Geographical heterogeneity of multidrug-resistant tuberculosis in Georgia, January 2009 to June 2011.

In 2011, Georgia, in the Caucasus, reported that 11% of new and 32% of previously treated tuberculosis (TB) cases nationally had multidrug-resistant TB (MDR-TB). To help understand the mechanisms driving these high risks of drug-resistance and plan for targeted interventions, we identified geographical variability in the MDR-TB burden in Georgia and patient-level MDR-TB risk factors. We used routinely collected surveillance data on notified TB cases to estimate the MDR-TB incidence/100,000 people and the percentage of TB cases with MDR-TB for each of 65 districts and regression modelling to identify patient-level MDR-TB risk factors. 1,795 MDR-TB cases were reported (January 2009­June 2011); the nationwide notified MDR-TB incidence was 16.2/100,000 but far higher (837/100,000) in the penitentiary system. We found substantial geographical heterogeneity between districts in the average annual MDR-TB incidence/100,000 (range: 0.0­5.0 among new and 0.0­18.9 among previously treated TB cases) and the percentage of TB cases with MDR-TB (range: 0.0%­33.3% among new and 0.0%­75.0% among previously treated TB cases). Among treatment-naïve individuals, those in cities had greater MDR-TB risk than those in rural areas (increased odds: 43%; 95% confidence interval: 20%­72%). These results suggest that interventions for interrupting MDR-TB transmission are urgently needed in prisons and urban areas.

Building social equity and person-centred innovation into the end TB response.

Reducing systemic inequities in testing, access to care, social protection - and in the scientific process - is essential to end TB. Incorporating social science methods and expertise on inequity into the mainstream TB response would help ensure that political commitments to equity move beyond symbolic gestures. We convened a meeting between TB social scientists, people with lived experience, civil society and community members to discuss equity within the global TB response. Here, we propose five means by which a social science lens can strengthen equitable, person-centred responses and reconcile the public health significance of TB with the principles of social justice.

Best practices for the care of pregnant people living with TB.

BACKGROUND: Each year more than 200,000 pregnant people become sick with TB, but little is known about how to optimize their diagnosis and therapy. Although there is a need for further research in this population, it is important to recognize that much can be done to improve the services they currently receive.METHODS: Following a systematic review of the literature and the input of a global team of health professionals, a series of best practices for the diagnosis, prevention and treatment of TB during pregnancy were developed.RESULTS: Best practices were developed for each of the following areas: 1) screening and diagnosis; 2) reproductive health services and family planning; 3) treatment of drug-susceptible TB; 4) treatment of rifampicin-resistant/multidrug-resistant TB; 5) compassionate infection control practices; 6) feeding considerations; 7) counseling and support; 8) treatment of TB infection/TB preventive therapy; and 9) research considerations.CONCLUSION: Effective strategies for the care of pregnant people across the TB spectrum are readily achievable and will greatly improve the lives and health of this under-served population.

Clinical standards for the management of adverse effects during treatment for TB.

BACKGROUND: Adverse effects (AE) to TB treatment cause morbidity, mortality and treatment interruption. The aim of these clinical standards is to encourage best practise for the diagnosis and management of AE.METHODS: 65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards.RESULTS: We identified eight clinical standards. Each person commencing treatment for TB should: Standard 1, be counselled regarding AE before and during treatment; Standard 2, be evaluated for factors that might increase AE risk with regular review to actively identify and manage these; Standard 3, when AE occur, carefully assessed and possible allergic or hypersensitivity reactions considered; Standard 4, receive appropriate care to minimise morbidity and mortality associated with AE; Standard 5, be restarted on TB drugs after a serious AE according to a standardised protocol that includes active drug safety monitoring. In addition: Standard 6, healthcare workers should be trained on AE including how to counsel people undertaking TB treatment, as well as active AE monitoring and management; Standard 7, there should be active AE monitoring and reporting for all new TB drugs and regimens; and Standard 8, knowledge gaps identified from active AE monitoring should be systematically addressed through clinical research.CONCLUSION: These standards provide a person-centred, consensus-based approach to minimise the impact of AE during TB treatment.

