Hepatitis B virus (HBV) (sub)genotypes A1, D3 and E circulate in sub-Saharan Africa, the region with one of the highest incidences of HBV-associated hepatocellular carcinoma globally. Although genotype E was identified more than 20 years ago, and is the most widespread genotype in Africa, it has not been extensively studied. The current knowledge status and gaps in its origin and evolution, natural history of infection, disease progression, response to antiviral therapy and vaccination are discussed. Genotype E is an African genotype, with unique molecular characteristics that is found mainly in Western and Central Africa and rarely outside Africa except in individuals of African descent. The low prevalence of this genotype in the African descendant populations in the New World, phylogeographic analyses, the low genetic diversity and evidence of remnants of genotype E in ancient HBV samples suggests the relatively recent re-introduction into the population. There is scarcity of information on the clinical and virological characteristics of genotype E-infected patients, disease progression and outcomes and efficacy of anti-HBV drugs. Individuals infected with genotype E have been characterised with high hepatitis B e antigen-positivity and high viral load with a lower end of treatment response to interferon-alpha. A minority of genotype E-infected participants have been included in studies in which treatment response was monitored. Of concern is that current guidelines do not consider patients infected with genotype E. Thus, there is an urgent need for further large-scale investigations into genotype E, the neglected genotype of HBV.

The antibiotic resistance profiles of Escherichia coli (E. coli), isolated from different water sources in the Mmabatho locality were evaluated. Water samples were collected from the local wastewater- and water-treatment plants, the Modimola Dam and homes in the area, and then analysed for the presence of E. coli, using standard methods. Presumptive isolates obtained were confirmed by the analytical profile index test. Antibiotic susceptibility testing was performed by the disc diffusion method. Of the 230 E. coli isolates tested, marked antibiotic resistances (over 70%) were observed for erythromycin, tetracycline, ampicillin, chloramphenicol and norfloxacin. Multiple antibiotic resistance patterns were also compiled. Overall, the phenotype T-Ap-E was frequent for E. coli isolated from the local wastewater and water-treatment plants, Modimola Dam and tap water. Cluster analysis performed showed a unique antibiotic resistance pattern which suggested a link between isolates from all sampling points. The findings indicated that improper wastewater treatment may have a potential impact on the dissemination and survival of E. coli, as well as other pathogenic bacteria in water for human and animal consumption. This may result in water- and food-borne disease outbreaks with a negative effect on antibiotic therapy.

cHepatitis C virus (HCV) exists as six major genotypes that differ in geographical distribution, pathogenesis, and response to antiviral therapy. In vitro replication systems for all HCV genotypes except genotype 5 have been reported. In this study, we recovered genotype 5a full-length genomes from four infected voluntary blood donors in South Africa and established a G418-selectable subgenomic replicon system using one of these strains. The replicon derived from the wild-type sequence failed to replicate in Huh-7.5 cells. However, the inclusion of the S2205I amino acid substitution, a cell culture-adaptive change originally described for a genotype 1b replicon, resulted in a small number of G418-resistant cell colonies. HCV RNA replication in these cells was confirmed by quantification of viral RNA and detection of the nonstructural protein NS5A. Sequence analysis of the viral RNAs isolated from multiple independent cell clones revealed the presence of several nonsynonymous mutations, which were localized mainly in the NS3 protein. These mutations, when introduced back into the parental backbone, significantly increased colony formation. To facilitate convenient monitoring of HCV RNA replication levels, the mutant with the highest replication level was further modified to express a fusion protein of firefly luciferase and neomycin phosphotransferase. Using such replicons from genotypes 1a, 1b, 2a, 3a, 4a, and 5a, we compared the effects of various HCV inhibitors on their replication. In conclusion, we have established an in vitro replication system for HCV genotype 5a, which will be useful for the development of pangenotype anti-HCV compounds. H epatitis C virus (HCV) currently infects approximately 185 million people worldwide, increasing their risk of developing liver cirrhosis and hepatocellular carcinoma (1). No vaccine is available against HCV infection, and the standard of care until 2011, consisting of PEGylated interferon (IFN) and ribavirin, cured only 50% of patients. However, the addition of direct-acting antiviral agents (DAAs) over the past few years has revolutionized HCV treatment, with cure rates now approaching 80 to 90% (2-5). The recently published results of phase 3 clinical trials report even better regimens with Ͼ95% cure rates (6, 7). These are exciting developments, yet the issues of drug resistance, side effects, and drug-drug interactions will remain a challenge. Therefore, the quest to find safe drugs with a pan-genotype activity and a high barrier to drug resistance will continue. To aid these efforts, it is important to have cell culture replication systems for all HCV genotypes. Of the six major HCV genotypes, replication systems for HCV genotypes 1 and 2 were developed over a decade ago (8-10) and provided a strong foundation for the development of currently approved antivirals. Recently, replication systems for genotypes 3, 4, and 6 have also been reported (11)(12)(13)(14). However, a similar system for genotype 5 is still lacking. This genotype is restricted mainly to South Afri...

Access to hepatitis C virus (HCV) testing and treatment is limited in Myanmar. We assessed an integrated HIV and viral hepatitis testing and HCV treatment strategy. Sofosbuvir/velpatasvir (SOF/VEL) ± weight‐based ribavirin for 12 weeks was provided at three treatment sites in Myanmar and sustained virologic response (SVR) assessed at 12 weeks after treatment. Participants co‐infected with HBV were treated concurrently with tenofovir. Cost estimates in 2018 USD were made at Yangon and Mandalay using standard micro‐costing methods. 803 participants initiated SOF/VEL; 4.8% were lost to follow‐up. SVR was achieved in 680/803 (84.6%) by intention‐to‐treat analysis. SVR amongst people who inject drugs (PWID) was 79.7% (381/497), but 92.5% among PWID on opioid substitution therapy (OST) (74/80), and 97.4% among non‐PWID (298/306). Utilizing data from 492 participants, of whom 93% achieved SVR, the estimated average cost of treatment per patient initiated was $1030 (of which 54% were medication costs), with a production cost per successful outcome (SVR) of $1109 and real‐world estimate of $1250. High SVR rates were achieved for non‐PWID and PWID on OST. However, the estimated average cost of the intervention (under the assumption of no genotype testing and reduced real‐world effectiveness) of $1250/patient is unaffordable for a national elimination strategy. Reductions in the cost of antivirals and linkage to social and behavioural health services including substance use disorder treatment to increase retention and adherence to treatment are critical to HCV elimination in this population.