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PloS One 2017Drug-resistant tuberculosis (TB) undermines control efforts and its burden is poorly understood in resource-limited settings. We performed a systematic review and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Drug-resistant tuberculosis (TB) undermines control efforts and its burden is poorly understood in resource-limited settings. We performed a systematic review and meta-analysis to provide an up-to-date summary of the extent of drug-resistant TB in Nigeria.
METHODS
We searched PubMed, Scopus, Embase, HINARI, AJOL, the Cochrane library, Web of Science, and Google Scholar for reports published before January 31 2017, that included any resistance, mono-resistance or multidrug resistance to anti-TB drugs in Nigeria. Summary estimates were calculated using random effects models.
RESULTS
We identified 34 anti-TB drug resistance surveys with 8002 adult TB patients consisting of 2982 new and 5020 previously-treated cases. The prevalence rate of any drug resistance among new TB cases was 32.0% (95% CI 24.0-40.0%; 734/2892) and among previously-treated cases, the rate was 53.0% (95% CI 35.0-71.0%; 1467/5020). Furthermore, multidrug resistance among new and previously-treated cases was 6.0% (95% CI 4.0-8.0%;161/2502)and 32.0% (95%CI 20.0-44.0; 357/949), respectively. There was significant heterogeneity between the studies (p<0.001, I2 tests). The prevalence of drug-resistant TB varied according to methods of drug susceptibility testing and geographic region of Nigeria.
CONCLUSION
The burden of drug-resistant TB in Nigeria is high. We recommend that a national anti-TB drug resistance survey be carried out, and strategies for case detection and programmatic management of drug-resistant TB in Nigeria need to be strengthened.
Topics: Adult; Antitubercular Agents; Humans; Nigeria; Prevalence; Risk Factors; Tuberculosis, Multidrug-Resistant
PubMed: 28704459
DOI: 10.1371/journal.pone.0180996 -
Bulletin of the World Health... Aug 2017To assess the effectiveness of decentralized treatment and care for patients with multidrug-resistant (MDR) tuberculosis, in comparison with centralized approaches. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the effectiveness of decentralized treatment and care for patients with multidrug-resistant (MDR) tuberculosis, in comparison with centralized approaches.
METHODS
We searched ClinicalTrials.gov, the Cochrane library, Embase®, Google Scholar, LILACS, PubMed®, Web of Science and the World Health Organization's portal of clinical trials for studies reporting treatment outcomes for decentralized and centralized care of MDR tuberculosis. The primary outcome was treatment success. When possible, we also evaluated, death, loss to follow-up, treatment adherence and health-system costs. To obtain pooled relative risk (RR) estimates, we performed random-effects meta-analyses.
FINDINGS
Eight studies met the eligibility criteria for review inclusion. Six cohort studies, with 4026 participants in total, reported on treatment outcomes. The pooled RR estimate for decentralized versus centralized care for treatment success was 1.13 (95% CI: 1.01-1.27). The corresponding estimate for loss to follow-up was RR: 0.66 (95% CI: 0.38-1.13), for death RR: 1.01 (95% CI: 0.67-1.52) and for treatment failure was RR: 1.07 (95% CI: 0.48-2.40). Two of three studies evaluating health-care costs reported lower costs for the decentralized models of care than for the centralized models.
CONCLUSION
Treatment success was more likely among patients with MDR tuberculosis treated using a decentralized approach. Further studies are required to explore the effectiveness of decentralized MDR tuberculosis care in a range of different settings.
