Journal Article > ResearchFull Text
Bull World Health Organ. 1 November 2023; Volume 101 (Issue 11); 730-737.; DOI:10.2471/BLT.23.290901
Gupta-Wright A, den Boon S, MacLean E, Cirillo DM, Cobelens F, et al.
Bull World Health Organ. 1 November 2023; Volume 101 (Issue 11); 730-737.; DOI:10.2471/BLT.23.290901
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The World Health Organization has developed target product profiles containing minimum and optimum targets for key characteristics for tests for tuberculosis treatment monitoring and optimization. Tuberculosis treatment optimization refers to initiating or switching to an effective tuberculosis treatment regimen that results in a high likelihood of a good treatment outcome. The target product profiles also cover tests of cure conducted at the end of treatment. The development of the target product profiles was informed by a stakeholder survey, a cost-effectiveness analysis and a patient-care pathway analysis. Additional feedback from stakeholders was obtained by means of a Delphi-like process, a technical consultation and a call for public comment on a draft document. A scientific development group agreed on the final targets in a consensus meeting. For characteristics rated of highest importance, the document lists: (i) high diagnostic accuracy (sensitivity and specificity); (ii) time to result of optimally ≤ 2 hours and no more than 1 day; (iii) required sample type to be minimally invasive, easily obtainable, such as urine, breath, or capillary blood, or a respiratory sample that goes beyond sputum; (iv) ideally the test could be placed at a peripheral-level health facility without a laboratory; and (v) the test should be affordable to low- and middle-income countries, and allow wide and equitable access and scale-up. Use of these target product profiles should facilitate the development of new tuberculosis treatment monitoring and optimization tests that are accurate and accessible for all people being treated for tuberculosis.
Journal Article > ResearchFull Text
Lancet. 8 December 2001; Volume 358 (Issue 9297); DOI:10.1016/S0140-6736(01)06995-1
Shafer J, Falzon D, Small I, Kittle D, Ford NP
Lancet. 8 December 2001; Volume 358 (Issue 9297); DOI:10.1016/S0140-6736(01)06995-1
Journal Article > ResearchFull Text
Eur J Public Health. 1 March 2003; Volume 13 (Issue 1); 87-89.; DOI:10.1093/eurpub/13.1.87
Small I, Falzon D, van der Meer J, Ford NP
Eur J Public Health. 1 March 2003; Volume 13 (Issue 1); 87-89.; DOI:10.1093/eurpub/13.1.87
The environmental adversities around the Aral Sea in Central Asia have been the subject of recent research. Attempts at sustainable provision of palatable drinking water in low chemical and microbial contaminants for the 4 million people in the two countries around the Aral littoral have been largely unsuccessful. In the last few years, severe drought has further depleted the amount of available water. This shortage has negatively impacted on agriculture, and accentuated the out migration of people. An appeal is made to assist the local population in this arid area to cope with the acute and chronic deterioration of water security.
Journal Article > ResearchFull Text
Environ Health Perspect. 1 August 2003; Volume 111 (Issue 10); 1306-1311.; DOI:10.1289/ehp.5907
Muntean N, Jermini M, Small I, Falzon D, Fürst P, et al.
Environ Health Perspect. 1 August 2003; Volume 111 (Issue 10); 1306-1311.; DOI:10.1289/ehp.5907
A 1999 study heightened long-standing concerns over persistent organic pollutant contamination in the Aral Sea area, detecting elevated levels in breast milk and cord blood of women in Karakalpakstan (western Uzbekistan). These findings prompted a collaborative research study aimed at linking such human findings with evidence of food chain contamination in the area. An international team carried out analyses of organochlorine and organophosphate pesticides, polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) on samples of 12 foods commonly produced and consumed in Karakalpakstan. Analysis consistently detected long-lasting organochlorine pesticides and their metabolites in all foods of animal origin and in some vegetables such as onions and carrots--two low-cost components of many traditional dishes. Levels of PCBs were relatively low in all samples except fish. Analyses revealed high levels of PCDDs and PCDFs (together often termed "dioxins") in sheep fat, dairy cream, eggs, and edible cottonseed oil, among other foodstuffs. These findings indicate that food traditionally grown, sold, and consumed in Karakalpakstan is a major route of human exposure to several persistent toxic contaminants, including the most toxic of dioxins, 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). Intake estimations demonstrate that consumption of even small amounts of locally grown food may expose consumers to dioxin levels that considerably exceed the monthly tolerable dioxin intake levels set by the World Health Organization. Data presented in this study allow a first assessment of the risk associated with the consumption of certain food products in Karakalpakstan and highlight a critical public health situation.
