The potential impact of preventive therapy against tuberculosis in the WHO South-East Asian Region: a modelling approach.

BACKGROUND: The prevention of tuberculosis (TB) is key for accelerating current, slow declines in TB burden. The 2018 World Health Organization (WHO) guidelines on eligibility for preventive therapy to treat latent TB infection (LTBI) include people living with human immunodeficiency virus (PLHIV), household contacts of TB patients including children, and those with clinical conditions including silicosis, dialysis, transplantation, etc. and other country-specific groups. We aimed to estimate the potential impact of full implementation of these guidelines in the WHO South-East Asian (SEA) Region, which bears the largest burden of TB and LTBI amongst the WHO regions. METHODS: We developed mathematical models of TB transmission dynamics, calibrated individually to each of the 11 countries in the region. We modelled preventive therapy in the absence of other TB interventions. As an alternative comparator, reflecting ongoing developments in TB control in the region, we also simulated improvements in the treatment cascade for active TB, including private sector engagement and intensified case-finding. Relative to both scenarios, for each country in the region, we projected TB cases and deaths averted between 2020 and 2030, by full uptake of preventive therapy, defined as comprehensive coverage amongst eligible populations as per WHO guidelines, and assuming outcomes consistent with clinical trials. We also performed sensitivity analysis to illustrate impact under less-than-optimal conditions. RESULTS: At the regional level, full uptake of preventive therapy amongst identified risk groups would reduce annual incidence rates in 2030 by 8.30% (95% CrI 6.48-10.83) relative to 2015, in the absence of any additional interventions. If implemented against a backdrop of improved TB treatment cascades, preventive therapy would achieve an incremental 6.93 percentage points (95% CrI 5.81-8.51) of reduction in annual incidence rates, compared to 2015. At the regional level, the numbers of individuals with latent TB infection that need to be treated to avert 1 TB case is 64 (95% CrI 55-74). Sensitivity analysis illustrates that results for impact are roughly proportional to 'effective coverage' (the product of actual coverage and effectiveness of the regimen). CONCLUSIONS: Full implementation of WHO guidelines is important for ending TB in the SEA Region. Although future strategies will need to be expanded to the population level, to achieve large declines in TB incidence, the uptake of current tools can offer a valuable step in this direction.

Strategies for ending tuberculosis in the South-East Asian Region: A modelling approach.

Background & objectives: To support recent political commitments to end tuberculosis (TB) in the World Health Organization South-East Asian Region (SEAR), there is a need to understand by what measures, and with what investment, these goals could be reached. These questions were addressed by using mathematical models of TB transmission by doing the analysis on a country-by-country basis in SEAR. Methods: A dynamical model of TB transmission was developed, in consultation with each of the 11 countries in the SEAR. Three intervention scenarios were examined: (i) strengthening basic TB services (including private sector engagement), (ii) accelerating TB case-finding and notification, and (iii) deployment of a prognostic biomarker test by 2025, to guide mass preventive therapy of latent TB infection. Each scenario was built on the preceding ones, in successive combination. Results: Comprehensive improvements in basic TB services by 2020, in combination with accelerated case-finding to increase TB detection by at least two-fold by 2020, could lead to a reduction in TB incidence rates in SEAR by 67.3 per cent [95% credible intervals (CrI) 65.3-69.8] and TB deaths by 80.9 per cent (95% CrI 77.9-84.7) in 2035, relative to 2015. These interventions alone would require an additional investment of at least US$ 25 billion. However, their combined effect is insufficient to reach the end TB targets of 80 per cent by 2030 and 90 per cent by 2035. Model projections show how additionally, deployment of a biomarker test by 2025 could end TB in the region by 2035. Targeting specific risk groups, such as slum dwellers, could mitigate the coverage needed in the general population, to end TB in the Region. Interpretation & conclusions: While the scale-up of currently available strategies may play an important role in averting TB cases and deaths in the Region, there will ultimately be a need for novel, mass preventive measures, to meet the end TB goals. Achieving these impacts will require a substantial escalation in funding for TB control in the Region.

