Amoak S, Soldera J. Blastocystis hominis as a cause of chronic diarrhea in low-resource settings: A systematic review. World J Meta-Anal 2024; 12(3): 95631 [DOI: 10.13105/wjma.v12.i3.95631]
Corresponding Author of This Article
Jonathan Soldera, MD, MSc, PhD, Tutor, Acute Medicine and Gastroenterology, University of South Wales, Llantwit Rd, Pontypridd, Cardiff CF37 1DL, United Kingdom. jonathansoldera@gmail.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Systematic Reviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Author contributions: Soldera J, Amoak S participated in the concept and design research, drafted the manuscript and contributed to data acquisition, analysis and interpretation; Soldera J contributed to study supervision; all authors contributed to critical revision of the manuscript for important intellectual content.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest pertaining to the subject matter discussed in this paper.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jonathan Soldera, MD, MSc, PhD, Tutor, Acute Medicine and Gastroenterology, University of South Wales, Llantwit Rd, Pontypridd, Cardiff CF37 1DL, United Kingdom. jonathansoldera@gmail.com
Received: April 14, 2024 Revised: August 24, 2024 Accepted: September 4, 2024 Published online: September 18, 2024 Processing time: 151 Days and 14.1 Hours
Abstract
BACKGROUND
Blastocystis hominis (B. hominis), an anaerobic unicellular protist parasite, is known for its diverse clinical manifestations upon infecting the human gastrointestinal tract. Although globally distributed, it is particularly prevalent in developing nations. Examining the symptoms and treatment outcomes of B. hominis infection in low-resource settings holds immense significance, providing healthcare practitioners with valuable insights to enhance patient care.
AIM
To synthesize existing evidence on the symptomatology and treatment outcomes of B. hominis infection in low-resource settings.
METHODS
Following the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, a systematic review was conducted. The search spanned electronic databases including PubMed, Scopus, and Google Scholar. After a comprehensive screening process, a thorough examination of the papers, adhering to inclusion and exclusion criteria, and data extraction from eligible studies was conducted. The findings underwent summarization through simple descriptive analysis.
RESULTS
The search yielded 1200 papers, with 17 meeting inclusion criteria. Chronic diarrhea due to B. hominis infection was reported in only two studies, while abdominal pain, diarrhea, flatulence, constipation, and nausea/vomiting emerged as the most commonly documented symptoms. Recovery rates after one week of treatment ranged from 71.8% to 100%, and after two weeks, from 60% to 100%.
CONCLUSION
In low-resource settings, chronic diarrhea resulting from B. hominis infection is infrequent. Common symptoms include abdominal pain, diarrhea, flatulence, constipation, and nausea/vomiting. Post-treatment, clinical outcomes are notably favorable, supporting the recommendation for treatment. Metronidazole is advocated as the first-line agent, with consideration for switching to a second-line option in cases of treatment failure or poor response.
Core Tip: This systematic review highlights the symptomatology and treatment outcomes of Blastocystis hominis (B. hominis) infection in low-resource settings. Notably, chronic diarrhea due to B. hominis is rare in these contexts. Abdominal pain, diarrhea, flatulence, constipation, and nausea/vomiting are the predominant symptoms reported. Post-treatment recovery rates are promising, ranging from 60% to 100% after two weeks of treatment. Metronidazole is recommended as the initial treatment, with consideration for alternative options if needed. These findings provide valuable insights for healthcare practitioners managing B. hominis infections in resource-limited settings.
Citation: Amoak S, Soldera J. Blastocystis hominis as a cause of chronic diarrhea in low-resource settings: A systematic review. World J Meta-Anal 2024; 12(3): 95631
Blastocystis spp. stand as anaerobic unicellular protist parasites categorized within the protozoan class Blastocystea. A part of the diverse and intricate stramenopiles group, they lack flagella and have the propensity to infect humans and various animals, establishing themselves as the most prevalent protozoa affecting the human gastrointestinal tract[1-3]. Recognized as the sole organism in this group causing human infections, Blastocystis hominis (B. hominis) is a significant focus of research and clinical attention[2-5].
The genetic diversity of Blastocystis spp. is evident through the polymorphic regions of its small subunit ribosomal ribonucleic acid gene (the small subunit ribosomal deoxyribonucleic acid), revealing at least 17 subtypes (ST1–ST17). While some subtypes are exclusive to humans, others are present in various hosts. Among the nine human subtypes (ST1–ST9), ST3 emerges as the most prevalent, followed by ST1, ST2, and ST4[6-10].
Global distribution characterizes Blastocystis spp., affecting over 1 billion people worldwide, with higher prevalence in developing countries, ranging from 22.1% to 100.0%[5,11-16]. Various socio-economic, demographic, and epidemiological factors contribute to the higher prevalence observed in these regions[11,13-15,17]. Despite some studies confirming its pathogenicity in humans, there is inconclusive and controversial evidence, possibly due to Blastocystis spp.'s association with normal gut microbiota while being capable of causing opportunistic infections in immunocompromised patients[3,4,18-21].
