ABSTRACT
BACKGROUND: The value, speed of completion and robustness of the evidence generated by TB treatment trials could be improved by implementing standards for best practice.METHODS: A global panel of experts participated in a Delphi process, using a 7-point Likert scale to score and revise draft standards until consensus was reached.RESULTS: Eleven standards were defined: Standard 1, high quality data on TB regimens are essential to inform clinical and programmatic management; Standard 2, the research questions addressed by TB trials should be relevant to affected communities, who should be included in all trial stages; Standard 3, trials should make every effort to be as inclusive as possible; Standard 4, the most efficient trial designs should be considered to improve the evidence base as quickly and cost effectively as possible, without compromising quality; Standard 5, trial governance should be in line with accepted good clinical practice; Standard 6, trials should investigate and report strategies that promote optimal engagement in care; Standard 7, where possible, TB trials should include pharmacokinetic and pharmacodynamic components; Standard 8, outcomes should include frequency of disease recurrence and post-treatment sequelae; Standard 9, TB trials should aim to harmonise key outcomes and data structures across studies; Standard 10, TB trials should include biobanking; Standard 11, treatment trials should invest in capacity strengthening of local trial and TB programme staff.CONCLUSION: These standards should improve the efficiency and effectiveness of evidence generation, as well as the translation of research into policy and practice.
Subject(s)
Tuberculosis , Humans , Biological Specimen Banks , Tuberculosis/drug therapy , Clinical Trials as TopicABSTRACT
The production of guidelines for the management of drug-resistant tuberculosis (TB) fits the mandate of the World Health Organization (WHO) to support countries in the reinforcement of patient care. WHO commissioned external reviews to summarise evidence on priority questions regarding case-finding, treatment regimens for multidrug-resistant TB (MDR-TB), monitoring the response to MDR-TB treatment, and models of care. A multidisciplinary expert panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. The recommendations support the wider use of rapid drug susceptibility testing for isoniazid and rifampicin or rifampicin alone using molecular techniques. Monitoring by sputum culture is important for early detection of failure during treatment. Regimens lasting ≥ 20 months and containing pyrazinamide, a fluoroquinolone, a second-line injectable drug, ethionamide (or prothionamide), and either cycloserine or p-aminosalicylic acid are recommended. The guidelines promote the early use of antiretroviral agents for TB patients with HIV on second-line drug regimens. Systems that primarily employ ambulatory models of care are recommended over others based mainly on hospitalisation. Scientific and medical associations should promote the recommendations among practitioners and public health decision makers involved in MDR-TB care. Controlled trials are needed to improve the quality of existing evidence, particularly on the optimal composition and duration of MDR-TB treatment regimens.
Subject(s)
Tuberculosis, Multidrug-Resistant/prevention & control , Tuberculosis, Multidrug-Resistant/therapy , Ambulatory Care , Antitubercular Agents/pharmacology , Communicable Disease Control , Extensively Drug-Resistant Tuberculosis/prevention & control , Extensively Drug-Resistant Tuberculosis/therapy , Guidelines as Topic , Humans , Mycobacterium tuberculosis/metabolism , Public Health , Sputum , Treatment Outcome , World Health OrganizationABSTRACT
SUMMARY
Multidrug-resistant (MDR) and extensively drug-resistant tuberculosis (XDR-TB) are global concerns, with stagnant treatment success rates of roughly 54% and 30%, 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 1%. 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.ABSTRACT
SETTING: The Philippines, a high burden country for tuberculosis (TB). STUDY DESIGN: Health Operational Study. OBJECTIVE: To describe preliminary data from the Makati Medical Center (MMC)-DOTS Plus pilot project. METHODS: Patients were consecutively enrolled after confirmation of MDR-TB status. Individualized treatment regimens were based on drug susceptibility testing and history of previous intake for the other drugs that were not tested. Treatment outcome in those who had completed at least 18 months of therapy and interim outcome for those who received more than 12 months but less than 18 months were analyzed. RESULTS: One hundred forty-nine patients with MDR-TB were enrolled from April 1999 to 30 May 2002 at the MMC DOTS Clinic. Referrals were from private institutions and practicing physicians in 73.2% of cases. Approximately 30% of isolates tested were resistant to all five first-line drugs, 39.4% to four, 16.8% to three, 12.1% to two. Fluoroquinolone resistance was noted in 40.9% of all the isolates, including 54.5% of those resistant to five drugs and 34.6% of those resistant to four drugs. The outcome of 23 patients who completed therapy and 62 who have received more than 12 months therapy showed cure and likely cure in 73.4% of cases and failure in 3.8% and likely failure in 6.3%. Death occurred in 3.8% and default was observed in 11.4%. CONCLUSION: The MMC DOTS-Plus pilot project is a public-private collaboration in TB Control. Response to therapy was encouraging. Complete subsidy of medicines and laboratory and clinic services and DOT were essential in the successful implementation of the program. DOTS-Plus and DOTS should go hand in hand in TB control if MDR-TB is highly prevalent.
Subject(s)
Antitubercular Agents/therapeutic use , Directly Observed Therapy/methods , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Pulmonary/drug therapy , Adolescent , Adult , Aged , Drug Monitoring/methods , Female , Humans , International Cooperation , Male , Microbial Sensitivity Tests , Middle Aged , Philippines , Pilot Projects , Program Evaluation , Prospective Studies , Treatment OutcomeABSTRACT
SETTING: A hospital-based study at the Makati Medical Center, Makati City, Philippines, a hyperendemic area for tuberculosis (TB). OBJECTIVE: To determine the susceptibility of Mycobacterium tuberculosis to ciprofloxacin and ofloxacin. DESIGN: Retrospective analysis of drug susceptibility tests (DST) of M. tuberculosis isolated from 1995-2000. RESULTS: Resistance to ciprofloxacin was 26.8%, ofloxacin 35.3%, and multidrug resistance (MDR) was 17.2%. Of the MDR strains, 51.4% were resistant to ciprofloxacin and ofloxacin. Acquired resistance was significantly higher for all first-line drugs and for ciprofloxacin, but not for ofloxacin. A significant increase in resistance to ciprofloxacin and ofloxacin was noted compared to 1989-1994, while resistance to the firstline drugs was not significantly different. CONCLUSION: Ciprofloxacin and ofloxacin are now a significantly less effective alternative therapy in tuberculosis, particularly MDR-TB, due to a selection pressure from their widespread use in the treatment of TB and possibly other infections in the community, which is hyperendemic for tuberculosis.
Subject(s)
Anti-Infective Agents/pharmacology , Ciprofloxacin/pharmacokinetics , Drug Resistance, Multiple , Hospitals , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/isolation & purification , Ofloxacin/pharmacokinetics , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Pulmonary/drug therapy , Anti-Infective Agents/therapeutic use , Ciprofloxacin/therapeutic use , Culture Media , Drug Resistance, Microbial , Humans , In Vitro Techniques , Microbial Sensitivity Tests , Ofloxacin/therapeutic use , Philippines , Retrospective Studies , Sputum/microbiologyABSTRACT
SETTING: DOTS Clinic with a DOTS-Plus pilot project for the management of multidrug-resistant tuberculosis (MDR-TB) in a high burden country. OBJECTIVE: To determine the prevalence of tuberculosis (TB) infection and disease among pediatric household contacts of patients with pulmonary TB (PTB). DESIGN: Cross-sectional study. METHODOLOGY: One hundred and fifty-three children aged 0-15 years in the households of 62 bacteriologically confirmed PTB patients, including 44 with MDR-TB, were studied. BCG scars were noted, and tuberculin skin test (TST), screening chest radiography, and sputum or gastric aspirate smear and culture for Mycobacterium tuberculosis in those with radiographic findings suggestive of PTB were done. RESULTS: For children in this study, the prevalences of latent TB infection (LTBI), radiographically diagnosed pulmonary TB, and bacillary pulmonary TB were 69.2%, 3.3%, and 0.65%, respectively. Only age > or = 5 years was found to be a significant predictor of LTBI (OR 3.17, 95%CI 1.43-7.01). CONCLUSION: Contact investigation for active case-finding and early treatment of TB in children from households of patients with active PTB is essential for TB control. Further study on a more precise definition of TB infection and strategies for control in this population will be pursued.
