• Screening of patients with diabetes mellitus for tuberculosis in India

      Kumar, A; Gupta, D; Nagaraja, S B; Nair, S A; Satyanarayana, S; Zachariah, R; Harries, A D (Blackwell Publishing Ltd, 2013-05)
      To assess the feasibility, results and challenges of screening patients with diabetes mellitus (DM) for tuberculosis (TB) within the healthcare setting of six DM clinics in tertiary hospitals across India.
    • Screening of patients with tuberculosis for diabetes mellitus in China.

      Li, L; Lin, Y; Mi, F; Tan, S; Liang, B; Guo, C; Shi, L; Liu, L; Gong, F; Li, Y; et al. (2012-07-25)
      Objective  There is a high burden of both diabetes (DM) and tuberculosis (TB) in China, and this study aimed to assess feasibility and results of screening patients with TB for DM within the routine healthcare setting of six health facilities. Method  Agreement on how to screen, monitor and record was reached in May 2011 at a stakeholders' meeting, and training was carried out for staff in the six facilities in July 2011. Implementation started in September 2011, and we report on 7 months of activities up to 31 March 2012. Results  There were 8886 registered patients with TB. They were first asked whether they had DM. If the answer was no, they were screened with a random blood glucose (RBG) followed by fasting blood glucose (FBG) in those with RBG ≥ 6.1 mm (one facility) or with an initial FBG (five facilities). Those with FBG ≥ 7.0 mm were referred to DM clinics for diagnostic confirmation with a second FBG. Altogether, 1090 (12.4%) patients with DM were identified, of whom 863 (9.7%) had a known diagnosis of DM. Of 8023 patients who needed screening for DM, 7947 (99%) were screened. This resulted in a new diagnosis of DM in 227 patients (2.9% of screened patients), and of these, 226 were enrolled to DM care. In addition, 575 (7.8%) persons had impaired fasting glucose (FBG 6.1 to <7.0 mm). Prevalence of DM was significantly higher in patients in health facilities serving urban populations (14.0%) than rural populations (10.6%) and higher in hospital patients (13.5%) than those attending TB clinics (8.5%). Conclusion  This pilot project shows that it is feasible to screen patients with TB for DM in the routine setting, resulting in a high yield of patients with known and newly diagnosed disease. Free blood tests for glucose measurement and integration of TB and DM services may improve the diagnosis and management of dually affected patients.
    • Screening of patients with tuberculosis for diabetes mellitus in India

      Kumar, A; Jain, D C; Gupta, D; Satyanarayana, S; Zachariah, R; Harries, A D (2013-05)
      To assess feasibility and results of screening patients with tuberculosis (TB) for diabetes mellitus (DM) within the routine healthcare setting across the country at: eight tertiary care hospitals and more than 60 peripheral health institutions in eight tuberculosis units.
    • Self-administered treatment for tuberculosis among pastoralists in rural Ethiopia: how well does it work?

      Khogali, M; Zachariah, R; Reid, T; Alipon, S C; Zimble, S; Mahama, G; Etienne, W; Veerman, R; Dahmane, A; Weyeyso, T; et al. (Oxford University Press, 2014-03-16)
      In the Somali Regional State, Ethiopia, where most of the population are pastoralists, conventional TB treatment strategies based on directly observed treatment (DOT) at health facilities are not adapted to the mobile pastoralist lifestyle and treatment adherence is poor. From a rural district, we report on treatment outcomes of a modified self-administered treatment (SAT) strategy for pastoralists with TB.
    • Self-Administered Tuberculosis Treatment Outcomes in a Tribal Population on the Indo-Myanmar Border, Nagaland, India.

      Das, M; Isaakidis, P; Shenoy, R; Anicete, R; Sharma, H K; Ao, I; Osah, K; Mansoor, H; Saranchuk, P; Abraham, S (2014-09-26)
      Multiple strategies are being adopted by national tuberculosis (TB) programmes to achieve universal coverage of tuberculosis treatment. However, populations living in 'hard-to-reach' areas of north-east India have poor access to health services. Our study aimed to detail treatment outcomes in TB program supported by Médecins Sans Frontières (MSF) and using an alternative model of TB treatment delivery in Mon district, Nagaland, India.
    • Sequence analyses of just four genes to detect extensively drug-resistant Mycobacterium tuberculosis strains in multidrug-resistant tuberculosis patients undergoing treatment

