Helminth Infections and Diabetes: Mechanisms Accounting for Risk Amelioration.

The global prevalence of type 2 diabetes is increasing rapidly, with an anticipated 600 million cases by 2035. While infectious diseases such as helminth infections have decreased due to improved sanitation and health care, recent research suggests a link between helminth infections and type 2 diabetes mellitus (T2D), with helminths such as Schistosoma, Nippostrongylus, Strongyloides, and Heligmosomoides potentially mitigating or slowing down T2D progression in human and animal models. Helminth infections enhance host immunity by promoting interactions between innate and adaptive immune systems. In T2D, type 1 immune responses are suppressed and type 2 responses are augmented, expanding regulatory T cells and innate immune cells, particularly type 2 immune cells and macrophages. This article reviews recent research shedding light on the favorable effects of helminth infections on T2D. The potential defense mechanisms identified include heightened insulin sensitivity and reduced inflammation. The synthesis of findings from studies investigating parasitic helminths and their derivatives underscores promising avenues for defense against T2D.

Unique cellular immune signatures of multisystem inflammatory syndrome in children.

The clinical presentation of MIS-C overlaps with other infectious/non-infectious diseases such as acute COVID-19, Kawasaki disease, acute dengue, enteric fever, and systemic lupus erythematosus. We examined the ex-vivo cellular parameters with the aim of distinguishing MIS-C from other syndromes with overlapping clinical presentations. MIS-C children differed from children with non-MIS-C conditions by having increased numbers of naïve CD8+ T cells, naïve, immature and atypical memory B cells and diminished numbers of transitional memory, stem cell memory, central and effector memory CD4+ and CD8+ T cells, classical, activated memory B and plasma cells and monocyte (intermediate and non-classical) and dendritic cell (plasmacytoid and myeloid) subsets. All of the above alterations were significantly reversed at 6-9 months post-recovery in MIS-C. Thus, MIS-C is characterized by a distinct cellular signature that distinguishes it from other syndromes with overlapping clinical presentations. Trial Registration: ClinicalTrials.gov clinicaltrial.gov. No: NCT04844242.

QuantiFERON Supernatant-Based Host Biomarkers Predicting Progression to Active Tuberculosis Disease Among Household Contacts of Tuberculosis Patients.

BACKGROUND: The positive predictive value of tuberculin skin test and current generation interferon gamma release assays are very low leading to high numbers needed to treat. Therefore, it is critical to identify new biomarkers with high predictive accuracy to identify individuals bearing high risk of progression to active tuberculosis (TB). METHODS: We used stored QuantiFERON supernatants from 14 household contacts of index TB patients who developed incident active TB during a 2-year follow-up and 20 age and sex-matched non-progressors. The supernatants were tested for an expanded panel of 45 cytokines, chemokines, and growth factors using the Luminex Multiplex Array kit. RESULTS: We found significant differences in the levels of TB-antigen induced production of several analytes between progressors and non-progressors. Dominance analysis identified 15 key predictive biomarkers based on relative percentage importance. Principal component analysis revealed that these biomarkers could robustly distinguish between the 2 groups. Receiver operating characteristic analysis identified interferon-γ inducible protein (IP)-10, chemokine ligand (CCL)19, interferon (IFN)-γ, interleukin (IL)-1ra, CCL3, and granulocyte-macrophage colony-stimulating factor (GM-CSF) as the most promising predictive markers, with area under the curve (AUC) ≥90. IP-10/CCL19 ratio exhibited maximum sensitivity and specificity (100%) for predicting progression. Through Classification and Regression Tree analysis, a cutoff of 0.24 for IP-10/CCL19 ratio was found to be ideal for predicting short-term risk of progression to TB disease with a positive predictive value of 100 (95% confidence interval [CI] 85.8-100). CONCLUSIONS: The biomarkers identified in this study will pave way for the development of a more accurate test that can identify individuals at high risk for immediate progression to TB disease for targeted intervention.

Alterations of adipokines, pancreatic hormones and incretins in acute and convalescent COVID-19 children.

