Palliative care needs among patients with advanced illnesses in Bhutan.

BACKGROUND: Palliative care improves the quality of lives of patients and families affected by advanced illnesses through the prevention and relief of suffering. While palliative care is well established in developed countries, it is inadequate or non-existent in most developing countries. Palliative care is an emerging concept in Bhutan, a tiny Himalayan Kingdom. A small community palliative care service is available in the national referral hospital with three dedicated inpatient palliative care beds. This study explored the needs for palliative care among patients diagnosed with advanced illnesses and is a component of a larger project aimed to inform a suitable palliative care model for the country. METHODS: This is a cross-sectional descriptive study. A survey, using a structured questionnaire including the EORTC QLQ-C30, was carried out among patients with advanced illness in hospitals, primary care units and communities across the country. Purposeful and snowball sampling strategies were used to recruit study participants. RESULTS: Seventy (76%), out of 93 eligible patients, agreed to participate in the survey. Participants reported low to moderate scores on physical, role, emotional, cognitive and social functioning, a moderate score for the global health/ quality of life scale and moderately high (worse) scores in symptoms including fatigue, pain, insomnia, loss of appetite and the financial impact from the disease. CONCLUSIONS: The symptom burden experienced by patients affected by advanced illnesses demonstrates the need for palliative care in Bhutan. These findings will help inform the development of a public health-focused palliative care model, modified to the Bhutanese context, as recommended by the World Health Organization.

Mycobacteriophages as Potential Therapeutic Agents against Drug-Resistant Tuberculosis.

The current emergence of multi-, extensively-, extremely-, and total-drug resistant strains of Mycobacterium tuberculosis poses a major health, social, and economic threat, and stresses the need to develop new therapeutic strategies. The notion of phage therapy against bacteria has been around for more than a century and, although its implementation was abandoned after the introduction of drugs, it is now making a comeback and gaining renewed interest in Western medicine as an alternative to treat drug-resistant pathogens. Mycobacteriophages are genetically diverse viruses that specifically infect mycobacterial hosts, including members of the M. tuberculosis complex. This review describes general features of mycobacteriophages and their mechanisms of killing M. tuberculosis, as well as their advantages and limitations as therapeutic and prophylactic agents against drug-resistant M. tuberculosis strains. This review also discusses the role of human lung micro-environments in shaping the availability of mycobacteriophage receptors on the M. tuberculosis cell envelope surface, the risk of potential development of bacterial resistance to mycobacteriophages, and the interactions with the mammalian host immune system. Finally, it summarizes the knowledge gaps and defines key questions to be addressed regarding the clinical application of phage therapy for the treatment of drug-resistant tuberculosis.

What causes high costs for rural tuberculosis inpatients? Evidence from five counties in China.

BACKGROUND: Tuberculosis (TB) still causes high economic burden on patients in China, especially for rural patients. Our study aims to explore the risk factors associated with the high costs for TB inpatients in rural China from the aspects of inpatients' socio-demographic and institutional attributes. METHODS: Generalized linear models were utilized to investigate the factors associated with TB inpatients' total costs and out-of-pocket (OOP) expenditures. Quantile regression (QR) models were applied to explore the effect of each factor across the different costs range and identify the risk factors of high costs. RESULTS: TB inpatients with long length of stay and who receive hospitalization services cross provincially, in tertiary and specialized hospitals were likely to face high total costs and OOP expenditures. QR models showed that high total costs occurred in Dingyuan and Funan Counties, but they were not accompanied by high OOP expenditures. CONCLUSIONS: Early diagnosis, standard treatment and control of drug-resistant TB are still awaiting for more efforts from the government. TB inpatients should obtain medical services from appropriate hospitals. The diagnosis and treatment process of TB should be standardized across all designated medical institutions. Furthermore, the reimbursement policy for migrant workers who suffered from TB should be ameliorated.

A case report of a child with probable drug resistant tuberculous pericarditis with a review of challenges involved in diagnosis, treatment and follow up of children with DR-TB pericarditis.

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.

Ease and equity of access to free DR-TB services in Nigeria- a qualitative analysis of policies, structures and processes.

