|Year : 2022 | Volume
| Issue : 2 | Page : 94-98
Cyclosporiasis in immunocompetent and immunocompromised patients – A Twelve years experience from a tertiary care centre in Northern India
Ujjala Ghoshal1, Tasneem Siddiqui1, Nidhi Tejan1, Sheetal Verma2, Ankita Pandey1, Uday C Ghoshal3
1 Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
2 Department of Microbiology, King George's Medical University, Lucknow, Uttar Pradesh, India
3 Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
|Date of Submission||13-Sep-2021|
|Date of Decision||26-Oct-2021|
|Date of Acceptance||22-Dec-2021|
|Date of Web Publication||24-Nov-2022|
Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Rae Bareli Road, Lucknow - 226 014, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Context: Cyclosporiasis is an emerging enteric coccidian parasitic disease worldwide, caused by the parasite Cyclospora cayetanensis. There is scanty data from India, especially among immunocompetent patients.
Aims: The aim is to evaluate the occurrence of Cyclosporiasis in immunocompetent and immunocompromised patients.
Settings and Design: It is a prospective cohort study conducted from June 2006 to May 2018 at our tertiary care center.
Materials and Methods: Stool samples were collected from the 900 patients with diarrhea (both immunocompetent and immunocompromised) and 170 healthy controls to look for Cyclospora by modified Kinyoun staining.
Statistical Analysis: Mann–Whitney U test/Fisher exact test were used for statistical analysis.
Results: Oocysts of C. cayetanensis were detected in 10/900 patients and none of the healthy controls. The median age of patients was 38.5 years (10-65 years) and males (6/10) outnumbered the females in harboring the parasite. Eight patients were immunocompromised (five postrenal transplant cases and one-one patient each with HIV, non-Hodgkin's lymphoma, and juvenile polyarthritis), and two patients were immunocompetent. Cyclospora infection was more common in immunocompromised patients (8/300, 2.67%) than the immunocompetent patients (2/600, 0.33%); P < 0.001. Eight patients responded well to trimethoprim-sulfamethoxazole, one died, and one was lost to follow-up. Coinfection with Cryptosporidium spp. was seen in one patient.
Conclusion: Cyclospora causes diarrhea in both immunocompromised and immunocompetent persons. Its burden may be underestimated due to a lack of awareness and appropriate diagnostic methods. Special staining techniques are important for diagnosis as they may be missed by routine microscopy.
Keywords: Cyclospora, opportunistic intestinal parasite, transplant recipients
|How to cite this article:|
Ghoshal U, Siddiqui T, Tejan N, Verma S, Pandey A, Ghoshal UC. Cyclosporiasis in immunocompetent and immunocompromised patients – A Twelve years experience from a tertiary care centre in Northern India. Trop Parasitol 2022;12:94-8
|How to cite this URL:|
Ghoshal U, Siddiqui T, Tejan N, Verma S, Pandey A, Ghoshal UC. Cyclosporiasis in immunocompetent and immunocompromised patients – A Twelve years experience from a tertiary care centre in Northern India. Trop Parasitol [serial online] 2022 [cited 2023 Mar 29];12:94-8. Available from: https://www.tropicalparasitology.org/text.asp?2022/12/2/94/361957
| Introduction|| |
Cyclospora cayetanensis is an opportunistic coccidian parasite causing diarrheal illness called cyclosporiasis. It causes mild-to-moderate self-limiting diarrhea in immunocompetent and prolonged severe diarrhea in immunocompromised individuals. It has been associated with acquired immunodeficiency syndrome (AIDS), hematological malignancy, and renal transplantation.,, There are scanty studies regarding the incidence of Cyclospora infections among hospitalized patients (especially immunocompetent) in India, therefore, we conducted this prospective study over a period of 12 years to study:
- Incidence of cyclosporiasis in immunocompetent and immunocompromised patients
- Demographic details and clinical presentation of patients with Cyclospora infections
- Seasonal trends in the detection of Cyclospora infections
- Coinfections in these patients.
| Material and Methods|| |
Study population and duration
This was a prospective cohort study conducted from June 2007 to July 2019 in the parasitology division of the Department of Microbiology of a tertiary care center of northern India. The 900 eligible patients presenting with diarrhea (either immunocompetent or immunocompromised, who agreed to participate in the study and answered the questionnaire) were included in the study. Similarly, 170 age-and gender-matched healthy controls (without any gastrointestinal complaints who visited the department during the study period and agreed to participate and answered the questionnaire) were purposefully selected to look for “oocysts of Cyclospora.”
