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Background Outcomes of retreatment for rifampicin-resistant tuberculosis (RR-TB) are rarely reported. We report ‘definitive outcomes’ after a cascade approach to RR-TB treatment. After a bacteriologically adverse outcome for the 9-months fluoroquinolone-based Short Treatment Regimen (STR), patients were retreated with a bedaquiline-based regimen (BDQ-regimen). Methods A Retrospective cohort study of RR-TB patients treated with the STR during 2012–2019 and retreated with a BDQ-regimen in case of failure or relapse was conducted. Definitive relapse-free cure took into account BDQ-regimen outcomes. Results Of 367 patients treated with the STR, 20 (5.4%) experienced failure or relapse. Out of these 20 patients, 14 started a BDQ-regimen, of whom none experienced failure or relapse. Definitive end of treatment outcomes of STR after revising with third-line BDQ-regimen outcomes, 84.7% (311/367) were cured relapse-free, 10.6% (39/367) died during treatment and 3.0% (11/367) were lost to follow-up during treatment with either the STR or BDQ-regimen. Six patients (1.6%; 6/367) with STR failure/relapse died before starting a BDQ-regimen. No patient had definitive treatment failure or relapse and remained without treatment. Conclusions If fluoroquinolone resistance is excluded or rare, it is beneficial to use fluoroquinolone as the core drug for a first RR-TB treatment regimen and to safeguard bedaquiline for those in need of retreatment.

BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR).METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement).RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR.CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD.

sec id="st1"titleSETTING/titleNiger National Tuberculosis Programme./secsec id="st2"titleOBJECTIVE/titleTo describe the outcomes and adverse events (AEs) in a cohort of adults, children and adolescents with multidrug-resistant tuberculosis (MDR-TB) who were treated with the 'short-course regimen'./secsec id="st3"titleDESIGN/titleThe regimen comprised an intensive phase of 4-6 months with kanamycin, medium-high dose of isoniazid and prothionamide, and high doses of gatifloxacin, clofazimine, ethambutol and pyrazinamide throughout. Sixty-five patients were treated with a regimen of 12-14 months and 55 patients with a regimen of 9-11 months./secsec id="st4"titleRESULTS/titleOf the 120 patients evaluated, 110 (92%) were adults (median age 31 years) and 10 (8%) were children or adolescents (median age 17 years). The treatment success rate was respectively 88% and 83% with the 9-month regimen, and 90% and 75% with the 12-month regimen in adults and children/adolescents. Initial resistance to ethambutol and prothionamide did not affect treatment success rates but resistance to fluoroquinolones did, although this was not statistically significant. Vomiting was the most frequently encountered AE, followed by ototoxicity and hepatotoxicity. AEs experienced were mild or moderate in severity in most patients, and did not lead to treatment interruption./secsec id="st5"titleCONCLUSION/titleThese results confirm the programmatic effectiveness and tolerability of the shorter regimen in second-line drug-naïve patients./sec.