BACKGROUND: The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), accountable for Coronavirus disease 2019 (COVID-19), may cause hyperglycemia and additional systemic complexity in metabolic parameters. It is unsure even if the virus itself causes type 1 or type 2 diabetes mellitus (T1DM or T2DM). Furthermore, it is still unclear whether even recuperating COVID-19 individuals have an increased chance to develop new-onset diabetes. METHODS: We wanted to determine the impact of COVID-19 on the levels of adipokines, pancreatic hormones, incretins and cytokines in acute COVID-19, convalescent COVID-19 and control children through an observational study. We performed a multiplex immune assay analysis and compared the plasma levels of adipocytokines, pancreatic hormones, incretins and cytokines of children presenting with acute COVID-19 infection and convalescent COVID-19. RESULTS: Acute COVID-19 children had significantly elevated levels of adipsin, leptin, insulin, C-peptide, glucagon and ghrelin in comparison to convalescent COVID-19 and controls. Similarly, convalescent COVID-19 children had elevated levels of adipsin, leptin, insulin, C-peptide, glucagon, ghrelin and Glucagon-like peptide-1 (GLP-1) in comparison to control children. On the other hand, acute COVID-19 children had significantly decreased levels of adiponectin and Gastric Inhibitory Peptide (GIP) in comparison to convalescent COVID-19 and controls. Similarly, convalescent COVID-19 children had decreased levels of adiponectin and GIP in comparison to control children. Acute COVID-19 children had significantly elevated levels of cytokines, (Interferon (IFN)) IFNγ, Interleukins (IL)-2, TNFα, IL-1α, IL-1ß, IFNα, IFNß, IL-6, IL-12, IL-17A and Granulocyte-Colony Stimulating Factors (G-CSF) in comparison to convalescent COVID-19 and controls. Convalescent COVID-19 children had elevated levels of IFNγ, IL-2, TNFα, IL-1α, IL-1ß, IFNα, IFNß, IL-6, IL-12, IL-17A and G-CSF in comparison to control children. Additionally, Principal component Analysis (PCA) analysis distinguishes acute COVID-19 from convalescent COVID-19 and controls. The adipokines exhibited a significant correlation with the levels of pro-inflammatory cytokines. CONCLUSION: Children with acute COVID-19 show significant glycometabolic impairment and exaggerated cytokine responses, which is different from convalescent COVID-19 infection and controls.

Restoration of dendritic cell homeostasis and Type I/Type III interferon levels in convalescent COVID-19 individuals.

BACKGROUND: Plasmacytoid and myeloid dendritic cells play a vital role in the protection against viral infections. In COVID-19, there is an impairment of dendritic cell (DC) function and interferon secretion which has been correlated with disease severity. RESULTS: In this study, we described the frequency of DC subsets and the plasma levels of Type I (IFNα, IFNß) and Type III Interferons (IFNλ1), IFNλ2) and IFNλ3) in seven groups of COVID-19 individuals, classified based on days since RT-PCR confirmation of SARS-CoV2 infection. Our data shows that the frequencies of pDC and mDC increase from Days 15-30 to Days 61-90 and plateau thereafter. Similarly, the levels of IFNα, IFNß, IFNλ1, IFNλ2 and IFNλ3 increase from Days 15-30 to Days 61-90 and plateau thereafter. COVID-19 patients with severe disease exhibit diminished frequencies of pDC and mDC and decreased levels of IFNα, IFNß, IFNλ1, IFNλ2 and IFNλ3. Finally, the percentages of DC subsets positively correlated with the levels of Type I and Type III IFNs. CONCLUSION: Thus, our study provides evidence of restoration of homeostatic levels in DC subset frequencies and circulating levels of Type I and Type III IFNs in convalescent COVID-19 individuals.

Effect of SARS-CoV-2 seropositivity on antigen - specific cytokine and chemokine responses in latent tuberculosis.

