Abstract
Background:
Blastocystis spp. is known as one of the few intestinal parasites, prevalent in more than 5% and 30 - 60% of the population in industrialized and developing countries, respectively. In this respect, immunocompromised individuals, such as patients undergoing chemotherapy or those with malignancies, are at risk of the clinical symptoms of Blastocystis infection; however, the given condition is often self-limiting in healthy individuals.Objectives:
The current study aimed at evaluating the prevalence of Blastocystis infection in children with malignancies receiving chemo drugs.Methods:
The current descriptive, cross-sectional study was conducted on 52 stool specimens collected from patients with cancer admitted to the Oncology Ward of Shahid Baqaei 2 Hospital, Ahvaz, Iran, for six months. A standardized questionnaire was filled out for all cases. Each specimen was also prepared using direct smear, the Lugol iodine staining, and the formalin-ether condensation method.Results:
Blastocystis spp. was detected in 21.1% of the cases among them, 11.5% demonstrated gastrointestinal symptoms; therefore, a significant relationship was observed between Blastocystis infection and gastrointestinal symptoms.Conclusion:
Patients undergoing chemotherapy should be screened for opportunistic parasitic infections such as Blastocystis to avoid potentially life-threatening outcomes. Besides, further studies are required to identify the subtypes of Blastocystis.Keywords
Blastocystis Children with Cancer Chemotherapy Immunocompromised Individuals
1. Background
Infectious diseases, especially opportunistic ones, are significant complications among immunocompromised patients (1). Blastocystis is the most common single-celled opportunistic parasite found in humans and a wide range of animal stool specimens. The Blastocystis infection prevalence in humans varies from 0.5% to 30% in the industrialized and 30% to 76% in developing countries (2, 3). In a study in Tehran, Iran, the parasitic infection prevalence was 32.5% in primary immunodeficiency, 25.9% in cancer, and 28% in organ transplanted groups. The prevalence of B. hominis infection in patients with primary immunodeficiency disorders (PIDs) was 16.2%. Blastocystis hominis causes the most prevalent intestinal parasitic infection in patients with cancer (22.3%) (4). Many Blastocystis spp. carriers are asymptomatic, and the term infection is often used for those manifesting pathological symptoms (5). This infection is generally self-limiting, and fecal-oral is the main route of transmission due to poor hygiene, close contact with infected animals, and consumption of contaminated food or water, resulting in a wide range of prevalence in different types (6, 7). Nevertheless, the non-specific gastrointestinal symptoms of Blastocystis infection- e g, diarrhea, abdominal pain, flatulence, nausea, vomiting, constipation, weight loss, or fatigue, lead to a poor understanding of its pathogenesis (8). A large rising trend in the incidence of cancers is projected in the following years, and the best existing treatment is chemotherapy. Although chemotherapy improves survival rate and quality of life in patients, it is associated with long-term changes in immunological parameters, etc. (9). The clinical manifestations of Blastocystis infection are more highlighted among patients with immunodeficiency and cancer compared with healthy individuals since such people have quantitative or qualitative changes in their immune responses that prevent it from functioning effectively. Self-limiting diarrhea caused by Blastocystis infection in healthy individuals can manifest as severe diarrhea in immunocompromised patients and cause complications such as weight loss, anorexia, malabsorption syndrome, fever, and abdominal pain (10-14).
Many symptoms in patients with PIDs could be mimics parasitic infestation-e g, fever, and diarrhea; therefore, the diagnosis of parasitic infections varies across clinical signs and symptoms.
2. Objectives
The current study aimed at investigating the prevalence of Blastocystis infection in pediatric patients with malignancy admitted to the Oncology Ward of Baqaei 2 Hospital in Ahvaz, Iran.
