Maryline Bonnet

Detection of drug-resistant tuberculosis by Xpert MTB/RIF in Swaziland.

Rapid diagnosis of drug-resistant tuberculosis is important in determining proper management. This letter reports on limitations of the Xpert MTB/RIF assay in determining rifampin resistance in tuberculosis isolates in Swaziland.

Adherence to Self-Administered Tuberculosis Treatment in a High HIV-Prevalence Setting: A Cross-Sectional Survey in Homa Bay, Kenya

Background Good adherence to treatment is crucial to control tuberculosis (TB). Efficiency and feasibility of directly observed therapy (DOT) under routine program conditions have been questioned. As an alternative, Médecins sans Frontières introduced self-administered therapy (SAT) in several TB programs. We aimed to measure adherence to TB treatment among patients receiving TB chemotherapy with fixed dose combination (FDC) under SAT at the Homa Bay district hospital (Kenya). A second objective was to compare the adherence agreement between different assessment tools. Methods We conducted a cross-sectional survey amongst a series of new TB patients receiving 6 months of standard TB chemotherapy with FDC under SAT. Adherence was assessed at home with urine testing for Isoniazid (INH), pill count, interviewer-administered questionnaire and visual analogue scale (VAS). Results In November 2008 and in June 2009, 212 of 279 eligible patients were assessed for adherence. Overall, 95.2% [95%CI: 91.3–97.7] of the patients reported not having missed a tablet in the last 4 days. On the VAS, complete adherence was estimated at 92.5% [95%CI: 88.0–95.6]. INH urine test was positive for 97.6% [95%CI: 94.6–99.2] of the patients. Pill count could be assessed among only 70% of the interviewed patients. Among them, it was complete for 82.3% [95%CI: 75.1–88.1]. Among the 212 surveyed patients, 193 (91.0%) were successfully treated (cured or treatment completed). The data suggest a fair agreement between the questionnaire and the INH urine test (ku200a=u200a0.43) and between the questionnaire and the VAS (ku200a=u200a0.40). Agreement was poor between the other adherence tools. Conclusion These results suggest that SAT, together with the FDC, allows achieving appropriate adherence to antituberculosis treatment in a high TB and HIV burden area. The use of a combination of a VAS and a questionnaire can be an adequate approach to monitor adherence to TB treatment in routine program conditions.

Use of Colorimetric Culture Methods for Detection of Mycobacterium tuberculosis Complex Isolates from Sputum Samples in Resource-Limited Settings

ABSTRACT Despite recent advances, tuberculosis (TB) diagnosis remains imperfect in resource-limited settings due to its complexity and costs, poor sensitivity of available tests, or long times to reporting. We present a report on the use of colorimetric methods, based on the detection of mycobacterial growth using colorimetric indicators, for the detection of Mycobacterium tuberculosis in sputum specimens. We evaluated the nitrate reductase assay (NRA), a modified NRA using para-nitrobenzoic acid (PNB) (NRAp), and the resazurin tube assay using PNB (RETAp) to differentiate tuberculous and nontuberculous mycobacteria. The performances were assessed at days 18 and 28 using mycobacterium growth indicator tube (MGIT) and Löwenstein-Jensen (LJ) medium culture methods as the reference standards. We enrolled 690 adults with suspected pulmonary tuberculosis from a regional referral hospital in Uganda between March 2010 and June 2011. At day 18, the sensitivities and specificities were 84.6% and 90.0% for the NRA, 84.1% and 92.6% for the NRAp, and 71.2% and 99.3% for the RETAp, respectively. At day 28, the sensitivity of the RETAp increased to 82.6%. Among smear-negative patients with suspected TB, sensitivities at day 28 were 64.7% for the NRA, 61.3% for the NRAp, and 50% for the RETAp. Contamination rates were found to be 5.4% for the NRA and 6.7% for the RETAp, compared with 22.1% for LJ medium culture and 20.4% for MGIT culture. The median times to positivity were 10, 7, and 25 days for colorimetric methods, MGIT culture, and LJ medium culture,respectively. Whereas the low specificity of the NRA/NRAp precludes it from being used for TB diagnosis, the RETAp might provide an alternative to LJ medium culture to decrease the time to culture results in resource-poor settings.

Identification of patients who could benefit from bedaquiline or delamanid: a multisite MDR-TB cohort study.