The protist primarily colonizes the colon and cecum, showcasing a diverse clinical presentation[4,15]. In addition to common symptoms like diarrhea, constipation, flatulence, and abdominal pain, it can manifest extraintestinal clinical symptoms, including anorexia, urticaria, hypersalivation, fatigue, and anal pruritus. While fever is uncommon, associations with conditions such as irritable bowel syndrome (IBS) and chronic diarrhea are noted[4,5].
Morphologically, B. hominis exists in four distinct forms (cyst, ameboid, granular, and vacuolar) with the cyst form exhibiting a high resistance to chlorination and the ability to endure low gastric pH. The infection initiates with cyst ingestion, followed by excystation in the colon, leading to vacuolar forms. These vacuolar forms undergo binary fission, resulting in ameboid or granular forms. Ultimately, encystation may occur in the large intestine, leading to cyst shedding in stool[2]. The life cycle of Blastocystis spp. is not fully understood, but it is postulated that the cyst form is the infectious stage, while the vacuolar form is predominantly found in human stool specimens, with replication likely occurring via binary fission. Other morphologic forms, such as ameboid and granular forms, have been observed, though their biological roles require further investigation[22].
Diagnosis relies on detecting these characteristic forms in stool samples, with B. hominis being the most prevalent eukaryote in human stool samples[3]. Xenic culture and quantitative polymerase chain reaction assays are established diagnostic methods, especially when the infective cyst form is present, as direct smear detection can be challenging[2,5]. Currently, SSU-rDNA genotyping stands as the ultimate and preferred diagnostic technique in the literature and in clinical practice[23,24].
For the pharmacologic treatment of blastocystosis (i.e., B. hominis infection), metronidazole is the reported drug of choice[20]. Second-line pharmacologic agents which may be considered include cotrimoxazole (trimethoprim/sulfamethoxazole), iodoquinol, tinidazole, ornidazole, paromomycin, nitazoxanide, chloroquine, pentamidine, emetine, furazolidone, and iodochlorhydroxyquin[20].
Gaining insights into the symptoms and treatment outcomes of B. hominis is crucial, particularly in resource-constrained settings. A systematic synthesis of existing literature and evidence can unearth patterns, treatment efficacy, and potential knowledge gaps. This study aims to present a comprehensive overview of B. hominis infection, encompassing its clinical manifestations and the efficacy of diverse treatment approaches in low-resource areas.
The research contributes valuable insights into the clinical presentation of B. hominis infection, enhancing our understanding of its symptomatology. Moreover, by scrutinizing the effectiveness of different treatment strategies in resource-limited settings, the review serves as a valuable resource for healthcare practitioners in such environments. This contribution aids in optimizing and enhancing patient care and management concerning B. hominis infection.
The principal aim of this research was to explore the symptomatology and treatment outcomes associated with B. hominis infection, particularly in low-resource settings (i.e., developing countries).
MATERIALS AND METHODS
Study design
The study followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines[25]. The goal was to evaluate evidence from studies on the symptomatology of individuals infected with B. hominis in low-resource settings, examining the treatments administered and the clinical responses observed.
Eligibility criteria
The systematic review exclusively incorporated peer-reviewed studies published in English, with no constraints on study designs. Excluded from consideration were preclinical studies, reviews, conference abstracts, editor's notes, commentaries, and unpublished works. For eligibility and inclusion, studies had to align with the Population, Intervention, Comparison, and Outcome criteria, which encompassed the following: (1) Population: Patients residing in low-resource settings (i.e., developing countries) diagnosed with B. hominis infection before initiating treatment; (2) Intervention: Various antimicrobial and medical treatments; (3) Comparison: The same patients in low-resource settings with B. hominis infection but assessed after treatment; and (4) Outcome: Evaluation of response rates and symptom amelioration following treatment.
Information sources and search strategy
A comprehensive literature search was conducted in August 2023 on the electronic databases PubMed (Medline), Scopus, and Google Scholar using the search term ["blastocystis" (All Fields) OR "blastocystosis" (All Fields) OR "b hominis" (All Fields)] AND ["treatment" (All Fields) OR "diagnosis" (All Fields) OR "epidemiology" (All Fields)] AND [humans (Filter)]. No publication date or study design limitations (other than review papers) were applied, but the language of publication was restricted to English.
Selection process
The identified studies from databases underwent an initial screening based on titles, abstracts, and keywords. Both authors conducted the screening and data collection independently, ensuring a thorough and unbiased selection process. Subsequently, full-text retrieval and comprehensive screening were conducted in accordance with the eligibility criteria, leading to the exclusion of studies that did not meet the specified criteria. The detailed process of study selection is delineated in Figure 1, employing the PRISMA 2020 flow diagram for new systematic reviews, encompassing searches of databases and registers exclusively[25,26].