Objectif : Decrire les aspects epidemiologiques, diagnostiques, therapeutiques et evolutifs de la tuberculose pulmonaire en milieu carceral au Niger. Il s’agissait d’une etude transversale realisee sur 3ans incluant tous les cas confirmes de tuberculose pulmonaire a microscopie positive (TPM+), les co-infections VIH/ tuberculose et les cas de tuberculose pulmonaire a microscopie negative (TPM-). Resultats : Au total 3322 etaient detenus avec une prevalence de la tuberculose de 0,84%. Tous les patients etaient des hommes. La moyenne d’âge etait de 36 ans avec des extremes allant de 21 a 62 ans. 17,85% exercaient dans le secteur informel.35, 71% provenaient des milieux urbains. Sur le plan juridique 71,48% des patients etaient des condamnes et 36% des patients avaient une duree de detention de plus de 3ans au moment du diagnostic. La triade faite de toux (100% de cas) –fievre (92,85% de cas) -expectoration (67,85% de cas) dominait le tableau clinique. L’amaigrissement (46,42% de cas) et la cachexie (42,46% de cas) constituaient l’essentiel des signes generaux. Le taux de co-infection VIH/SIDA- tuberculose s’elevait a 21,42%. Sur le plan therapeutique 82,14% des patients etaient de la categorie 1. 53,56% des patients avaient fait l’objet d’une hospitalisation tandis que 46,44% avaient observe le traitement selon un mode ambulatoire. La guerison etait de 46,42% de cas, le deces etait 28,53 %. Conclusion : Des mesures preventives et therapeutiques efficaces sont indispensables en milieu penitencier. Objectives: Describe the epidemiological, diagnostic, therapeutic and evolutionary aspects of pulmonary tuberculosis in prisons in Niger. This was a cross-sectional 3-year study that included all confirmed cases of smear-positive pulmonary tuberculosis, HIV / TB co-infections, and smearnegative pulmonary tuberculosis (TPM-). Results: A total of 3322 inmates and the prevalence of tuberculosis was 0.84%. All the patients were men. The average age was 36 years old with extremes ranging from 21 to 62 years old. 17.85% were in the informal sector. 35 71% came from urban areas. In legal terms, 71.48% of patients were convicted and 36% of patients had a detention period of more than 3 years at the time of diagnosis. The triad made of cough (100% of cases) -fever (92.85% of cases) -expectoration (67.85% of cases) dominated the clinical picture. Weight loss (46.42% of cases) and cachexia (42.46% of cases). The clinical signs, the bacteriological examination of the sputum as well as the x-ray (50% of the patients) formed the basis of the diagnosis with miliary predominance. The HIV / AIDS-TB co-infection rate was 21.42%. 82.14% of patients were in Category 1. 53.56% of patients had been hospitalized while 46.44% had been on ambulatory therapy. The therapeutic success was 46, 42% and the death rate was 28.53%. Conclusion: Effective preventive and therapeutic measures are essential in a penitentiary environment.

Tuberculosis (TB) treatment management of patients becomes more difficult with increasing drug resistance. Monitoring of TB treatment is therefore of utmost importance to increase the success rate and prevent complications. This chapter provides an overview of the most critical microbiological, clinical and drug-related parameters at the start and during the treatment of tuberculosis. Therapeutic drug monitoring has been recommended in order to further minimize drug-related adverse reactions and optimize treatment response. An approach on how to include personalized management in programmatic treatment is included.

The short treatment regimen (STR) achieves a >80% cure in rifampicin-resistant tuberculosis (RR-TB) patients. However, ototoxicity induced by the injectable is a concern. This is the first study to evaluate the replacement of injectables by linezolid in patients with audiometry abnormalities at baseline or during the treatment.We conducted a retrospective cohort study of all RR-TB patients started on the STR between 2016 and June, 2019, in Niger. Patients underwent audiometry every 2 months in 2016 and every month since 2017.Of 195 patients, 16.9% (33 out of 195) received linezolid from the start (n=17), or switched from injectables to linezolid during treatment (n=16), based on audiometry abnormalities. In 2016, two patients developed severe ototoxicity despite switching to linezolid. Since 2017, no patient developed severe hearing loss or complete deafness. Severe haematological toxicity was observed in 18.1% (six out of 33) of patients on linezolid, none of which was life threatening. The use of linezolid was associated with severe but manageable adverse events (hazard ratio 8.9, 95% CI 2.5–31.5; p=0.001). A total of 90.9% (30 out of 33) of patients on a linezolid-containing STR were cured, and none experienced treatment failure. Three died, but not due to adverse events.Baseline and monthly audiometry monitoring and using linezolid after detection of hearing abnormalities appears effective to prevent severe ototoxicity, while keeping high treatment success and manageable adverse events.