INTRODUCTION: Persistent low rates of case notification and treatment coverage reflect that accessing diagnosis and treatment for drug-resistant tuberculosis (DR-TB) in Nigeria remains a challenge, even though it is provided free of charge to patients. Equity in health access requires availability of comparable, appropriate services to all, based on needs, and irrespective of socio-demographic characteristics. Our study aimed to identify the reasons for Nigeria's low rates of case-finding and treatment for DR-TB. To achieve this, we analyzed elements that facilitate or hinder equitable access for different groups of patients within the current health system to support DR-TB management in Nigeria. METHODS: We conducted documentary review of guidelines and workers manuals, as well as 57 qualitative interviews, including 10 focus group discussions, with a total of 127 participants, in Nigeria. Between August and November 2017, we interviewed patients who were on treatment, their treatment supporter, and providers in Ogun and Plateau States, as well as program managers in Benue and Abuja. We adapted and used Levesque's patient-centered access to care framework to analyze DR-TB policy documents and interview data. RESULTS: Thematic analysis revealed inequitable access to DR-TB care for some patient socio-demographic groups. While patients were mostly treated equally at the facility level, some patients experienced more difficulty accessing care based on their gender, age, occupation, educational level and religion. Health system factors including positive provider attitudes and financial support provided to the patients facilitated equity and ease of access. However, limited coverage and the absence of patients' access rights protection and considerations in the treatment guidelines and workers manuals likely hampered access. CONCLUSION: In the context of Nigeria's low case-finding and treatment coverage, applying an equity of access framework was necessary to highlight gaps in care. Differing social contexts of patients adversely affected their access to DR-TB care. We identified several strengths in DR-TB care delivery, including the current financial support that should be sustained. Our findings highlight the need for government's commitment and continued interventions.

Factors contributing to drug-resistant tuberculosis treatment outcome in five countries in the Eastern Europe and Central Asia region.

Drug-resistant tuberculosis (DR-TB) is a global challenge and a major contributor of death from anti-microbial resistance. With the main aim to determine factors contributing to treatment outcomes observed among DR-TB patients in the countries in Eastern Europe and Central Asia (EECA), a multi-method study was conducted in: Azerbaijan, Belarus, Romania, Tajikistan and Ukraine. Both quantitative and qualitative methodologies were used for data collection and analysis. The quantitative approaches included a desk review of documents related to the DR-TB responses and an analysis of clinical records of DR-TB patients in selected health facilities of the five countries. Qualitative methods included in-depth interviews with national TB programme (NTP) managers, other healthcare providers and non-governmental organizations (NGOs) workers, as well as interviews and Focus Group Discussions (FGDs) with DR-TB patients. The desk review of 38 reports identified as the main challenges to address DR-TB financial and/or management issues and adverse events of the medicines. The most common recommendations related to treatment outcome focussed on general programme management, treatment regimen composition, clinical management and social support for the patients. In all the five countries the NTPs still have a vertical structure. Some integration into the primary health care system (PHC) already exists but further involvement of PHC facilities is feasible and recommended. Interviews with stakeholders indicated that alcoholism and homelessness and a lack of appropriate response to these issues remain as major challenges for a sub-set of patients. Civil society groups, NGOs and communities are substantially engaged in providing different services to DR-TB patients, especially in Ukraine, Romania and Tajikistan. Data from clinical records of 212 patients revealed that independent risk factors for unfavourable treatment outcome (death, loss to follow-up, failure) were culture-positivity at two months of treatment, history of treatment with second-line drugs and homelessness. More powerful, less toxic and shorter oral treatment regimens as well as comprehensive patient support are needed to improve treatment outcome of patients with DR-TB.

Evaluation of the Impact of a Sequencing Assay for Detection of Drug Resistance on the Clinical Management of Tuberculosis.

