Assessing knowledge of sickle cell disease and health beliefs on premarital genetic screening among healthcare trainees at a tertiary institution: A cross-sectional study.

Background: The uptake of sickle cell trait (SCT) test is challenged by several factors. A community of healthcare professionals educating the public to undergo screening is critical in reducing the disease burden. We investigated knowledge and attitude towards premarital SCT screening among healthcare trainee students who are the next generation of healthcare practitioners. Methods: A cross-sectional design was employed, and quantitative data were collected from 451 female students pursuing healthcare programs at a tertiary institution in Ghana. Descriptive, bivariate, and multivariate logistic regression analysis was performed. Results: More than half of the participants were 20-24 years (54.55%) and had good knowledge (71.18%) about sickle cell disease (SCD). Age and school or social media as sources of information were significantly associated with good knowledge about SCD. Students between the age 20-24 (adjusted odds ratio [AOR] = 2.54, confidence interval [CI] = 1.30-4.97) and knowledge (AOR = 2.19, CI = 1.41-3.39) were 3 times and 2 times more likely to have a positive perception about SCD severity. Students who have SCT (AOR = 5.16, CI = 2.46-10.82), whose source of information was family member/friends (AOR = 2.83, CI = 1.44-5.59) and social media (AOR = 4.59, CI = 2.09-10.12) were 5 times, 2 times and 5 times likely to have a positive perception about the susceptibility of SCD. Students whose source of information is school (AOR = 2.06, CI = 1.11-3.81) and who have good knowledge of SCD (AOR = 2.25, CI = 1.44-3.52) were 2 times more likely to have a positive perception about the benefits of testing. Students with SCT (AOR = 2.64, CI = 1.36-5.13) and source of information was social media (AOR = 3.01, CI = 1.36-6.64) were about 3 times more likely to have a positive perception about the barriers to testing. Conclusion: Our data shows that high level of SCD knowledge influences positive perceptions about the severity of SCD, the benefits and relatively low barriers to SCT or SCD testing and genetic counseling. Dissemination of SCT, SCD and premarital genetic counseling education should be intensified especially in schools.

Antibiotic resistance and mecA characterization of Staphylococcus hominis from filarial lymphedema patients in the Ahanta West District, Ghana: A cross-sectional study.

Background and Aim: Filarial infections affect over 150 million people in the tropics. One of the major forms of filarial pathologies is lymphedema; a condition where the immune response is significantly altered, resulting in changes in the normal flora. Staphylococcus hominis, a human skin commensal, can also be pathogenic in immunocompromised individuals. Therefore, there is the possibility that S. hominis could assume a different behavior in filarial lymphedema patients. To this end, we investigated the levels of antibiotic resistance and extent of mecA gene carriage in S. hominis among individuals presenting with filarial lymphedema in rural Ghana. Method: We recruited 160 individuals with stages I-VII lymphedema, in a cross-sectional study in the Ahanta West District of the Western Region of Ghana. Swabs from lymphedematous limb ulcers, pus, and cutaneous surfaces were cultured using standard culture-based techniques. The culture isolates were subjected to Matrix-Assisted Laser Desorption/Ionization Time of Flight (MALDI-TOF) mass spectrometry for bacterial identification. Antimicrobial susceptibility testing (AST) was performed using the Kirby-Bauer method. mecA genes were targeted by polymerase chain reaction for strains that were cefoxitin resistant. Results: In all, 112 S. hominis were isolated. The AST results showed resistance to chloramphenicol (87.5%), tetracycline (83.3%), penicillin (79.2%), and trimethoprim/sulphamethoxazole (45.8%). Of the 112 strains of S. hominis, 51 (45.5%) were resistant to cefoxitin, and 37 (72.5%) of the cefoxitin-resistant S. hominis haboured the mecA gene. Conclusion: This study indicates a heightened level of methicillin-resistant S. hominis isolated among filarial lymphedema patients. As a result, opportunistic infections of S. hominis among the already burdened filarial lymphedema patients in rural Ghana may have reduced treatment success with antibiotics.

