[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.
[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.
[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.
PLoS ONE 05/2015; 10(5):e0126716. DOI:10.1371/journal.pone.0126716 · 3.23 Impact Factor
[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.
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.
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.
[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.
The International Journal of Tuberculosis and Lung Disease 01/2015; 19(1):70-3. DOI:10.5588/ijtld.14.0403 · 2.32 Impact Factor
[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.
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.
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.
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.
[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.
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.
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.
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.
Journal of Infection 10/2014; 70(4). DOI:10.1016/j.jinf.2014.10.003 · 4.44 Impact Factor
[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.
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.
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.
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.
European and Developing Countries Clinical Trials Partnership, German Federal Ministry of Education and Research, and Swiss National Science Foundation.
[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.
[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.
The International Journal of Tuberculosis and Lung Disease 12/2013; 17(12):1607-12. DOI:10.5588/ijtld.13.0317 · 2.32 Impact Factor
[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.
[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.
The Lancet 10/2013; 383(9915). DOI:10.1016/S0140-6736(13)62073-5 · 45.22 Impact Factor
[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.
The Lancet Respiratory Medicine 08/2013; 1(6):462-70. DOI:10.1016/S2213-2600(13)70119-X · 9.63 Impact Factor
[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.
[Show abstract][Hide abstract] ABSTRACT: In this pilot study, we evaluated the Xpert® MTB/RIF assay in an active case-finding strategy, using two spot sputum samples collected within a 1-hour interval from household contacts of smear-positive TB index cases. Tuberculosis (TB) confirmed by culture served as the reference standard. Among 219 enrolled contacts, the yield of active TB was 2.3%. While the sensitivity of smear microscopy was 60% (95%CI 14.7-94.7), Xpert MTB/RIF achieved a sensitivity of 100% (95%CI 47.81-100.0). All culture-confirmed cases tested positive by Xpert MTB/RIF on the first submitted sample, suggesting that the evaluation of only one sample could be sufficient for TB diagnosis in this context.
The International Journal of Tuberculosis and Lung Disease 09/2012; 16(11):1468-70. DOI:10.5588/ijtld.12.0127 · 2.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
A high burden of tuberculosis (TB) occurs in sub-Saharan African countries and many cases of active TB and drug-resistant TB remain undiagnosed. Tertiary care hospitals provide an opportunity to study TB co-morbidity with non-communicable and other communicable diseases (NCDs/CDs). We evaluated the burden of undiagnosed pulmonary TB and multi-drug resistant TB in adult inpatients, regardless of their primary admission diagnosis, in a tertiary referral centre.
In this prospective study, newly admitted adult inpatients able to produce sputum at the University Teaching Hospital, Lusaka, Zambia, were screened for pulmonary TB using fluorescent smear microscopy and automated liquid culture. The burden of pulmonary TB, unsuspected TB, TB co-morbidity with NCDs and CDs was determined. Sputum was analysed from 900 inpatients (70.6% HIV infected) 277 (30.8%) non-TB suspects, 286 (31.8%) TB suspects and 337 (37.4%) were already receiving TB treatment. 202/900 (22.4%) of patients had culture confirmed TB. TB co-morbidity was detected in 20/275 (7.3%) NCD patients, significantly associated with diabetes (P = 0.006, OR 6.571, 95%CI: 1.706–25.3). 27/202 (13.4%) TB cases were unsuspected. There were 18 confirmed cases of MDR-TB, 5 of which were unsuspected.
A large burden of unsuspected pulmonary TB co-morbidity exists in inpatients with NCDs and other CDs. Pro-active sputum screening of all inpatients in tertiary referral centres in high TB endemic countries is recommended. The scale of the problem of undiagnosed MDR-TB in inpatients requires further study.
PLoS ONE 07/2012; 7(7). DOI:10.1371/journal.pone.0040774 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background. There were 1.45 million deaths from tuberculosis (TB) in 2011. A substantial proportion of active pulmonary TB cases in countries where tuberculosis, human immunodeficiency virus (HIV) infection, and AIDS are highly endemic remain undiagnosed because of the reliance on sputum-smear microscopy. This study evaluated the performance of the Xpert MTB/RIF assay at a tertiary care referral center in Zambia, a country where the burden of TB and HIV infection is high. Methods. A total of 881 adult inpatients admitted to University Teaching Hospital in Lusaka who were able to produce sputum were enrolled and analyzed in the study, irrespective of admission diagnosis. Sputum specimens were analyzed by fluorescence smear microscopy, the Xpert MTB/RIF assay, mycobacterial growth indicator tube (MGIT) culture, and MGIT drug-susceptibility testing. The sensitivity and specificity of the Xpert MTB/RIF assay were evaluated using culture as the gold standard. Results. Culture-confirmed TB was found in 201 of 881 patients (22.8%). The specificity of the Xpert MTB/RIF assay was 95.0% (95% confidence interval [CI], 92.4%-96.8%), and the sensitivity was 86.1% (95% CI, 80.3%-90.4%). In sputum smear-negative, culture-positive cases, the assay was 74.7% sensitive (95% CI, 64.6%-82.8%), identifying 71 additional TB cases that were not detected by smear microscopy. A total of 18 of 111 patients with TB who were tested (16.2%) had multidrug-resistant (MDR) TB. The sensitivity and specificity of the Xpert MTB/RIF assay for detecting culture-confirmed, rifampicin-resistant TB was 81.3% (95% CI, 53.7%-95.0%) and 97.5% (95% CI, 90.4%-99.6%), respectively. Conclusions. The Xpert MTB/RIF assay performs better than smear microscopy in an inpatient setting in a country where TB and HIV infection are highly endemic. Assessment of its usefulness and cost-effectiveness for increased detection of TB cases missed by sputum smear and for concomitant screening for MDR TB among adult inpatients attending tertiary care referral centers in other countries with a high burden of TB and HIV infection is warranted.
[Show abstract][Hide abstract] ABSTRACT: Diagnosis and timely treatment of tuberculosis in children is hampered by the absence of fast and reliable tests, especially in the era of human immunodeficiency virus (HIV). The aim of this study was to evaluate the diagnostic performance of the Xpert MTB/RIF assay (Xpert) in children with suspected tuberculosis in a high tuberculosis/HIV-burden setting.
In a prospective study with a minimum follow-up of 12 months, 164 children with suspected tuberculosis were assigned to predefined diagnostic subgroups, based on microbiological and clinical findings. Results of smear microscopy and culture were compared against diagnostic performance of Xpert.
Twenty-eight of 164 children (17.1%) had confirmed tuberculosis. Xpert detected 100% (95% confidence interval [CI], 59.0%-100%) of smear-positive cases and 66.6% (95% CI, 43.0%-85.4%) of culture-positive but smear-negative cases. In the per-sample analysis, Xpert displayed a similar sensitivity (54.7% [95% CI, 42.7%-66.2%]) compared with culture methods. Xpert detected 3-fold more confirmed tuberculosis cases than smear microscopy but with equal rapidity. Four additional cases (8.5%) with clinical tuberculosis but negative culture were diagnosed by Xpert. Testing second and third samples increased sensitivity by 20% and an additional 16%, respectively. When tuberculosis was reliably excluded, Xpert's specificity was 100%. HIV infection did not affect diagnostic accuracy of Xpert.
Xpert was easy to perform and displayed similar diagnostic accuracy as culture methods in children with suspected tuberculosis. Rapid turnaround times should reduce treatment delay and improve patient outcome, although sensitivity remains suboptimal and access is dependent on local laboratory infrastructure.