BACKGROUND: In 2012, the California Department of Public Health began using pyrosequencing (PSQ) to detect mutations associated with resistance to isoniazid, rifampin, quinolones and injectable drugs in Mycobacterium tuberculosis complex. We evaluated the impact of the PSQ assay on the clinical management of tuberculosis (TB) in California. METHODS: TB surveillance and laboratory data for specimens submitted 1 August 2012 through 31 December 2016 were analyzed to determine time to effective treatment initiation. A survey of clinicians was used to assess how PSQ results influenced clinical decision making. RESULTS: Of 1957 specimens tested with PSQ, 52% were sediments and 46% were culture isolates, submitted a median of 8 and 35 days, respectively, after collection. Among 36 patients with multidrug-resistant (MDR) TB who had a sediment specimen submitted for PSQ, median time from specimen collection to MDR-TB treatment initiation was 12 days vs 51 days when PSQ was not used. Completed surveys were returned for 303 patients, 177 of whom reported a treatment change; 75 (42%) of clinicians reported PSQ as a reason for change. Twenty-one patients either had an MDR-TB risk factor and a smear-positive sputum specimen, but had PSQ performed on a culture isolate (9/36 [25%]); or did not have PSQ used for MDR-TB diagnosis (12/38 [32%]) and thus had an opportunity for earlier MDR-TB diagnosis with PSQ on sediment. CONCLUSIONS: Patients with MDR-TB initiated effective treatment 5 weeks earlier when PSQ was used compared to those without PSQ. Survey data suggest clinicians use PSQ to devise effective TB drug regimens. To maximize the benefit of PSQ, earlier submission of specimens should be prioritized.

Precision medicine in the clinical management of respiratory tract infections including multidrug-resistant tuberculosis: learning from innovations in immuno-oncology.

PURPOSE OF REVIEW: In the light of poor management outcomes of antibiotic-resistant respiratory tract infection (RTI)-associated sepsis syndrome and multidrug-resistant tuberculosis (MDR-TB), new management interventions based on host-directed therapies (HDTs) are warranted to improve morbidity, mortality and long-term functional outcomes. We review developments in potential HDTs based on precision cancer therapy concepts applicable to RTIs including MDR-TB. RECENT FINDINGS: Immune reactivity, tissue destruction and repair processes identified during studies of cancer immunotherapy share common pathogenetic mechanisms with RTI-associated sepsis syndrome and MDR-TB. T-cell receptors (TCRs) and chimeric antigen receptors targeting pathogen-specific or host-derived mutated molecules (major histocompatibility class-dependent/ major histocompatibility class-independent) can be engineered for recognition by TCR γδ and natural killer (NK) cells. T-cell subsets and, more recently, NK cells are shown to be host-protective. These cells can also be activated by immune checkpoint inhibitor (ICI) or derived from allogeneic sources and serve as potential for improving clinical outcomes in RTIs and MDR-TB. SUMMARY: Recent developments of immunotherapy in cancer reveal common pathways in immune reactivity, tissue destruction and repair. RTIs-related sepsis syndrome exhibits mixed immune reactions, making cytokine or ICI therapy guided by robust biomarker analyses, viable treatment options.

Health-related quality of life of patients with multidrug-resistant tuberculosis in Yemen: prospective study.

