Investigation of serum level relationship of pro-inflammatory and anti-inflammatory cytokines with vitamin D among healthy Ghanaian population.

BACKGROUND: The interplay between vitamin D status and inflammatory cytokines in a supposedly sufficient sunshine environment has not well been evaluated. The study sought to determine their association. METHODS: This cross-sectional study involved 500 healthy adult blood donors from some selected hospitals in Ghana enrolled from June to November 2016. Venous blood samples were obtained from participants, 25(OH)D, TNF-alpha, IFN-gamma, and IL 10 were measured using enzyme linked immunosorbent assay (ELISA) technique. Serum levels of 25(OH)D < 20ng/ml were classified as being deficient or low. RESULTS: The average age of the participants was 27.97 years. No statistically significant association was established between 25(OH) D status, mean age (p = 0.1693), and gender (p = 0.5461) of study participants. Similarly, the median 25(OH) D (p = 0.8392), IL-10 (p = 0.5355), TNF-alpha (p = 0.9740), and IFN-gamma (p = 0.6908) were not significantly different across gender. There was a significantly increased levels of TNF-alpha (p < 0.0001) and IFN-gamma (p < 0.0001) among participants with 25(OH) D deficiency compared to those without deficiency. Concurrently, participants with 25(OH)D deficiency had a significantly reduced levels of IL-10 (p < 0.0001) compared to those without 25 (OH) D deficiency. The most accurate biochemical markers for identifying 25 (OH) D deficiency were IFN-gamma (AUC = 0.879; p < 0.0001) followed by TNF-gamma (AUC = 0.849; p < 0.0001) and IL-10 (AUC = 0.707; p < 0.0001). CONCLUSION: There was a significant association between vitamin D levels and pro-inflammatory cytokines (TNF-alpha, IFN-gamma) and anti-inflammatory cytokine (IL 10) among healthy Ghanaian populace.

Demographic, Clinical Profile of Rheumatoid Arthritis Patients and Their Association with Disease Severity in Ghana.

Background: Rheumatoid arthritis (RA) is one of the frequent chronic, systemic, inflammatory autoimmune disorders with an estimated global prevalence of 1%. RA leads to joint destruction and disability if left untreated. Ghana has seen very few studies on RA, and little is known about the disease's severity and related variables. This study sought to characterize the clinical presentation and determine disease severity and associated risk factors with disease severity among RA patients in a tertiary hospital in Ghana. Methods: This cross-sectional study was conducted between September 2020 and August 2021. This study included 56 consecutively consenting RA patients from the Komfo Anokye Teaching Hospital orthopaedic unit. Diagnosis of RA was based on the updated American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2022 rheumatoid arthritis classification criteria by a rheumatologist. A study questionnaire was used to gather participant demographics and clinical features, and results from the laboratory were taken from the patients' charts and medical records. The patients' disease severity was evaluated based on the rheumatoid arthritis disease activity score, which is based on a 28-joint count (DAS28), and their functioning was evaluated using the modified health assessment questionnaire. Results: The participants' mean age was 51.25 ± 13.22 years. Out of the total participants, 46 were females, and 10 were males (female-to-male ratio 4.6 : 1). Moreover, 37.50% had arthritis of the hand; 5.30% had severe disease, and 94.60% were not severe. A majority (76.80%) were on methotrexate medication. The most frequently involved joints were the knee (42.90%), wrist (32.10%), and elbow (12.50%). There was no statistically significant association with disease severity and a functional status score of >0.5 (cOR: 10.60, 95% CI (0.52-217.30); p = 0.124). In addition, marital status (p = 0.04), disease duration (p = 0.04), family complaints (p = 0.02), and ESR (p = 0.03) were significantly associated with disease severity. Conclusion: RA is predominant among elder populations and females. Disease duration, family complaints, and ESR are associated with disease severity. The findings of this study call for interventions towards ensuring early diagnosis of RA among high-risk populations to enhance good management practices.

Malaria elimination in Ghana: recommendations for reactive case detection strategy implementation in a low endemic area of Asutsuare, Ghana.

