The rise of non-typhoidal Salmonella: an emerging global public health concern

Abstract

In recent years, non-typhoidal Salmonella (NTS) infections have become a considerable threat to public health. This pathogen has increased in incidence and is a health concern mostly regarded as foodborne. It is highly important to appreciate the magnitude of the problem and act decisively and systematically to curb it. NTS infections are acquired mainly via food which is contaminated such as undercooked chicken, eggs, and even unpasteurized milk (Antony, 2023). An estimated 94% of salmonellosis cases result from the consumption of contaminated food (Ehuwa et al., 2021). Numerous studies have highlighted the role of non-typhoidal Salmonella (NTS) in foodborne outbreaks, identifying various serovars as significant contributors. For instance, Salmonella Heidelberg has been implicated in outbreaks (Eikmeier et al., 2018;Motladiile, 2019), alongside S. Typhimurium (Yang et al., 2017;Eikmeier et al., 2018) and S. Enteritidis, which remains a dominant serovar linked to foodborne transmission (Yang et al., 2017;Eikmeier et al., 2018;Sevilla-Navarro et al., 2020).Additionally, S. Infantis (Sevilla-Navarro et al., 2020), S. Newport, and S. Saintpaul (Eikmeier et al., 2018) have been recognized as causes of outbreaks across various geographical regions.Unlike typhoidal Salmonella which causes typhoid fever, NTS usually cause gastroenteritis with less severe cases with symptoms such as diarrhea, vomiting and pains in the abdomen, however, it is often taken lightly (Sears et al., 2023). Most of those infected remain asymptomatic, which spreads the idea that NTS is just another case of food poisoning. On the contrary, in people whose immunity is compromised, e.g. people living with HIV or those undergoing chemotherapy, NTS can infrequently cross barriers and become deleterious. Among such individuals, moderate to severe disease may also lead to hospitalization or vegetative state and lethal outcomes in some cases. The disparity in outcomes implies that whereas recovery would be swift for a good proportion of people, some of them would have to fight for their lives. This paper aims to provide a comprehensive overview of NTS as an emerging public health concern, focusing on its epidemiology, rising incidence rates, and research trends across diverse regions focusing on region-specific scientific contributions, the growing challenge of antimicrobial resistance, and the economic burden associated with NTS infections, highlighting the critical need for enhanced global research and public health strategies.Salmonella species, and especially non-typhoidal ones (NTS), are of serious global health concern causing most cases of gastroenteritis that amount to approximately 93.8 million incidences and almost 155,000 deaths per annum, and the most affected region is Sub-Saharan Africa where invasive NTS death rate stands at 85.9% and specifically this region further kills under five-year-old children where in such cases the active case fatality increases to 20%. In Asia, NTS are comparatively rare, but still in Pakistan, an incidence rate of 7.2 per 100,000 people years has been reported (Table 1). The presence of risk factors like inadequate food safety measures, poor sanitation, and lack of safe drinking water explain the increased burden of NTS infections in such areas, placing additional pressure on weak health systems already (Ao et al., 2015;Das et al., 2022;Sanni et al., 2023). The two most common serovars, Salmonella Typhimurium and Salmonella Enteritidis account for the largest raft of cases globally (WHO, 2018;Balasubramanian et al., 2019;Stanaway et al., 2019;Mohakud et al., 2022;Crump et al., 2023). Salmonella Typhimurium is predominant in Africa and the United States (Hagedoorn et al., 2024), where it is frequently associated with beef and poultry. In contrast, Salmonella Enteritidis is more prevalent in Europe and Asia (Hagedoorn et al., 2024), commonly linked to imported chicken (Bloomfield et al., 2023;Mkangara, 2023). Beyond these, several other non-typhoidal Salmonella (NTS) serovars significantly contribute to foodborne illnesses worldwide.Salmonella Infantis is increasingly linked to human infections and is commonly found in chicken, pork, and retail foods in the UK (Bloomfield et al., 2023). Salmonella Newport, associated with beef, is a notable serovar in the U.S. with invasive disease potential. Salmonella Dublin, primarily tied to cattle, is prevalent in Europe and Africa but also infects humans. Salmonella Heidelberg is mainly found in the Americas, frequently linked to poultry. Meanwhile, Salmonella Weltevreden is prominent in seafood from Asia and North America (Hagedoorn et al., 2024). During the literature review, using the Scopus database, a bibliometric analysis of NTS research publications from 1982 to 2024 shows that most studies have been conducted in the USA, Brazil, European countries, African nations, India, China, Pakistan, and Bangladesh (Figure 1). Although this analysis highlights the geographic regions where NTS research is concentrated, it does not perfectly align with the actual epidemiological data. However, it suggests that these are the areas where NTS cases are being most actively reported and studied.The disproportionate focus on certain regions, coupled with the lack of comprehensive data from resource-limited countries, underlines the need for more focused research in these underserved areas to better understand the disease's true impact. More targeted epidemiological studies are essential to guide public health strategies and interventions in the regions most affected by NTS. The incidence of NTS infections has been steadily increasing, particularly affecting vulnerable groups such as young children, the elderly, and immunocompromised individuals. In these populations, NTS can escalate into severe and invasive infections, including bacteremia and meningitis, requiring prompt medical intervention (Arii et al., 2002;Magwedere et al., 2015;Ballal et al., 2016;Chen et al., 2023). However, in low-resource settings, where access to timely healthcare is often limited, the risk of life-threatening outcomes is heightened.As indicated by the bibliometric analysis of research publications from 1982 to 2024, there has been a noticeable rise in the number of studies focused on NTS outbreaks worldwide (Figure 2). While this increase in research publications does not directly reflect the epidemiology of NTS, it signals a growing recognition of the issue and the efforts being made to address it globally.The rising number of NTS cases can be attributed to several factors, including inadequate food safety measures, poor hygiene, and limited public health awareness. In areas with weaker health infrastructures, the challenge of controlling NTS is more pronounced, underscoring the urgent need for comprehensive strategies to tackle this escalating public health threat. One of the most pressing challenges with NTS is the growing occurrence of antibiotic-resistant strains. Over the years, this pathogen has become resistant to several key antibiotic classes, such as fluoroquinolones and third-generation cephalosporins, which are often used to treat severe infections.Globally, non-typhoidal Salmonella (NTS) shows high levels of antibiotic resistance. Among them, some regions like Guangzhou, China, documented ampicillin resistance up to 92.16%, while among Southeast Asia, which includes the Philippines, resistance to ciprofloxacin is at 8.7% (Gong et al., 2022;Sia et al., 2023). Researches indicate a sharp rise in resistance to ciprofloxacin and ceftriaxone in recent years, with some regions reporting resistance rates of up to 30% for ciprofloxacin and 25%for ceftriaxone (Hengkrawit and Tangjade, 2022;Yang et al., 2023). In countries such as Vietnam and Taiwan, multidrug resistance (MDR) among NTS strains has reached concerning levels, with studiesshowing that up to 53.8% of isolates were MDR between 2014 and 2019 (Hengkrawit and Tangjade, 2022). Th