Comprehensive information, including authorship, publication year, study location, study design, population demographics, clinical manifestations, treatment modalities, and treatment outcomes, was systematically extracted from all incorporated studies. Both authors were involved in the data extraction process, which encompassed three primary variables: The documented clinical symptoms reported by individuals infected with B. hominis, particularly emphasizing chronic diarrhea; the specific treatments administered to patients; and the treatment response observed at one week, two weeks, and up to four weeks post-treatment. Response to treatment was categorized into fully recovered, improved but not fully recovered, or unchanged, and the percentages at each specified time frame were recorded.
RESULTS
Search results, study selection and study characteristics
A total of 1200 records were found upon applying the search term across three online databases, namely PubMed, Scopus, and Google Scholar. Preceding the screening process, eight duplicates were identified and promptly excluded. An additional 59 papers were excluded due to their classification as review papers, while 12 records, comprising books, book sections, or conference papers, were also excluded.
Subsequent to this initial culling, the remaining 1121 studies underwent thorough scrutiny based on title, abstract, and keywords, aligning with the predetermined inclusion criteria. This meticulous screening led to the removal of 1058 papers. In the ensuing phase, 63 papers were earmarked for retrieval; however, 14 proved unattainable. Factors contributing to the unavailability of these 14 papers ranged from their antiquity, non-English language, to unresponsiveness from corresponding authors despite requests for full texts.
Ultimately, 49 full texts were successfully retrieved and subjected to a meticulous screening process, resulting in the exclusion of 32 papers. The rationale for removing these 32 papers rested on their classification as letters, comments, notes, or editorials, language disparities, or their origin from high-resource settings (i.e., developed countries). The data extracted from the final selection of 17 studies were then analyzed to identify patterns, derive conclusive results, and form the basis for the study's conclusions. Figure 1 provides a PRISMA flow diagram illustrating the systematic selection of studies (Figure 1).
The 17 studies incorporated into this analysis were disseminated across peer-reviewed journals spanning the time frame from 1987 to 2020. These reports emanated from diverse geographical locations, representing four continents: 11 studies originated in Asia, three in Africa, two in North America, and one in Europe. A detailed breakdown by country reveals that five studies were conducted in Turkey[27-31], two in Egypt[32,33], and one each in Bosnia and Herzegovina[34], China[35], India[4], Iran[36], Iraq[37], Jamaica[38], Malaysia[39], Mexico[40], Morocco[41], and Saudi Arabia[42].
In entirety, there was a cumulative total of eight case reports sourced from six studies[4,27,34,38,39,41], two randomized controlled trials[28,33], one non-randomized trial[31], and one case-control prospective study[32]. The remaining seven studies were either retrospective[40] or prospective[29,30,35-37,42]. The total number of patients included in the review is 949. The reported sex distribution encompassed 494 males and 455 females. Table 1 comprehensively outlines the characteristics of the 17 studies incorporated in the analysis.
Table 1 Characteristics of systematically reviewed studies.
92.3% (36/39) FR at 2 weeks for intestinal symptoms; 50% (1/2) FR at 2 weeks for extraintestinal symptoms except weight loss; 0% (0/1) FR at 2 weeks for weight loss
Chronic diarrhea in B. hominis infection: In terms of clinical presentation, chronic diarrhea was present in two studies[34,35] while data remain inconclusive for the study by Dinleyici et al[28]. In this particular study, a randomized single-blinded clinical trial, participants were required to exhibit symptoms for at least two weeks to qualify for inclusion.
In the case report conducted by Rajič et al[34], a previously healthy 49-year-old male with no underlying medical conditions developed angioedema, urticaria, and inconsistent stool with a 'mushy' appearance lasting a month. Unresponsive to a combination of a restrictive diet and loratadine, further investigations led to the diagnosis of B. hominis infection and Hashimoto’s thyroiditis.
The study conducted by Tai et al[35] focused on six patients (equally divided between males and females and all aged 30–51 years) experiencing symptoms, such as diarrhea, persisting for durations ranging from eight to 26 months. Notably, all these patients were individuals with ulcerative colitis, showing resistance to standard treatments for the condition. Their stool examinations yielded positive results for B. hominis with no evidence of other pathogens.
Other symptoms of B. hominis infection: In addition to chronic diarrhea, the included studies reported an extensive array of symptoms, exceeding 25, attributed to or associated with B. hominis infection. The most frequently documented symptoms, in descending order, included abdominal pain, diarrhea, flatulence, constipation, and nausea/vomiting. In contrast, less common symptoms encompassed urticaria, arthralgia, joint stiffness, joint swelling, angioedema, depression, abdominal distension, headache, weight loss and peri-anal pruritus.
Beyond clinical symptoms, B. hominis infection demonstrated a capacity to mimic, cause, or contribute to other diagnoses or clinical syndromes. For instance, in two studies, the infection manifested as acute abdomen, particularly in the form of acute appendicitis[27,41]. Additionally, it was linked to urticaria, angioedema, and Hashimoto’s thyroiditis, as reported by Rajič et al[34]. In another study, it was associated with seronegative polyarthritis[38].
