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

Study of diabetes mellitus among patients with hepatitis C virus

IntroductionHepatitis C virus (HCV) infection and type 2 diabetes are two common disorders with high impact on health worldwide. There is growing evidence to support the concept that HCV is associated with type 2 diabetes. PurposeThis work aimed to study the clinical phenotype of type 2 diabetes in HCV patients. Patients and methods Our study was conducted upon 100 nonobese, noncirrhotic hepatitis C positive patients who were classified into two groups according to homeostatic model assessment (HOMA) test for insulin resistance (HOMA IR). This study also included 15 nonobese type 2 diabetic patients negative for HCV and hepatitis B virus infection classified as control groups. We excluded alcoholics and drug addicts and patients with conditions that affect blood glucose such as endocrine diseases associated with disordered glucose metabolism and use of drugs. All participants were subjected to full history taking and complete clinical examination including BMI and the following investigations: complete blood count, fasting blood sugar, 2 h postprandial blood sugar, glycosylated hemoglobin, fasting insulin level, cholesterol level, HDL, LDL, triglyceride, serum urea, creatinine, complete urine analysis, liver function tests: total bilirubin, alkaline phosphatase, albumin, prothrombin time, INR, SGOT, SGPT, quantitative PCR for determination of HCV-RNA, surface antigen (HbsAg), abdominal ultrasonography, liver biopsy when needed and possible for HCV patients, and ECG. Results In this study, we found that the prevalence of type 2 diabetes in group I is 24%. HCV can independently contribute to IR with viral genotypes 1 or 4. We noticed significant positive correlation between fasting insulin and HOMA IR in hepatitis C +ve patients. IR in HCV-infected patients is high irrespective of the degree of liver injury even before a minimal fibrosis is present. Both IR and diabetes can adversely affect the course of chronic hepatitis C, leading to enhanced steatosis and liver fibrosis, and even increase the risk of hepatocellular carcinoma. A significant correlation between HOMA IR and steatosis, a significant positive correlation between fasting insulin and steatosis and a negative correlation between steatosis and BMI in HCV patients was found. No correlation was found between HOMA IR and the viral load (quantitative HCV RNA). Conclusion We can concluded that diabetic HCV patients had intermediate clinical phenotype lower BMI and LDL than control and development of type 2 diabetes mellitus in HCV patients was significantly higher in nontreated patients than treated patients. Antiviral therapy and clearance of HCV improves IR, β-cell function, the blood glucose abnormalities

Wilms Tumor 1 Gene Mutations in Patients with Cytogenetically Normal Acute Myeloid Leukemia

OBJECTIVE: This study aimed to assess the prognostic impact of Wilms tumor 1 (WT1) mutations in cytogenetically normal acute myeloid leukemia (CN-AML) among Egyptian patients. METHODS: Exons 1, 2, 3, 7, 8, and 9 of WT1 were screened for mutations in samples from 82 CNAML patients out of 203 newly diagnosed AML patients, of age ranging from 21 to 74 years, using high-resolution capillary electrophoresis. RESULTS: Eleven patients out of 82 (13.41%) harbored WT1 mutations. Mutations were detected in exon 7 (n=7), exon 9 (n=2), exon 8 (n=1), and exon 3 (n=1), but not in exons 1 or 2. There was no statistically significant difference between the WT1 mutants and wild types as regards age, sex, French-American-British subtypes, and the prevalence of success of induction remission therapy (p=0.966; 28.6% vs. 29.3%). Patients with WT1 mutations had overall survival lower than patients with the wild type (HR=1.38; 95% CI 4.79-6.86; p=0.004). CONCLUSION: CN-AML patients with WT1 mutations have poor clinical outcome. We recommend molecular testing for WT1 mutations in patients with CN-AML at diagnosis in order to improve risk stratification of those patients

Clinical utility of serum Galactin-9 in evaluation of systemic lupus erythematosus patients

Aim of the work: To evaluate the levels of serum Galactin-9 (Gal-9) in systemic lupus erythematosus (SLE) patients and to assess its association with disease activity, severity, and renal affection. Patients and methods: The study included 50 SLE patients and 50 matched controls. SLE disease activity index (SLEDAI) was assessed and patients subdivided into active (SLEDAI > 4) and inactive (SLEDAI ≤ 4). Renal affection in SLE patients was assessed by rSLEDAI. Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI) was assessed.Serum Gal-9 levels were measuredby Enzyme-Linked Immunosorbent Assay (ELISA). Results: The mean age of SLE patients was 31.1 ± 8.7 years and the majority of studied groups were females. Gal-9 was significantly higher in SLE patients in comparison to healthy control (890.1 ± 1740.4 vs. 266.8 ± 37.9 ng/L); p < 0.0001) and in active compared to inactive LN patients (1377.9 ± 2273.8 vs. 317.6 ± 40.4, P < 0.001) was detected. Serum Gal-9 correlated with anti-dsDNA positivity (r = 0.29, p = 0.04), SLEDAI (r = 0.61, p ≤ 0.0001), and rSLEDAI (r = 0.61, p ≤ 0.0001). At a cut-off value of 299 ng/l Gal-9 can significantly differentiate SLE patients from controls (AUC 0.97; p < 0.0001) at a sensitivity of 88 %, specificity of 75 %, and accuracy of 83.3 %. Gal-9 at a cut-off value 335 ng/l can significantly differentiate active from inactive SLE patients (AUC 0.94; p < 0.0001) at a sensitivity of 90 %, specificity of 84.2 %, and accuracy of 88 %. Gal-9 was significant predictor for SLE activity. Conclusion: The serum Gal-9 levels were significantly high in SLE patients compared to healthy controls and these high levels were associated with disease activityand renal affection in SLE patients

Expression of the IL-6 receptor alpha-chain (CD126) in normal and abnormal plasma cells in monoclonal gammopathy of undetermined significance and smoldering myeloma

IL-6 activity in normal plasma cells (nPCs) and abnormal plasma cells (aPCs) is CD126 (subunit of IL-6 receptor) dependent. We quantified CD126 expression on nPCs and aPCs in monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma (SMM), and multiple myeloma (MM). CD126 was detected on all nPCs and aPCs indicating that CD126 does not have diagnostic utility. CD126 expression was higher in aPCs than in nPCs in 85% SMM but only 41% MGUS and there was evidence that CD126 was higher in aPCs than nPCs in the SMM (p = .048) but not MGUS (p = .96) patients. There is also a greater association between nPC and aPC CD126 expression in low risk MGUS than observed in high risk MGUS and SMM, suggesting normal regulation of CD126 decreases with disease progression. Future studies need to elucidate the role of bone marrow milieu versus escape from normal CD126 regulation in malignant transformation of clonal plasma cells

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially