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1.
Background
Tuberculosis (TB) is an important cause of human suffering and death. Human immunodeficiency virus (HIV), multi-drug resistant TB (MDR-TB), and extensive drug resistant tuberculosis (XDR-TB) have emerged as threats to TB control. The association between MDR-TB and HIV infection has not yet been fully investigated. We conducted a systematic review and meta-analysis to summarize the evidence on the association between HIV infection and MDR-TB.Methods and Results
Original studies providing Mycobacterium tuberculosis resistance data stratified by HIV status were identified using MEDLINE and ISI Web of Science. Crude MDR-TB prevalence ratios were calculated and analyzed by type of TB (primary or acquired), region and study period. Heterogeneity across studies was assessed, and pooled prevalence ratios were generated if appropriate. No clear association was found between MDR-TB and HIV infection across time and geographic locations. MDR-TB prevalence ratios in the 32 eligible studies, comparing MDR-TB prevalence by HIV status, ranged from 0.21 to 41.45. Assessment by geographical region or study period did not reveal noticeable patterns. The summary prevalence ratios for acquired and primary MDR-TB were 1.17 (95% CI 0.86, 1.6) and 2.72 (95% CI 2.03, 3.66), respectively. Studies eligible for review were few considering the size of the epidemics. Most studies were not adjusted for confounders and the heterogeneity across studies precluded the calculation of a meaningful overall summary measure.Conclusions
We could not demonstrate an overall association between MDR-TB and HIV or acquired MDR-TB and HIV, but our results suggest that HIV infection is associated with primary MDR-TB. Future well-designed studies and surveillance in all regions of the world are needed to better clarify the relationship between HIV infection and MDR-TB. 相似文献2.
Bonnet M Pardini M Meacci F Orrù G Yesilkaya H Jarosz T Andrew PW Barer M Checchi F Rinder H Orefici G Rüsch-Gerdes S Fattorini L Oggioni MR Melzer J Niemann S Varaine F 《PloS one》2011,6(8):e23081
Introduction
Emerging antituberculosis drug resistance is a serious threat for tuberculosis (TB) control, especially in Eastern European countries.Methods
We combined drug susceptibility results and molecular strain typing data with treatment outcome reports to assess the influence of drug resistance on TB treatment outcomes in a prospective cohort of patients from Abkhazia (Georgia). Patients received individualized treatment regimens based on drug susceptibility testing (DST) results. Definitions for antituberculosis drug resistance and treatment outcomes were in line with current WHO recommendations. First and second line DST, and molecular typing were performed in a supranational laboratory for Mycobacterium tuberculosis (MTB) strains from consecutive sputum smear-positive TB patients at baseline and during treatment.Results
At baseline, MTB strains were fully drug-susceptible in 189/326 (58.0%) of patients. Resistance to at least H or R (PDR-TB) and multidrug-resistance (MDR-TB) were found in 69/326 (21.2%) and 68/326 (20.9%) of strains, respectively. Three MDR-TB strains were also extensively resistant (XDR-TB). During treatment, 3/189 (1.6%) fully susceptible patients at baseline were re-infected with a MDR-TB strain and 2/58 (3.4%) PDR-TB patients became MDR-TB due to resistance amplification. 5/47 (10.6%) MDR- patients became XDR-TB during treatment. Treatment success was observed in 161/189 (85.2%), 54/69 (78.3%) and 22/68 (32.3%) of patients with fully drug susceptible, PDR- and MDR-TB, respectively. Development of ofloxacin resistance was significantly associated with a negative treatment outcome.Conclusion
In Abkhazia, a region with high prevalence of drug resistant TB, the use of individualized MDR-TB treatment regimens resulted in poor treatment outcomes and XDR-TB amplification. Nosocomial transmission of MDR-TB emphasizes the importance of infection control in hospitals. 相似文献3.
