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Hedt B.L.,Harvard University | Van Leth F.,Amsterdam Institute for Global Health and Development | Van Leth F.,KNCV Tuberculosis Foundation | Zignol M.,World Health Organization | And 7 more authors.
Epidemiology | Year: 2012

Background: Current methodology for multidrug-resistant tuberculosis (MDR TB) surveys endorsed by the World Health Organization provides estimates of MDR TB prevalence among new cases at the national level. On the aggregate, local variation in the burden of MDR TB may be masked. This paper investigates the utility of applying lot quality-assurance sampling to identify geographic heterogeneity in the proportion of new cases with multidrug resistance. Methods: We simulated the performance of lot quality-assurance sampling by applying these classification-based approaches to data collected in the most recent TB drug-resistance surveys in Ukraine, Vietnam, and Tanzania. We explored 3 classification systems - two-way static, three-way static, and three-way truncated sequential sampling - at 2 sets of thresholds: low MDR TB = 2%, high MDR TB = 10%, and low MDR TB = 5%, high MDR TB = 20%. Results: The lot quality-assurance sampling systems identified local variability in the prevalence of multidrug resistance in both high-resistance (Ukraine) and low-resistance settings (Vietnam). In Tanzania, prevalence was uniformly low, and the lot quality-assurance sampling approach did not reveal variability. The three-way classification systems provide additional information, but sample sizes may not be obtainable in some settings. New rapid drug-sensitivity testing methods may allow truncated sequential sampling designs and early stopping within static designs, producing even greater efficiency gains. Conclusions: Lot quality-assurance sampling study designs may offer an efficient approach for collecting critical information on local variability in the burden of multidrug-resistant TB. Before this methodology is adopted, programs must determine appropriate classification thresholds, the most useful classification system, and appropriate weighting if unbiased national estimates are also desired. Copyright © 2012 by Lippincott Williams & Wilkins.


Fatima R.,National Tuberculosis Control Program | Qadeer E.,National Tuberculosis Control Program | Enarson D.A.,International Union Against Tuberculosis and Lung Disease | Enarson D.A.,Stellenbosch University | And 4 more authors.
International Journal of Tuberculosis and Lung Disease | Year: 2014

BACKGROUND: In Pakistan, patients with symptoms suggestive of tuberculosis (TB) seek care from a wide array of health care providers, many of whom do not notify cases to the National TB Programme (NTP). SETTING: We evaluated an active case detection intervention in five randomly selected districts in urban slums of Sindh Province, Pakistan. OBJECTIVE: To evaluate the increase in case notification of smear-positive TB by active case finding at community-based chest camps by engaging the private providers. DESIGN: A cross-sectional study of TB case detection associated with a project using integrated intervention and chest camps. RESULTS: From April 2011 to September 2012, the total number of clients seen in the camps was 165 280. Of all the attendees, 13 481 (12.7%) were examined by sputum smear microscopy. The proportion of smear-positive results was significantly higher among those from engaged private providers than among those referred from camps (OR 1.54, 95%CI 1.42-1.66). During the project, the total number of smear-positive TB notifications increased over the intervention period from 5158 to 8275. CONCLUSION: Active case detection by engaging private providers and chest camps can significantly increase the number of smear-positive TB case notifications. © 2014 The Union.


Van Oosterhout J.J.,Dignitas International | Dimba A.,National Tuberculosis Control Program | Davies G.,Malawi Liverpool Wellcome Trust Clinical Research Programme | Davies G.,University of Liverpool | And 2 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2015

