Search

Tuberculosis, caused by the Mycobacterium tuberculosis (Mtb) bacteria, is one of the world’s deadliest infectious diseases. Despite being the world’s oldest pandemic, tuberculosis is very much a challenge of the modern era. In high-incidence settings, all people are at risk, irrespective of whether they have common vulnerabilities to the disease warranting the current WHO recommendations for community-wide tuberculosis active case finding in these settings. Despite good evidence of effectiveness in reducing tuberculosis transmission, uptake of this strategy has been lacking in the communities that would derive greatest benefit. We consider the various complexities in eliminating tuberculosis from the first principles of the disease, including diagnostic and other challenges that must be navigated under an elimination agenda. We make the case that community-wide tuberculosis active case finding is the best strategy currently available to drive elimination forward in high-incidence settings and that no time should be lost in its implementation. Recognizing that high-incidence communities vary in their epidemiology and spatiosocial characteristics, tuberculosis research and funding must now shift towards radically supporting local implementation and operational research in communities. This “preparing of the ground” for scaling up to community-wide intervention centers the local knowledge and local experience of community epidemiology to optimize implementation practices and accelerate reductions in community-level tuberculosis transmission.

Active-case finding (ACF) using chest X-ray is an essential method of finding and diagnosing Tuberculosis (TB) cases that may be missed in Indonesia’s routine TB case finding. This study compares active and passive TB case-finding strategies. A retrospective study of TB case notification was conducted. Data between 1 January and 31 December 2021, was used. The population in this study were TB cases notified from Kulon Progo District health facilities, including those found through routine activities or active-case findings. A total of 249 TB cases were diagnosed in Kulon Progo in 2021, and 102 (41%) were bacteriologically confirmed. The TB patients’ ages ranged from 0 to 85 years (median 52, IQR 31–61). The majority of cases were male (59%, 147/249) and mostly among people aged 15–59 (61.4%, 153/249). The proportion of clinical TB diagnoses among cases found from active-case findings was 74.7% (68/91) while the proportion among passive-case findings was 50% (79/158). Active-case finding contributed 91 (36.5%) TB cases to the total cases detected in Kulon Progo in 2021. The use of chest X-rays in active-case findings likely contributed to the detection of a higher proportion of clinical TB than in passive-case findings.

In Indonesia, the implementation of tuberculosis (TB) contact investigation is limited, with low detection rates. We report the yield of and risk factors for TB disease and infection for household contacts (HHCs) investigated using chest X-ray (CXR) screening. We identified HHCs aged five years and above of bacteriologically confirmed index cases from 2018 to 2022 in Yogyakarta City and Kulon Progo. All HHCs were offered screening for TB symptoms; TB infection testing with either tuberculin skin testing or interferon gamma release assay; and referral for CXR. Sputum from those with symptoms or CXR suggestive of TB was tested with Xpert MTB/RIF. Risk factors for active TB disease and latent TB infection (LTBI) were identified by logistic regression models. We screened 2857 HHCs for TB between June 2020 and December 2022, with 68 (2.4%) diagnosed with active TB. Of 2621 HHCs eligible for LTBI investigation, 1083 (45.7%) were diagnosed with LTBI. The factors associated with active TB were age, being underweight, diabetes mellitus, urban living, and sleeping in the same house as an index case. Factors associated with LTBI were increasing age and male gender. Conclusions: Screening for HHC including CXR and TST/IGRA yielded a moderate prevalence of TB disease and infection.

Coverage of tuberculosis preventive treatment (TPT) in Indonesia is inadequate, and persons who start TPT often do not complete treatment. In 2020, Zero TB Yogyakarta implemented person-centered contact investigation and shorter TPT regimen provision in collaboration with primary health care centers. Between 1 January 2020 and 31 August 2022, we assessed eligibility for TPT among household contacts of persons with bacteriologically confirmed TB (index cases) and offered them a 3-month TPT regimen (3RH or 3HP). A dedicated nurse monitored contacts on TPT for treatment adherence and side effects every week in the first month and every two weeks in the next months. Contacts were also able to contact a nurse by phone or ask for home visits at any point if they had any concerns. A total of 1016 contacts were eligible for TPT: 772 (78.8%) started short regimen TPT with 706 (91.5%) completing their TPT. Side effects were reported in 26 (39%) of the non-completion group. We conclude that high rates of TPT uptake and completion among contacts assessed as eligible for TPT can be achieved through person-centered care and the use of shorter regimens. Side-effect monitoring and management while on TPT is vital for improving TPT completion.

