Stop TB Partnership Research Articles

Treatment adherence and clinical outcomes amongst in people with drug-susceptible tuberculosis using medication monitor and differentiated care approach compared with standard of care in South Africa: a cluster randomized trial

Poor treatment adherence contributes to lower treatment completion and higher loss to follow-up among people with tuberculosis (PWTB). Medication monitors have shown some evidence of improved adherence. We conducted a cluster randomised trial in 18 primary health clinics in South Africa between May 2019-February 2022. Persons (aged ≥ 2 years) with drug-sensitive tuberculosis (DS-TB) were enrolled. All participants were provided with monitors which were silent in the standard of care (SoC) arm. In the intevention arm, weekly adherence reports were reviewed and participants received intensified support as appropriate (text, phone call, home visit, motivational counselling). The primary outcome was adherence, which was calculated as days box was opened (proxy for drug taken)/total expected treatment days as a binary variable (<80% versus ≥80%). Analysis took into account clustered design. The trial was registered with the Pan African Trial Registry PACTR20190268115772. We enrolled 2727 participants (38% women, median age 36 (IQR 27-45 years), of whom 2584 had available adherence data. The primary outcome (measured as ≥80% adherence) was higher in intervention versus SoC arm (81.0% versus 50.8%, adjusted risk ratio (ARR) 1.51 (1.36-1.66). Similarly, overall percentage adherence was higher in intervention versus SoC arm (88.5% versus 69.7%, adjusted risk difference 16.8% (13.3%-20.4%)). People with DS-TB had improved treatment adherence in the intervention arm. We believe the effect on adherence is important and warrants continued use and evaluation of these technologies. The study is funded by Bill & Melinda Gates Foundation, Uinted States, the Stop TB Partnership, Switzerland, and the South African Medical Research Council, South Africa.

Leveraging the positives from the pandemic to strengthen infectious disease care in low-income and middle-income countries

Leveraging the positives from the pandemic to strengthen infectious disease care in low-income and middle-income countries

Access to vaccines: how can we leverage technology innovations to achieve greater vaccine equity?

Fatema Kazi is an Immunologist working at the WHO’s R&amp;D Blueprint Team–part of the Health Emergencies and Preparedness Response. Previously, she has worked at the Elizabeth Glaser Pediatric AIDS Foundation, GAVI, UNOPS, The Stop TB Partnership, and the Global TB Programme (WHO) focusing on research and development in innovative therapeutics, vaccines, and diagnostics. She has a PhD in Cellular Immunology and Infectious Diseases from the London School of Hygiene and Tropical Medicine, and pursued her postdoctoral career as a Senior Immunologist Research Fellow at Leiden University Medical Centre and the University of Oxford, as well as training as a molecular biologist for the Ministry of Defense, UK. In response to the pandemic, Fatema has been leading projects at WHO related to tracking, monitoring, and assessing the development of the COVID-19 vaccine candidates worldwide, conducting epidemiological reviews of vaccine effectiveness against variants of concern. She is now evaluating vaccines for Monkeypox, Lassa Fever and Sudan ebolavirus in response to the current outbreaks.Fatema Kazi works for the WHO, where she helps to assess the public health value of vaccine products and technologies in routine, campaign, and outbreak settings. We caught up with her to discuss how innovations in vaccine technology can help get vaccines to the people who need them.

Assessing the impact of a district multisectoral accountability framework for tuberculosis control in Pakistan

This is an opinion paper on the process leading to the initiation of a model multisectoral accountability framework (MAF) project in the coastal district of Sindh. Dopasi Foundation in collaboration with Stop TB Partnership Pakistan conducted several meetings with senior policymakers of Sindh province drawing their attention towards the international commitment for establishing a Multisectoral Accountability Framework (MAF) to control TB. Thereafter, operational meetings were held with key government functionaries and district Badin. Subsequently the first sensitization meeting of stakeholders comprising of the district MAF team was convened and a problem analysis encompassing the current case notification, intersectoral challenges were drawn from the discussion these includes; likely benefits, zakat provision, mapping of community services, augmenting the role of drug inspectors, sputum transport and various dimensions related to the control and elimination of TB was conducted. This problem analysis, MAF implemented in the district and found effective in case detection likewise; during 2020, 2,519 TB cases were notified as compared to 2,464 in 2019, depicting a nominal increase, despite an overall decline of 17% in TB notifications owing to COVID-19 nationwide, while promoting self-reliance, pooling of resources and comparative advantages of each partner. This extremely cost-effective exercise based on WHO principles showed promising results, although the COVID-19 related disruption rendered a proper program evaluation impracticable. It is recommended that the government leaders need to work effectively with ministerial officials, civil society and affected communities, parliamentarians, private sector and academia, involved in diverse sectors including health and social protection, justice, labor, among others through this effective MAF.

