World Health Organization End Tuberculosis Research Articles

Retreatment and Anti-tuberculosis Therapy Outcomes in Brazil Between 2015 and 2022: A Nationwide Study.

Adherence to anti-tuberculosis treatment (ATT) in Brazil remains a challenge in achieving the goals set by the World Health Organization (WHO). Patients who are lost to follow-up during treatment pose a significant public health problem. This study aimed to investigate the factors associated with unfavorable ATT outcomes among those undergoing retreatment in Brazil. We conducted an observational study of patients aged ≥18 years with tuberculosis (TB) reported to the Brazilian National Notifiable Disease Information System between 2015 and 2022. Clinical and epidemiologic variables were compared between the study groups (new cases and retreatment). Regression models identified variables associated with unfavorable outcomes. Among 743 823 reported TB cases in the study period, 555 632 cases were eligible, consisting of 462 061 new cases and 93 571 undergoing retreatments (44 642 recurrent and 48 929 retreatments after loss to follow-up [RLTFU]). RLTFU (odds ratio [OR], 3.96 [95% confidence interval {CI}, 3.83-4.1]) was a significant risk factor for any type of unfavorable ATT. Furthermore, RLTFU (OR, 4.93 [95% CI, 4.76-5.11]) was the main risk factor for subsequent LTFU. For death, aside from advanced age, living with HIV (OR, 6.28 [95% CI, 6.03-6.54]) was the top risk factor. Retreatment is a substantial risk factor for unfavorable ATT outcomes, especially after LTFU. The rates of treatment success in RLTFU are distant from the WHO End TB Strategy targets throughout Brazil. These findings underscore the need for targeted interventions to improve treatment adherence and outcomes in persons who experience RLTFU.

Suppression of host gene expression is associated with latent TB infection: a possible diagnostic biomarker

The World Health Organization End TB strategy aims for a 90% reduction of tuberculosis (TB) incidence by 2035. Systematic testing and treatment of latent TB infection (LTBI) among contacts of active TB patients is recommended as one of the ways to curtail TB incidence. However, there is a shortage of tools to accurately diagnose LTBI. We assessed the appropriateness of whole blood host transcriptomic markers (TM) to diagnose LTBI among household contacts of bacteriologically confirmed index cases compared to HIV negative healthy controls (HC). QuantiFERON-TB Gold Plus Interferon gamma release assay (IGRA) and reverse-transcriptase quantitative PCR were used to determine LTBI and quantify TM expression respectively. Association between TM expression and LTBI was evaluated by logistic regression modelling. A total of 100 participants, 49 TB exposed (TBEx) household contacts and 51 HC, were enrolled. Twenty-five (51%) TBEx individuals tested positive by IGRA, and were denoted as LTBI individuals, and 37 (72.5%) HC were IGRA-negative. Expression of 11 evaluated TM was significantly suppressed among LTBI compared to HC. Out of the 11 TM, ZNF296 and KLF2 expression were strongly associated with LTBI and successfully differentiated LTBI from HC. Paradoxically, 21 (49%) TBEx participants who tested IGRA negative exhibited the same pattern of suppressed TM expression as IGRA positive (LTBI-confirmed individuals). Results suggest that suppression of gene expression underlies LTBI and may be a more sensitive diagnostic biomarker than standard-of-care IGRA.

Perspectives on development and advancement of new tuberculosis vaccines

Tuberculosis (TB) remains a leading cause of death worldwide and is estimated to have caused 1.3 million deaths worldwide in 2022. Approximately one quarter of the world's population are infected with Mycobacterium tuberculosis, of whom up to 10% will progress to developing active TB disease. Achieving the World Health Organization End TB Strategy targets of a 95% reduction in TB mortality and a 90% reduction in TB incidence worldwide by 2035 remains a daunting task. The continuing spread of multidrug-resistant TB adds another obstacle to achieving global TB control. Larger funding pledges coupled with technological advances have recently enabled the enhancement of TB vaccine development efforts. These are yielding a pipeline of over 17 products currently in different stages of clinical trials. Emerging promising phase I and II trial results and advancement to phase III trials have necessitated “vaccine preparedness” in parallel so that a smooth transition from any positive clinical trial result to phase IV evaluation and implementation into policy and practice can follow. Promotion of a human rights–based approach, which recognizes and upholds the fundamental rights of all affected by the disease, is essential to ensure universal access to quality TB vaccines, regardless of their background or personal circumstances.