Abstract Background Globally rifampicin-resistant tuberculosis disease affects around 460,000 people each year. Currently recommended regimens are 9–24 months duration, have poor efficacy and carry significant toxicity. A shorter, less toxic and more efficacious regimen would improve outcomes for people with rifampicin-resistant tuberculosis. Methods TB-PRACTECAL is an open-label, randomised, controlled, phase II/III non-inferiority trial evaluating the safety and efficacy of 24-week regimens containing bedaquiline and pretomanid to treat rifampicin-resistant tuberculosis. Conducted in Uzbekistan, South Africa and Belarus, patients aged 15 and above with rifampicin-resistant pulmonary tuberculosis and requiring a new course of therapy were eligible for inclusion irrespective of HIV status. In the first stage, equivalent to a phase IIB trial, patients were randomly assigned one of four regimens, stratified by site. Investigational regimens include oral bedaquiline, pretomanid and linezolid. Additionally, two of the regimens also included moxifloxacin (arm 1) and clofazimine (arm 2) respectively. Treatment was administered under direct observation for 24 weeks in investigational arms and 36 to 96 weeks in the standard of care arm. The second stage of the study was equivalent to a phase III trial, investigating the safety and efficacy of the most promising regimen/s. The primary outcome was the percentage of unfavourable outcomes at 72 weeks post-randomisation. This was a composite of early treatment discontinuation, treatment failure, recurrence, lost-to-follow-up and death. The study is being conducted in accordance with ICH-GCP and full ethical approval was obtained from Médecins sans Frontières ethical review board, London School of Hygiene and Tropical Medicine ethical review board as well as ERBs and regulatory authorities at each site. Discussion TB-PRACTECAL is an ambitious trial using adaptive design to accelerate regimen assessment and bring novel treatments that are effective and safe to patients quicker. The trial took a patient-centred approach, adapting to best practice guidelines throughout recruitment. The implementation faced significant challenges from the COVID-19 pandemic. The trial was terminated early for efficacy on the advice of the DSMB and will report on data collected up to the end of recruitment and, additionally, the planned final analysis at 72 weeks after the end of recruitment. Trial registration Clinicaltrials.gov NCT02589782. Registered on 28 October 2015.

Abstract Background Molecular mechanisms determining the transmission and prevalence of drug resistant tuberculosis (DR-TB) in Papua New Guinea (PNG) are poorly understood. We used genomic and drug susceptibility data to explore the evolutionary history, temporal acquisition of resistance and transmission dynamics of DR-TB across PNG. Methods We performed whole genome sequencing on isolates from Central Public Health Laboratory, PNG, collected 2017–2019. Data analysis was done on a composite dataset that also included 100 genomes previously sequenced from Daru, PNG (2012–2015). Results Sampled isolates represented 14 of the 22 PNG provinces, the majority (66/94; 70%) came from the National Capital District (NCD). In the composite dataset, 91% of strains were Beijing 2.2.1.1, identified in 13 provinces. Phylogenetic tree of Beijing strains revealed two clades, Daru dominant clade (A) and NCD dominant clade (B). Multi-drug resistance (MDR) was repeatedly and independently acquired, with the first MDR cases in both clades noted to have emerged in the early 1990s, while fluoroquinolone resistance emerged in 2009 (95% highest posterior density 2000–2016). We identified the presence of a frameshift mutation within Rv0678 (p.Asp47fs) which has been suggested to confer resistance to bedaquiline, despite no known exposure to the drug. Overall genomic clustering was significantly associated with rpoC compensatory and inhA promoter mutations (p