Establishing a parliamentary caucus to provide oversight to tuberculosis control in Pakistan

Background: The National TB Control Program and its partners advocated for a caucus of parliamentarians to galvanize political support for tuberculosis control. The process urged political representatives from all parties to join the call to action for a TB-free Pakistan by supporting timely decisions and adequate resource allocation for TB prevention and cure.&#x0D; Methods: National TB Control Program Pakistan and Stop TB Partnership ensured an effective advocacy stream of activities leading to formulating a parliamentary caucus. The forum has held several meetings to support political decisions for TB control and cure in the country.&#x0D; Results: A total of 13 Parliamentarians initially agreed to be a caucus member, attended its launch and two follow-up meetings, and supported decisions. The parliamentarians signed a declaration to address the barriers in providing TB diagnostic and treatment care across the country, irrespective of any discrimination.

World Tuberculosis Day 2022: aligning COVID-19 and tuberculosis innovations to save lives and to end tuberculosis

World Tuberculosis Day 2022: aligning COVID-19 and tuberculosis innovations to save lives and to end tuberculosis

Engaging frontline providers: an important key to eliminating tuberculosis in Canada, and other high-income countries.

The greatest human cost of the rapidly moving pandemic of SARS-CoV-2 may be due to its impact on the response to other diseases. One such other disease is tuberculosis (TB). All indications suggest that COVID-19-related diversions of healthcare resources and disruptions to public health programming will exacerbate the slower moving pandemic of TB. This is expected to set back TB elimination efforts by years. This is a prediction that is especially relevant to Canada, which has repeatedly failed to meet pre-set targets for the elimination of TB even before the COVID-19 pandemic began. A collaborative approach to achieve TB elimination, one that engages all care providers, has recently been emphasized by the STOP-TB Partnership. Among TB elimination strategies, frontline providers (e.g., family physicians, emergency room physicians, and others) are well positioned to identify candidates for the treatment of latent TB infection, and make the diagnosis of infection-spreading cases of TB in a timely manner, thereby interrupting forward-moving chains of transmission. Electronic medical records offer the promise of automating these processes. In this commentary, we promote broader engagement of the workforce across multiple sectors of medicine to reduce TB associated morbidity and mortality, interrupt transmission, and shrink the reservoir of latent TB infection.

Innovative approaches to end TB in Pakistan: a review of TB REACH projects from 2010 to 2020

Background: TB REACH is a grant-making initiative launched by the Stop TB Partnership in January 2010 to support innovative approaches and technologies to find and treat people with active TB disease, drug-resistant TB, or TB infection. Since then, TB REACH has launched eight Waves of funding to pilot untested, but promising technologies, tools, and approaches. The objective of this paper was to review the grants implemented in Pakistan in the decade since TB REACH’s inception and to summarize the approaches used, document the results, and assess the impact of these projects on local and international policy. Methods: We searched the TB REACH’s Grant Management System (GMS), which is a database for information on all grants awarded through the initiative, for recipient organisations in Pakistan from 2010 until June 2020. Data was abstracted for the following topic areas: type of grant, focus of work, case finding strategies, risk groups screened and impact on case finding. Results: Through eight waves of funding, TB REACH has supported 28 grants for 21 different interventions in Pakistan worth a total of USD 13.4 million. Overall, 19 of these projects aimed to improve detection, linkage to treatment and reporting of TB and two were product innovation grants for developing resources and materials to aide TB service delivery. Conclusion: TB REACH support has facilitated the introduction of new technologies, establishment of innovative processes in both public and private sector and approaches for addressing TB in key populations. The TB response in Pakistan and globally will continue to require innovation and disruption of ‘business as usual' approaches if we are to End TB.

