Introduction
Campylobacter are gram-negative, flagellated bacteria that can cause zoonotic infections in both humans and animals. It poses a significant threat to human communities as it colonizes animal reservoirs and spreads through livestock feces, contaminating water sources, the environment, and the food chain.1 Furthermore, it was demonstrated that the agents of Campylobacter infections possess several genes associated with pathogenicity and antibiotic resistance. 2 Each year, approximately 525,000 children under the age of five lose their lives due to diarrheal disease, making it the second prominent cause of death in children.3 Campylobacter is widely recognized as a notable agent of acute diarrhea, particularly in individuals under the age of 5 and those who are 65 years old and above. 4 Moreover, concurrent infection with C. jejuni in symptomatic children has been shown to increase the severity of symptoms, and a higher risk of complications.5 In addition, C. jejuni was demonstrated as gent of peritonitis among children in some instances.6 The invasiveness of C. jejuni was linked to the possession of certain genetic elements that play an essential role in these types of infections. 7 The Campylobacter infection in children may be predicted by observing essential manifestations, such as a brief period of emesis, the presence of blood and mucus in their feces, and lower levels of Aspartate Transaminase. 8 C. jejuni infection has become increasingly prevalent worldwide over the last century, affecting both developed and developing nations with a particular impact on children. 9 This infection can occur as a result of multiple factors, such as exposure to natural reservoirs of Campylobacter like fowls and aquatic repositories, non-literate caregivers, and lack of proper personal sanitation. 10, 11 The efficiency of immune system for infected group, dietary patterns that result in the intake of undercooked food, disparities in way of life and nutritional habits as well as more direct contact with animals and the surroundings, can enhance this infection. 12, 13, 14, 15 Studies in low-resource environments discovered connections between Campylobacter infection and poor nutrition as well as intestinal inflammation among children.16
Although C. jejuni is a bacterial infection commonly associated with gastrointestinal illness, it has emerged as a significant prior infection in the context of Guillain-Barré Syndrome (GBS). The GBS is an immune-mediated condition characterized by flaccid paralysis. 17 Likewise, many studies have suggested an association between an infection with C. jejuni and an increased risk of developing Irritable bowel syndrome (IBS). IBS is a chronic gastrointestinal disorder characterized by persistent abdominal pain, bloating, and altered bowel habits.18 As well, C. jejuni may be associated with the development of reactive arthritis, Reiter's syndrome, hemolytic uremic syndrome, and Miller Fisher syndrome. 19, 20 This outline the need for preventive measures to reduce the burden of Campylobacter infections and their long-term effects on child growth. 21 While data on Campylobacteriosis within the Middle East is unfortunately limited, this highlights a disconcerting situation. Notably, the rates of both the infection itself and the resistance to antibiotics used for its treatment are alarmingly high. 22 Campylobacter spp has been identified as one of the common bacterial agents associated with diarrheal infections among children in the Middle East. 23, 24
Although data on Campylobacter prevalence and antimicrobial susceptibility in Middle Eastern children is still limited, this review aims to grasp available studies to highlight the prevalence, antimicrobial resistance, and associated factors of campylobacteriosis in the Children of Middle East.
Materials and Method
This review searched English publications over the past 14 years on Campylobacter in children across Middle Eastern countries. Using Google Scholar and PubMed, the key terms “Campylobacter” or “Campylobacter jejuni” with “Children”, “Infant”, “Pediatric”, and the name of Middle Eastern Countries were combined with various keywords such as “Prevalence”, “Incidence”, “Burden”, “Epidemiology”, “Colonization”, and “Diarrhea”, “Antibiotic Resistance”, “Antimicrobial susceptibility”.
Our inclusive criteria included research conducted during the period from 2010 to 2023, prioritizing studies that focus on children or at least 50% of their samples are children or mention the age group prevalence (Figure 1). According to these criteria, the search produced a total of 170 publications related to Campylobacter spp in the Middle Eastern regions. One hundred forty-three were excluded as they either focused on animals, animal products, food, or humans with a children sample size less than 50% or lacked data about children. It is important to note that this article was based on existing research and did not involve any new investigations into human or animal subjects conducted by the authors.