Treatment outcomes
In all studies, patients received some form of treatment, with the exception of two studies where no treatments were provided to certain patients or groups[28,33]. The reported treatment regimens were diverse, encompassing the use of single or multiple antimicrobial agents, probiotic agents, or surgical intervention. These treatment modalities included metronidazole, trimethoprim/sulfamethoxazole, tinidazole, ceftriaxone, gentamicin, nitazoxanide, albendazole, mebendazole, rifaximin, secnidazole, lyophilized Saccharomyces boulardii, and appendectomy.
The reported duration of treatment generally ranged from one to two weeks[28–42]. However, the treatment duration was unknown in two studies[4,27].
Metronidazole alone was reported as a treatment modality in twelve studies[4,28,29,31,32,34,35,37-40,42], while in two studies, it was administered in combination with trimethoprim/sulfamethoxazole[27,36]. Trimethoprim/sulfamethoxazole was employed as a sole treatment agent in two studies[30,40] and nitazoxanide alone was reported in two studies[33,40]. A single study[40] detailed the use of albendazole, secnidazole, or rifaximin alone. Only one study[28] reported lyophilized Saccharomyces boulardii as a treatment modality. Conversely, Fréalle et al[41] utilized a combination of appendectomy, tinidazole, ceftriaxone, and gentamicin in treating a patient.
All studies included in the analysis documented some degree of symptomatic improvement in patients, regardless of whether they received treatment or not. However, treated patients consistently exhibited higher and more favorable response rates compared to their untreated counterparts.
In studies providing data, the full recovery rate at one week ranged from 71.8% to 100% among treated patients[37,38], whereas untreated patients had a recovery rate of 38%[33]. Regarding partial recovery at one week, treated patients showed a rate of 18.9%[30], with no available data for untreated individuals. Moreover, 7.5% of treated patients experienced no change in symptoms after one week[30].
The two-week response rate for full recovery ranged from 60% to 100% among treated patients[4,31,32,41], whereas untreated patients exhibited a recovery rate of 40%[28]. Partial recovery rates at two weeks varied between 18.9% and 100%[35,36]. In contrast, two cases reported by Rajamanikam et al[39] did not show improvement and instead worsened clinically despite receiving treatment for two weeks. Additionally, Moghaddam et al[36] reported a non-response rate of 1.9% following a two-week treatment. No data were reported for untreated patients regarding partial or non-response rates at two weeks.
At the four-week mark, treated patients exhibited a full recovery rate ranging from a minimum of 71.8%[37] to a maximum of 100%[32]. Unfortunately, no data were reported for untreated patients, and there is an absence of information on partial recovery and non-response rates regardless of the treatment provision.
Recovery rates were also documented without specific timelines. For instance, Andiran et al[27] reported a 100% full recovery rate following treatment in two case reports, but the duration of recovery was unspecified. In Toro Monjaraz et al's study[40], this figure decreased to 68.3%, with no documented timeframe for recovery, mirroring the previous study's lack of temporal details.
In cases where B. hominis infection was associated with other diagnoses or clinical syndromes, treatment often led to the resolution or improvement of these conditions. For instance, Rajič et al[34] reported that treatment for B. hominis resulted in the complete resolution of chronic urticaria, angioedema, and Hashimoto’s thyroiditis. Similarly, Lee et al[38] found that B. hominis treatment led to the disappearance of seronegative arthritis, with no recurrence observed up to four months of follow-up. Previous studies have highlighted a strong association between B. hominis infection and conditions such as inflammatory bowel disease (IBD), IBS, and other intestinal disorders. This association poses significant health risks and adversely impacts the quality of life of affected patients, underscoring the public health concern it represents in China[43].
DISCUSSION
Chronic diarrhea in B. hominis infection
Available epidemiological data demonstrates that, B. hominis exhibits significant prevalence in tropical and subtropical settings, notably in developing countries where inadequate sanitary and hygienic conditions lead to the consumption of contaminated food or water[44]. Extensive studies have consistently associated B. hominis infection with chronic diarrhea, as highlighted by the work of Graczyk et al[45] and more recently by Jha et al[46]. Notably, Jha et al[46] reported a substantial B. hominis infection prevalence of 30% among patients experiencing chronic diarrhea, contrasting with an overall prevalence of 1.6% among the general study participants. In the context of low-resource settings, the synthesis from this review affirms that B. hominis infection presenting as chronic diarrhea is infrequent in such environments. Furthermore, the presence of chronic diarrhea often signals the likelihood of comorbidities. Among the most frequently reported comorbidities in these instances are the chronic digestive disorders, namely, IBS and IBD[11,17,46].
Per the available evidence, there is no doubt that there exists a demonstrable relationship between B. hominis and IBS. However, the exact nature of this relationship is elusive, a mystery and is the subject of much debate with no definitive conclusions. The question remains as to whether B. hominis is causally related to IBS, is only associated with it, or simply mimics the condition[47-53].
