Concomitant Infection of Helicobacter pylori and Intestinal Parasites: Burden, Sociodemographic and Clinical Characteristics in Hospitalized Children and Adolescents in Northern Lebanon

Introduction

Gastrointestinal symptoms are common in the pediatric population, especially in developing countries. Co-infections involving bacteria and protozoa are an emerging phenomenon featuring concurrent ecological niches or shared transmission routes and risk factors (Akoolo et al., 2022). Consequently, co-infecting pathogens may interplay synergistically or antagonistically and modulate disease severity and host health outcomes (Hoarau et al., 2020; Devi et al., 2021). Intestinal parasites and the pathobiont bacterium Helicobacter pylori (H. pylori) are well known for their high prevalence in children, especially in low-resource settings.

H. pylori infection has been extensively investigated over the last 30 years. It may currently be the most well-studied chronic bacterial infection in humans in a specific biological niche, specifically in the gut territory, and one of the major public health problems (Hooi et al., 2017). H. pylori colonization is one of the most prevalent infectious diseases and is predominantly acquired during childhood. A higher burden was reported in developing countries at a younger age than in developed countries (Borka Balas et al., 2022). Despite the vast number of studies that have been conducted to extensively investigate the spread of H. pylori, its main route of transmission is still elusive and no predominant mode has been yet identified. It is widely believed that person-to-person transmission is the most common mode of transmission. Moreover, it has been proven that H. pylori can be transmitted vertically or horizontally by three possible pathways: the fecal-oral, the oral-oral, and the gastro-oral routes (Kayali et al., 2018). Of note, recently published data pointed out the probable role of untreated water and food products in the environmental transmission of H. pylori (Vesga et al., 2023). However, the scarcity of data failed to ascribe a definite foodborne transmission, thus extensive epidemiological studies should be performed to corroborate this hypothesis. Clinical manifestations are non-specific but some may be alarming in children such as persistent abdominal pain, vomiting, and gastrointestinal bleeding that require histopathologic examination of H. pylori (Aguilera Matos et al., 2020). Gastric reflux is often associated with H. pylori infection even without the presence of macroscopic lesions on gastroduodenal mucosa (Burkitt et al., 2017). In Lebanon, only a few studies have reported H. pylori infection in children. The fecoprevalence of H. pylori was 21% in asymptomatic children (Naous et al., 2007). Another study reported the prevalence of H. pylori infection at 16.5% in a Lebanese pediatric population who underwent upper gastrointestinal endoscopy (Al Kirdy et al., 2020).

Intestinal parasites are significant contributors to morbidity and mortality in the pediatric population. Their prevalence is significantly associated with poor sanitation and fecal contamination of water supplies (Hernández-Castro et al., 2024). Major burdens of intestinal parasitic infections in children are attributed to members of the Entamoeba complex (Entamoeba histolytica (E. histolytica), Entamoeba dispar and Entamoeba moshkovskii), Blastocystis hominis (B. hominis), Giardia lamblia (G. lamblia) (syn. Giardia intestinalis and Giardia duodenalis), and Cryptosporidium. Their transmission typically occurs through the fecal-oral route after direct or indirect contact (by contaminated food or water) with the infective forms (cysts/oocysts) (Ahmed, 2023). In Lebanon, recent studies reported cases of E. histolytica infection in South Lebanon and Beirut (Salami et al., 2019; El Achkar et al., 2023). Other protozoa including B. hominis, Entamoeba coli (E. coli), and G. lamblia were also found but at lower prevalence (El Achkar et al., 2023).

Several previous studies from different locations have highlighted a potential association between intestinal parasites and H. pylori (Ankarklev et al., 2012; Seid et al., 2018; Ibrahim et al., 2019). Since these pathogens are likely to share similar routes of transmission and risk factors, it is crucial to investigate this type of co-infection in the pediatric population. Co-infections can modulate disease dynamics through synergistic or antagonistic interactions. Interestingly, the co-existence of H. pylori and intestinal parasites may alter the disease severity and skew host immune responses (Jaka and Smith, 2024; Krzyżek and Gościniak, 2017). Not much data is available in Lebanon about the prevalence of H. pylori in this population and its potential association with intestinal parasitic infections. Understanding the prevalence pattern of H. pylori and intestinal parasite co-infections in the Lebanese pediatric population and their risk factors will aid in prioritizing public health efforts to better manage the burden of these infections and long-term complications.

