Strategies to Improve Antimicrobial Utilization with a Special Focus on Developing Countries.

Antimicrobial resistance (AMR) is a high priority across countries as it increases morbidity, mortality and costs. Concerns with AMR have resulted in multiple initiatives internationally, nationally and regionally to enhance appropriate antibiotic utilization across sectors to reduce AMR, with the overuse of antibiotics exacerbated by the COVID-19 pandemic. Effectively tackling AMR is crucial for all countries. Principally a narrative review of ongoing activities across sectors was undertaken to improve antimicrobial use and address issues with vaccines including COVID-19. Point prevalence surveys have been successful in hospitals to identify areas for quality improvement programs, principally centering on antimicrobial stewardship programs. These include reducing prolonged antibiotic use to prevent surgical site infections. Multiple activities centering on education have been successful in reducing inappropriate prescribing and dispensing of antimicrobials in ambulatory care for essentially viral infections such as acute respiratory infections. It is imperative to develop new quality indicators for ambulatory care given current concerns, and instigate programs with clear public health messaging to reduce misinformation, essential for pandemics. Regular access to effective treatments is needed to reduce resistance to treatments for HIV, malaria and tuberculosis. Key stakeholder groups can instigate multiple initiatives to reduce AMR. These need to be followed up.

Improving the Understanding of the Immunopathogenesis of Lymphopenia as a Correlate of SARS-CoV-2 Infection Risk and Disease Progression in African Patients: Protocol for a Cross-sectional Study.

BACKGROUND: The COVID-19 pandemic, caused by SARS-CoV-2, continues to impact health systems throughout the world with serious medical challenges being imposed on many African countries like Nigeria. Although emerging studies have identified lymphopenia as a driver of cytokine storm, disease progression, and poor outcomes in infected patients, its immunopathogenesis, as well as environmental and genetic determinants, remain unclear. Understanding the interplay of these determinants in the context of lymphopenia and COVID-19 complications in patients in Africa may help with risk stratification and appropriate deployment of targeted treatment regimens with repurposed drugs to improve prognosis. OBJECTIVE: This study is designed to investigate the role of vitamin D status, vasculopathy, apoptotic pathways, and vitamin D receptor (VDR) gene polymorphisms in the immunopathogenesis of lymphopenia among African people infected with SARS-CoV-2. METHODS: This cross-sectional study will enroll 230 participants, categorized as "SARS-CoV-2 negative" (n=69), "COVID-19 mild" (n=32), "hospitalized" (n=92), and "recovered" (n=37), from two health facilities in Lagos, Nigeria. Sociodemographic data, travel history, and information on comorbidities will be obtained from case files and through a pretested, interview-based structured questionnaire. Venous blood samples (5 mL) collected between 8 AM and 10 AM and aliquoted into EDTA (ethylenediaminetetraacetic acid) and plain tubes will be used for complete blood count and CD4 T cell assays to determine lymphopenia (lymphocyte count <1000 cells/µL) and CD4 T lymphocyte levels, as well as to measure the concentrations of vitamin D, caspase 3, soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble Fas ligand (sFasL) using an autoanalyzer, flow cytometry, and ELISA (enzyme-linked immunosorbent assay) techniques. Genomic DNA will be extracted from the buffy coat and used as a template for the amplification of apoptosis-related genes (Bax, Bcl-2, BCL2L12) by polymerase chain reaction (PCR) and genotyping of VDR (Apa1, Fok1, and Bsm1) gene polymorphisms by the PCR restriction fragment length polymorphism method and capillary sequencing. Total RNA will also be extracted, reverse transcribed, and subsequently quantitated by reverse transcription PCR (RT-PCR) to monitor the expression of apoptosis genes in the four participant categories. Data analyses, which include a test of association between VDR gene polymorphisms and study outcomes (lymphopenia and hypovitaminosis D prevalence, mild/moderate and severe infections) will be performed using the R statistical software. Hardy-Weinberg equilibrium and linkage disequilibrium analyses for the alleles, genotypes, and haplotypes of the genotyped VDR gene will also be carried out. RESULTS: A total of 45 participants comprising 37 SARS-CoV-2-negative and 8 COVID-19-recovered individuals have been enrolled so far. Their complete blood counts and CD4 T lymphocyte counts have been determined, and their serum samples and genomic DNA and RNA samples have been extracted and stored at -20 °C until further analyses. Other expected outcomes include the prevalence and distribution of lymphopenia and hypovitaminosis D in the control (SARS-CoV-2 negative), confirmed, hospitalized, and recovered SARS-CoV-2-positive participants; association of lymphopenia with CD4 T lymphocyte level, serum vitamin D, sVCAM-1, sFasL, and caspase 3 levels in hospitalized patients with COVID-19; expression levels of apoptosis-related genes among hospitalized participants with COVID-19, and those with lymphopenia compared to those without lymphopenia; and frequency distribution of the alleles, genotypes, and haplotypes of VDR gene polymorphisms in COVID-19-infected participants. CONCLUSIONS: This study will aid in the genotypic and phenotypic stratification of COVID-19-infected patients in Nigeria with and without lymphopenia to enable biomarker discovery and pave the way for the appropriate and timely deployment of patient-centered treatments to improve prognosis. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/21242.

COVID-19 rapid diagnostic test could contain transmission in low- and middle-income countries.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has impacted heavily on global health. Although real-time polymerase chain reaction (RT-PCR) is the current diagnostic method, challenges for low- and middle-income countries (LMICs) necessitate cheaper, higher-throughput, reliable rapid diagnostic tests (RDTs). OBJECTIVE: We reviewed the documented performance characteristics of available COVID-19 RDTs to understand their public health utility in the ongoing pandemic, especially in resource-scarce LMIC settings. METHODS: Using a scoping review methodology framework, common literature databases and documentary reports were searched up to 22 April 2020, irrespective of geographical location. The search terms included 'SARS-CoV-2 AND serological testing' and 'COVID-19 AND serological testing'. RESULTS: A total of 18 RDTs produced in eight countries, namely China (6; 33.33%), the United States (4; 22.22%), Germany (2; 11.11%), Singapore (2; 11.11%), Canada, Kenya, Korea and Belgium (1 each; 5.56%), were evaluated. Reported sensitivity ranged from 18.4% to 100% (average = 84.7%), whereas specificity ranged from 90.6% to 100% (average = 95.6%). The testing time ranged from 2 min to 30 min. Of the 12 validated RDTs, the IgM/IgG duo kit with non-colloidal gold labelling system was reported to elicit the highest sensitivity (98% - 100%) and specificity (98% - 99% for IgG and 96% - 99% for IgM). CONCLUSION: We found reports of high sensitivity and specificity among the developed RDTs that could complement RT-PCR for the detection of SARS-CoV-2 antibodies, especially for screening in LMICs. However, it is necessary to validate these kits locally.