Creating an Effective Routine Surveillance System for Drug-Resistant Tuberculosis Among Previously Treated Patients in Tanzania

Creating an Effective Routine Surveillance System for Drug-Resistant Tuberculosis Among Previously Treated Patients in Tanzania. Introduction: Tuberculosis routine surveillance is an essential tool for scrutinising the effectiveness of TB Programmes and especially for monitoring drug resistance. This study sought to understand the effectiveness of the existing Routine Surveillance System for drug-resistant Tuberculosis amongst previously treated TB patients in Tanzania, identify weaknesses and interventions leading to improvements, and then pilot these interventions. Methods: Both quantitative and qualitative methods were used to gather the current Routine Surveillance System information among previously treated tuberculosis patients. Quantitative data were collected from the routine laboratory databases over a three-year period (2011-2013). Qualitative data were collected using key informant interviews and focus group discussions. Based on the results, an intervention to improve the Routine Surveillance System was designed and a pilot study was implemented in the Mwanza region. The intervention considered the implementation of rapid molecular techniques such as Xpert MTB/RIF and Line Probe Assay at the Central Tuberculosis Reference Laboratory. Revised communication measures and request form completion strategies were also included. A further qualitative study was undertaken for comparison after implementation. Results: The initial quantitative analysis showed that, over the surveyed period, 2,750 specimens were received at the reference laboratory from across the country. This was only 32% of the anticipated numbers, although it reached 61% in 2013. The median and interquartile ranges of turnaround times for microscopy, culture and drug sensitivity testing were: 1(1, 1), 61(43, 71) and 129(72, 170) days respectively. Contamination was evident in both culture and susceptibility testing. The qualitative analysis showed a mixed picture; the system of sending specimens via post was seen to be efficient, though many challenges were noted, in particular: inadequate supplies, poor completion of forms, staff shortages and demotivation. Delays in the transportation of specimens were associated with inadequate funding, training and poor supervision. A revised routine surveillance system for drug-resistant tuberculosis amongst previously treated tuberculosis patients in Tanzania was designed to address many of the identified shortfalls. The revised system, piloted in Mwanza, increased the volume of specimens received from 75 in 2016 to 185 in 2017. The system reduced the time it took for specimens to reach the reference laboratory by 22% (from 9 to 7 days). The median time for results getting back to the requesters was shortened by 36% (from 11 to 7 days). Overall, the number of drug resistant cases increased by 67% (from 12 to 20). In the qualitative analysis undertaken following the pilot, stakeholders identified earlier diagnosis, timely feedback of results, strengthened communication and reliable specimen transportation arrangements as key gains. Conclusion: The routine surveillance system is critical to the effectiveness of the Tuberculosis Programme in Tanzania. The existing routine surveillance policy was poorly executed and lacked new technology, which led to long delays, specimen inertness, discontentment and compromised patient care. A revised routine surveillance system can overcome these weaknesses and increase MDR-TB detection. These lessons are highly relevant to other resource-limited settings, including elsewhere in sub-Saharan Africa

Assessment of the patient, health system, and population eff ects of Xpert MTB/RIF and alternative diagnostics for tuberculosis in Tanzania: an integrated modelling approach

