Atypical and dual biotypes variant of virulent SA-NAG-Vibrio cholerae: an evidence of emerging/evolving patho-significant strain in municipal domestic water sources

Introduction and purpose The recent cholera spread, new cases, and fatality continue to arouse concern in public health systems; however, interventions on control is at its peak yet statistics show continuous report. This study characterized atypical and patho-significant environmental Vibrio cholerae retrieved from ground/surface/domestic water in rural-urban-sub-urban locations of Amathole District municipality and Chris Hani District municipality, Eastern Cape Province, South Africa. Methods Domestic/surface water was sampled and 759 presumptive V. cholerae isolates were retrieved using standard microbiological methods. Virulence phenotypic test: toxin co-regulated pili (tcp), choleragen red, protease production, lecithinase production, and lipase test were conducted. Serotyping using polyvalent antisera (Bengal and Ogawa/Inaba/Hikojima) and molecular typing: 16SrRNA, OmpW, serogroup (Vc-O1/O139), biotype (tcpAClas/El Tor, HlyAClas/El Tor, rstRClas/El Tor, RS1, rtxA, rtxC), and virulence (ctxA, ctxB, zot, ace, cep, prt, toxR, hlyA) genes were targeted. Result Result of 16SrRNA typing confirmed 508 (66.9%) while OmpW detected/confirmed 61 (12.01%) V. cholerae strains. Phenotypic-biotyping scheme showed positive test to polymyxin B (68.9%), Voges proskauer (6.6%), and Bengal serology (11.5%). Whereas Vc-O1/O139 was negative, yet two of the isolates harbored the cholera toxin with a gene-type ctxB and hlyAClas: 2/61, revealing atypical/unusual/dual biotype phenotypic/genotypic features. Other potential atypical genotypes detected include rstR: 7/61, Cep: 15/61, ace: 20/61, hlyAElTor: 53/61, rtxA: 30/61, rtxC: 11/61, and prtV: 15/61 respectively. Conclusion Although additional patho-significant/virulent genotypes associated with epidemic/sporadic cholera cases were detected, an advanced, bioinformatics, and post-molecular evaluation is necessary. Such stride possesses potential to adequately minimize future cholera cases associated with dynamic/atypical environmental V. cholerae strains.

Estimating the Effects of Public Health Measures by SEIR(MH) Model of COVID-19 Epidemic in Local Geographic Areas

The COVID-19 pandemic of 2020–21 has been a major challenge to public health systems worldwide. Mathematical models of epidemic are useful tools for assessment of the situation and for providing decision-making support for relevant authorities. We developed and implemented SEIR(MH) model that extends the conventional SEIR model with parameters that define public lockdown (the level and start of lockdown) and the medical system capacity to contain patients. Comparative modeling of four regions in Europe that have similar population sizes and age structures, but different public health systems, was performed: Baden-Württemberg, Lombardy, Belgium, and Switzerland. Modeling suggests that the most effective measure for controlling epidemic is early lockdown (exponential effect), followed by the number of available hospital beds (linear effect if the capacity is insufficient, with diminishing returns when the capacity is sufficient). Dynamic management of lockdown levels is likely to produce better outcomes than strict lockdown.

2-Sulfonylpyrimidines as Privileged Warheads for the Development of S. aureus Sortase A Inhibitors

Staphylococcus aureus is one of the most frequent causes of nosocomial and community-acquired infections, with emerging multiresistant isolates causing a significant burden to public health systems. We identified 2-sulfonylpyrimidines as a new class of potent inhibitors against S. aureus sortase A acting by covalent modification of the active site cysteine 184. Series of derivatives were synthesized to derive structure-activity relationship (SAR) with the most potent compounds displaying low micromolar KI values. Studies on the inhibition selectivity of homologous cysteine proteases showed that 2-sulfonylpyrimidines reacted efficiently with protonated cysteine residues as found in sortase A, though surprisingly, no reaction occurred with the more nucleophilic cysteine residue from imidazolinium-thiolate dyads of cathepsin-like proteases. By means of enzymatic and chemical kinetics as well as quantum chemical calculations, it could be rationalized that the SNAr reaction between protonated cysteine residues and 2-sulfonylpyrimidines proceeds in a concerted fashion, and the mechanism involves a ternary transition state with a conjugated base. Molecular docking and enzyme inhibition at variable pH values allowed us to hypothesize that in sortase A this base is represented by the catalytic histidine 120, which could be substantiated by QM model calculation with 4-methylimidazole as histidine analog.

Big Data at the Service of the Public Health Systems

The great differential of organizations has been the strategic innovation through the best way to manage existing knowledge. The management of information and knowledge generated in the health area is no different, as is the case with the pharmaceutical sector. The major challenge of public health research is to promote the use of scientific and technological knowledge produced in more effective health policy and action strategies in order to provide effective health gains. New technologies are promising tools to support public health management. The current scenario, in which the world has been affected by the COVID-19 pandemic, has reinforced this understanding. This chapter aims to highlight the importance of using big data tools to make public health policies more effective. Examples of successful cases in different areas of Brazilian public management will be presented, aiming to reinforce the relevance of these tools for public health systems.

