Screening for Tuberculosis Co-Infection in HIV Infected Children

INTRODUCTION: India is one of the largest and most populated countries in the world, with over one billion inhabitants. Of this number, it's estimated that around 2.4 million people are currently living with HIV. In recent decades, the dramatic spread of the HIV epidemic in sub-Saharan Africa has resulted in notification rates of TB increasing up to 10 times in some countries. The incidence of TB is also increasing in other high HIV prevalence countries, where the population with HIV infection and TB overlap. Even those countries with well organized national tuberculosis programs have seen an increase in TB cases. This is the underlying factor that suggests that TB control will not make much head way in HIV prevalent settings unless HIV control is also achieved. TB is the most common treatable HIV-related disease and a leading killer of people living with HIV/AIDS (PLWHA). The World Health Organisation (WHO) cites TB treatment as one of the most cost-effective health interventions available – at a cost of only $10 for every year of life gained. BACKGROUND OF THE STUDY: As HIV progressively destroys the immune system, there is a greater chance of a child infected with HIV developing tuberculosis. The development of active TB accelerates the progression of HIV disease towards full-blown AIDS, because the replication rate of the HIV virus is increased during the active phase of TB. TB is curable, even in a children who is HIV positive. Curing an HIV positive children of TB not only improves their quality of life, and gives them several more years of life, it also reduces transmission to others in the community. TB is the most common treatable HIV-related disease and a leading killer of children living with HIV/AIDS. AIM OF THE STUDY: To screen for TB coinfection in HIV positive children registered in ART Centre , Madurai. DISCUSSION: 1.SEX DISTRIBUTION IN NEWLY DIAGNOSED CASES: Of the new HIV positive children, 57.7 %(n=26) and 42.2%(n=19) were male and female respectively. This was similar to S.Rajasekaran et al.,(40) study at Tambaram in which male & female children constituted 56.9 and 43.1 percent respectively . Male children outnumber female children by a small number. 2.CONTACT HISTORY: Of the 13 children screened positive for tuberculosis, 10 children ( 76.92%) had contact with an open case of TB and it was Statistically significant( p value <0.0001) This was similar to Ira shah et al(41) study in which 70.7% had contact with an adult suffering from TB Young children living in close contact with a source case of smear-positive pulmonary TB are at particular risk for TB infection and disease. The risk of infection is greatest if the contact is close and prolonged, such as that between an infant or toddler and the mother or other caregivers in the household. CONCLUSION: 1. HIV associated TB is a major public health problem. Tuberculosis co-infection in HIV infected children was found to be 12.6% in our study. This may be due to the impact of ART. ART has been shown to reduce the incidence of TB in treated cohorts even in high TB prevalence countries. 2. Source of childhood TB is usually an adult, who is in close contact with the children. 3. Mantoux is positive even in HIV- infected children. So mantoux is an important diagnostic tool even in HIV-infected children. 4. FNAC proved to be TB in only 2 cases . So Lymphnode – FNAC or biopsy is mandatory for children presenting with lymphadenopathy before starting empirical ATT. 5. With the conventional sputum positivity and Tuberculin test not providing an adequate diagnostic help, familiarity with clinco radiological spectrum of TB and HIV coinfection will help in early diagnosis

Intracellular immune sensing promotes inflammation via gasdermin D–driven release of a lectin alarmin

