Emergence of multidrug-resistant tuberculosis in a community-based directly observed treatment programme in rural South Africa.

OBJECTIVE: Although little studied in developing countries, multidrug-resistant tuberculosis (MDR-TB) is considered a major threat. We report the molecular epidemiology, clinical features and outcome of an emerging MDR-TB epidemic. METHODS: In 1996 all tuberculosis suspects in the rural Hlabisa district, South Africa, had sputum cultured, and drug susceptibility patterns of mycobacterial isolates were determined. Isolates with MDR-TB (resistant to both isoniazid and rifampicin) were DNA fingerprinted by restriction fragment length polymorphism (RFLP) using IS6110 and polymorphic guanine-cytosine-rich sequence-based (PGRS) probes. Patients with MDR-TB were traced to determine outcome. Data were compared with results from a survey of drug susceptibility done in 1994. RESULTS: The rate of MDR-TB among smear-positive patients increased six-fold from 0.36% (1/275) in 1994 to 2.3% (13/561) in 1996 (P = 0.04). A further eight smear-negative cases were identified in 1996 from culture, six of whom had not been diagnosed with tuberculosis. MDR disease was clinically suspected in only five of the 21 cases (24%). Prevalence of primary and acquired MDR-TB was 1.8% and 4.1%, respectively. Twelve MDR-TB cases (67%) were in five RFLP-defined clusters. Among 20 traced patients, 10 (50%) had died, five had active disease (25%) and five (25%) were apparently cured. CONCLUSIONS: The rate of MDR-TB has risen rapidly in Hlabisa, apparently due to both reactivation disease and recent transmission. Many patients were not diagnosed with tuberculosis and many were not suspected of drug-resistant disease, and outcome was poor.     

Effectiveness of urban community volunteers in directly observed treatment of tuberculosis patients: a field report from Haryana, North India.

A tuberculosis (TB) unit covering a population of 600000 in Gurgaon District of Haryana State, India, where the DOTS-based RNTCP has been implemented since April 2000. Treatment success rate, as recorded in the TB register, of new sputum smear-positive patients receiving directly observed treatment (DOT) from community volunteers was comparable with that of patients receiving DOT from government health workers (78% vs. 77%). The proportion of patients with community volunteers increased significantly with time (13% in 2000 to 25% in 2002), even in the absence of financial incentives. In this model of community volunteer involvement in an urban TB control programme, the primary responsibility for returning late patients to treatment was with the staff of the District TB Centre.     

A randomised controlled clinical trial of the efficacy of family-based direct observation of anti-tuberculosis treatment in an urban, developed-country setting.

SETTING: A randomised, controlled clinical trial of the effectiveness of a family-based programme of directly observed treatment (DOT) for tuberculosis. METHODS: TB patients seen in Victoria, Australia, were randomly allocated to DOT observed by a family member (FDOT), or to standard supervised but non-observed therapy (ST). The outcome measure was compliance, measured by blinded testing of isoniazid levels in urine. An intention-to-treat analysis was used. RESULTS: Of 173 patients, 87 were allocated to FDOT and 86 to ST. Only 58% in the FDOT group were able to receive FDOT, the major reason being living alone and not having a family member to observe treatment. The rate of non-compliance was 24% (41/173), with no significant difference between FDOT (22/87) and ST (19/86). No clinical or socio-demographic variable predicted compliance. CONCLUSIONS: We were unable to demonstrate a benefit of FDOT in an urban, industrialised country setting. FDOT may be more appropriate in developing countries, where extended family support is often available and the burden of TB is much higher. Poor compliance and the difficulty in predicting non-compliance shown in this study highlights the need for DOT for all TB patients.     

Effectiveness of multidisciplinary lifestyle intervention for hypertension: a randomised controlled trial

Lifestyle factors like weight, alcohol consumption, salt intake and physical activity have shown to be important in treating hypertension. There have been made some randomised trials about the effects of lifestyle interventions, but the numbers of patients have been relatively small and the durations of follow-ups have been short. No controlled trials assessing the effects of lifestyle intervention in a rehabilitation setting have been reported. In this study, the effects of multidisciplinary lifestyle intervention in rehabilitation centres among middle-aged hypertensive employees were described. A total of 731 hypertensives from 45 worksites were randomised to lifestyle intervention in a rehabilitation centre or to usual care in an occupational or primary health-care centre for 12 months. Standard measurements were conducted before the intervention and 1-year later. Blood pressure (BP) levels were clearly reduced in the intervention group, while only minor changes were observed in the control group. The net changes between the two groups both for systolic and diastolic BPs were -2.1 mmHg (95% confidence intervals (CI) -4.0 to -0.1) and -1.5 mmHg (95% CI -2.6 to -0.4), respectively. The net changes were greater among men than women. The multidisciplinary lifestyle intervention in a rehabilitation centre setting produced significant reductions in BP among middle-aged employees with hypertension.     