Subject(s)
Contact Tracing , Family Characteristics , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/transmission , Adolescent , Adult , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Infant , Male , Middle Aged , Philippines/epidemiology , Prevalence , Tuberculosis, Pulmonary/diagnosisABSTRACT
SETTING: Urban and rural communities and urban poor settlements in the Philippines. OBJECTIVE: To determine bacillary disease and action taking among individuals with symptoms of tuberculosis (TB), and to analyze their implications for TB control. STUDY DESIGN AND METHOD: Subjects aged 20 years and older were interviewed in the 1997 nationwide stratified multi-cluster survey. Sputum acid-fast smears and cultures were done in subjects with abnormal screening chest radiographs. RESULTS: Individuals with TB symptoms comprised 18.1% of the population studied. The prevalence of bacillary disease was 39/1000 in symptomatic subjects compared to 13/1000 in asymptomatic subjects. Symptom screening had a 14.3% positive predictive value and a 91.4% negative predictive value for bacillary disease. Significantly more symptomatic than asymptomatic subjects attended chest radiographic screening during the survey. However, in response to their symptoms, the majority (43.0%) took no action or self medicated (31.6%), while 11.8% consulted a private practitioner, 7.5% a public health center, 4.4% a hospital, and 1.7% a traditional healer. CONCLUSION: Sputum smear examination after symptom screening was acceptable for case finding. The health seeking behavior of subjects with TB symptoms was inappropriate. A health education program and public-private collaboration in directly observed therapy, short course (DOTS) are essential for TB control in the Philippines.
Subject(s)
Community Health Services/statistics & numerical data , Patient Acceptance of Health Care , Tuberculosis/prevention & control , Adult , Aged , Female , Humans , Logistic Models , Male , Middle Aged , Odds Ratio , Philippines/epidemiology , Prevalence , Rural Population , Self Medication , Tuberculosis/epidemiology , Urban PopulationABSTRACT
SETTING: A prevalence survey of tuberculosis (TB) infection was undertaken in the Philippines, a developing country in the Western Pacific region. OBJECTIVE: To determine the bacille Calmette Guerin (BCG) vaccination rate, the prevalence of TB infection and the annual risk of TB infection (ARTI). METHODS: A nationwide stratified multi-stage cluster survey of 21,960 individuals. BCG scar verification and tuberculin test were performed on those aged > or =2 months. The ARTI was calculated using the prevalence rates of TB infection in children aged 5-9 years. RESULTS: BCG scars were noted in 66% of the study population. The prevalence of TB infection was 63.4% among unvaccinated individuals. The prevalence rate was higher in males in both urban and rural areas. With both sexes combined, urban and rural communities had similar prevalence rates. In children aged 5-9 years, the prevalence rate was 16.1% (males 17.4%, females 14.9%), corresponding to an ARTI of 2.3% (males 2.5%, females 2.1%). CONCLUSION: BCG coverage increased substantially between 1981-1983 and 1997. The ARTI, however, was virtually unchanged, indicating that morbidity due to TB continued to be high.