Clinical standards for drug-susceptible TB in children and adolescents.

BACKGROUND: These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents.METHODS: Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document.RESULTS: Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent.CONCLUSION: These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.

Standards for clinical trials for treating TB.

BACKGROUND: The value, speed of completion and robustness of the evidence generated by TB treatment trials could be improved by implementing standards for best practice.METHODS: A global panel of experts participated in a Delphi process, using a 7-point Likert scale to score and revise draft standards until consensus was reached.RESULTS: Eleven standards were defined: Standard 1, high quality data on TB regimens are essential to inform clinical and programmatic management; Standard 2, the research questions addressed by TB trials should be relevant to affected communities, who should be included in all trial stages; Standard 3, trials should make every effort to be as inclusive as possible; Standard 4, the most efficient trial designs should be considered to improve the evidence base as quickly and cost effectively as possible, without compromising quality; Standard 5, trial governance should be in line with accepted good clinical practice; Standard 6, trials should investigate and report strategies that promote optimal engagement in care; Standard 7, where possible, TB trials should include pharmacokinetic and pharmacodynamic components; Standard 8, outcomes should include frequency of disease recurrence and post-treatment sequelae; Standard 9, TB trials should aim to harmonise key outcomes and data structures across studies; Standard 10, TB trials should include biobanking; Standard 11, treatment trials should invest in capacity strengthening of local trial and TB programme staff.CONCLUSION: These standards should improve the efficiency and effectiveness of evidence generation, as well as the translation of research into policy and practice.

Early mortality during rifampicin-resistant TB treatment.

BACKGROUND: Data suggest that treatment with newer TB drugs (linezolid [LZD], bedaquiline [BDQ] and delamanid [DLM]), used in Khayelitsha, South Africa, since 2012, reduces mortality due to rifampicin-resistant TB (RR-TB).METHODS: This was a retrospective cohort study to assess 6-month mortality among RR-TB patients diagnosed between 2008 and 2019.RESULTS: By 6 months, 236/2,008 (12%) patients died; 12% (78/651) among those diagnosed in 2008-2011, and respectively 8% (49/619) and 15% (109/738) with and without LZD/BDQ/DLM in 2012-2019. Multivariable analysis showed a small, non-significant mortality reduction with LZD/BDQ/DLM use compared to the 2008-2011 period (aOR 0.79, 95% CI 0.5-1.2). Inpatient treatment initiation (aOR 3.2, 95% CI 2.4-4.4), fluoroquinolone (FQ) resistance (aOR 2.7, 95% CI 1.8-4.2) and female sex (aOR 1.5, 95% CI 1.1-2.0) were also associated with mortality. When restricted to 2012-2019, use of LZD/BDQ/DLM was associated with lower mortality (aOR 0.58, 95% CI 0.39-0.87).CONCLUSIONS: While LZD/BDQ/DLM reduced 6-month mortality between 2012 and 2019, there was no significant effect overall. These findings may be due to initially restricted LZD/BDQ/DLM use for those with high-level resistance or treatment failure. Additional contributors include increased treatment initiation among individuals who would have otherwise died before treatment due to universal drug susceptibility testing from 2012, an effect that also likely contributed to higher mortality among females (survival through to care-seeking).

TB screening, prevention and treatment cascade in a Malawi prison.