Topics: Antitubercular Agents; Delivery of Health Care; Health Expenditures; Humans; Medication Adherence; Tuberculosis, Multidrug-Resistant
PubMed: 28804170
DOI: 10.2471/BLT.17.193375 -
PloS One 2016Multidrug-resistant tuberculosis (MDR-TB) represents a major obstacle towards successful TB control. Directly observed therapy (DOT) was recommended by WHO to improve... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multidrug-resistant tuberculosis (MDR-TB) represents a major obstacle towards successful TB control. Directly observed therapy (DOT) was recommended by WHO to improve adherence and treatment outcomes of MDR-TB patients, however, the effectiveness of DOT on treatment outcomes of MDR-TB patients was mixed in previous studies. We conducted this systematic review and meta-analysis to assess the association between DOT and treatment outcomes and to examine the impact of different DOT providers and DOT locations on successful treatment outcomes in MDR-TB patients.
METHODS
We searched studies published in English between January 1970 and December 2015 in major electronic databases. Two reviewers independently screened articles and extracted information of DOT, treatment success rate and other characteristics of studies. Random effects model was used to calculate the pooled treatment success rate and 95% confidence interval (CI). Sub-group analyses were conducted to access factors associated with successful treatment outcomes.
RESULTS
A total of 31 articles 7,466 participants were included. Studies reporting full DOT (67.4%, 95% CI: 61.4-72.8%) had significantly higher pooled treatment success rates than those reporting self-administration therapy (46.9%, 95% CI: 41.4-52.4%). No statistically difference was found among DOT provided by healthcare providers (65.8%, 95% CI: 55.7-74.7%), family members (72.0%, 95% CI: 31.5-93.5%) and private DOT providers (69.5%, 95% CI: 57.0-79.7%); and neither did we find significantly difference on pooled treatment success rates between patients having health facility based DOT (70.5%, 95% CI: 61.5-78.1%) and home-based DOT (68.4%, 95% CI: 51.5-81.5%).
CONCLUSION
Providing DOT for a full course of treatment associated with a higher treatment success rate in MDR-TB patients.
Topics: Antitubercular Agents; Directly Observed Therapy; Humans; Treatment Outcome; Tuberculosis, Multidrug-Resistant
PubMed: 26930287
DOI: 10.1371/journal.pone.0150511 -
PloS One 2018Knowledge of tuberculosis (TB) treatment outcomes is substantially needed to assess the performance of national TB controls programs (NTPs). To date, the overall... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Knowledge of tuberculosis (TB) treatment outcomes is substantially needed to assess the performance of national TB controls programs (NTPs). To date, the overall estimates of treatment outcomes have not been determined in Ethiopia. Therefore, this meta-analysis was undertaken to produce pooled estimates of TB treatment outcomes and to analyze the impact of prior anti-TB drug exposure and HIV co-infection.
METHODS
Potentially relevant studies were retrieved from PubMed, EMBASE, and MEDLINE online databases. The unpublished studies have been retrieved from the grey literature through Google and Google Scholar. The pooled estimates were calculated using random effect model. The summary estimates were also presented using Forest plots and Tables. The outcome measures were successful and unsuccessful treatment outcomes. Patients who were cured or with completed treatment defined as successful treatment outcome and patients meeting the definition of death, defaulting and failure are considered as unsuccessfully treated cases.
RESULTS
A total of 34 studies are included for meta-analysis. The pooled estimate of successful TB treatment outcomes amounts to 83.7% (95% CI 81.1%-86.3%). Of successfully treated cases, 33.9% were cured and the remaining completed cases. Besides, among patients with unsuccessful treatment outcome, nearly 50% were dead and the rest were treatment failures and defaulters. Sub-group analysis shows that high treatment success rate was estimated in Afar; 88.9% (95% CI 83.8%-94.2%), followed by Oromia; 88.5% (95% CI 82.6%-94.5%) and Gambella; 86.1% (95% CI 84.4%-87.9%), whereas relatively poor treatment outcome was noted in Tigray; 20.0% (95% CI 2.1%-37.9%) and Amhara; 19.0% (95% CI 12.6%-25.5%). The unsuccessful TB treatment outcome was found to be higher among HIV/TB co-infected cases with an odds ratio of 1.98 (95%CI, 1.56-2.52) and re-treated cases with an odds ratio of 2.17 (95%CI, 1.55-3.03). The time trend was assessed from 2003 to 2016, but it shows insignificant variation with treatment outcome (P = 0.108).
