A Retrospective Comparative Analysis of Use and Rate of Compliance of Hydroxyurea in Sickle Cell Disease Patients at University of Maryland and Barau Dikko Teaching Hospital/Kaduna State University Kaduna, Nigeria: A Global Health Prospective of Sickle Cell Disease Care

Background: Countries of Sub-Saharan Africa, middle east and subcontinent region bear the greatest burden of SCD-associated morbidity and mortality. Hydroxyurea (HU) reduces up to 50% of hospitalizations and blood transfusion rate associated with SCD. HU is being used routinely in high-income countries but still remains a challenge in resource-limited countries. HU is a cost-effective intervention so learning underlying factors associated with HU use can address this problem. There is not any study that compares developing and developed country regarding HU use. There is huge disparity between USA and Nigeria regarding mortality. Hence this study identified factors associated with disparity of care, morbidity & mortality. Methods: Charts of 75 SCD patients treated at UMMC from January 2019 to January 2020 were reviewed. Data of 18 patients who met the eligibility criteria were extracted and charts of 30 patients being treated at Nigerian hospital from same time interval were reviewed and extracted. To identify disparity of care, and difference in morbidity and mortality rate, data were collected regarding heart failure, pain crisis, hospitalization, stroke, HU compliance and acute chest syndrome (ACS). Results: Factors associated with low compliance in USA is treatment none-adherence and insurance issues, whereas in the Nigerian hospital is financial constraints and hydroxyurea availability. Regarding disparity of care, none of the Nigerian patients had any Hemoglobin F, Hemoglobin S percentage documentation, because a diagnosis of SCD is based on alkaline electrophoresis which does not quantify the hemoglobin type. Therefore, the phenotype in Nigerian cohort were not identified. In USA cohort all the patients had HbF percentage tested by high performance liquid chromatography (HPLC) prior to starting HU. There is no significant difference in compliance rate ((Nig 67% VS US 78% P value 0.52). Three patients in Nigerian cohort died prior to age of 35 but none in USA cohort. Fisher exact and chi square tests were used for analysis. P value of all the parameters is >0.05 except the ACS which is 0.0036. Hence findings are not statistically significant except ACS (75% US VS 18% P 0.0036). Conclusion: Sample size is small. Hence it is difficult to make conclusion but, data is showing that there is disparity in terms of mortality, morbidity, health care services (e.g., lab test, blood transfusion resources, screening test) and use of HU between these two counties

CD8+ T cell-mediated control of distant tumours following local photodynamic therapy is independent of CD4+ T cells and dependent on natural killer cells

Cancer survival rates decrease in the presence of disseminated disease. However, there are few therapies that are effective at eliminating the primary tumour while providing control of distant stage disease. Photodynamic therapy (PDT) is an FDA-approved modality that rapidly eliminates local tumours, resulting in cure of early disease and palliation of advanced disease. Numerous pre-clinical studies have shown that local PDT treatment of tumours enhances anti-tumour immunity. We hypothesised that enhancement of a systemic anti-tumour immune response might control the growth of tumours present outside the treatment field. To test this hypothesis we delivered PDT to subcutaneous (s.c.) tumours of mice bearing both s.c. and lung tumours and monitored the growth of the untreated lung tumours. Our results demonstrate that PDT of murine tumours provided durable inhibition of the growth of untreated lung tumours. The inhibition of the growth of tumours outside the treatment field was tumour-specific and dependent on the presence of CD8+ T cells. This inhibition was accompanied by an increase in splenic anti-tumour cytolytic activity and by an increase in CD8+ T cell infiltration into untreated tumours. Local PDT treatment led to enhanced anti-tumour immune memory that was evident 40 days after tumour treatment and was independent of CD4+ T cells. CD8+ T cell control of the growth of lung tumours present outside the treatment field following PDT was dependent upon the presence of natural killer (NK) cells. These results suggest that local PDT treatment of tumours lead to induction of an anti-tumour immune response capable of controlling the growth of tumours outside the treatment field and indicate that this modality has potential in the treatment of distant stage disease

Intratumoral IL-12 and TNF-α–Loaded Microspheres Lead To Regression of Breast Cancer and Systemic Antitumor Immunity

Background: Local, sustained delivery of cytokines at a tumor can enhance induction of antitumor immunity and may be a feasible neoadjuvant immunotherapy for breast cancer. We evaluated the ability of intratumoral poly-lactic-acid-encapsulated microspheres (PLAM) containing interleukin 12 (IL-12), tumor necrosis factor α (TNF-α), and granulocyte-macrophage colony stimulating factor (GM-CSF) in a murine model of breast cancer to generate a specific antitumor response.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41401/1/10434_2004_Article_147.pd

Selective functional deficit in dendritic cell - T cell interaction is a crucial mechanism in chronic hepatitis B virus infection

A defect in specific T cell immunity has long been assumed to be the central mechanism of persistent Hepatitis B virus (HBV) infection. Recent studies on HBV transgenic mice have suggested, however, that functional deficit of dendritic cells (DC) was an underlying cause for the T cell dysfunction. The functions of monocyte-derived DC were determined by studying 75 subjects that included chronic hepatitis B patients with low or high HBV load; antibody to hepatitis B surface antigen (anti-HBs) positive individuals who had recovered completely from previous acute HBV infection; healthy donors who had received hepatitis B vaccination and were anti-HBs positive; and immunologically naïve to HBV or the vaccine individual. Impaired interactions between monocyte-derived DC and T cells were shown in chronic HBV infection patients, especially in those with active virus replication. The dysfunctions included: (i) failure of DC to increase human leukocyte antigen (HLA-II), B7 expression and interleukin-12 secretion in responses to hepatitis B surface antigen (HBsAg), (ii) defective induction of T cell proliferative response to HBsAg, (iii) failure to activate T cells to produce cytokines and (iv) deficit in the induction of antigen specific cytotoxic T lymphocytes (CTLs). In vitro treatment of DC with tumour necrosis factor-α improved HLA-II and B7 expression, as well as Th cell and CTL responses. It is concluded that defective DC-T cell interactions may account for the specific T cell immune defects in chronic HBV infection. Immunotherapy that aims at restoring DC functions could offer a new opportunity for effectively managing persistent HBV infections.link_to_subscribed_fulltex

Effect of Malnutrition on the Expression of Cytokines Involved in Th1 Cell Differentiation

Malnutrition is a common cause of secondary immune deficiency and has been linked to an increased susceptibility to infection in humans. Malnutrition specifically affects T-cell-mediated immune responses. The aim of this study was to assess in lymphocytes from malnourished children the expression levels of IL-12, IL-18 and IL-21, molecules that induce the differentiation of T cells related to the immunological cellular response (Th1 response) and the production of cytokines related to the immunological cellular response (Th1 cytokines). We found that the expression levels of IL-12, IL-18 and IL-21 were significantly diminished in malnourished children compared to well-nourished children and were coincident with lower plasmatic levels of IL-2 and IFN-γ (Th1 cytokines). In this study, we show for the first time that the gene expression and intracellular production of cytokines responsible for Th1 cell differentiation (IL-12, IL-18 and IL-21) are diminished in malnourished children. As expected, this finding was related to lower plasmatic levels of IL-2 and IFN-γ. The decreased expression of Th1 cytokines observed in this study may contribute to the deterioration of the immunological Type 1 (cellular) response. We hypothesize that the decreased production of IL-12, IL-18 and IL-21 in malnourished children contributes to their inability to eradicate infections