The 2021 WHO Catalogue of &lt;i&gt;Mycobacterium Tuberculosis&lt;/i&gt; Complex Mutations Associated with Drug Resistance: A New Global Standard for Molecular Diagnostics

Background: Molecular diagnostics are considered the most promising route to achieving rapid, universal drug susceptibility testing for Mycobacterium tuberculosis . There is currently no WHO endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: A candidate gene approach was used to identify mutations as associated with resistance, or consistent with susceptibility, for 13 WHO endorsed anti-tuberculosis drugs. 38,215 M. tuberculosis isolates with paired whole-genome sequencing and phenotypic drug susceptibility data were amassed from 41 countries. Mutations were graded according to their odds ratio and associated false discovery rate corrected p-value, and their positive predictive value for phenotypic resistance. A series of expert rules were applied for final confidence grading of each mutation. Findings: 15,667 associations were computed for 13,211 unique mutations linked to one or more drugs. 1,149/15,667 (7·3%) mutations were classified as associated with phenotypic resistance and 107/15,667 (0·7%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations’ pooled sensitivity was >80%. Specificity was over 95% for all drugs except ethionamide (91·4%), moxifloxacin (91·6%) and ethambutol (93·3%). Only two resistance mutations were classified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: This first WHO endorsed catalogue of molecular targets for M. tuberculosis drug susceptibility testing provides a global standard for resistance interpretation. It will be expanded as data emerge on phenotypically resistant isolates, including for new and repurposed drugs. Funding: UNITAID, Wellcome, MRC, BMGF. Declaration of Interest: C.U.K. is a consultant Becton Dickinson, the Foundation for Innovative New Diagnostics and the TB Alliance. C.U.K. is collaborating with PZA Innovation and Thermo Fisher Scientific. C.U.K. worked as a consultant for QuantuMDx, the Stop TB Partnership, the World Health Organization (WHO) Global TB Programme and the WHO Regional Office for Europe. C.U.K. gave a paid educational talk for Oxford Immunotec. Hain Lifescience covered C.U.K.’s and accommodation to present at a meeting. C.U.K. is an unpaid advisor to BioVersys and GenoScreen. E.R. is employed by Public Health England and holds an honorary contract with Imperial College London. I.F.L. is Director of the Scottish Mycobacteria Reference Laboratory. S.N. receives funding from German Center for Infection Research, Excellenz Cluster Precision Medicine in Chronic Inflammation, Leibniz Science Campus Evolutionary Medicine of the LUNG (EvoLUNG)tion EXC 2167. P.S. is a consultant at Genoscreen. T.R. is funded by NIH and DoD and receives salary support from the non-profit organization FIND. T.R. is a cofounder, board member and shareholder of Verus Diagnostics Inc, a company that was founded with the intent of developing diagnostic assays. Verus Diagnostics was not involved in any way with data collection, analysis or publication of the results. T.R. has not received any financial support from Verus Diagnostics. UCSD Conflict of Interest office has reviewed and approved T.R.’s role in Verus Diagnostics Inc. T.R. is a co-inventor of a provisional patent for a TB diagnostic assay (provisional patent #: 63/048.989). T.R. is a co-inventor on a patent associated with the processing of TB sequencing data (European Patent Application No. 14840432.0 & USSN 14/912,918). T.R. has agreed to “donate all present and future interest in and rights to royalties from this patent” to UCSD to ensure that he does not receive any financial benefits from this patent. S.S. is working and holding ESOPs at HaystackAnalytics Pvt. Ltd. (Product: Using whole genome sequencing for drug susceptibility testing for Mycobacterium tuberculosis). G.F.G. is listed as an inventor on patent applications for RBDdimer- based CoV vaccines. No other authors declare a conflict of interest. Ethical Approval: Approval for CRyPTIC study was obtained by Taiwan Centers for Disease Control IRB No. 106209, University of KwaZulu Natal Biomedical Research Ethics Committee (UKZN BREC) (reference BE022/13) and University of Liverpool Central University Research Ethics Committees (reference 2286), Institutional Research Ethics Committee (IREC) of The Foundation for Medical Research, Mumbai (Ref nos. FMR/IEC/TB/01a/2015 and FMR/IEC/TB/01b/2015), Institutional Review Board of P.D. Hinduja Hospital and Medical Research Centre, Mumbai (Ref no. 915-15-CR [MRC]), scientific committee of the Adolfo Lutz Institute (CTC-IAL 47-J / 2017) and in the Ethics Committee (CAAE: 81452517.1.0000.0059) and Ethics Committee review by Universidad Peruana Cayetano Heredia (Lima, Peru) and LSHTM (London, UK).