Journal Article > ResearchFull Text
Eur Respir J. 20 March 2020; Volume 55 (Issue 3); 1901467.; DOI:10.1183/13993003.01467-2019
Abidi S, Achar J, Assao Neino MM, Bang D, Benedetti A, et al.
Eur Respir J. 20 March 2020; Volume 55 (Issue 3); 1901467.; DOI:10.1183/13993003.01467-2019
We sought to compare the effectiveness of two World Health Organization (WHO)-recommended regimens for the treatment of rifampin- or multidrug-resistant (RR/MDR) tuberculosis (TB): 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-TB. We used propensity score matched, mixed effects meta-regression to calculate adjusted odds ratios and adjusted risk differences (aRDs) for failure or relapse, death within 12 months of treatment initiation and loss to follow-up.
We included 2625 out of 3378 (77.7%) individuals from nine studies of shorter regimens and 2717 out of 13 104 (20.7%) individuals 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- -0.12). The risk difference for failure or relapse was slightly higher with the shorter regimen overall (aRD 0.02, 95% CI 0-0.05) and greater in magnitude with baseline resistance to pyrazinamide (aRD 0.12, 95% CI 0.07-0.16), prothionamide/ethionamide (aRD 0.07, 95% CI -0.01-0.16) or ethambutol (aRD 0.09, 95% CI 0.04-0.13).
In patients meeting WHO criteria for its use, the standardised shorter regimen was associated with substantially less loss to follow-up during treatment compared with individualised longer regimens and with more failure or relapse in the presence of resistance to component medications. Our findings support the need to improve access to reliable drug susceptibility testing.
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-TB. We used propensity score matched, mixed effects meta-regression to calculate adjusted odds ratios and adjusted risk differences (aRDs) for failure or relapse, death within 12 months of treatment initiation and loss to follow-up.
We included 2625 out of 3378 (77.7%) individuals from nine studies of shorter regimens and 2717 out of 13 104 (20.7%) individuals 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- -0.12). The risk difference for failure or relapse was slightly higher with the shorter regimen overall (aRD 0.02, 95% CI 0-0.05) and greater in magnitude with baseline resistance to pyrazinamide (aRD 0.12, 95% CI 0.07-0.16), prothionamide/ethionamide (aRD 0.07, 95% CI -0.01-0.16) or ethambutol (aRD 0.09, 95% CI 0.04-0.13).
In patients meeting WHO criteria for its use, the standardised shorter regimen was associated with substantially less loss to follow-up during treatment compared with individualised longer regimens and with more failure or relapse in the presence of resistance to component medications. Our findings support the need to improve access to reliable drug susceptibility testing.
Journal Article > ResearchFull Text
PLOS Med. 28 August 2012; Volume 9 (Issue 8); DOI:10.1371/journal.pmed.1001300
Ahuja SD, Ashkin D, Avendano M, Banerjee R, Bayona J, et al.
PLOS Med. 28 August 2012; Volume 9 (Issue 8); DOI:10.1371/journal.pmed.1001300
Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB.
Journal Article > ResearchFull Text
Eur Respir J. 1 September 2016; Volume 48 (Issue 4); DOI:10.1183/13993003.00462-2016
Mitnick CD, White RA, Lu C, Rodriguez CA, Bayona J, et al.
Eur Respir J. 1 September 2016; Volume 48 (Issue 4); DOI:10.1183/13993003.00462-2016
Debate persists about monitoring method (culture or smear) and interval (monthly or less frequently) during treatment for multidrug-resistant tuberculosis (MDR-TB). We analysed existing data and estimated the effect of monitoring strategies on timing of failure detection.We identified studies reporting microbiological response to MDR-TB treatment and solicited individual patient data from authors. Frailty survival models were used to estimate pooled relative risk of failure detection in the last 12 months of treatment; hazard of failure using monthly culture was the reference.Data were obtained for 5410 patients across 12 observational studies. During the last 12 months of treatment, failure detection occurred in a median of 3 months by monthly culture; failure detection was delayed by 2, 7, and 9 months relying on bimonthly culture, monthly smear and bimonthly smear, respectively. Risk (95% CI) of failure detection delay resulting from monthly smear relative to culture is 0.38 (0.34-0.42) for all patients and 0.33 (0.25-0.42) for HIV-co-infected patients.Failure detection is delayed by reducing the sensitivity and frequency of the monitoring method. Monthly monitoring of sputum cultures from patients receiving MDR-TB treatment is recommended. Expanded laboratory capacity is needed for high-quality culture, and for smear microscopy and rapid molecular tests.