BACKGROUND: Substantial efforts are currently focused on investigating and developing new multidrug-resistant tuberculosis (MDR-TB) drugs and diagnostic methods. In Yemen, however, the evaluation of health-related quality of life (HRQoL) and the effect of current MDR-TB treatment on the QoL are commonly ignored. This study evaluated the HRQoL during and after treatment and identified the risk factors that are predictive of HRQoL score differences. METHOD: A prospective cohort study was conducted in four of the five main MDR-TB centres in Yemen. The patients confirmed with MDR-TB completed the SF-36 V2 survey at the beginning of treatment, end of treatment (continous phase) and at the 1 year follow-up after completing treatment. A total normal base score (NBS) of < 47 reflects impairment of functions, whereas a mental component summary (MCS) score of < 43 indicates a risk of depression. RESULT: At the beginning of treatment, the mean scores for all health domains were < 47 NBS points (PF = 40.7, RP = 16.1, BP = 21.6, GH = 28.3, VT = 14.55, SF = 25.9, RE = 13.7, and MH = 14.7). At the completion of treatment, all eight health domains increase compare to beginning of treatment (PF = 59.3, RP = 31.1, BP = 40.9, GH = 48.5, VT = 30.5, SF = 46.6, RE =26.6 & MH = 27.7), but a follow-up duration of 1 year after completing treatment showed decreased NBS points in all domains (PF = 51.5, RP = 30.6, BP = 39.1, GH = 47.8, VT = 30.2, SF = 43.7, RE =26.4 & MH = 27.2). Age, history of streptomycin use, baseline lung cavity, marital status and length of sickness before MDR-TB diagnosis were predictive of in PCS score differences, whereas, age, smoking, baseline lung cavity, stigma, residence, marital status and length of sickness before MDR-TB diagnosis were predictive of MCS scores differences. CONCLUSION: The length of sickness before DR-TB diagnosis was found to be predictive of the trends in both PCS and MCS scores. Despite the positive outcome of MDR-TB treatment, the low HRQoL scores obtained for all heath domains and especially for mental health reflect a high depression status of patients even after 1 year of completing therapy. Moreover, the poor HRQoL, particularly regarding mental health, of study participants at the end of treatment demands the need for urgent attention from national tuberculosis control programme managers. Therefore, the Yemen Ministry of Health and the National Tuberculosis Control Programme should implement an intervention programme to enhance HRQoL at the end of treatment to avoid any further negative consequences of MDRTB in patients after treatment. Moreover, The HRQoL data of patients with MDR-TB must be collected at the different stages of MDR-TB treatment to provide an additional parameter for assessing the effectiveness of the treatment programme. TRIAL REGISTRATION: SNOYEM 1452. Registered 01 February 2013.

Being safe, feeling safe, and stigmatizing attitude among primary health care staff in providing multidrug-resistant tuberculosis care in Bantul District, Yogyakarta Province, Indonesia.

INTRODUCTION: Patient-centered care approach in multidrug-resistant tuberculosis care requires health worker safety that covers both being safe and feeling safe to conduct the services. Stigma has been argued as a barrier to patient-centered care. However, there has been relatively little research addressing the issues of safety and stigma among health staff. This paper explored the issue of being safe, feeling safe, and stigmatizing attitude among health staff working with multidrug-resistant tuberculosis cases in primary health care facilities in Indonesia. METHODS: Using a mixed methods research design, data was collected with structured questionnaires among 123 staff, observations of infection control in 17 primary health care facilities, and in-depth interviews among 22 staff. RESULTS: The findings showed suboptimal infection control infrastructures for the primary health care facilities. The knowledge and motivation to follow multidrug-resistant tuberculosis care protocols are suboptimal. Feeling unsafe is related to stigmatizing attitude in providing multidrug-resistant tuberculosis care. CONCLUSION: Being safe, feeling unsafe, and stigmatizing attitude are challenges in providing patient-centered multidrug-resistant tuberculosis care in primary health care facilities in Indonesia. Serious efforts are needed on all levels to ensure safety and prevent irrational stigma.

Survival analysis of time to cure on multi-drug resistance tuberculosis patients in Amhara region, Ethiopia.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is caused by bacteria that are resistant to the most effective anti-tuberculosis drug. The MDR-TB is an increasing global problem and the spread of MDR-TB has different recovery time for different patients. Therefore, this study aimed to investigate the recovery time of MDR-TB patients in Amhara region, Ethiopia. METHOD: A retrospective study was carried out in seven hospitals having MDR-TB treatment center of Amhara region, Ethiopia from September 2015 to February 2018. An accelerated failure time and parametric shared frailty models were employed. RESULTS: The study revealed that the recovery time of MDR-TB patients in Amhara region was 21 months. Out of the total MDR-TB patients, 110 (35.4%) censored and 201 (64.6%) cured of MDR-TB. The clustering effect of frailty model was hospitals and the Weibull-gamma shared frailty model was selected among all and hence used for this study. The study showed that extra pulmonary MDR-TB patients had longer recovery time than that of seamier pulmonary MDR-TB patients in Amhara region, Ethiopia. According to this study, male MDR-TB patients, MDR-TB patients with co-morbidity and clinical complication were experiencing longer recovery time than that of the counter groups. This study also showed that MDR-TB patients with poor adherence had longer recovery time than those with good adherence MDR-TB patients. CONCLUSION: Among different factors considered in this study, MDR-TB type, clinical complication, adherence, co-morbidities, sex, and smoking status had a significant effect on recovery time of MDR-TB patients in Amhara region, Ethiopia. In conclusion, the Regional and Federal Government of Ethiopia should take immediate steps to address causes of recovery time of MDR-TB patients in Amhara region through encouraging adherence, early case detection, and proper handling of drug-susceptibility according to WHO guidelines.