Background: Treatment outcomes of the shorter regimen for rifampicin-resistant tuberculosis are not completely established. We report on these outcomes two years after treatment completion among patients enrolled in an observational cohort study in nine African countries. Methods: 1,006 patients treated with the nine-month regimen were followed every six months with sputum cultures up to 24 months after treatment completion. The risk of any unfavourable outcome, of failure and relapse, and of death during and after treatment was analysed according to patient's characteristics and initial drug susceptibility by Cox proportional hazard models. Findings: Respectively 67.8% and 57.2% patients had >=1 culture result six months and 12 months after treatment completion. Fourteen relapses were diagnosed. The probability of relapse-free success was 79.3% (95% confidence interval [CI] 76.6–82.0%) overall, 80.9% (95% CI 78.0–84.0%) among HIV-negative and 72.5% (95% CI 66.5–78.9%) among HIV-infected patients. Initial fluoroquinolone (adjusted hazard ratio [aHR] 6.7 [95% CI 3.4–13.1]) and isoniazid resistance (aHR 9.4 [95% CI 1.3–68.0]) were significantly associated with increased risk of failure/relapse and of any unfavourable outcome. Interpretation: The close to 80% relapse-free success indicates the good outcome of the regimen in low-and middle-income settings. Results confirm the lesser effectiveness of the regimen in patients with initial resistance to fluoroquinolones and support the use of high-dose isoniazid, but do not support exclusion of patients for resistance to drugs other than fluoroquinolones. Funding: Expertise-France and Agence Française de Développement. Keywords: Tuberculosis, Multidrug-resistance, Treatment outcome, Recurrence, Cohort studies, Proportional hazard models, Short regimen, Developing countries, Isoniazid, Fluoroquinolones

h2SUMMARY/h2Multidrug-resistant (MDR) and extensively drug-resistant tuberculosis (XDR-TB) are global concerns, with stagnant treatment success rates of roughly 54percnt; and 30percnt;, respectively. Despite adverse events associated with several DR-TB drugs, newly developed drugs and shorter regimens are bringing hope; recent concern has focused on drugs that prolong the corrected QT interval (QTc). QTc prolongation is a risk factor for torsades de pointe (TdP), a potentially lethal cardiac arrhythmia. While QTc prolongation is used in research as a surrogate marker for drug safety, the correlation between QTc and TdP is not perfect and depends on additional risk factors. The electrocardiogram (ECG) monitoring that has been recommended when new drugs are used has created alarm among clinicians and National Tuberculosis Programmes (NTPs). ECG monitoring is often challenging in high-burden settings where treatment alternatives are limited. According to a review of studies, the prevalence of sudden death directly attributable to TdP by QTc-prolonging DR-TB drugs is likely less than 1percnt;. The risk of death from an ineffective MDR-TB/XDR-TB regimen thus far exceeds the risk of death from arrhythmia. In patients with QTc prolongation who develop cardiac events, other significant risk factors in addition to the drugs themselves are nearly always present. Clinicians and NTPs should be aware of and manage all possible circumstances that may trigger an arrhythmia (hypopotassaemia and human immunodeficiency virus infection are probably the most frequent in DR-TB patients). We present the limited but growing evidence on QTc prolongation and DR-TB management and propose a clinical approach to achieve an optimal balance between access to life-saving drugs and patient safety.

Current World Health Organization guidelines for the formulation of treatment regimens for multidrug-resistant tuberculosis (MDR-TB) pay too little attention to the microbiological activity of anti-tuberculosis drugs. Here, we draw lessons from the pioneering work done on shorter MDR-TB treatment regimens and the current knowledge of the bactericidal and sterilizing properties of the drugs to inform the composition of treatment regimens for MDR-TB. We propose to reserve the term 'core drug' for the one drug in a regimen that contributes most to relapse-free cure. The core drug has both moderate to high bactericidal and sterilizing activity, is given throughout treatment, is well tolerated, and has no cross-resistance with the core drug used in the previous regimen. Currently used core drugs include rifampicin in the first-line 6-month regimen, and fourth-generation fluoroquinolones and bedaquiline in regimens for drug-resistant TB. All other drugs are 'companion drugs', used to avert treatment failure due to acquired drug resistance against the core drug. Some also help further reduce the risk of relapse. Moreover, toxic drugs should be avoided if there is an alternative. A regimen must always include the core drug, plus at least one companion drug with high bactericidal activity, a second bactericidal companion drug, plus two sterilizing companion drugs.