BACKGROUND Incarcerated individuals, especially in high HIV and TB burden settings, are at increased risk of latent TB infection and/or TB disease. We implemented a comprehensive HIV-TB intervention in a Malawi prison and studied its feasibility.METHODS Between February and December 2019, consenting individuals underwent screening for HIV, TB infection and TB disease. HIV-positive individuals without TB disease were treated with a fixed-dose combination of isoniazid, cotrimoxazole and vitamin B6 (INH-CTX-B6). HIV-negative persons with TB infection received 12 weeks of isoniazid and rifapentine (3HP).RESULTS Of 1,546 consenting individuals, 1,498 (96.9%) were screened and 1,427 (92.3%) included in the analysis: 96.4% were male, the median age was 31 years (IQR 25-38). Twenty-nine (2.1%) participants were diagnosed with TB disease, of whom 89.7% started and 61.5% completed TB treatment. Of the 1,427 included, 341 (23.9%) were HIV-positive, of whom 98.5% on antiretroviral therapy and 95% were started on INH-CTX-B6. Among 1,086 HIV-negative participants, 1,015 (93.5%) underwent the tuberculin skin test (TST), 670 (65.9%) were TST-positive, 666 (99.4%) started 3HP and 570 (85.5%) completed 3HP treatment.CONCLUSION A comprehensive TB screening and treatment package among incarcerated individuals was acceptable and feasible, and showed high prevalence of HIV, TB disease and TB infection. Treatment uptake was excellent, but treatment completion needs to be improved. Greater investment in comprehensive HIV-TB services, including access to shorter TB regimens and follow-up upon release, is needed for incarcerated individuals.

Causes of loss to follow-up from drug-resistant TB treatment in Khayelitsha, South Africa.

Patients initiated on drug-resistant TB(DR-TB) treatment in 2019 in Khayelitsha, South Africa, with a loss to follow-up outcome were evaluated to better understand reasons for loss to follow-up and to determine if any had returned to care. Of a total of 187 patients, 28 (15%) were lost to follow-up (LTFU), 24 (86%) of whom were traced: 20/24 (83%) were found when they re-presented to facilities and 8/28 (29%) were linked back to DR-TB care. People with DR-TB continue to seek care even after being LTFU; thus better coordination between different components of the healthcare system are required to re-engage with these patients. Interventions to mitigate the socio-economic challenges of people on DR-TB treatment are needed. Many people who were LTFU and symptomatic were willing to re-engage with DR-TB care, which highlights the importance of for compassionate interventions to welcome them back.

Les patients placés sous traitement pour TB pharmacorésistante (DR-TB) en 2019 à Khayelitsha, Afrique du Sud, et ayant été perdus de vue ont été évalués afin de mieux comprendre les raisons de la perte de vue et de déterminer si certains étaient de nouveau suivis. Sur 187 patients, 28 (15%) ont été perdus de vue, dont 24 (86%) ont été retrouvés : 20/24 (83%) ont été retrouvés lorsqu'ils se sont de nouveau présentés en consultation et 8/28 (29%) ont été réinsérés dans le parcours de soins de la DR-TB. Les patients atteints de DR-TB sont toujours en demande de soins, même après avoir été perdus de vue. Ainsi, une meilleure coordination entre les différentes composantes du système de santé est nécessaire afin de rétablir le lien avec ces patients. Des interventions visant à atténuer les problèmes socio-économiques des patients sous traitement pour DR-TB sont nécessaires. De nombreux patients symptomatiques ayant été perdus de vue étaient enclins à reprendre leur traitement de la DR-TB. Il est donc important de mettre en place des programmes compassionnels afin de les réinsérer dans le parcours de soins.

Clinical standards for drug-susceptible pulmonary TB.

BACKGROUND: The aim of these clinical standards is to provide guidance on 'best practice´ for diagnosis, treatment and management of drug-susceptible pulmonary TB (PTB).METHODS: A panel of 54 global experts in the field of TB care, public health, microbiology, and pharmacology were identified; 46 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all 46 participants.RESULTS: Seven clinical standards were defined: Standard 1, all patients (adult or child) who have symptoms and signs compatible with PTB should undergo investigations to reach a diagnosis; Standard 2, adequate bacteriological tests should be conducted to exclude drug-resistant TB; Standard 3, an appropriate regimen recommended by WHO and national guidelines for the treatment of PTB should be identified; Standard 4, health education and counselling should be provided for each patient starting treatment; Standard 5, treatment monitoring should be conducted to assess adherence, follow patient progress, identify and manage adverse events, and detect development of resistance; Standard 6, a recommended series of patient examinations should be performed at the end of treatment; Standard 7, necessary public health actions should be conducted for each patient. We also identified priorities for future research into PTB.CONCLUSION: These consensus-based clinical standards will help to improve patient care by guiding clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment for PTB.