Dalila Martínez Gustavo Heudebert Carlos Seas German Henostroza Martin Rodriguez Carlos Zamudio Robert M. Centor Cesar Herrera Eduardo Gotuzzo Carlos Estrada 《PloS one》2010,5(8)
Background
Multidrug-resistant tuberculosis (MDR-TB), resistance to at least isoniazid and rifampin, is a worldwide problem.Objective
To develop a clinical prediction rule to stratify risk for MDR-TB among patients with pulmonary tuberculosis.Methods
Derivation and internal validation of the rule among adult patients prospectively recruited from 37 health centers (Perú), either a) presenting with a positive acid-fast bacillus smear, or b) had failed therapy or had a relapse within the first 12 months.Results
Among 964 patients, 82 had MDR-TB (prevalence, 8.5%). Variables included were MDR-TB contact within the family, previous tuberculosis, cavitary radiologic pattern, and abnormal lung exam. The area under the receiver-operating curve (AUROC) was 0.76. Selecting a cut-off score of one or greater resulted in a sensitivity of 72.6%, specificity of 62.8%, likelihood ratio (LR) positive of 1.95, and LR negative of 0.44. Similarly, selecting a cut-off score of two or greater resulted in a sensitivity of 60.8%, specificity of 87.5%, LR positive of 4.85, and LR negative of 0.45. Finally, selecting a cut-off score of three or greater resulted in a sensitivity of 45.1%, specificity of 95.3%, LR positive of 9.56, and LR negative of 0.58.Conclusion
A simple clinical prediction rule at presentation can stratify risk for MDR-TB. If further validated, the rule could be used for management decisions in resource-limited areas. 相似文献4.
Chadha SS Sharath BN Reddy K Jaju J Vishnu PH Rao S Parmar M Satyanarayana S Sachdeva KS Wilson N Harries AD 《PloS one》2011,6(11):e26659
Background
Revised National TB Control Programme (RNTCP), Andhra Pradesh, India. There is limited information on whether MDR-TB suspects are identified, undergo diagnostic assessment and are initiated on treatment according to the programme guidelines.Objectives
To assess i) using the programme definition, the number and proportion of MDR-TB suspects in a large cohort of TB patients on first-line treatment under RNTCP ii) the proportion of these MDR-TB suspects who underwent diagnosis for MDR-TB and iii) the number and proportion of those diagnosed as MDR-TB who were successfully initiated on treatment.Methods
A retrospective cohort analysis, by reviewing RNTCP records and reports, was conducted in four districts of Andhra Pradesh, India, among patients registered for first line treatment during October 2008 to December 2009.Results
Among 23,999 TB patients registered for treatment there were 559 (2%) MDR-TB suspects (according to programme definition) of which 307 (55%) underwent diagnosis and amongst these 169 (55%) were found to be MDR-TB. Of the MDR-TB patients, 112 (66%) were successfully initiated on treatment. Amongst those eligible for MDR-TB services, significant proportions are lost during the diagnostic and treatment initiation pathway due to a variety of operational challenges. The programme needs to urgently address these challenges for effective delivery and utilisation of the MDR-TB services. 相似文献5.
Brewer TF Choi HW Seas C Krapp F Zamudio C Shah L Ciampi A Heymann SJ Gotuzzo E 《PloS one》2011,6(10):e25861
Background
Multiple drug-resistance in new tuberculosis (TB) cases accounts for the majority of all multiple drug-resistant TB (MDR-TB) worldwide. Effective control requires determining which new TB patients should be tested for MDR disease, yet the effectiveness of global screening recommendations of high-risk groups is unknown.Methods
Sixty MDR-TB cases with no history of previous TB treatment, 80 drug-sensitive TB and 80 community-based controls were recruited in Lima, Peru between August and December, 2008 to investigate whether recommended screening practices identify individuals presenting with MDR-TB. Odd ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression to study the association of potential risk factors with case/control variables.Results
MDR-TB cases did not differ from drug-sensitive TB and community controls in rates of human immunodeficiency virus infection, reported hospital or prison visits in the 3 years prior to diagnosis. MDR-TB cases were more likely than drug-sensitive TB controls to have had a recent MDR-TB household contact (OR 4.66, (95% CI 1.56–13.87)); however, only 15 cases (28.3%) reported this exposure. In multivariate modeling, recent TB household contact, but not contact with an MDR-TB case, remained predictive of MDR-TB, OR 7.47, (95% CI 1.91–29.3). Living with a partner rather than parents was associated with a lower risk of MDR-TB, OR 0.15, (95% CI 0.04–0.51).Conclusion
Targeted drug susceptibility testing (DST) linked to reported MDR-TB contact or other high-risk exposures does not identify the majority of new TB cases with MDR disease in Lima where it is endemic. All new TB cases should be screened with DST to identify MDR patients. These findings are likely applicable to other regions with endemic MDR-TB. 相似文献6.