In a case study by Hahm[47], a 32-year-old male had a five-year history of bloating (his predominate symptom), chronic diarrhea, and rectal urgency. This was associated with abdominal pain and in addition, bowel motion was not a relieving factor for the bloating sensation. He reported negative symptoms for blood or mucus in his stool as well as weight loss. Having been previously diagnosed with IBS (diarrhea predominant) by a gastroenterologist, he received a probiotic and modified diet as his treatment regimen. Regardless, these interventions failed to ameliorate his condition. Laboratory studies of his stool were positive for B. hominis and on that basis, treatment with metronidazole was commenced. This therapy did lead to a complete alleviation of his symptoms after 14 days. Accordingly, the author concluded that B. hominis mimics IBS, further arguing that patients presenting with IBS symptoms should undergo early testing for B. hominis as this may be beneficial[47]. This proposition is buttressed further by Ragavan et al[50] who recommend colonoscopy with PCR examination of stool aspirates, in IBS patients suspected to have B. hominis infection but who otherwise report a negative stool exam.
In a review article by Lepczyńska et al[48], it is argued that the concept of B. hominis being etiologically linked with IBS is inconclusive owing to the controversial nature of the organism as a human pathogen. On one hand, the authors affirm that the non-specific symptoms of blastocystosis are very much IBS-like and since enteric inflammation has been postulated to be one of the mechanisms in the pathogenesis of IBS, infection with B. hominis may be a contributory factor. Additional evidence in support of this causal posture is the fact that the protozoan is able to colonize the bowel by producing a proteolytic enzyme (cysteine protease) that breaks up IgA antibody, causing gut inflammation and a disturbance of the intestinal barrier function. However, it appears that it is some subtypes of B. hominis (ST4 and ST7) that possess this pathogenic ability and are able to cause disease in some but not all patients.
The notion that there is inconclusive evidence on the association between B. hominis infection and IBS is further articulated in an epidemiological study by Salvador et al[51]. In their study, 36 asymptomatic patients were compared with IBS patients of an equal number and the prevalence of blastocystosis was determined in each group. Interestingly, the healthy controls reported a higher prevalence than their IBS counterparts but this finding was not statistically significant. Accordingly, the authors concluded that further studies are required to provide clarity on the relationship.
In summary, piecing together the available evidence lends credence to the conclusion that there is indeed a growing suspicion among authors that Blastocystis spp. plays a role in the pathogenesis of IBS[47-53]. This suspicion gains support from numerous studies indicating a higher incidence of the organism in patients with IBS compared to healthy individuals[49]. While these studies do not definitively establish B. hominis as a causative agent for IBS or IBD, they underscore its contributory role in the pathogenesis of these conditions.
The evidence derived from the present synthesis aligns with this pattern, as both of the included studies reporting chronic diarrhea also identified comorbidities in affected patients, specifically Hashimoto’s thyroiditis[43] and ulcerative colitis[35]. While the third study, a randomized single-blinded clinical trial conducted by Dinleyici et al[28] among children at the Eskisehir Osmangazi University Faculty of Medicine Hospital in Turkey, may have involved participants with chronic diarrhea, the explicit duration of their symptoms, particularly whether lasting for at least four weeks, remains unknown. However, in contrast to the previous two studies, these children reported no comorbidities. Remarkably, the study's exclusion criteria encompassed hospitalization for any reason, medication use in the preceding month, presence of a comorbidity, and a positive stool result for any other infective organism besides B. hominis. Consequently, it is plausible that in low-resource settings, B. hominis is not only associated with chronic diarrhea but may indeed be a causative factor, even if such occurrences are infrequent.
Other symptoms of B. hominis infection
The additional symptoms outlined in this comprehensive review align with those documented in prior studies, supporting the notion that infection with the protist can manifest clinically in diverse ways[15,54]. Given that the gastrointestinal tract, particularly the colon and cecum, serves as the typical habitat for the organism, gastrointestinal symptoms like abdominal pain, diarrhea, flatulence, constipation, and nausea/vomiting are notably prevalent and expected[15,54]. Intriguingly, in this investigation, abdominal pain surpassed diarrhea as the most frequently reported symptom, a departure from the observations of Roberts et al[54] and Salvador et al[55], where diarrhea claimed the top spot in frequency. This divergence could potentially reflect the influence of different settings, as the mentioned studies were conducted in high-resource localities. The outcomes of this study imply that, when evaluating patients with the specified symptoms, suspicion of B. hominis infection should be considered and included in the differential diagnoses, particularly in cases involving the ingestion of contaminated food or water, or when stool examination yields negative results for other common pathogens such as Giardia lamblia, Cryptosporidium sp., Dientamoeba fragilis, Entamoeba sp., Cyclospora sp., and Cystoisospora sp.
Despite the aforementioned considerations, the study also revealed that blastocystosis might present atypically, manifesting in less common ways, including urticaria, angioedema, joint stiffness, and joint swelling. This atypical presentation can be attributed to the protist's potential dissemination to extraintestinal parts of the body, akin to other infections. In such instances, additional and localized symptoms may surface. Moreover, acting as a foreign entity, the organism may trigger an immunological response, resulting in cutaneous lesions such as urticaria and angioedema.