CONCLUSION
The rate of successful treatment outcome in Ethiopia appears generally high, only slightly below the threshold suggested by the World Health Organization. History of tuberculosis treatment and HIV/TB co-infection were inversely associated with favorable treatment outcomes.
Topics: Anti-HIV Agents; Antitubercular Agents; Coinfection; Ethiopia; HIV Infections; Humans; Treatment Outcome; Tuberculosis
PubMed: 29554144
DOI: 10.1371/journal.pone.0194675 -
Annals of Clinical Microbiology and... Jun 2016Treatment options for drug-resistant tuberculosis are still limited. Linezolid has been recommended for treatment of patients with multidrug-resistant (MDR) or... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety profile of linezolid in the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis: a systematic review and meta-analysis.
BACKGROUND
Treatment options for drug-resistant tuberculosis are still limited. Linezolid has been recommended for treatment of patients with multidrug-resistant (MDR) or extensively-drug-resistant (XDR) tuberculosis, although uncertainties remain regarding its safety and tolerability in these circumstances.
OBJECTIVE
To systematically evaluate the existing evidence regarding the efficacy and tolerability of linezolid in the treatment of MDR or XDR tuberculosis.
METHODS
We conducted a systematic review and meta-analysis in accordance with the PRISMA guidelines. Searches were conducted in PubMed, Web of Science and EMBASE followed by direct search of abstracts in the International Journal of Tuberculosis and Lung Disease to retrieve primary studies published between January 2000 and January 2016 assessing linezolid efficacy and safety in the treatment of drug-resistant TB. We evaluated the occurrence of outcomes including culture conversion, treatment success and incidence of adverse events such as myelosuppression and neuropathy.
RESULTS
Twenty-three (23) studies conducted in fourteen (14) countries and involving 507 patients were retrieved. Only 1 randomized controlled trial was identified and none of the identified studies involved participants from Africa. The pooled proportion for treatment success was 77.36 % (95 % CI = 71.38-82.83 %, I(2) = 37.6 %) with culture conversion rate determined as 88.45 % (95 % CI = 83.82-92.38 %, I(2) = 45.4 %). There was no strong evidence for both culture conversion (p = 0.0948) and treatment success (p = 0.0695) between linezolid daily doses ≤ 600 and > 600 mg. Only myelosuppression showed a strong statistical significance (p < 0.0001) between dose comparisons. The incidence of neuropathy and other adverse events leading to permanent discontinuation of linezolid also showed no significance upon dose comparisons (p = 0.3213, p = 0.9050 respectively).
CONCLUSION
Available evidence presents Linezolid as a viable option in the treatment of MDR/XDR TB although patients ought to be monitored closely for the incidence of major adverse events such as myelosuppression and neuropathy. Additionally, highly powered randomized controlled trials including participants from endemic regions are urgently needed to better inform the magnitude and significance of Linezolid treatment effect in MDR and XDR TB patients.
Topics: Antitubercular Agents; Drug Administration Schedule; Extensively Drug-Resistant Tuberculosis; Humans; Linezolid; Mycobacterium tuberculosis; Myeloid Cells; Polyneuropathies; Treatment Outcome; Tuberculosis, Pulmonary
PubMed: 27334498
DOI: 10.1186/s12941-016-0156-y -
Tropical Medicine & International... Nov 2010To assess the yield of finding additional TB or diabetes mellitus (DM) cases through systematic screening and to determine the effectiveness of preventive TB therapy in... (Review)
Review
OBJECTIVE
To assess the yield of finding additional TB or diabetes mellitus (DM) cases through systematic screening and to determine the effectiveness of preventive TB therapy in people with DM.