BACKGROUND: Progress toward malaria elimination is increasing as many countries near zero indigenous malaria cases. In settings nearing elimination, interventions will be most effective at interrupting transmission when targeted at the residual foci of transmission. These foci may be missed due to asymptomatic infections. To solve this problem, the World Health Organization recommends reactive case detection (RACD). This case study was conducted to identify individuals with asymptomatic malaria, their predisposing risk factors and recommend RACD in Asutsuare, Ghana based on literature review and a cross sectional study. METHODS: The study involved a search on PubMed and Google Scholar of literature published between 1st January, 2009-14th August, 2023 using the search terms "malaria" in "Asutsuare". Furthermore, structured questionnaires were administered to one hundred individuals without symptoms of malaria and screened using rapid diagnostic test (RDT) kits, microscopy and real-time polymerase chain reaction (rt-PCR). Malaria prevalence based on the three diagnostic techniques as well as potential malaria risk factors were assessed through questionnaires in a cross-sectional study. RESULTS: Cumulatively, sixty-four (64) studies (Google Scholar, 57 and PubMed, 7) were reviewed and 22 studies included in the literature on malaria in Asutsuare, Ghana. Significant risk factors were occupation, distance from a house to a waterbody, age group and educational level. Out of the 100 samples, 3 (3%) were positive by RDT, 6 (6%) by microscopy and 9 (9%) by rt-PCR. Ages 5-14.9 years had the highest mean malaria parasite densities of 560 parasites/µl with Plasmodium falciparum as the dominant species in 4 participants. Moreover, in the age group ≥ 15, 2 participants (1 each) harboured P. falciparum and Plasmodium malariae parasites. RDT had a higher sensitivity (76.54%; CI95 66.82-85.54) than rt-PCR (33.33%; CI95 4.33-77.72), while both rt-PCR and RDT were observed to have a higher specificity (92.55; CI95 85.26-96.95) and (97.30; CI95 93.87-99.13), respectively in the diagnosis of malaria. CONCLUSION: In Asutsuare, Ghana, a low endemic area, the elimination of malaria may require finding individuals with asymptomatic infections. Given the low prevalence of asymptomatic individuals identified in this study and as repleted in the literature review, which favours RACD, Asutsuare is a possible setting receptive for RACD implementation.

Evaluating circulating soluble markers of endothelial dysfunction and risk factors associated with PE: A multicentre longitudinal case control study in northern Ghana.

Serpin E1/PAI-1, N-terminal pro-brain natriuretic peptide (NTpro-BNP) and neuropilin-1 are markers which have been associated with endothelial dysfunction. However, data on the levels of these markers in PE is limited. The limited data on the pathophysiology of PE in relation to these markers necessitated the study. This was a multicentre case-control study conducted at the Obstetrics and Gynaecology Department of the Tamale Teaching Hospital, the Bawku Presbyterian Hospital and the Bolgatanga Regional Hospital. Out of 520 consenting pregnant women, 127 pregnant women met the inclusion criteria (53 with PE and 74 controls) and were included in this study. Venous, placental, cord and peripheral blood were collected for biomarker assay, haematological parameters and placental parasite determination. Placental tissue sections were obtained for placental malaria and histopathological lesions associated with hypoperfusion. Maternal heart rate and foetal umbilical artery Doppler impedance indices; resistance index (RI) and systolic diastolic (SD) ratio were determined to confirm utero-placental hypoperfusion. Significantly higher proportions of foeto-maternal complications; eclampsia, low birth weight (LBW), neonatal intensive care unit admissions (NICU), intrauterine growth restriction (IUGR), caesarian deliveries and early gestational age at delivery were associated with PE. Women with PE had lower concentrations of platelet (p = 0.02) whereas red cell distribution width (RDW) was markedly elevated (p = 0.01). NTPro-BNP concentration was markedly elevated (p = 0.01) in women with PE whereas neuropilin-1 concentration was lower (p = 0.03) compared to the non-PE group. Maternal heart rate was elevated in women with PE and Doppler resistance indices (RI and SD) were significantly elevated in foetuses of PE women than foetuses of the controls. Placental mal-perfusion lesions were higher in women with PE compared to the non-PE group. Women with PE had increased risk of adverse foeto-maternal complications, significantly associated with placental mal-perfusion lesions, had reduced platelet concentration and elevated RDW-CV levels. NTPro-BNP, RI and SD are elevated in women with PE whereas neuropilin-1 concentration is reduced. Significant changes in these pathological variables in PE women is indicative of significant derangement in endothelial function culminating in adverse maternal and perinatal outcomes of pregnancy.

Association between endothelial nitric oxide synthase (eNOS) gene variants and nitric oxide production in preeclampsia: a case-control study in Ghana.

Evidence suggests that a major cause of PE is endothelial dysfunction emanating from the reduced bioavailability of Nitric oxide (NO). Variants of endothelial nitric oxide synthase (eNOS) gene may lead to decreased NO levels. We explored the association between eNOS gene variants and nitric oxide levels among preeclamptic women in the Ghanaian population. This case-control study included 75 preeclamptic women and 75 healthy normotensive pregnant women attending antenatal care at the Nkawie-Toase Government Hospital, Ghana. A well-structured questionnaire was used to collect socio-demographic, obstetric and clinical data. Blood was obtained for DNA extraction; the gene variants were determined using PCR and RFLP. Preeclamptic women had significantly lower NO concentration compared to the normotensives (p < 0.0001) and was significantly different between VNTR variants (p < 0.0001). A significant difference in VNTR intron 4 distribution was also observed between the preeclamptic and normotensive women with 4c4c" (12.0%) and "4a4c" (1.3%) genotypes found predominantly in preeclamptic women (p < 0.0001). There was significantly higher distribution of "TC" genotype in preeclamptic women (44.0%) compared to normotensives (22.7%) (p = 0.019). However, possessing "4a4b" (cOR: 0.17, 95% CI 0.04-0.64) and "4b4b" (cOR: 0.09, 95% CI 0.02-0.38) significantly decreased the likelihood of experiencing preeclampsia by 83% and 91% respectively. Nitric oxide is reduced in preeclamptic women. NO levels in preeclampsia are altered by VNTR intron 4 variants but not T786C variants. Possessing VNTR intron 4 "4b" allele decreases the risk of PE while the "4c" allele increases the risk of PE. There is the need for eNOS variant screening and nitric oxide estimation among pregnant women for early prediction of women at risk of preeclampsia.