Treatment outcomes
Treatment for blastocystosis is typically initiated when patients exhibit chronic or persistent symptoms, have compromised immune systems, or present other pathogens in their stool examination[2,20]. While various antimicrobial agents have been reported in other studies for treating B. hominis infection, such as ornidazole, paromomycin, chloroquine, pentamidine, emetine, furazolidone, paromomycin, iodoquinol, and iodochlorhydroxyquin, these were not employed in the studies reviewed here.
Nevertheless, the evidence synthesized in this study aligns with other research, highlighting metronidazole as the most frequently utilized agent, solidifying its status as the primary antibiotic treatment choice[20,27,33,54]. The first comprehensive assessment of metronidazole's efficacy was carried out in a large-scale placebo-controlled trial by Nigro et al[56]. Conducted among immunocompetent patients with B. hominis as the sole intestinal parasite, the study showcased the drug's effectiveness in resolving diarrhea and inducing clinical remission. By implication, this trial substantiated the organism's capacity to trigger intestinal disease.
In terms of clinical outcomes, patients may spontaneously recover or witness symptom improvements even in the absence of formal treatment. This review unequivocally illustrates that within a week of treatment initiation, a minimum of approximately 70% of patients achieve full recovery, and by the end of a month, this rate escalates, approaching 100%. Clearly, treatment yields superior outcomes and proves highly favorable. However, the review also highlights instances of treatment failure, wherein patients exhibit no improvement, and some even experience exacerbated symptoms. The potential cause of this variable drug susceptibility is attributed to drug resistance stemming from mutations, such as the ATP-binding cassette transporters identified in the ST7 genome[2,57].
As emphasized by Roberts et al[54], instances of treatment failure underscore the necessity for extensive antimicrobial testing, expanding the arsenal of treatment alternatives available for managing blastocystosis when treatment proves ineffective. Despite this challenge, second-line agents (trimethoprim/sulfamethoxazole, iodoquinol, tinidazole, ornidazole, paromomycin, nitazoxanide, chloroquine, pentamidine, emetine, furazolidone, and iodochlorhydroxyquin) can be employed in such cases to enhance treatment outcomes[2,20].
In low-resource settings, the occurrence of chronic diarrhea due to B. hominis infection is infrequent. Conversely, when chronic diarrhea is evident, the likelihood of an additional diagnosis being present or causative is higher. Consequently, it is imperative to conduct a comprehensive clinical assessment or investigation to identify other potential diagnoses or pathogens in such scenarios, such as IBS[58], IBD[59-63], celiac disease[64,65], other chronic or acute infections[66-69], neoplasm[70] and drug induced diarrhea[71-73].
More frequently, symptoms such as abdominal pain, diarrhea, flatulence, constipation, and nausea/vomiting may manifest following B. hominis infection. It is crucial to recognize that the protozoan's infection can exhibit atypical presentations, including urticaria, depression, arthralgia, joint stiffness, joint swelling, angioedema, and peri-anal pruritus. Additionally, B. hominis has been associated with acute appendicitis, as highlighted by a recent case report of a 9-year-old boy who developed appendicular peritonitis due to this pathogen[74]. Furthermore, instances of B. hominis being identified in peritoneal fluid, even in patients undergoing peritoneal dialysis, underline the protozoan's potential pathogenicity in non-intestinal sites[75,76]. Thus, B. hominis should be considered in these clinical scenarios, particularly when treatments for presumed and more conventional diagnoses yield minimal or no response.
Despite the generally favorable clinical outcomes observed in individuals infected with B. hominis, treatment markedly improves results, leading to a quicker recovery rate with antimicrobial or alternative therapies. Treatment also aids in resolving comorbidities triggered or worsened by B. hominis infection. Therefore, while patients with mild symptoms may recover spontaneously or due to resource limitations, it is advisable to treat those with moderate to severe symptoms to optimize clinical outcomes. Metronidazole is recommended as the initial treatment, with a switch to a second-line option in cases of treatment failure or inadequate response.
However, it should be noted that the study's reliance on a limited number of databases may have constrained the scope of the literature review, which is a limitation that should be considered when interpreting the results. Additionally, the lack of prospective registration of this review in PROSPERO is a limitation that may impact the transparency and reproducibility of the study's findings. Furthermore, the absence of a formal bias assessment tool in this review is a limitation that may affect the evaluation of the included studies' quality. Additionally, the inclusion of 6 case reports out of 17 articles highlights a limitation in the scope of evidence available, which may impact the generalizability of the findings.
CONCLUSION
Future research, including meta-analyses and randomized controlled trials, is needed to better understand treatment response rates for B. hominis and identify the most effective therapies, especially in low-resource settings. A key area for investigation is distinguishing B. hominis infection from IBS-D. As IBS-D is a common cause of chronic diarrhea, it's important to test for B. hominis in patients who do not respond to standard IBS-D treatments. Improved diagnostic clarity will help ensure more accurate treatment and better outcomes for patients with chronic diarrhea.
