Assessment of resistance in multi drug resistant tuberculosis patients

Objective: To study MDR-TB isolates and to identify primary and secondary resistance at microbiology laboratory Aga Khan University, Karachi, Pakistan. Methods: All samples positive for Mycobacterium tuberculosis (MTB) received during January - September 2004 were reviewed for drug resistance pattern as well as for history of previous antituberculous drugs exposure. Results: Out of 216 Mycobacterium tuberculosis cultures, 138 (64%) showed resistance to one or more agents. Multi drug resistance (MDR) was observed in 102 (47%) isolates. Of 138 drug resistant isolates; primary resistance to any one or more agent was noted in 31(39%) and secondary (acquired) resistance in 107 (79%) isolates. On analysis of the 102 MDR-TB strains 8 (10%) showed primary resistance while 94 (69%) showed secondary resistance. CONCLUSION: In this group MDR-TB was mainly associated with previous anti-tuberculous treatment. However, primary MDR was also observed and reflects dissemination of MDR cases within the community

A low-cost intervention for cleaner drinking water in Karachi, Pakistan

Objective: To pilot test an inexpensive, home-based water decontamination and storage system in a low-income neighborhood of Karachi.Methods: Fifty households received a 20-L plastic water storage vessel with a high-quality spout and a regular supply of diluted hypochlorite solution. Twenty-five control households were recruited. Water samples were collected at baseline and during unannounced follow-up visits 1, 3, 6, and 10 weeks later.Results: Baseline drinking water samples among intervention households were contaminated with a mean 9397 colony-forming units (cfu)/100 mL of thermotolerant coliforms compared with a mean 10,990 cfu/100 mL from controls. After intervention the mean concentration of thermotolerant coliforms decreased by 99.8% among the intervention households compared with an 8% reduction among controls. Two years after vessel distribution, 34 (68%) of the families were still using the vessel. Thirteen of the households had stopped using their vessel because it had broken after more than 6 months of use, a pattern most consistent with ultraviolet radiation-induced degradation of the plastic.CONCLUSIONS: In a highly contaminated environment, a specifically designed water storage container and in-home water chlorination was acceptable and markedly improved water quality. Where plastic water vessels will be exposed to substantial sunlight, ultraviolet light stabilizers should be incorporated into the plastic

Evaluation of a microcolony detection method and phage assay for rapid detection of Mycobacterium tuberculosis in sputum samples

Early and rapid diagnosis of tuberculosis is necessary for both treatment and control of the disease. This study evaluated two microcolony observation techniques based on liquid and solid media and a mycobacteriophage assay, to evaluate their effectiveness in the diagnosis of pulmonary TB compared with a standard culture (BACTEC 460 and LJ medium). Middlebrook7H9 (M7H9) broth based on microcolony determination detected 57/61 positives cultures (n = 200) with a sensitivity of 93.4% and a specificity of 87.1%. M7H11 agar detected 57/62 positive cultures (n = 198) with a sensitivity of 91.9% and a specificity of 89.7%. The mycobacteriophage assay detected 98/143 (68.5%) of positive samples. The time to positivity was 48 hours in the mycobacteriophage assay versus 7 days in both the M7H9 broth and M7H11 agar. The costs in comparison with the culture (BACTEC 460 and LJ) were 33% and 48% for the microcolony and mycobacteriophage methods, respectively. Microcolony methods were rapid and cost effective compared to standard cultures. The mycobacteriophage assay, despite its lower sensitivity, has a short turn around time, and may be recommended as a screening test in countries with a low prevalence of tuberculosis

Trends in Mycobacterium tuberculosis resistance, Pakistan, 1990-2007

Objective:To determine resistance trends including the emergence of extensive drug resistance (XDR) in Mycobacterium tuberculosis (MTB) isolates from Pakistan. Methods: This was a retrospective analysis of MTB isolates (January 1990-June 2007) collected from the four provinces of Pakistan. Standard methods were used to isolate MTB. Susceptibility against rifampin, isoniazid, streptomycin, ethambutol, ethionamide, capreomycin, cycloserine, and ciprofloxacin was tested using the agar proportion method, while susceptibility to pyrazinamide was determined using BACTEC. Resistance over the study period was assessed using Chisquare for trend analysis. Results: Resistance in 15 343 MTB isolates showed a steady increase over the study period, a significant trend of increasing resistance was noted in three of the four provinces included in the study. XDR-tuberculosis was first seen in 1998, to date 22 XDR cases have been documented. MTB resistance was significantly lower (p \u3c 0.001) in Patients under 5 and over 60 years of age, and significantly higher in males than females (p \u3c 0.001). MTB resistance was also higher in pulmonary than extrapulmonary isolates (p \u3c 0.001). Conclusion: This study documenting a steady increase in resistance among MTB isolates and the emergence of XDR strains is concerning. The data highlight the need to ensure adequate treatment of cases in order to prevent a further increase in multidrug resistance within the country. The importance of developing systems for monitoring drug resistance through nationwide surveillance is emphasized

Enhanced disease surveillance through private health care sector cooperation in Karachi, Pakistan: experience from a vaccine trial

INTRODUCTION: In research projects such as vaccine trials, accurate and complete surveillance of all outcomes of interest is critical. In less developed countries where the private sector is the major health-care provider, the private sector must be included in surveillance systems in order to capture all disease of interest. This, however, poses enormous challenges in practice. The process and outcome of recruiting private practice clinics for surveillance in a vaccine trial are described. METHODS: The project started in January 2002 in two urban squatter settlements of Karachi, Pakistan. At the suggestion of private practitioners, a phlebotomy team was formed to provide support for disease surveillance. Children who had a reported history of fever for more than three days were enrolled for a diagnosis. RESULTS: Between May 2003 and April 2004, 5540 children younger than 16 years with fever for three days or more were enrolled in the study. Of the children, 1312 (24%) were seen first by private practitioners; the remainder presented directly to study centres. In total, 5329 blood samples were obtained for microbiology. The annual incidence of Salmonella typhi diagnosed by blood culture was 407 (95% confidence interval (95% CI), 368-448) per 100 000/year and for Salmonella paratyphi A was 198 (95% CI, 171-227) per 100 000/year. Without the contribution of private practitioners, the rates would have been 240 per 100 000/year (95% CI, 211-271) for S. typhi and 114 (95% CI, 94-136) per 100 000/year for S. paratyphi A. CONCLUSION: The private sector plays a major health-care role in Pakistan. Our experience from a surveillance and burden estimation study in Pakistan indicates that this objective is possible to achieve but requires considerable effort and confidence building. Nonetheless, it is essential to include private health care providers when attempting to accurately estimate the burden of disease in such settings

Enhanced disease surveillance through private health care sector cooperation in Karachi, Pakistan: experience from a vaccine trial.

INTRODUCTION: In research projects such as vaccine trials, accurate and complete surveillance of all outcomes of interest is critical. In less developed countries where the private sector is the major health-care provider, the private sector must be included in surveillance systems in order to capture all disease of interest. This, however, poses enormous challenges in practice. The process and outcome of recruiting private practice clinics for surveillance in a vaccine trial are described. METHODS: The project started in January 2002 in two urban squatter settlements of Karachi, Pakistan. At the suggestion of private practitioners, a phlebotomy team was formed to provide support for disease surveillance. Children who had a reported history of fever for more than three days were enrolled for a diagnosis. RESULTS: Between May 2003 and April 2004, 5540 children younger than 16 years with fever for three days or more were enrolled in the study. Of the children, 1312 (24%) were seen first by private practitioners; the remainder presented directly to study centres. In total, 5329 blood samples were obtained for microbiology. The annual incidence of Salmonella typhi diagnosed by blood culture was 407 (95% confidence interval (95% CI), 368-448) per 100 000/year and for Salmonella paratyphi A was 198 (95% CI, 171-227) per 100 000/year. Without the contribution of private practitioners, the rates would have been 240 per 100 000/year (95% CI, 211-271) for S. typhi and 114 (95% CI, 94-136) per 100 000/year for S. paratyphi A. CONCLUSION: The private sector plays a major health-care role in Pakistan. Our experience from a surveillance and burden estimation study in Pakistan indicates that this objective is possible to achieve but requires considerable effort and confidence building. Nonetheless, it is essential to include private health care providers when attempting to accurately estimate the burden of disease in such settings

Four-Month High-Dose Rifampicin Regimens for Pulmonary Tuberculosis

BACKGROUND Shorter but effective tuberculosis treatment regimens would be of value to the tuberculosis treatment community. High-dose rifampicin has been associated with more rapid and secure lung sterilization and may enable shorter tuberculosis treatment regimens. METHODS We randomly assigned adults who were given a diagnosis of rifampicin-susceptible pulmonary tuberculosis to a 6-month control regimen, a similar 4-month regimen of rifampicin at 1200 mg/d (study regimen 1 [SR1]), or a 4-month regimen of rifampicin at 1800 mg/d (study regimen 2 [SR2]). Sputum specimens were collected at regular intervals. The primary end point was a composite of treatment failure and relapse in participants who were sputum smear positive at baseline. The noninferiority margin was 8 percentage points. Using a sequence of ordered hypotheses, noninferiority of SR2 was tested first. RESULTS Between January 2017 and December 2020, 672 patients were enrolled in six countries, including 191 in the control group, 192 in the SR1 group, and 195 in the SR2 group. Noninferiority was not shown. Favorable responses rates were 93, 90, and 87% in the control, SR1, and SR2 groups, respectively, for a country-adjusted absolute risk difference of 6.3 percentage points (90% confidence interval, 1.1 to 11.5) comparing SR2 with the control group. The proportions of participants experiencing a grade 3 or 4 adverse event were 4.0, 4.5, and 4.4% in the control, SR1, and SR2 groups, respectively. CONCLUSIONS Four-month high-dose rifampicin regimens did not have dose-limiting toxicities or side effects but failed to meet noninferiority criteria compared with the standard 6-month control regimen for treatment of pulmonary tuberculosis. (Funded by the MRC/Wellcome Trust/DFID Joint Global Health Trials Scheme; ClinicalTrials.gov number, NCT02581527.