Limited data address the impact of HIV coinfection on the pharmacokinetics (PK) of antituberculosis drugs in sub-Saharan Africa. A total of 47 Malawian adults underwent rich pharmacokinetic sampling at 0, 0.5, 1, 2, 3, 4, 6, 8, and 24 h postdose. Of the subjects, 51% were male, their mean age was 34 years, and 65% were HIV-positive with a mean CD4 count of 268 cells/μl. Antituberculosis drugs were administered as fixed-dose combinations (150 mg rifampin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol) according to recommended weight bands. Plasma drug concentrations were determined by high-performance liquid chromatography (rifampin and pyrazinamide) or liquid chromatography-mass spectrometry (isoniazid and ethambutol). Data were analyzed by noncompartmental methods and analysis of variance of log-transformed summary parameters. The pharmacokinetic parameters were as follows (median [interquartile range]): for rifampin, maximum concentration of drug in plasma (Cmax) of 4.129 μg/ml (2.474 to 5.596 μg/ml), area under the curve from 0 to 24 h (AUC0-∞) of 21.32 μg/ml · h (13.57 to 28.60 μg/ml · h), and half-life of 2.45 h (1.86 to 3.08 h); for isoniazid, Cmax of 3.97 μg/ml (2.979 to 4.544 μg/ml), AUC0-24 of 22.5 (14.75 to 34.59 μg/ml · h), and half-life of 3.93 h (3.18 to 4.73 h); for pyrazinamide, Cmax of 34.21 μg/ml (30.00 to 41.60 μg/ml), AUC0-24 of 386.6 μg/ml · h (320.0 to 463.7 μg/ml · h), and half-life of 6.821 h (5.71 to 8.042 h); and for ethambutol, Cmax of 2.278 μg/ml (1.694 to 3.098 μg/ml), AUC0-24 of 20.41 μg/ml · h (16.18 to 26.27 μg/ml · h), and half-life of 7.507 (6.517 to 8.696 h). The isoniazid PK data analysis suggested that around two-thirds of the participants were slow acetylators. Dose, weight, and weight-adjusted dose were not significant predictors of PK exposure, probably due to weight-banded dosing. In this first pharmacokinetic study of antituberculosis drugs in Malawian adults, measures of pharmacokinetic exposure were comparable with those of other studies for all first-line drugs except for rifampin, for which the Cmax and AUC0-24 values were notably lower. Contrary to some earlier observations, HIV status did not significantly affect the AUC of any of the drugs. Increasing the dose of rifampin might be beneficial in African adults, irrespective of HIV status. Current co-trimoxazole prophylaxis was associated with an increase in the half-life of isoniazid of 41% (P=0.022). Possible competitive interactions between isoniazid and sulfamethoxazole mediated by the N-acetyltransferase pathway should therefore be explored further. Copyright © 2015, van Oosterhout et al.


Saqib M.A.N.,Pmas Arid Agriculture University | Awan I.N.,Pmas Arid Agriculture University | Rizvi S.K.A.,Pmas Arid Agriculture University | Shahzad M.I.,Pmas Arid Agriculture University | And 4 more authors.
BMC Research Notes | Year: 2011

Background: Delay in diagnosis and treatment of tuberculosis (TB) may enhance the chances of morbidity and mortality and play a key role in continuous transmission of the bacilli. The objective of this study was to describe health care seeking behavior of suspected TB patients and initial diagnostic work up prior to consultation and diagnosis at National TB Center (NTC). Findings. Interviews of 252 sputum smear positive patients were taken from NTC, Rawalpindi. The duration between on-set of symptoms and start of treatment was considered as the total delay and correlated with general characteristics of TB patients. The proportion of males and females were 49.6% and 50.4% with median age of 25 and 24 years respectively. A median delay of 56 days (8 weeks) was observed which was significantly associated with age, cough and fever. More than 50% of the current patients had a history of contact with previously diagnosed TB patients. The majority of patients (63%) visited health care providers within three weeks of appearance of symptoms but only thirty five percent were investigated for TB diagnosis. Conclusion: Cough and fever are being ignored as likely symptoms of TB by patients as well as health care providers resulting in delay. Engaging private practitioners through public private mix (PPM) approach for expansion of TB diagnosis and increasing public awareness could be more beneficial to reduce delay. © 2011 Khanum et al; licensee BioMed Central Ltd.


PubMed | San Francisco General Hospital, University of Zimbabwe, National Tuberculosis Control Program and Biomedical Research & Training Institute
Type: Journal Article | Journal: The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease | Year: 2016

Patients at elevated risk of drug-resistant tuberculosis (TB) are prioritized for Xpert() MTB/RIF testing; however, the clinical usefulness of the test in this population is understudied.From November 2011 to June 2014, consecutive out-patients with a history of previous TB in high-density suburbs of Harare, Zimbabwe, were tested using Xpert, solid and liquid culture, and the microscopic observation drug susceptibility assay. Diagnostic accuracy for rifampin (RMP) resistance and time to initiation of second-line regimens were ascertained. The rpoB gene was sequenced in cases with culture-confirmed RMP resistance and genotypic susceptibility.Among 352 retreatment patients, 71 (20%) were RMP-resistant, 98 (28%) RMP-susceptible, 64 (18%) culture-negative/Xpert-positive, and 119 (34%) culture-negative/Xpert-negative. Xpert had a sensitivity of 86% (95%CI 75-93) and a specificity of 98% (95%CI 92-100) for RMP-resistant TB. The positive predictive value of Xpert-determined RMP resistance for multidrug-resistant TB (MDR-TB) was 82% (95%CI 70-91). Of 71 (83%) participants, 59 initiated treatment with second-line drugs, with a median time to treatment initiation of 18 days (IQR 10-44).The diagnostic accuracy of Xpert for RMP resistance is high, although the predictive value for MDR-TB was lower than anticipated. Xpert allows for faster initiation of second-line treatment than culture-based drug susceptibility testing under programmatic conditions.