SARS-CoV-2 and latent Mycobacterium tuberculosis infection are both highly co-prevalent in many parts of the globe. Whether exposure to SARS-CoV-2 influences the antigen specific immune responses in latent tuberculosis has not been investigated. We examined the baseline, mycobacterial antigen and mitogen induced cytokine and chemokine responses in latent tuberculosis (LTBI) individuals with or without SARS-CoV-2 seropositivity, LTBI negative individuals with SARS-CoV-2 seropositivity and healthy control (both LTBI and SARS-CoV-2 negative) individuals. Our results demonstrated that LTBI individuals with SARS-CoV-2 seropositivity (LTBI+/IgG +) were associated with increased levels of unstimulated and TB-antigen stimulated IFNγ, IL-2, TNFα, IL-17, IL-1ß, IL-6, IL-12, IL-4, CXCL1, CXCL9 and CXCL10 when compared to those without seropositivity (LTBI+/IgG-). In contrast, LTBI+/IgG+ individuals were associated with decreased levels of IL-5 and IL-10. No significant difference in the levels of cytokines/chemokines was observed upon mitogen stimulation between the groups. SARS-CoV-2 seropositivity was associated with enhanced unstimulated and TB-antigen stimulated but not mitogen stimulated production of cytokines and chemokines in LTBI+ compared to LTBI negative individuals. Finally, most of these significant differences were not observed when LTBI negative individuals with SARS-CoV-2 seropositivity and controls were examined. Our data clearly demonstrate that both baseline and TB - antigen induced cytokine responses are augmented in the presence of SARS-CoV-2 seropositivity, suggesting an augmenting effect of prior SARS-CoV-2 infection on the immune responses of LTBI individuals.

Helminth Coinfection Alters Monocyte Activation, Polarization, and Function in Latent Mycobacterium tuberculosis Infection.

Helminth infections are known to influence T and B cell responses in latent tuberculosis infection (LTBI). Whether helminth infections also modulate monocyte responses in helminth-LTBI coinfection has not been fully explored. To this end, we examined the activation, polarization, and function of human monocytes isolated from individuals with LTBI with (n = 25) or without (n = 25) coincident Strongyloides stercoralis infection (S. stercoralis-positive and S. stercoralis-negative respectively). Our data reveal that the presence of S. stercoralis infection is associated with lower frequencies of monocytes expressing CD54, CD80, CD86 at baseline (absence of stimulation) and in response to mycobacterial-Ag stimulation than monocytes from S. stercoralis-negative individuals. In contrast, S. stercoralis infection was associated with higher frequencies of M2-like monocytes, as determined by expression of CD206 and CD163. Monocytes from S. stercoralis-positive individuals had a reduced capacity to phagocytose or exhibit respiratory burst activity following mycobacterial-Ag or LPS stimulation and were less capable of expression of IL-1ß, TNF-α, IL-6, and IL-12 at baseline and/or following Ag stimulation compared with those without S. stercoralis infection. In addition, definitive treatment of S. stercoralis infection resulted in a significant reversal of the altered monocyte function 6 mo after anthelmintic therapy. Finally, T cells from S. stercoralis-positive individuals exhibited significantly lower activation at baseline or following mycobacterial-Ag stimulation. Therefore, our data highlight the induction of dampened monocyte activation, enhanced M2 polarization, and impaired monocyte function in helminth-LTBI coinfection. Our data also reveal a different mechanism by which helminth infection modulates immune function in LTBI.

Diminished Circulating Levels of Angiogenic Factors and Rage Ligands in Helminth-Diabetes Comorbidity and Reversal Following Anthelmintic Treatment.