In this study, we analyzed the M. tuberculosis complex (MTBc) population structure among multidrug-resistant TB (MDR-TB) patients in Niger and tested whether the Cameroon family displayed a slower response to MDR-TB treatment. We genotyped baseline clinical isolates that had been collected from pulmonary MDR-TB patients recruited consecutively between 2008 and 2016 in Niger. Spoligotyping was used to analyze the genetic diversity of mycobacterial lineages, and Kaplan Meier's analysis to compare treatment outcomes. A total of 222 MTBc isolates were genotyped; 204 (91,9%) were identified as the Euro-American L4 lineage, with the Ghana family (106, 47,4%) and the Cameroon family (63, 28,4%) being predominant. Patients infected by Cameroon family isolates 61(96,8%) showed faster conversion (log-rank p < 0.01) than those infected with Ghana family isolates (91,5%), and were more likely to experience favorable outcome (adjusted odds ratio [aOR] 4.4; 95%CI 1.1-17.9]; p = 0.015). We found no association between MTBc families and second-line drug resistance profiles (p > 0.05). Our findings show that MDR-TB in Niger is caused by major spoligotypes of the Euro-American L4; with more rapid smear and culture conversion in patients infected with the Cameroon family. These first insights may alert clinicians that slow conversion may be associated with the type of infecting strain.

About ten years ago, the first results of the so-called “Bangladesh regimen”, a short regimen lasting nine months instead of 20 months, revolutionized multidrug-resistant tuberculosis (MDR-TB) treatment. Similar short regimens were studied in different settings, relying for their efficacy on a later generation fluoroquinolone, either gatifloxacin, moxifloxacin, or levofloxacin. We review the published material on short MDR-TB regimens, describe their different compositions, their results in national tuberculosis programs in middle- and low-income countries, the risk of acquiring resistance to fluoroquinolone, and the occurrence of adverse events. With over 80% success, the regimen performs much better than longer regimens (usually around 50%). Monitoring of adverse events allows adapting its composition to prevent severe adverse events such as deafness. We discuss the current applicability and usefulness of the short injectable-containing regimen given the 2019 recommendation of the World Health Organization (WHO) for a new long all-oral regimen. We conclude that the most effective fluoroquinolone is gatifloxacin, currently not listed as an essential medicine by WHO. It is a priority to restore its status as an essential medicine.

SETTING: Data were collected from patients starting one of the shorter treatment regimens (STRs) for multidrug-resistant tuberculosis (MDR-TB) in Bangladesh, Niger or Cameroon.OBJECTIVE: To estimate the effect of either a gatifloxacin (GFX), moxifloxacin (MFX) or levofloxacin (LVX) based STR on bacteriological effectiveness.DESIGN: Retrospective study of prospectively collected data.RESULTS: Among 1530 patients, bacteriological effectiveness was 96.7% overall. Stratified by treatment with a GFX-, LVX- or MFX-based regimen effectiveness was respectively 97.5%, 95.5% and 94.7%. Compared to those on a GFX-based regimen, the estimated summary odds ratio of having an adverse outcome was more than double (OR 2.05, 95% CI 1.09–3.90) in patients treated with either an LVX-based or MFX-based regimen. After adjusting for initial resistance, patients treated with an LVX-based regimen and MFX-based regimen had respectively a 4.5- and 8.4-fold times larger odds of an adverse bacteriological outcome. None among 859 patients at risk treated with a GFX-based compared to at least 4 of 228 among those on an MFX-based regimen acquired fluoroquinolone resistance.CONCLUSION: GFX-based regimens had superior bacteriological effectiveness than MFX-based or LVX-based regimens. As GFX is currently unavailable in most MDR-TB programs, its reintroduction should be prioritised.

The 2018 World Health Organization (WHO) treatment guidelines for multidrug-/rifampicin-resistant tuberculosis (MDR/RR-TB) give preference to all-oral long regimens lasting for 18-20 months. The guidelines strongly recommend combining bedaquiline, levofloxacin (or moxifloxacin) and linezolid, supplemented by cycloserine and/or clofazimine. The effectiveness of this combination in a long regimen has not been tested in any study to date, with corresponding uncertainty. The guidelines indicate that, ideally, all MDR-TB patients should have - as a minimum - the isolate tested for fluoroquinolones, bedaquiline and linezolid susceptibility before the start of treatment. Unfortunately, the capacity for drug susceptibility testing is insufficient in resource-limited settings. The risk of acquired bedaquiline resistance cannot be ignored, especially in patients with undetected resistance to fluoroquinolones. Both linezolid and cycloserine are known for their high frequency of serious adverse events. The combination of bedaquiline, moxifloxacin and clofazimine in the same regimen may excessively increase the QT interval. These expected adverse effects are difficult to monitor and manage in resource-limited settings, and may result in frequent modifications and a less effective regimen. The final STREAM results have confirmed the non-inferiority of the short regimen compared with the long regimen. Before evidence on the all-oral long and modified all-oral short treatment regimens is available, the WHO-recommended short MDR-TB regimens, with monitoring for ototoxicity, remain a better treatment option for the management of MDR/RR-TB patients who are eligible for short regimens in low- and middle-income countries. National tuberculosis programmes should also strengthen their capacity in the detection and management of fluoroquinolone-resistant MDR-TB following the WHO guidelines.

