Trends in Tuberculosis Mortality Across India: Improvements Despite the COVID-19 Pandemic.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has had significant health implications across the globe. India is a country that has faced a double burden of COVID-19 and tuberculosis (TB) since 2020. There is a need to understand the impacts of COVID-19 on tuberculosis control programs in India. Therefore, our study aimed to determine the changes in TB mortality across India between 2019 and 2021. METHODS: In our study, we described trends in TB and COVID-19 cases reported across India. Next, we compared death totals for TB between 2019, 2020, and 2021 in India at the national and state level. We considered total TB deaths, as well as deaths by TB for tribal populations, and for those living with human immunodeficiency virus (HIV). Percent changes were calculated. RESULTS: In 2020, compared to 2019, there was a 15.4% decrease in TB death totals, with 28 out of India's 36 states showing a decrease during this time period. While total deaths increased in 2021 compared to 2020, decreases did occur in 2021 compared to 2019. Deaths by TB for individuals living with HIV decreased by 16.0% across India. At a national level, there was a notable rise in TB deaths among tribal populations, though this was not universal across states. CONCLUSION: While the majority of the world has seen an increase in new TB cases and TB deaths annually since the start of the COVID-19 pandemic, there have instead been decreases in India during this time period. More research is required to understand the factors that have led to this decrease in TB deaths. Furthermore, additional allocation of resources is required to better support vulnerable populations in states where TB death totals have increased, especially among tribal populations.

Diabetes and tuberculosis syndemic in India: A narrative review of facts, gaps in care and challenges.

Both diabetes mellitus (DM) and tuberculosis (TB) are prevalent all across in India. TB-DM comorbidity has emerged as a syndemic and needs more attention in India considering gaps in screening, clinical care, and research. This paper is intended to review published literature on TB and DM in India to understand the burden of the dual epidemic and its trajectory and to obtain perspectives on the gaps, constraints, and challenges in care and treatment of this dual epidemic. A literature search was carried out on PubMed, Scopus, and Google Scholar, using the key words 'Tuberculosis' OR 'TB' AND 'Diabetes' OR 'Diabetes Mellitus' AND 'India', focusing on the research published between the year 2000 to 2022. The prevalence of DM is high in patients with TB. Quantitative data on the epidemiological situation of TB/DM in India such as incidence, prevalence, mortality, and management are lacking. During the last 2 years convergence of TB-DM syndemic with the COVID-19 pandemic has increased cases with uncontrolled DM but also made coordinated control of TB-DM operationally difficult and of low effectiveness. Research regarding TB-DM comorbidity is required in the context of epidemiology and management. Detection and bidirectional screening are aggressively warranted. Management of DM in those with TB-DM comorbidity needs more efforts, including training and supervision of frontline workers.

Stool Xpert MTB/RIF as a possible diagnostic alternative to sputum in Africa: a systematic review and meta-analysis.

Introduction: Worldwide, COVID-19 pandemic lead to a large fall in the number of newly reported TB cases. In sub-Saharan Africa, microbiological diagnosis of TB is generally based on smear microscopy and Xpert MTB/RIF on sputum samples, but good quality sputum samples are often difficult to obtain, leading clinicians to rely on more invasive procedures for diagnosis. Aim of this study was to investigate pooled sensitivity and specificity of Xpert MTB/RIF on stool samples compared to respiratory microbiological reference standards in African countries. Methods: Four investigators independently searched PubMed, SCOPUS, and Web of Science until 12th October 2022, then screened titles and abstracts of all potentially eligible articles. The authors applied the eligibility criteria, considered the full texts. All the studies reported the data regarding true positive (TP), true negative (TN), false positive (FP) and false negative (FN). Risk of bias and applicability concerns were assessed with the Quadas-2 tool. Results: overall, among 130 papers initially screened, we evaluated 47 works, finally including 13 papers for a total of 2,352 participants, mainly children. The mean percentage of females was 49.6%, whilst the mean percentage of patients reporting HIV was 27.7%. Pooled sensitivity for Xpert MTB/RIF assay for detecting pulmonary tuberculosis was 68.2% (95%CI: 61.1-74.7%) even if characterized by a high heterogeneity (I2=53.7%). Specificity was almost 100% (99%, 95%CI: 97-100%; I2 = 45.7%). When divided for reference standard, in the six studies using sputum and nasogastric aspirate the accuracy was optimal (AUC = 0.99, SE = 0.02), whilst in the studies using only sputum for tuberculosis detection the AUC was 0.85 (with a SE = 0.16). The most common source of bias was exclusion of enrolled patients in the analysis. Conclusions: Our study confirms that, in Africa, stool Xpert MTB/RIF may be a useful rule-in test for children above and below 5 years of age under evaluation for pulmonary tuberculosis. Sensitivity increased substantially when using both sputum and nasogastric aspirate as reference samples.