Cost-effectiveness of treating multidrug- and extensively drug-resistant tuberculosis: A systematic review.

OBJECTIVE: Tuberculosis (TB), along with the human immunodeficiency virus, is one of the leading causes of death from infectious diseases. Its prevalence has rendered the treatment of drug-resistant TB a major public health problem that threatens the progress made in TB care and control worldwide. Our objectives were to conduct a systematic review of the cost-effectiveness of treatment for multidrug-resistant and extensively drug-resistant TB (MDR-TB/XDR-TB) and to synthesise available data from scientific research. METHODS: Using English keywords, we searched for papers over reputable databases, such as Scopus, PubMed, Cochrane and Google Scholar, from Jan. 23 to Mar. 23, 2019. RESULTS: The search and screening yielded 13 articles, whose results were extracted and reviewed to draw conclusions on the cost-effectiveness of MDR-TB/XDR-TB treatment. The data extraction table used to cull and categorise the results comprised the characteristics of a given study, as well as its objectives, the perspectives used to guide the investigation, methods and results (outcome, sensitivity analysis). The measured outcome was the incremental cost-effectiveness ratio. CONCLUSIONS: The review indicated that MDR -TB/XDR-TB treatment can be very cost-effective in countries with low to high incomes, regardless of whether minimal or considerable disease burdens exist.

High use of private providers for first healthcare seeking by drug-resistant tuberculosis patients: a cross-sectional study in Yangon, Myanmar.

BACKGROUND: Drug resistance is a growing challenge to tuberculosis (TB) control worldwide, but particularly salient to countries such as Myanmar, where the health system is fragmented across the public and private sector. A recent systematic review has identified a critical lack of evidence for local policymaking, particularly in relation to drivers of drug-resistance that could be the target of preventative efforts. To address this gap from a health systems perspective, our study investigates the healthcare-seeking behavior and preferences of recently diagnosed patients with drug-resistant tuberculosis (DR-TB), focusing on the use of private versus public healthcare providers. METHODS: The study was conducted in ten townships across Yangon with high DR-TB burden. Patients newly-diagnosed with DR-TB by GeneXpert were enrolled, and data on healthcare-seeking behavior and socio-economic characteristics were collected from patient records and interviews. A descriptive analysis of healthcare-seeking behavior was followed by the investigation of relationships between socio-economic factors and type of provider visited upon first feeling unwell, through univariate logistic regressions. RESULTS: Of 202 participants, only 8% reported first seeking care at public facilities, while 88% reported seeking care at private facilities upon first feeling unwell. Participants aged 25-34 (Odds Ratio = 0.33 [0.12-0.95]) and males (Odds Ratio = 0.39 [0.20-0.75]) were less likely to visit a private clinic or hospital than those aged 18-24 and females, respectively. In contrast, participants with higher income were more likely to utilize private providers. Prior to DR-TB diagnosis, 86% of participants took medications from private providers. After DR-TB diagnosis, only 7% of participants continued to take medications from private providers. CONCLUSION: In urban Myanmar, most patients shifted to being managed exclusively in the public sector after being formally diagnosed with DR-TB. However, since the vast majority of DR-TB patients first visited private providers in the period leading to diagnosis, related issues such as unregulated quality of care, potential delays to diagnosis, and lack of care continuity may greatly influence the emergence of drug-resistance. A greater understanding of the health system and these healthcare-seeking behaviors may simultaneously strengthen TB control programmes and reduce government and out-of-pocket expenditures on the management of DR-TB.