Iron stores in steady-state sickle cell disease children accessing care at a sickle cell disease clinic in Kumasi, Ghana: A cross-sectional study.

Background and Aims: Children with sickle cell disease (SCD) have an increased risk of multiple hemotransfusions and this can predispose them to elevated iron stores. The objectives of the study were to determine the extent of elevated iron stores and the associated risk factors in a population of steady-state SCD children in Ghana. Methods: This cross-sectional study was conducted at the pediatric sickle cell clinic at the Komfo Anokye Teaching Hospital. Complete blood count and serum ferritin assay were performed for (n = 178) steady-state SCD children. Descriptive and multivariate logistic regression analysis were performed. Elevated iron stores were defined as serum ferritin levels >300 ng/ml. Statistical significance was considered at p < 0.05. Results: The mean (standard deviation) age of the participants was 9.61 (±4.34) years, and 51% of them were males. About 17% of SCD children had elevated iron stores and receiving at least three hemotransfusions during the last 12 months was strongly associated with elevated iron stores (p < 0.001). History of chronic hemotransfusion increased the odds of having elevated iron store (adjusted odds ratio [aOR] = 11.41; 95% confidence interval [CI] = 3.11-30.85; p < 0.001) but SCD patients on hydroxyurea treatment had reduced-odds of having elevated iron stores (aOR = 0.18; 95% CI = 0.06-0.602; p = 0.006). Moreover, red blood cell (Coef. = -0.84; 95% CI = -0.37, -1.32; p = 0.001), hemoglobin (Coef. = -0.83; 95% CI = -0.05, -1.61; p = 0.04), hematocrit (Coef. = -0.85; 95% CI = -0.08, -1.63; p = 0.03), mean cell volume (Coef. = 0.02; 95% CI = 0.01, 0.03; p = 0.001) and mean cell hemoglobin (Coef. = 0.04; 95% CI = 0.01, 0.07; p = 0.002) could significantly predict serum ferritin levels. Conclusion: The magnitude of elevated iron stores was high among children with SCD in steady-state. Red cell indices could provide invaluable information regarding the risk of elevated iron stores. SCD children who have a history of chronic hemotransfusion or had received at least three hemotransfusions in a year should be monitored for elevated iron stores.

Plasmodium falciparum coinfection is associated with improved IgE and IgG3 response against hookworm antigens.

Background: Plasmodium falciparum and Hookworm infections are prevalent in West Africa and they cause iron deficiency anemia and protein malnutrition in Children. Immune response of these parasites interact and their interactions could have repercussions on vaccine development and efficacy. The current goal of hookworm eradication lies on vaccination. We evaluated the effect of P. falciparum coinfection and albendazole treatment on naturally acquired antibody profile against hookworm L3 stage larvae antigen. Methods: In a longitudinal study, 40 individuals infected with Necator americanus only, 63 participants infected with N. americanus and P. falciparum, and 36 nonendemic controls (NECs) were recruited. The study was done in the Kintampo North Metropolis of Ghana. Stool and blood samples were taken for laboratory analyses. Serum samples were obtained before hookworm treatment and 3 weeks after treatment. Results: The malaria-hookworm (N. americanus and P. falciparum) coinfected subjects had significantly higher levels of IgE (ß = 0.30, 95% CI = [0.12, 0.48], p = 0.023) and IgG3 (ß = 0.15, 95% CI = [0.02, 0.52], p = 0.004) compared to those infected with hookworm only (N. americanus). The N. americanus groups had significantly higher levels of IgG3 (ß = 0.39, 95% CI = [0.14-0.62], p = 0.002) compared to the control group. Similarly, N. americanus and P. falciparum coinfected participants had significantly higher levels of IgE (ß = 0.35, 95% CI = [0.70-0.39], p = 0.002) and IgG3 (ß = 0.54, 95% CI = [0.22-0.76], p = 0.002). Moreover, albendazole treatment led to a significant reduction in IgE, IgA, IgM, and IgG3 antibodies against hookworm L3 stage larvae (p < 0.05). Conclusion: P. falciparum is associated with improved IgE and IgG response against hookworm L3 stage larvae. Treatment with single dose of albendazole led to reduction in naturally acquired immune response against hookworm infection. Thus, P. falciparum infection may have a boosting effect on hookworm vaccine effectiveness.