Sputum smear conversion during directly observed treatment for tuberculosis

Setting: Treatment program for tuberculosis in a refugee camp in Thailand.Objectives: To determine the cumulative frequency of conversion of sputum smears examined by direct microscopy by month of treatment and to identify factors predicting failure to convert.Methods: Analysis of conversion based on three sputum smear examinations (performed monthly) in a cohort of patients with sputum smear-positive tuberculosis treated with a directly observed daily regimen containing rifampicin throughout. Nested case-control study of patients failing to convert definitively within four months compared to controls who did convert.Results: Sputum conversion after the 2-month intensive phase was 75.0%, with a range from 61.7% to 90.9% in patients with initially strongly- and weakly-positive smears, respectively. The strongest predictor identified for no definitive conversion within four months of treatment was a positive sputum smear result at the end of the 2-month intensive phase (adjusted relative odds 4.2, 95% confidence interval 1.5–11.4). Of those patients who did not convert, positive smears were an isolated phenomenon in 15, repeatedly in four who definitely converted with a prolongation of treatment, and persistently positive in two requiring a re-treatment regimen.Conclusions: Definitive sputum smear conversion is judged to be slower if a strict program of sputum smear examination is undertaken than under routine program conditions, but positive results late in the course are commonly an isolated phenomenon and possibly of little significance. Sputum smear results at two months strongly predict bacteriologic results beyond three months of treatment, and thus identify cases who might benefit from a prolongation of the intensive phase.     

Evaluation of efficacy of community-based vs. institutional-based direct observed short-course treatment for the control of tuberculosis in Kilombero district,Tanzania

Tuberculosis (TB) has reappeared as a serious public health problem. Non-compliance to antituber-culous drug treatment is cited as one of the major obstacles to the containment of the epidemic. Compliance may be optimized by Directly Observed Treatment (DOT) and short-course treatment regimens. Since 1986, Tanzanian TB patients have received daily DOT at health facilities for the first 2 months of the treatment course. However, adherence and cure rates have been falling as the number of TB cases continues to increase and the burden on already stretched health facilities threatens to become unmanageable. We used an open cluster randomized controlled trial to compare community-based DOT (CBDOT) using a short-course drug regimen with institutional-based DOT (IBDOT). A total of 522 (301 IBDOT and 221 CBDOT) patients with sputum-positive TB were recruited. Overall, there was no significant difference in conversion and cure rates between the two strategies [M-H pooled odds ratio (OR) 0.62; 95% confidence interval (CI) 0.23, 1.71 and OR = 1.58; 95% CI 0.32, 7.88, respectively] suggesting that CBDOT may be a viable alternative to IBDOT. CBDOT may be particularly useful in parts of the country where people live far from health facilities.     

A randomised controlled trial of lay health workers as direct observers for treatment of tuberculosis.

SETTING: Study conducted in a suburb of Cape Town, South Africa. OBJECTIVE: Comparison of successful tuberculosis treatment outcome rates between self supervision, supervision by lay health worker (LHW), and supervision by clinic nurse. METHODS: Open, randomised, controlled trial with intention-to-treat analysis. RESULTS: All groups (n = 156) achieved similar outcomes (LHW vs. clinic nurse: risk difference 17.2%, 95% confidence interval [CI] -0.1-34.5; LHW vs. self supervision 15%, 95%CI -3.7-33.6). New patients benefit from LHW supervision (LHW vs clinic nurse: risk difference 24.2%, 95%CI 6-42.5, LHW vs. self supervision 39.1%, 95%CI 17.8-60.3) as do female patients (LHW vs. clinic nurse 48.3%, 95%CI 22.8-73.8, LHW vs. self supervision 32.6%, 95%CI 6.4-58.7). CONCLUSIONS: LHW supervision approaches statistically significant superiority, but fails to reach it most likely due to the study's limitation, the small sample size. It is possible that subgroups (new and female patients) do well under LHW supervision. LHW supervision could be offered as one of several supervision options within TB control programmes.     

Combination diuretic treatment in severe heart failure: a randomised controlled trial.

OBJECTIVES--(a) To test the hypothesis that a fixed 3 day course of the combination of a thiazide and loop diuretic is as effective as more prolonged treatment in the management of severe resistant cardiac failure. (b) To compare two thiazide diuretics (bendrofluazide and metolazone) in combination with loop diuretics in the treatment of severe resistant cardiac failure. DESIGN--Randomised study with a 2 x 2 factorial design. SETTING--Provincial teaching hospital. PATIENTS--33 consecutive patients (40 episodes) admitted with severe congestive cardiac failure (New York Heart Association class III or IV) unresponsive to intravenous loop diuretics for 48 hours. MAIN OUTCOME MEASURES--Change in daily weight and serum electrolytes and clinical improvement in heart failure. RESULTS--Diuresis was established during 37 of 40 episodes; of the rest two patients died in hospital. On 36 occasions improvement was sufficient to allow discharge from hospital. Median (range) maximal weight loss was -5.05 (-11.3 to 1.6) kg after the addition of bendrofluazide and -5.6 (-12.2 to 4.8) kg after the addition of metolazone (NS). Area under the body weight loss against time curves showed no significant difference between the two thiazide diuretics. Median (range) maximal weight loss after three days of treatment was -5.4 (-12.2 to 4.8) kg and -5.5 (-10.3 to 1) kg after a more prolonged course of median (range) 5.6 (1 to 13) days (NS). Area under the body weight loss time curves showed no significant difference between the two durations of treatment. Bendrofluazide was associated with fewer electrolyte disturbances. CONCLUSIONS--Bendrofluazide and metolazone were equally effective in establishing a diuresis in patients with severe congestive cardiac failure resistant to loop diuretics. A fixed three day course of the combination was as effective as a longer course.     

A randomized clinical trial of community-based directly observed therapy as an adherence intervention for HAART among substance users

BACKGROUND: Adherence interventions for HAART can impact challenging populations, such as active substance users. Community-based modified directly observed therapy (MDOT) is a promising approach that needs to be critically evaluated. METHODS: This study was a randomized clinical trial. HIV seropositive substance users were randomized to either standard of care (SOC) or MDOT, stratified by HAART experience. All participants were placed on a once-daily regimen and were met by an outreach worker for all 7 days during the first 3 months. We used an intent-to-treat analysis to evaluate differences in viral load suppression [> 2 log drop in plasma viral load (PVL) or PVL < 50] and changes in PVL and CD4 cell count from baseline to 3 months. RESULTS: A total of 87 participants were enrolled (43 in SOC, 44 in MDOT), Using repeated measures logistic regression, MDOT participants were more likely to achieve PVL suppression (odds ratio, 2.16; 95% confidence interval, 1.0-4.7), driven primarily by those HAART experienced (odds ratio, 2.88; 95% confidence interval, 1.2-7.0). A significant treatment effect was also found in CD4 cell count change (P < 0.05). No differences were found by arm in undetectable PVL. CONCLUSION: This study provides evidence that MDOT is an effective strategy to reduce viral load and increase CD4 cell counts in HAART experienced substance users. MDOT should be included in the spectrum of options to enhance adherence in this population.     

A randomised controlled trial of high-dose isoniazid adjuvant therapy for multidrug-resistant tuberculosis.

SETTING: Tertiary care hospital in Kanpur, India. BACKGROUND: The need for a standardised treatment protocol for multidrug-resistant tuberculosis (MDR-TB) in resource-limited countries is being increasingly recognised. OBJECTIVE: To assess the effectiveness of high-dose isoniazid (INH) (16-18 mg/kg) adjuvant to second-line therapy in documented cases of MDR-TB. DESIGN: The present study is a double blind, randomised controlled trial with three treatment arms, high-dose INH, normal-dose INH and placebo, in addition to second-line drugs. Primary outcomes of the study were time to sputum culture conversion and proportion with sputum culture negative 6 months after treatment initiation. Secondary outcomes were radiological improvement at 1 year post treatment and development of toxicity. RESULTS: After adjustment for potential confounders, subjects who received high-dose INH became sputum-negative 2.38 times (95%CI 1.45-3.91, P = 0.001) more rapidly than those who did not receive it, and had a 2.37 times (95%CI 1.46-3.84, P < 0.001) higher likelihood of being sputum-negative at 6 months. These subjects showed significantly better radiological improvement without an increased risk of INH toxicity. CONCLUSION: In low-resource scenarios where a standardised therapeutic protocol is used for MDR-TB, the protocol can be significantly improved by including high-dose INH as an adjuvant.