Sokhan Khann Eang Tan Mao Yadav Prasad Rajendra Srinath Satyanarayana Sharath Burugina Nagaraja Ajay M. V. Kumar 《PloS one》2013,8(4)
Setting
National Tuberculosis Programme, Cambodia.Objective
In a cohort of TB patients, to ascertain the proportion of patients who fulfil the criteria for presumptive MDR-TB, assess whether they underwent investigation for MDR-TB, and the results of the culture and drug susceptibility testing (DST).Methods
A cross sectional record review of TB patients registered for treatment between July-December 2011.Results
Of 19,236 TB patients registered, 409 (2%) fulfilled the criteria of presumptive MDR-TB; of these, 187 (46%) were examined for culture. This proportion was higher among relapse, failure, return after default (RAD) and non-converters at 3 months of new smear positive TB patients (>60%) as compared to non-converters at 2 months of new TB cases (<20%). Nearly two thirds (n = 113) of the samples were culture positive; of these, three-fourth (n = 85) grew Mycobacterium tuberculosis complex (MTBc) and one-fourth (n = 28) grew non-tuberculous Mycobacteria. DST results were available for 96% of the MTBc isolates. Overall, 21 patients were diagnosed as MDR-TB (all diagnosed among retreatment TB cases and none from non-converters) and all of them were initiated on MDR-TB treatment.Conclusion
There is a need to strengthen mechanisms for linking patients with presumptive MDR-TB to culture centers. The policy of testing non-converters for culture and DST needs to be reviewed. 相似文献7.
Background
One of the main strategies to control tuberculosis (TB) is to find and treat people with active disease. Unfortunately, the case detection rates remain low in many countries. Thus, we need interventions to find and treat sufficient number of patients to control TB. We investigated whether involving health extension workers (HEWs: trained community health workers) in TB control improved smear-positive case detection and treatment success rates in southern Ethiopia.Methodology/Principal Finding
We carried out a community-randomized trial in southern Ethiopia from September 2006 to April 2008. Fifty-one kebeles (with a total population of 296, 811) were randomly allocated to intervention and control groups. We trained HEWs in the intervention kebeles on how to identify suspects, collect sputum, and provide directly observed treatment. The HEWs in the intervention kebeles advised people with productive cough of 2 weeks or more duration to attend the health posts. Two hundred and thirty smear-positive patients were identified from the intervention and 88 patients from the control kebeles. The mean case detection rate was higher in the intervention than in the control kebeles (122.2% vs 69.4%, p<0.001). In addition, more females patients were identified in the intervention kebeles (149.0 vs 91.6, p<0.001). The mean treatment success rate was higher in the intervention than in the control kebeles (89.3% vs 83.1%, p = 0.012) and more for females patients (89.8% vs 81.3%, p = 0.05).Conclusions/Significance
The involvement of HEWs in sputum collection and treatment improved smear-positive case detection and treatment success rate, possibly because of an improved service access. This could be applied in settings with low health service coverage and a shortage of health workers.Trial Registration
ClinicalTrials.gov NCT00803322 相似文献8.