ABSTRACT We report the findings of a prospective laboratory diagnostic accuracy study to evaluate the sensitivity, specificity, and predictive values of the Xpert MTB/RIF Ultra assay for Mycobacterium tuberculosis detection in fresh stool specimens from children under 15 years of age with confirmed tuberculosis (TB) disease from Dushanbe, Tajikistan. Six hundred eighty-eight (688) participants were enrolled from April 2019 to October 2021. We identified 16 participants (2.3%) with confirmed TB disease, defined as ≥1 TB sign/symptom plus microbiologic confirmation. With the Xpert MTB/RIF Ultra assay for stool, we found a sensitivity of 68.8% (95% CI, 46.0 to 91.5) and a specificity of 98.7% (95% CI, 97.8 to 99.5) in confirmed TB disease. Our results are comparable to other published studies; however, our cohort was larger and our confirmed TB disease rate lower than most. We also demonstrated that this assay was feasible to implement in a centralized hospital laboratory in a low-middle-income Central Asian country. However, we encountered obstacles such as lack of staffing, material ruptures, outdated government protocols, and decreased case presentation due to COVID-19. We found eight patients whose only positive test was an Xpert Ultra stool assay. None needed treatment during the study; however, three were treated later, suggesting such cases require close observation. Our report is the first from Central Asia and one of a few from a low-middle-income country. We believe our study demonstrates the generalizability of the Xpert MTB/RIF Ultra assay on fresh stool specimens from children and provides further evidence supporting WHO’s approval of this diagnostic strategy. IMPORTANCE The importance of this report is that it provides further support for WHO’s recent recommendation that fresh stool is an acceptable sample for GeneXpert TB testing in children, especially small children who often cannot produce an adequate sputum sample. Diagnosing TB in this age group is difficult, and many cases are missed, leading to unacceptable rates of TB illness and death. In our large cohort of children from Dushanbe, Tajikistan, the GeneXpert stool test was positive in 69% of proven cases of TB, and there were very few false-positive tests. We also showed that this diagnostic strategy was feasible to implement in a low-middle-income country with an inefficient health care delivery system. We hope that many more programs will adopt this form of diagnosing TB in children.

The World Health Organization recommends using chest X-ray (CXR) in active case finding (ACF) to improve case detection. This study aimed to describe the spectrum and outcomes of TB disease diagnosed through a mobile community based ACF program in Yogyakarta. This prospective cohort study included people attending a TB ACF program in Yogyakarta between 1 January 2021 to 30 June 2022. Participants ≥10 years old underwent CXR, symptom screening, and Xpert MTB/RIF testing of sputum. Subclinical TB was defined as asymptomatic active TB, whether bacteriologically confirmed or not. Treatment outcome data were obtained from the national program TB database. 47,735 people attended the ACF program; the yield of TB disease was 0.86% (393/45,938). There were 217 symptomatic cases, of whom 72 (33.2%) were bacteriologically confirmed, and 176 asymptomatic cases, with 52 (29.5%) bacteriologically confirmed. Treatment success was 70.7% with high loss to follow up (9%) and not evaluated (17.1%). Multivariate analysis demonstrated weak evidence for lower unsuccessful outcomes in symptomatic versus subclinical TB (aOR 0.6, 95% CI 0.36–0.998). TB ACF programs utilizing CXR may diagnose a high proportion of subclinical TB. Linkage to care in ACF program is important to increase successful treatment outcomes.

Healthcare workers (HCWs) are at risk of contracting TB, particularly when in high tuberculosis (TB) burden settings. Routine surveillance data and evidence are limited on the burden of TB amongst HCWs in Indonesia. We aimed to measure the prevalence of TB infection (TBI) and disease among HCWs in four healthcare facilities in Yogyakarta province in Indonesia, and explore risk factors for TBI. A cross-sectional TB screening study targeted all HCWs from four pre-selected facilities (1 hospital, 3 primary care) in Yogyakarta, Indonesia. Voluntary screening included symptom assessment, Chest X-ray (CXR), Xpert MTB/RIF (if indicated) and tuberculin skin test (TST). Analyses were descriptive and included multivariable logistic regression. Of 792 HCWs, 681 consented (86%) to the screening; 59% (n = 401) were female, 62% were medical staff (n = 421), 77% worked in the one participating hospital (n = 524), and the median time working in the health sector was 13 years (IQR: 6-25 years). Nearly half had provided services for people with TB (46%, n = 316) and 9% reported ever having TB (n = 60). Among participants with presumptive TB (15%, n = 99/662), none were diagnosed microbiologically or clinically with active TB disease. TBI was detected in 25% (95% CI: 22-30; n = 112/441) of eligible HCWs with a TST result. A significant association was found between TB infection and being male (adjusted Odds Ratio (aOR) 2.02 (95%CI: 1.29-3.17)), currently working in the participating hospital compared to primary care (aOR 3.15 (95%CI: 1.75-5.66)), and older age (1.05 OR increase per year of life between 19-73 years (95%CI: 1.02-1.06)). This study supports prioritisation of HCWs as a high-risk group for TB infection and disease, and the need for comprehensive prevention and control programs in Indonesia. Further, it identifies characteristics of HCWs in Yogyakarta at higher risk of TBI, who could be prioritised in screening programs if universal coverage of prevention and control measures cannot be achieved.