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.

In silico drug repurposing for filarial infection predicts nilotinib and paritaprevir as potential inhibitors of the Wolbachia 5'-aminolevulinic acid synthase.

Filarial infections affect millions of individuals and are responsible for some notorious disabilities. Current treatment options involve repeated mass drug administrations, which have been met with several challenges despite some successes. Administration of doxycycline, an anti-Wolbachia agent, has shown clinical effectiveness but has several limitations, including long treatment durations and contraindications. We describe the use of an in silico drug repurposing approach to screening a library of over 3200 FDA-approved medications against the filarial endosymbiont, Wolbachia. We target the enzyme which catalyzes the first step of heme biosynthesis in the Wolbachia. This presents an opportunity to inhibit heme synthesis, which leads to depriving the filarial worm of heme, resulting in a subsequent macrofilaricidal effect. High throughput virtual screening, molecular docking and molecular simulations with binding energy calculations led to the identification of paritaprevir and nilotinib as potential anti-Wolbachia agents. Having higher binding affinities to the catalytic pocket than the natural substrate, these drugs have the structural potential to bind and engage active site residues of the wolbachia 5'-Aminolevulinic Acid Synthase. We hereby propose paritaprevir and nilotinib for experimental validations as anti-Wolbachia agents.

Molecular characterization of interactions between the D614G variant of SARS-CoV-2 S-protein and neutralizing antibodies: A computational approach.

The D614G variant of SARS-CoV-2 S-protein emerged in early 2020 and quickly became the dominant circulating strain in Europe and its environs. The variant was characterized by the higher viral load, which is not associated with disease severity, higher incorporation into the virion, and high cell entry via ACE-2 and TMPRSS2. Previous strains of the coronavirus and the current SARS-CoV-2 have demonstrated the selection of mutations as a mechanism of escaping immune responses. In this study, we used molecular dynamics simulation and MM-PBSA binding energy analysis to provide insights into the behaviour of the D614G S-protein at the molecular level and describe the neutralization mechanism of this variant. Our results show that the D614G S-protein adopts distinct conformational dynamics which is skewed towards the open-state conformation more than the closed-state conformation of the wild-type S-protein. Residue-specific variation of amino acid flexibility and domain-specific RMSD suggest that the mutation causes an allosteric conformational change in the RBD. Evaluation of the interaction energies between the S-protein and neutralizing antibodies show that the mutation may enhance, reduce or not affect the neutralizing interactions depending on the neutralizing antibody, especially if it targets the RBD. The results of this study have shed insights into the behaviour of the D614G S-protein at the molecular level and provided a glimpse of the neutralization mechanism of this variant.

The role of nuclear factor kappa B (NF-κB) in filarial pathology.

The transcription factor NF-κB promotes immunity by controlling the expression of genes involved in inflammation. Cytokines and pathogen-associated molecular patterns stimulate cell surface receptors, including toll-like receptors, to initiate a signalling cascade resulting in the activation of NF-κB. NF-κB drives the expression of target genes that mediate cell proliferation and release antimicrobial molecules and cytokines to activate an immune response. Filariasis is one of the most complex infections of humans. The actual causes of the heterogeneity in infection are not well understood. However, they have been attributed to differences in inflammatory processes that are immune-mediated, secondary bacterial infections, and host immune-genetics. Elevated production of angiogenic molecules (VEGFs, CEACAM and MMPs) in filarial pathology has been shown to be dependent on phosphorylation and intracellular activation of NF-κB. This review examines the role of NF-κB in filarial pathology and its potential therapeutic options for individuals with the disease.

High prevalence of antibiotic resistance in commensal Escherichia coli from healthy human sources in community settings.