Background
Multidrug-resistant tuberculosis (MDR-TB) is resistant to both rifampicin (RIF) and isoniazid (INH). Whereas many TB diagnostics detect RIF-resistance, few detect INH-monoresistance, which is common and may increase risk of acquired MDR-TB. Whether inclusion of INH-resistance in a first-line rapid test for TB would have an important impact on MDR-TB rates remains uncertain.Methods
We developed a transmission model to evaluate three tests in a population similar to that of India: a rapid molecular test for TB, the same test plus RIF-resistance detection (“TB+RIF”), and detection of RIF and INH-resistance (“TB+RIF/INH”). Our primary outcome was the prevalence of INH-resistant and MDR-TB at ten years.Results
Compared to the TB test alone and assuming treatment of all diagnosed MDR cases, the TB+RIF test reduced the prevalence of MDR-TB among all TB cases from 5.5% to 3.8% (30.6% reduction, 95% uncertainty range, UR: 17–54%). Despite using liberal assumptions about the impact of INH-monoresistance on treatment outcomes and MDR-TB acquisition, expansion from TB+RIF to TB+RIF/INH lowered this prevalence only from 3.8% to 3.6% further (4% reduction, 95% UR: 3–7%) and INH-monoresistant TB from 15.8% to 15.1% (4% reduction, 95% UR: (-8)-19%).Conclusion
When added to a rapid test for TB plus RIF-resistance, detection of INH-resistance has minimal impact on transmission of TB, MDR-TB, and INH-monoresistant TB. 相似文献9.
Steven J. Reynolds Cissy Kityo Claire W. Hallahan Geoffrey Kabuye Diana Atwiine Frank Mbamanya Francis Ssali Robin Dewar Marybeth Daucher Richard T. Davey Jr Peter Mugyenyi Anthony S. Fauci Thomas C. Quinn Mark R. Dybul 《PloS one》2010,5(4)
Background
Short cycle treatment interruption could reduce toxicity and drug costs and contribute to further expansion of antiretroviral therapy (ART) programs.Methods
A 72 week, non-inferiority trial enrolled one hundred forty six HIV positive persons receiving ART (CD4+ cell count ≥125 cells/mm3 and HIV RNA plasma levels <50 copies/ml) in one of three arms: continuous, 7 days on/7 days off and 5 days on/2 days off treatment. Primary endpoint was ART treatment failure determined by plasma HIV RNA level, CD4+ cell count decrease, death attributed to study participation, or opportunistic infection.Results
Following enrollment of 32 participants, the 7 days on/7 days off arm was closed because of a failure rate of 31%. Six of 52 (11.5%) participants in the 5 days on/2 days off arm failed. Five had virologic failure and one participant had immunologic failure. Eleven of 51 (21.6%) participants in the continuous treatment arm failed. Nine had virologic failure with 1 death (lactic acidosis) and 1 clinical failure (extra-pulmonary TB). The upper 97.5% confidence boundary for the difference between the percent of non-failures in the 5 days on/2 days off arm (88.5% non-failure) compared to continuous treatment (78.4% non failure) was 4.8% which is well within the preset non-inferiority margin of 15%. No significant difference was found in time to failure in the 2 study arms (p = 0.39).Conclusions
Short cycle 5 days on/2 days off intermittent ART was at least as effective as continuous therapy.Trial Registration
ClinicalTrials.gov NCT00339456 相似文献10.
Otero L Krapp F Tomatis C Zamudio C Matthys F Gotuzzo E Van der Stuyft P Seas C 《PloS one》2011,6(10):e26276
Introduction
In high multidrug resistant (MDR) tuberculosis (TB) prevalence areas, drug susceptibility testing (DST) at diagnosis is recommended for patients with risk factors for MDR. However, this approach might miss a substantial proportion of MDR-TB in the general population. We studied primary MDR in patients considered to be at low risk of MDR-TB in Lima, Peru.Methods
We enrolled new sputum smear-positive TB patients who did not report any MDR-TB risk factor: known exposure to a TB patient whose treatment failed or who died or who was known to have MDR-TB; immunosuppressive co-morbidities, ex prison inmates; prison and health care workers; and alcohol or drug abuse. A structured questionnaire was applied to all enrolled participants to confirm the absence of these factors and thus minimize underreporting. Sputum from all participants was cultured on Löwenstein-Jensen media and DST for first line drugs was performed using the 7H10 agar method.Results
Of 875 participants with complete data, 23.2% (203) had risk factors for MDR-TB elicited after enrolment. Among the group with no reported risk factors who had a positive culture, we found a 6.3% (95%CI 4.4–8.3) (37/584) rate of MDR-TB. In this group no epidemiological characteristics were associated with MDR-TB. Thus, in this group, multidrug resistance occurred in patients with no identifiable risk factors.Conclusions
We found a high rate of primary MDR-TB in a general population with no identifiable risk factors for MDR-TB. This suggests that in a high endemic area targeting patients for MDR-TB based on the presence of risk factors is an insufficient intervention. 相似文献11.