Towards tuberculosis elimination: an action framework for low-incidence countries.

This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards "pre-elimination" (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions.

Ending TB in South-East Asia: flagship priority and response transformation.

Over the decades, the global tuberculosis (TB) response has evolved from sanatoria-based treatment to DOTS (Directly Observed Therapy Shortcourse) strategy and the more recent End TB Strategy. The WHO South-East Asia Region, which accounted for 45% of new TB patients and 50% of deaths globally in 2021, is pivotal to the global fight against TB. "Accelerate Efforts to End TB" by 2030 was adopted as a South-East Asia Regional Flagship Priority (RFP) in 2017. This article illustrates intensified and transformed approaches to address the disease burden following the adoption of RFP and new challenges that emerged during the COVID-19 pandemic. TB case notifications improved by 25% and treatment success rates improved by 6% between 2016 and 2019 due to interventions ranging from galvanising political commitments to empowering and engaging communities. Cumulative TB programme budget allocations in 2022 reached US$ 1.4 billion, about two and a half times the budget in 2016. An ambitious Regional Strategic Plan towards ending TB, 2021-2025, identifies priority interventions that will need investments of up to US$ 3 billion a year to fully implement them. Moving forward, countries in the Region need to leverage RFP and take up intensified, people-centred, holistic interventions for prevention, diagnosis, treatment and care of TB with commensurate investments and cross-ministerial and multi-sectoral coordination.

Global, regional, and national estimates of tuberculosis incidence and case detection among incarcerated individuals from 2000 to 2019: a systematic analysis.

BACKGROUND: People who are incarcerated are at high risk of developing tuberculosis. We aimed to estimate the annual global, regional, and national incidence of tuberculosis among incarcerated populations from 2000 to 2019. METHODS: We collected and aggregated data for tuberculosis incidence and prevalence estimates among incarcerated individuals in published and unpublished literature, annual tuberculosis notifications among incarcerated individuals at the country level, and the annual number of incarcerated individuals at the country level. We developed a joint hierarchical Bayesian meta-regression framework to simultaneously model tuberculosis incidence, notifications, and prevalence from 2000 to 2019. Using this model, we estimated trends in absolute tuberculosis incidence and notifications, the incidence and notification rates, and the case detection ratio by year, country, region, and globally. FINDINGS: In 2019, we estimated a total of 125 105 (95% credible interval [CrI] 93 736-165 318) incident tuberculosis cases among incarcerated individuals globally. The estimated incidence rate per 100 000 person-years overall was 1148 (95% CrI 860-1517) but varied greatly by WHO region, from 793 (95% CrI 430-1342) in the Eastern Mediterranean region to 2242 (1515-3216) in the African region. Global incidence per 100 000 person-years between 2000 and 2012 among incarcerated individuals decreased from 1884 (95% CrI 1394-2616) to 1205 (910-1615); however, from 2013 onwards, tuberculosis incidence per 100 000 person-years was stable, from 1183 (95% CrI 876-1596) in 2013 to 1148 (860-1517) in 2019. In 2019, the global case detection ratio was estimated to be 53% (95% CrI 42-64), the lowest over the study period. INTERPRETATION: Our estimates suggest a high tuberculosis incidence rate among incarcerated individuals globally with large gaps in tuberculosis case detection. Tuberculosis in incarcerated populations must be addressed with interventions specifically tailored to improve diagnoses and prevent transmission as a part of the broader global tuberculosis control effort. FUNDING: National Institutes of Health.

Experience on the first national anti-TB drug resistance survey (DRS) in Timor-Leste.