Background Several promising new diagnostic methods and algorithms for tuberculosis have been endorsed by WHO. National tuberculosis programmes now face the decision on which methods to implement and where to place them in the diagnostic algorithm. Methods We used an integrated model to assess the eff ects of diff erent algorithms of Xpert MTB/RIF and lightemitting diode (LED) fl uorescence microscopy in Tanzania. To understand the eff ects of new diagnostics from the patient, health system, and population perspective, the model incorporated and linked a detailed operational component and a transmission component. The model was designed to represent the operational and epidemiological context of Tanzania and was used to compare the eff ects and cost-eff ectiveness of diff erent diagnostic options. Findings Among the diagnostic options considered, we identifi ed three strategies as cost eff ective in Tanzania. Full scale-up of Xpert would have the greatest population-level eff ect with the highest incremental cost: 346 000 disability-adjusted life-years (DALYs) averted with an additional cost of US$36·9 million over 10 years. The incremental cost-eff ectiveness ratio (ICER) of Xpert scale-up ($169 per DALY averted, 95% credible interval [CrI] 104–265) is below the willingness-to-pay threshold ($599) for Tanzania. Same-day LED fl uorescence microscopy is the next most eff ective strategy with an ICER of$45 (95% CrI 25–74), followed by LED fl uorescence microscopy with an ICER of $29 (6–59). Compared with same-day LED fl uorescence microscopy and Xpert full rollout, targeted use of Xpert in presumptive tuberculosis cases with HIV infection, either as an initial diagnostic test or as a followon test to microscopy, would produce DALY gains at a higher incremental cost and therefore is dominated in the context of Tanzania. Interpretation For Tanzania, this integrated modelling approach predicts that full rollout of Xpert is a cost-eff ective option for tuberculosis diagnosis and has the potential to substantially reduce the national tuberculosis burden. It also estimates the substantial level of funding that will need to be mobilised to translate this into clinical practice. This approach could be adapted and replicated in other developing countries to inform rational health policy formulation

Preservation of sputum samples with cetylpyridinium chloride (CPC) for tuberculosis cultures and Xpert MTB/RIF in a low-income country

Culture contamination with environmental bacteria is a major challenge in tuberculosis (TB) laboratories in hot and humid climate zones. We studied the effect of cetylpyridinium chloride (CPC) preservation on culture results and performance of Xpert MTB/RIF.; Consecutive sputum samples from microscopy smear-positive TB patients were collected. Two-hundred samples were equally split in two aliquots, one aliquot was treated with CPC and stored at ambient temperature for 7 days. The second aliquot was immediately processed. Samples were decontaminated for 20, 15 or 10 min, and subsequently cultured on Löwenstein-Jensen medium. Furthermore, 50 samples were stored for 7, 14 and 21 days, and 100 CPC-pretreated samples tested by Xpert MTB/RIF.; CPC pretreated samples showed a higher culture yield compared to non-treated sputum samples across all decontamination times: 94% vs. 73% at 10 min (p = 0.01), 94% vs. 64% at 15 min (p = 0.004), and 90% vs. 52% at 20 min (p < 0.001). The quantitative culture grading was consistently higher in CPC treated compared to non-CPC treated samples. The proportion of contaminated cultures was lower in CPC pretreated samples across all decontamination times (range 2-6%) compared to non-CPC treated samples (15-16%). For storage times of CPC treated samples of 7, 14, and 21 days, 84, 86, and 84% of the respective cultures were positive. Of 91 CPC treated samples with a positive culture, 90 were also Xpert MTB/RIF positive.; CPC increases culture yield, decreases the proportion of contamination, and does not alter the performance of Xpert MTB/RIF

Reducing delays to multidrug-resistant tuberculosis case detection through a revised routine surveillance system

Background: Implementation of an effective Tuberculosis Routine Surveillance System in low-income countries like Tanzania is problematic, despite being an essential tool for the detection and effective monitoring of drug resistant tuberculosis. Long delays in specimen transportation from the facilities to reference laboratory and results dissemination back to the health facilities, result in poor patient management, particularly where multidrug-resistant tuberculosis disease is present. Methods: Following a detailed qualitative study, a pilot intervention of a revised Tuberculosis Routine Surveillance System was implemented in Mwanza region, Tanzania. This included the use of rapid molecular methods for the detection of both tuberculosis and drug resistance using Xpert MTB/RIF in some Mwanza sites, the use of Xpert MTB/RIF and Line Probe Assay at the Central Tuberculosis Reference Laboratory, a revised communication strategy and interventions to address the issue of poor form completion. A before and after comparison of the intervention on the number of drug resistant tuberculosis cases identified and the time taken for results feedback to the requesting site was reported. Results: The revised system for previously treated cases tested at the Central Reference Laboratory was able to obtain the following findings; the number of cases tested increased from 75 in 2016 to 185 in 2017. The times for specimen transportation from health facilities to the reference laboratory were reduced by 22% (from 9 to 7 days). The median time for the district to receive results was reduced by 36% (from 11 to 7 days). Overall the number of drug resistant tuberculosis cases starting treatment increased by 67% (from 12 to 20). Conclusion: Detection of drug resistance could significantly be enhanced, and delays reduced by introduction of new technologies and improved routine surveillance system, including better communication using mobile applications such as ‘WhatsApp’ and close follow-ups. A larger scale study is now merited to ascertain if these benefits are robust across different context