Subject(s)
Tuberculosis/epidemiology , Tuberculosis/prevention & control , Adolescent , Adult , Aged , BCG Vaccine , Child , Child, Preschool , Cluster Analysis , Female , Humans , Infant , Male , Middle Aged , Philippines/epidemiology , Prevalence , Tuberculin TestABSTRACT
SETTING: The Philippines is a developing country where tuberculosis (TB) remains a significant public health problem. OBJECTIVE: To determine the prevalence of TB as a basis for setting the targets of the National Tuberculosis Control Program. STUDY POPULATION AND METHODS: A multi-stage cluster survey of a random sample of 21960 subjects from 36 clusters nationwide was undertaken from 2 April to 31 July 1997. BCG scar verification and tuberculin testing was performed for subjects aged 2 months and over, and chest radiography screening was done on subjects 10 years and older. Sputum samples were collected from individuals who were initially assessed to have abnormal chest radiographs to determine the prevalence of bacillary tuberculosis. Acid-fast smear by modified Kinyoun's technique and culture on Löwenstein Jensen were done to demonstrate Mycobacterium tuberculosis. RESULTS: The prevalence of active pulmonary TB was 42/1000 population. The prevalence of culture-positive and smear-positive cases was 8.1 and 3.1/1000, respectively. The prevalence was similar in urban and rural areas. CONCLUSION: Morbidity from TB remains high. Allowing for methodological differences from the survey in 1981-1983, the prevalence of active pulmonary TB was unchanged. There was only a minimal decrease, of 37% for smear-positive cases and 25% for culture-positive cases, in the 14-year interval.
Subject(s)
Tuberculosis, Pulmonary/epidemiology , Adolescent , Adult , Age Distribution , Aged , Child , Cluster Analysis , Confidence Intervals , Developing Countries , Female , Health Surveys , Humans , Infant , Male , Middle Aged , Philippines/epidemiology , Prevalence , Risk Factors , Sex Distribution , Survival Rate , Tuberculin Test , Tuberculosis, Pulmonary/diagnosisABSTRACT
SETTING: Urban poor settlements in the Philippines. OBJECTIVE: To determine the magnitude of the tuberculosis problem in urban poor settlements in comparison with urban areas studied in the Nationwide Tuberculosis Prevalence Survey. STUDY DESIGN AND METHOD: A multistage cluster survey of BCG scar, tuberculin test, chest radiography and sputum examination for bacillary disease, in urban poor areas. RESULTS: The prevalences of culture-positive and smear-positive tuberculosis were 17.5 +/- 2.3 (95% CI 13.3-22.4) and 7.9 +/- 2.3 per thousand (95% CI 2.611.5), respectively. Extrapolated to the total population, the rates in the urban poor settlements were 12.4 +/- 1.7 (95% CI 9.6-16.2) and 5.6 +/- 1.6 per thousand population (95% CI 1.3-8.3), respectively. The prevalence of active pulmonary tuberculosis in subjects aged 10 years or more was 66 +/- 5.6/1000 (95% CI 55-77). The BCG vaccination rate was 72%. The overall prevalence of tuberculosis infection was 66%, and 39% in those aged 5-9 years, corresponding to an annual risk of infection (ARI) of 6.5%. CONCLUSION: The problem of tuberculosis was substantial in the urban poor settlements, and was appreciably worse than that in the general urban population.
Subject(s)
Poverty Areas , Tuberculosis, Pulmonary/epidemiology , Urban Health , Adolescent , Adult , BCG Vaccine , Child , Female , Health Surveys , Humans , Male , Middle Aged , Philippines/epidemiology , Prevalence , Tuberculosis, Pulmonary/diagnosisABSTRACT
SETTING: In the Philippines, programmatic treatment of drug-resistant tuberculosis (TB) was initiated by the Tropical Disease Foundation in 1999 and transitioned to the National TB Program in 2006. OBJECTIVE: To determine patient and socio-demographic characteristics associated with default, and the impact of patient support measures on default. DESIGN: Retrospective cohort analysis of 583 MDR-TB patients treated from 1999 to 2006. RESULTS: A total of 88 (15%) patients defaulted from treatment. The median follow-up time for patients who defaulted was 289 days (range 1-846). In multivariate analysis adjusted for age, sex and previous TB treatment, receiving a greater number of treatment drugs (≥ 5 vs. 2-3 drugs, HR 7.2, 95%CI 3.3-16.0, P < 0.001) was significantly associated with an increased risk of default, while decentralization reduced the risk of default (HR 0.3, 95%CI 0.2-0.7, P < 0.001). CONCLUSION: Improving access to treatment for MDR-TB through decentralization of care to centers near the patient's residence reduced the risk of default. Further research is needed to evaluate the feasibility, impact and cost-effectiveness of decentralized care models for MDR-TB treatment.