      Feuerriegel, S; Cox, H S; Zarkua, N; Karimovich, H A; Braker, K; Rüsch-Gerdes, S; Niemann, S; Research Center Borstel, National Reference Center for Mycobacteria, Parkallee 18, 23845 Borstel, Germany; Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia; Medecins Sans Frontieres, Tashkent, Uzbekistan; Ministry of Health, Nukus, Karakalpakstan, Uzbekistan; Medecins Sans Frontieres, Berlin, Germany (2009-05-26)
      The rapid detection of Mycobacterium tuberculosis isolates resistant to second-line drugs is crucial for the institution of appropriate treatment regimens as early as possible. Although molecular methods have successfully been used for the rapid detection of resistance to first-line drugs, there are limited data on mutations that confer resistance to second-line drugs. To address this question, we analyzed Mycobacterium tuberculosis strains resistant to ofloxacin (n = 26) and to capreomycin and/or amikacin (n = 48) from Uzbekistan for variations in target genes (gyrA, gyrB, rrs, and tlyA). Strains susceptible to ofloxacin (n = 49) and capreomycin and/or amikacin (n = 39) were included as controls. Mutations in gyrA or gyrB were found in 96% (25/26 strains) of the ofloxacin-resistant strains, while none of the susceptible strains displayed mutations in those two genes. The most common mutation occurred in gyrA at codon 94 (17/26 strains [65.4%]), followed by mutations at codons 90 and 91. Two strains showed a mutation in gyrB, at codons 485 and 543, respectively; both mutations have not been reported previously. The most frequent mutation in strains resistant to both amikacin and capreomycin was A1401G in rrs (34/40 strains [85.0%]). Three strains had mutations in tlyA, of which two (at codons 18 and 118) were associated with resistance to capreomycin alone. Overall, none of the 10 resistant strains (5 amikacin-resistant and capreomycin-susceptible strains) and none of the 39 susceptible control strains had mutations in the genes investigated. Our results clearly demonstrate the potential of sequence analyses of short regions of relatively few target genes for the rapid detection of resistance to second-line drugs among strains isolated from patients undergoing treatment for multidrug-resistant tuberculosis. The mechanisms that confer amikacin resistance in this setting remain unclear.
    • Short communication: antituberculosis drug-induced hepatotoxicity is unexpectedly low in HIV-infected pulmonary tuberculosis patients in Malawi.

      Tostmann, A; Boeree, M J; Harries, A D; Sauvageot, D; Banda, H T; Zijlstra, E E; Department of Pulmonary Diseases, Radboud University Nijmegen Medical Centre and University Lung Centre Dekkerswald, Nijmegen, The Netherlands. A.Tostmann@ulc.umcn.nl (2007-07)
      The proportion of patients with antituberculosis drug-induced hepatotoxicity (ATDH) was unexpectedly low during a trial on cotrimoxazole prophylaxis in Malawian HIV-positive pulmonary tuberculosis patients. About 2% of the patients developed grade 2 or 3 hepatotoxicity during tuberculosis (TB) treatment, according to WHO definitions. Data on ATDH in sub-Saharan Africa are limited. Although the numbers are not very strong, our trial and other papers suggest that ATDH is uncommon in this region. These findings are encouraging in that hepatotoxicity may cause less problem than expected, especially in the light of combined HIV/TB treatment, where drug toxicity is a major cause of treatment interruption.
    • Shortened Multidrug-Resistant Tuberculosis Treatment in Settings with a High Prevalence of Ofloxacin Resistance

      Guglielmetti, L; Varaine, F; Huerga, H; Bonnet, M; Rich, M; Mitnick, C (European Respiratory Society, 2017-07-20)
    • Should Sputum Smear Examination Be Carried Out at the End of the Intensive Phase and End of Treatment in Sputum Smear Negative Pulmonary TB Patients?