Routine surveillance for the identification of drug resistant Tuberculosis in Tanzania: A cross-sectional study of stakeholders' perceptions

<p>Background: Routine surveillance is required to monitor the performance of tuberculosis diagnostic programme and is essential for the rapid detection of drug resistance. The main objective of this study was to explore the effectiveness and stakeholder perception of the current routine surveillance system for previously treated tuberculosis cases in Tanzania with a view to identify interventions to improve and accelerate positive patient outcomes.<b></b></p> <p>Methods:<b> </b>A study using quantitative and qualitative methods of data collection including in-depth interviews and focus group discussions with health care service providers was conducted in four regions. Quantitative data were extracted from the routine databases to assess performance.</p> <p>Results: Quantitative findings from 2011 to 2013 showed 2,750 specimens from previously treated TB cases were received at the reference laboratory. The number increased year on year, but even in the most recent year was only 61% of that expected. The median and interquartile range of turnaround time in days from specimen reception to results reported for smear microscopy, culture and drug susceptibility testing were 1(1, 1), 61(43, 71) and 129(72, 170) respectively. Contaminated specimens were reported in 3.6% of cases. The qualitative analysis showed the system of sending specimens using postal services was seen to be efficient by participants. However, there were many challenges and significant delays in specimens reaching the reference laboratory associated with lack of funds to transfer specimens, weak form completion, inadequate training and poor supervision. These all adversely affected the implementation of the routine surveillance system.</p> Conclusions: Many issues limit the effectiveness of the routine surveillance system in Tanzania. Priority areas for strengthening are; specimen transportation, supervision and availability of commodities. A pilot study of a revised routine surveillance system that takes into account the observations from this study alongside improved access to drug susceptibility testing using Xpert MTB/RIF should be considere

Implementation of a national anti-tuberculosis drug resistance survey in Tanzania

A drug resistance survey is an essential public health management tool for evaluating and improving the erformance of National Tuberculosis control programmes. The current manuscript describes the implementation of the first national drug resistance survey in Tanzania. Description of the implementation process of a national anti-tuberculosis drug esistance survey in Tanzania, in relation to the study protocol and Standard Operating Procedures. Factors contributing positively to the implementation of the survey were a continuous commitment of the key stakeholders, the existence of a well organized National Tuberculosis Programme, and a detailed design of cluster-specific arrangements for rapid sputum transportation. Factors contributing negatively to the implementation were a long delay between training and actual survey activities, limited monitoring of activities, and an unclear design of the data capture forms leading to difficulties in form-filling. Careful preparation of the survey, timing of planned activities, a strong emphasis on data capture tools and data management, and timely supervision are essential for a proper implementation of a national drug resistance survey

Insights into the genetic diversity of Mycobacterium tuberculosis in Tanzania.