Thyroid dysfunction and glycaemic control among Type 2 diabetes mellitus patients in Ghana: A comparative cross-sectional study.

INTRODUCTION: Thyroid disorders and diabetes mellitus coexist and are prevalent endocrinopathies among adult population. Thyroid dysfunction contributes to metabolic imbalances, increase beta-cell apoptosis and glucose intolerance. There is paucity of data and contradicting findings on how thyroid dysfunction influence glycaemic control. Therefore, we evaluated thyroid dysfunction and glycaemic control among Type 2 diabetes mellitus (T2DM) patients in Ghana. METHODS: A comparative cross-sectional study was conducted among 192 T2DM patients from Effia Nkwanta Regional Hospital. Three consecutive monthly fasting plasma glucose (FBG) and glycated haemoglobin (HbA1c) were analysed and the results were classified as, moderate hyperglycaemia (MH) (FBG = 6.1-12.0 mmol/L, HbA1c < 7%), severe hyperglycaemia (SH) (FBG ≥ 12.1 mmol/L, HbA1c > 7%) and good glycaemic controls (GC) (FBG = 4.1-6.0 mmol/L, HbA1c < 7%). Thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4), body mass index (BMI) and other clinical parameters were measured. Data analysis was done using R language version 4.0.2 and p < .05 was considered statistically significant. RESULTS: There were no significant differences in age (years) between patients in the various glycaemic groups (p = .9053). The overall prevalence of thyroid disorders was 7.8% among T2DM patients. The prevalence of thyroid disorders was higher in patients with SH (11.7%) followed by those with MH (7.5%) and then those with GC (5.4%). Serum levels of TSH and FT3/FT4 ratio were significantly lower in T2DM patients with SH compared to those with MH and the GC (p < .0001). However, FT4 was significantly higher in SH patients compared to the good glycaemic controls (p < .01). The first tertiles of TSH [aOR = 10.51, 95% CI (4.04-17.36), p < .0001] and FT3 [aOR = 2.77, 95% CI (1.11-6.92), p = .0290] were significantly and independently associated with increased odds of hyperglycaemia. CONCLUSION: The prevalence of thyroid dysfunction is high in T2DM and increases with hyperglycaemia. Reduced TSH and T3 may worsen glycaemic control. Periodic monitoring of thyroid function should be incorporated into management guidelines among T2DM patients in Ghana.

Receptors expressions on peripheral lymphocytes and CD4+ CD183+ as a diagnostics biomarker for rheumatoid arthritis: A case-control study in Ghana.

BACKGROUND: T cell receptors play important roles in the development and progression of rheumatoid arthritis (RA). Their involvement has been reported in inflammatory autoimmune diseases. However, their role in predicting RA is still under exploration. This study evaluated the expression of CD183 (CXCR3) receptors on T-cells and other relevant biomarkers for detecting RA and determine their relationship with disease activity. METHODS: This unmatched case-control study included 48 newly diagnosed RA patients and 30 apparent healthy controls from the orthopedic units of Komfo Anokye Teaching Hospital (KATH), Kumasi and Korle-Bu Teaching Hospital (KBTH), Accra, Ghana. Sociodemographic data was obtained, and blood samples were also collected and processed for flow cytometric analysis. Statistical analyses were done using SPSS version 26.0 and R programming language. p < .05 was considered statistically significant. RESULTS: This study found a significant difference in age group (p < .0001), marital status (p = .0210), occupation (p = .0140), educational level (p = .0210) and religion (p = .0100) between RA patients and healthy controls. Moreover, hemoglobin level (p = .0010), waist circumference (p < .0001) and hip circumference (p = .0040) were significantly different between RA patients and controls. RA patients had significantly lower levels of CD4+ CD183+ compared with the control group (p < .001), and was positively correlated with DAS score (r = .0397, p = .789). In Receiver Operator Characteristics analysis, CD4+ CD183+ could significantly detect RA with a high area under the curve (AUC = 0.687, p = .018). At a cut-off of 0.082, CD4+ CD183+ was the best receptor biomarker for detecting RA with a sensitivity of 90.0%, specificity of 25.9%, a positive predictive value of 69.2%, and a negative predictive value of 58.3%. CONCLUSION: CD4+ CD183+ best predict RA and is positively correlated with disease activity. CD4+ CD183+ could serve as diagnostics and disease-monitoring biomarker for RA; however, it demonstrates low specificity. Future studies should be directed on CD4+ CD183+ and other biomarkers to augment their diagnostics performances and routine management in RA.

