Why pathogen genomics is crucial in Africa’s public health

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The need for a balanced hospital-based care (HBC) and home- and community-based care (HCBC) approach for COVID-19 pandemic in sub-Saharan Africa

The onslaught of COVID-19 pandemic has greatly overwhelmed some of the best healthcare systems in the world. Medical practitioners working in hospitals at the epicenters of COVID-19 pandemic have emphasized on the need to manage mildly ill and convalescent COVID-19 patients at home or community facilities rather than at hospitals during a pandemic. In this article, we highlight that a standardized home- and community-based (HCBC) approach for management of COVID-19 patients will be a key component for preparing hospitals in sub-Saharan Africa (SSA) for a potential surge in COVID-19 cases. So far, based on the trajectory of infection, we think that SSA seems to have a window of opportunity, albeit narrowing, for implementing HCBC. However there are challenges that will need to be addressed in order to implement and maintain HCBC. Successful implementation and maintenance of HCBC in SSA will require international agencies and key donors to work closely with the national governments; providing them with policy, technical, and financial assistance. HCBC is also important because it can play a role in advocacy, education, training, and health promotion during COVID-19 pandemic. We further underscore the need for a delicate balance between HCBC and hospital-based care (HBC) approach as well as with COVID-19 mitigation and suppression measures in order to reduce the risk of SARS-CoV-2 community transmission and allow optimal continuity of the HBC. We conclude by emphasizing once again that, for countries in SSA to adequately prepare for the worst-case scenario of COVID-19 pandemic in the absence of a cure, policy makers of member states need to act collectively and fast.https://deepblue.lib.umich.edu/bitstream/2027.42/156028/1/REV_Onywera et al_AFM.pdfDescription of REV_Onywera et al_AFM.pdf : Main Articl

The Cumulative Effects of Polymorphisms in the DNA Mismatch Repair Genes and Tobacco Smoking in Oesophageal Cancer Risk

The DNA mismatch repair (MMR) enzymes repair errors in DNA that occur during normal DNA metabolism or are induced by certain cancer-contributing exposures. We assessed the association between 10 single-nucleotide polymorphisms (SNPs) in 5 MMR genes and oesophageal cancer risk in South Africans. Prior to genotyping, SNPs were selected from the HapMap database, based on their significantly different genotypic distributions between European ancestry populations and four HapMap populations of African origin. In the Mixed Ancestry group, the MSH3 rs26279 G/G versus A/A or A/G genotype was positively associated with cancer (OR = 2.71; 95% CI: 1.34–5.50). Similar associations were observed for PMS1 rs5742938 (GG versus AA or AG: OR = 1.73; 95% CI: 1.07–2.79) and MLH3 rs28756991 (AA or GA versus GG: OR = 2.07; 95% IC: 1.04–4.12). In Black individuals, however, no association between MMR polymorhisms and cancer risk was observed in individual SNP analysis. The interactions between MMR genes were evaluated using the model-based multifactor-dimensionality reduction approach, which showed a significant genetic interaction between SNPs in MSH2, MSH3 and PMS1 genes in Black and Mixed Ancestry subjects, respectively. The data also implies that pathogenesis of common polymorphisms in MMR genes is influenced by exposure to tobacco smoke. In conclusion, our findings suggest that common polymorphisms in MMR genes and/or their combined effects might be involved in the aetiology of oesophageal cancer

Delineation of the HPV11E6 and HPV18E6 Pathways in Initiating Cellular Transformation

Although high-risk human papillomaviruses (HPVs) are the major risk factors for cervical cancer they have been associated with several other cancers, such as head and neck and oral cancers. Since integration of low-risk HPV11 DNA has been demonstrated in esophageal tumor genomes, this study compared the effects of low-risk HPV11E6 and high-risk HPV18E6 on cellular gene expression. The HPV11E6 and HPV18E6 genes were cloned into an adenoviral vector and expressed in human keratinocytes (HaCaT) in order to investigate early events and to eliminate possible artifacts introduced by selective survival of fast growing cells in stable transfection experiments. HPV11E6 had very little effect on p21 and p53 gene expression, while HPV18E6 resulted in a marked reduction in both these proteins. Both HPV11E6 and HPV18E6 enabled growth of colonies in soft agar, but the level of colony formation was higher in HPV18E6 infected cells. DNA microarray analysis identified significantly differentially regulated genes involved in the cellular transformation signaling pathways. These findings suggest that HPV11E6 and HPV18E6 are important in initiating cellular transformation via deregulation of signaling pathways such as PI3K/AKT and pathways that are directly involved in DNA damage repair, cell survival, and cell proliferation. This study shows that the low-risk HPV11E6 may have similar effects as the high-risk HPV18E6 during the initial stages of infection, but at a much reduced level

