Charles Chinedum Onyenekwe

Modulation of the immune response to Mycobacterium tuberculosis during Malaria/M. tuberculosis co‐infection

Tuberculosis (TB) causes significant morbidity and mortality on a global scale. The African region has 24% of the worlds TB cases. TB overlaps with other infectious diseases such as malaria and HIV, which are also highly prevalent in the African region. TB is a leading cause of death among HIV‐positive patients and co‐infection with HIV and TB has been described as a syndemic. In view of the overlapping epidemiology of these diseases, it is important to understand the dynamics of the immune response to TB in the context of co‐infection. We investigated the cytokine response to purified protein derivative (PPD) in peripheral blood mononuclear cells from TB patients co‐infected with HIV or malaria and compared it to that of malaria‐ and HIV‐free TB patients. A total of 231 subjects were recruited for this study and classified into six groups; untreated TB‐positive, TB positive subjects on TB drugs, TB‐ and HIV‐positive, TB‐ and malaria‐positive, latent TB and apparently healthy control subjects. Our results demonstrate maintenance of interferon (IFN)‐γ production in HIV and malaria co‐infected TB patients in spite of lower CD4 counts in the HIV‐infected cohort. Malaria co‐infection caused an increase in the production of the T helper type 2 (Th2)‐associated cytokine interleukin (IL)‐4 and the anti‐inflammatory cytokine IL‐10 in PPD‐stimulated cultures. These results suggest that malaria co‐infection diverts immune response against M. tuberculosis towards a Th‐2/anti‐inflammatory response which might have important consequences for disease progression.

Evaluation of some haemostatic parameters in falciparum malaria and HIV co-infection

Abstract Background: Studies from sub-Saharan Africa where malaria is endemic have observed high incidences of malaria and HIV co-infection. It has long been accepted that malaria causes alterations in haemostatic parameters and that HIV is associated with a wide range of haematological changes. We assessed the effect of the overlap of these infections on routine haemostatic parameters. Method: The study involved 337 subjects grouped according to their HIV and malaria status: Group 1 ‘Asymptomatic HIV seropositive, Plasmodium falciparum positive’ (n = 61); Group 2 ‘Asymptomatic HIV seropositive, P. falciparum negative’ (n = 73); Group 3 ‘Symptomatic HIV seropositive, P. falciparum positive’ (n = 49); Group 4 ‘Symptomatic HIV positive P. falciparum negative’ (n = 56); Group 5 ‘Control HIV negative, P. falciparum positive’ (n = 52) and Group 6 ‘Control HIV negative, P. falciparum negative’ (n = 46). Blood samples were taken for HIV testing, diagnosis of falciparum malaria and malaria parasite density counts. Citrated samples were used within one hour of collection for prothrombin time (PT) and activated partial thromboplastin time (APTT). CD4+ T cell counts, platelet count and haematocrit (Hct) were also performed. Results: Our results demonstrate greater alterations in APTT, PT and platelet count with prolongation of APTT, PT and lower platelet counts in HIV and malaria co-infection. In spite of this, the co-infected subjects with mild to moderate parasitaemia did not show a bleeding tendency; however, the risk is higher in severe malaria. Conclusion: These results suggest that co-infected subjects with severe malaria have a higher risk of bleeding and would require greater monitoring.

Assessment of Serum Prostate Specific Antigen, Some Renal Indices and Uric Acid Levels in Subjects with Benign Prostatic Hyperplasia at Lokoja, Nigeria

Background: Prostate disorders (prostatitis, BPH and Pca) can contribute to renal impairment. Benign prostatic hyperplasia (BPH) and renal impairment (RI) such as chronic kidney disease are important public health problems in older men. The present study aimed to assess serum levels of prostate specific antigen, urea, creatinine, protein and uric acids in subjects with BPH at Federal Medical Center, Lokoja, Kogi State, Nigeria. A population-based sample of one hundred and ten (110) men aged (51-70) years were conveniently recruited and divided into three groups designation A= BPH with RI, (n=35) B=BPH without RI, (n=35) and C=Control, (n=40). Methods: Blood samples were collected from all the participants and serum separated and stored at -20˚C until analyzed for prostate specific antigen using Enzyme Linked Immunosorbent Assay (ELISA) and colorimetric assay method for creatinine, urea, protein and uric acid. Data were analyzed using SPSS software application (version 17.0). Pearson correlation and Receiving Operating Characteristics of the groups were done. Results: The result showed that urea and creatinine levels were significantly higher in BPH subjects with or without renal impairment when compared with controls (p<0.05 respectively). Similarly, total prostate specific antigen (tPSA), free prostate specific antigen (fPSA), complex prostate specific antigen (cPSA) and percent free prostate specific antigen (%fPSA) were significantly higher in BPH subjects with or without RI when compared with controls (p<0.05 respectively). Urea, creatinine and uric acid were significantly higher while total protein was significantly lower in BPH with RI when compared with BPH without RI (p<0.05 respectively). Conclusion: The significantly higher urea, creatinine and uric acid levels in BPH subjects showed that BPH subjects with RI may have decrease excretion and accumulation of uric acid by the kidney suggesting possible risk of progression to CKD while BPH subjects without RI tends to be more prone to developing renal dysfunction. The significant correlation between %fPSA, creatinine and urea shows an association between BPH and renal diseases. Using receiving operating characteristic (ROC) curves to assess diagnostic performance of various parameters in various groups for the prediction of BPH with or without renal disease, there was evidence that fPSA and %fPSA have higher predictive value in the diagnosis of BPH while uric acid, urea, creatinine and protein have higher predictive value in the diagnosis of renal disease. It is therefore, recommended that people with prostate disorders should be screened for renal diseases and vice versa.