Disseminated tuberculosis and diagnosis delay during the COVID-19 era in a Western European country: a case series analysis.

Background: Disseminated tuberculosis is frequently associated with delayed diagnosis and a poorer prognosis. Objectives: To describe case series of disseminated TB and diagnosis delay in a low TB burden country during the COVID-19 period. Methodology: We consecutively included all patients with of disseminated TB reported from 2019 to 2021 in the reference hospital of the Northern Crown of the Metropolitan Area of Barcelona. We collected socio-demographic information, clinical, laboratory and radiological findings. Results: We included all 30 patients reported during the study period-5, 9, and 16 in 2019, 2020, and 2021 respectively-20 (66.7%) of whom were male and whose mean age was 41 years. Twenty-five (83.3%) were of non-EU origin. The most frequent system involvement was central nervous system (N = 8; 26.7%) followed by visceral (N = 7; 23.3%), gastro-intestinal (N = 6, 20.0%), musculoskeletal (N = 5; 16.7%), and pulmonary (N = 4; 13.3%). Hypoalbuminemia and anemia were highly prevalent (72 and 77%). The median of diagnostic delay was 6.5 months (IQR 1.8-30), which was higher among women (36.0 vs. 3.5 months; p = 0.002). Central nervous system involvement and pulmonary involvement were associated with diagnostic delay among women. We recorded 24 cured patients, two deaths, three patients with post-treatment sequelae, and one lost-to-follow up. We observed a clustering effect of patients in low-income neighborhoods (p < 0.001). Conclusion: There was a substantial delay in the diagnosis of disseminated TB in our study region, which might impacted the prognosis with women affected more negatively. Our results suggest that an increase in the occurrence of disseminated TB set in motion by diagnosis delay may have been a secondary effect of the COVID-19 pandemic.

Biapenem, a Carbapenem Antibiotic, Elicits Mycobacteria Specific Immune Responses and Reduces the Recurrence of Tuberculosis.

Tuberculosis (TB) still tops the list of global health burdens even after COVID-19. However, it will sooner transcend the current pandemic due to the prevailing risk of reactivation of latent TB in immunocompromised individuals. The indiscriminate misuse and overuse of antibiotics have resulted in the emergence of deadly drug-resistant variants of Mycobacterium tuberculosis (M.tb). This study aims to characterize the functionality of the carbapenem antibiotic-Biapenem (BPM) in generating long-lasting immunity against TB. BPM treatment significantly boosted the activation status of the innate immune arm-macrophages by augmenting p38 signaling. Macrophages further primed and activated the adaptive immune cells CD4+ and CD8+ T-cells in the lung and spleen of the infected mice model. Furthermore, BPM treatment significantly amplified the polarization of T lymphocytes toward inflammatory subsets, such as Th1 and Th17. The treatment also helped generate a long-lived central memory T-cell subset. The generation of central memory T lymphocyte subset upon BPM treatment in the murine model led to a significant curtailing in the recurrence of TB due to reactivation and reinfection. These results suggest the potentiality of BPM as a potent adjunct immunomodulator to improve host defense against M.tb by enriching long-term protective memory cells. IMPORTANCE Tuberculosis (TB) caused by Mycobacterium tuberculosis (M.tb) tops the list of infectious killers around the globe. The emergence of drug-resistant variants of M.tb has been a major hindrance toward realizing the "END TB" goal. Drug resistance has amplified the global burden toward the quest for novel drug molecules targeting M.tb. Host-directed therapy (HDT) offers a lucrative alternative to tackle emerging drug resistance and disease relapse by strengthening the host's immunity. Through our present study, we have tried to characterize the functionality of the carbapenem antibiotic-Biapenem (BPM). BPM treatment significantly augmented long-lasting immunity against TB by boosting the innate and adaptive immune arms. The generation of long-lived central memory T lymphocyte subset significantly improved the disease outcome and provided sterilizing immunity in the murine model of TB. The present investigation's encouraging results have helped us depict BPM as a potent adjunct immunomodulator for treating TB.

A new tractable method for generating human alveolar macrophage-like cells in vitro to study lung inflammatory processes and diseases.

Alveolar macrophages (AMs) are unique lung resident cells that contact airborne pathogens and environmental particulates. The contribution of human AMs (HAMs) to pulmonary diseases remains poorly understood due to the difficulty in accessing them from human donors and their rapid phenotypic change during in vitro culture. Thus, there remains an unmet need for cost-effective methods for generating and/or differentiating primary cells into a HAM phenotype, particularly important for translational and clinical studies. We developed cell culture conditions that mimic the lung alveolar environment in humans using lung lipids, that is, Infasurf (calfactant, natural bovine surfactant) and lung-associated cytokines (granulocyte macrophage colony-stimulating factor, transforming growth factor-ß, and interleukin 10) that facilitate the conversion of blood-obtained monocytes to an AM-like (AML) phenotype and function in tissue culture. Similar to HAM, AML cells are particularly susceptible to both Mycobacterium tuberculosis and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. This study reveals the importance of alveolar space components in the development and maintenance of HAM phenotype and function and provides a readily accessible model to study HAM in infectious and inflammatory disease processes, as well as therapies and vaccines.IMPORTANCEMillions die annually from respiratory disorders. Lower respiratory track gas-exchanging alveoli maintain a precarious balance between fighting invaders and minimizing tissue damage. Key players herein are resident AMs. However, there are no easily accessible in vitro models of HAMs, presenting a huge scientific challenge. Here, we present a novel model for generating AML cells based on differentiating blood monocytes in a defined lung component cocktail. This model is non-invasive, significantly less costly than performing a bronchoalveolar lavage, yields more AML cells than HAMs per donor, and retains their phenotype in culture. We have applied this model to early studies of M. tuberculosis and SARS-CoV-2. This model will significantly advance respiratory biology research.

Superimposed Pulmonary Tuberculosis (PTB) in a 26-Year-Old Female with No Underlying Co-Morbidities Recovering from COVID-19-Case Report.

Tuberculosis before the COVID-19 pandemic is said to have killed more people globally than any other communicable disease and is ranked the 13th cause of death, according to the WHO. Tuberculosis also still remains highly endemic, especially in LIMCs with a high burden of people living with HIV/AIDS, in which it is the leading cause of mortality. Given the risk factors associated with COVID-19, the cross similarities between tuberculosis and COVID-19 symptoms, and the paucity of data on how both diseases impact each other, there is a need to generate more information on COVID-19-TB co-infection. In this case report, we present a young female patient of reproductive age with no underlying comorbidities recovering from COVID-19, who later presented with pulmonary tuberculosis. It describes the series of investigations performed and treatments given during the follow-up. There is a need for more surveillance for possible COVID-19-TB co-infection cases and further research to understand the impact of COVID-19 on tuberculosis and vice versa, especially in LMICs.

Antibiotic Resistance and Its Impact on Disease Management.

Antibiotic resistance has been a challenge to the medical fraternity and has had a massive impact on disease management. The overuse of antibiotics and careless prescription by doctors have been one of the primary reasons for the development of antibiotic resistance among the masses. This article draws attention to the significant reasons causing antibiotic resistance, such as overuse, antibiotic resistance genes, and extensive use of antibiotics in agriculture. It also brings forward the challenges posed by antibiotic resistance in the management of various diseases like tuberculosis, COVID-19, and vancomycin-resistant enterococci infections. The article includes a case study that depicts the threat posed by antibiotic resistance in tuberculosis treatment. This article also shows the effects of antibiotic resistance on COVID-19 patient care and treatment. It further includes methods that can be implemented on international levels as well as individual ground levels to curb antibiotic resistance. One of the methods has a recent finding in which proteins produced in the body are being modified and used in treatments to reduce the use of antibiotics, which ultimately serves the goal of curbing antibiotic resistance by reducing overuse.

Controlled human infection models in COVID-19 and tuberculosis: current progress and future challenges.

Controlled Human Infection Models (CHIMs) involve deliberately exposing healthy human volunteers to a known pathogen, to allow the detailed study of disease processes and evaluate methods of treatment and prevention, including next generation vaccines. CHIMs are in development for both tuberculosis (TB) and Covid-19, but challenges remain in their ongoing optimisation and refinement. It would be unethical to deliberately infect humans with virulent Mycobacteria tuberculosis (M.tb), however surrogate models involving other mycobacteria, M.tb Purified Protein Derivative or genetically modified forms of M.tb either exist or are under development. These utilise varying routes of administration, including via aerosol, per bronchoscope or intradermal injection, each with their own advantages and disadvantages. Intranasal CHIMs with SARS-CoV-2 were developed against the backdrop of the evolving Covid-19 pandemic and are currently being utilised to both assess viral kinetics, interrogate the local and systemic immunological responses post exposure, and identify immune correlates of protection. In future it is hoped they can be used to assess new treatments and vaccines. The changing face of the pandemic, including the emergence of new virus variants and increasing levels of vaccination and natural immunity within populations, has provided a unique and complex environment within which to develop a SARS-CoV-2 CHIM. This article will discuss current progress and potential future developments in CHIMs for these two globally significant pathogens.

Beneficial or detrimental activity of regulatory T cells, indoleamine 2,3-dioxygenase, and heme oxygenase-1 in the lungs is influenced by the level of virulence of Mycobacterium tuberculosis strain infection.

Tuberculosis (TB) caused by the complex Mycobacterium tuberculosis (Mtb) is the main cause of death by a single bacterial agent. Last year, TB was the second leading infectious killer after SARS-CoV-2. Nevertheless, many biological and immunological aspects of TB are not completely elucidated, such as the complex process of immunoregulation mediated by regulatory T cells (Treg cells) and the enzymes indoleamine 2,3-dioxygenase (IDO) and heme oxygenase 1 (HO-1). In this study, the contribution of these immunoregulatory factors was compared in mice infected with Mtb strains with different levels of virulence. First Balb/c mice were infected by intratracheal route, with a high dose of mild virulence reference strain H37Rv or with a highly virulent clinical isolate (strain 5186). In the lungs of infected mice, the kinetics of Treg cells during the infection were determined by cytofluorometry and the expression of IDO and HO-1 by RT-PCR and immunohistochemistry. Then, the contribution of immune-regulation mediated by Treg cells, IDO and HO-1, was evaluated by treating infected animals with specific cytotoxic monoclonal antibodies for Treg cells depletion anti-CD25 (PC61 clone) or by blocking IDO and HO-1 activity using specific inhibitors (1-methyl-D,L-tryptophan or zinc protoporphyrin-IX, respectively). Mice infected with the mild virulent strain showed a progressive increment of Treg cells, showing this highest number at the beginning of the late phase of the infection (28 days), the same trend was observed in the expression of both enzymes being macrophages the cells that showed the highest immunostaining. Animals infected with the highly virulent strain showed lower survival (34 days) and higher amounts of Treg cells, as well as higher expression of IDO and HO-1 one week before. In comparison with non-treated animals, mice infected with strain H37Rv with depletion of Treg cells or treated with the enzymes blockers during late infection showed a significant decrease of bacilli loads, higher expression of IFN-g and lower IL-4 but with a similar extension of inflammatory lung consolidation determined by automated morphometry. In contrast, the depletion of Treg cells in infected mice with the highly virulent strain 5186 produced diffuse alveolar damage that was similar to severe acute viral pneumonia, lesser survival and increase of bacillary loads, while blocking of both IDO and HO-1 produced high bacillary loads and extensive pneumonia with necrosis. Thus, it seems that Treg cells, IDO and HO-1 activities are detrimental during late pulmonary TB induced by mild virulence Mtb, probably because these factors decrease immune protection mediated by the Th1 response. In contrast, Treg cells, IDO and HO-1 are beneficial when the infection is produced by a highly virulent strain, by regulation of excessive inflammation that produced alveolar damage, pulmonary necrosis, acute respiratory insufficiency, and rapid death.