Memory B-cells are enriched in the blood of patients with acute Buruli ulcer disease: a prospective observational study.

BACKGROUND: Buruli ulcer disease (BUD) caused by Mycobacterium (M.) ulcerans is characterized by necrotic skin lesions. As for other mycobacterial infections, e.g., tuberculosis, the immune response is important for host protection. B-cells may play a role in antimycobacterial immunity but studies characterizing the B-cell repertoire and memory generation in BUD and during the course of treatment are scarce. METHODS: We investigated the adaptive immune cell repertoire in children with BUD and healthy matched controls by flow cytometry. Analyses prior to treatment, also in a study group of patients with tuberculosis, as well as three time points during BUD treatment (i.e., week 8, 16, and 32) were performed. In addition, BUD disease severity as well as treatment response were analysed for association with B-cell repertoire differences. RESULTS: Children with BUD had comparable total B- and T-cell proportions but differed largely in B-cell subsets. Memory B-cell (B mem) proportions were higher in children with BUD whereas regulatory B-cell (B reg) proportions were lower as compared to healthy controls and tuberculosis patients. Lower naïve (B naïve) and higher transitional B-cell (B trans) proportions characterized children with BUD in comparison with tuberculosis patients. Under treatment, B mem proportions decreased significantly whereas proportions of B reg and B naive increased concomitantly in children with BUD. Also, we found significant correlation between lesion size and B mem as well as B reg. However, we did not detect associations between treatment efficacy and B-cell proportions. CONCLUSIONS: These results suggest a role of B-cell subsets in the immune response against M. ulcerans. Furthermore, changes in B-cell subset proportions may be used as markers for treatment monitoring in BUD.

Comparison of Modified Manual Acid-Phenol Chloroform Method and Commercial RNA Extraction Kits for Resource Limited Laboratories.

Method: In a comparative experimental cross-sectional study, RNA was extracted from oral swabs and blood samples from 25 healthy individuals at the Department of Molecular Medicine, KNUST. RNA was extracted by the manual AGPC extraction method and commercial RNA extraction kits. The quantity (ng/µl) and purities (260/280 nm) of the extracted RNA were measured spectrophotometrically using the IMPLEN NanoPhotometer® N60. The presence of RNA in the extracts was confirmed using 2% agarose gel electrophoresis. Statistical analyses were conducted using R language. Results: The yield of RNA extracted from blood and oral swab samples using modified AGPC was significantly higher compared to the commercial methods (p < 0.0001). However, the purity of RNA extracted by the manual AGPC method from blood was significantly lower than the commercial methods (p < 0.0001). Moreover, the purity from oral swabs using the manual AGPC method was significantly lower compared to QIAamp (p < 0.0001) and the OxGEn kits method (p < 0.001). Conclusion: The modified manual AGPC method has a very high yield of RNA extracts using blood samples, which could serve as an alternate cost-effective method for RNA extraction in resource-limited laboratories; however, its purity may not be suitable for downstream processes. Moreover, the manual AGPC method may not be suitable for extracting RNA from oral swab samples. Future investigation is needed to improve the purity of the manual AGPC RNA extraction method and also confirmation of the obtained results by PCR amplification and RNA purity verification by sequencing.

Diversity of cervicovaginal human papillomavirus (HPV) genotypes and naturally occurring E6/E7 DNA polymorphisms of HPV-16 in Ghana.

Human papillomavirus (HPV) E6 and E7 oncogene expression is essential for cervical carcinogenesis. Evidence exists that E6/E7 variants may have different transforming activities while the risk of HPV-16 variants (A/D) differs by race/ethnicity. We determined the type-specific diversity of HPV infection in women with high grade cervical disease or cervical cancer in Ghana and investigated naturally occurring E6/E7 DNA variants in this population. HPV genotyping was carried out on 207 cervical swab samples collected from women referred to a gynaecology clinic at two teaching hospitals in Ghana. HPV-16, HPV-18 and HPV-45 were detected in 41.9%, 23.3% and 16.3% of cases respectively. HPV-16 E6/E7 DNA sequencing was performed in 36 samples. Thirty samples contained E6/E7 variants of the HPV-16-B/C lineage. 21/36 samples were of the HPV-16C1 sublineage variant and all contained the E7 A647G(N29S) single nucleotide polymorphism (SNP). This study reveals the diversity of E6/E7 DNA and the dominance of HPV16 B/C variants in cervicovaginal HPV infection in Ghana. Type-specific HPV diversity analysis indicates that most Ghanaian cervical disease cases are vaccine preventable. The study provides an important baseline from which for the impact of vaccine and antivirals on clinically relevant HPV infection and associated disease can be measured.