Background: Health worker training is an important component of a holistic outbreak response, and travel restrictions resulting from the COVID-19 pandemic have highlighted the potential of virtual training. Evaluation of training activities is essential for understanding the effectiveness of a training program on knowledge and clinical practice. We conducted an evaluation of the online COVID-19 Healthcare E-Learning Platform (CoHELP) in Papua New Guinea (PNG) to assess its effectiveness, measure engagement and completion rates, and determine barriers and enablers to implementation, in order to inform policy and practice for future training in resource-limited settings. Methods: The evaluation team conducted a mixed methods evaluation consisting of pre- and post-knowledge quizzes; quantification of engagement with the online platform; post-training surveys; qualitative interviews with training participants, non-participants, and key informants; and audits of six health facilities. Results: A total of 364 participants from PNG signed up to participate in the CoHELP online training platform, with 41% (147/360) completing at least one module. Of the 24 participants who completed the post-training survey, 92% (22/24) would recommend the program to others and 79% (19/24) had used the knowledge or skills gained through CoHELP in their clinical practice. Qualitative interviews found that a lack of time and infrastructural challenges were common barriers to accessing online training, and participants appreciated the flexibility of online, self-paced learning. Conclusions: Initially high registration numbers did not translate to ongoing engagement with the CoHELP online platform, particularly for completion of evaluation activities. Overall, the CoHELP program received positive feedback from participants involved in the evaluation, highlighting the potential for further online training courses in PNG.

Abstract Background There are unique challenges in the diagnosis and management of multi drug resistant tuberculosis (MDR-TB) in children. It is difficult to obtain confirmatory microbiological diagnosis in TB pericarditis. It is essential to differentiate between drug sensitive and drug resistant forms of TB as it has a major bearing on the regimen used, and inappropriate TB treatment combined with steroid use for pericarditis can lead to deterioration. With lack of samples, the treatment decision relies on the drug resistance pattern of the close contact if available. Therapeutic challenges of MDR-TB management in a child involve use of toxic drugs that need to be judiciously handled. We report a 2 years 4 months old male child who was diagnosed with TB pericarditis and treated based on the resistance pattern of his mother who was on treatment for pulmonary MDR-TB. Case presentation This 2 years 4 months old male child was diagnosed with TB involving his pericardium. Getting him started on an appropriate regimen was delayed due to the difficulty in establishing microbiological confirmation and drug susceptibility. He was commenced on a regimen based on his mother’s drug resistance pattern and required surgery due to cardiac failure during the course of his treatment. He successfully completed 2 years of therapy. Conclusions This child’s case demonstrates that despite unique challenges in diagnosis and management of drug resistant extra pulmonary tuberculosis in children, treatment of even complex forms can be successful. The need for high suspicion of MDR-TB, especially when there is close contact with pulmonary TB, careful design of an effective regimen that is tolerated by the child, indications for invasive surgical management of pericarditis, appropriate follow-up and management of adverse effects are emphasised.

Background In 2016, World Health Organization guidelines conditionally recommended standardised shorter 9–12-month regimens for multidrug-resistant (MDR) tuberculosis (TB) treatment. We conducted a prospective study of a shorter standardised MDR-TB regimen in Karakalpakstan, Uzbekistan. Methods Consecutive adults and children with confirmed rifampicin-resistant pulmonary TB were enrolled between September 1, 2013 and March 31, 2015; exclusions included prior treatment with second-line anti-TB drugs, and documented resistance to ofloxacin or to two second-line injectable agents. The primary outcome was recurrence-free cure at 1 year following treatment completion. Results Of 146 enrolled patients, 128 were included: 67 female (52.3%), median age 30.1 (interquartile range 23.8–44.4) years. At the end of treatment, 71.9% (92 out of 128) of patients achieved treatment success, with 68% (87 out of 128) achieving recurrence-free cure at 1 year following completion. Unsuccessful outcomes during treatment included 22 (17.2%) treatment failures with fluoroquinolone-resistance amplification in 8 patients (8 out of 22, 36.4%); 12 (9.4%) lost to follow-up; and 2 (1.5%) deaths. Recurrence occurred in one patient. Fourteen patients (10.9%) experienced serious adverse events. Baseline resistance to both pyrazinamide and ethambutol (adjusted OR 6.13, 95% CI 2.01; 18.63) and adherence

We present a case report describing outcomes in a 21 year old HIV-negative man who received treatment with bedaquiline. Due to error, dosage received comprised 4 pills of 100 mg every second day in the 60 days following the first two weeks of 4 pills of 100 mg every day. On detection, treatment was continued as per standard dosing of 200 mg given three times per week, with enhanced monitoring of ECG and liver function. The man was asymptomatic, with no signs of jaundice, abdominal pain, or abnormal heart rhythm. Toxic effects at this dosage were therefore not observed. Keywords: Tuberculosis, Bedaquiline, Adverse events, Therapeutic index, Tolerability

The World Health Organization’s (WHO) END-TB strategy has set the world on course to climb the highest of medical mountains by 2035, with a targeted peak of reductions in TB deaths by 95%, TB cases by 90%, and no burden of catastrophic expenses on families due to TB [...]

Abstract Background Extensively drug-resistant (XDR) tuberculosis (TB) and multidrug resistant (MDR)-TB with additional resistance to injectable agents or fluoroquinolones are challenging to treat due to lack of available, effective drugs. Linezolid is one of the few drugs that has shown promise in treating these conditions. Long-term linezolid use is associated with toxicities such as peripheral and optic neuropathies. Diabetes mellitus (DM), especially when uncontrolled, can also result in peripheral neuropathy. The global burden of DM is increasing, and DM has been associated with a three-fold increased risk of developing TB disease. TB and DM can be a challenging combination to treat. DM can inhibit the host immune response to tuberculosis infection; and TB and some anti-TB drugs can worsen glycaemic control. A child experiencing neuropathy that is a possible complication of both DM and linezolid used to treat TB has not been reported previously. We report peripheral neuropathy in a 15-year-old boy with type 1 DM, diagnosed with MDR-TB and additional resistance to injectable TB medications. Case presentation The boy was treated with a linezolid-based regimen, but after 8 months developed peripheral neuropathy. It was unclear whether the neuropathy was caused by the DM or the linezolid therapy. He had clinical improvement following cessation of linezolid and was declared cured following 21 months of treatment. Following completion of treatment, nerve conduction studies demonstrated significant improvement in neuropathy. Conclusions To the best of our knowledge, this is the first case of peripheral neuropathy reported in a diabetic child on long-term linezolid therapy for tuberculosis. This case study underlines the importance of stringent follow-up for side effects of linezolid, especially when associated with co-morbidity such as DM that increases the chances of adverse effects. The presence of both DM and TB should alert a physician to strive for optimal glycaemic control to minimize the risk of complications as well as optimizing the chances of recovery from TB. Our case report shows the need for close and frequent monitoring for neuropathy to enable early intervention and thereby a favourable outcome in children who may otherwise suffer a long-lasting, debilitating, and painful neuropathy.

