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

Microbiological analysis of nosocomial pneumonia at Tanta University Chest Hospital

Abstract Background Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) represent a major health problem among hospitalized patients leading to consequent morbidity and mortality specially after Covid-19 era and spread of multidrug-resistance organisms)MDRO) in hospitals. Aim This study aimed to analyze the commonest microorganisms responsible for HAP and VAP at Tanta University Chest Hospital. Methods This prospective observational study was done at Chest Department, Faculty of Medicine, started from June 2022 to February 2023. Fifty HAP patients’ sputum samples and 50 VAP patients (25 endotracheal aspirates and 25 bronchoalveolar lavages) were included. All collected samples were submitted to standard microbiological tests at Microbiology Department, Tanta Faculty of Medicine. Results A total number of 50 HAP and 50 VAP cases were included. Microbial isolates were relatively the same in both groups, where Klebsiella pneumoniae was the predominant isolates (56) followed by Staphylococcus aureus (25), Escherichia coli (14), Pseudomonas aeruginosa (13), Acinetobacter baumannii (5), Streptococcus pneumoniae (4), Enterococci (3), Stenotrophomonas maltophilia (2), Citrobacter freundii (2), Streptococcus pyogenes (2), Providencia stuartii (1), and 7 isolates of Candida. Antimicrobial susceptibility showed predominance of drug-resistance organisms in VAP (78%) versus HAP (28%), P-value: < 0.001. Klebsiella pneumonia showed higher rates of resistance (37 out of 56 isolates, P-value = 0.020). Four out of 5 Acinetobacter baumannii isolates were multidrug resistant, and 2 isolates of Stenotrophomonas maltophilia were polydrug resistant. Multivariate logistic regression analysis showed that intravenous antibiotic administration within last 3 months was associated with risk for MDR-HAP, while univariate regression analysis showed that intravenous antibiotic administration within the last 3 months was the strongest predictor for MDR-VAP. A higher mortality rate was recorded in VAP group (66%), versus (14%) in HAP group (P-value: < 0.001). Conclusion Microbial isolates were relatively the same in both HAP and VAP, but VAP showed significant predominance of drug-resistant organisms. The most significant predictor for risk of MDRO infection in HAP and VAP was intravenous antibiotic administration within last 3 months; so, raising attention towards antibiotic choice may improve the outcome. Finally, VAP was associated with higher mortality compared to HAP

Molecular detection, phylogenetic analysis and genetic diversity of recently isolated foot-and-mouth disease virus serotype A African topotype, Genotype IV

Background Surveillance for circulating emerging diseases of economic importance has a major role in the rapid response to major pathogen outbreaks. Foot-and-mouth disease virus (FMDV) is one of the significant endemic viruses in Egypt. FMDV is periodically investigated for monitoring evolution and emergence of new variants. The genetic characterization of foot-and-mouth disease (FMD) virus serotype A responsible for recent outbreaks of FMD in Egypt was determined. Methods Samples were collected from different locations and virus isolation was performed using BHK-21 cells. Viral RNA was extracted and samples were screened for FMDV using real-time RT-PCR. DNA sequence analysis was performed and computational and bioinformatics analyses were used to determine the substitution rates and phylogenetic relationship. Results Sequence and phylogenetic analyses of full-length 1D region of FMDV samples collected from different governorates in 2020 showed close similarity to Egyptian FMDV strains from serotype A-African topotype-G-IV with genetic variation of 6.5%. Recently isolated FMDV strains showed high genetic variations from locally used vaccine strains in the major antigenic sites of VP1 region. Conclusions Although, efforts made by the veterinary authorities to implement an effective mass vaccination plan, the recently detected FMDV strains in this study could not be subtyped using the FMDV primers routinely used for molecular serotyping. These dissimilarities raise the alarm for reconsideration of the FMDV isolates used in vaccine manufacture. Clearly close monitoring of FMD in Egypt is urgently required to define the risks of future outbreaks and to ensure appropriate control measures against FMD major outbreaks

Structures and Chemical Equilibria of Some N-Heterocycles Containing Amide Linkages

Structures and chemical equilibria of 5-carboxy-2-thiouracil (1), 5,6-diphenyl-3-hydroxy-1,2,4-triazine (2), 1-phenyl-3-methyl-5-pyrazolone (3) and 2-mercapto-4,6-dimethylpyrimidine hydrochloride (4) are reported. Their electronic transitions are assigned and pK values are evaluated and discussed

Bioefficacy of Epaltes divaricata (L.) n-Hexane Extracts and Their Major Metabolites against the Lepidopteran Pests Spodoptera litura (fab.) and Dengue Mosquito Aedes aegypti (Linn.)