[Dynamics of the structure of renal tuberculosis over 20 years].

BACKGROUND: Tuberculosis is a serious medical and social problem that does not lose its importance, despite all the advances in pharmacology and surgery. Diagnosis of urogenital tuberculosis (UGTB), as a rule, is delayed due to low index of suspicion to tuberculosis and the absence of pathognomonic symptoms. AIM: Determining the change in the ratio of clinical forms of renal tuberculosis from 1999 to 2020. MATERIALS AND METHODS: A retrospective cohort comparative non-interventional study on the spectrum of the incidence of extrapulmonary tuberculosis (EPTB) was carried out. Among all 13852 extrapulmonary tuberculosis patients which were diagnosed from 1999 to 2020, patients with renal tuberculosis were selected, and the spectrum of their clinical forms in three periods was analyzed: 1st period 1999-2004 (1155 patients), second period 2005-2014 (2657 patients), and the third period 2015-2020 (671 patients). The clinical features of nephrotuberculosis in 88 patients was also estimated. RESULTS: Over the 20 years of the analyzed period, the number of patients with UGTB decreased by 80.6%; for the year of the COVID-19 pandemic, this figure fell by another third. In the first period, destructive complicated forms of nephrotuberculosis prevailed (922 patients - 79.8%), while the so-called "minor forms" were diagnosed in 233 patients (20.2%). In the second period, the situation was statistically significantly more favorable: the proportion of destructive and complicated forms of renal tuberculosis decreased to 43.8% (1124 patients), "small forms" were diagnosed in 1443 patients (56.2%). In the third period, destructive and complicated forms of nephrotuberculosis were diagnosed in 531 patients (77.6%), and the proportion of "small forms" in comparison with the previous period decreased by half, to 22.4%. Analysis of the clinical features of renal tuberculosis, depending on the prevalence of the destruction, showed that an asymptomatic course is possible, and pain, dysuria, intoxication and renal colic are present with different frequencies, and the clinical picture of tuberculosis of the renal parenchyma differs significantly from the clinical picture of tuberculous papillitis, cavernous nephrotuberculosis and symptoms of renal tuberculosis as whole. CONCLUSION: Currently, there is no screening on urogenital tuberculosis at all. Patients are diagnosed by referral, with a long history, after receiving multiple courses of antibacterial treatment; mainly through the pathomorphological examination of the operating material. Thus, a sharp decrease in the proportion of UGTB patients does not mean the disappearance of tuberculosis of this localization, but only states the tragic defects in timely diagnosis and low index of suspicion of medical doctors in relation to UGTB.

Tuberculosis in Poland in 2020.