BACKGROUND: A national drug resistance survey (DRS) was implemented for the first time in Timor-Leste (TL) in 2019. The primary objective of the survey was to assess the prevalence of drug resistance among new and previously treated pulmonary TB patients in the country. METHODS: This nation-wide cross-sectional survey was conducted in 2019 targeting all new and previously treated sputum smear-positive pulmonary TB patients. Sputum samples were submitted to the National TB Reference Laboratory for confirmation of TB and to determine resistance to rifampicin by Xpert MTB/RIF. Culture was performed on solid media, and culture isolates of confirmed TB cases were shipped to the WHO Supranational TB Reference Laboratory in Chennai, India for whole genome sequencing (WGS). Survey summary statistics, data cross-tabulations and analysis of potential risk factors of rifampicin-resistant TB (RR-TB) were conducted using R statistical software (version 3.5.2). RESULTS: A total of 953 sputum-smear positive patients were enrolled, of which 917 were confirmed as positive for TB by either Xpert MTB/RIF or culture. An electronic web-based system was used for entry and storage of the data. Rifampicin resistance was detected among 0.6% (95% CI 0.2-1.3) of new cases and 2.7% (95% CI 0.5- 8.2) of previously treated cases. WGS was conducted for validation purposes on 65 randomly selected isolates (29% of RR-TB (2/7) and 7% of RS-TB (63/910) by Xpert MTB/RIF or pDST). The original test results agreed with the WGS validation results for 62/64 isolates (97%). CONCLUSION: The prevalence of RR-TB in Timor-Leste is relatively low compared to the estimated proportions of RR-TB in the WHO South-East Asia Region (2.5% [95% CI 1.9-3.3] among new cases and 14% [95% CI 7.7-21] among previously treated cases). The rapid sputum collection and transportation mechanism implemented in the survey demonstrates its feasibility in low resource settings and should be replicated for routinely transporting TB specimens from microscopy labs to GeneXpert sites. Establishment of in-country capacity for rapid molecular diagnostics for both first- and second-line DST is an immediate need for achieving universal drug susceptibility testing (DST) to guide appropriate patient management.

Framework for planning and monitoring active TB case finding interventions to meet the global targets in the COVID-19 era and beyond: South-East Asia perspective.

There was an estimated 20-40% decline in tuberculosis (TB) case detection in the South-East Asia Region (SEA Region) during 2020 due to COVID-19 outbreak. This is over and above a million people with TB who were missed each year, prior to the pandemic. Active case finding (ACF) for TB has been gaining considerable interest and investment in the SEA Region and will be even more essential for finding people with TB missed due to the COVID-19 pandemic. Many countries in the Region have incorporated ACF activities into national strategic plans and are conducting large scale activities with varying results. ACF can reach people with TB earlier than routine approaches, can lead to increases in the numbers of people diagnosed, and is often needed for certain key populations who face stigma, social, and economic barriers. However, ACF is not a one size fits all approach, and has higher costs than routine care. So, planning interventions in consultation with relevant stakeholders including the affected communities is critical. Furthermore, continuous monitoring during the intervention and after completion is crucial as national TB programmes review progress and decide on the effective utilization of limited resources. Planning and monitoring become more relevant in the COVID-19 era because of constraints posed by resource diversion towards pandemic control. Here, we summarize different aspects of planning and monitoring of ACF approaches to inform national TB programmes and partners based on experiences in the SEA Region, as programmes look to reach those who are missed and catch-up on progress towards ending TB.

Perspective on coronary interventions & cardiac surgeries in India.

Cardiovascular disease has become the leading cause of morbidity and mortality in India during the last 3 decades. The genetic predisposition and acquisition of traditional risk factors at a rapid rate as a result of urbanization seems to be the major cause. While efforts are being made to contain this epidemic by educating public and applying preventive measures, the ever increasing burden of patients with symptomatic and life threatening manifestations of the disease is posing a major challenge. This requires a concerted effort to develop modern facilities to treat these patients. The healthcare facilities to manage these high risk patients by contemporary methods like percutaneous coronary revascularization and surgical methods have shown a very promising trend during the last decade. The facilities of modern diagnostic methods and new proven techniques to offer symptomatic relief and improve their prognosis are available in most parts of the country. The lack of social security and health insurance for the large majority of the population, however, is a serious limitation. Unregulated availability of some of the newer devices for these techniques had become a very concerning issue. However, in the last few years serious efforts have been made to streamline these procedures. Indigenous research and scientific data acquisition in relation to the modern technology for achieving coronary revascularization has also started on a promising note.

