'I'm fed up': experiences of prior anti-tuberculosis treatment in patients with drug-resistant tuberculosis and HIV

To understand the impact of past experiences of anti-tuberculosis treatment among patients co-infected with the human immunodeficiency virus and multidrug-resistant tuberculosis (MDR-TB) on perceptions and attitudes towards treatment

Time to Culture Conversion and Regimen Composition in Multidrug-Resistant Tuberculosis Treatment

Sputum cultures are an important tool in monitoring the response to tuberculosis treatment, especially in multidrug-resistant tuberculosis. There has, however, been little study of the effect of treatment regimen composition on culture conversion. Well-designed clinical trials of new anti-tuberculosis drugs require this information to establish optimized background regimens for comparison. We conducted a retrospective cohort study to assess whether the use of an aggressive multidrug-resistant tuberculosis regimen was associated with more rapid sputum culture conversion. We conducted Cox proportional-hazards analyses to examine the relationship between receipt of an aggressive regimen for the 14 prior consecutive days and sputum culture conversion. Sputum culture conversion was achieved in 519 (87.7%) of the 592 patients studied. Among patients who had sputum culture conversion, the median time to conversion was 59 days (IQR: 31–92). In 480 patients (92.5% of those with conversion), conversion occurred within the first six months of treatment. Exposure to an aggressive regimen was independently associated with sputum culture conversion during the first six months of treatment (HR: 1.36; 95% CI: 1.10, 1.69). Infection with human immunodeficiency virus (HR 3.36; 95% CI: 1.47, 7.72) and receiving less exposure to tuberculosis treatment prior to the individualized multidrug-resistant tuberculosis regimen (HR: 1.58; 95% CI: 1.28, 1.95) were also independently positively associated with conversion. Tachycardia (HR: 0.77; 95% CI: 0.61, 0.98) and respiratory difficulty (HR: 0.78; 95% CI: 0.62, 0.97) were independently associated with a lower rate of conversion. This study is the first demonstrating that the composition of the multidrug-resistant tuberculosis treatment regimen influences the time to culture conversion. These results support the use of an aggressive regimen as the optimized background regimen in trials of new anti-TB drugs

Aggressive Regimens for Multidrug-Resistant Tuberculosis Decrease All-Cause Mortality

Rationale: A better understanding of the composition of optimal treatment regimens for multidrug-resistant tuberculosis (MDR-TB) is essential for expanding universal access to effective treatment and for developing new therapies for MDR-TB. Analysis of observational data may inform the definition of an optimized regimen. Objectives: This study assessed the impact of an aggressive regimen–one containing at least five likely effective drugs, including a fluoroquinolone and injectable–on treatment outcomes in a large MDR-TB patient cohort. Methods: This was a retrospective cohort study of patients treated in a national outpatient program in Peru between 1999 and 2002. We examined the association between receiving an aggressive regimen and the rate of death. Measurements and Main Results: In total, 669 patients were treated with individualized regimens for laboratory-confirmed MDR-TB. Isolates were resistant to a mean of 5.4 (SD 1.7) drugs. Cure or completion was achieved in 66.1% (442) of patients; death occurred in 20.8% (139). Patients who received an aggressive regimen were less likely to die (crude hazard ratio [HR]: 0.62; 95% CI: 0.44,0.89), compared to those who did not receive such a regimen. This association held in analyses adjusted for comorbidities and indicators of severity (adjusted HR: 0.63; 95% CI: 0.43,0.93). Conclusions: The aggressive regimen is a robust predictor of MDR-TB treatment outcome. TB policy makers and program directors should consider this standard as they design and implement regimens for patients with drug-resistant disease. Furthermore, the aggressive regimen should be considered the standard background regimen when designing randomized trials of treatment for drug-resistant TB

Novel pediatric delivery systems for second-line anti-tuberculosis medications: a case study

Tens of thousands of children are sick with multidrugresistant forms of tuberculosis (MDR-TB), but there are limited child-friendly delivery systems for second-line medications. This case study presents the devel opment of a granular dosing spoon pediatric delivery system for para-aminosalicylic acid. This product is the first of its kind for MDR-TB and could serve as a model for the development of other urgently needed pediatric delivery systems for second-line anti-tuberculosis drugs

Novel pediatric delivery systems for second-line anti-tuberculosis medications: a case study

Tens of thousands of children are sick with multidrugresistant forms of tuberculosis (MDR-TB), but there are limited child-friendly delivery systems for second-line medications. This case study presents the devel opment of a granular dosing spoon pediatric delivery system for para-aminosalicylic acid. This product is the first of its kind for MDR-TB and could serve as a model for the development of other urgently needed pediatric delivery systems for second-line anti-tuberculosis drugs

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis.