Inflammatory caspase sensing of cytosolic lipopolysaccharide (LPS) triggers pyroptosis and the concurrent release of damage-associated molecular patterns (DAMPs). Collectively, DAMPs are key determinants that shape the aftermath of inflammatory cell death. However, the identity and function of the individual DAMPs released are poorly defined. Our proteomics study revealed that cytosolic LPS sensing triggered the release of galectin-1, a β-galactoside-binding lectin. Galectin-1 release is a common feature of inflammatory cell death, including necroptosis. In vivo studies using galectin-1-deficient mice, recombinant galectin-1 and galectin-1-neutralizing antibody showed that galectin-1 promotes inflammation and plays a detrimental role in LPS-induced lethality. Mechanistically, galectin-1 inhibition of CD45 (Ptprc) underlies its unfavorable role in endotoxin shock. Finally, we found increased galectin-1 in sera from human patients with sepsis. Overall, we uncovered galectin-1 as a bona fide DAMP released as a consequence of cytosolic LPS sensing, identifying a new outcome of inflammatory cell death.Fil: Russo, Ashley J.. UConn Health School of Medicine; Estados UnidosFil: Vasudevan, Swathy O.. UConn Health School of Medicine; Estados UnidosFil: Mendez Huergo, Santiago Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Kumari, Puja. UConn Health School of Medicine; Estados UnidosFil: Menoret, Antoine. UConn Health School of Medicine; Estados UnidosFil: Duduskar, Shivalee. Jena University Hospital; AlemaniaFil: Wang, Chengliang. UConn Health School of Medicine; Estados UnidosFil: Pérez Sáez, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Fettis, Margaret M.. University of Florida; Estados UnidosFil: Li, Chuan. UConn Health School of Medicine; Estados UnidosFil: Liu, Renjie. University of Florida; Estados UnidosFil: Wanchoo, Arun. University of Florida; Estados UnidosFil: Chandiran, Karthik. UConn Health School of Medicine; Estados UnidosFil: Ruan, Jianbin. UConn Health School of Medicine; Estados UnidosFil: Vanaja, Sivapriya Kailasan. UConn Health School of Medicine; Estados UnidosFil: Bauer, Michael. Jena University Hospital; AlemaniaFil: Sponholz, Christoph. Jena University Hospital; AlemaniaFil: Hudalla, Gregory A.. University of Florida; Estados UnidosFil: Vella, Anthony T.. UConn Health School of Medicine; Estados UnidosFil: Zhou, Beiyan. UConn Health School of Medicine; Estados UnidosFil: Deshmukh, Sachin D.. Jena University Hospital; AlemaniaFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Rathinam, Vijay A.. UConn Health School of Medicine; Estados Unido

Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics.

Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention

SARS-CoV-2 seroprevalence among the general population and healthcare workers in India, December 2020–January 2021

Background: Earlier serosurveys in India revealed seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) of 0.73% in May–June 2020 and 7.1% in August–September 2020. A third serosurvey was conducted between December 2020 and January 2021 to estimate the seroprevalence of SARS-CoV-2 infection among the general population and healthcare workers (HCWs) in India. Methods: The third serosurvey was conducted in the same 70 districts as the first and second serosurveys. For each district, at least 400 individuals aged ≥10 years from the general population and 100 HCWs from subdistrict-level health facilities were enrolled. Serum samples from the general population were tested for the presence of immunoglobulin G (IgG) antibodies against the nucleocapsid (N) and spike (S1-RBD) proteins of SARS-CoV-2, whereas serum samples from HCWs were tested for anti-S1-RBD. Weighted seroprevalence adjusted for assay characteristics was estimated. Results: Of the 28,598 serum samples from the general population, 4585 (16%) had IgG antibodies against the N protein, 6647 (23.2%) had IgG antibodies against the S1-RBD protein, and 7436 (26%) had IgG antibodies against either the N protein or the S1-RBD protein. Weighted and assay-characteristic-adjusted seroprevalence against either of the antibodies was 24.1% [95% confidence interval (CI) 23.0–25.3%]. Among 7385 HCWs, the seroprevalence of anti-S1-RBD IgG antibodies was 25.6% (95% CI 23.5–27.8%). Conclusions: Nearly one in four individuals aged ≥10 years from the general population as well as HCWs in India had been exposed to SARS-CoV-2 by December 2020

Biolink Model: A universal schema for knowledge graphs in clinical, biomedical, and translational science

&lt;h2&gt;What's Changed&lt;/h2&gt; &lt;ul&gt; &lt;li&gt;Documentation and repo hierarchy refactoring by @sierra-moxon in https://github.com/biolink/biolink-model/pull/1418&lt;/li&gt; &lt;/ul&gt; &lt;p&gt;Summary: 4.0.0 is a major release that includes many changes to the documentation for Biolink Model as well as the reorganization of the repository to support the new documentation structure and comply with LinkML best practices. The model itself has not changed significantly, but the documentation has been updated to reflect the current state of the model, and includes new visualizations of the model, additional text-based documentation, and a new gh-pages documentation layout.&lt;/p&gt; &lt;p&gt;&lt;strong&gt;Full Changelog&lt;/strong&gt;: https://github.com/biolink/biolink-model/compare/v3.6.0...v4.0.0&lt;/p&gt;Please cite the following works when using this software