Strategies to detect and manage latent tuberculosis infection among household contacts of pulmonary TB patients in high TB burden countries ‐ a systematic review and meta‐analysis

OBJECTIVE: To summarise latent tuberculosis infection (LTBI) management strategies among household contacts of bacteriologically confirmed pulmonary tuberculosis (TB) patients in high‐TB burden countries. METHODS: PubMed/MEDLINE (NCBI) and Scopus were searched (January 2006 to December 2021) for studies reporting primary data on LTBI management. Study selection, data management and data synthesis were protocol‐driven (PROSPERO‐CRD42021208715). Primary outcomes were the proportions of LTBI, initiating and completing tuberculosis preventive treatment (TPT). Reported factors influencing the LTBI care cascade were qualitatively synthesised. RESULTS: From 3694 unique records retrieved, 58 studies from 23 countries were included. Most identified contacts were screened (median 99%, interquartile range [IQR] 82%–100%; 46 studies). Random‐effects meta‐analysis yielded pooled proportions for: LTBI 41% (95% confidence interval [CI] 33%–49%; 21,566 tested contacts); TPT initiation 91% (95% CI 79%–97%; 129,573 eligible contacts, 34 studies); TPT completion 65% (95% CI 54%–74%; 108,679 TPT‐initiated contacts, 28 studies). Heterogeneity was significant (I (2) ≥ 95%–100%) and could not be explained in subgroup analyses. Median proportions (IQR) were: LTBI 44% (28%–59%); TPT initiation 86% (60%–100%); TPT completion 68% (44%–82%). Nine broad themes related to diagnostic testing, health system structure and functions, risk perception, documentation and adherence were considered likely to influence the LTBI care cascade. CONCLUSION: The proportions of household contacts screened, detected with LTBI and initiated on TPT, though variable was high, but the proportions completing TPT were lower indicating current strategies used for LTBI management in high TB burden countries are not sufficient

Cytokine and Protein Markers of Leprosy Reactions in Skin and Nerves: Baseline Results for the North Indian INFIR Cohort

Leprosy affects skin and peripheral nerves. Although we have effective antibiotics to treat the mycobacterial infection, a key part of the disease process is the accompanying inflammation. This can worsen after starting antibacterial treatment with episodes of immune mediated inflammation, so called ‘reactions’. These reactions are associated with worsening of the nerve damage. We recruited a cohort of 303 newly diagnosed leprosy patients in North India with the aim of understanding and defining the pathological processes better. We took skin and nerve biopsies from patients and examined them to define which molecules and mediators of inflammation were present. We found high levels of the cytokines Tumour Necrosis Factor alpha, Transforming Growth Factor beta and inducible Nitric Oxide Synthase in biopsies from patients with reactions. We also found high levels of bacteria and inflammation in the nerves. These experiments tell us that we need to determine which other molecules are present and to explore ways of switching off the production of these pro-inflammatory molecules

leprosy

phosphorylation pattern in the immune cells o

Protein phosphorylation pattern in the immune cells of leprosy affected individuals

Background: Leprosy is an infectious disease in which the susceptibility to the pathogen Mycobacterium leprae and the clinical manifestations are attributed to host immune cell response. Receptor mediated events and signalling in the immune cells are mediated by protein phosphorylation. The main signalling pathways and protein kinases known to be involved in the regulation of immune cells are cAMP dependent kinases, calcium/calmodulin dependent kinases, protein kinase C and mitogen activatedprotein kinases. The cumulative consequence of alterations in signalling pathways can be evaluated by intrinsic cellular protein phosphorylation by ã-P32 ATP. The present study was designed to assess the protein phosphorylation in the immune cells of leprosy patients as compared with normal individuals.Methodology: Lymphocyte protein phosphorylation was conducted in 15 leprosy patients and 9 normal individuals. Protein phosphorylation of lymphocytes was carried out in the presence/absence of protein kinase modulators. The phosphorylation patterns were documented and analysed consequent to SDS-PAGE, staining, destaining, drying and autoradiography.Results: The major phosphorylated proteins in lymphocytes were of molecular weights 20-22, 24-29, 30-35, 43, 46-50 and 66- 68 kDa. In general, the major phosphorylated proteins were similar in the controls and in the patients. The phosphorylatability of these proteins varied with different modulators. Variations in the phosphorylation pattern were observed in 25% of the leprosy patients where there was a decrease of the 66kDa protein and a decrease of 20-22kDa protein phosphorylation.Conclusion: The observed alterations in the protein phosphorylation pattern could be due to alteration in kinases and/or their substrates or due to the effect of M. leprae on immune cells

Additional file 1: of Mandatory TB notification in Mysore city, India: Have we heard the private practitioner’s plea?

The semi-structured questionnaire. (DOCX 14 kb

Delayed-type hypersensitivity in dermal nerve.

<p>Skin - BT in Type 1 Reaction showing aggressive DTH with epithelioid granuloma destroying a deep dermal nerve, areas of necrosis and focal lymphocytic response. H&E staining ×20.</p

Nerve stained for CD68 cells.

<p>Nerve showing CD68 positive macrophages. IHC staining ×40.</p

Immuno-staining in skin biopsies for CD68, TNF-α, TGF-β and iNOS.^*

<p>*Figures are rounded to 1 decimal place.</p><p>**Borderline tuberculoid leprosy;</p><p>***Borderline lepromatous leprosy;</p>†<p>Lepromatous leprosy;</p>‡<p>Reversal reaction.</p>§<p>Erythema Nodosum Leprosum;</p>∥<p>The following molecules were assessed as marker for TIR in skin biopsies: CD68+ (sensitivity 82%, specificity 52%), TNF-α (sensitivity 59%, specificity 80%), iNOS (sensitivity 58%, specificity 69%) and TGF-β (sensitivity 88%, specificity 57%).</p

Immuno-staining in nerve biopsies for CD68, TNF-α, TGF-β and iNOS.^*

<p>*Percentages rounded to nearest integer because of small numbers.</p><p>**Borderline tuberculoid leprosy;</p><p>***Borderline lepromatous leprosy;</p>†<p>Lepromatous leprosy;</p>‡<p>Reversal reaction.</p