The TB REACH Initiative: Supporting TB Elimination Efforts in the Asia-Pacific.

After many years of TB ‘control’ and incremental progress, the TB community is talking about ending the disease, yet this will only be possible with a shift in the way we approach the TB response. While the Asia-Pacific region has the highest TB burden worldwide, it also has the opportunity to lead the quest to end TB by embracing the four areas laid out in this series: using data to target hotspots, initiating active case finding, provisioning preventive TB treatment, and employing a biosocial approach. The Stop TB Partnership’s TB REACH initiative provides a platform to support partners in the development, evaluation and scale-up of new and innovative technologies and approaches to advance TB programs. We present several approaches TB REACH is taking to support its partners in the Asia-Pacific and globally to advance our collective response to end TB.

Tackling two pandemics: a plea on World Tuberculosis Day

Tackling two pandemics: a plea on World Tuberculosis Day

Assessing tuberculosis control priorities in high-burden settings: a modelling approach

In the context of WHO's End TB strategy, there is a need to focus future control efforts on those interventions and innovations that would be most effective in accelerating declines in tuberculosis burden. Using a modelling approach to link the tuberculosis care cascade to transmission, we aimed to identify which improvements in the cascade would yield the greatest effect on incidence and mortality. We engaged with national tuberculosis programmes in three country settings (India, Kenya, and Moldova) as illustrative examples of settings with a large private sector (India), a high HIV burden (Kenya), and a high burden of multidrug resistance (Moldova). We collated WHO country burden estimates, routine surveillance data, and tuberculosis prevalence surveys from 2011 (for India) and 2016 (for Kenya). Linking the tuberculosis care cascade to tuberculosis transmission using a mathematical model with Bayesian melding in each setting, we examined which cascade shortfalls would have the greatest effect on incidence and mortality, and how the cascade could be used to monitor future control efforts. Modelling suggests that combined measures to strengthen the care cascade could reduce cumulative tuberculosis incidence by 38% (95% Bayesian credible intervals 27-43) in India, 31% (25-41) in Kenya, and 27% (17-41) in Moldova between 2018 and 2035. For both incidence and mortality, modelling suggests that the most important cascade losses are the proportion of patients visiting the private health-care sector in India, missed diagnosis in health-care settings in Kenya, and drug sensitivity testing in Moldova. In all settings, the most influential delay is the interval before a patient's first presentation for care. In future interventions, the proportion of individuals with tuberculosis who are on high-quality treatment could offer a more robust monitoring tool than routine notifications of tuberculosis. Linked to transmission, the care cascade can be valuable, not only for improving patient outcomes but also in identifying and monitoring programmatic priorities to reduce tuberculosis incidence and mortality. US Agency for International Development, Stop TB Partnership, UK Medical Research Council, and Department for International Development.

ASAP-GxNet project in Burkina Faso: fulfil country capacity gaps to ensure efficient utilisation of GeneXpert instruments in tuberculosis care and cascade.

Improving availability, accessibility and quality of national GeneXpert networks through ASAP-GxNet http://ow.ly/umaZ30mGRpE

World Tuberculosis Day 2016

In 1997, Directly Observed Treatment, Short Course (DOTS) was declared as a biggest step taken against TB by the WHO in the press conference of Berlin. Due to the global situation of this epidemic disease, almost 200 organizations were joined to perform the awareness activities on the World Tuberculosis Day of 1998 where top 22 most affected countries with TB were announced by the WHO in the press conference in London. A new network “Stop TB Partnership” has been established by the various organizations to fight against TB by highlighting the scope of prevention and cure of the disease to the common public. Currently, the International Committee of the Red Cross (ICRC) is assisting people to fight against TB in prisons due to the poor nutrition and overcrowding. The theme of the World Tuberculosis Day celebration was different year by year, while the theme of the year 2016 would be “Unite to End TB”. Editorial

The procurement landscape of pediatric tuberculosis treatment: a Global Drug Facility perspective.