      Malhotra, S; Zodpey, S P; Chandra, S; Vashist, R P; Satyanaryana, S; Zachariah, R; Harries, A D; All India Institute of Medical Sciences, New Delhi, India. (PLoS, 2012-11)
      The Indian guidelines on following up sputum smear-negative Pulmonary tuberculosis (PTB) patients differ from the current World Health Organization (WHO) guidelines in that the former recommends two follow up sputum examinations (once at the end of intensive phase and the other at the end of treatment) while the latter recommends only one follow up sputum smear microscopy examination, which is done at the end of the intensive phase. This study was conducted to examine if there was any added value in performing an additional sputum smear examination at the end of treatment within the context of a national TB program.
    • Should urine-LAM tests be used in TB symptomatic HIV-positive patients when no CD4 count is available? A prospective observational cohort study from Malawi

      Huerga, H; Mathabire, SR; Bastard, M; Dimba, A; Kamba, C; Amoros, I; Szumilin, E (Lippincott, Williams & Wilkins, 2019-10-16)
      Background: Current eligibility criteria for urine lateral-flow-lipoarabinomannan assay (LF-LAM) in ambulatory, HIV-positive patients rely on the CD4 count. We investigated the diagnostic yield of LF-LAM and the 6-month mortality in ambulatory, TB symptomatic, HIV-positive patients regardless of their CD4 count. Methods: We conducted a prospective, observational study that included all ambulatory, >15-year-old, TB symptomatic (cough, weight loss, fever, or night sweats) HIV-positive patients presenting at 4 health facilities in Malawi. Patients received a clinical examination and were requested urine LF-LAM, sputum microscopy and Xpert MTB/RIF. TB was defined as bacteriologically confirmed if Xpert was positive. Results: Of 485 patients included, 171 (35.3%) had a CD4<200 and 32 (7.2%) were seriously ill. Median CD4 count was 341 cells/µL (IQR: 129-256). LAM was positive in 24.9% patients with CD4<200 (50% LAM Grades 2-4) and 12.5% with CD4≥200 (12.8% LAM Grades 2-4). Xpert was positive in 14.1% (44/312). Among Xpert-positive patients, LAM-positivity was: 56.7% (CD4<200) and 42.9% (CD4≥200), p=0.393. Of the patients without an Xpert result, 13.4% (23/172) were LAM-positive (i.e. potentially missed patients). Overall mortality was 9.2% (44/478). More pronounced LAM-positive patients had higher mortality than LAM-negative (Grades 2-4: 36.0%; Grade 1: 9.1%; Negative: 7.4%; p<0.001). LAM-positive patients with CD4<200 cells/µL had higher risk of mortality than LAM-negatives (aHR:3.2, 95CI:1.4-7.2, p=0.006), particularly those with LAM Grades 2-4 (aHR:4.9, 95CI:1.8-13.3, p=0.002). Conclusions: Urine-LAM testing can be useful for TB diagnosis in HIV-positive TB-symptomatic patients with no CD4 cell count. LAM grade can identify patients at higher risk of death in this situation.
    • 'SILVAMP TB LAM' rapid urine tuberculosis test predicts mortality in hospitalized HIV patients in South Africa.

      Sossen, B; Broger, T; Kerkhoff, AD; Schutz, C; Trollip, A; Moreau, E; Schumacher, SG; Burton, R; Ward, A; Wilkinson, RJ; et al. (Oxford University Press, 2020-01-09)
      Reducing diagnostic delay is key towards decreasing tuberculosis-associated deaths in people living with HIV. In tuberculosis patients with retrospective urine testing, the point-of-care Fujifilm SILVAMP TB LAM (FujiLAM) could have rapidly diagnosed tuberculosis in up to 89% who died. In FujiLAM negative patients, the probability of 12-week survival was 86-97%.
    • Sputum, sex and scanty smears: new case definition may reduce sex disparities in smear-positive tuberculosis

      Ramsay, A; Bonnet, M; Gagnidze, L; Githui, W; Varaine, F; Guérin, P J; Liverpool School of Tropical Medicine, Liverpool, UK; Epicentre, Paris, France; Kenya Medical Research Institute, Nairobi, Kenya; Médecins Sans Frontières, Paris, France (2009-05-01)
      SETTING: Urban clinic, Nairobi. OBJECTIVES: To evaluate the impact of specimen quality and different smear-positive tuberculosis (TB) case (SPC) definitions on SPC detection by sex. DESIGN: Prospective study among TB suspects. RESULTS: A total of 695 patients were recruited: 644 produced > or =1 specimen for microscopy. The male/female sex ratio was 0.8. There were no significant differences in numbers of men and women submitting three specimens (274/314 vs. 339/380, P = 0.43). Significantly more men than women produced a set of three 'good' quality specimens (175/274 vs. 182/339, P = 0.01). Lowering thresholds for definitions to include scanty smears resulted in increases in SPC detection in both sexes; the increase was significantly higher for women. The revised World Health Organization (WHO) case definition was associated with the highest detection rates in women. When analysis was restricted only to patients submitting 'good' quality specimen sets, the difference in detection between sexes was on the threshold for significance (P = 0.05). CONCLUSIONS: Higher SPC notification rates in men are commonly reported by TB control programmes. The revised WHO SPC definition may reduce sex disparities in notification. This should be considered when evaluating other interventions aimed at reducing these. Further study is required on the effects of the human immuno-deficiency virus and instructed specimen collection on sex-specific impact of new SPC definition.
    • Standardised shorter regimens versus individualised longer regimens for multidrug-resistant TB