Methods

Results

Assessment of the clinical manifestations among the different groups

The most frequently reported symptoms among children and adolescents were vomiting (56.6%), abdominal pain (39.4%), mild diarrhea (33.3%), and fever (28.3%) with no statistically significant differences between study groups (p > 0.005) as observed in Table 3 and Figure 1. On the other hand, children infected with H. pylori only or co-infected reported higher frequencies of reflux (37.5% and 17.1% respectively) than those with intestinal parasitic infection only (5.3%) or without infection (6.6%) (p = 0.001). However, patients infected with H. pylori alone or free of both infections had zero or lower percentages of severe diarrhea (0.0% and 15.9% respectively) compared to those infected with intestinal parasitic infections (36.8%) or both H. pylori and intestinal parasitic infections (25.7%) with a statistically significant difference between the study infectious groups (p = 0.013).

Table 3. Comparative assessment of the clinical manifestations among the different groups (n, %), (N = 297).

Clinical manifestation	IP infection (n = 19)	HP infection (n = 16)	HP-IP co-infection (n = 35)	Free infection (n = 227)	Total (n = 297)	p-value
Bloating	0 (0.0)	0 (0.0)	0 (0.0)	21 (9.3)	21 (7.1)	0.100*
Nausea	2 (10.5)	1 (6.3)	3 (8.6)	33 (14.5)	39 (13.1)	0.769*
Vomiting	14 (73.7)	7 (43.8)	21 (60.0)	126 (55.5)	168 (56.6)	0.307
Abdominal pain	9 (47.4)	5 (31.3)	11 (31.4)	92 (40.5)	117 (39.4)	0.572
Gastric reflux	1 (5.3)	6 (37.5)	6 (17.1)	15 (6.6)	28 (9.4)	0.001*
Loss of appetite	0 (0.0)	0 (0.0)	0 (0.0)	2 (0.9)	2 (0.7)	1.000*
Fever	9 (47.4)	4 (25.0)	7 (20.0)	64 (28.2)	84 (28.3)	0.210*
Mild diarrhea	11 (57.9)	7 (43.8)	16 (45.7)	86 (37.9)	99 (33.3)	0.321
Severe diarrhea	7 (36.8)	0 (0.0)	9 (25.7)	36 (15.9)	54 (18.2)	0.013*

* Cells have expected count less than 5 – used Fisher’s test instead of Pearson Chi-Square.

Figure 1. Comparative assessment of gastric reflux and severe diarrhea percentages among the different groups (%), (N = 297).

Discussion

Gastrointestinal complaints including gastric reflux, diarrhea, and vomiting are one of the major indications for pediatric hospital admissions (Dipasquale et al. 2018). H. pylori, E. histolytica, and G. lamblia are the most common intestinal pathogens in humans residing in low- and middle-income countries. In the present study, the overall prevalence of intestinal parasitic infection was found to be 54%, among them E. histolytica was the predominant protozoan parasite (77.8%). It is worth noting that our findings indicate that the North Lebanese pediatric population was at higher risk of intestinal parasitic infections than their counterparts admitted to a private tertiary care hospital located in South Lebanon (26.3%) (Ghssein et al., 2018). In addition, a recent retrospective study addressed the prevalence of intestinal parasites in all age groups of patients at a tertiary care center in Beirut where E. histolytica accounted for 7% and 10% of the cases during the pre-COVID and post-COVID periods, respectively (El Achkar et al., 2023). Although these three governorates belong to the same biogeographic region and share similar geographical and climatic conditions, the observed discrepancies could be explained by intrinsic differences in sanitation infrastructures and facilities. Moreover, this difference can be also associated with compounded crises following the deteriorated economic condition, and most importantly the Syrian influx that is greatly pronounced in the Northern region of Lebanon.