Wolbachia Ferrochelatase as a potential drug target against filarial infections.

Filarial infections are among the world's most disturbing diseases caused by 3 major parasitic worms; Onchocerca volvulus, Wuchereria bancrofti, and Brugia malayi, affecting more than 500 million people worldwide. Currently used drugs for mass drug administration (MDA) have been met with several challenges including the development of complications in individuals with filaria co-infections and parasitic drug resistance. The filarial endosymbiont, Wolbachia, has emerged as an attractive therapeutic target for filariasis elimination, due to the dependence of the filaria on this endosymbiont for survival. Here, we target an important enzyme in the Wolbachia heme biosynthetic pathway (ferrochelatase), using high-throughput virtual screening and molecular dynamics with MM-PBSA calculations. We identified four drug candidates; Nilotinib, Ledipasvir, 3-benzhydryloxy-8-methyl-8-azabicyclo[3.2.1]octane, and 2-(4-Amino-piperidin-1-yl)-ethanol as potential small molecules inhibitors as they could compete with the enzyme's natural substrate (Protoporphyrin IX) for active pocket binding. This prevents the worm from receiving the heme molecule from Wolbachia for their growth and survival, resulting in their death. This study which involved targeting enzymes in biosynthetic pathways of the parasitic worms' endosymbiont (Wolbachia), has proven to be an alternative therapeutic option leading to the discovery of new drugs, which will help facilitate the elimination of parasitic infections.

Reactive Case Detection Strategy for Malaria Control and Elimination: A 12 Year Systematic Review and Meta-Analysis from 25 Malaria-Endemic Countries.

Reactive case detection (RACD) is the screening of household members and neighbors of index cases reported in passive surveillance. This strategy seeks asymptomatic infections and provides treatment to break transmission without testing or treating the entire population. This review discusses and highlights RACD as a recommended strategy for the detection and elimination of asymptomatic malaria as it pertains in different countries. Relevant studies published between January 2010 and September 2022 were identified mainly through PubMed and Google Scholar. Search terms included "malaria and reactive case detection", "contact tracing", "focal screening", "case investigation", "focal screen and treat". MedCalc Software was used for data analysis, and the findings from the pooled studies were analyzed using a fixed-effect model. Summary outcomes were then presented using forest plots and tables. Fifty-four (54) studies were systematically reviewed. Of these studies, 7 met the eligibility criteria based on risk of malaria infection in individuals living with an index case < 5 years old, 13 met the eligibility criteria based on risk of malaria infection in an index case household member compared with a neighbor of an index case, and 29 met the eligibility criteria based on risk of malaria infection in individuals living with index cases, and were included in the meta-analysis. Individuals living in index case households with an average risk of 2.576 (2.540-2.612) were more at risk of malaria infection and showed pooled results of high variation heterogeneity chi-square = 235.600, (p < 0.0001) I2 = 98.88 [97.87-99.89]. The pooled results showed that neighbors of index cases were 0.352 [0.301-0.412] times more likely to have a malaria infection relative to index case household members, and this result was statistically significant (p < 0.001). The identification and treatment of infectious reservoirs is critical to successful malaria elimination. Evidence to support the clustering of infections in neighborhoods, which necessitates the inclusion of neighboring households as part of the RACD strategy, was presented in this review.

Effect of iron fortification on anaemia and risk of malaria among Ghanaian pre-school children with haemoglobinopathies and different ABO blood groups.

BACKGROUND: Haemoglobinopathies such as sickle cell disorder and glucose-6-phosphate dehydrogenase (G6PD) deficiency as well as differences in ABO blood groups have been shown to influence the risk of malaria and/or anaemia in malaria-endemic areas. This study assessed the effect of adding MNP containing iron to home-made weaning meals on anaemia and the risk of malaria in Ghanaian pre-school children with haemoglobinopathies and different ABO blood groups. METHODS: This study was a double-blind, randomly clustered trial conducted within six months among infants and young children aged 6 to 35 months in rural Ghana (775 clusters, n = 860). Participants were randomly selected into clusters to receive daily semiliquid home-prepared meals mixed with either micronutrient powder without iron (noniron group) or with iron (iron group; 12.5 mg of iron daily) for 5 months. Malaria infection was detected by microscopy, blood haemoglobin (Hb) levels were measured with a HemoCue Hb analyzer, the reversed ABO blood grouping microtube assay was performed, and genotyping was performed by PCR-RFLP analysis. RESULTS: The prevalence of G6PD deficiency among the study participants was 11.2%. However, the prevalence of G6PD deficiency in hemizygous males (8.5%) was significantly higher than that in homozygous females (2.7%) (p = 0.005). The prevalence rates of sickle cell traits (HbAS and HbSC) and sickle cell disorder (HbSS) were 17.5% and 0.5%, respectively. Blood group O was dominant (41.4%), followed by blood group A (29.6%) and blood group B (23.3%), while blood group AB (5.7%) had the least frequency among the study participants. We observed that children on an iron supplement with HbAS had significantly moderate anaemia at the endline (EL) compared to the baseline level (BL) (p = 0.004). However, subjects with HbAS and HbAC and blood groups A and O in the iron group had a significantly increased number of malaria episodes at EL than at BL (p < 0.05). Furthermore, children in the iron group with HbSS (p < 0.001) and the noniron group with HbCC (p = 0.010) were significantly less likely to develop malaria. CONCLUSIONS: Iron supplementation increased anaemia in children with HbAS genotypes and provided less protection against malaria in children with HbAC and AS and blood groups A and O. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01001871 . Registered 27/10/2009. REGISTRATION NUMBER: https://clinicaltrials.gov/ct2/show/record/NCT01001871 .