Tuberculosis patients face high treatment support costs in Colombia, 2021.

To estimate the baseline to measure one of the three indicators of the World Health Organization (WHO) End TB strategy (2015-2035), measure the costs incurred by patients affected by tuberculosis (TB) during a treatment episode and estimate the proportion of households facing catastrophic costs (CC) and associated risk factors, in Colombia, 2021. A nationally representative cross-sectional survey was conducted among participants on TB treatment in Colombia, using telephone interviews due to the exceptional context of the COVID-19 pandemic. The survey collected household costs (direct [medical and non-medical out-of-pocket expenses] and indirect) over an episode of TB, loss of time, coping measures, self-reported income, and asset ownership. Total costs were expressed as a proportion of annual household income and analyzed for risk factors of CC (defined as costs above 20% annual household income). The proportion of TB-affected households incurring in costs above 20% annual household income (CC) was 51.7% (95%CI: 45.4-58.0) overall, 51.3% (95%CI: 44.9-57.7) among patients with drug-sensitive (DS) TB, and 65.0% (95%CI: 48.0-82.0) among drug-resistant (DR). The average patient cost of a TB case in Colombia was $1,218 (95%CI 1,106-1,330) including $860.9 (95%CI 776.1-945.7) for non-medical costs, $339 (95%CI 257-421) for the indirect costs, and $18.1 (95%CI 11.9-24.4) for the medical costs. The factors that influenced the probability of facing CC were income quintile, job loss, DR-TB patient, and TB type. Main cost drivers for CC were non-medical out-of-pocket expenses and income loss (indirect costs). Current social protection programs ought to be expanded to mitigate the proportion of TB-affected households facing CC in Colombia, especially those with lower income levels.

The economic burden of households affected by tuberculosis in Brazil: First national survey results, 2019-2021.

One of the three main targets of the World Health Organization (WHO) End TB Strategy (2015-2035) is that no tuberculosis (TB) patients or their households face catastrophic costs (defined as exceeding 20% of the annual household income) because of the disease. Our study seeks to determine, as a baseline, the magnitude and main drivers of the costs associated with TB disease for patients and their households and to monitor the proportion of households experiencing catastrophic costs in Brazil. A national cross-sectional cluster-based survey was conducted in Brazil in 2019-2021 following WHO methodology. TB patients of all ages and types of TB were eligible for the survey. Adult TB patients and guardians of minors (<18 years old) were interviewed once about costs, time loss, coping measures, income, household expenses, and asset ownership. Total costs, including indirect costs measured as reported household income change, were expressed as a percentage of annual household income. We used descriptive statistics to analyze the cost drivers and multivariate logistic regression to determine factors associated with catastrophic costs. We interviewed 603 patients, including 538 (89%) with drug-sensitive (DS) and 65 (11%) with drug-resistant (DR) TB. Of 603 affected households, 48.1% (95%CI: 43-53.2) experienced costs above 20% of their annual household income during their TB episode. The proportion was 44.4% and 78.5% among patients with DS- and DR-TB, respectively. On average, patients incurred costs of US$1573 (95%CI: 1361.8-1785.0) per TB episode, including pre-diagnosis and post-diagnosis expenses. Key cost drivers were post-diagnosis nutritional supplements (US$317.6, 95%CI: 232.7-402.6) followed by medical costs (US$85.5, 95%CI: 54.3-116.5) and costs of travel for clinic visits during treatment (US$79.2, 95%CI: 61.9-96.5). In multivariate analysis, predictors of catastrophic costs included positive HIV status (aOR = 3.0, 95%CI:1.1-8.6) and self-employment (aOR = 2.7, 95%CI:1.1-6.5); high education was a protective factor (aOR = 0.1, 95%CI:0.0-0.9). Although the services offered to patients with TB are free of charge in the Brazilian public health sector, the availability of free diagnosis and treatment services does not alleviate patients' financial burden related to accessing TB care. The study allowed us to identify the costs incurred by patients and suggest actions to mitigate their suffering. In addition, this study established a baseline for monitoring catastrophic costs and fostering a national policy to reduce the costs to patients for TB care in Brazil.