Mitigating the impact of the COVID-19 pandemic on progress towards ending tuberculosis in the WHO South-East Asia Region.

Almost half of the deaths worldwide caused by tuberculosis in 2018 occurred in the World Health Organization (WHO) South-East Asia Region, home to around a quarter of the global population. Maintaining robust progress in this region is therefore essential if the global goal of ending the tuberculosis epidemic is to be realized. Substantial gains have been made in the region, but the threat to health worldwide posed by the coronavirus disease 2019 (COVID-19) pandemic includes not only the direct effects of the pandemic but also the potential eclipsing of the global tuberculosis emergency. The results of modelling studies present stark warnings of a reversal of years of progress and a significant resurgence in deaths from tuberculosis. The COVID-19 pandemic has had variable impacts in the WHO South-East Asia Region to date, but in the countries most affected there has been targeted diversion and repurposing of tuberculosis services, health-care workers and diagnostic equipment. The combined effects of COVID-19, containment measures and fragmentation of tuberculosis services have resulted in delays in diagnosis or non-diagnosis and disruption in treatment resulting in increased morbidity, mortality, transmission and drug resistance. Countries of the region have made attempts to ensure continuity of services and civil society and nongovernmental organizations have instituted a range of innovative mechanisms to support national programmes. However, a comprehensive approach - including scaling up successful initiatives, empowering community leadership, harnessing digital tools, and implementing easily accessible cash transfers and nutrition support - will be critical to success. As COVID-19 recedes, countries will need "catch-up plans" to deploy supplementary measures to address the increased tuberculosis burden. Urgent, targeted and agile responses have the potential to mitigate and reverse the impact of the COVID-19 pandemic on tuberculosis in South-East Asia.

Ending TB in Southeast Asia: current resources are not enough.

The Southeast Asia Region continues to battle tuberculosis (TB) as one of its most severe health and development challenges. Unless there is a substantial increase in investments for TB prevention, diagnosis, care and treatment, there will be catastrophic effects for the region. The uncontrolled TB burden impacts socioeconomic development and increase of drug resistance in the region. Based on epidemiological inputs from a mathematical model, a costing analysis estimates that the desired targets of ending TB are achievable with additional interventions, and critical thresholds require an increase in spending by almost double the current levels. The data source for financial allocation to TB programmes is the report submitted by countries to WHO, while projections are based on modelling. The model accounts for funding needs for all strategies based on published data and accounts for programme and patient costs. This paper delineates the resource needs, availability and gaps of ending TB in the region. It is estimated that close to US$2 billion per year are needed in the region for TB-related activities for a meaningful bending of the incidence curve towards ending TB.

Air travel and pulmonary embolism: "economy class syndrome".

Air travel is implicated as a predisposing factor for thromboembolism, which at times can have catastrophic consequences. We present three cases who developed deep vein thrombosis (DVT) and subsequent pulmonary thromboembolism (PTE) after transatlantic air travel.

Myocardial Bridge in association with fixed atherosclerotic lesions treated with drug-eluting stents: a follow-up report with quantitative coronary analysis.

Stenting of muscle bridge is still a controversial issue with concerns regarding high restenosis rates, plaque prolapse and stent fracture. We report a case with significant atherosclerotic disease of right coronary artery and left anterior descending artery associated with a muscle bridge, proximal to the diseased segment which became more prominent after stenting the fixed lesion. This was managed by implanting another drug eluting stent, covering the bridge. Angiographic follow-up at 9 months revealed no difference in quantitative coronary angiography parameters in the stented segment of the bridge, as compared to other stented segments.

Angiographic follow-up of genous bioengineered stent in acute myocardial infarction (GENAMI)-a pilot study.