Subject(s)
Antitubercular Agents/therapeutic use , Medication Adherence , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Pulmonary/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Child , Cohort Studies , Female , Humans , Male , Middle Aged , Motivation , Patients , Philippines , Retrospective Studies , Risk Factors , Socioeconomic Factors , Treatment Refusal , Young AdultABSTRACT
OBJECTIVE: To identify predictors of initial sputum culture conversion, estimate the usefulness of persistent positive cultures at different time points in predicting treatment failure, and evaluate different definitions of culture conversion for predicting failure among patients with multidrug-resistant tuberculosis (MDR-TB) in five countries, 2000-2004. METHODS: Predictors of time to conversion were identified using multivariate Cox proportional hazards regression modeling. Receiver operating characteristic curves were plotted to visualize the effect of using different definitions of 'culture conversion' on the balance between sensitivity and specificity. RESULTS: Overall, 1209/1416 (85%) of patients with baseline positive cultures converted in a median of 3.0 months (interquartile range 2.0-5.0). Independent predictors of less likely conversion included baseline positive smear (hazard ratio [HR] 0.60, 95%CI 0.53-0.68), resistance to pyrazinamide (HR 0.82, 95%CI 0.70-0.96), fluoroquinolones (FQs; HR 0.65, 95%CI 0.51-0.83) or thioamide (HR 0.83, 95%CI 0.71-0.96), previous use of FQs (HR 0.71, 95%CI 0.60-0.83), poor outcome of previous anti-tuberculosis treatment (HR 0.69, 95%CI 0.54-0.88) and alcoholism (HR 0.74, 95%CI 0.63-0.87). The maximum combined sensitivity (84%) and specificity (94%) in predicting treatment failure was based on lack of culture conversion at month 9 of treatment, assuming conversion is defined as five consecutive negative cultures. CONCLUSION: Patients with identified risk factors were less likely to achieve sputum culture conversion during MDR-TB treatment.
Subject(s)
Antitubercular Agents/therapeutic use , Mycobacterium tuberculosis/isolation & purification , Sputum/microbiology , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Pulmonary/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Mycobacterium tuberculosis/drug effects , Predictive Value of Tests , ROC Curve , Retrospective Studies , Tuberculosis, Multidrug-Resistant/microbiology , Tuberculosis, Pulmonary/microbiology , Young AdultABSTRACT
SETTING: Prior treatment has been associated with multidrug-resistant tuberculosis (MDR-TB) in many settings. The Philippines ranks fifth among 27 priority countries for MDR-TB. OBJECTIVE: To determine the rate of MDR-TB among previously treated patients referred for MDR screening and management. DESIGN: Descriptive study of the rate of MDR-TB among 4705 previously treated patients screened from 2003 to 2008. RESULTS: MDR-TB was present in 76% of 2438 screened patients who had positive cultures. The proportion of patients with MDR-TB was the same among patients referred from public or DOTS facilities and private or non-DOTS facilities. MDR-TB occurred most frequently among patients who failed treatment with the Category 2 regimen (97%), those who did not demonstrate culture conversion after 3 months of Category 2 treatment (91%), and Category 1 failures (83%). MDR-TB rates were respectively 78% and 57% for Category 2 relapse and return after default (RAD), and respectively 33% and 22% for Category 1 relapse and RAD. CONCLUSION: MDR-TB is frequent among previously treated patients in the Philippines. Screening with culture and drug susceptibility testing should be considered for these patients.