Doxycycline Treatment of Mansonella perstans-Infected Individuals Affects Immune Cell Activation and Causes Long-term T-cell Polarization.

BACKGROUND: Doxycycline is used for treatment of Mansonella perstans infection. Immune modulatory effects of both M. perstans and doxycycline have been described but long-term implications on host immune response are not defined. Here we determined multiple immune parameters of M. perstans-infected individuals before and after doxycycline treatment to characterize doxycycline effects on host T-cell immunity. METHODS: Immune characterization of doxycycline-treated M. perstans-infected individuals was performed as part of an open-label randomized clinical trial. Immune cell population phenotyping by flow cytometry and functional in vitro T-cell assays were performed at baseline, 6 months, and "long term" (18-24 months) after treatment start. Treatment efficacy, based on peripheral blood microfilaria (mf) burden, was correlated with immune parameters and effects on immune response against concomitant Mycobacterium tuberculosis infection were determined. RESULTS: Immune population phenotyping indicated changes in functional T-cell responses after doxycycline treatment. Constitutive and superantigen-induced T-cell activation and polarization towards T-helper type (TH) 1 phenotype at baseline declined after doxycycline treatment, whereas low proportions of TH17 and TH1* cells at baseline increased significantly at follow-up. In accordance, long-term decline in antigen-specific TH1 responses against concomitant M. tuberculosis infection was seen. Notably, only TH17 and TH1* changes after 6 months and TH17 at baseline were negatively correlated with M. perstans microfilaria burden or reduction, whereas long-term changes were not associated with treatment efficacy. CONCLUSIONS: We found long-term immune modulatory effects of doxycycline treatment leading to decreased constitutive T-cell activation, polarization towards TH17/TH1*, and impaired immune response against concomitant M. tuberculosis infection.

T-Cell Responses Against Mycobacterium ulcerans and Mycobacterium tuberculosis Protein Extracts Identify Children With Buruli Ulcer Disease.

Immune-based diagnosis of Buruli ulcer disease (BUD) in children is difficult due to cross-reactivity between mycobacteria. We found that T-cell IFNγ/TNFα responses against Mycobacterium (M.) ulcerans and M. tuberculosis (PPDMulc, PPDMtub) were different between children with BUD (n = 27) and TB (n = 20) but only ratios (PPDMtub/PPDMulc) discriminated the study groups efficiently.

Factors associated with viral suppression and rebound among adult HIV patients on treatment: a retrospective study in Ghana.

BACKGROUND: Viral suppression remains the most desired outcome in the management of patients with Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) and this can be achieved by an effective Antiretroviral Therapy (ART). However, some patients who achieve viral suppression may experience viral rebound with dire consequence. We evaluated viral suppression and rebound and their associated factors among adult patients on ART in Kumasi, Ghana. METHODS: This hospital-based retrospective study was conducted at the Komfo Anokye Teaching Hospital in Ghana. We reviewed the medical records of 720 HIV patients on ART. Statistical analyses were performed using SPSS Version 26.0 and GraphPad prism version 8.0. p < 0.05 was considered statistically significant. RESULTS: Proportions of patients with viral suppression and viral rebound were 76.1% and 21.0% respectively. Being diagnosed at WHO stage I [aOR = 11.40, 95% CI (3.54-36.74), p < 0.0001], having good adherence to ART [aOR = 5.09, 95% CI (2.67-9.73), p < 0.0001], taking Nevirapine-based regimen [aOR = 4.66, 95% CI (1.20-18.04), p = 0.0260] and increasing duration of treatment (p < 0.0001) were independently associated with higher odds of viral suppression. However, being diagnosed at WHO stage II (aOR = 7.39, 95% CI 2.67-20.51; p < 0.0001) and stage III (aOR = 8.62, 95% CI 3.16-23.50; p < 0.0001), having poor adherence (aOR = 175.48, 95% CI 44.30-695.07; p < 0.0001), recording baseline suppression value of 20-49 copies/mL (aOR = 6.43, 95% CI 2.72-15.17; p < 0.0001) and being treated with Zidovudine/Lamivudine/Efavirenz (aOR = 6.49, 95% CI 1.85-22.79; p = 0.004) and Zidovudine/Lamivudine/Nevirapine (aOR = 18.68, 95% CI 1.58-220.90; p = 0.02) were independently associated with higher odds of viral rebound. CONCLUSION: Approximately 76% viral suppression rate among HIV patients on ART in Kumasi falls below the WHO 95% target by the year 2030. Choice of ART combination, drug adherence, WHO clinical staging and baseline viral load are factors associated with suppression or rebound. These clinical characteristics of HIV patients must be monitored concurrently with the viral load.