Discussion
Campylobacter jejuni infection in Middle Eastern children with gastroenteritis
The rate of Campylobacteriosis across human populations exhibits substantial variability, being observed in low-income countries at 1.7% to 62.7%. While, in animals, the prevalence of Campylobacter shows considerable variation, ranging from 1.2% to 80%.1 it has been demonstrated that the rate of Campylobacter among the human population in the Middle East ranges from 1% to 22%. 25, 26 A study conducted in Syria has demonstrated a low rate of campylobacter infection in children. The study also revealed a significant positive association between C. jejuni infection and cases of childhood diarrhea. 27 In addition the low prevalence of campylobacter infections also reported in Palestine and Qatar according to the available data. 28, 29 While, the moderate rates of campylobacteriosis were listed among children of Jordan,30 Lebanon, 31, 32 Iran, 33, 34, 35, 36, 37, 38 Iraq, 39, 40, 41 Oman, 42 and Yemen. 43 On other hand, high prevalence rates of pediatric campylobacteriosis reported in Egypt, 10, 44, 45 Israel, 46 and Turkey. 24 According to the published data, there were discrepancies in the rates of Campylobacter infections among children in the Middle East (Table 1). The fluctuations in the rate are linked to disparities in the detection methods, variations in the age of the targeted population, and additional factors that may enhance infection. Research conducted in both industrialized and developing nations has identified specific risk factors that may cause differences in rate of campylobacteriosis among children, including female gender, shortened natural lactation periods, lower education among younger mothers, and the lack of regular water purification source.16, 47, 48 Furthermore, Campylobacter species are reported more frequently in diarrheal cases within many low-and middle-income countries that share similar conditions to those in the Middle East. For example, the prevalence rate of Campylobacter infections in South Asian children ranges from 3.2% to 17.4%, compared to 0% to 13% in non-diarrheal cases. 47 Moreover, recent data from Pakistan documented that 54.6% of diarrheic stool samples from hospitalized children under 5 years old tested positive for C. jejuni culture. 49 Likewise, in a low-resource tropical community in Peru, recent data from whole-genome shotgun metagenomic sequencing indicated that over 65% of the acute diarrheal samples of children under 2 years contained co-infections with multiple Campylobacter species within a single stool sample. 50
It was demonstrated that C. jejuni serotype HS4c had the highest occurrence worldwide, accounting for 12.6% of cases. Nevertheless, the primary capsule variations differed depending on the geographic location. In particular regions, serotypes such as HS2, HS3c, HS4c, HS5/31, HS8/17, and HS10 were among the top ten frequently observed. 51 A recent data pointed out that C. jejuni CC21 and CC257 clonal complexes were common among children in Iran and HS23/36, HS2, HS4 and HS19 were prominent capsular genotypes of isolates.33
While the data on pediatric Campylobacteriosis in the Middle East remains limited (Figure 2), the available information underscores the significance of compylobacteriosis as a prominent health challenge, particularly within low-and-middle-income countries of Middle East. This gap highlights the need for further studies and underscores the public health importance of addressing Campylobacter infections in children, providing a more complete picture of its challenges in this region.
Table 1
Epidemiology of Campylobacter Infection in children of Middle Eastern countries.
Figure 2
There was no data included in this article from Kuwait, Saudi Arabia, and the United Arab Emirates. While one publication from each of Oman, Lebanon, and Syria, as well as two publications from each of the following countries: Israel, Palestine, Qatar, and Yemen, were included in this review. The remaining publications coming from Egypt, Iran, Iraq, and Turkey.
Antimicrobial resistance of C jejuni in pediatric papulation in middle East
Antimicrobial resistance of campylobacter spp affects both developed and developing nations, this may be related to many factor including introduction of antibiotics in animal husbandry, notably poultry feed. 53, 54 There were indications revealed that the resistant C. jejuni may not only be present in chicken supplies but also in animals and feral fowls, serving as potential reservoirs and posing a risk for the spread of resistant bacteria. 55, 29 In addition, studies in the Middle East regions have demonstrated an increase in the resistance rate of Campylobacter spp. 56, 57 The presence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant (PDR) Campylobacter species has also been reported in the Middle East. 44
There are five primary categories of antibiotics commonly used to treat campylobacter infections. These categories include aminoglycosides, beta-lactams, fluoroquinolones, macrolides, and tetracyclines, antibiotics typically reserved for use in severe illness to aid recovery rather than being necessary for every infection.58 Campylobacter species have evolved multiple mechanisms to counter the selective pressure caused by using antibiotics in both veterinary and human medicine. These mechanisms include modifying or mutating the targets of antimicrobial agents, modifying or inactivating antibiotics directly, and reducing the accumulation of drugs as result of drug efflux pumps. These adaptations allow Campylobacter to acquire resistance to antibiotics, enabling its survival and proliferation in environments where these drugs are present. 59 It was demonstrated that the presence of imipenem-resistant isolates with metallo-β-lactamase (MBL) genes raises concerns for public health in the third world. 49 Furthermore, Campylobacter shows high Tetracycline and Ciprofloxacin resistance via CmeABC efflux pumps and acquired resistance genes like tetO and gyrA. These multiple, simultaneous mechanisms demonstrate the organism's advanced strategies to develop high antibiotic tolerance, overcoming diverse antimicrobial classes.60, 61 Moreover, the genetic elements of Campylobacter that harbor clusters of genes conferring resistance to aminoglycosides and macrolides were discovered. These discrete genetic elements concentrate various resistance determinants against these two antibiotic classes in one location. It enables Campylobacter to readily develop cross-resistance against these important antibiotic categories. 59