Simple, quality-assured, child-friendly formulations of existing first-line anti-tuberculosis (TB) drugs in the correct dosages are now becoming available. Efforts are currently underway by the TB Alliance, the World Health Organization (WHO), and its partners to make appropriate medicines available to treat children diagnosed with TB. The functioning of the current market and the distribution pathways in pediatric TB drugs now require characterization and understanding in order to develop appropriate strategies for delivery of these and other future pediatric TB medicines. The Stop TB Partnership's Global Drug Facility (GDF) plays a major role in supplying pediatric TB medications worldwide. GDF is considered to be the largest procurer of pediatric TB treatment and the largest supplier to national TB programs of quality pediatric drugs. Between 2007 and 2013, the GDF delivered more than 580, 000 treatments to children in over 50 countries, 14 of which are among the 22 high TB burden countries. We analyzed this data set in the context of WHO estimates of pediatric TB as well as other available information to assess the functioning of the current market, lessons learnt from the GDF experience in the market, and opportunities for future products.

The experience of patients living with human-immunodeficiency virus/tuberculosis co-infection: a systematic review of qualitative evidence protocol

The experience of patients living with human-immunodeficiency virus/tuberculosis co-infection: a systematic review of qualitative evidence protocol

When collaborative governance scales up: lessons from global public health about compound collaboration

Global diseases require collaboration at multiple scales – from local to global. This article examines the experience of three international global public health partnerships – UNAIDS, the Stop TB Partnership and the Roll Back Malaria Partnership. These partnerships must be understood as compound collaborations. Such collaboration can often exhibit a marked tension between loose and tight coupling. Strategically designed to be loose or flexible in order to build initial support, loose institutional arrangements can also render these partnerships ineffective. Focal institutions, however, can help to align and facilitate the contributions of different partners operating on different scales.

Editorial introductions

Editorial introductions

Scope and Perspectives of New TB Drugs and Vaccines

Tuberculosis remains a major threatening infectious disease claiming millions of lives every year; hence increasing the global burden of TB disease. Co-infection with human immuno-deficiency virus and emergence of multi-drug resistant tuberculosis, extremely drug resistant tuberculosis and totally drug resistant tuberculosis enhances deadly effect of tuberculosis. To eliminate TB disease from human population several partnerships are working together like Stop TB Partnership, TB Alliance, Tuberculosis vaccine initiative, Global Alliance for TB Drug Development and many other partners. Till now almost 10 drugs and 11 vaccines are under various clinical trials. Anti-Tuberculosis drugs like bedaquiline and clofazimine are being developed for treatment of tuberculosis as well as for treating MDR-TB, XDR-TB and TDR-TB but till now, no drugs are available for treatment of TDR-TB. PA-824 and SQ-109 showed their potent activity against tuberculosis and thought to reduce the treatment duration in infected patients. Several vaccines are also being developed for enhancing the effect of Bacillus-Calmette-Guerin as well for replacing it. New anti-tuberculosis drugs offer hopes of shortened treatment regimens for drug susceptible, drug resistant and latent infection. The quest for better vaccines for controlling tuberculosis among human population in future continues.

Reducing the price of treatment for multidrug-resistant tuberculosis through the Global Drug Facility.

ProblemMany countries have limited experience of securing the best prices for drugs and have little negotiating power. This is particularly true for the complex, lengthy and expensive regimens used to treat multidrug-resistant tuberculosis.ApproachThe Stop TB Partnership’s Global Drug Facility is dedicated to improving worldwide access to antituberculosis medicines and diagnostic techniques that meet international quality standards.Local settingThe Global Drug Facility is able to secure price reductions through competitive tendering among prequalified drug manufacturers and by consolidating orders to achieve large purchase volumes. Consolidating the market in this way increases the incentives for suppliers of quality-assured medicines.Relevant changesIn 2013 the Global Drug Facility reduced the price of the second-line drugs it supplies for multidrug-resistant tuberculosis: the overall cost of the longest and most expensive treatment regimen for a patient decreased by 26% – from 7890 United States dollars (US$) in 2011 to US$ 5822 in 2013.Lessons learntThe price of treatment for multidrug-resistant tuberculosis supplied by the Global Drug Facility was reduced by consolidating orders to achieve large purchase volumes, by international, competitive bidding and by the existence of donor-funded medicine stockpiles. The rise in the number of suppliers of internationally quality-assured drugs was also important. The savings achieved from lower drug costs could be used to increase the number of patients on high-quality treatment.