Antibiotic resistance is a global health crisis that requires urgent action to stop its spread. To counteract the spread of antibiotic resistance, we must improve our understanding of the origin and spread of resistant bacteria in both community and healthcare settings. Unfortunately, little attention is being given to contain the spread of antibiotic resistance in community settings (i.e., locations outside of a hospital inpatient, acute care setting, or a hospital clinic setting), despite some studies have consistently reported a high prevalence of antibiotic resistance in the community settings. This study aimed to investigate the prevalence of antibiotic resistance in commensal Escherichia coli isolates from healthy humans in community settings in LMICs. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we synthesized studies conducted from 1989 to May 2020. A total of 9363 articles were obtained from the search and prevalence data were extracted from 33 articles and pooled together. This gave a pooled prevalence of antibiotic resistance (top ten antibiotics commonly prescribed in LMICs) in commensal E. coli isolates from human sources in community settings in LMICs of: ampicillin (72% of 13,531 isolates, 95% CI: 65-79), cefotaxime (27% of 6700 isolates, 95% CI: 12-44), chloramphenicol (45% of 7012 isolates, 95% CI: 35-53), ciprofloxacin (17% of 10,618 isolates, 95% CI: 11-25), co-trimoxazole (63% of 10,561 isolates, 95% CI: 52-73), nalidixic acid (30% of 9819 isolates, 95% CI: 21-40), oxytetracycline (78% of 1451 isolates, 95% CI: 65-88), streptomycin (58% of 3831 isolates, 95% CI: 44-72), tetracycline (67% of 11,847 isolates, 95% CI: 59-74), and trimethoprim (67% of 3265 isolates, 95% CI: 59-75). Here, we provided an appraisal of the evidence of the high prevalence of antibiotic resistance by commensal E. coli in community settings in LMICs. Our findings will have important ramifications for public health policy design to contain the spread of antibiotic resistance in community settings. Indeed, commensal E. coli is the main reservoir for spreading antibiotic resistance to other pathogenic enteric bacteria via mobile genetic elements.

Production of IgG autoantibody requires expression of activation-induced deaminase in early-developing B cells in a mouse model of SLE.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of pathogenic IgG antinuclear antibodies. Pathogenic IgG autoantibody production requires B-cell activation, leading to the production of activation-induced deaminase (AID) and class switching of IgM genes to IgG. To understand how and when B cells are activated to produce these IgG autoantibodies, we studied cells from 564Igi, a mouse model of SLE. 564Igi mice develop a disease profile closely resembling that found in human SLE patients, including the presence of IgG antinucleic acid Abs. We have generated 564Igi mice that conditionally express an activation-induced cytidine deaminase transgene (Aicda(tg) ), either in all B cells or only in mature B cells. Here, we show that class-switched pathogenic IgG autoantibodies were produced only in 564Igi mice in which AID was functional in early-developing B cells, resulting in loss of tolerance. Furthermore, we show that the absence of AID in early-developing B cells also results in increased production of self-reactive IgM, indicating that AID, through somatic hypermutation, contributes to tolerance. Our results suggest that the pathophysiology of clinical SLE might also be dependent on AID expression in early-developing B cells.

Dosage of X-linked Toll-like receptor 8 determines gender differences in the development of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a high incidence in females and a complex phenotype. Using 564Igi mice, a model of SLE with knock-in genes encoding an autoreactive anti-RNA Ab, we investigated how expression of Toll-like receptors (TLRs) in B cells and neutrophils affects pathogenesis. We established that TLR signaling through MyD88 is necessary for disease. Autoantibody was produced in mice with single deletions of Tlr7, Tlr8, or Tlr9 or combined deletions of Tlr7 and Tlr9. Autoantibody was not produced in the combined absence of Tlr7 and Tlr8, indicating that TLR8 contributes to the break in tolerance. Furthermore, TLR8 was sufficient for the loss of B-cell tolerance, the production of class-switched autoantibody, heightened granulopoiesis, and increased production of type I IFN by neutrophils as well as glomerulonephritis and death. We show that dosage of X-linked Tlr8 plays a major role in the high incidence of disease in females. In addition, we show that the negative regulation of disease by TLR9 is exerted primarily on granulopoiesis and type I IFN production by neutrophils. Collectively, we suggest that individual TLRs play unique roles in the pathogenesis of systemic lupus erythematosus, suggesting new targets for treatment.