Clinical standards for the assessment, management and rehabilitation of post-TB lung disease.

BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR).METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement).RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR.CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD.

Breastfeeding in women living with tuberculosis.

Breast milk provides optimal nutrition, and is recommended for neonates and infants. In women with TB, there has been uncertainty about optimal feeding practices due to the risk of transmission to the neonate and the possibility of drug exposure via breast milk. For women who have drug-susceptible TB (DS-TB) who are no longer infectious, it is safe to breastfeed as breast milk does not contain Mycobacterium tuberculosis bacilli and only minor, non-toxic quantities of the drugs pass into breast milk. Most guidelines therefore encourage breastfeeding in women with DS-TB. However, there is uncertainty and guidelines vary regarding women with DS-TB who are still infectious and in women with rifampicin-resistant TB (RR-TB). Although the transmission dynamics of DS- and RR-TB are similar, additional infection control precautions for RR-TB may be necessary until the mother is responding to treatment, as second-line therapy may be less efficacious and preventive therapy is not widely offered to infants. In addition, there are no published data describing the extent to which second-line drugs are secreted into breast milk or subsequent exposure in breastfed infants. The implications of limited information on policy and consequent dilemmas regarding patient care are illustrated in a patient scenario. Areas for future research are suggested.

New TB drugs for the treatment of children and adolescents with rifampicin-resistant TB in Mumbai, India.

SETTING: Médecins Sans Frontières (MSF) clinic in Mumbai, India.OBJECTIVE: To determine the final treatment outcomes, culture conversion and adverse events (AEs) during treatment among children and adolescents (0-19 years) with rifampicin-resistant tuberculosis (RR-TB) who received ambulatory injectable-free treatment, including bedaquiline (BDQ) and/or delamanid (DLM) during September 2014-January 2020.DESIGN: This was a retrospective cohort study based on review of routinely collected programme data.RESULTS: Twenty-four patients were included; the median age was 15.5 years (min-max 3-19) and 15 (63%) were females. None were HIV-coinfected. All had fluoroquinolone resistance. Twelve received treatment, including BDQ and DLM, 11 received DLM and one BDQ. The median exposure to BDQ (n = 13) and DLM (n = 23) was 82 (IQR 80-93) and 82 (IQR 77-96) weeks, respectively. Seventeen (94%) patients with positive culture at baseline (n = 18) had negative culture during treatment; median time for culture-conversion was 7 weeks (IQR 5-11). Twenty-three (96%) had successful treatment outcomes: cured (n = 16) or completed treatment (n = 7); one died. Eleven (46%) had 17 episodes of AEs. Two of 12 serious AEs were associated with new drugs (QTcF >500 ms).CONCLUSION: Based on one of the largest global cohorts of children and adolescents to receive new TB drugs, this study has shown that injectable-free regimens containing BDQ and/or DLM on ambulatory basis were effective and well-tolerated among children and adolescents and should be made routinely accessible to these vulnerable groups.

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.

Bedaquiline and delamanid result in low rates of unfavourable outcomes among TB patients in Eswatini.