METHODS
We systematically reviewed studies that had screened for active TB or implemented preventive therapy for TB among people with DM, and those that screened for DM among patients with TB. We searched published literature through PubMed and EMBASE and included studies that reported the number of TB cases identified among people with DM; the number of DM cases identified among patients with TB, or the relative incidence of TB between people with DM who received a TB prophylaxis and those who did not. We assessed the yield of screening by estimating the prevalence of TB or DM in each study, the prevalence ratio and difference where comparison populations were available, and the number of persons to screen to detect an additional case of TB or DM.
RESULTS
Twelve studies on screening for TB in people with DM and 18 studies on screening for DM in patients with TB met our inclusion criteria. Screening for TB in persons with DM demonstrated that TB prevalence in this population is high, ranging from 1.7% to 36%, and increasing with rising TB prevalence in the underlying population as well as with DM severity. Screening patients with TB for DM also yielded high prevalences of DM ranging from 1.9% to 35%. Two studies examining the role of TB preventive therapy in people with DM did not provide sufficient details for clear evidence of the effectiveness.
CONCLUSION
Active screening leads to the detection of more TB and DM with varying yield. This review highlights the need for further research in screening and preventive therapy.
Topics: Adolescent; Adult; Aged; Antitubercular Agents; Diabetes Complications; Diabetes Mellitus; Female; Humans; Male; Mass Screening; Middle Aged; Opportunistic Infections; Tuberculosis; Young Adult
PubMed: 20958887
DOI: 10.1111/j.1365-3156.2010.02632.x -
The Cochrane Database of Systematic... Nov 2016Tuberculosis (TB) of the gastrointestinal tract and any other organ within the abdominal cavity is abdominal TB, and most guidelines recommend the same six-month regimen... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tuberculosis (TB) of the gastrointestinal tract and any other organ within the abdominal cavity is abdominal TB, and most guidelines recommend the same six-month regimen used for pulmonary TB for people with this diagnosis. However, some physicians are concerned whether a six-month treatment regimen is long enough to prevent relapse of the disease, particularly in people with gastrointestinal TB, which may sometimes cause antituberculous drugs to be poorly absorbed. On the other hand, longer regimens are associated with poor adherence, which could increase relapse, contribute to drug resistance developing, and increase costs to patients and health providers.
OBJECTIVES
To compare six-month versus longer drug regimens to treat people that have abdominal TB.
SEARCH METHODS
We searched the following electronic databases up to 2 September 2016: the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase (accessed via OvidSP), LILACS, INDMED, and the South Asian Database of Controlled Clinical Trials. We searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for ongoing trials. We also checked article reference lists.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) that compared six-month regimens versus longer regimens that consisted of isoniazid, rifampicin, pyrazinamide, and ethambutol to treat adults and children that had abdominal TB. The primary outcomes were relapse, with a minimum of six-month follow-up after completion of antituberculous treatment (ATT), and clinical cure at the end of ATT.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, extracted data, and assessed the risk of bias in the included trials. For analysis of dichotomous outcomes, we used risk ratios (RR) with 95% confidence intervals (CIs). Where appropriate, we pooled data from the included trials in meta-analyses. We assessed the quality of the evidence using the GRADE approach.
MAIN RESULTS
We included three RCTs, with 328 participants, that compared six-month regimens with nine-month regimens to treat adults with intestinal and peritoneal TB. All trials were conducted in Asia, and excluded people with HIV, those with co-morbidities and those who had received ATT in the previous five years. Antituberculous regimens were based on isoniazid, rifampicin, pyrazinamide, and ethambutol, and these drugs were administered daily or thrice weekly under a directly observed therapy programme. The median duration of follow-up after completion of treatment was between 12 and 39 months.Relapse was uncommon, with two cases among 140 participants treated for six months, and no events among 129 participants treated for nine months. The small number of participants means we do not know whether or not there is a difference in risk of relapse between the two regimens (very low quality evidence). At the end of therapy, there was probably no difference in the proportion of participants that achieved clinical cure between six-month and nine-month regimens (RR 1.02, 95% CI 0.97 to 1.08; 294 participants, 3 trials, moderate quality evidence). For death, there were 2/150 (1.3%) in the six-month group and 4/144 (2.8%) in the nine-month group. All deaths occurred in the first four months of treatment, so was not linked to the duration of treatment in the included trials. Similarly, the number of participants that defaulted from treatment was small in both groups, and there may be no difference between them (RR 0.50, 95% CI 0.10 to 2.59; 294 participants, 3 trials, low quality evidence). Only one trial reported on adherence to treatment, with only one participant allocated to the nine-month regimen presenting poor adherence to treatment. We do not know whether six-month regimens are associated with fewer people experiencing adverse events that lead to treatment interruption (RR 0.53, 95% CI 0.18 to 1.55; 318 participants, 3 trials, very low quality evidence).