Diarrhea was defined as change in consistency (i.e., soft or liquid) and an increase in frequency of bowel movements to ≥3 stools per day. Acute diarrhea is defined as the abrupt onset of diarrhea of ≤14 days in duration. Persistent diarrhea lasts longer than 2 weeks and <4 weeks and chronic diarrhea lasts at least 4 weeks. Immunocompetent patients were defined as those who did not give a history of solid organ transplantation, immunosuppressive treatment, hematological malignancy, and positive serological test for human immunodeficiency virus (HIV) infection.
Stool samples of 900 patients with diarrhea presenting to our tertiary care center were analyzed for the presence of enteric pathogens. Six hundred patients were immunocompetent and 300 were immunocompromised (HIV, transplant recipients, and those with malignancy and autoimmune disease). Stool specimens from 170 healthy controls without any gastrointestinal complaints were also included in this study. Demographic, clinical details, and laboratory data of all the patients and healthy controls were recorded on a predesigned proforma.
Sample collection, sample size, and processing
Attempts were made to collect three consecutive stool samples from each patient and healthy controls during the study period. However, in seven patients and two controls, two and one samples, respectively, could be collected. Only stool specimens were collected in clean, wide-mouthed, screw-capped disposable containers and processed preferably within 1 h for routine microscopy using normal saline and iodine mounts and the modified Kinyoun technique and bacteriological cultures.
Formol-ether concentration technique
It was performed by the standard method, as previously reported by us. The supernatant was discarded and sediment was collected for the modified Kinyoun technique.
Modified Kinyoun technique
It was performed with a few modifications, as previously reported. The smear was scanned on a 10× eyepiece and oil immersion objective 100× of the light microscope, with an effective magnification of 1000×. Oocysts of Cyclospora were seen as bright pink acid-fast round structures, 8-10 μm in size, giving a wrinkled cellophane paper appearance [Figure 1].
|Figure 1: Size, shape, and overall morphologic features of the (a) oocysts of Cyclospora cayetanensis and (b) Cyptosporidium parvum-stained bright pink with modified acid-fast stain (oil, ×1000)|
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Bacterial stool culture
Stool samples were also subjected to culture on MacConkey, Deoxycholate Citrate Agar, and dextrose Sorbitol Rhamnose Agar media as per the standard microbiological technique to exclude bacterial agents causing diarrhea such as Salmonella More Details spp. and Shigella spp.
Ethical clearance was obtained from the Institutional ethics committee (Ref. number PGI/PhD/IEC/57/21.10.2011).
Duration of diarrhea was presented in median (minimum, maximum, or “Range”) and compared by MannWhitney U test. Categorical variables were presented in frequency (%) and compared by Fisher exact test. A P < 0.05 was considered statistically significant. The Statistical Package of social sciences, version-23 (SPSS-23, IBM, Chicago, USA) was used for statistical analysis.
| Results|| |
In the present study, oocysts of Cyclospora cayetanensis were detected in 1.1% (10/900) patients and none (0%) of the healthy control. Of 300 immunocompromised patients, 27% (n = 81) patients were HIV/AIDS-positive, 21% (n = 63) had hematological malignancies, 50.3% (n = 151) patients were renal transplant recipients, and 1.7% (n = 5) had autoimmune diseases. The mean age of 900 patients was 38.79 ± 14.63 and male-to female-ratio was 3.4. However, the median age of patients with cyclosporiasis was 38.5 years (range 10-65). C. cayetanensis predominantly infected adults (9 of 10) in the study except one, who was a 10-year-old child. Six of ten patients were males and four were females [Table 1]. The immunocompromised group (8 out of 10) with cyclosporiasis comprised five postrenal transplant cases and one-one case each of HIV seropositive patients, non-Hodgkin's lymphoma, and juvenile polyarthritis. Two patients did not have any history of immunocompromised status. Cyclospora infection was more common in immunocompromised patients with diarrhea (2.67%, 8 of 300 cases) than the immunocompetent group (0.33%, 2 of 600 cases) which was statistically significant (P < 0.001).
All cases of cyclosporiasis were detected from May to August [Figure 2]. Yearly trend of cyclosporiasis showed one case each of cyclosporiasis from 2007 to 2010, one case in 2012, two and three cases were detected in 2018 and 2019, respectively [Figure 3].
|Table 1: Clinico-demographic profile of 10 patients with Cyclospora infection|
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The common clinical presentation among the patients with cyclosporiasis infection were prolonged diarrhea (9/10, 90%), vomiting (5/10, 50%), abdominal pain (3/10, 30%), fever (3/10, 30%), loss of appetite (2/10,20%), and unintentional weight loss (5/10, 50%), but there was no significant difference in clinical features of patients with diarrhea in the immunocompromised group and immunocompetent group [Table 2].