AIM OF THE STUDY: To evaluate the main features of epidemiology of tuberculosis (TB) in 2020 in Poland and to compare with the situation in the European Union and European Economic Area (EU/EEA) countries. MATERIAL AND METHODS: Analysis of case-based data on TB patients from National TB Register, data on anti-TB drug susceptibility in cases notified in 2020, data from Statistics Poland on deaths from tuberculosis in 2019, data from National Institute of Public Health NIH - National Research Institute (NIPH NIH - NRI) on HIV-positive subjects for whom TB was an AIDS-defining disease, data from the report "European Centre for Disease Prevention and Control, WHO Regional Office for Europe. Tuberculosis surveillance and monitoring in Europe 2022 - 2020 data. Copenhagen: WHO Regional Office for Europe and Stockholm: European Centre for Disease Prevention and Control; 2022." RESULTS: In 2020, 3,388 TB cases were reported in Poland. The incidence rate was 8.8 cases per 100,000 with large variability between voivodeships from 5.5 to 13.3 per 100,000. A decrease in the incidence was found in 15 voivodeships, the most significant in Slaskie voivodship (63.9%). The number of all pulmonary tuberculosis cases was 3,237 i.e. 8.4 per 100,000. Pulmonary cases represented 95.5% of all TB cases. In 2020, 151 extrapulmonary TB cases were notified (4.5% of all TB cases). Pulmonary tuberculosis was bacteriologically confirmed in 2,573 cases (79.5% of all pulmonary TB cases, the incidence rate 6.7 per 100,000). The number of smear-positive pulmonary TB cases was 1,771 i.e. 4.6 per 100,000 (54.7% of all pulmonary TB cases). In 2020, there were 38 cases (15 of foreign origin) with multidrug resistant TB (MDR-TB) representing 1.6% of cases with known drug sensitivity. The incidence rates of tuberculosis were growing along with increasing age from 0.7 per 100,000 among children (0-14 years) to 15.0 per 100,000 among subjects in the age group 45-64 years, the incidence rate in the age group ≥65 years was 12.1 per 100,000. There were 39 cases in children up to 14 years of age (1.2% of the total) and 49 cases in adolescents between 15 and 19 years of age - rates 0.7 and 2.7 per 100,000 respectively. In 2020, there were 2,506 cases of tuberculosis in men and 882 in women. The TB incidence in men - 13.5 per 100,000 was 3.0 times higher than among women - 4.5. The biggest difference in the TB incidence between the two sex groups occurred in persons aged 50-54 years - 26.8 vs. 4.1 and in age group 55 to 59 years - 28.7 vs. 4.8. In 2020, there were 116 patients of foreign origin among all cases of tuberculosis in Poland (3.4%). In 2019, TB was the cause of death for 456 people (mortality rate - 1.2 per 100,000). CONCLUSIONS: TB incidence in Poland in 2020 was 36.7% lower than in 2019. Such significant declines in the incidence have not been observed in the last two decades. As in previous years, there were differences in incidence rates between voivodeships with an unexpectedly sharp decrease in incidence in Silesia (Slaskie voivodeship). The percentage of tuberculosis cases with bacteriological confirmation exceeded 78%, more than in EU/EEA countries (67.3%). The percentage of MDR-TB cases was still lower than the average in EU/EEA countries (1.6% vs. 3.8%). The highest incidence rates were found in Poland in the older age groups (EU/EEAaged 25 to 44). The percentage of children up to 14 years of age among the total number of TB patients was 1.2%, less than the average in EU/EEA countries (3.8%). The incidence of tuberculosis in men was three times higher than in women in Poland, and six times higher in patients aged 50 to 59. The impact of migration on the TB pattern in Poland has not yet become significant in 2020. The percentage of foreigners among TB patients was 3.4% (33% in EU/EEA countries).

Drug Reaction With Eosinophilia and Systemic Symptoms-Associated Perimyocarditis After Initiation of Anti-tuberculosis Therapy: A Case Report.

A 34-year-old female who was recently placed on anti-tuberculosis medication with rifampin, isoniazid, pyrazinamide, and levofloxacin therapy for suspected tuberculosis reinfection presented with subjective fevers, rash, and generalized fatigue. Labs showed signs of end-organ damage with eosinophilia and leukocytosis. One day later, the patient became hypotensive with a worsening fever, and an electrocardiogram showed new diffuse ST segment elevations with an elevated troponin. An echocardiogram revealed a reduction in ejection fraction with diffuse hypokinesis, and cardiac magnetic resonance imaging (MRI) showed circumferential myocardial edema with subepicardial and pericardial inflammation. Prompt diagnosis of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome using the European Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) criteria and discontinuation of therapy was initiated. Due to the hemodynamic instability of the patient, the patient was started on systemic corticosteroids and cyclosporine, with the improvement of her symptoms and rash. A skin biopsy was performed, which revealed perivascular lymphocytic dermatitis, consistent with DRESS syndrome. As the patient's ejection fraction improved spontaneously with corticosteroids, the patient was discharged with oral corticosteroids, and a repeat echocardiogram showed full recovery of ejection fraction. Perimyocarditis is a rare complication of DRESS syndrome that is associated with degranulation and the release of cytotoxic agents into myocardial cells. Early discontinuation of offending agents and initiation of corticosteroids are essential to rapid recovery of ejection fraction and improved clinical outcomes. Multimodality imaging, including MRI, should be used to confirm perimyocardial involvement and guide the necessity for mechanical support or transplant. Further research should be on the mortality of DRESS syndrome with and without myocardial involvement, with an increased emphasis on cardiac evaluation in DRESS syndrome.

