Tuberculosis Mortality Research Articles

RETROSPECTIVE ANALYSIS OF THE MAIN EPIDEMIOLOGICAL INDICATORS OF TUBERCULOSIS IN IVANO-FRANKIVSK REGION DURING 2011-2021

The diagnosis and treatment of tuberculosis have changed over the past few years. Tuberculosis remains the leading infectious cause of death worldwide, while drug-resistant tuberculosis poses a significant threat to the population. The epidemiological situation on tuberculosis in Ukraine has experienced stabilization of some indicators in recent decades. It remains, however, tense and predictably unfavorable as the indicators are continuously exceeding the epidemic threshold.
 The aim of the research: to analyze the epidemiological situation on tuberculosis in Ivano-Frankivsk region during 2011-2021.
 Materials and Methods. When writing this article, official sources, including the assessment of the indicators in Ukraine from the analytical and statistical reports of the Public Health Center of the Ministry of Health of Ukraine were analyzed and studied. We performed a retrospective cohort analysis. Data regarding the region were obtained from the annual reports of the Ivano-Frankivsk Regional Phthisiopulmonological Center of Ivano-Frankivsk Regional Council.
 Results. Despite the reduction in all key epidemiological indicators, the situation on tuberculosis in Ivano-Frankivsk region remains tense. During 2011-2021, the incidence of pulmonary tuberculosis (new cases + recurrent cases) gradually reduced by 59%. Tuberculosis mortality rate reduced from 10.9 cases per 100,000 population in 2011 to 3.3 cases per 100,000 population in 2021. We share the leading Ukrainian scientists’ opinion that the indicators of TB incidence exceed the epidemic threshold despite the reduced number of new cases. Considering the global Covid-19 pandemic and the martial law in Ukraine, one should not expect positive epidemiological changes in the next few years [3, 12, 13]. The identification of destructive TB forms, indicating late diagnosis and more advanced disease stage, helps us to understand this situation. From 2016 to 2021, the incidence of destructive TB forms increased from 34.3% to 56.0% of all pulmonary TB cases, while the proportion of cavity formation was almost the same (24-27%) during 2011-2015.
 During 2011-2021, the incidence of tuberculosis among the rural population ranged from 2% to 20%, being higher as compared to urban residents. During 2011-2014, the incidence of tuberculosis and HIV/AIDS co-infection increased from 2.2 to 4.1 cases per 100,000 population, reducing to 1.0 case per 100,000 population by 2021. The incidence of extrapulmonary tuberculosis reduced from 5.4 to 2.7 cases per 100,000 population, possibly due to inadequate diagnosis, reforms, and the coronavirus infection. During 2014-2021, the incidence rate of tuberculosis among all the healthcare workers in Ukraine reduced from 6.7 to 1.47 cases per 10,000 healthcare workers. However, during 2014-2018, the indicators ranged from 6.7 to 5.6 cases per 10,000 healthcare workers. During 2013-2020, the incidence rate of newly diagnosed multidrug-resistant tuberculosis, including extensively drug-resistant tuberculosis, reduced by 177 cases, or from 260 to 49 patients.
 Conclusions. Over the past 10 years, there has been a slight reduction in the incidence of all active tuberculosis forms. However, they remain above the epidemic threshold, i.e., the tuberculosis epidemic has stabilized. Assessing the situation in our country, no positive changes in the tuberculosis epidemic in the coming years should be expected. The awareness of TB knowledge among all the population segments and control of TB situation during the period of healthcare reforms in Ukraine, according to which the anti-tuberculosis service is being reorganized, restructured, and reformed, are advisable.

Associations of hyponatremia and SIADH with increased mortality, young age and infection parameters in patients with tuberculosis.

Background and objectiveHyponatremia and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) are associated with and can be caused by tuberculosis (TB) through meningitis by locally invading the hypothalamus, adrenal, or pituitary glands or possibly through ectopic ADH production. This study assessed the association of TB mortality with hyponatremia and SIADH in a large cohort of a university hospital in Austria.MethodsThis retrospective study enrolled patients with hyponatremia and patients diagnosed with TB from 01/2001-11/2019 to assess the prevalence of TB in hyponatremia and TB morbidity and mortality in patients with and without hyponatremia. Sex, age, microbiological results, laboratory tests and comorbidities were analysed and used to calculate survival rates.ResultsOf 107.532 patients with hyponatremia (0.07%) and 186 patients with TB (43%), 80 patients were diagnosed with both—hyponatremia and TB. Only three TB patients had SIADH, precluding further SIADH analysis. In hyponatremia, young age and high CRP levels showed significant associations with TB diagnosis (p<0.0001). Survival rates of patients diagnosed with TB with moderate to profound hyponatremia were significantly lower than those without hyponatremia (p = 0.002).ConclusionIn this study of a large cohort from a tertiary care hospital in a non-endemic area of TB, 0.07% of patients presenting with hyponatremia, but especially younger patients and patients with high CRP values, were diagnosed with TB. Crucially, patients with moderate to profound hyponatremia had a significantly higher mortality rate and thus required increased medical care.