Diagnostic performance of host protein signatures as a triage test for active pulmonary TB.

The current four-symptom screen recommended by the World Health Organization (WHO) is widely used as screen to initiate diagnostic testing for active pulmonary tuberculosis (TB), yet the performance is poor especially when TB prevalence is low. In contrast, more sensitive molecular tests are less suitable for placement at primary care level in low-resource settings. In order to meet the WHO End TB targets, new diagnostic approaches are urgently needed to find the missing undiagnosed cases. Proteomics-derived blood host biomarkers have been explored because protein detection technologies are suitable for the point-of-care setting and could meet cost targets. This study aimed to find a biomarker signature that fulfills WHO's target product profile (TPP) for a TB screening. Twelve blood-based protein biomarkers from three sample populations (Vietnam, Peru, and South Africa) were analyzed individually and in combinations via advanced statistical methods and machine learning algorithms. The combination of I-309, SYWC and kallistatin showed the most promising results to discern active TB throughout the data sets meeting the TPP for a triage test in adults from two countries (Peru and South Africa). The top-performing individual markers identified at the global level (I-309 and SYWC) were also among the best-performing markers at country level in South Africa and Vietnam. This analysis clearly shows that a host protein biomarker assay is feasible in adults for certain geographical regions based on one or two biomarkers with a performance that meets minimal WHO TPP criteria.

Evaluation of drug-resistant tuberculosis treatment outcome in Limpopo province, South Africa.

South Africa has the second-highest tuberculosis (TB) incidence globally. Drug-resistant TB (DR-TB) treatment has less successful treatment outcomes as compared with susceptible TB, and it hinders TB control and management programmes. This study aimed to evaluate drug-resistant TB treatment outcomes and factors associated with successful treatment outcomes. The study was conducted in five districts in Limpopo province. The study design was retrospective and descriptive. Patients' demographic data, data on clinical characteristics and treatment outcomes data were extracted from the electronic drug-resistant tuberculosis register (EDRWeb) database system for the period, 2010-2018, in Limpopo province. Frequency, percentages and bivariate and multivariate logistic regression were used to analyse data using Statistical Package for Social Sciences version 27.0. The significance difference was determined at a 95% confidence interval and p 0.05. A total of 385 drug-resistant records were included in this study. The treatment success rate was 223 (57.9%). A total of 197 (51.2%) patients were cured, 26 (6.8%) completed treatment, 19 (4.9%) treatment failure, 62 (16.1%) died, 78 (20.6%) were recorded as the loss to follow-up, 1 (0.3%) moved to another country and 2 (0.5%) were transferred out. The treatment success rate was 57.9%, which is still below targets set by National Strategic Plan in South Africa and World Health Organization End TB targets.Contribution: The findings of the study reveal that to achieve successful DR-TB control programme and attain End TB targets, monitoring of treatment outcomes is crucial.

Barriers and Facilitators to Integrating Depression Treatment Within a TB Program and Primary Care in Brazil.