BACKGROUND: Various epidemiological and experimental studies propose that helminths could play a preventive role against the progression of type 2 diabetes mellitus (T2DM). T2DM induces microvascular and large vessel complications mediated by elevated levels of angiogenic factors and soluble receptor for advanced glycation end product (RAGE) ligands. However, the interactions between helminths and host angiogenic factors and RAGE ligands are unexplored. METHODS: To assess the relationship between a soil-transmitted helminth, Strongyloides stercoralis (Ss), and T2DM, we measured plasma levels of vascular endothelial growth factor (VEGF)-A, -C, and -D; angiopoietins 1 and 2 (Ang-1 and Ang-2); and their receptors VEGF-R1, -R2, and -R3 as well as soluble RAGE (sRAGE) and their ligands advanced glycation end products (AGEs), S100A12, and high mobility group box 1 (HMGB-1) in individuals with T2DM with or those without Ss infection. In Ss-infected individuals, we also measured the levels of aforementioned factors 6 months following anthelmintic therapy. RESULTS: Ss-infected individuals exhibited significantly decreased levels of VEGF-A, VEGF-C, VEGF-D, Ang-1, and Ang-2 and their soluble receptors VEGF-R1, -R2, and -R3, that increased following anthelmintic therapy. Likewise, Ss-infected individuals exhibited significantly decreased levels of AGEs and their ligands sRAGE, S100A12, and HMGB-1, which reversed following anthelmintic therapy. CONCLUSIONS: Our data suggest that Ss infection could play a beneficial role by limiting or delaying T2DM-related vascular complications.

Coexistent Helminth Infection-Mediated Modulation of Chemokine Responses in Latent Tuberculosis.

Coexistent helminth infections are known to modulate T cell and cytokine responses in latent infection with Mycobacterium tuberculosis However, their role in modulating chemokine responses in latent tuberculosis (LTB) has not been explored. Because chemokines play a vital role in the protective immune responses in LTB, we postulated that coexistent helminth infection could modulate chemokine production in helminth-LTB coinfection. To test this, we measured the levels of a panel of CC and CXC chemokines at baseline and following mycobacterial Ag or mitogen stimulation in individuals with LTB with (Strongyloides stercoralis +LTB+) or without S. stercoralis (S. stercoralis -LTB+) infection and in individuals without both infections, healthy controls (HC). At baseline (in the absence of a stimulus), S. stercoralis +LTB+ individuals exhibited significantly diminished production of CCL1, CCL2, CCL4, CCL11, CXCL9, CXCL10, and CXCL11 in comparison with S. stercoralis -LTB+ and/or HC individuals. Upon mycobacterial Ag stimulation, S. stercoralis +LTB+ individuals exhibited significantly diminished production of CCL1, CCL2, CCL4, CCL11, CXCL2, CXCL9, and CXCL10 in comparison with S. stercoralis -LTB+ and/or HC individuals. No differences were observed upon mitogen stimulation. Finally, after anthelmintic treatment, the baseline levels of CCL1, CCL2, CCL4, CCL11, and CXCL11 and mycobacterial Ag-stimulated levels of CCL1, CCL2, CCL11, CXCL2, and CXCL10 were significantly increased in S. stercoralis +LTB+ individuals. Thus, our data demonstrate that S. stercoralis +LTB+ individuals are associated with a compromised ability to express both CC and CXC chemokines and that this defect is at least partially reversible upon treatment. Hence, coexistent helminth infection induces downmodulation of chemokine responses in LTB individuals with likely potential effects on tuberculosis pathogenesis.

Impact of malnutrition on systemic immune and metabolic profiles in type 2 diabetes.

BACKGROUND: While obesity and overweight status are firmly established risk factors for Type 2 diabetes mellitus (T2DM), a substantial proportion of diabetic individuals, especially in Africa and Asia, are often underweight or normal weight. However, very little is known about the immunological and metabolic profiles of these individuals. METHODS: This study aimed to assess the relationship between malnutrition and Type 2 diabetes mellitus (T2DM). We examined a variety of analytes associated with the immunological and metabolic profiles of T2DM individuals with low (< 18.5 kg/m2) or normal (18.5-24.9 kg/m2) body mass index (BMI). To this end, we measured plasma levels of HbA1c, glucose, insulin, glucagon, adipocytokines and Type 1, Type 2, Type 17, pro-inflammatory and regulatory cytokines in T2DM individuals with low BMI (LBMI) or normal BMI (NBMI) with small sample size n = 44 in each group. RESULTS: LBMI individuals exhibited significantly higher levels of HbA1c, random blood glucose, insulin and glucagon compared to NBMI individuals. Similarly, LBMI individuals exhibited significantly higher levels of adiponectin and adipsin and significantly lower levels of leptin in comparison to NBMI individuals. LBMI individuals also exhibited significantly lower levels of the Type 1, Type 2, Type 17, pro-inflammatory and regulatory cytokines in comparison to NBMI individuals. Finally, while the metabolic parameters exhibited a significant negative correlation with BMI, the immunological parameters exhibited a significant positive correlation with BMI. CONCLUSIONS: Malnutrition is associated with a significant modulation of glycemic, hormonal and cytokine parameters in T2DM. Hence, the biochemical and immunological profiles of T2DM is significantly influenced by BMI.