The emergence and spread of multidrug-resistant tuberculosis (MDR-TB) poses a major threat to the global targets for TB control. In recent years, an evolving science and evidence base for MDR-TB has led to much needed changes in international guidelines promoting the use of newer TB drugs and regimens for MDR-TB, however, there remains a significant implementation gap. Due to the complexity of treating MDR-TB, management of cases is often supported by an expert multidisciplinary team, or clinical expert group. This service is often centralized, and may be delivered through a telemedicine platform. We have implemented a Web-based “store-and-forward” telemedicine service to optimize MDR-TB patient care in Daru, a remote and resource limited setting in Papua New Guinea (PNG). From April 2016 to February 2019, 237 cases were discussed using the service. This encompassed diagnostic (presumptive) and treatment cases, and more recently, support to the scale up of preventative therapy for latent TB infection. There were 75 cases in which the use of Bedaquiline was discussed or mentioned, with a high frequency of discussions occurring in the initial period (26 cases in the first 12 months), which has appeared to decrease as clinicians gained familiarity with use of the drug (15 cases in the last 12 months). This service has supported high quality clinical care and fostered collaboration between clinicians and technical experts in a shared learning environment.

We describe 27 children and adolescents

The emergence of resistance to anti-tuberculosis (DR-TB) drugs and the HIV epidemic represent a serious threat for reducing the global burden of TB. Although data on HIV-negative DR-TB treatment outcomes are well published, few data on DR-TB outcomes among HIV co-infected people is available despite the great public health importance.We retrospectively reported and compared the DR-TB treatment outcomes of HIV-positive and HIV-negative patients treated with an individualized regimen based on WHO guidelines in seven countries: Abkhazia, Armenia, Colombia, Kenya, Kyrgyzstan, Swaziland and Uzbekistan.Of the 1,369 patients started DRTB treatment, 809 (59.1%) were multi-drug resistant (MDR-TB) and 418 (30.5%) were HIV-positive. HIV-positive patients were mainly from African countries (90.1%) while HIV-negative originated from Former Soviet Union (FSU) countries. Despite a higher case fatality rate (19.0% vs 9.4%), HIV-positive MDR-TB patients had a 10% higher success rate than HIV-negative patients (64.0% vs 53.2%, p = 0.007). No difference in treatment success was found among polydrug-resistant (PDR-TB) patients. Overall, lost to follow-up rate was much higher among HIV-negative (22.0% vs. 8.4%). Older age and not receiving ART were the only factors associated with unfavorable treatment outcome among HIV-positive patients.As already known for HIV-negative patients, success rate of DR-TB HIV-positive patients remains low and requires more effective DR-TB regimen using new drugs also suitable to HIV-infected patients on ART. The study also confirms the need of ART introduction in HIV co-infected patients.

Fewer than 20% of patients with multidrug-resistant (MDR) tuberculosis are receiving treatment and there is an urgent need to scale up treatment programmes. One of the biggest barriers to scale-up is the treatment regimen, which is lengthy, complex, ineffective, poorly tolerated and expensive. For the first time in over 50 years, new drugs have been developed specifically to treat tuberculosis, with bedaquiline and potentially delamanid expected to be available soon for treatment of MDR cases. However, if the new drugs are merely added to the current treatment regimen, the new regimen will be at least as lengthy, cumbersome and toxic as the existing one. There is an urgent need for strategy and evidence on how to maximize the potential of the new drugs to improve outcomes and shorten treatment. We devised eight key principles for designing future treatment regimens to ensure that, once they are proven safe in clinical trials, they will be clinically effective and programmatically practicable. Regimens should contain at least one new class of drug; be broadly applicable for use against MDR and extensively drug-resistant Mycobacterium tuberculosis complex strains; contain three to five effective drugs, each from a different drug class; be delivered orally; have a simple dosing schedule; have a good side-effect profile that allows limited monitoring; last a maximum of 6 months; and have minimal interaction with antiretrovirals. Following these principles will maximize the potential of new compounds and help to overcome the clinical and programmatic disadvantages and scale-up constraints that plague the current regimen.