Tuberculosis (TB) and depression is common and is associated with poor TB outcomes. The World Health Organization End TB Strategy explicitly calls for the integration of TB and mental health services. Interpersonal Counseling (IPC) is a brief evidence-based treatment for depression that can be delivered by non-mental health specialists with expert supervision. The goal of this study was to explore potential barriers and facilitators to training non-specialist providers to deliver IPC within the TB Control Program and primary care in Itaboraí, Rio de Janeiro state. Data collection consisted of six focus groups (n = 42) with health professionals (n = 29), program coordinators (n = 7), and persons with TB (n = 6). We used open coding to analyze the data, followed by deductive coding using the Chaudoir multi-level framework for implementation outcomes. The main structural barriers identified were poverty, limited access to treatment, political instability, violence, and social stigma. Organizational barriers included an overburdened and under-resourced health system with high staff turnover. Despite high levels of stress and burnout among health professionals, several provider-level facilitators emerged including a high receptivity to, and demand for, mental health training; strong community relationships through the community health workers; and overall acceptance of IPC delivered by any type of health provider. Patients were also receptive to IPC being delivered by any type of professional. No intervention-specific barriers or facilitators were identified. Despite many challenges, integrating depression treatment into primary care in Itaboraí using IPC was perceived as acceptable, feasible, and desirable.

Drivers determining TB disease screening yield in four European screening programmes: a comparative analysis.

The WHO End-TB Strategy emphasises screening for early diagnosis of tuberculosis (TB) in high-risk groups, including migrants. We analysed key drivers of TB yield differences in four large migrant TB screening programmes to inform TB control planning and feasibility of a European approach. We pooled individual TB screening episode data from Italy, the Netherlands, Sweden, and the UK and analysed predictors and interactions for TB case yield using multivariable logistic regression models. Between 2005-2018 in 2,302,260 screening episodes among 2,107,016 migrants to four countries; the programmes identified 1,658 TB cases (yield 72.0 per 100,000; 95% confidence interval, CI68.6-75.6). In logistic regression analysis, we found associations between TB screening yield and age (>55 years odds ratio, OR2.91, CI2.24-3.78), being an asylum seeker (OR3.19, CI1.03-9.83) or on a settlement visa (OR1.78, CI1.57-2.01), close TB contact (OR12.25, 11.73-12.79), and higher TB incidence in the country of origin (CoO). We demonstrated interactions between migrant typology and age, as well as CoO. For asylum seekers, the elevated TB risk remained similar above CoO incidence thresholds of 100 per 100,000. Key determinants of TB yield included close contact, increasing age, incidence in CoO and specific migrant groups including asylum seekers and refugees. For most migrants such as UK students and workers, TB yield significantly increased with levels of incidence in CoO. The high, CoO-independent TB risk in asylum seekers above a 100 per 100,000 threshold could reflect higher transmission and reactivation risk of migration routes; with implications for selecting populations for TB screening.

Pooling sputum testing to diagnose tuberculosis using xpert MTB/RIF and xpert ultra: a cost-effectiveness analysis

BackgroundThe World Health Organization (WHO) recommends the diagnosis of tuberculosis (TB) using molecular tests, such as Xpert MTB/RIF (MTB/RIF) or Xpert Ultra (Ultra). These tests are expensive and resource-consuming, and cost-effective approaches are needed for greater coverage.MethodsWe evaluated the cost-effectiveness of pooling sputum samples for TB testing by using a fixed amount of 1,000 MTB/RIF or Ultra cartridges. We used the number of people with TB detected as the indicator for cost-effectiveness. Cost-minimization analysis was conducted from the healthcare system perspective and included the costs to the healthcare system using pooled and individual testing.ResultsThere was no significant difference in the overall performance of the pooled testing using MTB/RIF or Ultra (sensitivity, 93.9% vs. 97.6%, specificity 98% vs. 97%, p-value > 0.1 for both). The mean unit cost across all studies to test one person was 34.10 international dollars for the individual testing and 21.95 international dollars for the pooled testing, resulting in a savings of 12.15 international dollars per test performed (35.6% decrease). The mean unit cost per bacteriologically confirmed TB case was 249.64 international dollars for the individual testing and 162.44 international dollars for the pooled testing (34.9% decrease). Cost-minimization analysis indicates savings are directly associated with the proportion of samples that are positive. If the TB prevalence is ≥ 30%, pooled testing is not cost-effective.ConclusionPooled sputum testing can be a cost-effective strategy for diagnosis of TB, resulting in significant resource savings. This approach could increase testing capacity and affordability in resource-limited settings and support increased testing towards achievement of WHO End TB strategy.