Cytotoxic T-Lymphocyte-Associated Antigen 4 (CTLA-4)- and Programmed Death 1 (PD-1)-Mediated Regulation of Monofunctional and Dual Functional CD4+ and CD8+ T-Cell Responses in a Chronic Helminth Infection.

Chronic helminth infections are known to be associated with the modulation of antigen-specific T-cell responses. Strongyloides stercoralis infection is characterized by the downmodulation of antigen-specific Th1 and Th17 responses and the upregulation of Th2 and Th9 responses. Immune homeostasis is partially maintained by negative regulators of T-cell activation, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1), which dampen effector responses during chronic infections. However, their roles in S. stercoralis infection are yet to be defined. Therefore, we sought to determine the role of CTLA-4 and PD-1 in regulating CD4+ and CD8+ T-cell responses and examined the frequencies of monofunctional and dual functional Th1/T cytotoxic type 1 (Tc1), Th17/Tc17, Th2/Tc2, and Th9/Tc9 cells in S. stercoralis infection in 15 infected individuals stimulated with parasite antigen following CTLA-4 or PD-1 blockade. Our data reveal that CTLA-4 or PD-1 blockade results in significantly enhanced frequencies of monofunctional and dual functional Th1/Tc1 and Th17/Tc17 cells and, in contrast, diminishes the frequencies of monofunctional and dual functional Th2/Tc2 and Th9/Tc9 cells with parasite antigen stimulation in whole-blood cultures. Thus, we demonstrate that CTLA-4 and PD-1 limit the induction of particular T-cell subsets in S. stercoralis infection, which suggests the importance of CTLA-4 and PD-1 in immune modulation in a chronic helminth infection.

Metabolic Consequences of Concomitant Strongyloides stercoralis Infection in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Human and animal studies have demonstrated that helminth infections are associated with a decreased prevalence of type 2 diabetes mellitus (T2DM). However, very little is known about their biochemical and immunological interactions. METHODS: To assess the relationship between a soil-transmitted helminth, Strongyloides stercoralis (Ss), and T2DM, we examined analytes associated with glycemic control, metabolic processes, and T-cell-driven inflammation at the time of Ss diagnosis and 6 months after definitive anthelmintic treatment. We measured plasma levels of hemoglobin A1c, glucose, insulin, glucagon, adipocytokines, and T-helper (TH) 1-, 2-, and 17- associated cytokines in patients with T2DM with (INF group) or without (UN group) Ss infection. In INF individuals, we again assessed the levels of these analytes 6 months following anthelmintic treatment. RESULTS: Compared to UN individuals, INF individuals exhibited significantly diminished levels of insulin and glucagon that increased significantly following therapy. Similarly, INF individuals exhibited significantly diminished levels of adiponectin and adipsin that reversed following therapy. INF individuals also exhibited significantly decreased levels of the TH1- and TH17- associated cytokines in comparison to UN individuals; again, anthelmintic therapy augmented these levels. As expected, INF individuals had elevated levels of TH2-associated and regulatory cytokines that normalized following definitive therapy. Multivariate analysis revealed that these changes were independent of age, sex, body mass index, and liver and renal function. CONCLUSIONS: Strongyloides stercoralis infection is associated with a significant modulation of glycemic, hormonal, and cytokine parameters in T2DM and its reversal following anthelmintic therapy. Hence, Ss infection has a protective effect on diabetes-related parameters.

Microbial Translocation Associated with an Acute-Phase Response and Elevations in MMP-1, HO-1, and Proinflammatory Cytokines in Strongyloides stercoralis Infection.

Microbial translocation, characterized by elevated levels of lipopolysaccharide (LPS) and related markers, is a common occurrence in HIV and some parasitic infections. This is usually associated with extensive inflammation and immune activation. To examine the occurrence of microbial translocation and the associated inflammatory response in asymptomatic Strongyloides stercoralis infection, we measured the plasma levels of LPS and other microbial translocation markers, acute-phase proteins, inflammatory markers, and proinflammatory cytokines in individuals with (infected [INF]) or without (uninfected [UN]) S. stercoralis infections. Finally, we also measured the levels of all of these markers in INF individuals following treatment of S. stercoralis infection. We show that INF individuals exhibit significantly higher plasma levels of microbial translocation markers (LPS, soluble CD14 [sCD14], intestinal fatty acid-binding protein [iFABP], and endotoxin core IgG antibody [EndoCAb]), acute-phase proteins (α-2 macroglobulin [α-2M], C-reactive protein [CRP], haptoglobin, and serum amyloid protein A [SAA]), inflammatory markers (matrix metalloproteinase 1 [MMP-1] and heme oxygenase 1 [HO-1]), and proinflammatory cytokines (interleukin-6 [IL-6], IL-8, monocyte chemoattractant protein 1 [MCP-1], and IL-1ß) than do UN individuals. INF individuals exhibit significantly decreased levels of tissue inhibitor of metalloproteinases 4 (TIMP-4). Following treatment of S. stercoralis infection, the elevated levels of microbial translocation markers, acute-phase proteins, and inflammatory markers were all diminished. Our data thus show that S. stercoralis infection is characterized by microbial translocation and accompanying increases in levels of acute-phase proteins and markers of inflammation and provide data to suggest that microbial translocation is a feature of asymptomatic S. stercoralis infection and is associated with an inflammatory response.

Elucidating systemic immune responses to acute and convalescent SARS-CoV-2 infection in children and elderly individuals.

BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), a causative pathogen of the COVID-19 pandemic, affects all age groups. However, various studies have shown that COVID-19 presentation and severity vary considerably with age. We, therefore, wanted to examine the differences between the immune responses of children with COVID-19 and elderly COVID-19 individuals. METHODS: We analyzed cytokines, chemokines, growth factors, and acute phase proteins in acute and convalescent COVID-19 children and the elderly with acute and convalescent COVID-19. RESULTS: We show that most of the pro-inflammatory cytokines (interferon [IFN]γ, interleukin [IL]-2, tumor necrosis factor-α [TNFα], IL-1α, IFNα, IFNß, IL-6, IL-12, IL-3, IL-7, IL-1Ra, IL-13, and IL-10), chemokines (CCL4, CCL11, CCL19, CXCL1, CXCL2, CXCL8, and CXL10), growth factors (vascular endothelial growth factor and CD40L) and acute phase proteins (C-reactive protein, serum amyloid P, and haptoglobin) were decreased in children with acute COVID 19 as compared with elderly individuals. In contrast, children with acute COVID-19 exhibited elevated levels of cytokines- IL-1ß, IL-33, IL-4, IL-5, and IL-25, growth factors-fibroblast growth factor-2, platelet- derived growth factors-BB, and transforming growth factorα as compared with elderly individuals. Similar, differences were manifest in children and elderly with convalescent COVID-19. CONCLUSION: Thus, COVID-19 children are characterized by distinct cytokine/chemokine/growth factor/acute phase protein markers that are markedly different from elderly COVID-19 individuals.

Impact of Strongyloides stercoralis infection on complement activation in Type 2 diabetes mellitus: Insights from a clinical and anthelmintic intervention study.

