Parasitic appendicitis, what do we know?—a literature review

Introduction

Background

Acute appendicitis (AA) is a leading cause of emergency abdominal surgery worldwide, with an estimated incidence of 233 cases per 100,000 population per year (1). Despite its high incidence, the diagnosis of AA remains a clinical diagnosis. History, physical exam, laboratory investigations and imaging all serve a role in the diagnosis of this medical emergency; however, a large emphasis is placed on the clinical acumen of the diagnosing physician (2). The inherent challenges and uncertainty associated with the diagnosis of AA have prompted physicians to explore new methods of treatment, which have evolved over time. Historically, open appendectomy was the mainstay of treatment, succeeded by laparoscopic appendectomy. Currently there is an increasing body of evidence supporting the use of antibiotics as the sole treatment for uncomplicated AA (3).

Rationale and knowledge gap

Just as the treatment of AA has evolved over time, so have the human migration patterns. Today, high-income countries are relatively unaffected by parasitic infections as a result of advanced public health measures and sanitation methods (4). However, globalization is changing this landscape. Increasing numbers of immigrants, refugees, and travelers are contributing towards an increase in parasitic infections in developed countries where these diseases were previously rare (5). Notably, the World Health Organization estimates that 24% of the world’s population is infected with intestinal parasites (6). Intestinal parasitosis remains a major cause of morbidity, often contributing to malnutrition, anemia, and impaired growth, particularly in vulnerable populations (5). These infections can persist undiagnosed, complicating clinical presentations and increasing the risk of surgical emergencies such as appendicitis. Certain subpopulations are at increased risk of intestinal parasitosis, including children, immunocompromised individuals, those living in low- and middle-income countries (LMICs), migrants and travelers from endemic regions, and residents of rural communities or areas with limited access to sanitation and hygiene (5). Consequently, it is essential for physicians worldwide to be aware of these increasingly common parasitic infections and their potential impact on medical practice, even in regions where they are not traditionally prevalent.

Various etiologies of AA have been discovered, ranging from fecaliths to tumours. However, one highly debated etiology is the role of parasites in the development of AA (7). Individual studies have reported rates as high as 1.2–8% for parasites in pathological specimens post-appendectomy, though the causal relationship remains debated (7-9).

Objective

The objective of this review is to compile and narratively synthesize the existing evidence regarding the association between various parasitic infections and AA. By examining the literature, we also aim to better inform clinicians of this phenomenon with the goal of better informing diagnostic and management considerations. We present this article in accordance with the Narrative Review reporting checklist (available at https://tgh.amegroups.com/article/view/10.21037/tgh-24-148/rc).

Methods

A review of the literature was conducted to investigate the implication of parasitic infection in clinical AA. Publication date restrictions were imposed from 1949–2023. Results were limited to English and French manuscripts.

In June 2023, a search strategy was developed and ran on PubMed, Ovid and Embase. The following key words as well as their variations were used in the search which included abstracts, titles and text: “Appendicitis”, “Acute appendicitis”, “appendectomy”, “parasite” and “parasitic” (Appendix 1).

The initial search yielded 575 articles which were screened using Covidence. After removing 66 duplicates, 509 articles underwent title and abstract screening by two independent reviewers. Subsequently, 120 articles were selected for full-text analysis. Following full text review, only articles referencing Schistosoma spp., Enterobius vermicularis (E. vermicularis), Taenia spp., and Ascaris lumbricoides (A. lumbricoides) were considered. This decision was made as other parasitic species were too rarely mentioned to draw conclusions on. This decision was made if a parasite’s association with AA was mentioned in fewer than three articles, or with fewer than four patients. Parasites excluded were Trichuris trichura, Cryptosporidium parvum, Dientamoeba fragilis, Giardia intestinalis, Strongyloides spp., and Blastocystis hominis. After full text review and screening, it was determined that 71 studies met our inclusion criteria and were included in our analysis (Table 1, Figure S1).

We will use the following three terms throughout the text: “cause”, “mimic” and “indeterminate”. To clarify and ease the reading of the following sections, the term “cause” is defined as an author presenting a case of AA diagnosed surgically or by histopathology with a parasitic infection of the appendix and stating a causal relationship. While we acknowledge that a causal relationship has not been definitively established, this term is used to accurately convey the conclusions drawn by the respective authors. The term “mimic” refers to an author presenting a case of a patient who clinically was diagnosed with AA but had a negative appendectomy. Finally, the term “indeterminate” refers to an author who presents a case of AA in a patient also positive for parasitic infection and does not conclude on a causal relationship between the two variables, but notes an association. By employing these terms, we aim to clearly differentiate how the relationship between parasites and AA has been interpreted and presented in the reviewed literature while acknowledging the current lack of definitive evidence for causation.

Results

Following screening and review of 575 articles, 71 articles were selected for inclusion. These articles, published between 1966 and 2022, included retrospective analyses and case reports. The demographics covered both pediatric and adult populations, with patient ages ranging from 5 to 79 years. The sex distribution was balanced, with 32 articles reporting on men, 28 on women, 37 on both, and 1 without indication of sex.