Global tuberculosis incidence has declined marginally over the past decade, and tuberculosis remains out of control in several parts of the world including Africa and Asia. Although tuberculosis control has been effective in some regions of the world, these gains are threatened by the increasing burden of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. XDR tuberculosis has evolved in several tuberculosis-endemic countries to drug-incurable or programmatically incurable tuberculosis (totally drug-resistant tuberculosis). This poses several challenges similar to those encountered in the pre-chemotherapy era, including the inability to cure tuberculosis, high mortality, and the need for alternative methods to prevent disease transmission. This phenomenon mirrors the worldwide increase in antimicrobial resistance and the emergence of other MDR pathogens, such as malaria, HIV, and Gram-negative bacteria. MDR and XDR tuberculosis are associated with high morbidity and substantial mortality, are a threat to health-care workers, prohibitively expensive to treat, and are therefore a serious public health problem. In this Commission, we examine several aspects of drug-resistant tuberculosis. The traditional view that acquired resistance to antituberculous drugs is driven by poor compliance and programmatic failure is now being questioned, and several lines of evidence suggest that alternative mechanisms-including pharmacokinetic variability, induction of efflux pumps that transport the drug out of cells, and suboptimal drug penetration into tuberculosis lesions-are likely crucial to the pathogenesis of drug-resistant tuberculosis. These factors have implications for the design of new interventions, drug delivery and dosing mechanisms, and public health policy. We discuss epidemiology and transmission dynamics, including new insights into the fundamental biology of transmission, and we review the utility of newer diagnostic tools, including molecular tests and next-generation whole-genome sequencing, and their potential for clinical effectiveness. Relevant research priorities are highlighted, including optimal medical and surgical management, the role of newer and repurposed drugs (including bedaquiline, delamanid, and linezolid), pharmacokinetic and pharmacodynamic considerations, preventive strategies (such as prophylaxis in MDR and XDR contacts), palliative and patient-orientated care aspects, and medicolegal and ethical issues

Management of mental health disorders in HIV-positive patients

These guidelines are intended as a reference document to assist HIV nurse and doctor clinicians in managing mental health disorders. It is intended to improve awareness, knowledge and capacity to support patients living with HIV and mental health disorders

The Ethics of Ethics Reviews in Global Health Research: Case Studies Applying a New Paradigm

With increasing calls for global health research there is growing concern regarding the ethical challenges encountered by researchers from high-income countries (HICs) working in low or middle-income countries (LMICs). There is a dearth of literature on how to address these challenges in practice. In this article, we conduct a critical analysis of three case studies of research conducted in LMICs.We apply emerging ethical guidelines and principles specific to global health research and offer practical strategies that researchers ought to consider. We present case studies in which Canadian health professional students conducted a health promotion project in a community in Honduras; a research capacity-building program in South Africa, in which Canadian students also worked alongside LMIC partners; and a community-university partnered research capacity-building program in which Ecuadorean graduate students, some working alongside Canadian students, conducted community-based health research projects in Ecuadorean communities.We examine each case, identifying ethical issues that emerged and how new ethical paradigms being promoted could be concretely applied.We conclude that research ethics boards should focus not only on protecting individual integrity and human dignity in health studies but also on beneficence and non-maleficence at the community level, explicitly considering social justice issues and local capacity-building imperatives.We conclude that researchers from HICs interested in global health research must work with LMIC partners to implement collaborative processes for assuring ethical research that respects local knowledge, cultural factors, the social determination of health, community participation and partnership, and making social accountability a paramount concern

Opportunities from a new disease for an old threat: extending COVID-19 efforts to address tuberculosis in South Africa

The COVID-19 pandemic and phased nationwide lockdown have impacted negatively on individuals with tuberculosis (TB) and routine TB services. Through a literature review and the perspective of members of a national TB Think Tank task team, we describe the impact of the pandemic and lockdown on TB patients and services as well as the potential long-term setback to TB control in South Africa (SA). Strategies to mitigate risk and impact are explored, together with opportunities to leverage synergies from both diseases to the benefit of the National TB Programme (NTP). With the emergence of COVID-19, activities to address this new pandemic have been prioritised across all sectors. Within the health system, the health workforce and resources have been redirected away from routine services towards the new disease priority. The social determinants of health have deteriorated during the lockdown, potentially increasing progression to TB disease and impacting negatively on people with TB and their households, resulting in additional barriers to accessing TB care, with early reports of a decline in TB testing rates. Fewer TB diagnoses, less attention to adherence and support during TB treatment, poorer treatment outcomes and consequent increased transmission will increase the TB burden and TB-related mortality. People with TB or a history of TB are likely to be vulnerable to COVID-19. Modifications to current treatment practices are suggested to reduce visits to health facilities and minimise the risks of COVID 19 exposure. The COVID-19 pandemic has the potential to negatively impact on TB control in TB-endemic settings such as SA. However, there are COVID-19-related health systems-strengthening developments that may help the NTP mitigate the impact of the pandemic on TB control. By integrating TB case finding into the advanced screening, testing, tracing and monitoring systems established for COVID-19, TB case finding and linkage to care could increase, with many more TB patients starting treatment. Similarly, integrating knowledge and awareness of TB into the increased healthcare worker and community education on infectious respiratory diseases, behavioural practices around infection prevention and control, and cough etiquette, including destigmatisation of mask use, may contribute to reducing TB transmission. However, these potential gains could be overwhelmed by the impact of increasing poverty and other social determinants of health on the burden of TB