Persistent Circulating Immune Complexes: Potential Source of Epimutation and Cancer Poor Prognosis

Estimation of serum level of circulating immune complexes and its use for monitoring treatments have been carried out extensively in various disease conditions including autoimmune diseases and cancer, but little or no work has considered persistent circulation of immune complexes consequent to physiological anomalies that could mediate epimutation and subsequent epigenetic cell alteration and tumourigenesis. This review looked into the immuno-physiological activities of circulating immune complexes to expose its possible epigenomic consequences and potential role in epimutation. The environmental link between epigenetic cell alteration and formation of circulating immune complexes makes this review a unique one but on the other hand, gives room for concern. Immune complexes have strong capacity to stimulate various immune responses, yet the immunological activities of these circulating immune complexes are over looked or under estimated. Immune complexes is a normal immunological phenomenon but its persistence and subsequent deposition could induce endogenous assaults that would continuously and adversely perturb the epigenomic activities by fuelling chronic inflammation, activating transcription factors (NFkB), generation of reactive oxygen species (ROS) and frequent release of cytokines leading to epigenetic cell alteration especially in developing countries where environmental pollution is a serious factor.

Assessment of DNA methylation patterns in breast tumours and apparently healthy subjects in Anambra state, Nigeria

Epigenetic cell alteration is an environmentally induced epimutation that could lead to tumourigenesis. Thus we considered its assessment to be of utmost importance in regional areas with serious environmental challenges such as Nigeria with respect to increasing rate of breast tumours. Fasting blood sample was collected from 24 subjects with benign breast tumour, 25 subjects with malignant breast tumour and 50 apparently healthy control subjects, for cell free DNA extraction. The DNA was subjected to epigenomic tests to determine the methylation patterns using Enzyme Linked Immuno-Assay (colorimetric) method (Epigentek USA). Significant association between tumors and Demethylation (hypomethylated DNA and Unmethylated DNA) was observed (X2= P=0.000); also significant association between tumors and hypermethylation was observed (X2= P=0.014). Up to 10(20%) out of the 50 apparently healthy control subjects were demethylated. Increased expression of aberrant DNA Methylation was observed in late stages of breast malignant tumour. Epigenomic Cell alteration is indicated to be a significant influential risk factor to breast tumourigenesis, and of significant increase in this locality. Therefore, being an abnormal genomic development, its detection in apparently healthy subjects, is an indicator for intrinsic genomic alteration and could be a marker for development of tumour micro-environment if not tumourigenesis, thus could be used for early detection of tumourigenesis even earlier than physical breast examination.

Possible Changes in Maternal Plasma Cortisol, AdrenocorticotropicHormones, Pregnancy Associated Plasma Protein-A and Alpha-fetoproteinin HIV Pregnant Women at NAUTH Nnewi, Nigeria

Background: There is limited information on if HIV infection induces stress in pregnancy. HIV can possibly contribute to the alterations in some fetal viability hormones thereby lead to adverse pregnancy outcome. The present study aimed to assess the possible changes in maternal cortisol, Adrenocorticotropic (ACTH), Pregnancy associated plasma protein-A (PAPP-A) and alpha-fetoprotein (AFP) hormone concentrations in HIV-infected pregnant women and their pregnancy outcomes. Methods: A cross sectional study of 80 (Eighty) volunteer pregnant women aged (18-49) years recruited during routine antenatal clinics in Nnamdi Azikiwe Teaching Hospital, Nnewi, Anambra State, Nigeria was conducted. The participants were divided into groups: 40 (forty) apparently healthy pregnant and 40 (forty) HIV-infected pregnant women. 5 ml of morning blood samples were collected from each subject in their 1st and 2nd trimesters for estimation of Cortisol, ACTH, AFP and PAPP-A using ELISA method. Results: The result showed that the mean systolic and diastolic blood pressures (mmHg) of HIV pregnant women were significantly higher than control (p<0.05 respectively). The mean value of cortisol (ng/ml) in HIV pregnant women was significantly higher when compared with control subjects (p<0.05). Cortisol showed inverse significant correlation with AFP in HIV-infected pregnant women. Maternal outcomes showed thatt HIV-infected pregnant women had significantly higher incidence of miscarriages and preeclampsia with higher incidence of perinatal outcomes such as low birth weight babies (LBW), preterm delivery, spontaneous abortion, still birth and low Apgar scores when compared with apparently normal pregnant women (P<0.05 respectively). Conclusion: the significantly higher cortisol level and BP in HIV pregnant women is indicative of oxidative stress due to perceived stress by HIV infection which might predispose the affected women to hypertension and preeclampsia. The highest adverse reactions observed in HIV pregnant women might be related to the damaged immune system by HIV infection however, the placental defect associated with increased placental permeability to AFP and the activity of the insulin-like growth factor (IGF) system is not related to the activity of stress thereby do not influence their birth outcomes.