Potential Repurposed Drug Candidates for Tuberculosis Treatment: Progress and Update of Drugs Identified in Over a Decade.

The devastating impact of Tuberculosis (TB) has been a menace to mankind for decades. The World Health Organization (WHO) End TB Strategy aims to reduce TB mortality up to 95% and 90% of overall TB cases worldwide, by 2035. This incessant urge will be achieved with a breakthrough in either a new TB vaccine or novel drugs with higher efficacy. However, the development of novel drugs is a laborious process involving a timeline of almost 20-30 years with huge expenditure; on the other hand, repurposing previously approved drugs is a viable technique for overcoming current bottlenecks in the identification of new anti-TB agents. The present comprehensive review discusses the progress of almost all the repurposed drugs that have been identified to the present day (∼100) and are in the development or clinical testing phase against TB. We have also emphasized the efficacy of repurposed drugs in combination with already available frontline anti-TB medications along with the scope of future investigations. This study would provide the researchers a detailed overview of nearly all identified anti-TB repurposed drugs and may assist them in selecting the lead compounds for further in vivo/clinical research.

Analysis of the current status of TB transmission in China based on an age heterogeneity model.

Tuberculosis (TB) is an infectious disease transmitted through the respiratory system. China is one of the countries with a high burden of TB. Since 2004, an average of more than 800,000 cases of active TB has been reported each year in China. Analyzing the case data from 2004 to 2018, we found significant differences in TB incidence by age group. A model of TB is put forward to explore the effect of age heterogeneity on TB transmission. The nonlinear least squares method is used to obtain the key parameters in the model, and the basic reproduction number Rv = 0.8017 is calculated and the sensitivity analysis of Rv to the parameters is given. The simulation results show that reducing the number of new infections in the elderly population and increasing the recovery rate of elderly patients with the disease could significantly reduce the transmission of TB. Furthermore, the feasibility of achieving the goals of the World Health Organization (WHO) End TB Strategy in China is assessed, and we obtained that with existing TB control measures it will take another 30 years for China to reach the WHO goal to reduce 90% of the number of new cases by the year 2049. However, in theory it is feasible to reach the WHO strategic goal of ending TB by 2035 if the group contact rate in the elderly population can be reduced, though it is difficult to reduce the contact rate.

Ending tuberculosis: the cost of missing the World Health Organization target in a low-incidence country.

BackgroundEnding tuberculosis (TB) is a global priority and targets for doing so are outlined in the World Health Organization (WHO) End TB Strategy. For low-incidence countries, eliminating TB requires high levels of wealth, low levels of income inequality and effective TB programmes and services that can meet the needs of people who have not benefited from these and are still at risk of TB. In Ireland, numerous reports have noted a need for more funding for TB prevention and control.AimThe aim of this research was to estimate the cost of not meeting the WHO End TB target of a 90% reduction in TB incidence in Ireland between 2015 and 2035.MethodsThe cost of projected TB cases between 2022 and 2035 is estimated based on trends in surveillance data for the period 2015 to 2019 and outcomes reported in the literature.ResultsBetween 2022 and 2035, it is projected that a failure to meet the WHO End TB Strategy target will result in an additional 989 cases of TB, 577.3 disability-adjusted life years and 35 deaths with TB in Ireland. The cost of this is estimated to be €70.779 million.ConclusionGiven the estimated cost, Ireland’s current prospects of eliminating TB and the tendency towards programmatic funding internationally, greater investment in TB prevention and control in Ireland is justifiable. A national elimination strategy with actions at the levels of the social determinants of health, the health system and the TB programme should be funded.