ACKNOWLEDGEMENTS
We extend our appreciation to the Faculty of Life Sciences and Education at the University of South Wales for the Acute Medicine MSc program and their invaluable support in our work. We sincerely acknowledge the efforts of the University of South Wales and commend them for their commitment to providing life-long learning opportunities and advanced life skills to Health care professionals.
Footnotes
Provenance and peer review: Invited article; Externally peer reviewed.
Peer-review model: Single blind
Corresponding Author's Membership in Professional Societies: Federação Brasileira De Gastroenterologia; Grupo de Estudos da Doença Inflamatória Intestinal do Brasil; Sociedade Brasileira de Endoscopia Digestiva.
Specialty type: Medicine, research and experimental
Country of origin: United Kingdom
Peer-review report’s classification
Scientific Quality: Grade B, Grade C
Novelty: Grade B, Grade C
Creativity or Innovation: Grade B, Grade C
Scientific Significance: Grade B, Grade C
P-Reviewer: Arredondo Montero J S-Editor: Liu H L-Editor: A P-Editor: Guo X
Fasihi Karami M, Beiromvand M, Rafiei A, Cheraghian B, Beigzadeh E. Evaluating the Knowledge and Practice of Physicians Regarding Blastocystis hominis.Jundishapur J Health Sci. 2023;15.
[PubMed] [DOI][Cited in This Article: ]
Delshad A, Saraei M, Alizadeh SA, Niaraki SR, Alipour M, Hosseinbigi B, Bozorgomid A, Hajialilo E. Distribution and molecular analysis of Blastocystis subtypes from gastrointestinal symptomatic and asymptomatic patients in Iran.Afr Health Sci. 2020;20:1179-1189.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 4][Cited by in F6Publishing: 3][Article Influence: 0.8][Reference Citation Analysis (0)]
El Safadi D, Gaayeb L, Meloni D, Cian A, Poirier P, Wawrzyniak I, Delbac F, Dabboussi F, Delhaes L, Seck M, Hamze M, Riveau G, Viscogliosi E. Children of Senegal River Basin show the highest prevalence of Blastocystis sp. ever observed worldwide.BMC Infect Dis. 2014;14:164.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 146][Cited by in F6Publishing: 173][Article Influence: 17.3][Reference Citation Analysis (0)]
El Safadi D, Cian A, Nourrisson C, Pereira B, Morelle C, Bastien P, Bellanger AP, Botterel F, Candolfi E, Desoubeaux G, Lachaud L, Morio F, Pomares C, Rabodonirina M, Wawrzyniak I, Delbac F, Gantois N, Certad G, Delhaes L, Poirier P, Viscogliosi E. Prevalence, risk factors for infection and subtype distribution of the intestinal parasite Blastocystis sp. from a large-scale multi-center study in France.BMC Infect Dis. 2016;16:451.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 56][Cited by in F6Publishing: 70][Article Influence: 8.8][Reference Citation Analysis (0)]
Osman M, El Safadi D, Cian A, Benamrouz S, Nourrisson C, Poirier P, Pereira B, Razakandrainibe R, Pinon A, Lambert C, Wawrzyniak I, Dabboussi F, Delbac F, Favennec L, Hamze M, Viscogliosi E, Certad G. Prevalence and Risk Factors for Intestinal Protozoan Infections with Cryptosporidium, Giardia, Blastocystis and Dientamoeba among Schoolchildren in Tripoli, Lebanon.PLoS Negl Trop Dis. 2016;10:e0004496.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 64][Cited by in F6Publishing: 92][Article Influence: 11.5][Reference Citation Analysis (0)]
Audebert C, Even G, Cian A; Blastocystis Investigation Group, Loywick A, Merlin S, Viscogliosi E, Chabé M. Colonization with the enteric protozoa Blastocystis is associated with increased diversity of human gut bacterial microbiota.Sci Rep. 2016;6:25255.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 162][Cited by in F6Publishing: 174][Article Influence: 21.8][Reference Citation Analysis (0)]
Bednarska M, Jankowska I, Pawelas A, Piwczyńska K, Bajer A, Wolska-Kuśnierz B, Wielopolska M, Welc-Falęciak R. Prevalence of Cryptosporidium, Blastocystis, and other opportunistic infections in patients with primary and acquired immunodeficiency.Parasitol Res. 2018;117:2869-2879.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 26][Cited by in F6Publishing: 25][Article Influence: 4.2][Reference Citation Analysis (0)]
Poirier P, Wawrzyniak I, Albert A, El Alaoui H, Delbac F, Livrelli V. Development and evaluation of a real-time PCR assay for detection and quantification of blastocystis parasites in human stool samples: prospective study of patients with hematological malignancies.J Clin Microbiol. 2011;49:975-983.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 137][Cited by in F6Publishing: 128][Article Influence: 9.8][Reference Citation Analysis (0)]
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hróbjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Whiting P, Moher D. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.BMJ. 2021;372:n71.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 32381][Cited by in F6Publishing: 29275][Article Influence: 9758.3][Reference Citation Analysis (0)]
Kaya S, Cetin ES, Aridoğan BC, Arikan S, Demirci M. Pathogenicity of Blastocystis hominis, a clinical reevaluation.Turkiye Parazitol Derg. 2007;31:184-187.