BACKGROUNDnThe World Health Organization recommends adding bedaquiline or delamanid to multidrug-resistant tuberculosis (MDR-TB) regimens for which four effective drugs are not available, and delamanid for patients at high risk of poor outcome.nnnOBJECTIVEnTo identify patients at risk of unfavourable outcomes who may benefit from the new drugs.nnnMETHODSnRetrospective cohort study of treatment outcomes involving four to five effective drugs for 15-24 months in programmes in Uzbekistan, Georgia, Armenia, Swaziland and Kenya between 2001 and 2011.nnnRESULTSnOf 1433 patients, 48.5% had body mass index (BMI) <18.5 kg/m(2), 72.9% had a high bacillary load, 16.7% were resistant to two injectables, 2.9% were resistant to ofloxacin (OFX) and 3.0% had extensively drug-resistant TB (XDR-TB). Treatment success ranged from 59.7% (no second-line resistance) to 27.0% (XDR-TB). XDR-TB (aOR 8.16, 95%CI 3.22-20.64), resistance to two injectables (aOR 1.90, 95%CI 1.00-3.62) or OFX (aOR 5.56, 95%CI 2.15-14.37), past incarceration (aOR 1.88, 95%CI 1.11-3.2), history of second-line treatment (aOR 3.24, 95%CI 1.53-6.85), low BMI (aOR 2.22, 95%CI 1.56-3.12) and high bacillary load (aOR 2.32, 95%CI 1.15-4.67) were associated with unfavourable outcomes. Patients started on capreomycin rather than kanamycin were more likely to have an unfavourable outcome (aOR 1.54, 95%CI 1.04-2.28).nnnCONCLUSIONnIn our cohort, patients who may benefit from bedaquiline and delamanid represented up to two thirds of all MDR-TB patients.

Incidence of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome and impact on patient outcome.

Objectives and Design We used data from a randomized trial of HIV-tuberculosis co-infected patients in Mozambique to determine the incidence and predictors of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (IRIS) occurring within 12 weeks of starting antiretroviral therapy, and to evaluate its association with patient outcome at 48 weeks. Methods HIV-tuberculosis co-infected and antiretroviral therapy-naïve adults with less than 250 CD4/mm3 were randomized to a nevirapine or efavirenz-based antiretroviral therapy initiated 4 to 6 weeks after starting tuberculosis treatment, and were then followed for 48 weeks. Tuberculosis cases were diagnosed using WHO guidelines, and tuberculosis-IRIS by case definitions of the International Network for the Study of HIV-associated IRIS. Results The 573 HIV-tuberculosis co-infected patients who initiated antiretroviral therapy had a median CD4 count of 92 cells/mm3 and HIV-1 RNA of 5.6 log10 copies/mL. Mortality at week 48 was 6.1% (35/573). Fifty-three (9.2%) patients presented a tuberculosis-IRIS within 12 weeks of starting antiretroviral therapy. Being female and having a low CD4 count, high HIV-1 RNA load, low body mass index and smear-positive pulmonary tuberculosis were independently associated with tuberculosis-IRIS. After adjustment for baseline body mass index, CD4 count and hemoglobin, occurrence of tuberculosis-IRIS was independently associated with 48-week mortality (aOR 2.72 95%CI 1.14-6.54). Immunological and HIV-1 virological responses and tuberculosis treatment outcomes were not different between patients with and without tuberculosis-IRIS. Conclusion In this large prospective cohort, tuberculosis-IRIS occurrence within 12 weeks of starting antiretroviral therapy was independently associated with the mortality of HIV-tuberculosis co-infected patients at 48 weeks post antiretroviral therapy initiation.

Male Gender is independently associated with pulmonary tuberculosis among sputum and non-sputum producers people with presumptive tuberculosis in Southwestern Uganda

BackgroundLittle is known about the association between gender and risk of TB infection. We sought to assess the impact of gender on TB prevalence among people with presumptive tuberculosis at a regional referral hospital in a high TB and HIV prevalence setting.MethodsWe analyzed data from two diagnostic TB studies conducted in rural, southwestern Uganda. People with presumptive tuberculosis were evaluated by chest X-ray, fluorescence microscopy, TB culture, and HIV testing. Our primary outcome of interest was TB infection, as defined by a positive TB culture. Our primary explanatory variable of interest was gender. We fit univariable and multivariable logistic regression models to investigate associations between TB infection and gender, before and after adjusting or possible confounding factors, including ability to produce sputum, age and residence.ResultsBetween April 2010 and September 2012, 863 people with presumptive tuberculosis (PWPTB) were enrolled in the two studies at Mbarara Regional Referral Hospital (MRRH) in Uganda. Among them 664 (76.9%) were able to produce sputum. X-ray was suggestive of TB for 258 (66.5%) of males and 175 (44.8%) of female (pu2009<u20090.001). using microscopy 84 (20%) of males and 48 (10.9%) of females were diagnosed with TB (pu2009<u20090.001) while 122 (30.3%) of males and 76 (18.4%) of females were diagnosed with TB (pu2009<u20090.001) using TB culture.In multivariable logistic regression models, the odds of having TB was higher in males than females (AOR 2.2 (1.56-3.18 95% CI°, Pu2009<u20090.001), after adjustment for age, HIV status, ability to produce sputum, and residence.ConclusionIn Southwestern Uganda, TB prevalence is higher among male than female people with presumptive TB. The increased risk of TB among males is independent of other TB risk factors. These findings emphasize the need for gender-focused interventions aimed at reducing TB transmission.