Factors Influencing Job Satisfaction Among Recently Qualified Resident Doctors: A qualitative study

Introduction: Public health systems throughout the world are constantly being confronted with serious shortages of doctors. The Saudi health system acknowledges the risks involved in its heavy dependence on non-Saudi doctors and has gradually expanded its efforts to nationalize its medical staff by improving the capacity of the medical education system through increasing the number of medical colleges. The objective of this study was to explore the most crucial factors that influence job satisfaction among recently qualified resident doctors in Saudi Arabia. Methods: The study used a qualitative approach, with in-depth interviews that were conducted with recently qualified resident doctors to gather information on the factors that were the most critical in affecting their job satisfaction early in their careers. Twenty-five qualified resident doctors were purposively selected for interviews. The participants were selected from various areas of specialization, such as internal medicine, surgery, pediatrics, obstetrics, gynecology, and emergency medicine. Results: This study emphasized the importance of improving the satisfaction levels of recently qualified resident doctors with respect to a range of job-related factors. The following seven themes emerged from the data: education and development, recognition and respect, professionalism, workload, healthcare facilities, patient adherence, and salary. Conclusion: An increased investment in medical education is recommended to improve educational outcomes. The satisfaction that recently qualified resident doctors have with regard to their salaries should be monitored continuously, and further evidence is needed to determine whether modifications are required. Improving the satisfaction levels of the resident doctors in the seven specific areas of their jobs can result in greater retention.

Adequacy of Existing Surveillance Systems to Monitor Racism, Social Stigma and COVID Inequities: A Detailed Assessment and Recommendations

The populations impacted most by COVID are also impacted by racism and related social stigma; however, traditional surveillance tools may not capture the intersectionality of these relationships. We conducted a detailed assessment of diverse surveillance systems and databases to identify characteristics, constraints and best practices that might inform the development of a novel COVID surveillance system that achieves these aims. We used subject area expertise, an expert panel and CDC guidance to generate an initial list of N > 50 existing surveillance systems as of 29 October 2020, and systematically excluded those not advancing the project aims. This yielded a final reduced group (n = 10) of COVID surveillance systems (n = 3), other public health systems (4) and systems tracking racism and/or social stigma (n = 3, which we evaluated by using CDC evaluation criteria and Critical Race Theory. Overall, the most important contribution of COVID-19 surveillance systems is their real-time (e.g., daily) or near-real-time (e.g., weekly) reporting; however, they are severely constrained by the lack of complete data on race/ethnicity, making it difficult to monitor racial/ethnic inequities. Other public health systems have validated measures of psychosocial and behavioral factors and some racism or stigma-related factors but lack the timeliness needed in a pandemic. Systems that monitor racism report historical data on, for instance, hate crimes, but do not capture current patterns, and it is unclear how representativeness the findings are. Though existing surveillance systems offer important strengths for monitoring health conditions or racism and related stigma, new surveillance strategies are needed to monitor their intersecting relationships more rigorously.

Limited Impact of Delta Variant’s Mutations on the Effectiveness of Neutralization Conferred by Natural Infection or COVID-19 Vaccines in a Latino Population

The SARS-CoV-2 pandemic has impacted public health systems all over the world. The Delta variant seems to possess enhanced transmissibility, but no clear evidence suggests it has increased virulence. Our data show that pre-exposed individuals had similar neutralizing activity against the authentic COVID-19 strain and the Delta and Epsilon variants. After only one vaccine dose, the neutralization capacity expanded to all tested variants in pre-exposed individuals. Healthy vaccinated individuals showed a limited breadth of neutralization. One vaccine dose did induce similar neutralizing antibodies against the Delta as against the authentic strain. However, even after two doses, this capacity only expanded to the Epsilon variant.

Artificial Intelligence and Antibiotic Discovery

Over recent decades, a new antibiotic crisis has been unfolding due to a decreased research in this domain, a low return of investment for the companies that developed the drug, a lengthy and difficult research process, a low success rate for candidate molecules, an increased use of antibiotics in farms and an overall inappropriate use of antibiotics. This has led to a series of pathogens developing antibiotic resistance, which poses severe threats to public health systems while also driving up the costs of hospitalization and treatment. Moreover, without proper action and collaboration between academic and health institutions, a catastrophic trend might develop, with the possibility of returning to a pre-antibiotic era. Nevertheless, new emerging AI-based technologies have started to enter the field of antibiotic and drug development, offering a new perspective to an ever-growing problem. Cheaper and faster research can be achieved through algorithms that identify hit compounds, thereby further accelerating the development of new antibiotics, which represents a vital step in solving the current antibiotic crisis. The aim of this review is to provide an extended overview of the current artificial intelligence-based technologies that are used for antibiotic discovery, together with their technological and economic impact on the industrial sector.