AUTHORS' CONCLUSIONS
We found no evidence to suggest that six-month treatment regimens are inadequate for treating people that have intestinal and peritoneal TB, but numbers are small. We did not find any incremental benefits of nine-month regimens regarding relapse at the end of follow-up, or clinical cure at the end of therapy, but our confidence in the relapse estimate is very low because of size of the trials. Further research is required to make confident conclusions regarding the safety of six-month treatment for people with abdominal TB. Larger studies that include HIV-positive people, with long follow-up for detecting relapse with reliability, would help improve our knowledge around this therapeutic question.
Topics: Abdomen; Antitubercular Agents; Drug Administration Schedule; Ethambutol; Humans; Isoniazid; Pyrazinamide; Randomized Controlled Trials as Topic; Recurrence; Rifampin; Time Factors; Tuberculosis, Gastrointestinal
PubMed: 27801499
DOI: 10.1002/14651858.CD012163.pub2 -
Clinical Infectious Diseases : An... Oct 2012Human immunodeficiency virus (HIV) infection increases the risk of poor outcomes in active tuberculosis. We updated a systematic review and meta-analysis assessing the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Human immunodeficiency virus (HIV) infection increases the risk of poor outcomes in active tuberculosis. We updated a systematic review and meta-analysis assessing the effects of duration of rifamycins, schedule of dosing, and antiretroviral therapy (ART) on failure, relapse, death during treatment, and acquired drug resistance (ADR) in patients with HIV and active tuberculosis.
METHODS
We searched for randomized control trials (RCTs) and observational studies published between January 2008 and November 2011. We pooled risk differences (RD) from RCTs comparing rifampin for ≥9 months and 6 months. Within strata of the 3 treatment covariates, we calculated pooled risks and adjusted odds ratios (aORs) using outcomes from RCTs and observational studies.
RESULTS
After screening 2293 citations, 7 studies were added in the update. Risk of relapse was lowered with rifampin treatment for ≥9 months compared with 6 months (pooled RD = -9.1%; 95% CI, -16.5, -1.8). Odds of relapse were higher with shorter durations of rifamycins (aOR 2 vs ≥8 months = 5.0 [1.9, 13.2]; 6 vs ≥8 months = 2.4 [1.2, 5.0]) and in the absence of ART (aOR = 14.3, [2.1, 97.8]). Post hoc meta-regression restricted to arms with ART demonstrated no associations between rifamycin duration, dosing schedule, and outcomes.
CONCLUSIONS
In patients with HIV and active tuberculosis, ART reduces the risk of TB relapse. Use of rifamycins for ≥8 months and daily dosing in the intensive phase also improve TB treatment outcomes; however, a paucity of evidence makes their importance less clear for patients on ART. There is an urgent need to increase the number of coinfected patients receiving ART.
Topics: Anti-Retroviral Agents; Antibiotics, Antitubercular; Coinfection; HIV Infections; Humans; Rifampin; Tuberculosis
PubMed: 22820541
DOI: 10.1093/cid/cis630 -
International Journal of Molecular... Mar 2016Carbapenems (ertapenem, imipenem, meropenem) are used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB), even if the published... (Review)
Review
BACKGROUND
Carbapenems (ertapenem, imipenem, meropenem) are used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB), even if the published evidence is limited, particularly when it is otherwise difficult to identify the recommended four active drugs to be included in the regimen. No systematic review to date has ever evaluated the efficacy, safety, and tolerability of carbapenems.