Effective interventions and decline of antituberculosis drug resistance in Eastern Taiwan, 2004-2008
Background
The Taiwan health authority recently launched several tuberculosis (TB) control interventions, which may have an impact on the epidemic of drug-resistant TB. We conducted a population-based antituberculosis drug resistance surveillance program in Eastern Taiwan to measure the proportions of notified TB patients with anti-TB drug resistance and the trend from 2004 to 2008.Methods and Findings
All culture-positive TB patients were enrolled. Drug susceptibility testing results of the first isolate of each TB patient in each treatment course were analyzed. In total, 2688 patients were included, of which 2176 (81.0%) were new TB cases and 512 (19.0%) were previously treated cases. Among the 2176 new TB cases, 97 (4.5%) were retreated after the first episode of TB treatment within the study period. The proportion of new patients with any resistance, isoniazid resistance but not multidrug-resistant TB (resistant to at least isoniazid and rifampin, MDR-TB), and MDR-TB was 16.4%, 7.5%, and 4.0%, respectively, and that among previously treated cases was 30.9%, 7.9%, and 17.6%, respectively. The combined proportion of any resistance decreased from 23.3% in 2004 to 14.3% in 2008, and that of MDR-TB from 11.5% to 2.4%.Conclusions
The proportion of TB patients with drug-resistant TB in Eastern Taiwan remains substantial. However, an effective TB control program has successfully driven the proportion of drug resistance among TB patients downward. 相似文献12.
Clara Menéndez Azucena Bardají Betuel Sigauque Sergi Sanz John J. Aponte Samuel Mabunda Pedro L. Alonso 《PloS one》2010,5(2)
Background
In the global context of a reduction of under-five mortality, neonatal mortality is an increasingly relevant component of this mortality. Malaria in pregnancy may affect neonatal survival, though no strong evidence exists to support this association.Methods
In the context of a randomised, placebo-controlled trial of intermittent preventive treatment (IPTp) with sulphadoxine-pyrimethamine (SP) in 1030 Mozambican pregnant women, 997 newborns were followed up until 12 months of age. There were 500 live borns to women who received placebo and 497 to those who received SP.Findings
There were 58 infant deaths; 60.4% occurred in children born to women who received placebo and 39.6% to women who received IPTp (p = 0.136). There were 25 neonatal deaths; 72% occurred in the placebo group and 28% in the IPTp group (p = 0.041). Of the 20 deaths that occurred in the first week of life, 75% were babies born to women in the placebo group and 25% to those in the IPTp group (p = 0.039). IPTp reduced neonatal mortality by 61.3% (95% CI 7.4%, 83.8%); p = 0.024].Conclusions
Malaria prevention with SP in pregnancy can reduce neonatal mortality. Mechanisms associated with increased malaria infection at the end of pregnancy may explain the excess mortality in the malaria less protected group. Alternatively, SP may have reduced the risk of neonatal infections. These findings are of relevance to promote the implementation of IPTp with SP, and provide insights into the understanding of the pathophysiological mechanisms through which maternal malaria affects fetal and neonatal health.Trial Registration
ClinicalTrials.gov NCT00209781 相似文献13.