A public health approach to palliative care in the response to drug resistant TB: an ethnographic study in Bengaluru, India.

BACKGROUND: The treatment of Multidrug-Resistant Tuberculosis represents one of the most significant challenges to global health. Despite guidance on improving treatment outcomes, there is little focus on how to support individuals in their suffering. Palliative care is therefore proposed as a necessary component in the global strategy to fight Tuberculosis. We aim to describe the informal resources and networks available to persons affected by Multidrug-Resistant Tuberculosis, how they are accessed and how they are integrated into everyday lives. METHODS: In-depth ethnographic research was conducted in Bengaluru, India. Informal interactions and observations were recorded across a range of palliative care and tuberculosis treatment providers over a month-long period. In addition, ten individuals with Multidrug-Resistant Tuberculosis were asked for in-depth interviews, and five agreed. RESULTS: Multidrug-Resistant Tuberculosis caused a dynamic chain of events that transgress through physical and psychological domains to cause human suffering. Participants utilised support from their family and friends to build a network of care that was of therapeutic benefit. Informal care networks were similar to the holistic model of care practice by specialist palliative care services and represent an underused resource with enormous potential. CONCLUSION: Patient suffering is poorly addressed in current Tuberculosis treatment programmes. A community-based palliative care approach may extend peoples' support networks, helping to alleviate suffering. Further research on existing support structures and integration of these services into Tuberculosis control programmes is required.

Current Status of Delamanid in the Management of MDR Tuberculosis.

Delamanid is a nitro-dihydro-imidazooxazole compound which was developed by a Japanese company, Otsuka Holdings inc. and has shown in-vitro and in-vivo activity against drug resistant tuberculosis. The drug exerts its anti-mycobacterial activity by inhibition of mycolic acid biosynthesis, leading to defective cell wall formation ultimately leading to bacterial death. Following the promising results in Phase 2 trials, Delamanid received approval in European Union in 2014, following which it was also approved in Japan and Korea in the same year. It was approved in India recently in August, 2017. Though relatively well tolerated, there have been concerns due to QT prolongation associated with the use of Delamanid. WHO has currently recommended use of Delamanid in combination with optimized background regimen in patients with pulmonary TB (conditional recommendation). More data from clinical trials and observational studies is awaited regarding use of Delamanid in children, HIV co-infection, pregnant women and use in combination with Bedaquiline.

Using Patient Pathway Analysis to Design Patient-centered Referral Networks for Diagnosis and Treatment of Tuberculosis: The Case of the Philippines.

Background: Tuberculosis (TB) is the 8th leading cause of death in the Philippines. A recent prevalence survey found that there were nearly 70% more cases of tuberculosis than previously estimated. Given these new data, the National TB Program (NTP), operating through a decentralized health system, identified about 58% of the estimated new drug-sensitive (DS) TB patients in 2016. However, the NTP only identified and commenced treatment for around 17% of estimated new drug-resistant patients. In order to reach the remaining 42% of drug-sensitive patients and 83% of drug-resistant patients, it is necessary to develop a better understanding of where patients seek care. Methods: National and regional patient pathway analyses (PPAs) were undertaken using existing national survey and NTP data. The PPA assessed the alignment between patient care seeking and the availability of TB diagnostic and treatment services. Results: Systemic referral networks from the community-level Barangay Health Stations (BHSs) to diagnostic facilities have enabled more efficient detection of drug-sensitive tuberculosis in the public sector. Approximately 36% of patients initiated care in the private sector, where there is limited coverage of appropriate diagnostic technologies. Important differences in the alignment between care seeking patterns and diagnostic and treatment availability were found between regions. Conclusions: The PPA identified opportunities for strengthening access to care for all forms of tuberculosis and for accelerating the time to diagnosis by aligning services to where patients initiate care. Geographic variations in care seeking may guide prioritization of some regions for intensified engagement with the private sector.

World Health Organization treatment guidelines for drug-resistant tuberculosis, 2016 update.