BACKGROUND Human tuberculosis (TB) is caused by seven phylogenetic lineages of the Mycobacterium tuberculosis complex (MTBC), Lineage 1-7. Recent advances in rapid genotyping of MTBC based on single nucleotide polymorphisms (SNP), allow for phylogenetically robust strain classification, paving the way for defining genotype-phenotype relationships in clinical settings. Such studies have revealed that, in addition to host and environmental factors, strain variation in the MTBC influences the outcome of TB infection and disease. In Tanzania, such molecular epidemiological studies of TB however are scarce in spite of a high TB burden. METHODS AND FINDINGS Here we used SNP-typing to characterize a nationwide collection of 2,039 MTBC clinical isolates representative of 1.6% of all new and retreatment TB cases notified in Tanzania during 2012 and 2013. Four lineages, namely Lineage 1-4 were identified within the study population. The distribution and frequency of these lineages varied across regions but overall, Lineage 4 was the most frequent (n = 866, 42.5%), followed by Lineage 3 (n = 681, 33.4%) and 1 (n = 336, 16.5%), with Lineage 2 being the least frequent (n = 92, 4.5%). We found Lineage 2 to be independently associated with female sex (adjusted odds ratio [aOR] 2.14; 95% confidence interval [95% CI] 1.31 - 3.50, p = 0.002) and retreatment cases (aOR 1.67; 95% CI 0.95 - 2.84, p = 0. 065) in the study population. We found no associations between MTBC lineage and patient age or HIV status. Our sublineage typing based on spacer oligotyping on a subset of Lineage 1, 3 and 4 strains revealed the presence of mainly EAI, CAS and LAM families. Finally, we detected low levels of multidrug resistant isolates among a subset of 144 retreatment cases. CONCLUSIONS This study provides novel insights into the MTBC lineages and the possible influence of pathogen-related factors on the TB epidemic in Tanzania

Modelling the impacts of new diagnostic tools for tuberculosis in developing countries to enhance policy decisions

The introduction and scale-up of new tools for the diagnosis of Tuberculosis (TB) in developing countries has the potential to make a huge difference to the lives of millions of people living in poverty. To achieve this, policy makers need the information to make the right decisions about which new tools to implement and where in the diagnostic algorithm to apply them most effectively. These decisions are difficult as the new tools are often expensive to implement and use, and the health system and patient impacts uncertain, particularly in developing countries where there is a high burden of TB. The authors demonstrate that a discrete event simulation model could play a significant part in improving and informing these decisions. The feasibility of linking the discrete event simulation to a dynamic epidemiology model is also explored in order to take account of longer term impacts on the incidence of TB. Results from two diagnostic districts in Tanzania are used to illustrate how the approach could be used to improve decisions

Assessment of the patient, health system, and population effects of Xpert MTB/RIF and alternative diagnostics for tuberculosis in Tanzania: an integrated modelling approach

Summary Background Several promising new diagnostic methods and algorithms for tuberculosis have been endorsed by WHO. National tuberculosis programmes now face the decision on which methods to implement and where to place them in the diagnostic algorithm. Methods We used an integrated model to assess the effects of different algorithms of Xpert MTB/RIF and lightemitting diode (LED)fluorescence microscopy in Tanzania. To understand the eff ects of new diagnostics from the patient, health system, and population perspective, the model incorporated and linked a detailed operational component and a transmission component. The model was designed to represent the operational and epidemiological context of Tanzania and was used to compare the effects and cost-eff ectiveness of different diagnostic options. Findings Among the diagnostic options considered, we identified three strategies as cost effective in Tanzania. Full scale-up of Xpert would have the greatest population-level effect with the highest incremental cost: 346 000 disability-adjusted life-years (DALYs) averted with an additional cost of US$36·9 million over 10 years. The incremental cost-eff ectiveness ratio (ICER) of Xpert scale-up ($169 per DALY averted, 95% credible interval [CrI]104–265) is below the willingness-to-pay threshold ($599) for Tanzania. Same-day LED fl uorescence microscopy is the next most effective strategy with an ICER of$45 (95% CrI 25–74), followed by LED fl uorescence microscopy with an ICER of $29 (6–59). Compared with same-day LED fl uorescence microscopy and Xpert full rollout, targeted use of Xpert in presumptive tuberculosis cases with HIV infection, either as an initial diagnostic test or as a followon test to microscopy, would produce DALY gains at a higher incremental cost and therefore is dominated in the context of Tanzania. Interpretation For Tanzania, this integrated modelling approach predicts that full rollout of Xpert is a cost-eff ective option for tuberculosis diagnosis and has the potential to substantially reduce the national tuberculosis burden. It also estimates the substantial level of funding that will need to be mobilised to translate this into clinical practice. This approach could be adapted and replicated in other developing countries to inform rational health policy formulation