Takele Lakew Jenafir House Kevin C. Hong Elizabeth Yi Wondu Alemayehu Muluken Melese Zhaoxia Zhou Kathryn Ray Stephanie Chin Emmanuel Romero Jeremy Keenan John P. Whitcher Bruce D. Gaynor Thomas M. Lietman 《PLoS neglected tropical diseases》2009,3(2)
Background
Antibiotics are a major tool in the WHO''s trachoma control program. Even a single mass distribution reduces the prevalence of the ocular chlamydia that causes trachoma. Unfortunately, infection returns after a single treatment, at least in severely affected areas. Here, we test whether additional scheduled treatments further reduce infection, and whether infection returns after distributions are discontinued.Methods
Sixteen communities in Ethiopia were randomly selected. Ocular chlamydial infection in 1- to 5-year-old children was monitored over four biannual azithromycin distributions and for 24 months after the last treatment.Findings
The average prevalence of infection in 1- to 5-year-old children was reduced from 63.5% pre-treatment to 11.5% six months after the first distribution (P<0.0001). It further decreased to 2.6% six months after the fourth and final treatment (P = 0.0004). In the next 18 months, infection returned to 25.2%, a significant increase from six months after the last treatment (P = 0.008), but still far lower than baseline (P<0.0001). Although the prevalence of infection in any particular village fluctuated, the mean prevalence of the 16 villages steadily decreased with each treatment and steadily returned after treatments were discontinued.Conclusion
In some of the most severely affected communities ever studied, we demonstrate that repeated mass oral azithromycin distributions progressively reduce ocular chlamydial infection in a community, as long as these distributions are given frequently enough and at a high enough coverage. However, infection returns into the communities after the last treatment. Sustainable changes or complete local elimination of infection will be necessary.Trial Registration
ClinicalTrials.gov NCT00221364 相似文献14.
Tamara D. Clark Denise Njama-Meya Bridget Nzarubara Catherine Maiteki-Sebuguzi Bryan Greenhouse Sarah G. Staedke Moses R. Kamya Grant Dorsey Philip J. Rosenthal 《PloS one》2010,5(7)
Background
Combination therapies are now recommended to treat uncomplicated malaria. We used a longitudinal design to assess the incidence of malaria and compare the efficacies of 3 combination regimens in Kampala, Uganda.Methodology/Principal Findings
Children aged 1–10 years were enrolled from randomly selected households in 2004–05 and 2007, and were followed at least monthly through 2008. Insecticide-treated bednets (ITNs) were provided in 2006. Children were randomized upon their first episode, and then treated for all episodes of uncomplicated malaria with amodiaquine/sulfadoxine-pyrimethamine (AQ/SP), artesunate/amodiaquine (AS/AQ), or artemether/lumefantrine (AL). Risks of parasitological failure were determined for each episode of uncomplicated malaria and clinical parameters were followed. A total of 690 children experienced 1464 episodes of malaria. 96% of these episodes were uncomplicated malaria and treated with study drugs; 94% were due to Plasmodium falciparum. The rank order of treatment efficacy was AL > AS/AQ > AQ/SP. Failure rates increased over time for AQ/SP, but not the artemisinin-based regimens. Over the 4-year course of the study the prevalence of asymptomatic parasitemia decreased from 11.8% to 1.4%, the incidence of malaria decreased from 1.55 to 0.32 per person year, and the prevalence of anemia (hemoglobin <10 gm/dL) decreased from 5.9% to 1.0%. No episodes of severe malaria (based on WHO criteria) and no deaths were seen.Conclusions/Significance
With ready access to combination therapies and distribution of ITNs, responses were excellent for artemisinin-containing regimens, severe malaria was not seen, and the incidence of malaria and prevalence of parasitemia and anemia decreased steadily over time.Trial Registration
isrctn.org ISRCTN37517549 相似文献15.