      Abidi, S; Achar, J; Neino, M; Bang, D; Benedetti, A; Brode, S; Campbell, J; Casas, E; Conradie, F; Dravniece, G; et al. (European Respiratory Society (ERS), 2019-12-20)
      We sought to compare the effectiveness of two WHO-recommended regimens for the treatment of rifampin- or multidrug-resistant (RR/MDR) tuberculosis: a standardised regimen of 9-12 months (the "shorter regimen"), and individualised regimens of ≥20 months ("longer regimens").We collected individual patient data from observational studies identified through systematic reviews and a public call for data. We included patients meeting WHO eligibility criteria for the shorter regimen: not previously treated with second-line drugs, and with fluoroquinolone- and second-line injectable agent-susceptible RR/MDR tuberculosis. We used propensity score matched, mixed-effects meta-regression to calculate adjusted odds ratios and adjusted risk differences (aRD) for failure or relapse, death within 12 months of treatment initiation, and loss to follow-up.We included 2625/3378 (77.7%) individuals from 9 studies of shorter regimens, and 2717/13104 (20.7%) from 53 studies of longer regimens. Treatment success was higher with the shorter regimen than with longer regimens (pooled proportions: 80.0% versus 75.3%), due to less loss to follow-up with the former (aRD, -0.15 95%CI: -0.17 to -0.12). The risk difference for failure or relapse was slightly higher with the shorter regimen overall (0.02, 95%CI: 0 to 0.05), and greater in magnitude with baseline resistance to pyrazinamide (0.12, 95%CI: 0.07 to 0.16), prothionamide/ethionamide (0.07, 95%CI: -0.01 to 0.16), or ethambutol (0.09, 95%CI: 0.04 to 0.13).In patients meeting WHO criteria for its use, the standardised shorter regimen was associated with substantially less loss to follow-up during treatment as compared to individualised longer regimens, and with more failure/relapse in the presence of resistance to component medications. Our findings support the need to improve access to reliable drug susceptibility testing.
    • Strategies for reducing treatment default in drug-resistant tuberculosis: systematic review and meta-analysis [Review article].

      Toczek, A; Cox, H; Cros, P du; Cooke, G; Ford, N (2012-12-04)
      BACKGROUND: Scaling up treatment for multidrug-resistant tuberculosis is a global health priority. However, current treatment regimens are long and associated with side effects, and default rates are consequently high. This systematic review aimed to identify strategies for reducing treatment default.METHODS: We conducted a systematic search up to May 2012 to identify studies describing interventions to support patients receiving treatment for multidrug-resistant tuberculosis (MDR-TB). The potential influence of study interventions were explored through subgroup analyses.RESULTS: A total of 75 studies provided outcomes for 18 294 patients across 31 countries. Default rates ranged from 0.5% to 56%, with a pooled proportion of 14.8% (95%CI 12.4-17.4). Strategies identified to be associated with lower default rates included the engagement of community health workers as directly observed treatment (DOT) providers, the provision of DOT throughout treatment, smaller cohort sizes and the provision of patient education.CONCLUSION: Current interventions to support adherence and retention are poorly described and based on weak evidence. This review was able to identify a number of promising, inexpensive interventions feasible for implementation and scale-up in MDR-TB programmes. The high default rates reported from many programmes underscore the pressing need to further refine and evaluate simple intervention packages to support patients.
    • Successful expansion of community-based drug-resistant TB care in rural Eswatini - a retrospective cohort study.

