Chronic and Occult Hepatitis B Virus Infection in Pregnant Women in Botswana

The hepatitis B virus (HBV) is a global problem; however, the burden of HBV infection in pregnant women in Botswana is unknown. We sought to determine the prevalence of chronic and occult HBV infection in human immunodeficiency virus (HIV)-infected and -uninfected pregnant women in Botswana. Samples from 752 pregnant women were tested for hepatitis B surface antigen (HBsAg), and HBsAg-positive samples were tested for hepatitis B e antigen (HBeAg) and HBV DNA load. Samples that were HBsAg negative were screened for occult HBV infection by determining the HBV DNA load. HBV genotypes were determined based on a 415-base-pair fragment of the surface gene. Among the 752 women tested during pregnancy or early postpartum, 16 (2.1%) (95% confidence interval (CI): 2.0–2.2) were HBsAg-positive. The prevalence of chronic HBV infection was higher (3.1%) among HIV-infected (95% CI: 3.0–3.2) compared with HIV-uninfected women (1.1%) (95% CI: 1.07–1.1, p = 0.057). Among the 622 HBsAg-negative women, the prevalence of occult HBV infection was 6.6% (95% CI: 6.5–6.7). Three of thirteen HBsAg-positive participants were HBeAg-positive, and all were HIV-negative. Of the 11 maternal samples successfully genotyped, five (45.5%) were genotype D3, five (45.5%) were genotype A1, and one was genotype E (9%). Low and similar proportions of HIV-infected and -uninfected pregnant women in Botswana had occult or chronic HBV infection. We identified a subset of HIV-negative pregnant women who had high HBV DNA levels and were HBeAg-positive, and thus likely to transmit HBV to their infants

Translational control during viral infection, investigating the role of severe acute respiratory syndrome non-structural protein 1 and enterovirus 71 internal ribosome entry site.

Translation of mRNA into protein represents the final step in the gene-expression pathway, driving the formation of the proteome from genomic information. The regulation of this process is a mechanism that is used to modulate gene expression in a wide range of biological situations. Protein synthesis is principally regulated at the initiation stage, allowing for rapid, reversible control of gene expression. Progress over recent years in determining the structures and activities of regulatory factors, and in mapping their interactions, have advanced our understanding of the complex translation initiation process. These developments have provided a solid foundation for studying the regulation of translation initiation by mechanisms that include the modulation of initiation factor activity, internal ribosome initiation and through sequence-specific RNA-binding proteins. This thesis focused on translational control during viral infection, where we investigated the role of Severe Acute Respiratory Syndrome non-structural protein 1 and Enterovirus 71 Internal Ribosome Entry Site in this process. To establish the function of SARS NSP1 protein in translation regulation we attempted the identification of NSP1 protein partners using several types of protein affinity chromatography. Using a wide range of approaches, we could not detect nor confirm the association of NSP1 with any cellular proteins. To dissect the role of FBP2, we engineered a wide range of recombinant FBP2 proteins of different lengths and analysed their interactions with IRES elements using biochemical techniques. This allowed us to characterize the interaction of EV71 IRES with initiation factors eIF4A, eIF4E, eIF4G and FBP2. Finally, we used chemical probing of RNA structure in solution to establish the secondary structure of the BiP IRES. We identified the formation of a structured RNA scaffold of 220 nucleotides comprising 3 major domains

Antibacterial Activity of 2-Picolyl-polypyridyl-Based Ruthenium (II/III) Complexes on Non-Drug-Resistant and Drug-Resistant Bacteria

A new hexadentate 2-picolyl-polypyridyl-based ligand (4, 4'-(butane-1, 4-diylbis(oxy))bis(N, N-bis(pyridin-2-ylmethyl)aniline)) (2BUT) (1) and its corresponding Ru(II/III) complexes were synthesized and characterized, followed by assessment of their possible bioactive properties towards drug-resistant and non-drug-resistant bacteria. Spectroscopic characterization of the ligand was done using proton NMR, FTIR, and ESI-MS, which showed that the ligand was successfully synthesized. The Ru(II/III) complexes were characterized by FTIR, UV/Vis, elemental analysis, proton NMR, ESI-MS, and magnetic susceptibility studies. The analysis of ESI-MS data of the complexes showed that they were successfully synthesized. Empirical formulae derived from elemental analysis of the complexes also indicated successful synthesis and relative purity of the complexes. The important functional groups of the ligands could be observed after complexation using FTIR. Magnetic susceptibility data and electronic spectra indicated that both complexes adopt a low spin configuration. The disc diffusion assay was used to test the compounds for antibiotic activity on two bacteria species and their drug-resistant counterparts. The compounds displayed antibiotic activity towards the two non-drug-resistant bacteria. As for the drug-resistant organisms, only [Ru2(2BUT)(DMF)2(DPA)2](BH4)43 and 2, 2-dipyridylamine inhibited the growth of MRSA. Gel electrophoresis DNA cleavage studies showed that the ligands had no DNA cleaving properties while all the complexes denatured the bacterial DNA. Therefore, the complexes may have DNA nuclease activity towards the bacterial genomic material