The prevalence of antimicrobial drug resistance of non-typhoidal Salmonella in human infections in sub-Saharan Africa: a systematic review and meta-analysis.

INTRODUCTION: Non-typhoidal Salmonella (NTS) bacteremia is common in sub-Saharan Africa. We examined the prevalence of antibiotic resistance to fluoroquinolones, third-generation cephalosporins, and multi-drug resistance (MDR) in NTS human isolates from sub-Saharan Africa. METHODS: A systematic review was conducted using a search in Ovid Medline, Embase, and African Index Medicus of publications between 2000 and 2021. A random-effects model meta-analysis was performed using data from 66 studies that included 29,039 NTS blood and 1,065 stool isolates. RESULTS: The pooled prevalence proportions of MDR were 0.685 (95% CI 0.574-0.778) and 0.214 (0.020-0.785) in blood vs. stool isolates. The corresponding estimates of fluoroquinolones resistance were 0.014 (0.008-0.025) vs. 0.021 (0.012-0.036) and third-generation cephalosporins resistance 0.019 (0.012-0.031) vs. 0.035 (0.006-0.185). Similar results were found for children and adults. Resistance prevalence to these antibiotics in blood isolates increased between 2000-2010 and 2011-2021. The guidelines employed to determine antimicrobial resistance and epidemiological characteristics (e.g. sample size, study duration) correlated with the resistance prevalence. CONCLUSIONS: The prevalence of MDR and resistance to fluoroquinolones and third-generation cephalosporins in NTS in sub-Saharan Africa is alarming. EXPERT OPINION: Standardized surveillance of antimicrobial drug resistance in NTS in sub-Saharan Africa is warranted to guide healthcare policymaking and antibiotic stewardship programs.

Non-typhoidal Salmonella (NTS) usually causes diarrheal disease, but some patients might develop bloodstream infection. The occurrence and case fatality of bloodstream infections caused by NTS are high in sub-Saharan Africa. However, the information on antibiotic resistance of these bacteria in this region is scarce. We performed a systematic review and meta-analysis to examine the prevalence of multi-drug resistance (MDR) and resistance to antibiotics used to treat NTS bloodstream infection: fluoroquinolones and third-generation cephalosporins in NTS isolates from patients from sub-Saharan Africa.We used data from 66 studies. In NTS blood isolates, the combined prevalence was 1.4% for fluoroquinolones resistance, 1.9% for resistance to third-generation cephalosporins, and 68.5% for MDR. These estimates were 2.1%, 3.5%, and 21.4% in stool isolates. The prevalence of resistance to fluoroquinolones and third-generation cephalosporins in blood isolates has increased in the past 2 decades. The guidelines employed to determine antimicrobial resistance and the study epidemiological characteristics were related to the resistance prevalence.The high prevalence of MDR in NTS raises concerns, and the emergence of resistance to fluoroquinolones and third-generation cephalosporins is worrisome. Strengthening the monitoring of antimicrobial drug resistance in NTS is essential to guide patients' care and policymaking in sub-Saharan Africa.

Predictors of reinfection with pre-Omicron and Omicron variants of concern among individuals who recovered from COVID-19 in the first year of the pandemic.

OBJECTIVES: The predictors of SARS-CoV-2 reinfection are unclear. We examined predictors of reinfection with pre-Omicron and Omicron variants among COVID-19-recovered individuals. METHODS: Randomly selected COVID-19-recovered patients (N = 1004) who donated convalescent plasma during 2020 were interviewed between August 2021 and March 2022 regarding COVID-19 vaccination and laboratory-proven reinfection. The sera from 224 (22.3%) participants were tested for antispike (anti-S) immunoglobulin G and neutralizing antibodies. RESULTS: The participants' median age was 31.1 years (78.6% males). The overall reinfection incidence rate was 12.8%; 2.7% versus 21.6% for the pre-Omicron (mostly Delta) versus Omicron variants. Negative associations were found between fever during the first illness and pre-Omicron reinfection: relative risk 0.29 (95% confidence interval 0.09-0.94), high anti-N level at first illness and Omicron reinfection: 0.53 (0.33-0.85), and overall reinfection: 0.56 (0.37-0.84), as well as between subsequent COVID-19 vaccination with the BNT162b2 vaccine and pre-Omicron 0.15 (0.07-0.32), Omicron 0.48 (0.25-0.45), and overall reinfections 0.38 (0.25-0.58). These variables significantly correlated with immunoglobulin G anti-S follow-up levels. High pre-existing anti-S binding and neutralizing antibody levels against the SARS-CoV-2 Wuhan and Alpha strains predicted protection against Omicron reinfections. CONCLUSION: Strong immune responses after the first COVID-19 infection and subsequent vaccination with the BNT162b2 vaccine provided cross-protection against reinfections with the Delta and Omicron variants.

Multicenter Surveillance of Antimicrobial Resistance among Gram-Negative Bacteria Isolated from Bloodstream Infections in Ghana.