SETTING: Since 2015, Eswatini has been scaling up bedaquiline (BDQ) and delamanid (DLM) based drug-resistant TB treatment regimens under programmatic conditions.OBJECTIVE: Identification of factors associated with treatment outcomes in patients receiving BDQ and/or DLM either as a new treatment initiation or drug substitution.DESIGN: This is a retrospective cohort study of patients receiving BDQ and/or DLM in Eswatini between March 2015 and October 2018. We describe factors associated with unfavourable treatment outcomes (death, lost to follow-up, treatment failure and amplification of resistance) and culture conversion using multivariable flexible parametric survival and competing-risks regression analyses.RESULTS: Of 352 patients receiving BDQ and/or DLM, 7.8% and 21.2% had an unfavourable treatment outcome at 6 and 24 months, respectively. Predictors were age ≥ 60 years (adjusted hazard ratio aHR 4.49, 95%CI 1.61-12.57) vs. age 20-39 years, and a treatment regimen combining both drugs (aHR 4.49, 95%CI 1.61-12.57) vs. BDQ only. The probability of culture conversion was increased for two health facilities and patients with a poly resistance profile (adjusted sub-hazard ratio 2.01, 95%CI 1.13-3.59) vs. multidrug resistance.CONCLUSION: Single use of BDQ or DLM was associated with low rates of unfavourable outcomes, suggesting that these medications may be effectively adopted at scale under routine programmatic conditions. Combined use of BDQ and DLM was a risk factor for unfavourable outcomes and should prompt for collection of more data on the combined use of these medications.

Clinical perspectives on treatment of rifampicin-resistant/multidrug-resistant TB.

Rapid diagnostics, newer drugs, repurposed medications, and shorter regimens have radically altered the landscape for treating rifampicin-resistant TB (RR-TB) and multidrug-resistant TB (MDR-TB). There are multiple ongoing clinical trials aiming to build a robust evidence base to guide RR/MDR-TB treatment, and both observational studies and programmatic data have contributed to advancing the treatment field. In December 2019, the WHO issued their second 'Rapid Communication´ related to RR-TB management. This reiterated their prior recommendation that a majority of people with RR/MDR-TB receive all-oral treatment regimens, and now allow for specific shorter duration regimens to be used programmatically as well. Many TB programs need clinical advice as they seek to roll out such regimens in their specific setting. In this Perspective, we highlight our early experiences and lessons learned from working with National TB Programs, adult and pediatric clinicians and civil society, in optimizing treatment of RR/MDR-TB, using shorter, highly-effective, oral regimens for the majority of people with RR/MDR-TB.

Barriers and solutions to finding rifampicin-resistant tuberculosis cases in older children and adolescents.

Little is known about the barriers to post-exposure management of rifampicin-resistant tuberculosis (RR-TB) in older children and adolescents. We report on implementation lessons from a pilot programme targeting household-exposed individuals aged 6-18 years in Khayelitsha, South Africa. Barriers included misperceptions regarding risk of exposure, multiple research and implementation stakeholders, additional workload for an overburdened healthcare system, logistical issues faced by families, and insufficient human and financial resources. Solutions to these barriers are possible, but creativity and persistence are required. Our experience can guide others looking to roll-out care for children and adolescents exposed to RR-TB.

On connaît mal les entraves à la prise en charge post-exposition de la tuberculose résistante à la rifampicine (RR-TB) chez les enfants plus âgés et les adolescents. Nous rapportons les leçons de la mise en œuvre d'un programme pilote ciblant les individus exposés dans leurs foyers, âgés de 6­18 ans, à Khayelitsha, Afrique du Sud. Les obstacles ont inclus des perceptions erronées à propos du risque d'exposition, la multiplicité des partenaires de recherche et de mise en œuvre, la charge de travail supplémentaire pour un système de santé déjà surchargé, les problèmes logistiques auxquels sont confrontées les familles, et l'insuffisance des ressources humaines et financières. Il y a des solutions possibles à ces obstacles mais elles demandent de la créativité et de la détermination. Notre expérience peut guider ceux qui veulent lancer la prise en charge des enfants et des adolescents exposés à la RR-TB.

Se conoce poco sobre los factores que obstaculizan la atención después de la exposición a un caso de tuberculosis resistente a rifampicina (RR-TB) en los niños mayores y los adolescentes. En el presente artículo se describen las enseñanzas aprendidas durante la ejecución de un programa piloto dirigido a los contactos domiciliarios expuestos entre los 6 y los 18 años de edad, en Khayelitsha, Suráfrica. Entre los obstáculos observados se pueden citar las percepciones equivocadas sobre el riesgo de exposición, la multiplicidad de interesados directos en la investigación y la ejecución, la carga de trabajo adicional en un sistema de salud sobresaturado, los problemas organizativos afrontados por las familias y la insuficiencia de recursos humanos y de financiamiento. Las soluciones a estos problemas son posibles, pero exigen creatividad y persistencia. Esta experiencia puede orientar a otros equipos que intenten poner en marcha la atención de los niños y los adolescentes expuestos a la RR-TB.