Our findings showed an increase in the prevalence of H. pylori infection with overcrowding and infrequent washing of vegetables before eating. These factors may facilitate the transmission of H. pylori within households and support the intra-familial clustering of this pathogen (Palanduz et al., 2018). These findings were consistent with recent reports from different countries where living in crowded households was found to be a significant risk factor for H. pylori infection (Aitila et al., 2019; Che et al., 2022). Moreover, our findings support and extend evidence reported in several studies worldwide regarding the transmission of H. pylori through unwashed vegetables (Szaflarska-Popławska and Soroczyńska-Wrzyszcz, 2019; Yisak et al., 2022). This can be explained by the direct contamination of vegetables by the bacterium or by irrigation with untreated wastewater (Kayali et al., 2018). In addition, vegetables may provide a suitable niche for H. pylori survival thanks to the ability of this bacteria to form biofilm and microcolonies on vegetable surfaces for an extended period (Ng et al., 2017). Thus, vegetables may potentially serve as a transmission vehicle for H. pylori, however, this hypothesis is still poorly documented.

Intestinal parasites and H. pylori share similar predisposing factors, thus a better understanding of the epidemiology of H. pylori infection in children infected with intestinal parasites is crucial to investigate whether H. pylori provides a favorable niche for intestinal parasitic infections or vice versa. We did not find any statistical significance between HP and a specific IP infection, so our analysis was based on HP-IP co-infections. Our findings showed that higher H. pylori colonization was found among individuals infected with intestinal parasites than non-infected subjects. The most frequent intestinal parasites were protozoa, and specifically, the association of H. pylori with E. histolytica was the most prevalent. Comparative data highlighting these co-infections were reported in African countries. A similar E. histolytica and H. pylori co-infection (12%) was reported in a Sudanese study that included individuals from all age groups (Yousif Abd Elbagi et al., 2019). Another cross-sectional study enrolled children aged 14 years or younger living in Ethiopia and showed a 23% prevalence of coinfection with any intestinal parasite and H. pylori. Maternal education was described as a significant risk factor for co-infection (Spotts et al., 2020). Abd El Hameed et al. (2021) showed an association between H. pylori and parasitic infections, especially G. lamblia (35.9%), in Egyptian children aged between 1 and 15 years. In Europe, a single study conducted in Northeastern Italy found a significant association between H. pylori and concomitant parasitic infection in different ethnicities, with Blastocystis being the most frequent co-infecting parasite (Pomari et al., 2020). Fuenmayor-Boscán et al. (2016) reported a significant association with helminths in South American children aged less than 5 years old. Nonetheless, their finding disagreed with ours which showed an inverse association between H. pylori and G. lamblia, indicating an antagonistic interaction that may hinder the colonization of the gut by exogenous intestinal pathogens. These associations detected in different countries support the similar fecal-oral route in the transmission of the etiologic agents. However, the environmental exposure factors to the fecal-oral transmission route investigated herein were associated with H. pylori only regarding the infrequency of washing vegetables before eating (p = 0.01) and handwashing with soap after defecating (p = 0.046). Regarding the epidemiological factors associated with co-infections, children and adolescents of mothers with primary education or less were significantly more likely to be co-infected compared with children from mothers with higher educational levels (p = 0.025). The educational level of mothers is associated with their knowledge and traditional practices with children regarding treatment and prevention of the disease (Wangda et al., 2017). It is noteworthy that the homogenous lifestyle of this study population may have masked any possible association between this environmental factor and intestinal infections or co-infections. Moreover, urease production by H. pylori converts urea into carbon dioxide and ammonia resulting in buffering the environment and thus enhancing bacterial colonization. Changes in the local environment could result in a higher incidence of intestinal parasitic infections by modulating the host’s immune responses. Furthermore, H. pylori was described as a candidate training of immune cells, especially primary human monocytes, towards subsequent microbial pathogens (Frauenlob et al., 2023).