Subject(s)
Antitubercular Agents/pharmacology , Mycobacterium tuberculosis/drug effects , Tuberculosis, Multidrug-Resistant/epidemiology , Directly Observed Therapy , Humans , Microbial Sensitivity Tests , Mycobacterium tuberculosis/isolation & purification , Philippines/epidemiology , Sputum/microbiology , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/microbiologyABSTRACT
During a recent Food and Drug Administration workshop on clinical trials to evaluate new TB drugs, questions were raised regarding the use of bacteriologic endpoints such as treatment failure and relapse as measures of improvement in health status and long term outcome after treatment. FDA scientists asked how patients' clinical signs and symptoms changed during therapy, noting that while such information is usually collected during clinical trials, it is not often reported. We analyzed data from an international phase 3 TB treatment trial that included systematic assessments of symptoms. The percentage of subjects with self-reported symptoms at baseline ranged from 30% for dyspnea to 81% for cough, with 51% reporting fever. During therapy, fever, sweats, and dyspnea decreased most rapidly, with near resolution by the end of therapy. Chest pain and cough resolved more slowly; 13% of subjects reported cough at six months. Symptom resolution during treatment did not differ between those who relapsed and those who did not. Among those with microbiological relapse, symptoms returned with significant increases in the proportion with fever, cough, and chest pain. At the time of relapse, cough was the most frequent symptom, occurring in 75% of subjects who relapsed but only 12% of those who did not. Our data support the continued use of bacteriologic endpoints based on sputum culture as surrogate measures of the relief of symptoms, improvement in health status and favorable long term treatment outcome in TB drug trials.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Cough/epidemiology , Dyspnea/epidemiology , Fever/epidemiology , Tuberculosis/drug therapy , Tuberculosis/epidemiology , Adolescent , Adult , Biomarkers , Brazil/epidemiology , Clinical Trials as Topic , Cough/microbiology , Dyspnea/microbiology , Female , Fever/microbiology , Humans , Male , Middle Aged , Philippines/epidemiology , Recurrence , Treatment Failure , Uganda/epidemiology , United States , United States Food and Drug Administration , Young AdultABSTRACT
Monthly culture is usually recommended to monitor treatment of multidrug-resistant tuberculosis (MDR-TB). As mycobacterial laboratory capacity is limited in many settings, TB programs need evidence to decide whether monthly cultures are necessary compared to other approaches. We simulated three alternative monitoring strategies (culture every 2 or 3 months, and monthly smears alone) in a cohort of MDR-TB patients in Estonia, Latvia, Philippines, Russia and Peru from 2000 to 2004. This retrospective analysis illustrated that less frequent testing delays confirmation of bacteriological conversion. This would prolong intensive treatment, hospitalization and respiratory isolation, increasing cost and toxicity. After conversion, less frequent testing could delay diagnosis of possible treatment failure.
Subject(s)
Antitubercular Agents/therapeutic use , Bacteriological Techniques , Drug Monitoring/methods , Drug Resistance, Multiple, Bacterial , Mycobacterium tuberculosis/drug effects , Tuberculosis, Multidrug-Resistant/diagnosis , Adult , Computer Simulation , Europe/epidemiology , Female , Humans , Male , Mycobacterium tuberculosis/growth & development , Mycobacterium tuberculosis/isolation & purification , Peru/epidemiology , Philippines/epidemiology , Predictive Value of Tests , Retrospective Studies , Sputum/microbiology , Time Factors , Treatment Failure , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Multidrug-Resistant/microbiologyABSTRACT
BACKGROUND: Multidrug-resistant tuberculosis programs in DOTS-Plus pilot sites in five countries. OBJECTIVES: To calculate sputum conversion time and its relationship to treatment outcome, document the frequency of culture reversions and examine concordance of smear and culture to assess the potential consequences of monitoring by smear microscopy alone. DESIGN: Retrospective cohort analysis of 1926 patients receiving individualized, second-line therapy. RESULTS: Among 1385 sputum culture-positive cases at baseline, 1146 (83%) experienced at least one culture conversion during treatment. Conversion, however, was not sustained in all patients: 201 (15%) experienced initial culture conversion and at least one subsequent culture reversion to positive; 1064 (77%) achieved sustained culture conversion. Median time to culture conversion was 3 months. Among 206 patients whose nal conversion occurred 7-18 months after the initiation of therapy, 71% were cured or had completed treatment. CONCLUSIONS: Prolonged treatment for patients with delayed conversion may be beneficial, as 71% of late converters still achieved cure or completed treatment. This has implications for programs with de ned end points for treatment failure. The interval between rst and nal conversion among patients whose initial con- version is not sustained raises concern with respect to the ongoing debate regarding duration of treatment and the definition of cure.