Munyaradzi Dimairo Peter MacPherson Tsitsi Bandason Abbas Zezai Shungu S. Munyati Anthony E. Butterworth Stanley Mungofa Simba Rusikaniko Katherine Fielding Peter R. Mason Elizabeth L. Corbett 《PloS one》2010,5(7)
Background
Cases of smear-negative TB have increased dramatically in high prevalence HIV settings and pose considerable diagnostic and management challenges.Methods and Findings
Between February 2006 and July 2007, a cohort study nested within a cluster-randomised trial of community-based case finding strategies for TB in Harare, Zimbabwe was undertaken. Participants who had negative sputum smears and remained symptomatic of TB were follow-up for one year with standardised investigations including HIV testing, repeat sputum smears, TB culture and chest radiography. Defaulters were actively traced to the community. The objectives were to investigate the incidence and risk factors for TB. TB was diagnosed in 218 (18.2%) participants, of which 39.4% was bacteriologically confirmed. Most cases (84.2%) were diagnosed within 3 months, but TB incidence remained high thereafter (111.3 per 1000 person-years, 95% CI: 86.6 to 146.3). HIV prevalence was 63.3%, and HIV-infected individuals had a 3.5-fold higher risk of tuberculosis than HIV-negative individuals.Conclusion
We found that diagnosis of TB was insensitive and slow, even with early radiography and culture. Until more sensitive and rapid diagnostic tests become widely available, a much more proactive and integrated approach towards prompt initiation of ART, ideally from within TB clinics and without waiting for TB to be excluded, is needed to minimise the risk and consequences of diagnostic delay. 相似文献16.
Pushpa Malla Elisabeth Eva Kanitz Mohammad Akhtar Dennis Falzon Knut Feldmann Christian Gunneberg Shyam Sundar Jha Bhagwan Maharjan Mohan Kumar Prasai Bhabana Shrestha Sharat Chandra Verma Matteo Zignol 《PloS one》2009,4(12)
Objective
The aim of this study was to describe treatment outcomes for multi-drug resistant tuberculosis (MDR-TB) outpatients on a standardized regimen in Nepal.Methodology
Data on pulmonary MDR-TB patients enrolled for treatment in the Green Light Committee-approved National Programme between 15 September 2005 and 15 September 2006 were studied. Standardized regimen was used (8Z-Km-Ofx-Eto-Cs/16Z-Ofx-Eto-Cs) for a maximum of 32 months and follow-up was by smear and culture. Drug susceptibility testing (DST) results were not used to modify the treatment regimen. MDR-TB therapy was delivered in outpatient facilities for the whole course of treatment. Multivariable analysis was used to explain bacteriological cure as a function of sex, age, initial body weight, history of previous treatment and the region of report.Principal Findings
In the first 12-months, 175 laboratory-confirmed MDR-TB cases (62% males) had outcomes reported. Most cases had failed a Category 2 first-line regimen (87%) or a Category 1 regimen (6%), 2% were previously untreated contacts of MDR-TB cases and 5% were unspecified. Cure was reported among 70% of patients (range 38%–93% by Region), 8% died, 5% failed treatment, and 17% defaulted. Unfavorable outcomes were not correlated to the number of resistant drugs at baseline DST. Cases who died had a lower mean body weight than those surviving (40.3 kg vs 47.2 kg, p<0.05). Default was significantly higher in two regions [Eastern OR = 6.2; 95%CL2.0-18.9; Far West OR = 5.0; 95%CL1.0-24.3]. At logistic regression, cure was inversely associated with body weight <36 kg [Adj.OR = 0.1; 95%CL0.0-0.3; ref. 55–75 kg] and treatment in the Eastern region [Adj.OR = 0.1; 95%CL0.0-0.4; ref. Central region].Conclusions
The implementation of an ambulatory-based treatment programme for MDR-TB based on a fully standardized regimen can yield high cure rates even in resource-limited settings. The determinants of unfavorable outcome should be investigated thoroughly to maximize likelihood of successful treatment. 相似文献17.