PubMed | Association for Social Development, Ministry of Health, National Tuberculosis Control Program and Pakistan Medical Research Council
Type: Journal Article | Journal: JPMA. The Journal of the Pakistan Medical Association | Year: 2015

To assess the knowledge of lady health visitors and midwives working at primary healthcare facilities about neonatal resuscitation.The cross-sectional survey was conducted in District Sheikhupura of Pakistans Punjab province from September to November 2013, and comprised lady health visitors and midwives at primary level healthcare facilities. Datas was gathered using a close-ended questionnaire. SPSS 16 was used for statistical analysis.Of the 103 health workers interviewed, 54(52.4%) were lady health visitors and 49(47.5%) were midwives. Overall, 71(69.90%) health workers had received training on neonatal resuscitation, while 32(30.10%) had no formal training. Basic neonatal resuscitative arrangements were available at all the 54(100%) basic health units and 7(100%) rural health centres. Basic neonatal care knowledge was found adequate but the knowledge of midwives on the subject was poor as only 24(49%) answered correctly.There is a need for regular in-service trainings of lady health visitors and midwives regarding Basic Neonatal Resuscitation.


PubMed | University of Malawi, University of Liverpool, United Kingdom Malawi Liverpool Wellcome Trust Clinical Research Programme and National Tuberculosis Control Program
Type: Clinical Trial | Journal: Antimicrobial agents and chemotherapy | Year: 2015

Limited data address the impact of HIV coinfection on the pharmacokinetics (PK) of antituberculosis drugs in sub-Saharan Africa. A total of 47 Malawian adults underwent rich pharmacokinetic sampling at 0, 0.5, 1, 2, 3, 4, 6, 8, and 24 h postdose. Of the subjects, 51% were male, their mean age was 34 years, and 65% were HIV-positive with a mean CD4 count of 268 cells/l. Antituberculosis drugs were administered as fixed-dose combinations (150 mg rifampin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol) according to recommended weight bands. Plasma drug concentrations were determined by high-performance liquid chromatography (rifampin and pyrazinamide) or liquid chromatography-mass spectrometry (isoniazid and ethambutol). Data were analyzed by noncompartmental methods and analysis of variance of log-transformed summary parameters. The pharmacokinetic parameters were as follows (median [interquartile range]): for rifampin, maximum concentration of drug in plasma (Cmax) of 4.129 g/ml (2.474 to 5.596 g/ml), area under the curve from 0 to 24 h (AUC0-) of 21.32 g/ml h (13.57 to 28.60 g/ml h), and half-life of 2.45 h (1.86 to 3.08 h); for isoniazid, Cmax of 3.97 g/ml (2.979 to 4.544 g/ml), AUC0-24 of 22.5 (14.75 to 34.59 g/ml h), and half-life of 3.93 h (3.18 to 4.73 h); for pyrazinamide, Cmax of 34.21 g/ml (30.00 to 41.60 g/ml), AUC0-24 of 386.6 g/ml h (320.0 to 463.7 g/ml h), and half-life of 6.821 h (5.71 to 8.042 h); and for ethambutol, Cmax of 2.278 g/ml (1.694 to 3.098 g/ml), AUC0-24 of 20.41 g/ml h (16.18 to 26.27 g/ml h), and half-life of 7.507 (6.517 to 8.696 h). The isoniazid PK data analysis suggested that around two-thirds of the participants were slow acetylators. Dose, weight, and weight-adjusted dose were not significant predictors of PK exposure, probably due to weight-banded dosing. In this first pharmacokinetic study of antituberculosis drugs in Malawian adults, measures of pharmacokinetic exposure were comparable with those of other studies for all first-line drugs except for rifampin, for which the Cmax and AUC0-24 values were notably lower. Contrary to some earlier observations, HIV status did not significantly affect the AUC of any of the drugs. Increasing the dose of rifampin might be beneficial in African adults, irrespective of HIV status. Current co-trimoxazole prophylaxis was associated with an increase in the half-life of isoniazid of 41% (P = 0.022). Possible competitive interactions between isoniazid and sulfamethoxazole mediated by the N-acetyltransferase pathway should therefore be explored further.


Orejel I.,National Tuberculosis Control Program | Castellanos M.,National Tuberculosis Control Program | Marin D.,Pontifical Bolivarian University | Mendoza A.,National Tuberculosis Control Program | Harries A.D.,International Union Against Tuberculosis and Lung Disease
Revista Panamericana de Salud Publica/Pan American Journal of Public Health | Year: 2016