Subject(s)
Antitubercular Agents/administration & dosage , Bacteriological Techniques , Directly Observed Therapy , Drug Monitoring/methods , Drug Resistance, Multiple, Bacterial , Mycobacterium tuberculosis/drug effects , Tuberculosis, Multidrug-Resistant/drug therapy , Drug Administration Schedule , Estonia , Female , Humans , Latvia , Male , Microbial Sensitivity Tests , Microscopy , Mycobacterium tuberculosis/isolation & purification , Peru , Philippines , Pilot Projects , Retrospective Studies , Russia , Sputum/microbiology , Time Factors , Treatment Outcome , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/microbiologyABSTRACT
SETTING: The Philippines ranks eighth among 27 priority countries for multidrug-resistant TB (MDR-TB). OBJECTIVE: To describe a model of public-private partnership in MDR-TB management. METHODS: An exploratory study of integrating MDR-TB management initiated in private-public mix DOTS into the National TB Programme (NTP). RESULTS: Recognising that MDR-TB was a threat to DOTS, the Tropical Disease Foundation initiated MDR-TB management in 1999. An official mandate for the integration of MDR-TB services into the NTP was issued by the Department of Health in 2008. With an increased government budget augmented by support from the Global Fund to Fight AIDS, Tuberculosis and Malaria, 1294 MDR-TB patients were placed on treatment from 1999 to 2008. The treatment success rate improved from 64% in 1999 to 75% in 2005. There are now five MDR-TB treatment centres with 181 treatment sites in Metro Manila, and three culture centres. People trained include 12 master trainers, 31 trainers, 25 treatment centre and 381 treatment site staff. CONCLUSION: Mainstreaming into the NTP of this unique model of MDR-TB management through a dynamic public-private collaboration can be considered best practice in implementation science of an evidence-based intervention leading to change in health care policy and practice.
Subject(s)
Antitubercular Agents/therapeutic use , Disease Outbreaks/prevention & control , Health Care Sector/organization & administration , Outcome Assessment, Health Care/methods , Program Evaluation , Tuberculosis, Multidrug-Resistant/prevention & control , Humans , Philippines/epidemiology , Retrospective Studies , Tuberculosis, Multidrug-Resistant/epidemiologyABSTRACT
BACKGROUND: The Philippines ranks ninth among the 22 high-burden countries for tuberculosis (TB). OBJECTIVE: To measure the burden of pulmonary tuberculosis (PTB) in the Philippines and determine the impact of the DOTS strategy. MATERIALS AND METHODS: The 2007 nationwide TB prevalence survey covered 50 clusters selected by multi-stage stratified random sampling from Metro Manila and other urban and rural areas. Subjects aged >or=10 years were screened radiographically for PTB to identify subjects for sputum examination and determine the prevalence of bacteriologically confirmed PTB, i.e., smear- and/or culture-positive PTB. RESULTS: In subjects aged >or=10 years, the 2007 prevalence of radiographic PTB was 6.3% (95%CI 5.5-7.1), bacteriologically confirmed PTB was 6.6 per 1000 (95%CI 5.1-8.1) and sputum smear-positive PTB was 2.6/1000 (95%CI 1.7-3.6). For the total population, the corresponding estimates were respectively 4.7%, 4.9/1000 and 2.0/1000. Between 1997 and 2007, there was a 31% reduction in bacteriologically confirmed PTB (P < 0.02) and a 27% reduction in smear-positive PTB (P = 0.18). This decline occurred despite the increasing poverty in the population. CONCLUSION: The survey demonstrated a significant decline in the TB burden 10 years after the implementation of DOTS, facilitated by a strategic public-private partnership.