Determining the potential human health risks posed by heavy metals present in municipal sewage sludge from a wastewater treatment plant

The study looked to establish the elemental composition of heavy metals such as Zn, Mn, Cu, Cr, Ni, Pb, As, and Co, present in sewage sludge and assessed their health risks. Samples were taken from the Gammams Wastewater Treatment Plant in Windhoek, Namibia and used for the analysis. Two samples of sludge were collected twice in the same week. The samples of sewage sludge were subjected to the hot-plate acid digestion method prior to the determination of the heavy metals using an Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). The evaluation of the health risks was performed according to the U.S Environmental Protection Agency (USEPA) and South African Guidelines. Their elemental contents ranged from 65.75 - 82.17 mg/kg for Zn, 29.31 - 56.98 mg/kg for Mn, 21.46 - 49.20 mg/kg for Cu, 19.44 - 29.20 mg/kg for Cr, 2.88 - 3.82 mg/kg for Ni, 1.84 - 4.22 mg/kg for Pb, 0.83 - 1.74 mg/kg for As and 0.26 - 0.98 mg/kg for Co. Each of the levels for the heavy metals were found to be below the standard permissible limits of the two regulations and therefore are considered safe for land-based applications (agriculture) and were also associated with low health risks. The risk assessment is considered for the estimation of potential human health risks which also evaluates the likelihood of adverse health risks. Furthermore, the study revealed that children are more susceptible to carcinogenic and non-carcinogenic health risks in comparison to adults via the ingestion pathway

Characterization of Shiga toxin-producing Escherichia coli in raw beef from informal and commercial abattoirs.

Shiga toxin-producing Escherichia coli are foodborne pathogens that are mostly associated with beef products and have been implicated in human illness. E.coli-associated illness range from asymptomatic conditions of mild diarrhoea to haemorrhagic colitis which can progress into life threatening haemolytic uremic syndrome (HUS). Beef from cattle are regarded as the main reservoir of Shiga toxin-producing E. coli (STEC) pathogen. The aim of this study was to assess the level and sources of contamination of raw beef with STEC, and determine the incidences of STEC strains in raw beef from informal and commercial abattoirs in Windhoek, Namibia. A total of 204 raw beef samples, 37 equipment and 29 hand swabs were collected and tested for STEC. The meat samples were first enriched with pre-warmed buffered peptone water, cultured on Tryptone Bile X-Glucuronide and CHROMagar STEC, and then sub-cultured on nutrient agar. The presence of E.coli in the samples was confirmed by using VITEK 2 E.coli identification cards and PCR. The overall prevalence of STEC in the meat samples from both the abattoirs was 41.66% raw beef samples; 5.40% equipment swabs; and none of the hand swabs was STEC positive. From the STEC positive meat samples 29.41% contained one of the major STEC strains. Moreover, 52% of the 25 samples that contained the major STECs were characterised by eae and stx1, 8% characterised by eae and stx2 while 40% were characterised by eae, stx1 and stx2 virulence genes. This study has revealed the necessity for proper training on meat safety (for meat handlers) as well as the development, implementation and maintenance of effective sanitary dressing procedures at abattoirs to eliminate beef contamination by STECs thereby ensuring the production of wholesome meat, and to prevent the occurrences of STEC infections

Effects of smoking and drinking on oesophageal cancer risk.

<p>Effects of smoking and drinking on oesophageal cancer risk.</p

Characteristics of study subjects.

<p>OSCC, oesophageal Squamous cell carcinoma; OAC, oesophageal adenocarcinoma.</p

Individual SNP effects on oesophageal cancer risk in two ethnic groups of South African population.

a<p>Minor alleles are different between the two ethnic groups, hence genetic model indicated in brackets was investigated in Mixed Ancestry group. Significant associations are printed in bold.</p><p>AOR, odds ratio adjusted for age, gender,smoking status, alcohol intake, place of birth and family history of cancer; CI, confidence interval; ND, not determined (zero genotypes were found in one genotype group).</p