      Kerschberger, B; Telnov, A; Yano, N; Cox, H; Zabsonre, I; Kabore, SM; Vambe, D; Ngwenya, S; Rusch, B; Luce, TM; et al. (Wiley-Blackwell, 2019-08-07)
      OBJECTIVES: Provision of drug-resistant tuberculosis (DR-TB) treatment is scarce in resource-limited settings. We assessed the feasibility of ambulatory DR-TB care for treatment expansion in rural Eswatini. METHODS: Retrospective patient-level data were used to evaluate ambulatory DR-TB treatment provision in rural Shiselweni (Eswatini), from 2008 to 2016. DR-TB care was either clinic-based led by nurses or community-based at the patient's home with involvement of community treatment supporters for provision of treatment to patients with difficulties in accessing facilities. We describe programmatic outcomes and used multivariate flexible parametric survival models to assess time to adverse outcomes. Both care models were costed in supplementary analyses. RESULTS: Of 698 patients initiated on DR-TB treatment, 57% were women and 84% were HIV-positive. Treatment initiations increased from 27 in 2008 to 127 in 2011 and decreased thereafter to 51 in 2016. Proportionally, community-based care increased from 19% in 2009 to 77% in 2016. Treatment success was higher for community-based care (79%) than clinic-based care (68%, P = 0.002). After adjustment for covariate factors among adults (n = 552), the risk of adverse outcomes (death, loss to follow-up, treatment failure) in community-based care was reduced by 41% (adjusted hazard ratio 0.59, 95% CI: 0.39-0.91). Findings were supported by sensitivity analyses. The care provider's per-patient costs for community-based (USD13 345) and clinic-based (USD12 990) care were similar. CONCLUSIONS: Ambulatory treatment outcomes were good, and community-based care achieved better treatment outcomes than clinic-based care at comparable costs. Contextualised DR-TB care programmes are feasible and can support treatment expansion in rural settings.
    • Surgical Interventions for Pulmonary Tuberculosis in Mumbai, India: Surgical Outcomes and Programmatic Challenges

      Shirodkar, S; Anande, L; Dalal, A; Desai, C; Corrêa, G; Das, M; Laxmeshwar, C; Mansoor, H; Remartinez, D; Trelles, M; et al. (International Union Against Tuberculosis and Lung Disease, 2016-09-21)
    • Symptom screen: diagnostic usefulness in detecting pulmonary tuberculosis in HIV-infected pregnant women in Kenya

      Kosgei, R J; Ndavi, P M; Ong'ech, J O; Abuya, J M; Siika, A M; Wools-Kaloustian, K; Mabeya, H; Fojo, T; Mwangi, A; Reid, T; et al. (TB Union, 2011-10)
    • Systematic, Point-of-Care Urine Lipoarabinomannan (Alere TB-LAM) Assay for Diagnosing Tuberculosis in Severely Immunocompromised HIV-Positive Ambulatory Patients

      Huerga, H; Cossa, L; Manhica, I; Bastard, M; Telnov, A; Molfino, L; Sanchez-Padilla, E (American Society of Tropical Medicine and Hygiene, 2020-01-20)
      Point-of-care urine-lipoarabinomannan (LAM) Alere Determine TB-LAM assay has shown utility diagnosing tuberculosis (TB) in HIV-positive, severely immunocompromised, TB-symptomatic patients. We assessed LAM results in severely immunocompromised patients, who had LAM systematically performed at new or follow-up HIV consultations. This was a prospective, observational study on consecutive ambulatory, > 15-year-old HIV-positive patients with CD4 < 100 cells/µL in Mozambique. Clinical assessments and LAM were performed for all and microscopy, Xpert, sputum culture, and chest X-ray for LAM-positive participants. Patients were followed up for 6 months. Of 360 patients, half were ART-naive. Lipoarabinomannan positivity was 11.9% (43/360), higher among symptomatic patients compared with asymptomatic: 18.5% (30/162), and 6.6% (13/198), respectively, P = 0.001. Tuberculosis was bacteriologically confirmed in 6/35 LAM-positive patients (2 of them asymptomatic). Lipoarabinomannan positivity was associated with higher risk of mortality (aOR:4.48, 95% CI: 1.24-16.23, P = 0.022). Systematic urine-LAM allows for rapid TB treatment initiation in severely immunocompromised HIV ambulatory patients and identifies patients at a higher risk of death.
    • Tackling mortality due to childhood tuberculosis

      Godreuil, S; Marcy, O; Wobudeya, E; Bonnet, M; Solassol, J (Elsevier, 2018-03-23)
    • Taking on the diabetes-tuberculosis epidemic in India: paving the way through operational research

      Satyanarayana, S; Kumar, A M V; Wilson, N; Kapur, A; Harries, A D; Zachariah, R (International Union Against Tuberculosis and Lung Disease, 2014-03-25)