A recent investigation carried out in Egypt on 120 isolates of C. jejuni and C. coli sourced from human samples and chickens pointed out that 75% of isolates were MDR, 20.8% were XDR, and 4.2% were PDR isolates. 44 The complete resistance against Ampicillin in C. jejuni was reported in Egypt, Iraq, and Yemen.41, 44, 62 Meanwhile, it was demonstrated that 40.3% of isolates in one Turkish study had Ampicillin non-susceptibility.52 On other hand approximately a quarter of isolated strains, exhibited a resistant capacity for Ampicillin in studies conducted in Lebanon, 31 and Iran.35 High Ciprofloxacin resistance rates were documented in research data from Israel, 63 Egypt, 44 Oman, 42 Turkey,52 and Iran.35 Unfortunately, C. jejuni showed completed non-susceptibility for Erythromycin in Egypt,44 as well as a high resistant rates were reported in Iraq and Palestine. 40, 42 In contrast moderate rate of resistance against Erythromycin was found in Iran. 35 While low Erythromycin non-susceptibility rate was documented in other regions of Middle East (Table 2). As well a high Gentamycin resistance was illustrated in Egypt, 44 in compare with low rate or no updated data in other countries. Complete Tetracycline non-susceptibility was listed in Egypt 44 and Iraq, 41 whereas high resistant rate was indicated in Israel, Iran, and Oman. 35, 42, 63 The resistant prevalence of C. jejuni against Trimethoprim Sulfamethoxazole was found at 100% in one investigation form Egypt. 44 At the same time the high resistance of Trimethoprim Sulfamethoxazole was demonstrated in publications from Iraq and Turkey. 40, 52
Although there is scant data about Campylobacter species isolated from children in the Middle East, multiple resistant strains of Campylobacter from human sources have been documented in many recent publications from the Middle East regions. 57, 64, 65 The observed resistance patterns in Campylobacter in the Middle East may be linked to several factors, with self-medication and antimicrobial abuse remaining a significant contributing factor that create such issue.66, 67, 68 This circumstance poses a significant challenge in the treatment of Campylobacter infections as some strains have become resistant to multiple antibiotics, limiting the effectiveness of available treatment options. Therefore, utilizing antibiotic sensitivity testing can help guide the selection of the most effective antibiotic for treatment. This approach ensures that the chosen antibiotic is tailored to the specific strain of Campylobacter, optimizing the chances of successful treatment, and minimizing the development of antibiotic resistance.69 However, it is important to observe that the occurrence of multi-drug resistance among microbes is widespread and has notable implications particularly in nations with lower economic resources and middle-income status.70
Table 2
Antimicrobial resistance of C. jejuni in children of middle east
Current challenges of campylobacter infections among middle eastern children
The access to public health interventions and healthcare is significantly limited in some regions of Middle East.71 Furthermore, the prevalence of diarrhea among children aged less than 5 years was high, especially in politically instable countries like Yemen where 29.07% of children were suffered from acute diarrhea. The highest rates were observed among those who were under 12 months old.72 The incidence of diarrhea among children under the age of five in Yemen was 7.0 (5.5-8.9) episodes per person-year. 73 Unfortunately, this challenges is compounded by self-medication that remains a common behavior in many regions of the Middle East. 66, 67, 68 Similarly, in some regions of the Middle East, physicians feel highly pressured to administer broad-spectrum antibiotics due to the unavailability of antimicrobial susceptibility tests that guide antibiotic choices for prescriptions.74 In addition, the diet significantly impacts C. jejuni infection, influencing micronutrient availability, microbiome composition, and triggering a lasting immune response in children exposed early. However, short-term consequences include poor nutrient absorption, oral vaccine failure, impaired cognitive function, and increased mortality rates in children under five. 75 Likewise, high antibiotic resistance rates have been reported in Campylobacter isolates collected from human, animals, animal products, and food sources across various regions of the Middle East. 2, 14, 26, 76, 77 Furthermore, many virulence genes have been demonstrated in Campylobacter isolates gathered from humans and other sources in the regions of the Middle East. 77 This complex situation poses significant challenges for the children of the Middle East and needs urgent interventions.
Conclusion
The limited availability of data on Campylobacter infections in Middle Eastern children, coupled with high rates of campylobacteriosis, potent virulence factors in regional Campylobacter isolates, high antimicrobial resistance, and political instability in areas such as Iraq, Syria, and Yemen pose significant challenges for children in the region. To overcome these challenges, it is necessary to implement targeted interventions, enhance healthcare accessibility, adopt appropriate antibiotic prescription practices, and apply infection control measures in this specific population and a need for research to shed light on this obscure topic that has not been adequately addressed in children of this setting of the world.
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