BACKGROUND: Antimicrobial resistance (AMR) in Gram-negative bacteria-causing bloodstream infections (BSIs), such as Klebsiella pneumoniae and non-typhoidal Salmonella (NTS), is a major public health concern. Nonetheless, AMR surveillance remains scarce in sub-Saharan Africa, where BSI treatment is largely empirical. The aim of the study was to determine the distribution and AMR patterns of BSI-causing NTS, K. pneumoniae, and other Gram-negative bacteria in Ghana. METHODS: A cross-sectional study was conducted between April and December 2021 at eleven sentinel health facilities across Ghana as part of a pilot study on the feasibility and implementation of the human sector AMR surveillance harmonized protocol in sub-Saharan Africa. Gram-negative bacteria recovered from blood specimens of febrile patients were identified using MALDI-TOF and evaluated for antimicrobial resistance using the BD Phoenix M50 analyzer and Kirby-Bauer disc diffusion. The Department of Medical Microbiology at the University of Ghana served as the reference laboratory. RESULTS: Out of 334 Gram-negative blood isolates, there were 18 (5.4%) NTS, 85 (25.5%) K. pneumoniae, 88 (26.4%) Escherichia coli, 40 (12.0%) Acinetobacter baumannii, 25 (7.5%) Pseudomonas aeruginosa, and 77 (23.1%) other Gram-negative bacteria. As a composite, the isolates displayed high resistance to the antibiotics tested-amoxicillin (89.3%), tetracycline (76.1%), trimethoprim-sulfamethoxazole (71.5%), and chloramphenicol (59.7%). Resistance to third-generation cephalosporins [ceftriaxone (73.7%), cefotaxime (77.8%), and ceftazidime (56.3%)] and fluoroquinolones [ciprofloxacin (55.3%)] was also high; 88% of the isolates were multidrug resistant, and the rate of extended-spectrum beta-lactamase (ESBL) production was 44.6%. Antibiotic resistance in K. pneumoniae followed the pattern of all Gram-negative isolates. Antibiotic resistance was lower in NTS blood isolates, ranging between 16.7-38.9% resistance to the tested antibiotics. Resistance rates of 38.9%, 22.2%, and 27.8% were found for cefotaxime, ceftriaxone, and ceftazidime, respectively, and 27.8% and 23.8% for ciprofloxacin and azithromycin, respectively, which are used in the treatment of invasive NTS. The prevalence of multidrug resistance in NTS isolates was 38.9%. CONCLUSIONS: Multicenter AMR surveillance of Gram-negative blood isolates from febrile patients was well-received in Ghana, and the implementation of a harmonized protocol was feasible. High resistance and multidrug resistance to first- or second-choice antibiotics, including penicillins, third-generation cephalosporins, and fluoroquinolones, were found, implying that these antibiotics might have limited effectiveness in BSI treatment in the country. Continuation of AMR surveillance in Gram-negative blood isolates is essential for a better understanding of the extent of AMR in these pathogens and to guide clinical practice and policymaking.

A nationwide analysis of population group differences in the COVID-19 epidemic in Israel, February 2020-February 2021.

BACKGROUND: Social inequalities affect the COVID-19 burden and vaccine uptake. The aim of this study was to explore inequalities in the incidence and mortality rate of SARS-CoV-2 infection and vaccine uptake in various sociodemographic and population group strata in Israel. METHODS: We analysed nationwide publicly available, aggregated data on PCR-confirmed SARS-CoV-2 infections and COVID-19 deaths between March 2020 and February 2021, as well as the first three months of COVID-19 immunisation according to sociodemographics, including population group and residential socioeconomic status (SES). We computed incidence and mortality rates of COVID-19. Comparisons between towns with predominantly Arab, ultra-Orthodox Jewish (the minorities), general Jewish populations, and according to SES, were conducted using generalised linear models with negative binomial distribution. FINDINGS: Overall, 774,030 individuals had SARS-CoV-2 infection (cumulative incidence 84•5 per 1,000 persons) and 5687 COVID-19 patients had died (mortality rate 62•8 per 100,000 persons). The highest mortality rate was found amongst the elderly. Most (>75%) individuals aged 60 years or above have been vaccinated with BNT162b2 vaccine. The risk of SARS-CoV-2 infection was higher in towns with predominantly Arab and ultra-Orthodox Jewish populations than in the general Jewish population, and in low SES communities. COVID-19 mortality rate was highest amongst Arabs. Conversely, vaccine uptake was lower amongst Arab and ultra-Orthodox Jewish populations and low SES communities. INTERPRETATION: Ethnic and religious minorities and low SES communities experience substantial COVID-19 burden, and have lower vaccine uptake, even in a society with universal accessibility to healthcare. Quantifying these inequalities is fundamental towards reducing these gaps, which imposes a designated apportion of resources to adequately control the pandemic. FUNDING: No external funding was available for this study.