In the patients with cyclosporiasis chronic diarrhea was the most common presentation (5/10, 50%) followed by persistent diarrhea (4/10, 40%) and only one child presented with acute diarrhea. The median frequency of diarrhea was more among the immunocompromised patients (8 stools/day) than immunocompetent ones (4 stools/day).
Bacterial stool culture was positive in five samples. The following agents were isolated: Shigella sonnei (2), Shigella dysenteriae (1), Salmonella paratyphi B (1), and Vibrio cholerae (1). One renal transplant recipient's stool examination also revealed oocysts of Cryptosporidium spp. by modified Kinyoun's acid-fast staining. The oocyst of Cryptosporidium are 4-6 μm in size, pink acid-fast round structures, and exhibit partial acid-fast staining. Eight patients responded well to trimethoprim-sulfamethoxazole therapy, one was lost to follow up, and one died during the treatment, but the cause of death was due to bacterial sepsis.
| Discussion|| |
This is a prospective cohort study from India showing seasonal trends, incidence of cyclosporiasis among renal transplant recipients and immunocompromised patients. The incidence of C. cayetanensis was 1.1% in the present study, which is quite low in comparison to that reported by other similar studies which have reported the variable prevalence of Cyclospora ranging from 2.4% to 22.2% in India.,, The disparity could be due to geographical factors and difference in number, duration, and patients recruited in these studies. Our institute is a tertiary care center so only referred patients who have already received empirical therapy reach us and this could be a reason of low incidence of cyclosporiasis in our study. Males (6/10, 60%) were more commonly affected with cyclosporiasis in our study which is consistent with other studies from India., In our study, we did not observe any difference in clinical features among patients with diarrhea in the immunocompromised group and immunocompetent group as reported by other studies from India. The frequency of diarrhea was more in immunocompromised patients than immunocompetent patients indicating more severe diarrhea in immunocompromised patients. Majority of patients presented with chronic and persistent diarrheal illness with the passage of watery and loose stools equally and duration of diarrhea ranged from 14 to 60 days which is in accordance with other studies.,,
Cyclospora infection in our study was more common in immunocompromised group (8/300, 2.67%) than immunocompetent group (2/600, 0.33%) which is in accordance with other studies., Cyclosporiasis was detected from May to August, i.e., in summer season before rainfall and during the rainy season which is in resonance with other studies.,
This is one of the few studies which has revealed high prevalence of Cyclospora infection in postrenal transplant recipients (5/10, 50%). Similar findings were observed by Ismail et al. who found a prevalence of 10% among 50 renal transplant recipients in their study. Yadav et al. from India, in their study on 38 transplant recipients comprising 29 postrenal recipients have reported an incidence of cyclosporiasis as 5%. In addition, Cyclospora infection were also documented in one case each of HIV-positive and non-Hodgkin's lymphoma patients on chemotherapy which is consistent with other studies.,, Infection in a child with juvenile idiopathic arthritis on immunosuppressive drugs is a new finding of our study. Interestingly, our study reveals high incidence of cyclosporiasis in immunocompetent adult patients (2/10, 20%) in contrast to Yadav et al. who have reported Cyclospora infection in immunocompetent patients as 4.3%. Mixed infection with Cryptosporidium spp. was documented in one transplant recipient which has been reported in other studies as well., It is suggested that the possibility of a mixed infection should also be considered, especially in renal transplant recipients.
| Conclusion|| |
Awareness must be spread among the clinicians about the occurrence of Cyclospora infection not only in immunocompromised but even in immunocompetent patients, causing gastrointestinal symptoms. Its infection can be diagnosed by a simple and inexpensive method of modified acid-fast staining. However, requisition forms with proper history must be sent to the laboratories because all laboratories might not be able to do this exercise for all the stool samples and hence these infections may be missed.
It is a single-center study, and majority of patients of our study were adults which might have been biased by the absence of pediatrics outpatient department in our institute.
A field-based study needs to be conducted to find the actual incidence of cyclosporiasis as a mild form of diseased patients do not reach tertiary care center.
Ethical clearance was obtained from the Institutional ethics committee (Ref. number PGI/PhD/IEC/57/21.10.2011).