Across the 71 articles reviewed, a total of 833 patients were reported to have had parasitic infections associated with AA symptoms. Our analysis identified four parasitic species most commonly associated with AA: Schistosoma spp. (27 articles), E. vermicularis (37 articles), Taenia spp. (4 articles), and A. lumbricoides (3 articles) (Figure 1). Other parasitic species were mentioned but excluded from this study due to limited mentions as explained above.

Figure 1 Number of studies reporting the relationship between parasitic infections and symptoms of acute appendicitis. Per number of assessed articles, reports of either direct causes, mimicry or indeterminate relationships of acute appendicitis and infections of Schistosoma spp., Enterobius vermicularis, Taenia spp. and Ascaris lumbricoides.

Among the four main parasitic infections identified, Schistosoma species were most frequently identified as a primary cause of AA, while E. vermicularis was most often identified as a mimicker of AA. Specifically, Schistosoma spp. was cited as the primary cause in 16 articles, E. vermicularis in 11, A. lumbricoides in 1, and Taenia spp. in 1. Conversely, E. vermicularis was identified as a mimicker in 24 articles, Schistosoma spp. in 6, Taenia spp. in 3, and A. lumbricoides in 1. Additionally, 8 articles were indeterminate regarding whether the parasitic infection caused or mimicked AA.

Findings analyzed at the individual patient level indicate the following trends regarding the association between parasitic infections and AA. Our analysis suggests that Schistosoma spp. and E. vermicularis more commonly cause AA rather than mimic it. Conversely, Taenia spp. more commonly mimics AA, while the effect of A. lumbricoides remains largely unknown.

Among 76 patients identified with Schistosoma infections, 40 (53%) had AA caused by the parasite, 32 (42%) had infections mimicking AA, and 4 (5%) were indeterminate. For E. vermicularis, out of 740 patients, 405 (55%) had AA caused by the parasite, 259 (35%) had infections mimicking AA, and 76 (10%) were indeterminate. Taenia spp. were reported in 4 patients, with 1 (25%) having AA and 3 (75%) having infections mimicking it. A. lumbricoides was reported in 13 patients, with 1 (7.7%) causing AA, 1 (7.7%) mimicking AA, and 11 (85%) cases being indeterminate (Figure 2).

Figure 2 Relationship between parasitic infections and symptoms of acute appendicitis at the individual level. Per number of patients, reports of either direct causes, mimicry or indeterminate relationships of acute appendicitis and infections of Schistosoma spp. (A), Enterobius vermicularis (B), Taenia spp. (C) and Ascaris lumbricoides (D).

A subgroup analysis of countries where parasitic infections led to AA symptoms revealed no major trends. Schistosoma spp. infections were reported in 13 countries, with the highest number of cases in Nigeria (n=27), Saudi Arabia (n=26), and Ghana (n=7). Notably, 16 of the 27 articles on Schistosoma indicated suspected parasitic contact in low- and middle-income countries. E. vermicularis infections were reported in 18 countries, with the highest incidences in Turkey (n=294), the United Kingdom (n=88), Pakistan (n=84), and Australia (n=64). Taenia infections associated with AA were identified in the United States, Brazil, India, and Turkey, with one patient each (7,10,11). A. lumbricoides was identified in India (n=12) and Brazil (n=1). This analysis indicates no clear trend or “hot spot” countries for parasitic infections causing AA, highlighting their occurrence in both middle- and high-income countries (Table 2). This suggests that physicians should consider parasitic infections in their differential diagnoses, particularly for patients at high risk of these infections.

Regarding the identification and management of parasitic appendicitis, all papers (100%) reported using clinical presentation as the primary factor for proceeding with appendectomy. Diagnostic adjuncts such as computed tomography (CT), ultrasound (US), magnetic resonance imaging (MRI), X-ray, blood, urine, and stool samples were also utilized to aid in diagnosis.

In two cases, parasitic infections were identified via US, and the patients were successfully treated with anti-parasitic medication rather than appendectomy. These patients were infected with A. lumbricoides and Taenia solium. Apart from these two cases, 69 out of 71 articles reported diagnosing the parasite post-operatively through histopathological examination. Overall, 42 articles reported positive findings for AA upon pathological examination, while 37 articles reported negative findings for AA.

Discussion

Laparoscopic and open appendectomy represent the mainstay treatment options for cases of AA. However, there is a growing body of literature that suggests the benefits of conservative management through a medical approach (12,13). Negative appendectomy refers to the surgical removal of a pathologically normal appendix, and a certain rate of negative procedures is typically deemed acceptable and part of good surgical practice (14,15). The incidence rate of negative appendectomy ranges from 25–30%, however these numbers decrease substantially with appropriate radiological investigations and more robust diagnostic workup (16,17). In fact, morbidity rates from such procedures range between 10–12% due to surgical site infections and postoperative adhesions, among other causes (18,19). Therefore, it is crucial to consider all possible alternate diagnoses prior to proceeding to surgical management.

Recently, an association was reported between viral infections [i.e., measles, influenza, dengue, human immunodeficiency virus (HIV), human herpesviruses, rotavirus, and adenovirus] and AA (20). Similarly, several reports have suggested potential correlations between AA cases and parasitic infection (7,21). Thus, in this report, we sought to further investigate this association and explore whether appropriate conservative management in this context may help further reduce rates of negative appendectomy.