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%

sec id="st1"titleOBJECTIVE/titleTo assess whether the revised 2013 World Health Organization (WHO) definitions for multidrug-resistant tuberculosis (MDR-TB) treatment outcomes apply to shorter treatment regimens in low- and middle-income countries and to propose modified criteria./secsec id="st2"titleMETHODS/titleCriteria for 'failure' and 'cure' outcomes were assessed using data on 1006 patients enrolled in an observational study on the standardised 9-11 month shorter MDR-TB regimen in Africa./secsec id="st3"titleRESULTS/titleAbsence of conversion in the intensive phase, a WHO criteria for failure, was the worst performing criterion; reversion had low sensitivity and other criteria provided limited added value. Based on our study results, we propose new definitions for 'treatment failure' as treatment termination or the permanent discontinuation of 2 anti-tuberculosis drugs due to 1) positive culture after 6 months of treatment (except for one isolated positive culture) or 2) at least two consecutive grade 2+ positive sputum smears after 6 months of treatment if culture is not available; and for 'cure' as treatment completion without proof of failure AND two consecutive negative cultures taken 30 days apart, one of which should be after 6 months of treatment./secsec id="st4"titleCONCLUSION/titleThe proposed new definitions are applicable to shorter regimens in low- and middle-income countries, and should also work for the newly recommended longer regimens./sec.

People living with the human immunodeficiency virus (HIV) (PLHIV) are at high risk for tuberculosis (TB), and TB is a major cause of death in PLHIV. Preventing TB in PLHIV is therefore a key priority. Early initiation of antiretroviral therapy (ART) in asymptomatic PLHIV has a potent TB preventive effect, with even more benefits in those with advanced immunodeficiency. Applying the most recent World Health Organization recommendations that all PLHIV initiate ART regardless of clinical stage or CD4 cell count could provide a considerable TB preventive benefit at the population level in high HIV prevalence settings. Preventive therapy can treat tuberculous infection and prevent new infections during the course of treatment. It is now established that isoniazid preventive therapy (IPT) combined with ART among PLHIV significantly reduces the risk of TB and mortality compared with ART alone, and therefore has huge potential benefits for millions of sufferers. However, despite the evidence, this intervention is not implemented in most low-income countries with high burdens of HIV-associated TB. HIV and TB programme commitment, integration of services, appropriate screening procedures for excluding active TB, reliable drug supplies, patient-centred support to ensure adherence and well-organised follow-up and monitoring that includes drug safety are needed for successful implementation of IPT, and these features would also be needed for future shorter preventive regimens. A holistic approach to TB prevention in PLHIV should also include other important preventive measures, such as the detection and treatment of active TB, particularly among contacts of PLHIV, and control measures for tuberculous infection in health facilities, the homes of index patients and congregate settings.