Rates and risk factors for nephrotoxicity and ototoxicity among tuberculosis patients in Tbilisi, Georgia.

SETTING: Treatment of multidrug-resistant tuberculosis (MDR-TB) is lengthy and utilizes second-line anti-TB drugs associated with frequent adverse drug reactions (ADRs).OBJECTIVE: To evaluate the prevalence of and risk factors for ADRs among patients with MDR- and extensively drug-resistant TB (XDR-TB).DESIGN: A retrospective chart review of patients initiating treatment for M/XDR-TB in 2010-2012 in Tbilisi, Georgia.RESULTS: Eighty (54%) and 38 (26%) of 147 patients developed nephrotoxicity per RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) classification and ototoxicity, respectively. Twenty-five (17%) patients required permanent interruption of injectables due to an ADR. Median hospital stay, total treatment duration and number of regimen changes were higher among those with nephrotoxicity and/or ototoxicity, compared to those without (P < 0.01). Multinomial logistic regression analysis identified increasing age (per year) as a risk factor for nephrotoxicity (aOR 1.08, 95%CI 1.03-1.12) and for both, nephro- and ototoxicity (aOR 1.11, 95%CI 1.05-1.17). Low baseline creatinine clearance (CrCl) was a significant risk factor for developing nephrotoxicity (aOR 1.05, 95%CI 1.02-1.07).CONCLUSION: Second-line injectable drug-related ADRs are common among M/XDR-TB patients. Patients with increasing age and low baseline CrCl should be monitored closely for injectable-related ADRs. Notably, our findings support WHO's latest recommendations on introduction of injectable free anti-TB treatment regimens.

Expanding global HIV treatment: case studies from the field.

In the last 25 years, human immunodeficiency virus (HIV) has become the leading infectious killer of adults globally, with an estimated 44 million people infected with the virus worldwide. Most of these individuals live in poor regions of the world, particularly sub-Saharan Africa. Although a great deal of work has been done in identifying and treating individuals with the disease, there has been little action to date to address the complex socioeconomic factors that lie at the heart of this global pandemic. Understanding and responding to such factors is of paramount importance if HIV infection is to be managed in a meaningful way. This article explores the social context of people living with HIV in three different geographic and epidemiologic settings and highlights the social factors that shape and define an individual's risk of acquiring HIV. It also discusses unique programs aimed at addressing the complex realities of the world in which HIV thrives. These programs can act as models of HIV prevention and treatment.

Treating multidrug-resistant tuberculosis in Tomsk, Russia: developing programs that address the linkage between poverty and disease.

Tuberculosis (TB) and multidrug-resistant TB (MDR-TB) are diseases of poverty. Because Mycobacterium tuberculosis exists predominantly in a social space often defined by poverty and its comorbidities--overcrowded or congregate living conditions, substance dependence or abuse, and lack of access to proper health services, to name a few--the biology of this organism and of TB drug resistance is intimately linked to the social world in which patients live. This association is demonstrated in Russia, where political changes in the 1990s resulted in increased socioeconomic inequality and a breakdown in health services. The effect on TB and MDR-TB is reflected both in terms of a rise in TB and MDR-TB incidence and increased morbidity and mortality associated with the disease. We present the case example of Tomsk Oblast to delineate how poverty contributed to a growing MDR-TB epidemic and increasing socioeconomic barriers to successful care, even when available. The MDR-TB pilot project implemented in Tomsk addressed both programmatic and socioeconomic factors associated with unfavorable outcomes. The result has been a strengthening of the overall TB control program in the region and improved case-holding for the most vulnerable patients. The model of MDR-TB care in Tomsk is applicable for other resource-poor settings facing challenges to TB and MDR-TB control.