Vitamin B-12 deficiency in type 2 diabetic patients on metformin: a cross-sectional study from South-Western part of Ghana

Introduction: Metformin is the most widely administered anti-diabetic medication among type 2 diabetes mellitus (T2DM) patients. However, metformin induces vitamin B12 malabsorption which may increase the risk of vitamin B12 deficiency among T2DM patients. We determined the prevalence of vitamin B12 deficiency and related risk factors among Ghanaian T2DM patients on metformin therapy. Methods: This cross-sectional study recruited 196 T2DM patients attending the outpatient diabetic clinic at the Effia Nkwanta Regional Hospital, Ghana. Fasting venous blood was collected for biochemical analysis. Vitamin B12 deficiency was defined as serum B12 \u3c 100 pg/ml and methylmalonic acid (MMA) ≥ 0.4µmol/L. Results: The prevalence of vitamin B12 deficiency based on serum vitamin B12, MMA, and the combination of both methods were 32.1%, 14.8%, and 14.3%, respectively. Longer duration of metformin use [5-9 years, aOR= 2.83, 95% CI (1.03-7.81), p=0.045 and ≥ 10 years, aOR= 4.17, 95% CI (1.41-12.33), p=0.010], higher daily dose of metformin [1000-2000 mg/day, aOR= 1.34, 95% CI (0.25-2.74), p=0.038 and \u3e 2000 mg/day, aOR= 1.13, 95% CI (0.39-2.97), p=0.047], and very high body fat [aOR= 2.98, 95% CI (1.47-6.05), p=0.020] were significantly associated with increased odds of vitamin B12 deficiency. For daily dose of metformin, a cutoff value of 1500 mg/day presented with a sensitivity, specificity, and AUC of 71.4%, 40.1%, and 0.54 (95% CI, 0.53-0.54), respectively, in predicting vitamin B12 deficiency. A ≥ six (6) years duration of metformin therapy presented with a sensitivity, specificity, and AUC of 70.4%, 62.9%, and 0.66 (95% CI, 0.57-0.75), respectively, in predicting vitamin B12 deficiency. Conclusion: Vitamin B12 deficiency is high among T2DM patients on metformin therapy in Ghana. There is the need for regular monitoring of vitamin B12 levels especially in T2DM patients on metformin daily dose of ≥ 1500 mg for duration of therapy ≥ 6 years

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

In silico screening of phytochemicals from Dissotis rotundifolia against Plasmodium falciparum Dihydrofolate Reductase

Background: Malaria remains a major health concern in developing countries with high morbidity and mortality, especially in pregnant women and infants. A major obstacle to the treatment of malaria is a low effectiveness and an increase resistance of the parasite to antimalarial drugs. As a result, there is an ongoing demand for new and potent antimalarial drugs. Medicinal plants remain a potential source for the development of new antimalarial drugs. Amongst them is Dissotis rotundifolia is an ethnomedical important plant used in West Africa to treat malaria. Purpose: This study aimed at identifying new potential antifolates by virtually screening phytochemicals characterized from the whole plant methanolic extract of D. rotundifolia against Plasmodium falciparum Dihydrofolate Reductase (PfDHFR). Methods: LC-ESI-Q-TOF-MS analysis was employed to identify the phytochemicals present in the whole plant methanolic extract of D. rotundifolia. These phytochemicals were docked against the catalytic site of PfDHFR. The docking protocol was evaluated using the Area Under the Curve (AUC) of a Receiver Operating Characteristic (ROC) curve. The binding mechanisms and the drug-likeness of the phytochemicals were characterized. A 100 ns Molecular Dynamics (MD) simulation and Molecular Mechanics-Poisson Boltzmann Surface Area (MM-PBSA) calculations were utilized to analyze the stability, the energy decomposition per residue and the binding free energy of the potential leads. Results: Twenty nine phytochemicals were characterized and docked against PfDHFR. Dimethylmatairesinol, flavodic acid, sakuranetin, and sesartemin were identified as potential leads with binding affinities of -8.4, -8.9, -8.6, and -8.9 kcal/mol respectively, greater than a stringent threshold of -8.0 kcal/mol. The potential leads also interacted hydrophobically with critical residue Phe58. A novel critical residue, Leu46 was identified to be crucial in the catalytic activity of PfDHFR. The potential leads were also predicted to be anti-protozoal with a probability of active (Pa) value ranging from 0.319 to 0.537. Conclusion: This study elucidates the potential inhibition of PfDHFR by dimethylmatairesinol, flavodic acid, sakuranetin and sesartemin present in D. rotundifolia. These compounds are druglike, do not violate Lipinski's rule of five, have a high binding affinity to PfDHFR, and interact with crucial residues involved in the catalytic activity PfDHFR. Dimethylmatairesinol, flavodic acid, sakuranetin and sesartemin could therefore be further investigated and developed as new antifolate drugs for malaria