BACKGROUND: Numerous studies indicate a potential protective role of helminths in diabetes mellitus (DM) progression. The complement system, vital for host defense, plays a crucial role in tissue homeostasis and immune surveillance. Dysregulated complement activation is implicated in diabetic complications. We aimed to investigate the influence of the helminth, Strongyloides stercoralis (Ss) on complement activation in individuals with type 2 DM (T2D). METHODOLOGY: We assessed circulating levels of complement proteins (C1q, C2, C3, C4, C4b, C5, C5a, and MBL (Lectin)) and their regulatory components (Factor B, Factor D, Factor H, and Factor I) in individuals with T2D with (n = 60) or without concomitant Ss infection (n = 58). Additionally, we evaluated the impact of anthelmintic therapy on these parameters after 6 months in Ss-infected individuals (n = 60). RESULTS: Ss+DM+ individuals demonstrated reduced levels of complement proteins (C1q, C4b, MBL (Lectin), C3, C5a, and C3b/iC3b) and complement regulatory proteins (Factor B and Factor D) compared to Ss-DM+ individuals. Following anthelmintic therapy, there was a partial reversal of these levels in Ss+DM+ individuals. CONCLUSION: Our findings indicate that Ss infection reduces complement activation, potentially mitigating inflammatory processes in individuals with T2D. The study underscores the complex interplay between helminth infections, complement regulation, and diabetes mellitus, offering insights into potential therapeutic avenues.

Relative contribution of biomedical, demographic, and socioeconomic factors to COVID-19 vaccine receipt in rural India.

BACKGROUND: In the first year of roll-out, vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevented almost 20 million deaths from coronavirus disease 2019 (COVID-19). Yet, little is known about the factors influencing access to vaccination at the individual level within rural poor settings of low-income countries. The aim of this study was to examine determinants of vaccine receipt in rural India. METHODS: A census of a rural village in Tamil Nadu was undertaken from June 2021 to September 2022. We surveyed 775 participants from 262 households. Household-level data on socioeconomic status (SES), water, sanitation, and hygiene practices, and individual-level demographic information, travel history, and biomedical data, including anthropometry, vital signs, and comorbidities, were collected. Logistic regression models with 5-fold cross-validation were used to identify the biomedical, demographic, and socioeconomic determinants of vaccine receipt and the timing of receipt within the first 30 days of eligibility. Vaccine ineligible participants were excluded leaving 659 eligible participants. There were 650 eligible participants with complete biomedical, demographic, and socioeconomic data. RESULTS: There were 68.0% and 34.0% of individuals (N = 650) who had received one and two vaccine doses, respectively. Participants with household ownership of a permanent account number (PAN) or ration card were 2.15 (95% CI:1.32-3.52) or 3.02 (95% CI:1.72-5.29) times more likely to receive at least one vaccine dose compared to households with no ownership of such cards. Participants employed as housewives or self-employed non-agricultural workers were 65% (95% CI:0.19-0.67) or 59% (95% CI:0.22-0.76) less likely to receive at least one vaccine dose compared to salaried workers. Household PAN card ownership, occupation and age were linked to the timing of vaccine receipt. Participants aged ≤18 and 45-60 years were 17.74 (95% CI:5.07-62.03) and 5.51 (95% CI:2.74-11.10) times more likely to receive a vaccine within 30 days of eligibility compared to 19-44-year-olds. Biomedical factors including BMI, vital signs, comorbidities, and COVID-19 specific symptoms were not consistently associated with vaccine receipt or timing of receipt. No support was found that travel history, contact with COVID-19 cases, and hospital admissions influenced vaccine receipt or timing of receipt. CONCLUSION: Factors linked to SES were linked to vaccine receipt, more so than biomedical factors which were targeted by vaccine policies. Future research should explore if government interventions including vaccine mandates, barriers to vaccine access, or peer influence linked to workplace or targeted vaccine promotion campaigns underpin these findings.

Sex-specific differences in systemic immune responses in MIS-C children.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare manifestation of Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) infection that can result in increased morbidity and mortality. Mounting evidence describes sex disparities in the clinical outcomes of coronavirus disease 2019 (COVID-19). However, there is a lack of information on sex-specific differences in immune responses in MIS-C. This study is an observational and cross-sectional study and we wanted to examine immune parameters such as cytokines, chemokines, acute phase proteins (APPs), growth factors, microbial translocation markers (MTMs), complement components and matrix metalloproteinases (MMPs) in MIS-C children, based on sex. Male children were associated with heightened levels of pro-inflammatory cytokines-IFNγ, IL-2, TNFα, IL-1α, IL-1ß, IL-6, IL-12, G-CSF and GM-CSF, chemokines-CCL2, CCL11, CXCL1, CXCL8 and CXCL10, acute phase proteins-α-2M, CRP, growth factors VEGF and TGFα, microbial translocation markers- iFABP, LBP, EndoCAb, complement components-C1q, MBL and C3 and matrix metalloproteinases MMP-8 and MMP-9 compared to female children with MIS-C. These results indicate that the heightened immune response in males is a characteristic feature of MIS-C. These findings might explain the differential disease pathogenesis in males compared to females with MIS-C and facilitate a deeper understanding of this disease.

Hookworm infection induces glycometabolic modulation in South Indian individuals with type 2 diabetes.

Objectives: A number of epidemiological studies have demonstrated that there is an inverse relationship between helminth infections and diabetes mellitus, suggesting that helminth infection may have a positive effect on type 2 diabetes mellitus (T2DM). However, the association between hookworm infection and T2DM has barely been studied. Hence, we aimed to investigate and analyze the interaction and association between hookworm infection and T2DM. Methods: We examined the effect of hookworm infection on biochemical parameters, including plasma random blood glucose, glycated hemoglobin, and the plasma levels of pancreatic hormones, incretins, and adipokines in individuals with T2DM with (INF, n = 35) or without (UN, n = 35) hookworm infection. Moreover, we re-evaluated these analyte concentrations in a subset of INF individuals 6 months following anthelmintic therapy. Results: Compared to UN individuals, INF individuals had significantly lowered levels of random blood glucose and glycated hemoglobin. INF individuals also exhibited significantly diminished levels of adiponectin, adipsin, C-peptide, insulin, and glucagon compared to UN individuals. In contrast, INF individuals displayed substantially elevated levels of visfatin and incretins compared to UN individuals. Interestingly, this effect was not seen following anthelmintic treatment. Conclusion: Our study findings indicate that concomitant hookworm infection exerts a beneficial effect on glycometabolic parameters in T2DM.

BCG vaccination induces enhanced humoral responses in elderly individuals.

BACKGROUND: Studies have reported the beneficial effects of Bacillus Calmette Guerin (BCG) vaccination, including non-specific cross-protection against other infectious diseases. METHODS: We investigated the impact of BCG vaccination on the frequencies of B cell subsets as well as total antibody levels in healthy elderly individuals at one month post vaccination. We also compared the above-mentioned parameters in post-vaccinated individuals to unvaccinated controls. RESULTS: Our results demonstrate that BCG vaccination induced enhanced frequencies of immature, classical and activated memory B cells and plasma cells and diminished frequencies of naïve and atypical memory B cells. BCG vaccination induced significantly increased levels of total IgG subclass isotypes compared to baseline. Similarly, all of the above parameters were significantly higher in vaccinated individuals compared to unvaccinated controls. CONCLUSION: BCG vaccination was associated with enhanced B cell subsets, suggesting its potential utility by enhancing heterologous immunity.

Cytokine upsurge among drug-resistant tuberculosis endorse the signatures of hyper inflammation and disease severity.

Tuberculosis (TB) elimination is possible with the discovery of accurate biomarkers that define the stages of infection. Drug-resistant TB impair the current treatment strategies and worsen the unfavourable outcomes. The knowledge on host immune responses between drug-sensitive and drug-resistant infection is inadequate to understand the pathophysiological differences and disease severity. The secreted proteins, cytokines display versatile behaviour upon infection with Mycobacterium tuberculosis (MTB) and their imbalances often tend to assist disease pathology than protection. Therefore, studying these soluble proteins across TB infection spectrum (drug-resistant TB, drug-sensitive TB, and latent TB) may unveil the disease mediated responses and unique stage specific cytokine signatures. Thus, we sought to determine the plasma cytokine levels from healthy, latently infected, drug-sensitive, and drug-resistant TB individuals. Our study revealed top 8 cytokines (IL-17, IL-1α, IL-2, IL-10, IL-5, IFN-γ, TNF-α and IL-6) and their biomarker abilities to discriminate different stages of infection.