The introduction of the nine-month short-treatment regimen (STR) has drastically improved outcomes of rifampicin-resistant tuberculosis (RR-TB) treatment. Adverse events (AE) commonly occur, including injectable-induced hearing loss. In Burundi we retrospectively assessed the frequency of adverse events and treatment modifications in all patients who initiated the STR between 2013&ndash, 2017. Among 225 included patients, 93% were successfully treated without relapse, 5% died, 1% was lost-to-follow-up, 0.4% had treatment failure and 0.4% relapsed after completion. AE were reported in 53%, with grade 3 or 4 AE in 4% of patients. AE occurred after a median of two months. Hepatotoxicity (31%), gastro-intestinal toxicity (22%) and ototoxicity (10%) were most commonly reported. One patient suffered severe hearing loss. Following AE, 7% of patients had a dose reduction and 1% a drug interruption. Kanamycin-induced ototoxicity led to 94% of modifications. All 18 patients with a modified regimen were cured relapse-free. In this exhaustive national RR-TB cohort, RR-TB was treated successfully with the STR. Adverse events were infrequent. To replace the present STR, all-oral regimens should be at least as effective and also less toxic. During and after transition, monitoring, management, and documentation of AE will remain essential.

The first step to reduce the risk of creating an epidemic of bedaquiline-resistant TB entails addressing the lack of access to rapid fluoroquinolone drug susceptibility testing in a high proportion of MDR-/RR-TB in low- and middle-income countrieshttps://bit.ly/2KbtyZ3

Setting Nine countries in West and Central Africa. Objective To assess outcomes and adverse drug events of a standardised 9-month treatment regimen for multidrug-resistant tuberculosis (MDR-TB) among patients never previously treated with second-line drugs. Design Prospective observational study of MDR-TB patients treated with a standardised 9-month regimen including moxifloxacin, clofazimine, ethambutol (EMB) and pyrazinamide (PZA) throughout, supplemented by kanamycin, prothionamide and high-dose isoniazid during an intensive phase of a minimum of 4 to a maximum of 6 months. Results Among the 1006 MDR-TB patients included in the study, 200 (19.9%) were infected with the human immunodeficiency virus (HIV). Outcomes were as follows: 728 (72.4%) cured, 93 (9.2%) treatment completed (81.6% success), 59 (5.9%) failures, 78 (7.8%) deaths, 48 (4.8%) lost to follow-up. The proportion of deaths was much higher among HIV-infected patients (19.0% vs. 5.0%). Treatment success did not differ by HIV status among survivors. Fluoroquinolone resistance was the main cause of failure, while resistance to PZA, ethionamide or EMB did not influence bacteriological outcome. The most important adverse drug event was hearing impairment (11.4% severe deterioration after 4 months). Conclusions The study results support the use of the short regimen recently recommended by the World Health Organization. Its high level of success even among HIV-positive patients promises substantial improvements in TB control.

Background In Niger, the Shorter Treatment Regimen (STR) has been implemented nationwide for rifampicin resistant tuberculosis (RR-TB), since 2008. No previous publication has shown the results from countrywide programmatic implementation using few exclusion criteria, nor exhaustively assessed the effect of initial resistance to companion drugs on outcomes. Methods The National Tuberculosis Programme and the Damien Foundation conducted a retrospective observational study to evaluate the management of RR-TB from 2008 to 2016. Baseline resistance to drugs was assessed phenotypically, complemented by screening the inhA, katG and pncA genes. Cured patients were followed-up for a period of one year after cure. Findings Among 1044 patients tested for rifampicin resistance, mainly previously treated patients, 332 were diagnosed with pulmonary RR/TB, 288 were enrolled on treatment and 255 started on STR. Six patients received a modified STR. Among 249 patients on standardised STR, 207 (83·1%) were cured relapse-free, eight (3·2%) had failure, 23 (9·2%) died, seven (2·8%) were lost to follow-up and four (1·6%) relapsed. The risk of unfavourable outcome was higher in patients with initial resistance to fluoroquinolones (aOR 20·4, 95%CI:5·6–74·6) and very severely underweight (aOR 3·9, 95%CI:1·5–10·1). Successful outcome was not affected by initial resistance to companion drugs. Serious ototoxicity was reported in eight patients (3·2%). Interpretation A comprehensive nationwide approach to multidrug-resistant tuberculosis management using the STR was feasible and successful. Outcomes were not affected by initial resistance to companion drugs. Our study confirms the effectiveness and safety of the STR. Funding Damien Foundation and Institute of Tropical Medicine-Antwerp.