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Shields JM, Olson BH. Cyclospora cayetanensis: A review of an emerging parasitic coccidian. Int J Parasitol 2003;33:371-91.
Deodhar L, Maniar JK, Saple DG. Cyclospora infection in acquired immunodeficiency syndrome. J Assoc Physicians India 2000;48:404-6.
Yadav P, Khalil S, Mirdha BR. Molecular appraisal of intestinal parasitic infection in transplant recipients. Indian J Med Res 2016;144:258-63.
] [Full text]
Iqbal J, Hira PR, Al-Ali F, Khalid N. Cyclospora cayetanensis: First report of imported and autochthonous infections in Kuwait. J Infect Dev Ctries 2011;5:383-90.
Guerrant RL, Van Gilder T, Steiner TS, Thielman NM, Slutsker L, Tauxe RV, et al.
Practice guidelines for the management of infectious diarrhea. Clin Infect Dis 2001;32:331-51.
Ghoshal U, Dey A, Ranjan P, Khanduja S, Agarwal V, Ghoshal UC. Identification of opportunistic enteric parasites among immunocompetent patients with diarrhoea from Northern India and genetic characterisation of cryptosporidium and microsporidia. Indian J Med Microbiol 2016;34:60-6.
] [Full text]
Cheesbrough M. District Laboratory Practice in Tropical Countries. UK: Cambridge University Press; 2006.
Yadav P, Khalil S, Mirdha BR, Makharia GK, Bhatnagar S. Molecular characterization of clinical isolates of Cyclospora cayetanensis
from patients with diarrhea in India. Indian J Med Microbiol 2015;33:351-6.
] [Full text]
Gupta S, Narang S, Nunavath V, Singh S. Chronic diarrhoea in HIV patients: Prevalence of coccidian parasites. Indian J Med Microbiol 2008;26:172-5.
] [Full text]
Dhanabal J, Selvadoss PP, Muthuswamy K. Comparative study of the prevalence of intestinal parasites in low socioeconomic areas from South Chennai, India. J Parasitol Res 2014;2014:630968.
Ashihabegum MA, Dhanabalan P, Sucilathangam G, Velvizhi G, Jeyamurugan T, Palaniappan N, et al.
Prevalence of Cyclospora cayetanensis
in HIV positive individuals in a tertiary care hospital. J Clin Diag Res 2012;6:382-4.
Saurabh K, Nag VL, Dash S, Maurya AK, Hada V, Agrawal R, et al.
Spectrum of parasitic infections in patients with diarrhoea attending a tertiary care hospital in Western Rajasthan, India. J Clin Diagn Res 2017;11:C01-4.
Jiang Y, Yuan Z, Zang G, Dan L, Wang Y, Zang Y, et al.
Cyclospora cayetanensis infections among diarrheal outpatients in Shanghai: A retrospective case study. Front Med 2018;12:98.
Mbae CK, Nokes DJ, Mulinge E, Nyambura J, Waruru A, Kariuki S. Intestinal parasitic infections in children presenting with diarrhoea in outpatient and inpatient settings in an informal settlement of Nairobi, Kenya. BMC Infect Dis 2013;13:243.
Sancak B, Akyon Y, Ergüven S. Cyclospora infection in five immunocompetent patients in a Turkish university hospital. J Med Microbiol 2006;55:459-62.
Mak JW. Important zoonotic intestinal protozoan parasites in Asia. Trop Biomed 2004;21:39-50.
Li J, Wang R, Chen Y, Xiao L, Zhang L. Cyclospora cayetanensis
infection in humans: Biological characteristics, clinical features, epidemiology, detection method and treatment. Parasitology 2020;147:160-70.
Tuli L, Gulati AK, Sundar S, Mohapatra TM. Correlation between CD4 counts of HIV patients and enteric protozoan in different seasons – An experience of a tertiary care hospital in Varanasi (India). BMC Gastroenterol 2008;8:36.
Ismail M, Fadl H. Cyclospora infection in renal transplant recipient. J Egypt Soc Parasitol 2019;49:727-30.
Helmy MM, Rashed LA, Abdel-Fattah HS. Co-infection with Cryptosporidium parvum
and Cyclospora cayetanensis
in immune compromised patients. J Egypt Soc Parasitol 2006;36:613-27.
Bhandari D, Tandukar S, Parajuli H, Thapa P, Chaudhary P, Shrestha D, et al
. Cyclospora infection among school children in Kathmandu, Nepal: Prevalence and associated risk factors. Trop Med Health 2015;43:211-6.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]