This study documented the number and results of mycobacterial culture and drug sensitivity testing (CDST) in Mexico from 2009-2013 and assessed whether states with a higher risk of multidrug-resistant tuberculosis (MDR-TB) performed more CDST and had more cultures showing MDR-TB. Data for this longitudinal, descriptive, operational research study came from the electronic records of 31 state public health laboratories in Mexico. The total number of CDSTs was 6 470, increasing from 2 143 in the first 2 years to 4 327 in the latter 3 years. There was a significant increase in the proportion of cultures showing sensitivity to all drugs, from 53.1% to 60.9% in 2011-2013 (P < 0.001) and a significant decrease in the proportion showing MDR-TB, from 28.2% in 2009 to 19.8% in 2013 (P < 0.001). Cases of extensively drug resistant tuberculosis were < 1% per year. In the 12 states with higher risk for MDR-TB, significantly more CDSTs (2 382 test) were done in 2011-2013 than in the other 19 states (1 945 tests). Also, for each year the proportion of cultures showing MDR-TB was significantly higher in high risk MDR-TB states than in lower risk ones (P < 0.001). During the 5-year study period, CDST was scaled up in Mexico, particularly in high-risk MDR-TB states where a higher proportion of cultures showed MDR-TB. Scale up and wider coverage of CDST should continue.


Dogar O.F.,11 Health | Shah S.K.,National Health Research Institute | Chughtai A.A.,National Tuberculosis Control Program | Qadeer E.,National Tuberculosis Control Program
BMC Infectious Diseases | Year: 2012

Background: Although globally, the number of notified TB cases is higher for males, a few countries in the Eastern Mediterranean Region (Afghanistan; Lebanon; Iran and Pakistan) of the World Health Organization have a relatively higher number of female cases. Pakistan ranks fifth amongst the highest TB burden countries and poses a rich ground for exploratory research to address the gender differences in TB cases. It is uniquely neighboured by India on the East, having higher number of cases in males than in females, and by Afghanistan and Iran on the West, having higher number of cases in females than in males. The objective is to see whether these gender differences are evenly distributed across the country or vary by geographies, to enable effective targeting of TB control strategies.Methods: Cross-sectional analysis was carried out on secondary data, obtained from National Tuberculosis Program. Disaggregated at the provincial level, the sex-specific case notification rates (CNR) were calculated and trends over a 10-year span (2001-2010) were examined. Sex-specific differences for the four Pakistani provinces were analyzed using chi-square test and odds ratios with corresponding confidence intervals. Cumulative countrywide sex-specific notification rates were used as the reference group.Results: The trends for 2001-2010 in the western provinces of Pakistan show higher female CNR as compared to those seen in the eastern provinces having slightly higher male CNR. The proportions of female notified TB cases are approximately twice as high in the western provinces when compared to the eastern provinces and Pakistan over all.Conclusions: These findings suggest that females are particularly affected by TB disease burden in the west parts of Pakistan. This gender disparity requires a coordinated regional and international effort to further explore triggers and moderators of increased acquisition and progression of TB disease among females in the region to guarantee effective TB control. © 2012 Dogar et al.; licensee BioMed Central Ltd.


Noeske J.,German Development Cooperation GIZ | Voelz N.,German Development Cooperation GIZ | Fon E.,Regional Tuberculosis Control Unit | Abena Foe J.-L.,National Tuberculosis Control Program
BMC Research Notes | Year: 2012

Background: The number of pulmonary tuberculosis (PTB) patients reported with resistance to first-line anti-tuberculosis drugs after a standardized retreatment regimen in Cameroon is increasing. Hence, the National Tuberculosis Control Program (NTP) implemented, in one of the ten Regions of the country, a pilot programme aimed at performing routine drug susceptibility testing (DST) for previously treated PTB cases. The objectives of the programme were to evaluate the feasibility of monitoring drug resistance among retreatment cases under programme conditions and to measure the presence and magnitude of anti-TB drug resistance in order to inform NTP policies. Findings. This retrospective cohort study was conducted in the Littoral Region of Cameroon in 2009. It included all sputum smear positive (SM+) PTB cases registered for retreatment. TB cases were identified and classified according to World Health Organization (WHO) recommendations for national TB programs. Bacterial susceptibility testing to first-line anti-TB drugs was performed using standard culture methods. In 2009, 5,668 TB cases were reported in the Littoral Region, of which 438 (7.7%) were SM + PTB retreatment cases. DST results were available for 216 (49.4%) patients. Twenty six patients (12%) harbored multi-drug resistant (MDR) strains. Positive treatment outcome rates were particularly low in retreatment patients with MDR-TB (46.2%; 95% CI: 27.1-66.3). Thirteen MDR-TB patients were treated using a standardized MDR treatment regimen. Delivery of laboratory results took on average 17 (12-26) weeks. Conclusions: WHO-recommended routine DST in retreatment patients seems feasible in Cameroon. However, coverage needs to be improved through better management. Moreover, diagnostic delay should be shortened by introducing more rapid diagnostic tools. The high risk of MDR in standard regimen failure cases virtually rules out the standard retreatment regimen for such patients without prior DST. © 2011 Noeske et al; licensee BioMed Central Ltd.

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