SUMMARY SETTING: Niger National Tuberculosis Programme. Regions supported by the Damien Foundation. OBJECTIVE: To evaluate the effectiveness of a shortcourse standardised treatment regimen for patients with proven multidrug-resistant tuberculosis (MDR-TB) previously untreated with second-line drugs. METHODS: Prospective study including all patients enrolled from 2008 to 2010. The 12-month standardised regimen comprised high doses of gatifloxacin, clofazimine, ethambutol and pyrazinamide throughout, supplemented by kanamycin, prothionamide and mediumhigh doses of isoniazid during the intensive phase of a minimum of 4 months. Patients were monitored using sputum smear and culture at start of treatment and every 2 months. Cured patients were followed up 6-monthly for 24 months. RESUL T S: Sixty-five patients with MDR-TB were included and analysed. One of 58 patients tested for human immunodeficiency virus (1.7%) infection was positive. Twenty-five patients (39.7%) were severely affected (body mass index 616 kg/m 2 ). Cure was achieved in 58 patients (89.2%, 95%CI 81.7–96.7), 6 died and 1 defaulted. All 49 patients assessed at the 24month follow-up after cure remained smear- and culture-negative. The main adverse events were vomiting (26.2%) and hearing impairment (20%), but no treatment had to be stopped.

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.

The World Health Organization (WHO) recommends that countries implement pharmacovigilance and collect information on active drug safety monitoring (aDSM) and management of adverse events.The aim of this prospective study was to evaluate the frequency and severity of adverse events to anti-tuberculosis (TB) drugs in a cohort of consecutive TB patients treated with new (i.e. bedaquiline, delamanid) and repurposed (i.e. clofazimine, linezolid) drugs, based on the WHO aDSM project. Adverse events were collected prospectively after attribution to a specific drug together with demographic, bacteriological, radiological and clinical information at diagnosis and during therapy. This interim analysis included patients who completed or were still on treatment at time of data collection.Globally, 45 centres from 26 countries/regions reported 658 patients (68.7% male, 4.4% HIV co-infected) treated as follows: 87.7% with bedaquiline, 18.4% with delamanid (6.1% with both), 81.5% with linezolid and 32.4% with clofazimine. Overall, 504 adverse event episodes were reported: 447 (88.7%) were classified as minor (grade 1–2) and 57 (11.3%) as serious (grade 3–5). The majority of the 57 serious adverse events reported by 55 patients (51 out of 57, 89.5%) ultimately resolved. Among patients reporting serious adverse events, some drugs held responsible were discontinued: bedaquiline in 0.35% (two out of 577), delamanid in 0.8% (one out of 121), linezolid in 1.9% (10 out of 536) and clofazimine in 1.4% (three out of 213) of patients. Serious adverse events were reported in 6.9% (nine out of 131) of patients treated with amikacin, 0.4% (one out of 221) with ethionamide/prothionamide, 2.8% (15 out of 536) with linezolid and 1.8% (eight out of 498) with cycloserine/terizidone.The aDSM study provided valuable information, but implementation needs scaling-up to support patient-centred care.

Moxifloxacin may not be a valid alternative to gatifloxacin in the treatment of multidrug-resistant tuberculosis http://ow.ly/uLby30hBItG

A potential standardised regimen to manage extensively drug-resistant tuberculosis (XDR-TB) and pre-XDR caseshttp://ow.ly/LucH30bUjjH

Objective : To determine the prevalence of and factors associated with pulmonary tuberculosis (PTB) in an urban prison in sub-Saharan Africa. Design : A cross-sectional survey. Setting : The Central Prison of Douala, Cameroon. Results : Two thousand four hundred and seventy four (87.4%) out of 2830 inmates underwent screening. Twenty seven (1.1%) of the inmates were under treatment for smear-positive PTB on commencement of the survey while 60 (2.4%) were diagnosed with smear and/or culture-positive PTB during the active case finding, resulting in a point prevalence of PTB of 3.5%. HIV seroprevalence in inmates without clinical signs of PTB was 111/1067 (10.4%) while it amounted to 6/24 (25%) in PTB patients. In multiple stepwise regression analysis, a low BMl, a prison stay of ≤12 months, and a history of previous incarceration were positively associated with PTB. Conclusion : The study results confirm the high prevalence rates of PTB in prison populations and underscore the need for urgent preventive measures. East African Medical Journal Vol. 83(1) 2006: 25-30