Indonesia has the third highest tuberculosis (TB) caseload internationally. A cornerstone for strengthening health systems to respond to TB is a well-trained workforce. In a partnership between Indonesian and Australian institutions, TB training was run during 2018 to strengthen the local capacity to meet End TB strategy targets. This paper aims to report on course design, delivery, training outcomes, and reflections. Seventy-six Indonesian healthcare workers, program staff, researchers, and policy-makers were selected from over 800 applicants. The structure comprised three trainings, each with a pre-course workshop (in Indonesia) to identify learning needs, a two-week block (Australia), and a post-course workshop (Indonesia). The training content delivered was a combination of TB technical knowledge and program/project theory, design, and logic, and the training utilised multiple teaching and learning methods. An innovative element of the training was participant-designed TB workplace projects focusing on context-specific priorities. Evaluation was undertaken using participant surveys and appraisal of the projects. Participants rated the course highly, while success in project implementation varied. Reflections include the importance of involving Indonesian experts in delivery of training, the need to understand participant learning requirements and adapt the training content accordingly, and the challenge of measuring tangible training outputs.

In the year-end editorial, the PLOS Medicine editors ask 11 researchers and clinicians about the most relevant challenges, promising research, and important initiatives in their fields as we head into 2016.

In 2011, Médecins Sans Frontières (MSF) established a blogging project, "TB&Me," to enable patients with multidrug-resistant tuberculosis (MDR-TB) to share their experiences. By September 2012, 13 MDR-TB patients had blogged, either directly or with assistance, from the UK, Australia, Philippines, Swaziland, Central African Republic, Uganda, South Africa, India, and Armenia. Due to the lack of research on the potential for social media to support MDR-TB treatment and the innovative nature of the blog, we decided to conduct a qualitative study to examine patient and staff experiences. Our aim was to identify potential risks and benefits associated with blogging to enable us to determine whether social media had a role to play in supporting patients with MDR-TB.Participants were identified and selected purposively. TB&Me bloggers, project staff, MSF headquarters staff involved with TB and WHO European Region TB policy advisors were invited to participate in a semi-structured interview. Twenty interviews were conducted (five with bloggers). Data analysis drew upon principles of grounded theory, with constant comparison of data, cases and categories, and attention to deviant cases. We found that the TB&Me blog was associated with identified health benefits, with no reported instances of harm. There were three main findings: blogging was reported as useful for adherence to DR-TB treatment and supportive of the treatment-taking process by all bloggers and project staff; blogging provided support to patients (peer support, shared experience and reduction in isolation); and the blog was perceived as giving patients strength and voice.The TB&Me blog was seen to be associated with positive identified health and emotional benefits. Component 5 of the Stop TB Global Plan highlights the importance of empowering TB patients and communities. Blogging could be a useful tool to help achieve that ambition.

OBJECTIVES: To identify associations between specific WHO stage 3 and 4 conditions diagnosed after ART initiation and all cause mortality for patients in resource-limited settings (RLS). DESIGN, SETTING: Analysis of routine program data collected prospectively from 25 programs in eight countries between 2002 and 2010. SUBJECTS, PARTICIPANTS: 36,664 study participants with median ART follow-up of 1.26 years (IQR 0.55-2.27). OUTCOME MEASURES: Using a proportional hazards model we identified factors associated with mortality, including the occurrence of specific WHO clinical stage 3 and 4 conditions during the 6-months following ART initiation. RESULTS: There were 2922 deaths during follow-up (8.0%). The crude mortality rate was 5.41 deaths per 100 person-years (95% CI: 5.21-5.61). The diagnosis of any WHO stage 3 or 4 condition during the first 6 months of ART was associated with increased mortality (HR: 2.21; 95% CI: 1.97-2.47). After adjustment for age, sex, region and pre-ART CD4 count, a diagnosis of extrapulmonary cryptococcosis (aHR: 3.54; 95% CI: 2.74-4.56), HIV wasting syndrome (aHR: 2.92; 95%CI: 2.21 -3.85), non-tuberculous mycobacterial infection (aHR: 2.43; 95% CI: 1.80-3.28) and Pneumocystis pneumonia (aHR: 2.17; 95% CI 1.80-3.28) were associated with the greatest increased mortality. Cerebral toxoplasmosis, pulmonary and extra-pulmonary tuberculosis, Kaposi's sarcoma and oral and oesophageal candidiasis were associated with increased mortality, though at lower rates. CONCLUSIONS: A diagnosis of certain WHO stage 3 and 4 conditions is associated with an increased risk of mortality in those initiating ART in RLS. This information will assist initiatives to reduce excess mortality, including prioritization of resources for diagnostics, therapeutic interventions and research.