Parasitic infections have a high, widespread incidence worldwide affecting greater than 1,000,000,000 people (22). While a high proportion of susceptible individuals live primarily in LMICs, several parasitoses are found in both North American and European countries (23,24). In our present analysis, patients diagnosed with Schistosoma spp. and E. vermicularis were identified in both LMICs and high-income countries. Therefore, in cases of suspected AA where there is parasitic involvement, appropriate work-up may be needed in both endemic and non-endemic regions. Additionally, with increased migration and international travel, suspicions should be raised if patients are returning from endemic countries for the aforementioned parasitic diseases.

Management can prove to be quite difficult as physicians often fail to diagnose the present parasitic infection prior to their decision to surgically remove the patient’s appendix. In our analysis, only 3 out of a total of 833 patients were given anti-parasitic medication rather than surgical procedure as a main method of treatment, owing to the failure of the treating staff to identify the parasitic infection prior to surgery. However, it is important to note that even with comorbid parasitic infection, appendectomy may be required. Furthermore, two studies reported having identified A. lumbricoides and Taenia species via US, allowing these patients to be successfully treated with appropriate medication instead of surgery (25,26). Additionally, one study demonstrated the ability to identify Schistosoma species on ejaculate microscopy post appendectomy, once again proving that pre-operative testing would have been useful (27). Finally, another study was able to identify E. vermicularis post-appendectomy via fecal study (28). A study conducted by Villamizar et al., focusing on patients with symptoms of intestinal obstruction, rather than appendicitis, also showed promising results having identified A. lumbricoides via abdominal roentgenograms in most cases (n=87), further demonstration that pre-operative workup is essential as parasites can be radiographically identified (29). These findings underscore the importance of including parasitic infections in the differential diagnosis for patients at high risk of parasitic infection who present with AA. Proper diagnosis can significantly influence case management and treatment outcomes. Based on these results, there is not enough evidence to suggest that certain manifestations of AA can be linked to certain parasites. Furthermore, as diagnosis of parasites has been extensively researched resulting in appropriate algorithms, we recommend screening for parasites in high-risk patients.

The present study is not without limitations, which should be considered when interpreting the findings. Firstly, as acknowledged, there is causal ambiguity in the relationship between parasites and AA limiting the robustness of conclusions drawn in case reports/retrospective studies utilized in this review. Additionally, our study only includes retrospective analyses and case reports, which inherently have limitations in establishing causality. Furthermore, most parasitic infections were diagnosed post-operatively, with only a few detected pre-operatively. This post-operative confirmation suggests a diagnostic gap, potentially affecting the true rate of parasitic-associated AA. Finally, some parasites, like Taenia spp. and A. lumbricoides, have very few cases, which limit the ability to draw robust conclusions. Further research is required to explore the association between intestinal parasites and AA. Specifically, future studies should be conducted as large-scale prospective cohort studies in endemic and non-endemic regions to better quantify prevalence and clinical significance of AA associated with parasitic infection. Additionally, investigations into the pathophysiologic mechanisms by which specific parasites contribute to inflammation or mimic AA symptoms could provide insight into this phenomenon. Finally, therapeutic trials evaluating the roles of antiparasitic treatments in conjunction with traditional treatments in patients presenting with AA symptoms in endemic regions would be insightful to determine whether such treatment can reduce the rate of negative appendectomies.

Conclusions

In conclusion, we assessed numerous articles stating an association between parasitic infections and clinical presentations of AA. Parasitic diseases were reported to cause AA in 53% and 58% of Schistosoma-infected and Enterobius-infected patients who have a clinical diagnosis of AA. Additionally, 42% of Schistosoma-infected and 35% of Enterobius-infected patients presented with symptoms consistent with AA but resulted in negative appendectomies. These findings highlight a variable association between parasitic infection and AA, influenced by demographic factors. However, it is critical to clarify that no causal relationship has been established. The presence of parasitic infections may mimic or exacerbate symptoms consistent with AA, leading to diagnostic ambiguity. However, the association remains clinically significant, as conservative management of AA cases, when feasible, may necessitate the inclusion of antiparasitic treatment. While the present study does not support a shift from surgical to medical management, it suggests that further investigation into the role of antiparasitic treatment in conjunction with traditional approaches may be warranted. Understanding the distinction is crucial for clinicians as failure to address the parasitic component can lead to ineffective management. Thus, these findings suggest that parasitic infections need to be considered as part of the differential diagnosis when faced with cases resembling AA as infections may be resolved without surgical involvement or may require antiparasitic medication in combination with surgery. We recommend that screening be considered in patients returning from travel in endemic regions or in new migrants who present with abdominal symptoms in an effort to reduce the rate of negative surgical procedures.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://tgh.amegroups.com/article/view/10.21037/tgh-24-148/rc

Peer Review File: Available at https://tgh.amegroups.com/article/view/10.21037/tgh-24-148/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://tgh.amegroups.com/article/view/10.21037/tgh-24-148/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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