3. Methods
The current descriptive, cross-sectional study was conducted on 52 stool specimens collected from children with cancer admitted to the Baqaei 2 Hospital from April to October 2019 after obtaining signed informed consent. The study protocol was approved by the Ethics Committee of Ahvaz Jundishapur University of Medical Sciences. Collected samples were examined by light microscopy using Lugol-stained smears at 100× and 400× magnifications to detect Blastocystis. A direct saline smear was prepared for each patient with trichrome staining and then examined by light microscopy. The specimens were screened using the formalin-ether condensation method, and the results were transferred into the questionnaire.
The duration of the first chemotherapy course in all the patients ranged from six months to three years (with a mean of one year), and they were treated with combinations of chemo drugs (Table 1).Neutropenia was also observed in 2% of the patients; 11% were treated with antifungal drugs and antibiotics. Supportive therapy included a three-day course of metronidazole. The interval between sampling and the last session of chemotherapy was 1 - 2 days. However, 41 (78.8%) patients were in the maintenance phase of treatment. To determine the prevalence of Blastocystis infection, a standardized questionnaire, comprised of demographic information, type of cancer, gastrointestinal symptoms (such as stomachache, cramps, nausea, vomiting, and diarrhea), stool appearance (color and consistency), and the stool test result, was designed and completed. Finally, the data were analyzed by SPSS software, and the Chi-square test was used for qualitative variables.
Types of Chemotherapy for Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, Neuroblastoma, and Ewing Sarcoma
| Type of Cancer | Chemotherapy |
|---|---|
| AML | Cytarabine + daunomycin |
| ALL | Vincristine, daunorubicin, cytarabine, L-asparaginase, mercaptopurine, methotrexate, cyclophosphamide, prednisone, dexamethasone, nelarabine |
| Neuroblastoma | Carboplatin, cyclophosphamide, doxorubicin, etoposide |
| Ewing sarcoma | Doxorubicin, cyclophosphamide, ifosfamide, vincristine, etoposide |
4. Results
In the current study, 52 stool specimens were obtained from children with cancer. According to the study findings, 28 (53.8%) patients were male, and 24 (46.2%) females. The prevalence of Blastocystis infection was 21. % (n = 11) in the studied patients. Based on Lugol-stained smears, Blastocystis was detected in 10 positive children with cancer (19%). The formalin-ether concentration technique detected 11 positive cases (21%). The trichrome-stained smear detected 11 positive cases (21%). The age range of the patients was from four months to 16 years, classified into four groups of ≤ 1 year [n = 8 (15.4%)], 1 - 5 years [n = 18 (34.6%)], 6 - 10 years [n = 12 (23%)], and 11 - 16 years [n = 14 (27%)] (Tables 2 and 3).
Demographic Characteristics of Children with Cancer
| Demographic Characteristics | No. (%) |
|---|---|
| Gender | |
| Male | 28 (53.8) |
| Female | 24 (46.2) |
| Age group (y) | |
| ≤ 1 | 8 (15.4) |
| 1 - 5 | 18 (34.6) |
| 6 - 10 | 12 (23) |
| 11 - 16 | 14 (27) |
| Total | 52 |
The Prevalence of Blastocystis Infection in Children with Cancer
| Demographic Characteristics | The Prevalence of Blastocystis Infection, No. (%) |
|---|---|
| Gender | |
| Male | 7 (13.4) |
| Female | 4 (7.7) |
| Age group | |
| ≤ 1 | 1 (1.9) |
| 1 - 5 | 2 (3.8) |
| 6 - 10 | 5 (9.6) |
| 11 - 16 | 3 (5.7) |
| Total | 11 |
The obtained results indicated no statistically significant differences in gender, age, and prevalence of Blastocystis infection among the subjects (P < 0.05). The results also highlighted that among 52 children with cancer, 11 were infected with Blastocystis spp. among which six (11.5%) had gastrointestinal symptoms, including stomachache, cramps, nausea, vomiting, and diarrhea. The correlation between the type of cancer and gastrointestinal symptoms in patients with Blastocystis infection is shown in Table 4.