Tuberculosis in Adults and Children in the Northwestern Federal District: Changes in Epidemiological Rates and Criteria for Their Assessment

The epidemic situation is monitored by numerous rates that may not reflect it objectively which will subsequently lead to higher incidence rates and severe forms of tuberculosis in both adults and children in the regions with the most unfavorable situation.The objective: to evaluate epidemiological rates for tuberculosis in the Northwestern Federal District to identify the most significant, and assess the epidemic situation in the region using these most significant rates.Subjects and Methods. We analyzed the main epidemiological rates of pediatric tuberculosis according to federal statistics (Forms 8 and 33) in 11 districts of the Northwestern District in 2019-2021. Annual figures were obtained from open demographic data of the state statistics (https://www.fedstat.ru). Statistical analysis was pe`rformed using the free software R (v.3.5.1) and the commercial Statistical Package for the Social Sciences (SPSS Statistics for Windows, Version 24.0, IBM Corp., 2016). Hierarchical cluster analysis and k-means clustering were used with the selection of the lowest and highest values of rates. A formula is proposed for calculating the coefficient of full coverage with preventive screening (COP) for tuberculosis of the population which allows adjusting the analyzed epidemic rates taking into account the maximum coverage of the population with preventive screening and determining the accuracy of previous analysis.Results. According to the data obtained, in 2017 and 2018, Vologda Oblast and Nenets Autonomous Okrug were epidemically favorable regions, while in 2020 and 2021 Kaliningrad, Leningrad and Novgorod Oblasts were regarded as favorable regions that were steadily improving their performance. Regions with unfavorable tuberculosis situation include Pskov Oblast, St. Petersburg and the Komi Republic. At the same time, the first two regions occupy this position stably from 2017 to 2021. The use of the coefficient of low coverage with screening for tuberculosis made it possible to determine that Murmansk Oblast, St. Petersburg, Leningrad and Pskov Oblasts in 2020 and 2021 are prognostically unfavorable regions despite a decline in official tuberculosis rates. The data obtained correlate with a high percentage of positive tests with the tuberculosis recombinant tuberculosis allergen (TRA) in children in the regions mentioned above.Conclusions. The analysis of the data clearly demonstrates the possibility of determining the epidemically most favorable or unfavorable regions using four rates: coverage with preventive screening, incidence in the adult population, incidence in children aged 0 to 17 years, and tuberculosis mortality. Cluster analysis using these rates, calculation of rates using the developed coefficient of low coverage with screening for tuberculosis, and analysis of positive results of TRA test in children allows identifying the most epidemically unfavorable regions, despite the decrease in some rates that can be regarded as favorable.

Extrapulmonary tuberculosis mortality according to clinical and point of care ultrasound features in Mozambique

In resource-limited settings, point-of-care ultrasound (POCUS) has great potential to support the timely diagnosis of extrapulmonary tuberculosis (EPTB). We aim to determine the in-hospital mortality due to EPTB according to clinical and POCUS features and risk factors in newly diagnosed patients hospitalized for EPTB in Chókwè district, Mozambique. We analyzed routinely collected data from paper medical files and electronic POCUS records of EPTB in infected patients aged 15 years or older and admitted to Carmelo Hospital of Chókwè from 2016 to 2020. Kaplan–Meier survival curves and adjusted Cox regression analyses were used to model predictors of mortality and time to death. The 390 included in-patients with EPTB and POCUS data contributed a total of 6240 in-hospital person-days of observation. The overall mortality rate was 2.16 per 100 person-days. Adjusted Cox regression showed a higher risk of death in those with abdominal tenderness (adjusted hazard ratio [aHR] 1.61, 95% confidence interval [CI] 1.00–2.82, p = 0.050), antiretroviral treatment (ART) for more than 90 days (aHR 4.03, 95% CI 1.50–10.78, p = 0.006), and mixed patterns on kidney POCUS (aHR 2.91, 95% CI 1.38–6.10, p = 0.005). An optimal immunovirological response to ART was a protective factor against death [aHR] 0.12, 95% CI 0.04–0.35, p < 0.001). Variables associated with an increased risk of death were male gender, abdominal pain, ART for more than three months (with immunovirological failure or non-response to ART) and having a mixed pattern of kidney POCUS characteristics. Early detection of these risk factors may have a direct impact on reducing TB mortality, and the POCUS approach as a complementary diagnostic method for EPTB provides a simple, feasible and affordable intervention in resource-limited settings like Mozambique.

