberculosis DNA with Xpert MTB/RIF correlated with smear grades (ρ=-0·74; p<0·0001), solid culture grades (ρ=-0·73; p<0·0001), and time to liquid culture positivity (ρ=0·73; p<0·0001). Compared with the combined binary smear and culture results as a reference standard, the Xpert MTB/RIF assay had high sensitivity (97·0%, 95% CI 95·8-97·9), but poor specificity (48·6%, 45·0-52·2). The poor specificity precludes the use of the Xpert MTB/RIF assay as a biomarker for monitoring tuberculosis treatment, and should not replace standard smear microscopy and culture. Global Alliance for TB Drug Development, Bill & Melinda Gates Foundation, UK Medical Research Council, German Ministry of Science and Technology.
    Full-text · Article · Aug 2013 · The Lancet Respiratory Medicine
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Rapid and accurate diagnosis of pulmonary tuberculosis in children remains challenging because of difficulties in obtaining sputum samples and the paucibacillary nature of the disease. The Xpert MTB/RIF assay is useful for rapid diagnosis of childhood tuberculosis with sputum and nasopharyngeal samples. We assessed this assay for the detection of tuberculosis and multidrug resistant (MDR) tuberculosis with gastric lavage aspirate (GLA) samples in children admitted to hospital. METHODS: We did a prospective study to assess the sensitivity and specificity of the Xpert MTB/RIF assay with GLA samples for the detection of pulmonary tuberculosis and MDR tuberculosis in new paediatric inpatient admissions at the University Teaching Hospital, Lusaka, Zambia. Children aged 15 years or younger were recruited between June, 2011, and May, 2012. GLA and sputum were analysed by standard smear-microscopy, mycobacterial growth indicator tube (MGIT) culture, MGIT drug-susceptibility testing, and the Xpert MTB/RIF assay. Sensitivity of the Xpert MTB/RIF assay was assessed with the Pearson χ(2) or Fishers exact test. FINDINGS: Of 930 children, 142 produced sputum and GLA was obtained from 788 non-sputum producers. Culture-positive tuberculosis was identified in 58 (6·2%) of 930 children: ten from sputum producers and 48 from GLA of non-sputum producers. The sensitivity and specificity of the Xpert MTB/RIF assay were similar: sensitivity was 68·8% (95% CI 53·6-80·9) for GLA versus 90·0% (54·1-99·5; p=0·1649) for sputum samples; specificity was 99·3% (98·3-99·8) for GLA and 98·5% (94·1-99·7; p=0·2871) for sputum samples. The Xpert MTB/RIF assay detected an extra 28 tuberculosis cases compared with smear microscopy and was significantly more sensitive than smear microscopy for both sputum (90·0% [54·1-99·5] vs 30·0% [8·1-64·6], p=0·01) and GLA (68·8% [53·6-80·9] vs 25·0% [14·1-40·0], p<0·0001). The assay load did not differ significantly by sample type (p=0·791). 22 children were infected with HIV and tuberculosis and significant differences in assay performance could not be detected when stratifying by HIV status for either sample type. The Xpert MTB/RIF assay detected rifampicin resistance in three GLA samples: two confirmed as MDR tuberculosis and one false positive. INTERPRETATION: Analyses of GLA samples with the Xpert MTB/RIF assay is a sensitive and specific method for rapid diagnosis of pulmonary tuberculosis in children who cannot produce sputum. The single site nature of our study invites caution. FUNDING: European Commission, European Developing Countries Clinical Trials Partnership, and UBS Optimus Foundation.
    Full-text · Article · Nov 2012 · The Lancet Infectious Diseases

Publication Stats

397 Citations
232.22 Total Impact Points

Institutions

  • 2014-2015
    • Deutsches Zentrum für Infektionsforschung DZIF
      Brunswyck, Lower Saxony, Germany
  • 2011-2015
    • Mbeya Medical Research Center
      Mbeya, Mbeya, Tanzania
    • National Institute for Medical Research (NIMR)
      Dār es Salām, Dar es Salaam, Tanzania
  • 2013-2014
    • Technische Universität München
      München, Bavaria, Germany
    • NIMR - Mbeya Medical Research Center
      Mbeya, Mbeya, Tanzania