Types of Cancer and Gastrointestinal Symptoms in Patients with Blastocystis Infection
| No. | Type of Cancer | Gastrointestinal Symptom |
|---|---|---|
| 1 | AML | Diarrhea |
| 2 | ALL | Abdominal pain |
| 3 | ALL | Fever, vomiting |
| 4 | Neuroblastoma | Diarrhea |
| 5 | Ewing sarcoma | Diarrhea |
Statistical analysis revealed a significant relationship between Blastocystis infection and gastrointestinal symptoms (P < 0.05).
5. Discussion
Blastocystis is an anaerobic and zoonotic micro-eukaryote with a global distribution, generally found in the large intestine of the human and a wide range of vertebrates (10), as reported by Allexief more than 100 years ago (15). Since the asymptomatic carriers of Blastocystis spp. are common, its pathogenicity remained uncertain (2). numerous digestive and non-digestive symptoms, such as diarrhea, abdominal pain, nausea, fatigue, constipation, flatulence, vomiting (11), cutaneous disorders, and chronic or acute urticaria, are attributed to Blastocystis infection (16). Blastocystis spp. can produce large quantities of proteases, hydrolases, and protease inhibitors, contributing to its pathophysiology. Instant serine protease can further result in stomachache, muscle contractions, and broad-spectrum pains (12). Cysteine protease can also cleave human secretory immunoglobulin A (IgA) and promote mucosal adhesion of pathogens (17). Many reports considered Blastocystis spp. as opportunistic pathogens in immunocompromised patients; therefore, their clinical symptoms are more intense (18). At the early stages of chemotherapy, a few cases colonized with Blastocystis spp. are undetectable. The immune system of patients is compromised during chemotherapy, and consequently, the parasitic disease develops and diminishes the effect of chemo drugs, and accordingly, cancer progresses (19). Among unicellular infections in immunocompromised individuals, Blastocystis is the most common one. The findings of the present study showed that the prevalence of Blastocystis infection was 21% (n = 11) in children with cancer, among which 11.5% had gastrointestinal symptoms; therefore, there was a significant relationship between Blastocystis infection and gastrointestinal symptoms. According to Hafeez-Abdel et al., the prevalence of Blastocystis infection in children with immunodeficiency was 12.1% in Egypt. Uysal et al., reported that 23. % of patients with common variable immune deficiency were infected with Blastocystis spp. in Turkey (20, 21). The data in the present study were also confirmed by Idris et al., reporting that 54.8% of 42 immunocompromised children with diarrhea were infected with Blastocystis spp. in Indonesia (22). Lack of significant differences in gender, age, and Blastocystis spp. infection among the patients was another finding of the present study; however, Ozlem Years et al., obtained quite different results. They noted that the prevalence of Blastocystis infection was higher in male patients than females, and interestingly, the rate of gastrointestinal symptoms was not significantly different between infected and non-infected cases (23). Moe et al., found an age-related susceptibility to Blastocystis infection in immunocompetent BALB/c mice. In the concerned investigation, juvenile mice were more susceptible than adult cases, and eight-week-old adult mice were resistant to Blastocystis infection (24). This difference might be related to various Blastocystis strains, the issue needs molecular studies. During chemotherapy, the risk of parasitic infections is minimized due to particular conditions, including lifestyle, diet, and environment; therefore, it can be claimed that it is the opportunity for opportunistic pathogens to invade and cause clinical problems (25). Fontanet believed that there was no significant difference in the prevalence of parasitic infections among people with and without immunodeficiency. On the other hand, in some studies, such as the one by Escobedo and Nunez, the prevalence of Blastocystis infection was reported higher in immunocompromised patients compared with healthy individuals (25). Under such circumstances, person-to-person was the main route of transmission. The limitation of the present study was the relatively small sample size.
5.1. Conclusion
Patients undergoing chemotherapy should be screened for opportunistic parasitic infections such as Blastocystis spp. to avoid potentially life-threatening outcomes, prevent person-to-person transmission, and help to improve patient responses to treatment. Further studies are required to identify the subtypes of Blastocystis.
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