OBJECTIVE: GENAMI, an angiographic follow-up study was undertaken to evaluate the safety and efficacy of a new generation endothelial progenitor cell (EPC) capture stent, GENOUS during primary angioplasty for ST-elevation myocardial infarction (MI). METHODS: Eleven consecutive patients with acute ST-elevation MI underwent primary percutaneous coronary intervention (PCI) using a bio-engineered GENOUS EPC stent. RESULTS: Procedural success was 100%. Ten patients who survived underwent a follow-up angiography at 8 months. There was no instance of stent thrombosis during the follow-up period up to 12 months. The quantitative angiographic (quantitative coronary analysis [QCA]) follow-up data showed a late loss at 8 months of 0.97 +/- 0.94 mm and the late loss index was 44.35 +/- 40.47% with angiographic restenosis seen in 5 of 10 patients (50%). One of these patients with provocable ischemia underwent repeat PCI. CONCLUSIONS: The QCA data of this study shows a high late loss with frequent angiographic restenosis during follow-up with this stent during primary PCI for acute STEMI. This observation, with important clinical implications, needs to be confirmed in larger studies.

Air travel and pulmonary embolism: "economy class syndrome".

Air travel is implicated as a predisposing factor for thromboembolism, which at times can have catastrophic consequences. We present 3 cases who developed deep vein thrombosis (DVT) and subsequent pulmonary thromboembolism (PTE) after transatlantic air travel. The relevant literature is discussed.

Common errors in ECG diagnosis of coronary artery disease.

A variety of clinical conditions not associated with ischemic heart disease can have ECG features mimicking those of ischemic etiology. Some of these entities are: ventricular hypertrophy, intraventricular conduction defects, pre-excitation syndrome, pericarditis, electrolyte disturbances, etc. This can lead to erroneous diagnosis and uncalled for hazardous treatment. A careful comprehensive evaluation with in depth analysis of the ECG can overcome such errors. We have reviewed some of these conditions and elaborated upon the differentiating features.

Diffuse unilateral pulmonary arteriovenous fistulae-a rare anomaly.

Diffuse pulmonary arteriovenous fistulae are rare, more so when unilateral. This article describes a 12-year-old boy with diffuse right-sided pulmonary arteriovenous fistula in whom prior percutaneous transcatheter coil occlusion has been attempted without success.The patient was subjected to ligation and transection of the right pulmonary artery and he is presently doing well.

Management of residual mucogingival defect resulting from the excision of recurrent peripheral ossifying fibroma by periodontal plastic surgical procedure.

Peripheral ossifying fibroma (POF) is a local gingival reactive lesion, thought to be originating from the superficial periodontal ligament. It is found most often in the anterior maxilla with predilection for females and high recurrence rate. Clinically, the lesion is observed in gingiva or interdental papilla and manifested either as sessile or pedunculated mass which may appear ulcerated or erythematous or exhibit no color difference from the adjacent healthy gingival tissue. The present case report describes the diagnosis, treatment of POF, and immediate management of residual functional and cosmetic mucogingival defect which originated as a sequel of excisional biopsy of recurrent POF by utilizing modification of Grupe and Warren technique (modified laterally displaced flap). Clinical healing was uneventful at 2 weeks, and excellent coverage of residual mucogingival defect without any evidence of recession and or recurrence of POF was observed at surgical site 9 months postoperatively.

Modified osteotome sinus floor elevation using combination platelet rich fibrin, bone graft materials, and immediate implant placement in the posterior maxilla.

The osteotome technique is more predictable with simultaneous implant placement when there is <5-7 mm of preexisting alveolar bone height beneath sinus. Proper combination of platelet rich fibrin, mineralized freeze-dried human bone allograft, and autogenous bone has been recommended for this situation. The purpose of this article was to describe the proper method and materials which can grow >10 mm bone with osteotome technique and grafting materials where the edentulous posterior maxilla radio-graphically showed less bone between the alveolar crest and sinus floor.