Vomiting was the most frequent complaint (60%) in co-infected children, and in patients infected with intestinal parasites (73.7%), while it was less frequently recorded in H. pylori-infected and in co-infected individuals (43.8% and 60%, respectively). In addition, gastric reflux was significantly associated (37.5%; p = 0.001) with H. pylori infection. On the other hand, severe diarrhea was less recorded in co-infected children (24.7%) than in those with intestinal parasitic infection (36.8%; p = 0.013). Consequently, co-infection could modulate the host immune response and, thus, the clinical manifestation of each pathogen regarding severe diarrhea. Indeed, it has been described that children who tested positive for H. pylori are at lower risk of diarrheal diseases, especially during giardiasis, than children who are negative for this infection (Abd El Hameed et al., 2021). These results suggest that pediatric infections with H. pylori may condition a balanced host immune response to subsequent infections by playing a potential protective role during the diarrheal episode in co-infected patients and suppressing hyperimmune responses in the gut. Previous investigations seem to support this argument. Interferon-gamma (IFN-γ) is secreted along with Th1 responses toward intestinal amebiasis and was shown to play a protective role by clearing the amebae (Deloer et al., 2017). It can be also expressed at a higher level in H. pylori-positive children than in healthy children (Yu et al., 2020). Thus, patients enrolled in our study can be at the early stage of amebiasis and IFN-γ may reduce the risk of severe outcomes in H. pylori-positive individuals. However, our findings are not consistent with previous reports that demonstrated that the presence of intestinal protozoa in the gut together with H. pylori amplifies the recruitment of Th1 cells. This leads to exaggerated inflammation and tissue damage and thus it may worsen the disease (Krzyżek and Gościniak, 2017).

H. pylori is a known contributor to gastric ulcers, chronic gastritis, and potentially gastric cancer (Malfertheiner et al., 2023). However, when parasitic infections occur simultaneously, they can intensify or obscure these symptoms, making diagnosis more challenging. Clinicians may need to adopt a broader differential diagnosis when evaluating gastrointestinal issues, ensuring both bacterial and parasitic infections are considered. Moreover, the interaction between H. pylori and parasitic infections may impact treatment options. For instance, standard H. pylori therapies like antibiotics might be less effective if parasitic infections are not treated concurrently. Administering antiparasitic therapies alongside H. pylori eradication could improve outcomes but may also introduce concerns about drug interactions or resistance. These findings may shape screening protocols, emphasize the importance of integrated treatment strategies, and prompt the development of guidelines for managing co-infections in clinical practice.

To the best of our knowledge, the present study is the first to report novel assessment and risk data on the association between H. pylori and intestinal parasites in a Lebanese pediatric population attending tertiary care hospitals. However, the findings may not be generalizable to the Lebanese population. The cross-sectional design did not allow for drawing causal conclusions. In addition, the recruitment of hospitalized patients with gastrointestinal symptoms may affect internal validity. Thus, future large-scale, multicenter epidemiological studies with appropriate control groups are needed. These studies should employ a variety of diagnostic methods to further validate our results and investigate the mechanistic interactions between H. pylori and specific parasitic infections. Additionally, metagenomics analyses of stool samples could help identify distinct pathogenic profiles (including parasites, viruses, and fungi) and their associations with H. pylori virulence factors, such as CagA, VacA, babA, and others. Understanding these interactions highlights the importance of considering and mitigating these co-infections by health authorities and decision-makers to improve the methods of detection and implement effective intervention measures and public health strategies.

Conclusion

The association between H. pylori and intestinal parasitic infections was assessed for the first time among Lebanese hospitalized children and adolescents. A moderate prevalence of H. pylori and intestinal parasite co-infection was observed and associated with the low educational level of the participants’ mothers. In regards to the clinical manifestations reported in this study, gastric reflux was significantly associated with H. pylori infection and severe diarrhea showed a significant relationship with intestinal parasitic infection. This study could provide valuable insights into the complexity of the interconnected relationship between enteric pathogens and how they can promote each other’s persistence in the gut, and thus affect child health and development.