Twenty-five years of sentinel laboratory-based surveillance of shigellosis in a high-income country endemic for the disease, Israel, 1998 to 2022.

BackgroundShigella is a leading cause of moderate-to-severe diarrhoea worldwide and diarrhoeal deaths in children in low- and-middle-income countries.AimWe investigated trends and characteristics of shigellosis and antimicrobial resistance of Shigella sonnei in Israel.MethodsWe analysed data generated by the Sentinel Laboratory-Based Surveillance Network for Enteric Pathogens that systematically collects data on detection of Shigella at sentinel laboratories, along with the characterisation of the isolates at the Shigella National Reference Laboratory. Trends in the shigellosis incidence were assessed using Joinpoint regression and interrupted time-series analyses.ResultsThe average incidence of culture-confirmed shigellosis in Israel declined from 114 per 100,000 population (95% confidence interval (CI): 112-115) 1998-2004 to 80 per 100,000 population (95% CI: 79-82) 2005-2011. This rate remained stable 2012-2019, being 18-32 times higher than that reported from the United States or European high-income countries. After decreasing to its lowest values during the COVID-19 pandemic years (19/100,000 in 2020 and 5/100,000 in 2021), the incidence of culture-confirmed shigellosis increased to 39 per 100,000 population in 2022. Shigella sonnei is the most common serogroup, responsible for a cyclic occurrence of propagated epidemics, and the proportion of Shigella flexneri has decreased. Simultaneous resistance of S. sonnei to ceftriaxone, ampicillin and sulphamethoxazole-trimethoprim increased from 8.5% (34/402) in 2020 to 92.0% (801/876) in 2022.ConclusionsThese findings reinforce the need for continuous laboratory-based surveillance and inform the primary and secondary prevention strategies for shigellosis in Israel and other endemic high-income countries or communities.

IgG Serum Antibodies to Shigella sonnei Lipopolysaccharide Are Inversely Associated with the Incidence of Culture-Proven S. sonnei Shigellosis in Israeli Children and Adolescents.

BACKGROUND: Shigella is a leading cause of moderate-to-severe diarrhea globally, with young children most affected. The burden of shigellosis drops increasingly with age, inferring the acquisition of natural immunity. We tested the hypothesis that IgG antibodies elicited against Shigella O-specific polysaccharide (O-SP) are correlates of age-acquired immunity. OBJECTIVES: We examined levels and determinants of serum IgG to S. sonnei LPS and the association with the incidence of S. sonnei shigellosis in Israeli children and adolescents. METHODS: We analyzed 1096 serum samples from 0- to 19-year-olds collected in 2008-2015 for IgG anti-S. sonnei LPS levels by ELISA. Corresponding age-specific incidences of culture-proven S. sonnei shigellosis from 2008 to 2015 were obtained. We compared ecologically IgG levels, prevalence above a proposed protective threshold, and S. sonnei shigellosis incidence. RESULTS: In a multivariable analysis model, children aged 1-4, 5-14, and 15-19 years were 6.71, 27.68, and 48.62 times more likely to have IgG anti-S. sonnei LPS above the threshold than those aged < 1 year, respectively (p < 0.001). Infants 0-3 months old had relatively high IgG anti-S. sonnei LPS levels of maternal origin that dropped thereafter. Children of low socioeconomic status had a 2.73 times higher likelihood of having IgG anti-S. sonnei LPS above the threshold (p < 0.001). A significant inverse correlation between age-specific IgG anti-S. sonnei LPS levels and S. sonnei shigellosis incidence was observed (Spearman rho= -0.76, p = 0.028). CONCLUSIONS: The study results support anti-S. sonnei LPS antibodies as correlates of protection that can inform Shigella vaccine development.

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.

Characterization of Antibiotic Treatment among Children Aged 0-59 Months Hospitalized for Acute Bacterial Gastroenteritis in Israel.

BACKGROUND: We examined the extent and correlates of appropriate antibiotic use among children hospitalized with bacterial acute gastroenteritis (AGE) in Israel, a high-income country setting. METHODS: Data were collected from children aged 0-59 months who participated in active hospital-based surveillance of AGE undertaken during 2007-2015. Bacterial AGE was defined as having a positive stool culture for Salmonella, Shigella, Campylobacter, or dysentery. Appropriate antibiotic use was defined as the administration of ciprofloxacin, azithromycin, or third-generation cephalosporins during hospitalization or at discharge. RESULTS: Overall, 550 children had bacterial AGE; of those, 369 (67.1% [95% CI 63.1-70.9]) received antibiotics, mostly azithromycin (61.8%) and third-generation cephalosporins (37.9%). Appropriate antibiotic treatment was given to 318/550 (57.8% [95% CI 53.7-61.9]). Children aged 0-11 months vs. 24-49 months were more likely to receive appropriate antibiotic treatment (OR = 1.90 [95% CI 1.09-3.33]). Having dysentery (OR = 5.30 [95% CI 3.35-8.39]), performing blood culture (OR = 1.59 [95% CI 1.02-2.48]), and C-reactive protein (CRP) levels (OR = 1.01 [95% CI 1.01-1.02]) were positively associated with receiving appropriate antibiotic treatment. CONCLUSIONS: Most children with bacterial AGE received appropriate antibiotic treatment, which correlated with young age, dysentery, CRP level, and performing blood culture, suggesting more severe illness, thus supporting the clinical decisions of physicians.

Review of Israel's action and response during the COVID-19 pandemic and tabletop exercise for the evaluation of readiness and resilience-lessons learned 2020-2021.

Background: Reevaluating response plans is essential to ensuring consistent readiness and resilience to the COVID-19 pandemic. The "During Action Review" and Tabletop (DART) methodology provides a retrospective and prospective assessment to inform the adaptive response. Israel introduced COVID-19 vaccinations in December 2020 and was the first country to implement booster vaccination to address waning immunity and surges caused by new variants. We assessed Israel's readiness and resilience related to COVID-19 response while capturing the pre-vaccination and vaccination periods. Methods: A DART analysis was conducted between December 2020 and August 2021 among experts involved in the management of the COVID-19 pandemic in Israel. During the retrospective stage, a role-based questionnaire and discussions were undertaken in a participant-led review of the response, focusing on epidemiology and surveillance, risk communication, and vaccines. The prospective stage included tabletop exercises to evaluate short to long-term simulated scenarios. Results: Participants emphasized the pivotal role of Israel globally by sharing experiences with the pandemic, and vaccination. Perceived strengths included multi-sectoral collaboration between the Ministry of Health, healthcare providers, academia, military, and others, stretching capacities, expanding laboratory workload, and establishing/maintaining surveillance. The vaccine prioritization plan and strong infrastructure, including computerized databases, enabled real-life assessment of vaccine uptake and impact. Challenges included the need to change case definitions early on and insufficient staffing. Quarantine of patients and contacts was particularly challenging among underprivileged communities. Risk communication approaches need to focus more on creating norms in behavior. Trust issues and limited cooperation were noted, especially among ethnic and religious minorities. To ensure readiness and resiliency, participants recommended establishing a nationally deployed system for bringing in and acting upon feedback from the field, especially concerning risk communication and vaccines. Conclusion: Our study appraised strengths and weaknesses of the COVID-19 pandemic response in Israel and led to concrete recommendations for adjusting responses and future similar events. An efficient response comprised multi-sectoral collaboration, policy design, infrastructure, care delivery, and mitigation measures, including vaccines, while risk communication, trust issues, and limited cooperation with minority groups were perceived as areas for action and intervention.