Polymorphism of protein tyrosine phosphatase non-receptor type 22 and protein arginine deiminase 4 gene among Ghanaian rheumatoid arthritis patients: A case-control study.

AIM: Rheumatoid arthritis (RA) is an autoimmune disease which affects millions of lives globally characterized by chronic inflammation in the joints of the body. There is no known cause for RA; however, genetic predisposition has been associated with its occurrence. The association between genetic predisposition and RA has been reported largely among Caucasians and Asians. However, few studies with limited data have reported genome-wide association studies of RA in Africa, especially in Ghana. In addition, there is genetic heterogeneity that exists geographically among different populations. This study therefore investigated the association of protein arginine deiminase type 4 (PAD4) and protein tyrosine phosphatase non-receptor type 22 (PTPN22) single nucleotide polymorphisms with susceptibility of RA among Ghanaians. METHODS: This case-control study included 75 RA patients and 75 healthy controls from the Komfo Anokye Teaching Hospital in Ghana. Validated questionnaires were used to obtain demographic data, and blood samples were collected and processed for DNA and polymerase chain reaction analysis. Statistical analysis was done using SPSS version 25.0. RESULTS: PTPN22 demonstrated a 100% minor allele frequency (GG) in both cases and healthy controls; however, an association could not be made for PTPN22 polymorphism with susceptibility of RA when comparing cases to controls. The homozygous minor allele (GG) of PAD4 was absent in the population. CONCLUSION: PAD4 polymorphism was absent, while PTPN22 was present in the Ghanaian population. The association between PTPN22 (rs2476601) and PAD4 (rs2240340) with RA susceptibility could not be established, thus may not contribute as risk factors for RA in the Ghanaian population.

Foeto-maternal complications associated with low birth weight: A prospective multicenter study in northern Ghana.

OBJECTIVE: The study evaluated the socio-demographic characteristics, obstetric variables and foeto-maternal complications associated with low birth weight (LBW) in order to provide better treatment and management options. METHODS: The prospective study conducted from February, 2019 to June, 2020 recruited 312 primigravid pregnant women who reported for antenatal care in three tertiary referral hospitals in northern Ghana. Their socio-demographic, obstetric and adverse foeto-maternal outcome information were obtained with a well-structured questionnaire according to the World Health Organisation (WHO) guidelines. Participants' blood samples were collected for haematological tests. Odds ratio [OR, 95% confidence interval (CI)] for the association between socio-demographic, obstetric characteristics, foeto-maternal complications and haematological tests in relation to LBW were assessed using logistic regression model. RESULTS: This study reported a LBW prevalence of 13.5%. Increasing maternal systolic blood pressure (SBP) and diastolic blood pressure (DBP) at 1st visit, before and after delivery significantly increased the odds of LBW. Preterm delivery (PTD<37 weeks) (COR = 9.92, 95% CI (4.87-2020), p<0.001), preeclampsia (PE) (COR = 5.94, 95% CI (2.96-11.94), p<0.001), blood transfusion (COR = 14.11, 95% CI (2.50-79.65), p = 0.003), caesarian delivery (COR = 3.86, 95% CI (1.96-7.58), p<0.001) and male sex neonates (COR = 2.25, 95%CI (1.14-4.47), P = 0.020) presented with increased odds of LBW. Increasing gestational age at delivery presented with 28% reduced odds of LBW (COR = 0.72, 95% CI (1.12-4.40), P = 0.023). Upon controlling for potential confounders in multivariate logistic regression, only gestational age at delivery (AOR = 0.67, 95% CI (0.47-0.96), P = 0.030) remained significantly associated with reduced odds of LBW. CONCLUSION: This study found that high blood pressure at 1st visit, before and after delivery results in increased chances of delivering a baby with LBW. Furthermore, PTD<37 weeks, having PE in current pregnancy, and male sex potentiate the risk of LBW. On the other hand, increasing gestational age reduces the risk of LBW. Thus, we recommend that midwives should intensify education to pregnant women on the benefits of regular ANC visits to aid in the early detection of adverse foeto-maternal complications. We also recommend proper clinical management of pregnancies associated with an elevated blood pressure at registration. Also, maternal intrapartum blood pressure measurement could be used to predict LBW in low resourced settings.