[PubMed] [DOI][Cited in This Article: ]
Toro Monjaraz EM, Vichido Luna MA, Montijo Barrios E, Cervantes Bustamante R, Zárate Mondragón F, Huante Anaya A, Cadena León J, Mendez MC, López Ugalde M, Ramirez Mayans JA. Blastocystis Hominis and Chronic Abdominal Pain in Children: Is there an Association between Them?J Trop Pediatr. 2018;64:279-283.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 9][Cited by in F6Publishing: 9][Article Influence: 1.5][Reference Citation Analysis (0)]
Zaman Wahid B, Haque MA, Gazi MA, Fahim SM, Faruque ASG, Mahfuz M, Ahmed T. Site-Specific Incidence Rate of Blastocystis hominis and Its Association with Childhood Malnutrition: Findings from a Multi-Country Birth Cohort Study.Am J Trop Med Hyg. 2023;108:887-894.
[PubMed] [DOI][Cited in This Article: ][Reference Citation Analysis (0)]
Jha S, Gupta P, Bhatia M. Blastocystis spp. infection in cases of diarrhea: A pilot study from a tertiary care teaching hospital in Rishikesh, Uttarakhand, with a brief review of literature.Trop Parasitol. 2021;11:113-121.
[PubMed] [DOI][Cited in This Article: ][Reference Citation Analysis (0)]
Lepczyńska M, Dzika E, Kubiak K, Korycińska J. The role of Blastocystis sp. as an etiology of irritable bowel syndrome.Pol Ann Med. 2016;23:57-60.
[PubMed] [DOI][Cited in This Article: ]
Salvador F, Lobo B, Goterris L, Alonso-Cotoner C, Santos J, Sulleiro E, Bailo B, Carmena D, Sánchez-Montalvá A, Bosch-Nicolau P, Espinosa-Pereiro J, Fuentes I, Molina I. Blastocystis sp. Carriage and Irritable Bowel Syndrome: Is the Association Already Established?Biology (Basel). 2021;10.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 3][Cited by in F6Publishing: 4][Article Influence: 1.3][Reference Citation Analysis (0)]
Denoeud F, Roussel M, Noel B, Wawrzyniak I, Da Silva C, Diogon M, Viscogliosi E, Brochier-Armanet C, Couloux A, Poulain J, Segurens B, Anthouard V, Texier C, Blot N, Poirier P, Ng GC, Tan KS, Artiguenave F, Jaillon O, Aury JM, Delbac F, Wincker P, Vivarès CP, El Alaoui H. Genome sequence of the stramenopile Blastocystis, a human anaerobic parasite.Genome Biol. 2011;12:R29.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 133][Cited by in F6Publishing: 126][Article Influence: 9.7][Reference Citation Analysis (0)]
Maghsood AH, Kayedimajd S, Motavallihaghi S, Abedian R, Kordi S, Davoodi L, Faizi F, Soleymani E. Irritable Bowel Syndrome Associated with Blastocystis hominis or Without Relationship to It? A Case-Control Study and Minireview.Acta Parasitol. 2024;69:639-647.
[PubMed] [DOI][Cited in This Article: ][Reference Citation Analysis (0)]
Dall'Oglio VM, Balbinot RS, Muscope ALF, Castel MD, Souza TR, Macedo RS, Oliveira TB, Balbinot RA, Balbinot SS, Brambilla E, Soldera J. Epidemiological profile of inflammatory bowel disease in Caxias do Sul, Brazil: a cross-sectional study.Sao Paulo Med J. 2020;138:530-536.
[PubMed] [DOI][Cited in This Article: ][Reference Citation Analysis (0)]
da Cruz ER, Forno AD, Pacheco SA, Bigarella LG, Ballotin VR, Salgado K, Freisbelen D, Michelin L, Soldera J. Intestinal Paracoccidioidomycosis: Case report and systematic review.Braz J Infect Dis. 2021;25:101605.
[PubMed] [DOI][Cited in This Article: ][Reference Citation Analysis (0)]
Fistarol CHDB, Silva FR, Passarin TL, Schmitz RF, Salgado K, Soldera J. Obscure gastrointestinal bleeding due to gastrointestinal stromal tumour of duodenum.GastroHep. 2021;3:169-171.
[PubMed] [DOI][Cited in This Article: ]
Arredondo Montero J, Sáez Álvarez S, Bronte Anaut M, López Medrano R, Remacha Esteras MA, Rodríguez Ruiz M, Izquierdo García FM. Blastocystis hominis -associated Acute Appendicular Peritonitis in a 9-Year-old Boy: A Case Report and a Comprehensive Review of the Literature.Pediatr Infect Dis J. 2024;43:e327-e330.
[PubMed] [DOI][Cited in This Article: ][Reference Citation Analysis (0)]