METHODS
A search of peer-reviewed, scientific evidence was carried out, aimed at evaluating the efficacy/effectiveness, safety, and tolerability of carbapenem-containing regimens in individuals with pulmonary/extra-pulmonary disease which was bacteriologically confirmed as M/XDR-TB. We used PubMed to identify relevant full-text, English manuscripts up to the 20 December 2015, excluding editorials and reviews.
RESULTS
Seven out of 160 studies satisfied the inclusion criteria: two on ertapenem, one on imipenem, and four on meropenem, all published between 2005 and 2016. Of seven studies, six were retrospective, four were performed in a single center, two enrolled children, two had a control group, and six reported a proportion of XDR-TB cases higher than 20%. Treatment success was higher than 57% in five studies with culture conversion rates between 60% and 94.8%.
CONCLUSIONS
The safety and tolerability is very good, with the proportion of adverse events attributable to carbapenems below 15%.
Topics: Antitubercular Agents; Carbapenems; Clinical Studies as Topic; Ertapenem; Extensively Drug-Resistant Tuberculosis; Humans; Imipenem; Meropenem; Thienamycins; Treatment Outcome; Tuberculosis, Multidrug-Resistant; beta-Lactams
PubMed: 26985890
DOI: 10.3390/ijms17030373 -
International Journal of Infectious... Aug 2014Antiretroviral therapy (ART) reduces the morbidity and mortality of patients infected with HIV. Standard ART includes either nevirapine or efavirenz, however the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Antiretroviral therapy (ART) reduces the morbidity and mortality of patients infected with HIV. Standard ART includes either nevirapine or efavirenz, however the efficacy of these drugs is limited in patients receiving rifampin treatment for tuberculosis (TB). We compared the efficacy and safety of nevirapine- and efavirenz-based ART regimens in patients co-infected with both HIV and TB through a systematic review and meta-analysis.
METHODS
A comprehensive search of the literature was carried out to identify clinical trials comparing the efficacy and safety of nevirapine- and efavirenz-based ART regimens in HIV-associated TB. Eligible clinical studies included at least one primary or secondary event; the primary event was virological response and secondary events were TB treatment outcomes, mortality, and safety profile.
RESULTS
This meta-analysis compared five randomized clinical trials and four retrospective clinical trials. Both included patients co-infected with HIV and TB; 833 received nevirapine, while 1424 received efavirenz. The proportion of patients achieving a virological response by the end of the follow-up was higher in the efavirenz group: plasma viral load <400 copies/ml, risk ratio (RR) 1.10, 95% confidence interval (CI) 1.03-1.17 (p = 0.004); plasma viral load<50 copies/ml, RR 1.07, 95% CI 0.98-1.16 (p = 0.146). No significant differences were found in either mortality (RR 0.70, 95% CI 0.44-1.13, p = 0.142) or TB treatment outcomes (RR 1.01, 95% CI 0.96-1.06, p = 0.766). Due to adverse advents, nevirapine-based regimens significantly increased the risk of discontinuation of assigned ART (RR 0.43, 95% CI 0.23-0.81, p = 0.009).
CONCLUSIONS
Although efavirenz-based ART was associated with more satisfactory virological outcomes, nevirapine-based ART could be considered an acceptable alternative for patients for whom efavirenz cannot be administered.
Topics: Alkynes; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Benzoxazines; CD4 Lymphocyte Count; Clinical Trials as Topic; Coinfection; Cyclopropanes; HIV Infections; Humans; Nevirapine; Rifampin; Treatment Outcome; Tuberculosis; Viral Load
PubMed: 24911886
DOI: 10.1016/j.ijid.2014.04.020