Linking nationwide health and social registry data to informthe policy for Tuberculosis contact tracing in Brazil.

ObjectivesMitigating the socioeconomic determinants of Tuberculosis (TB) and systematic screening of contacts and high-risk groups are targets of The World Health Organization (WHO) End TB Strategy by 2035. Our aim was to link socioeconomic information to TB datasets to inform policy makers in Brazil and contribute to addressing current challenges.&#x0D; ApproachFollowing a signed technical cooperation agreement with the Ministry of Health (MoH), we linked nationwide data on 1.405.682 registries of TB diagnosed between 2004 and 2019 in Brazil to 131.697.800 demographic and socioeconomic registries from the 100 Million Brazilian Cohort (2001-2018) previously linked to nationwide mortality data. We established close links with TB managers to understand the database, clean and deduplicate registries and to analyse the data. We took advantage of the data structure, to set up a cohort of household contacts of TB patients and produce estimates of TB incidence by subgroups of demographic and socioeconomic characteristics.&#x0D; ResultsThe interaction of the MoH was effective and facilitated by a robust TB Programme in the country. 567.999 (40,41%) TB cases were linked to the 100 Million Brazilian Cohort with high specificity (93.6%) and sensitivity (94.6%). Using family identifiers, we established the first TB case within a family unit (i.e., primary case) and followed their household contacts up to 15 years. We found the TB incidence among household contacts to be 427.8/100.000 person-years (95%CI 419.1-436.8). In the first year following the identification of the primary case, there was higher cumulative incidence among household contacts under 5 years of age, which was followed by a plateau of cases in this age group. Cummulative incidence in the other age groups presented a constant increase over time.&#x0D; ConclusionThe close collaboration with the MoH, the development of an effective linkage algorithm and the availability of large socioeconomic data allowed for a unique analysis of the high incidence of TB among household contacts. Findings reinforce need for constant dialogue among stakeholders to strengthen case detection by primary health care.

Impact of the COVID-19 Pandemic on the Diagnosis of Tuberculosis in Brazil: Is the WHO End TB Strategy at Risk?

Background: In 2014, the World Health Organization (WHO) launched the “post-2015 End TB strategy”, that aims to end the global tuberculosis (TB) epidemic by 2030. However, the COVID-19 pandemic has severely impacted global public health and the strict measures to control the coronavirus spread can affect the management of other diseases, such as TB. Herein, we aimed to assess the impact of the COVID-19 pandemic on the diagnosis of TB in Brazil, during 2020. Methods: We carried out an ecological and population-based study, using spatial analysis techniques. The variables used were the new cases of TB, pulmonary tuberculosis (PTB), and also baciloscopy-positive (BP) cases in Brazil between 2015 and 2020. The percentage of changes (% change) was calculated to verify if there was an increase or decrease of TB cases in 2020, along with time trend analyses given by Joinpoint regression model. Also, interrupted time series analyses were used to assess the trend of TB diagnosis before and after the onset of the COVID-19 in Brazil. Spatial distribution maps were elaborated, considering the % change of each Brazilian state. Findings: Data analyses showed a reduction in the diagnosis of TB (−8.3%) and PTB (−8.1%) in Brazil after the irruption of the COVID-19 pandemic. Likewise, 22 states depicted a reduction in TB diagnosis. An expressive reduction of BP cases (−17.1%) was also observed. Interestingly, interrupted time series analysis showed decline in TB and PTB diagnoses from March 2020. Spatial analyses revealed that all states had a progressive reduction of TB, PTB and PB cases, from March on, with the highest percentages of reduction in December (−100% to −75%). Interpretation: Taken together, our analyses demonstrated a reduction in TB diagnosis after the irruption of the COVID-19 pandemic in Brazil and its regions, signaling a serious impact on the WHO “End TB Strategy” global plan.