BACKGROUND: The Médecins Sans Frontières project of Uzbekistan has provided multidrug-resistant tuberculosis treatment in the Karakalpakstan region since 2003. Rates of default from treatment have been high, despite psychosocial support, increasing particularly since programme scale-up in 2007. We aimed to determine factors associated with default in multi- and extensively drug-resistant tuberculosis patients who started treatment between 2003 and 2008 and thus had finished approximately 2 years of treatment by the end of 2010. METHODS: A retrospective cohort analysis of multi- and extensively drug-resistant tuberculosis patients enrolled in treatment between 2003 and 2008 compared baseline demographic characteristics and possible risk factors for default. Default was defined as missing ≥60 consecutive days of treatment (all drugs). Data were routinely collected during treatment and entered in a database. Potential risk factors for default were assessed in univariate analysis using chi-square test and in multivariate analysis with logistic regression. RESULTS: 20% (142/710) of patients defaulted after a median of 6 months treatment (IQR 2.6-9.9). Factors associated with default included severity of resistance patterns (pre-extensively drug-resistant/extensively drug-resistant tuberculosis adjusted odds ratio 0.52, 95%CI: 0.31-0.86), previous default (2.38, 1.09-5.24) and age >45 years (1.77, 1.10-2.87). The default rate was 14% (42/294) for patients enrolled 2003-2006 and 24% (100/416) for 2007-2008 enrolments (p = 0.001). CONCLUSIONS: Default from treatment was high and increased with programme scale-up. It is essential to ensure scale-up of treatment is accompanied with scale-up of staff and patient support. A successful first course of tuberculosis treatment is important; patients who had previously defaulted were at increased risk of default and death. The protective effect of severe resistance profiles suggests that understanding disease severity or fear may motivate against default. Targeted health education and support for at-risk patients after 5 months of treatment when many begin to feel better may decrease default.

The HIV epidemic has increased the proportion of patients with smear-negative and extrapulmonary tuberculosis (TB) diagnoses, with related higher rates of poor TB treatment outcomes. Unlike in smear-positive pulmonary TB, no interim markers of TB treatment progress are systematically used to identify individuals most at risk of mortality. The objective of this study was to assess the association of body mass index (BMI) change at 1 month (±15 days) from TB treatment start with mortality among HIV-positive individuals with smear-negative and extrapulmonary TB.A retrospective cohort study of adult HIV-positive new TB patients in Médecins Sans Frontières (MSF) treatment programmes in Myanmar and Zimbabwe was conducted using Cox proportional hazards regression to estimate the association between BMI category change and mortality. A cohort of 1090 TB patients (605 smear-negative and 485 extrapulmonary) was followed during TB treatment with mortality rate of 28.9 per 100 person-years. In multivariable analyses, remaining severely underweight or moving to a lower BMI category increased mortality (adjusted hazard ratio 4.05, 95% confidence interval 2.77-5.91, p

OBJECTIVES: To determine the incidence of WHO clinical stage 3 and 4 conditions during early anti-retroviral therapy (ART) in resource limited settings (RLS). DESIGN/SETTING: A descriptive analysis of routine program data collected prospectively from 25 Médecins Sans Frontières supported HIV treatment programs in eight countries between 2002 and 2010. SUBJECTS/PARTICIPANTS: 35,349 study participants with median follow-up on ART of 1.33 years (IQR 0.51-2.41). OUTCOME MEASURES: Incidence in 100 person-years of WHO stage 3 or 4 conditions during 5 periods after ART initiation. Diagnoses of conditions were made according to WHO criteria and relied upon clinical assessments supported by basic laboratory investigations. RESULTS: The incidence of any WHO clinical stage 3 or 4 condition over 3 years was 40.02 per 100 person-years (31.77 for stage 3 and 8.25 for stage 4). The incidence of stage 3 and 4 conditions fell by over 97% between months 0-3 and months 25-36 (77.81 to 2.40 for stage 3 and 28.70 to 0.64 for stage 4). During months 0-3 pulmonary tuberculosis was the most common condition diagnosed in adults (incidence 22.24 per 100 person-years) and children aged 5-14 years (25.76) and oral candidiasis was the most common in children