Massive pulmonary embolism led to cardiac arrest two days after thoracoscopy in a young male with pleural tuberculosis.

TB itself is considered an independent risk factor for VTE; however, developing pulmonary embolism after medical thoracoscopy is extremely rare. Herein, we describe a 30-year-old previously healthy male with pleural tuberculosis developed a massive pulmonary embolism with subsequent cardiac arrest after a diagnostic medical thoracoscopy. Computed tomography pulmonary angiogram (CTPA) showed major right pulmonary embolism (PE). Unfortunately, the patient passed away despite resuscitation and extensive organ support in the intensive care unit (ICU). This case highlights the thrombotic risk in this population group in order to avoid such devastating complications.

A CRISPR-Cas12a-based platform for ultrasensitive rapid highly specific detection of Mycobacterium tuberculosis in clinical application.

Tuberculosis, caused by Mycobacterium tuberculosis (MTB), is the second leading cause of death after COVID-19 pandemic. Here, we coupled multiple cross displacement amplification (MCDA) technique with CRISPR-Cas12a-based biosensing system to design a novel detection platform for tuberculosis diagnosis, termed MTB-MCDA-CRISPR. MTB-MCDA-CRISPR pre-amplified the specific sdaA gene of MTB by MCDA, and the MCDA results were then decoded by CRISPR-Cas12a-based detection, resulting in simple visual fluorescent signal readouts. A set of standard MCDA primers, an engineered CP1 primer, a quenched fluorescent ssDNA reporter, and a gRNA were designed targeting the sdaA gene of MTB. The optimal temperature for MCDA pre-amplification is 67°C. The whole experiment process can be completed within one hour, including sputum rapid genomic DNA extraction (15 minutes), MCDA reaction (40 minutes), and CRISPR-Cas12a-gRNA biosensing process (5 minutes). The limit of detection (LoD) of the MTB-MCDA-CRISPR assay is 40 fg per reaction. The MTB-MCDA-CRISPR assay does not cross reaction with non-tuberculosis mycobacterium (NTM) strains and other species, validating its specificity. The clinical performance of MTB-MCDA-CRISPR assay was higher than that of the sputum smear microscopy test and comparable to that of Xpert method. In summary, the MTB-MCDA-CRISPR assay is a promising and effective tool for tuberculosis infection diagnosis, surveillance and prevention, especially for point-of-care (POC) test and field deployment in source-limited regions.

Impact of aging on immunity in the context of COVID-19, HIV, and tuberculosis.

Knowledge of aging biology needs to be expanded due to the continuously growing number of elderly people worldwide. Aging induces changes that affect all systems of the body. The risk of cardiovascular disease and cancer increases with age. In particular, the age-induced adaptation of the immune system causes a greater susceptibility to infections and contributes to the inability to control pathogen growth and immune-mediated tissue damage. Since the impact of aging on immune function, is still to be fully elucidated, this review addresses some of the recent understanding of age-related changes affecting key components of immunity. The emphasis is on immunosenescence and inflammaging that are impacted by common infectious diseases that are characterized by a high mortality, and includes COVID-19, HIV and tuberculosis.

Infections and the Kidney

Global infections are very frequent cause of AKI. Often this is due to the non-specific systemic effects of sepsis and volume depletion and therefore can occur with many infectious agents perhaps most searingly brought to our attention with the SARS-CoV-2 pandemic. The kidney can also be damaged by infections directly involving the renal parenchyma, because of persistent infection elsewhere in the body, as a post-infectious response and secondary diseases causing obstruction. Identifying, first, that kidney injury is due to infection and the particular infection causing the patient's presentation is critical to management. Some infections discussed in this chapter are confined to specific areas of the world, but with increasing global travel and migration, patients may present to healthcare facilities anywhere;thus, a thorough travel history is invaluable. © Springer Nature Switzerland AG 2014, 2022.