Tuberculosis mortality: quantifying agreement in clinical cause of death assessments

ObjectivesMortality is a key statistic for public health globally, and mortality reduction is a key target of ‘End TB’ strategy. However, cause of death in relation to tuberculosis (TB) may be controversial, and we aimed to evaluate classification in Australia. MethodsWe surveyed Australian clinicians and public health officers, presenting a variety of scenarios. Respondents were asked to classify each scenario with regards to whether TB was considered causative, contributory or not related to death. ResultsFifty‐nine individuals completed the survey. Respondents were experienced TB clinicians and public health officers (median 14 years of TB care experience), with a majority having recently been involved in death certification/classification. In most scenarios, there was substantial variation, particularly where death was related to TB medications, or if an alternative contributing process was recognised, such as cardiovascular complications. Variation in classification was not evidently associated with classification experience. ConclusionWe found significant variation in cause of death classification among experienced TB clinicians and public health officers, using representative TB death scenarios. Implications for public healthConsensus and transparency with regards to classification would assist in more uniform cause of death classification across jurisdictions and allow for better tracking of this critical performance measure.

Public health departments and the mortality transition in Latin America: Evidence from Puerto Rico

This paper examines the role of public health in reducing mortality prior to modern medicine by studying Puerto Rico in the early 20th century. From 1930 to 1960, Puerto Rico experienced one of the fastest increases in life expectancy in history and completed the first mortality transition outside of Europe and Western offshoots. Using municipal-level data in an event study framework, I show that public health units (county health departments) caused around half of the reduction in infant and tuberculosis mortality from 1923 to 1945, without significantly increasing public expenditures. Public health units also reduced maternal mortality and stillbirths. I present descriptive evidence that more assistant midwives per capita correspond to larger declines in maternal mortality, suggesting the importance of the training of midwives by health units. This investigation provides a window into Latin America more broadly, since most countries in Latin America subsequently adopted public health units.

Tuberculosis in an Aging World.

Tuberculosis (TB) is one of the leading causes of death due to its being an infectious disease, caused by the airborne pathogen Mycobacterium tuberculosis (M.tb). Approximately one-fourth of the world’s population is infected with latent M.tb, and TB is considered a global threat killing over 4000 people every day. The risk of TB susceptibility and mortality is significantly increased in individuals aged 65 and older, confirming that the elderly represent one of the largest reservoirs for M.tb infection. The elderly population faces many challenges that increase their risk of developing respiratory diseases, including TB. The challenges the elderly face in this regard include the following: decreased lung function, immuno-senescence, inflammaging, adverse drug effects, low tolerance to anti-TB drugs, lack of suitable diagnoses/interventions, and age-associated comorbidities. In order to find new therapeutic strategies to maintain lung homeostasis and resistance to respiratory infections as we age, it is necessary to understand the molecular and cellular mechanisms behind natural lung aging. This review focuses primarily on why the elderly are more susceptible to TB disease and death, with a focus on pulmonary function and comorbidities.

Time trends in tuberculosis mortality across the BRICS: an age-period-cohort analysis for the GBD 2019.

SummaryBackgroundTuberculosis is the leading cause of death from a single infectious agent among the HIV-negative population and ranks first among the HIV-positive population. However, few studies have assessed tuberculosis trends in Brazil, Russia, India, China and South Africa (BRICS) or with an emphasis on HIV status. This study assesses the time trends of tuberculosis mortality across the BRICS with an emphasis on HIV status from 1990 to 2019.MethodsWe obtained tuberculosis data from the Global Burden of Disease 2019 study (GBD 2019). We calculated the relative proportion of tuberculosis to all communicable, maternal, neonatal, and nutritional diseases by HIV status across the BRICS. We used age-period-cohort modelling to estimate cohort and period effects in tuberculosis from 1990 to 2019, and calculated net drift (overall annual percentage change), local drift (annual percentage change in each age group), longitudinal age curves (expected longitudinal age-specific rate), and period (cohort) relative risks.FindingsThere were 549,522 tuberculosis deaths across the BRICS in 2019, accounting for 39.3% of global deaths. Among HIV-negative populations, the age-standardised mortality rate (ASMR) of tuberculosis in BRICS remained far higher than that of high-income Asia Pacific countries, especially in India (36.1 per 100 000 in 2019, 95% UI [30.7, 42.6]) and South Africa (40.1 per 100 000 in 2019, 95% UI [36.8, 43.7]). China had the fastest ASMR reduction across the BRICS, while India maintained the largest tuberculosis death numbers with an annual decrease much slower than China's (-4.1 vs -8.0%). Among HIV-positive populations, the ASMR in BRICS surged from 0.24 per 100 000 in 1990 to 5.63 per 100 000 in 2005, and then dropped quickly to 1.70 per 100 000 in 2019. Brazil was the first country to reverse the upward trend of HIV/AIDS-tuberculosis (HIV-TB) mortality in 1995, and achieved the most significant reduction (-3.32% per year). The HIV-TB mortality in South Africa has realised much progress since 2006, but still has the heaviest HIV-TB burden across the BRICS (ASMR: 70.0 per 100 000 in 2019). We also found unfavourable trends among HIV-negative middle-aged (35-55) adults of India, men over 50 in the HIV-negative population and whole HIV-positive population of South Africa, and women aged 45-55 years of Russia. China had little progress in its HIV-positive population with worsening period risks from 2010 to 2019, and higher risks in the younger cohorts born after 1980.InterpretationBRICS’ actions on controlling tuberculosis achieved positive results, but the overall improvements were less than those in high-income Asia Pacific countries. BRICS and other high-burden countries should strengthen specified public health approaches and policies targeted at different priority groups in each country.FundingNational Natural Science Foundation of China (82073573; 72074009), Peking University Global Health and Infectious Diseases Group.

Failing upwards: Genetics-based strategies to improve antibiotic discovery and efficacy in Mycobacterium tuberculosis.

Therapeutic advances in the 20th century significantly reduced tuberculosis (TB) mortality. Nonetheless, TB still poses a massive global health challenge with significant annual morbidity and mortality that has been amplified during the COVID-19 pandemic. Unlike most common bacterial infectious diseases, successful TB treatment requires months-long regimens, which complicates the ability to treat all cases quickly and effectively. Improving TB chemotherapy by reducing treatment duration and optimizing combinations of drugs is an important step to reducing relapse. In this review, we outline the limitations of current multidrug regimens against TB and have reviewed the genetic tools available to improve the identification of drug targets. The rational design of regimens that sterilize diverse phenotypic subpopulations will maximize bacterial killing while minimizing both treatment duration and infection relapse. Importantly, the TB field currently has all the necessary genetic and analytical tools to screen for and prioritize drug targets in vitro based on the vulnerability of essential and non-essential genes in the Mtb genome and to translate these findings in in vivo models. Combining genetic methods with chemical screens offers a formidable strategy to redefine the preclinical design of TB therapy by identifying powerful new targets altogether, as well as targets that lend new efficacy to existing drugs.

Review on risk factors associated with tuberculosis death

Tuberculosis is a major public health problem threatening human health and life. Although the level of diagnosis and treatment of tuberculosis has greatly improved in recent years, it is still one of the major infectious diseases causing human death. Tuberculosis has the characteristics of both chronic and infectious diseases, and is affected by many factors. Identification of the risk factors associated with tuberculosis death has certain guiding value for the prevention and control of tuberculosis. This articled reviewed recent studies on risk factors associated with tuberculosis death both in China and abroad. Male, old age, smoking, drinking, low socioeconomic level, malnutrition, drug resistance, AIDS and diabetes mellitus were found to increase the risk of tuberculosis mortality. It is expected that these findings could provide useful information to clinicians for taking necessary interventions to reduce tuberculosis mortality.

Prevalence of Tuberculosis Among High Altitude Residents of Nepal

Introduction: Tuberculosis is a global health concern, and its prevalence can vary widely from one region to another. Factors such as altitude, climate, population density, and healthcare infrastructure can all influence the dynamics of Tuberculosis in a particular area. This study aimed to provide insights into whether altitude played a role in the occurrence of tuberculosis and its different forms in the specific region of Jumla the western rural district of Nepal. &#x0D; Methods: Jumla is a high-altitude mountainous region ranging from 915m- 4679 m with a population of 119,337 (2021) having 8 municipalities. Data were collected from all the municipalities over a period starting from July 15th2021-July 14th2022 and were compared with prior years in number and diagnosis with national data of Nepal. &#x0D; Results: A total of 84 cases were recorded of which 52.4% (n=44) were females. The group affected most was between the ages 16-30 years (34.5%) and 61-75yr (22.6%). The cases detected by the sputum Xpert MTB/RIF testing were 54.7%, with positive sputum Acid-fast bacilli being 27.4%. Most of the patients were diagnosed to have pulmonary bacteriologically confirmed (PBC) tuberculosis 52.4%, PCD (Pulmonary clinically diagnosed) 16.7%, Extra-pulmonary 28.6% with one case of each multi-drug resistant tuberculosis (MDR-TB), and Pre-XDR (Extensive drug resistant) TB. Among them, 12% of people had a history of TB undergone ATT (anti-tuberculosis drugs) in the past with 6% having a close contact history. &#x0D; Conclusions: Tuberculosis infection, disease, and mortality seem to be less common at high than low altitudes. As in Karnali Province, Humla with the second being Jumla has the lowest number of TB patients than other parts of Nepal, affecting younger people.

PULMONARY TUBERCULOSIS MORTALITY AND ITS RISK FACTORS AMONG PATIENTS WITH TYPE 2 DIABETES AND PULMONARY TUBERCULOSIS IN FOUR COMMUNITY HOSPITALS, CENTRAL THAILAND

Background: Tuberculosis (TB), a communicable disease, is currently a significant health problem in Thailand. Type 2 diabetes (T2D) is an indicator of poor TB outcomes; however, data according to specific antihyperglycemic use and tuberculosis outcomes in community hospital settings in Thailand remain limited. We aimed to determine TB mortality as well as explore the demographic and clinical risk factors among patients with pulmonary TB and underlying T2D.&#x0D; Methods: A retrospective cohort study was conducted between January 1, 2013, and December 31, 2020, to determine tuberculosis mortality and its risk factors among patients with T2D and pulmonary TB visiting three community hospitals, in central Thailand. T2D and pulmonary TB were determined according to the International Classification of Diseases, Tenth Revision codes presented in medical records. TB mortality data were reviewed and retrieved from the tuberculosis treatment cards. Patients were classified as “dead” when they died before completing treatment regardless of the causes. Multivariable cox proportional regression analysis was performed to obtain the adjusted hazard ratios (AHR) and 95% confidence interval (CI) of factors related to TB mortality.&#x0D; Results: A total of 133 patients with T2D and pulmonary TB were enrolled in the present study; 74 (55.6%) participants were males. At baseline, the average age of participants was 57.29+12.51 years. During the study period, the TB mortality rate was 15.74 (95% CI 8.13-27.50) deaths per 100 person-years. The independent risk factors for TB mortality included age ≥70 years (AHR 5.45, 95% CI; 1.36-21.84), use of insulin (AHR 4.62, 95% CI; 1.11-19.21), and positive sputum test result at 1st follow-up (AHR 16.10, 95% CI; 2.10-123.40).&#x0D; Conclusion: TB mortality among patients with T2D should be emphasized. Insulin use may be a proxy indicator for poor glycemic control associated with mortality. Additionally, elderly patients should be closely observed for successful treatment as well as monitoring for any adverse events.

Lung Effects of Household Air Pollution

Biomass fuel smoke, secondhand smoke, and oxides of nitrogen are common causes of household air pollution (HAP). Almost 2.4 billion people worldwide use solid fuels for cooking and heating, mostly in low- and middle-income countries. Wood combustion for household heating is also common in many areas of high-income countries, and minorities are particularly vulnerable. HAP in low- and middle-income countries is associated with asthma, acute respiratory tract infections in adults and children, chronic obstructive pulmonary disease, lung cancer, tuberculosis, and respiratory mortality. Although wood smoke exposure levels in high-income countries are typically lower than in lower-income countries, it is similarly associated with accelerated lung function decline, higher prevalence of airflow obstruction and chronic bronchitis, and higher all-cause and respiratory cause-specific mortality. Household air cleaners with high-efficiency particle filters have mixed effects on asthma and chronic obstructive pulmonary disease outcomes. Biomass fuel interventions in low-income countries include adding chimneys to cookstoves, improving biomass fuel combustion stoves, and switching fuel to liquid petroleum gas. Still, the impact on health outcomes is inconsistent. In high-income countries, strategies for reducing biomass fuel-related HAP are centered on community-level woodstove changeout programs, although the results are again inconsistent. In addition, initiatives to encourage home smoking bans have mixed success in households with children. Environmental solutions to reduce HAP have varying success in reducing pollutants and health problems. Improved understanding of indoor air quality factors and actions that prevent degradation or improve pollutedindoor air may lead to enhanced environmental health policies, but health outcomes must be rigorously examined.

Linkage to care and treatment outcomes for patients diagnosed with drug-susceptible tuberculosis using Xpert MTB/RIF assay in Thaba-Tseka district in Lesotho

To evaluate linkage to care and treatment outcomes of patients with tuberculosis (TB) confirmed by Xpert MTB/RIF assay in Thaba-Tseka district, Lesotho. This was a retrospective cohort study of adult patients diagnosed with drug-susceptible TB using the Xpert MTB/RIF assay at two laboratories in Thaba-Tseka district from January 2016 to December 2020. Six hundred and fifty-five eligible participants were identified for inclusion in this study. Their median age was 40 [interquartile range (IQR) 32-54] years, and 468 (71.45%) were male. Evidence of linkage to care was found for 459 (70.08%) participants, but there was no documentation on treatment initiation for 196 (29.92%) participants. The median time to treatment initiation was 0 days (same-day initiation) (IQR 0-4) and the treatment success rate was 86%. Treatment success was associated with negative sputum smear results after 2, 5 and 6 months (χ2, P<0.001). The overall mortality rate was 10%, with no trend of mortality reduction. There is a need to address the issue of linkage to care of patients diagnosed with TB in Thaba-Tseka district. Efforts should be made to reduce TB mortality in line with the World Health Organization's 'End TB strategy' target.

Two decades of tuberculosis surveillance reveal disease spread, high levels of exposure and mortality and marked variation in disease progression in wild meerkats.

Infections with tuberculosis (TB)-causing agents of the Mycobacterium tuberculosis complex threaten human, livestock and wildlife health globally due to the high capacity to cross trans-species boundaries. Tuberculosis is a cryptic disease characterized by prolonged, sometimes lifelong subclinical infections, complicating disease monitoring. Consequently, our understanding of infection risk, disease progression, and mortality across species affected by TB remains limited. The TB agent Mycobacterium suricattae was first recorded in the late 1990s in a wild population of meerkats inhabiting the Kalahari in South Africa and has since spread considerably, becoming a common cause of meerkat mortality. This offers an opportunity to document the epidemiology of naturally spreading TB in a wild population. Here, we synthesize more than 25 years' worth of TB reporting and social interaction data across 3420 individuals to track disease spread, and quantify rates of TB social exposure, progression, and mortality. We found that most meerkats had been exposed to the pathogen within eight years of first detection in the study area, with exposure reaching up to 95% of the population. Approximately one quarter of exposed individuals progressed to clinical TB stages, followed by physical deterioration and death within a few months. Since emergence, 11.6% of deaths were attributed to TB, although the true toll of TB-related mortality is likely higher. Lastly, we observed marked variation in disease progression among individuals, suggesting inter-individual differences in both TB susceptibility and resistance. Our results highlight that TB prevalence and mortality could be higher than previously reported, particularly in species or populations with complex social group dynamics. Long-term studies, such as the present one, allow us to assess temporal variation in disease prevalence and progression and quantify exposure, which is rarely measured in wildlife. Long-term studies are highly valuable tools to explore disease emergence and ecology and study host-pathogen co-evolutionary dynamics in general, and its impact on social mammals.

Tuberculosis and diabetes: increased hospitalisations and mortality associated with renal impairment.

Diabetes mellitus (DM) triples a person's risk of active tuberculosis (TB) and is associated with increased mortality. It is unclear whether diabetes status and/or the associated renal dysfunction is associated with poor TB outcomes in New Zealand, which has high diabetes screening. To characterise the population of TB-DM and TB-alone to assess the effect of diabetes status and renal function on hospitalisation and mortality. Clinical records from all adult patients diagnosed with TB in Auckland over a 6-year period (2010-2015) were reviewed. Baseline demographics, clinical presentation and microbiological data were assessed to compare the rates of hospitalisation and mortality between those with TB-DM and TB-alone. Statistical significance was defined as P < 0.05. A total of 701 patients was identified with TB; 120 (17%) had an unknown diabetes status and were excluded, and 135 had co-existing diabetes. The TB-DM and TB-alone groups had similar distribution of TB site and proportions of Mycobacterium tuberculosis culture positivity. Univariate analysis showed TB-DM patients had statistically significantly higher proportions of acute hospitalisation and mortality. Multivariate logistic regression showed only a reduced estimated glomerular filtration rate (eGFR) accounted for the higher rates of hospitalisation, with the odds of hospitalisation increasing by 2% for every unit decrease in eGFR. The odds of mortality increased by 6% for every year increase in age, and the odds of mortality increased by 3% for every unit reduction in eGFR. Diabetes is associated with higher TB hospitalisation and mortality; however, this is likely mediated by increased age and chronic kidney disease.

Epidemiology of Pediatric Tuberculosis and Factors Associated with Unsuccessful Treatment Outcomes in the Centre Region of Cameroon: A Three-Year Retrospective Cohort Study.

Background In Cameroon, there are limited data on treatment outcomes of pediatric tuberculosis (TB). We sought to identify the factors associated with unsuccessful treatment outcomes and the risk factors for mortality among children receiving TB treatment in the Centre Region of Cameroon. Methods This was a multicentre facility-based retrospective cohort study using routinely collected programmatic data. All children <15 years old treated for TB between 2018 and 2020 in 21 health facilities were included. We assessed risk factors for experiencing an unsuccessful treatment outcome and mortality through multivariable logistic regression analysis. Results Of the 610 children with TB, 307 (50.3%) were females and the median age was 6 years (IQR = 2–12). One hundred and fifty-three (25.1%) of the children were TB/HIV co-infected patients. TB treatment success (cases categorized as cured and completed treatment) was observed in 488 (80.0%) of the patients. Unsuccessful treatment outcomes were experienced by 122 (20.0%) children. Of these, 73 (12.0%) died, 4 (0.6%) had treatment failure, 25 (4.1%) were lost to follow-up, and the outcomes of 20 (3.3%) children were not evaluated. In multivariable analysis, HIV-positive status (adjusted odds ratio [AOR] = 2.43; 95% CI, 1.55–3.80, p < 0.001) and clinical method of TB diagnosis (AOR = 2.46; 95% CI, 1.55–3.91, p < 0.001] were associated with unsuccessful treatment outcomes. HIV-positive status (AOR = 4.23; 95% CI, 2.44–7.33, p < 0.001) and clinical method of TB diagnosis (AOR = 2.22; 95% CI, 1.25–3.91, p=0.006) were the risk factors for mortality among children on TB treatment. Conclusion The study found that HIV-TB co-infected children and those clinically diagnosed with TB were significantly more likely to have had unsuccessful TB treatment outcomes and mortality. Our findings underscore the need for healthcare workers to closely monitor and support HIV-TB co-infected children on TB treatment. TB/HIV collaborative activities should be strengthened by implementing TB preventive interventions among HIV-infected children.

Tuberculosis and Cardiovascular Complications: An Overview.

Tuberculosis (TB) is a dominant cause of mortality from a single infectious disease agent. It is a global health issue that has been tagged as a public health emergency for decades. The disease process, which is caused by Mycobacterium tuberculosis (MTB), affects the respiratory system as well as many other organ systems in the body, such as the lymphatic system, central nervous system (CNS), gastrointestinal system, and cardiovascular system (CVS). Generally, cardiovascular diseases are the leading cause of death worldwide, with most of the mortality in low and middle-income countries. Also, the high mortality rate of TB is skewed to these regions, making the mortality of TB with CVS involvement exceptionally high.The multisystemic involvement of TB impacts the cardiovascular system in various forms. While pericarditis caused by TB is quite common, other complications like myocarditis, coronary artery disease, and aortitis are rarer, necessitating a high index of suspicion and holistic management.This article reviews the pathophysiology of cardiovascular complications in TB, highlighting mechanisms of occurrence, common complications, management protocols, and prognostic factors. Our review highlights some of the gaps in understanding cardiovascular complications in TB, necessitating further research to investigate causal mechanisms and treatment.