Assessing the variability and the role of inflammatory cytokines and monocyte chemoattractant protein-1 (MCP-1) in predicting stroke among hypertensives: A case-control study.

Background: Atherosclerosis is a complex lipid-driven inflammatory disease in which numerous cell types and inflammatory mediators are involved in the progression of hypertension to stroke. Mediators' markers that could predict the progression of hypertension to stroke are of research importance. We assessed the predictive value of individual and combined cytokines and monocyte chemoattractant protein-1 (MCP-1) among hypertensives with or without stroke. Methods: In a case-control study, we enrolled 63 cases with stroke and hypertension (HPT-S), 59 stroke-free hypertensives (HPT), and 53 stroke free normotensives as controls (CS). Sociodemographic data and blood samples were collected for the estimation of Interleukin-10 (IL-10), IL-6, IL-8, IL-1ß and monocyte chemoattractant protein-1 (MCP-1) using commercially available ELISA kits from Biobase Biotech, Shanghai, China. The Receiver Operator Characteristics (ROC) analysis was used to calculate diagnostic accuracy for cytokines in predicting stroke among hypertensives. A combined bioscore model of IL-10 and MCP-1 was generated to predict stroke among hypertensives. The multiple logistic regression analysis was used to assess the chances of IL-10 and MCP-1 in predicting stroke among hypertensives. Statistical analyses were performed using R-language. Results: The HPT-S group had significantly higher levels of MCP-1 and IL-10 compared to the HPT and CS groups (p < 0.05). There was no significant difference in IL-1ß, IL-8 and IL-6 amongst the three study groups. MCP-1 and IL-10 were predictive of stroke occurrence among hypertensives and were used to develop a bioscore model. An elevated MCP-1 and IL-10 with a bioscore 2 had a predictive accuracy of 0.81, a sensitivity of 0.77 and specificity of 0.84. At a bioscore of 1, the sensitivity and specificity for predicting stroke among hypertensives was 97.0% and 61.0% respectively. In a binary logistic regression, having a bioscore of 1 [aOR = 20.43, 95% CI (2.17-192.62), p = 0.008] or 2 [aOR = 26.00, 95% CI (2.92-231.31), p = 0.003] were significantly associated with stroke occurrence among hypertensives. Conclusion: Higher levels of IL-10 with a concomitant level of MCP-1 could serve as a good predictor of stroke among hypertensives. Subsequently, MCP-1 may prove useful as a therapeutic target for atherosclerosis in hypertensives. Combined bioscore of MCP-1 and IL-10 could serve as a good predictor of stroke among hypertensives.

Factors associated with anti-retroviral therapy (ART) adherence among adult people living with HIV (PLWH): A 5-year retrospective multi-centre study in Kumasi, Ghana.

Background: Combined antiretroviral therapy (cART) is the recommended treatment regimen for people living with HIV (PLWH). Long-term HIV treatment of over 95% adherence inhibits increase in viral load and boosts immune system performance. On the contrary, non-adherence results in treatment failure, accelerated development of HIV drug-resistance and increased mortality. However, there is paucity of data on the prevalence of antiretroviral therapy (ART) adherence and its associated factors in Ghana. We assessed the prevalence, sociodemographic and clinical factors associated with ART adherence among registered PLWH. Methods: In a multi-centre hospital-based retrospective study, we collected data on 720 registered PLWH 18 years and above, who attend the HIV clinic at the University Hospital (KNUST), Komfo Anokye Teaching Hospital (KATH), and the Bomso Clinic, on ART and with up-to-date medical records. They were enrolled using a multistage sampling technique. Adherence was assessed retrospectively using missed doses and prescriptions renewal. All analysis were done using SPSS Version 26.0 and GraphPad prism version 8.0. Results: Of 720 registered PLWH, 51.8% had good ART adherence, 35.3% had fair ART adherence and 12.9% had poor ART adherence. Those diagnosed at WHO stage II (aOR = 0.45, 95% CI: (0.30-0.68); p < 0.0001) and stage III (aOR = 0.40, 95% CI: (0.27-0.59) < 0.0001) were independently associated with lower chances of good adherence to ART. Moreover, those treated with AZT/3TC/EFV (aOR = 0.33, 95% CI: (0.16-0.68); p = 0.0030), and AZT/3TC/NVP (aOR = 0.50, 95% CI: (0.26-0.98); p = 0.0410) were independently associated with lower likelihood of good ART adherence. On the contrary, PLWH who have been on treatment for 4 years (aOR = 3.56, 95% CI: (1.10-11.54); p = 0.0340) was an independent predictor of good ART adherence. Conclusion: About half of PLWH on treatment have good adherence to ART. Being diagnosed at WHO stage II and stage III, being treated with AZT/3TC/EFV, and AZT/3TC/NVP ART combination are associated with lesser chances of good ART adherence. However, increased duration of ART among PLWH influence good ART adherence. PLWH on ART should be monitored to achieve over 95% ART adherence for effective management of HIV/AIDS.