Nevirapine or efavirenz for tuberculosis and HIV coinfected patients: exposure and virological failure relationship

Objectives We describe nevirapine and efavirenz exposure on and off tuberculosis treatment and consequences for virological efficacy and tolerance in patients included in the ANRS 12146/12214-CARINEMO trial. Methods Participants were randomly selected to receive either nevirapine at 200 mg twice daily (nu200a=u200a256) or efavirenz at 600 mg daily (nu200a=u200a270), both combined with two nucleoside analogues. Blood samples were drawn 12 h after nevirapine or efavirenz administration, while on tuberculosis treatment and after tuberculosis treatment discontinuation. In 62 participants, samples taken 12 h after drug administration were drawn weekly for the first month of ART. Sixteen participants participated in an extensive pharmacokinetic study of nevirapine. Concentrations were compared with the therapeutic ranges of 3000–8000 ng/mL for nevirapine and 1000–4000 ng/mL for efavirenz. Results Nevirapine concentrations at the end of the first week of treatment (on antituberculosis drugs) did not differ from concentrations off tuberculosis treatment, but declined thereafter. Concentrations at steady-state were 4111 ng/mL at week 12 versus 6095 ng/mL at week 48 (Pu200a<u200a0.0001). Nevirapine concentrations <3000 ng/mL were found to be a risk factor for virological failure. Efavirenz concentrations were higher on than off tuberculosis treatment (2700 versus 2450 ng/mL, Pu200a<u200a0.0001). Conclusions The omission of the 2 week lead-in dose of nevirapine prevented low concentrations at treatment initiation but did not prevent the risk of virological failure. Results support the WHO recommendation to use efavirenz at 600 mg daily in patients on rifampicin-based antituberculosis therapy.

Field Evaluation of a Simple Fluorescence Method for Detection of Viable Mycobacterium tuberculosis in Sputum Specimens during Treatment Follow-Up

ABSTRACT Simple tuberculosis (TB) treatment monitoring tools are needed. We assessed the performance of fluorescein-diacetate (FDA) smear microscopy for detection of viable Mycobacterium tuberculosis in sputum specimens (n = 288) of TB cases under treatment compared to culture (17.4% culture positivity). FDA sensitivity was moderate (83.7% [95% confidence interval {CI}, 70.3 to 92.6]), and specificity was low (66.1% [59.5 to 72.2]). The good negative predictive value (94.8% [90.1 to 97.8]) and negative likelihood ratio (0.2) suggest using this method to rule out treatment failure in settings without access to culture.

Usefulness of the BACTEC MGIT 960 System for Isolation of Mycobacterium tuberculosis from Sputa Subjected to Long-Term Storage

ABSTRACT The recovery of Mycobacterium tuberculosis from sputa positive or negative for acid-fast bacilli that were stored for 17 ± 7 days and inoculated in the BACTEC MGIT 960 system (MGIT) was higher than that from sputa inoculated in Lowenstein-Jensen medium. MGIT is useful for isolation of M. tuberculosis from sputa subjected to long-term storage.

Light-emitting diode fluorescence microscopy for tuberculosis diagnosis: a meta-analysis

Light-emitting diode fluorescence microscopy (LED-FM) is recommended by the World Health Organization to replace conventional Ziehl–Neelsen microscopy for pulmonary tuberculosis diagnosis. Uptake of LED-FM has been slow. One reason is its reported loss of specificity compared with Ziehl–Neelsen microscopy. We aimed to determine the diagnostic accuracy of LED-FM for tuberculosis detection and explore potential factors that might affect its performance. A comprehensive search strategy based on pre-specified criteria was employed to identify eligible studies between January 1, 2000 and April 1, 2014 in 11 databases. Standardised study selection, data extraction and quality assessment were conducted. Pooled sensitivity and specificity of LED-FM using culture as the reference standard were estimated through meta-analyses using a bivariate random-effects model. Investigation of heterogeneity was performed by subgroup analyses. We identified 12 unique studies, half of which were from peripheral healthcare facilities. LED-FM achieved a pooled sensitivity of 66.9% (95% CI 60.5–72.7%) and pooled specificity of 96.8% (95% CI 93.1–98.6%). A pooled sensitivity of 53.0% (95% CI 42.8–63.0%) and pooled specificity of 96.1% (95% CI 86.0–99.0%) were obtained by LED-FM among HIV-infected patients. Study methodology factors and differences in the LED-FM procedure or device could also affect the performance. LED-FM specificity is high and should not be a barrier to device introduction, particularly among peripheral healthcare settings where this technology is meant to be used. Sensitivity is reduced in HIV-infected patients. Meta-analysis showed high performance of LED fluorescence microscopy in diagnosing pulmonary TB http://ow.ly/U3dxd