A systematic review and meta-analysis of the catastrophic costs incurred by tuberculosis patients

One of the strategies of the World Health Organization End Tuberculosis (TB) was to reduce the catastrophic costs incurred by TB-affected families to 0% by 2020.Catastrophic cost is defined by the total cost related to TB management exceeding 20% of the annual pre-TB household income. This study aimed to estimate the pooled proportion of TB affected households who incurred catastrophic costs. We searched PubMed, SciELO, Scopus, Embase, Google Scholar, ProQuest, SAGE, and Web of Science databases according to Preferred Reporting Items of the Systematic Reviews and Meta-Analysis (PRISMA) guidelines till November 20, 2020. Eligible studies were identified and data on catastrophic costs due to TB were extracted. We performed a meta-analysis to generate the pooled proportion of patients with TB facing catastrophic costs. From 5114 studies identified, 29 articles were included in the final analysis. The pooled proportion of patients faced catastrophic costs was (43%, 95% CI [34–51]). Meta-regression revealed that country, drug sensitivity, and Human immune-deficiency Virus (HIV) co-infection were the main predictors of such costs. Catastrophic costs incurred by drug sensitive, drug resistant, and HIV co-infection were 32%, 81%, and 81%, respectively. The catastrophic costs incurred were lower among active than passive case findings (12% vs. 30%). Half (50%) of TB-affected households faced catastrophic health expenditure at 10% cut-off point. The financial burden of patients seeking TB diagnosis and treatment continues to be a worldwide impediment. Therefore, the End TB approach should rely on socioeconomic support and cost-cutting initiatives.PROSPERO registration: CRD42020221283.

Understanding the interaction between cytomegalovirus and tuberculosis in children: The way forward.

Over 1 million children develop tuberculosis (TB) each year, with a quarter dying. Multiple factors impact the risk of a child being exposed to Mycobacterium tuberculosis (Mtb), the risk of progressing to TB disease, and the risk of dying. However, an emerging body of evidence suggests that coinfection with cytomegalovirus (CMV), a ubiquitous herpes virus, impacts the host response to Mtb, potentially influencing the probability of disease progression, type of TB disease, performance of TB diagnostics, and disease outcome. It is also likely that infection with Mtb impacts CMV pathogenesis. Our current understanding of the burden of these 2 diseases in children, their immunological interactions, and the clinical consequence of coinfection is incomplete. It is also unclear how potential interventions might affect disease progression and outcome for TB or CMV. This article reviews the epidemiological, clinical, and immunological literature on CMV and TB in children and explores how the 2 pathogens interact, while also considering the impact of HIV on this relationship. It outlines areas of research uncertainty and makes practical suggestions as to potential studies that might address these gaps. Current research is hampered by inconsistent definitions, study designs, and laboratory practices, and more consistency and collaboration between researchers would lead to greater clarity. The ambitious targets outlined in the World Health Organization End TB Strategy will only be met through a better understanding of all aspects of child TB, including the substantial impact of coinfections.

Unexpected slowdown in the decline of tuberculosis mortality rates in Brazil from 1997 to 2017: an ecological study.

Brazil is a signatory to the World Health Organization End TB Strategy and the United Nations Sustainable Development Goals. This study aims to characterize tuberculosis (TB) deaths and TB mortality rates in Brazil for the period 1997-2017. We performed an ecological study based on information for TB deaths between 1997 and 2017 extracted from the Mortality Information System of the Brazilian Ministry of Health. Data included gender, age group and geographic regions. The trends in mortality rates were estimated using Joinpoint regression analysis, which identifies years in which there is a change in slope of the time series by the Monte Carlo permutation. Between 1997 and 2017 there were 104172 recorded TB deaths in Brazil and the mortality rates were higher for men and the elderly. The age-adjusted mortality rate decreased from 4.2 per 100000 in 1997 to 3.0 per 100000 in 2003 to 2.0 per 100000 in 2017. The average percentage reduction from 1997 to 2003 was 6.2% (95% confidence interval [CI] -7.7 to -4.7) per year, while from 2003 to 2017 it was 3.0% (95% CI -3.4 to -2.5) per year, representing a slowdown in the rate of decline. The high number of deaths and the slowdown in the decline of mortality rates from TB in Brazil maintain the disease as an important public health concern and an obstacle to reaching goals set by international commitments.

Establishing targets for advanced HIV disease: A call to action.

The World Health Organization (WHO) has published a guideline for the management of individuals with advanced HIV disease (AHD) to reduce HIV-related deaths. The guideline consists of a package of recommendations including interventions to prevent, diagnose and treat common opportunistic infections, including tuberculosis (TB), cryptococcosis and severe bacterial infections, along with rapid initiation of antiretroviral treatment and enhanced adherence support. Currently no clear targets exist for these key interventions. Emerging programmatic data from Uganda, Tanzania and Nigeria suggest that an estimated 80% of eligible people continue to miss the recommended cryptococcal or TB testing, highlighting the remaining challenges to the effective implementation of WHO-recommended AHD packages of care in real-world resource-limited settings. The absence of mortality indicators for the leading causes of HIV-related deaths, because of the lack of mechanisms to ascertain cause of death, has had a negative impact on establishing interventions to reduce mortality. We suggest that setting 95-95-95 targets for CD4 testing, cryptococcal antigen and TB testing, and treatment that are aligned to the WHO AHD package of care would be a step in the right direction to achieving the greater goal of the WHO End TB strategy and the proposed new strategy to end cryptococcal meningitis deaths. However, these targets will only be achieved if there is healthcare worker training, expanded access to bedside point-of-care diagnostics for hospitalised patients and those in outpatient care who meet the criteria for AHD, and health systems strengthening to minimise delays in initiating the WHO-recommended therapies for TB and cryptococcal disease.

Implementation of revised national tuberculosis control program guidelines: Practitioner's perspective and awareness-a questionnaire based study

BackgroundStrengthening public health services, setting up directly observed therapy short course Centres, introduction of Revised National tuberculosis Control Program (RNTCP) are aimed to eradicate tuberculosis by 2025. The aim of this study was to assess physician's awareness, and perspectives about the recent RNTCP guidelines. MethodsThis was a cross-sectional, opinion deriving, study through a tested, validated, standardized questionnaire that covered the role of physician in the diagnosis or treatment of tuberculosis, and tested their awareness about various aspects of RNTCP guidelines. Descriptive statistics was used. ResultsOf the 96 participants, 61.5% were involved in diagnosis and management, 15.6% in diagnosis only, three in treatment aspect of tuberculosis, 19 (19.8%) were not involved in any activity. Awareness regarding RNTCP guidelines was high (90.6%). Forty-five (46.9%) opined that revised Indian program was different from the World Health Organization End Tuberculosis Strategy. Understanding the definitions of diagnosis (DoD) (92.7%), guideline (92.7%), implementation of revised DoD (89.6%), guidelines ((82.3%) was considered simple. Awareness regarding the implementation of revised DoD (86.5%) and guidelines (78.1%) was below expectation. Participants wereless aware (80.2%) of reporting adverse drug reactions to the deputy drug controller; 41.7% each responded that the treating physician or any of the listed persons can report. Reporting ADR to the supervising committee was not clear as >50% did not answer. Awareness about Nikshay (86.5%), procedure for procuring Nikshay ID (46.9%), Institute's Nikshay ID (53.1%) was less. ConclusionsKnowledge about RNTCP guidelines is satisfactory among participants. Extensive training, continued medical education programs are required to increase awareness.