The Epidemiological Tuberculosis Situation in the Russian Penitentiary System: Main Trends and Challenges

The article describes the current tuberculosis epidemiological situation in institutions of the penitentiary system including the combination of tuberculosis and HIV infection. The epidemic consequences of increased coverage of people living with HIV infection (PLHIV) with antiretroviral therapy (ART) were analyzed. By 2020, tuberculosis incidence dropped to 621 per 100,000. Tuberculosis mortality dropped to 6.8 per 100,000. The incidence of tuberculosis among PLHIV decreased from 3,490.6 per 100,000 population in 2014 to 2,014.2 per 100,000 population in 2020, while coverage of PLHIV with ART increased from 21.7 to 89.6%. The proportion of TB patients among PLHIV decreased from 10.4% in 2014 to 7.2% in 2020. The proportion of PLHIV among newly diagnosed TB patients remained high (34.4% in 2020). The prevalence of multiple drug resistant tuberculosis decreased to 557.6 per 100,000. Thus, in 2020, the epidemiological tuberculosis situation in the Russian penitentiary institutions continued to improve. The strategy to increase coverage of PLHIV with ART proved to be effective for prevention of tuberculosis in penitentiary settings. Multiple drug resistant tuberculosis presents a serious problem which forms the grounds for introduction of modern treatment protocols with innovative drugs to the Russian penitentiary institutions.

Infant BCG vaccination and risk of pulmonary and extrapulmonary tuberculosis throughout the life course: a systematic review and individual participant data meta-analysis

BCG vaccines are given to more than 100 million children every year, but there is considerable debate regarding the effectiveness of BCG vaccination in preventing tuberculosis and death, particularly among older children and adults. We therefore aimed to investigate the age-specific impact of infant BCG vaccination on tuberculosis (pulmonary and extrapulmonary) development and mortality. In this systematic review and individual participant data meta-analysis, we searched MEDLINE, Web of Science, BIOSIS, and Embase without language restrictions for case-contact cohort studies of tuberculosis contacts published between Jan 1, 1998, and April 7, 2018. Search terms included "mycobacterium tuberculosis", "TB", "tuberculosis", and "contact". We excluded cohort studies that did not provide information on BCG vaccination or were done in countries that did not recommend BCG vaccination at birth. Individual-level participant data for a prespecified list of variables, including the characteristics of the exposed participant (contact), the index case, and the environment, were requested from authors of all eligible studies. Our primary outcome was a composite of prevalent (diagnosed at or within 90 days of baseline) and incident (diagnosed more than 90 days after baseline) tuberculosis in contacts exposed to tuberculosis. Secondary outcomes were pulmonary tuberculosis, extrapulmonary tuberculosis, and mortality. We derived adjusted odds ratios (aORs) using mixed-effects, binary, multivariable logistic regression analyses with study-level random effects, adjusting for the variable of interest, baseline age, sex, previous tuberculosis, and whether data were collected prospectively or retrospectively. We stratified our results by contact age and Mycobacterium tuberculosis infection status. This study is registered with PROSPERO, CRD42020180512. We identified 14 927 original records from our database searches. We included participant-level data from 26 cohort studies done in 17 countries in our meta-analysis. Among 68 552 participants, 1782 (2·6%) developed tuberculosis (1309 [2·6%] of 49 686 BCG-vaccinated participants vs 473 [2·5%] of 18 866 unvaccinated participants). The overall effectiveness of BCG vaccination against all tuberculosis was 18% (aOR 0·82, 95% CI 0·74-0·91). When stratified by age, BCG vaccination only significantly protected against all tuberculosis in children younger than 5 years (aOR 0·63, 95% CI 0·49-0·81). Among contacts with a positive tuberculin skin test or IFNγ release assay, BCG vaccination significantly protected against tuberculosis among all participants (aOR 0·81, 95% CI 0·69-0·96), participants younger than 5 years (0·68, 0·47-0·97), and participants aged 5-9 years (0·62, 0·38-0·99). There was no protective effect among those with negative tests, unless they were younger than 5 years (0·54, 0·32-0·90). 14 cohorts reported on whether tuberculosis was pulmonary or extrapulmonary (n=57 421). BCG vaccination significantly protected against pulmonary tuberculosis among all participants (916 [2·2%] in 41 119 vaccinated participants vs 334 [2·1%] in 16 161 unvaccinated participants; aOR 0·81, 0·70-0·94) but not against extrapulmonary tuberculosis (106 [0·3%] in 40 318 vaccinated participants vs 38 [0·2%] in 15 865 unvaccinated participants; 0·96, 0·65-1·41). In the four studies with mortality data, BCG vaccination was significantly protective against death (0·25, 0·13-0·49). Our results suggest that BCG vaccination at birth is effective at preventing tuberculosis in young children but is ineffective in adolescents and adults. Immunoprotection therefore needs to be boosted in older populations. National Institutes of Health.