Antimicrobial resistance is a major global concern. Tuberculosis (TB) strains resistant to rifampicin and other TB medicines challenge patient survival and public health. The World Health Organization (WHO) has published treatment guidelines for drug-resistant TB since 1997 and last updated them in 2016 based on reviews of aggregated and individual patient data from published and unpublished studies. An international expert panel formulated recommendations following the GRADE approach. The new WHO guidelines recommend a standardised 9-12 months shorter treatment regimen as first choice in patients with multidrug- or rifampicin-resistant TB (MDR/RR-TB) strains not resistant to fluoroquinolones or second-line injectable agents; resistance to these two classes of core second-line medicines is rapidly detectable with molecular diagnostics also approved by WHO in 2016. The composition of longer regimens for patients ineligible for the shorter regimen was modified. A first-ever meta-analysis of individual paediatric patient data allowed treatment recommendations for childhood MDR/RR-TB to be made. Delamanid is now also recommended in patients aged 6-17 years. Partial lung resection is a recommended option in MDR/RR-TB care. The 2016 revision highlighted the continued shortage of high-quality evidence and implementation research, and reiterated the need for clinical trials and best-practice studies to improve MDR/RR-TB patient treatment outcomes and strengthen policy.

Tuberculosis: Is the landscape changing?

Robert Heinrich Herman Koch, a German physician and microbiologist, received Nobel Prize in 1905 for identifying the specific causative agent of tuberculosis (TB). During his time it was believed that TB was an inherited disease. However he was convinced that the disease was caused by a bacterium and was infectious, tested his postulates using guinea pigs, and found the causative agent to be slow growing mycobacterium tuberculosis. TB is the second most common cause of death from infectious diseases after HIV/AIDS. Drug-resistant TB poses serious challenge to effective management of TB worldwide. Multidrug-resistant TB accounted for about half a million new cases and over 200,000 deaths in 2013. Whole-genome sequencing (first done in 1998) technologies have provided new insight into the mechanism of drug resistance. For the first time in 50 y, new anti TB drugs have been developed. The World Health Organization (WHO) has recently revised their treatment guidelines based on 32 studies. In United States, latent TB affects between 10 and 15 million people, 10% of whom may develop active TB disease. QuantiFERON TB Gold and T-SPOT.TB test are used for diagnosis. Further research will look into the importance of newly discovered gene mutations in causing drug resistance.

Isolation unit for multidrug-resistant tuberculosis patients in a low endemic country, a step towards the World Health Organization End TB Strategy.

Tuberculosis (TB) remains a threat to public health and is the second cause of death due to a single infectious agent after HIV/AIDS. The worldwide distribution of TB is heterogeneous. The incidence is decreasing in most high-income regions, but the situation remains worrying in many parts of the world. The emergence of Mycobacterium tuberculosis strains resistant to key agents used in treatment (rifampin and isoniazid) contributes to TB transmission around the world. To achieve TB elimination, both high and low endemic countries must upscale their efforts to decrease disease transmission and improve cure rates. Management of drug-resistant TB is of particular importance. In this paper, we discuss the different models of care of multidrug-resistant TB (MDR-TB), the ethical considerations and the specific constraints present in high income countries. The management model chosen by the Belgian TB specialists in accordance with public health authorities as well as building of a specific MDR/XDR-TB isolation unit are also discussed.

Extensively drug-resistant tuberculosis in India: Current evidence on diagnosis & management.

Emergence of extensively drug-resistant tuberculosis (XDR-TB) has significantly threatened to jeopardize global efforts to control TB, especially in HIV endemic regions. XDR-TB is mainly an iatrogenically created issue, and understanding the epidemiological and risk factors associated with it is of paramount importance in curbing this menace. Emergence of this deadly phenomenon can be prevented by prompt diagnosis and effective treatment with second-line drugs in rifampicin-resistant TB (RR-TB) as well as multidrug-resistant TB (MDR-TB) patients. Optimal treatment of RR-TB, MDR-TB and XDR-TB cases alone will not suffice to reduce the global burden. The TB control programmes need to prioritize on policies focusing on the effective as well as rational use of first-line drugs in every newly diagnosed drug susceptible TB patients so as to prevent the emergence of drug resistance.