Journal Article > ReviewFull Text
Lancet Infect Dis. 24 March 2013; Volume 13 (Issue 5); DOI:10.1016/S1473-3099(13)70030-6
Abubakar I, Zignol M, Falzon D, Raviglione M, Ditui L, et al.
Lancet Infect Dis. 24 March 2013; Volume 13 (Issue 5); DOI:10.1016/S1473-3099(13)70030-6
Journal Article > ResearchFull Text
Public Health Action. 21 October 2014; Volume 4 (Issue 2); S24-8.; DOI:10.5588/pha.14.0042
Khaliaukin A, Kumar AMV, Skrahina A, Hurevich H, Rusovich V, et al.
Public Health Action. 21 October 2014; Volume 4 (Issue 2); S24-8.; DOI:10.5588/pha.14.0042
SETTINGS
Tuberculosis (TB) health facilities in the Gomel Region, Republic of Belarus-settings with a high burden of multidrug-resistant TB (MDR-TB) and human immunodeficiency virus (HIV) infection.
OBJECTIVE
To determine treatment outcomes among MDR-TB patients diagnosed in 2009-2010 and factors associated with unsuccessful outcomes (death, failure and loss to follow-up).
DESIGN
Retrospective cohort study involving a review of an electronic patient database maintained under the National Tuberculosis Control Programme.
RESULTS
Of 517 patients diagnosed, 78 (15%) did not start treatment. Among 439 patients who started treatment (84% males, median age 45 years, 15% HIV-infected), 291 (66%) had unsuccessful outcomes (35% deaths, 18% treatment failure and 13% lost to follow-up). Multivariate regression analysis showed that patients aged ⩾45 years (aRR 1.2, 95%CI 1.1-1.3), HIV-infected patients and those not receiving antiretroviral therapy (ART) (aRR 1.5, 95%CI 1.4-1.6) and those with a previous history of anti-tuberculosis treatment (aRR 1.2, 95%CI 1.1-1.4) had significantly higher risk of unsuccessful outcomes.
CONCLUSION
Treatment outcomes among MDR-TB patients were poor, with high rates of death, failure and loss to follow-up (including pre-treatment loss to follow-up). Urgent measures to increase ART uptake among HIV-infected MDR-TB patients, improved access to second-line anti-tuberculosis drug susceptibility testing and comprehensive patient support measures are required to address this grim situation.
Tuberculosis (TB) health facilities in the Gomel Region, Republic of Belarus-settings with a high burden of multidrug-resistant TB (MDR-TB) and human immunodeficiency virus (HIV) infection.
OBJECTIVE
To determine treatment outcomes among MDR-TB patients diagnosed in 2009-2010 and factors associated with unsuccessful outcomes (death, failure and loss to follow-up).
DESIGN
Retrospective cohort study involving a review of an electronic patient database maintained under the National Tuberculosis Control Programme.
RESULTS
Of 517 patients diagnosed, 78 (15%) did not start treatment. Among 439 patients who started treatment (84% males, median age 45 years, 15% HIV-infected), 291 (66%) had unsuccessful outcomes (35% deaths, 18% treatment failure and 13% lost to follow-up). Multivariate regression analysis showed that patients aged ⩾45 years (aRR 1.2, 95%CI 1.1-1.3), HIV-infected patients and those not receiving antiretroviral therapy (ART) (aRR 1.5, 95%CI 1.4-1.6) and those with a previous history of anti-tuberculosis treatment (aRR 1.2, 95%CI 1.1-1.4) had significantly higher risk of unsuccessful outcomes.
CONCLUSION
Treatment outcomes among MDR-TB patients were poor, with high rates of death, failure and loss to follow-up (including pre-treatment loss to follow-up). Urgent measures to increase ART uptake among HIV-infected MDR-TB patients, improved access to second-line anti-tuberculosis drug susceptibility testing and comprehensive patient support measures are required to address this grim situation.
Journal Article > CommentaryFull Text
Eur Respir J. 18 March 2015; Volume 45 (Issue 4); DOI:10.1183/09031936.00214014
Lonnroth K, Migliori GB, Abubakar I, DAmbrosio L, de Vries G, et al.
Eur Respir J. 18 March 2015; Volume 45 (Issue 4); DOI:10.1183/09031936.00214014
This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards "pre-elimination" (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions.