Decentralised, person-centred models of care-delivery for drug-resistant tuberculosis (DR-TB) con... more Decentralised, person-centred models of care-delivery for drug-resistant tuberculosis (DR-TB) continue to be under-resourced in high burden TB countries. The implementation of such models – made increasingly urgent by the COVID-19 pandemic – are key to addressing gaps in DR-TB care. We abstracted data of RR/MDR-TB patients initiated on treatment at 11 facilities between 2010 and 2017 in Sindh and Balochistan provinces of Pakistan. We analysed trends in treatment outcomes relating to program expansion to peri-urban and rural areas and estimated driving distance from patient residence to treatment facility. Among the 5586 RR/MDR-TB patients in the analysis, overall treatment success decreased from 82% to 66% between 2010 and 2017, as the program expanded. The adjusted risk ratio for unfavourable outcomes was 1.013 (95% CI 1.005-1.021) for every 20 kilometres of driving distance. Our analysis suggests that expanding DR-TB care to centralised hubs added to increased unfavourable outcome...
Background Completion of tuberculosis (TB) preventive treatment is important to optimize efficacy... more Background Completion of tuberculosis (TB) preventive treatment is important to optimize efficacy; treatment-related adverse events (AEs) sometimes result in discontinuation. This study describes the occurrence of AEs and their risk factors during a 6-month, 2-drug, fluoroquinolone-based preventive treatment for household contacts of patients with drug-resistant TB in Karachi, Pakistan. Methods The primary outcome was development of any clinical AE during preventive treatment. Adverse events were categorized using the AE grading tables of the National Institutes of Health. Time-to-event analysis with Kaplan-Meier curves and Cox proportional hazards models accounting for recurrence were used to analyze associated risk factors. Results Of the 172 household contacts on preventive treatment, 36 (21%) developed 64 AEs during 813 months of treatment. The incidence of AEs over 6 months of treatment was 7.9 per 100 person-months; 16 per 100 person-months with a fluoroquinolone and ethionami...
Background Observational studies have demonstrated the effectiveness of a fluoroquinolone-based r... more Background Observational studies have demonstrated the effectiveness of a fluoroquinolone-based regimen to treat individuals presumed to be infected with drug-resistant tuberculosis (DR-TB). We sought to assess the feasibility of this approach in an urban setting in South Asia. Methods From February 2016 until March 2017, all household contacts of DR-TB patients enrolled at the Indus Hospital were screened for TB symptoms at home. Children aged 0–17 years, symptomatic adults, and those with an immunocompromising condition (human immunodeficiency virus, diabetes, or malnutrition) were evaluated for TB disease. Contacts diagnosed with TB disease were started on treatment. Contacts without TB disease aged <5 years, contacts aged between 5 and 17 years with either a positive tuberculin skin test or an immunocompromising condition, or contacts aged ≥18 years with an immunocompromising condition were offered 6 months of treatment with a fluoroquinolone. Results One hundred households w...
The role of so-called "group 5" second-line drugs as a part of antibiotic therapy for m... more The role of so-called "group 5" second-line drugs as a part of antibiotic therapy for multidrug-resistant tuberculosis (MDR-TB) is widely debated. We performed an individual patient data meta-analysis to evaluate the effectiveness of several group 5 drugs including amoxicillin/clavulanic acid, thioacetazone, the macrolide antibiotics, linezolid, clofazimine and terizidone for treatment of patients with MDR-TB.Detailed individual patient data were obtained from 31 published cohort studies of MDR-TB therapy. Pooled treatment outcomes for each group 5 drug were calculated using a random effects meta-analysis. Primary analyses compared treatment success to a combined outcome of failure, relapse or death.Among 9282 included patients, 2191 received at least one group 5 drug. We found no improvement in treatment success among patients taking clofazimine, amoxicillin/clavulanic acid or macrolide antibiotics, despite applying a number of statistical approaches to control confoundin...
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2010
To describe the experience of strengthening laboratory diagnosis of tuberculosis (TB) in a resour... more To describe the experience of strengthening laboratory diagnosis of tuberculosis (TB) in a resource-limited country with high TB-HIV (human immunodeficiency virus) and multidrug-resistant TB (MDR-TB) prevalence. In the Kingdom of Lesotho, which is confronted with high levels of TB, MDR-TB and HIV prevalence, between 2006 and 2008 a coalition of the Foundation for Innovative New Diagnostics, Partners In Health and the World Health Organization renovated the National TB Reference Laboratory and reinforced microscopy services, streamlined conventional culture and drug susceptibility testing (DST) and introduced modern TB diagnostic methods. It was feasible to establish a biosafety level three facility for solid culture and DST and an external quality assessment programme for smear microscopy within 4 months, all in 2007. Liquid culture and DST were introduced a month later. Preliminary results were comparable to those found in laboratories in industrialised countries. A year later, lin...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 15, 2014
Individualized treatment for multidrug-resistant (MDR) tuberculosis and extensively drug-resistan... more Individualized treatment for multidrug-resistant (MDR) tuberculosis and extensively drug-resistant (XDR) tuberculosis depends upon reliable and valid drug susceptibility testing (DST) for pyrazinamide, ethambutol, and second-line tuberculosis drugs. However, the reliability of these tests is uncertain, due to unresolved methodological issues. We estimated the association of DST results for pyrazinamide, ethambutol, and second-line drugs with treatment outcomes in patients with MDR tuberculosis and XDR tuberculosis. We conducted an analysis of individual patient data assembled from 31 previously published cohort studies of patients with MDR and XDR tuberculosis. We used data on patients' clinical characteristics including DST results, treatment received, outcomes, and laboratory methods in each center. DST methods and treatment regimens used in different centers varied considerably. Among 8955 analyzed patients, in vitro susceptibility to individual drugs was consistently and sig...
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2006
Multidrug-resistant tuberculosis (MDR-TB) is a major problem in countries of the former Soviet Un... more Multidrug-resistant tuberculosis (MDR-TB) is a major problem in countries of the former Soviet Union in both the civilian and prison sectors. To evaluate outcomes of the MDR-TB treatment program (DOTS-Plus) in Tomsk, Russia. Retrospective case series of all patients enrolled in this program between 10 September 2000 and 10 September 2002. The program involves both the civilian and penitentiary TB services in Tomsk. Poor treatment outcome was defined as death, default and treatment failure. Among the 244 patients who received treatment, 77% were cured, 5% died, 7% failed, and 12% defaulted. In a multivariable analysis, alcohol consumption during treatment and the presence of both cavitary and bilateral disease were found to be the strongest predictors of poor treatment outcome. The integration of civilian and penitentiary TB services in the Tomsk MDR-TB treatment program has resulted in high cure rates and low rates of default. However, alcohol use among patients with MDR-TB is assoc...
<p>Authors' analysis of Doctors without Borders (MSF) data (see <a href="http:/... more <p>Authors' analysis of Doctors without Borders (MSF) data (see <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001738#pmed.1001738-Medecins1" target="_blank">[14]</a>). Proportions are calculated relative to the total cost of the regimen, and may not sum to 100 due to rounding.</p
<p>MDR-TB prevalence and treatment enrolment statistics are from the 2013 Global TB Report ... more <p>MDR-TB prevalence and treatment enrolment statistics are from the 2013 Global TB Report by the World Health Organization <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001738#pmed.1001738-World2" target="_blank">[5]</a> and represent notified cases of TB. The total burden of MDR-TB may be higher than these estimates. Health systems rankings are from the WHO's World Health Report 2010, Annex, table 10. The systems ranking was discontinued by the WHO in 2000 and has not been updated since then. Poverty statistics are from the 2013 Human Development Report by the United Nations Development Programme.</p><p>Disease burden and health and economic characteristics of the 27 high-burden MDR-TB countries.</p
Using data from 388 people diagnosed with tuberculosis through a community-based screening progra... more Using data from 388 people diagnosed with tuberculosis through a community-based screening program in Lima, Peru, we estimated that cough screening followed by sputum smear microscopy would have detected only 23% of cases found using an algorithm of radiographic screening followed by rapid nucleic acid amplification testing and clinical evaluation.
Decentralised, person-centred models of care-delivery for drug-resistant tuberculosis (DR-TB) con... more Decentralised, person-centred models of care-delivery for drug-resistant tuberculosis (DR-TB) continue to be under-resourced in high burden TB countries. The implementation of such models – made increasingly urgent by the COVID-19 pandemic – are key to addressing gaps in DR-TB care. We abstracted data of RR/MDR-TB patients initiated on treatment at 11 facilities between 2010 and 2017 in Sindh and Balochistan provinces of Pakistan. We analysed trends in treatment outcomes relating to program expansion to peri-urban and rural areas and estimated driving distance from patient residence to treatment facility. Among the 5586 RR/MDR-TB patients in the analysis, overall treatment success decreased from 82% to 66% between 2010 and 2017, as the program expanded. The adjusted risk ratio for unfavourable outcomes was 1.013 (95% CI 1.005-1.021) for every 20 kilometres of driving distance. Our analysis suggests that expanding DR-TB care to centralised hubs added to increased unfavourable outcome...
Background Completion of tuberculosis (TB) preventive treatment is important to optimize efficacy... more Background Completion of tuberculosis (TB) preventive treatment is important to optimize efficacy; treatment-related adverse events (AEs) sometimes result in discontinuation. This study describes the occurrence of AEs and their risk factors during a 6-month, 2-drug, fluoroquinolone-based preventive treatment for household contacts of patients with drug-resistant TB in Karachi, Pakistan. Methods The primary outcome was development of any clinical AE during preventive treatment. Adverse events were categorized using the AE grading tables of the National Institutes of Health. Time-to-event analysis with Kaplan-Meier curves and Cox proportional hazards models accounting for recurrence were used to analyze associated risk factors. Results Of the 172 household contacts on preventive treatment, 36 (21%) developed 64 AEs during 813 months of treatment. The incidence of AEs over 6 months of treatment was 7.9 per 100 person-months; 16 per 100 person-months with a fluoroquinolone and ethionami...
Background Observational studies have demonstrated the effectiveness of a fluoroquinolone-based r... more Background Observational studies have demonstrated the effectiveness of a fluoroquinolone-based regimen to treat individuals presumed to be infected with drug-resistant tuberculosis (DR-TB). We sought to assess the feasibility of this approach in an urban setting in South Asia. Methods From February 2016 until March 2017, all household contacts of DR-TB patients enrolled at the Indus Hospital were screened for TB symptoms at home. Children aged 0–17 years, symptomatic adults, and those with an immunocompromising condition (human immunodeficiency virus, diabetes, or malnutrition) were evaluated for TB disease. Contacts diagnosed with TB disease were started on treatment. Contacts without TB disease aged <5 years, contacts aged between 5 and 17 years with either a positive tuberculin skin test or an immunocompromising condition, or contacts aged ≥18 years with an immunocompromising condition were offered 6 months of treatment with a fluoroquinolone. Results One hundred households w...
The role of so-called "group 5" second-line drugs as a part of antibiotic therapy for m... more The role of so-called "group 5" second-line drugs as a part of antibiotic therapy for multidrug-resistant tuberculosis (MDR-TB) is widely debated. We performed an individual patient data meta-analysis to evaluate the effectiveness of several group 5 drugs including amoxicillin/clavulanic acid, thioacetazone, the macrolide antibiotics, linezolid, clofazimine and terizidone for treatment of patients with MDR-TB.Detailed individual patient data were obtained from 31 published cohort studies of MDR-TB therapy. Pooled treatment outcomes for each group 5 drug were calculated using a random effects meta-analysis. Primary analyses compared treatment success to a combined outcome of failure, relapse or death.Among 9282 included patients, 2191 received at least one group 5 drug. We found no improvement in treatment success among patients taking clofazimine, amoxicillin/clavulanic acid or macrolide antibiotics, despite applying a number of statistical approaches to control confoundin...
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2010
To describe the experience of strengthening laboratory diagnosis of tuberculosis (TB) in a resour... more To describe the experience of strengthening laboratory diagnosis of tuberculosis (TB) in a resource-limited country with high TB-HIV (human immunodeficiency virus) and multidrug-resistant TB (MDR-TB) prevalence. In the Kingdom of Lesotho, which is confronted with high levels of TB, MDR-TB and HIV prevalence, between 2006 and 2008 a coalition of the Foundation for Innovative New Diagnostics, Partners In Health and the World Health Organization renovated the National TB Reference Laboratory and reinforced microscopy services, streamlined conventional culture and drug susceptibility testing (DST) and introduced modern TB diagnostic methods. It was feasible to establish a biosafety level three facility for solid culture and DST and an external quality assessment programme for smear microscopy within 4 months, all in 2007. Liquid culture and DST were introduced a month later. Preliminary results were comparable to those found in laboratories in industrialised countries. A year later, lin...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 15, 2014
Individualized treatment for multidrug-resistant (MDR) tuberculosis and extensively drug-resistan... more Individualized treatment for multidrug-resistant (MDR) tuberculosis and extensively drug-resistant (XDR) tuberculosis depends upon reliable and valid drug susceptibility testing (DST) for pyrazinamide, ethambutol, and second-line tuberculosis drugs. However, the reliability of these tests is uncertain, due to unresolved methodological issues. We estimated the association of DST results for pyrazinamide, ethambutol, and second-line drugs with treatment outcomes in patients with MDR tuberculosis and XDR tuberculosis. We conducted an analysis of individual patient data assembled from 31 previously published cohort studies of patients with MDR and XDR tuberculosis. We used data on patients' clinical characteristics including DST results, treatment received, outcomes, and laboratory methods in each center. DST methods and treatment regimens used in different centers varied considerably. Among 8955 analyzed patients, in vitro susceptibility to individual drugs was consistently and sig...
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2006
Multidrug-resistant tuberculosis (MDR-TB) is a major problem in countries of the former Soviet Un... more Multidrug-resistant tuberculosis (MDR-TB) is a major problem in countries of the former Soviet Union in both the civilian and prison sectors. To evaluate outcomes of the MDR-TB treatment program (DOTS-Plus) in Tomsk, Russia. Retrospective case series of all patients enrolled in this program between 10 September 2000 and 10 September 2002. The program involves both the civilian and penitentiary TB services in Tomsk. Poor treatment outcome was defined as death, default and treatment failure. Among the 244 patients who received treatment, 77% were cured, 5% died, 7% failed, and 12% defaulted. In a multivariable analysis, alcohol consumption during treatment and the presence of both cavitary and bilateral disease were found to be the strongest predictors of poor treatment outcome. The integration of civilian and penitentiary TB services in the Tomsk MDR-TB treatment program has resulted in high cure rates and low rates of default. However, alcohol use among patients with MDR-TB is assoc...
<p>Authors' analysis of Doctors without Borders (MSF) data (see <a href="http:/... more <p>Authors' analysis of Doctors without Borders (MSF) data (see <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001738#pmed.1001738-Medecins1" target="_blank">[14]</a>). Proportions are calculated relative to the total cost of the regimen, and may not sum to 100 due to rounding.</p
<p>MDR-TB prevalence and treatment enrolment statistics are from the 2013 Global TB Report ... more <p>MDR-TB prevalence and treatment enrolment statistics are from the 2013 Global TB Report by the World Health Organization <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001738#pmed.1001738-World2" target="_blank">[5]</a> and represent notified cases of TB. The total burden of MDR-TB may be higher than these estimates. Health systems rankings are from the WHO's World Health Report 2010, Annex, table 10. The systems ranking was discontinued by the WHO in 2000 and has not been updated since then. Poverty statistics are from the 2013 Human Development Report by the United Nations Development Programme.</p><p>Disease burden and health and economic characteristics of the 27 high-burden MDR-TB countries.</p
Using data from 388 people diagnosed with tuberculosis through a community-based screening progra... more Using data from 388 people diagnosed with tuberculosis through a community-based screening program in Lima, Peru, we estimated that cough screening followed by sputum smear microscopy would have detected only 23% of cases found using an algorithm of radiographic screening followed by rapid nucleic acid amplification testing and clinical evaluation.
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Papers by Salmaan Keshavjee