The present research investigated the chemical characterization and insecticidal activity of n-Hexane extracts of Epaltes divaricata (NH-EDx) along with their chief derivatives n-Hexadecanoic acid (n-HDa) and n-Octadecanoic acid (n-ODa) against the dengue vector Aedes aegypti and lepidopteran pest Spodoptera litura. Chemical screening of NH-EDx through GC–MS analysis delivered nine major derivatives, and the maximum peak area percentage was observed in n-Hexadecanoic acid (14.63%) followed by n-Octadecadienoic acid (6.73%). The larvicidal activity of NH-EDx (1000 ppm), n-HDa (5 ppm), and n-ODa (5 ppm) against the A. aegypti and S. litura larvae showed significant mortality rate in a dose-dependent way across all the instars. The larvicidal activity was profound in the A. aegypti as compared to the S. litura across all the larval instars. The sublethal dosages of NH-EDx (500 ppm), n-HDa (2.5 ppm), and n-ODa (2.5 ppm) also showed alterations in the larval/pupal durations and adult longevity in both the insect pests. The enzyme activity revealed that the α- and β-carboxylesterase levels were decreased significantly in both the insect pests, whereas the levels of GST and CYP450 uplifted in a dose-dependent manner of NH-EDx, n-HDa, and n-ODa. Correspondingly, midgut tissues such as the epithelial layer (EL), gut lumen (GL), peritrophic matrix (Pm), and brush border membrane (BBM) were significantly altered in their morphology across both A. aegypti and S. litura against the NH-EDx and their bioactive metabolites. NH-EDx and their bioactive metabolites n-HDa and n-ODa showed significant larvicidal, growth retardant, enzyme inhibition, and midgut toxicity effects against two crucial agriculturally and medically challenging insect pest of ecological importance

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

Prevalence, years lived with disability, and trends in anaemia burden by severity and cause, 1990–2021: findings from the Global Burden of Disease Study 2021

Background: Anaemia is a major health problem worldwide. Global estimates of anaemia burden are crucial for developing appropriate interventions to meet current international targets for disease mitigation. We describe the prevalence, years lived with disability, and trends of anaemia and its underlying causes in 204 countries and territories. Methods: We estimated population-level distributions of haemoglobin concentration by age and sex for each location from 1990 to 2021. We then calculated anaemia burden by severity and associated years lived with disability (YLDs). With data on prevalence of the causes of anaemia and associated cause-specific shifts in haemoglobin concentrations, we modelled the proportion of anaemia attributed to 37 underlying causes for all locations, years, and demographics in the Global Burden of Disease Study 2021. Findings: In 2021, the global prevalence of anaemia across all ages was 24·3% (95% uncertainty interval [UI] 23·9–24·7), corresponding to 1·92 billion (1·89–1·95) prevalent cases, compared with a prevalence of 28·2% (27·8–28·5) and 1·50 billion (1·48–1·52) prevalent cases in 1990. Large variations were observed in anaemia burden by age, sex, and geography, with children younger than 5 years, women, and countries in sub-Saharan Africa and south Asia being particularly affected. Anaemia caused 52·0 million (35·1–75·1) YLDs in 2021, and the YLD rate due to anaemia declined with increasing Socio-demographic Index. The most common causes of anaemia YLDs in 2021 were dietary iron deficiency (cause-specific anaemia YLD rate per 100 000 population: 422·4 [95% UI 286·1–612·9]), haemoglobinopathies and haemolytic anaemias (89·0 [58·2–123·7]), and other neglected tropical diseases (36·3 [24·4–52·8]), collectively accounting for 84·7% (84·1–85·2) of anaemia YLDs. Interpretation: Anaemia remains a substantial global health challenge, with persistent disparities according to age, sex, and geography. Estimates of cause-specific anaemia burden can be used to design locally relevant health interventions aimed at improving anaemia management and prevention. Funding: Bill & Melinda Gates Foundation