Kwonjune J. Seung David B. Omatayo Salmaan Keshavjee Jennifer J. Furin Paul E. Farmer Hind Satti 《PloS one》2009,4(9)
Background
Little is known about treatment of multidrug-resistant tuberculosis (MDR-TB) in high HIV-prevalence settings such as sub-Saharan Africa.Methodology/Principal Findings
We did a retrospective analysis of early outcomes of the first cohort of patients registered in the Lesotho national MDR-TB program between July 21, 2007 and April 21, 2008. Seventy-six patients were included for analysis. Patient follow-up ended when an outcome was recorded, or on October 21, 2008 for those still on treatment. Fifty-six patients (74%) were infected with HIV; the median CD4 cell count was 184 cells/μl (range 5–824 cells/μl). By the end of the follow-up period, study patients had been followed for a median of 252 days (range 12–451 days). Twenty-two patients (29%) had died, and 52 patients (68%) were alive and in treatment. In patients who did not die, culture conversion was documented in 52/54 patients (96%). One patient had defaulted, and one patient had transferred out. Death occurred after a median of 66 days in treatment (range 12–374 days).Conclusions/Significance
In a region where clinicians and program managers are increasingly confronted by drug-resistant tuberculosis, this report provides sobering evidence of the difficulty of MDR-TB treatment in high HIV-prevalence settings. In Lesotho, an innovative community-based treatment model that involved social and nutritional support, twice-daily directly observed treatment and early empiric use of second-line TB drugs was successful in reducing mortality of MDR-TB patients. Further research is urgently needed to improve MDR-TB treatment outcomes in high HIV-prevalence settings. 相似文献18.
《PloS one》2013,8(7)
Background
Shortening tuberculosis (TB) treatment duration is a research priority. This paper presents data from a prematurely terminated randomized clinical trial, of 4-month moxifloxacin or gatifloxacin regimens, in South India.Methods
Newly diagnosed, sputum-positive HIV-negative pulmonary TB patients were randomly allocated to receive gatifloxacin or moxifloxacin, along with isoniazid and rifampicin for 4 months with pyrazinamide for first 2 months (G or M) or isoniazid and rifampicin for 6 months with ethambutol and pyrazinamide for first 2 months (C). All regimens were administered thrice-weekly. Clinical and bacteriological assessments were done monthly during treatment and for 24 months post-treatment. The Data and Safety Monitoring Board recommended termination of the trial due to high TB recurrence rates in the G and M regimens.Results
Of 416 patients in intent-to-treat analysis, 6 (5%) of 124, 2 (2%) of 110 and 2 (2%) of 137 patients with drug-susceptible TB in the G, M and C arms respectively had unfavorable response at the end of treatment; during the next 24 months, 17 (15%) of 115, 11 (11%) of 104 and 8 (6%) of 132 patients respectively, had TB recurrence. Of 38 drug-resistant patients 1 of 8 and 3 of 26 in the G and C arms respectively had unfavourable response at the end of treatment; and TB recurrence occurred in 2 of 7 and 2 of 23 patients, respectively. The differences in TB recurrence rates between the G and C arms was statistically significant (p = 0.02). Gastro-intestinal symptoms occurred in 23%, 22% and 9% of patients in the G, M and C arms respectively, but most reactions were mild and manageable with symptomatic measures; 1% required regimen modification.Conclusions
4-month thrice-weekly regimens of gatifloxacin or moxifloxacin with isoniazid, rifampicin and pyrazinamide, were inferior to standard 6-month treatment, in patients with newly diagnosed sputum positive pulmonary TB.Trial Registration
Clinical Trials Registry of India CTRI/2012/10/003060 相似文献19.
by HEWs in the health posts and general health workers at health facility were compared along a community-randomized trial. Costs were analysed from societal perspective in 2007 in US $ using standard methods. We prospectively enrolled smear positive patients, and calculated cost-effectiveness as the cost per patient successfully treated. The total cost for each successfully treated smear-positive patient was higher in health facility ($158.9) compared with community ($61.7). Community-based treatment reduced the total, patient and caregiver cost by 61.2%, 68.1% and 79.8%, respectively. Involving HEWs added a total cost of $8.80 (14.3% of total cost) on health service per patient treated in the community.
Conclusions/Significance
Community-based treatment by HEWs costs only 39% of what treatment by general health workers costs for similar outcomes. Involving HEWs in TB treatment is a cost effective treatment alternative to the health service, to the patients and the family. There is an economic and public health reason to consider involving HEWs in TB treatment in Ethiopia. However, community-based treatment requires initial investment to start its implementation, training and supervision.Trial Registration
ClinicalTrials.gov NCT00803322 相似文献20.