Abstract
Giardia intestinalis and Blastocystis hominis cause frequent infections in children in developing countries. However, the role of intestinal inflammation in their pathogenesis is still poorly understood. Faecal calprotectin (FC) level is used as an indicator of intestinal inflammation and neutrophil migration in the intestinal tract. The present study aimed to evaluate intestinal inflammation by measuring FC level among children infected with either G. intestinalis or B. hominis before and after treatment. Stool samples were collected from 282 children inhabiting a rural area in Egypt and examined microscopically for intestinal parasites. FC level was estimated in a group of children infected with G. intestinalis (n = 12) or B. hominis (n = 12) before and 3 weeks after receiving nitazoxanide (200 mg twice daily for 3 days) and compared to a control group (n = 18) of parasite-free children. Cases of mixed infection were excluded. Nitazoxanide cure rate was 83% in both infections with a remarkable reduction of infection intensity in uncured children. The difference in FC levels between infected children and controls was not statistically significant. Also, the difference between the pre- and post-treatment estimations was not statistically significant. Elevated levels were observed before treatment in three children (two infected with G. intestinalis and one with B. hominis) who displayed normal post-treatment levels. Although G. intestinalis and B. hominis infections appear to cause no remarkable intestinal inflammation, they may induce abnormally elevated FC levels in a subset of children.
Similar content being viewed by others
Availability of data and materials
The data supporting the findings of this study are contained within the manuscript. The raw data are available by the corresponding author when requested.
Code availability
Not applicable.
References
Asseman C, Mauze S, Leach MW, Coffman RL, Powrie F (1999) An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. J Exp Med 190(7):995–1004. https://doi.org/10.1084/jem.190.7.995
Cama VA, Mathison BA (2015) Infections by Intestinal Coccidia and Giardia duodenalis. Clin Lab Med 35(2):423–444. https://doi.org/10.1016/j.cll.2015.02.010
Campbell DI, McPhail G, Lunn PG, Elia M, Jeffries DJ (2004) Intestinal inflammation measured by fecal neopterin in Gambian children with enteropathy: association with growth failure, Giardia lamblia, and intestinal permeability. J Pediatr Gastroenterol Nutr 39(2):153–157. https://doi.org/10.1097/00005176-200408000-00005
Carrasco-Labra A, Lytvyn L, Falck-Ytter Y, Surawicz CM, Chey WD (2019) AGA technical review on the evaluation of functional diarrhea and diarrhea-predominant irritable bowel syndrome in adults (IBS-D). Gastroenterology 157(3):859–880. https://doi.org/10.1053/j.gastro.2019.06.014
Chen TL, Chen S, Wu HW et al (2013) Persistent gut barrier damage and commensal bacterial influx following eradication of Giardia infection in mice. Gut Pathog 5(1):26. https://doi.org/10.1186/1757-4749-5-26
Cotton JA, Motta JP, Schenck LP, Hirota SA, Beck PL, Buret AG (2014) Giardia duodenalis infection reduces granulocyte infiltration in an in vivo model of bacterial toxin-induced colitis and attenuates inflammation in human intestinal tissue. PLoS ONE 9(10):e109087. https://doi.org/10.1371/journal.pone.0109087
Damms A, Bischoff SC (2008) Validation and clinical significance of a new calprotectin rapid test for the diagnosis of gastrointestinal diseases. Int J Colorectal Dis 23(10):985–992. https://doi.org/10.1007/s00384-008-0506-0
D’Angelo F, Felley C, Frossard JL (2017) Calprotectin in daily practice: where do we stand in 2017? Digestion 95:293–301
Escobedo AA, Cimerman S (2007) Giardiasis: a pharmacotherapy review. Expert Opin Pharmacother 8(12):1885–1902. https://doi.org/10.1517/14656566.8.12.1885
Farthing MJ, Cevallos AM, Kelly P (2009) Intestinal protozoa. In: Cook GC, Zumla AL (eds) Manson’s tropical diseases, 22nd edn. Elsevier, London, pp 1375–1406
Fletcher SM, Stark D, Harkness J, Ellis J (2012) Enteric protozoa in the developed world: a public health perspective. Clin Microbiol Rev 25(3):420–449. https://doi.org/10.1128/CMR.05038-11
Garcia LS (2016) Macroscopic and microscopic examination of fecal specimens. In: Garcia LS (ed) Diagnostic medical parasitology, 6th edn. ASM Press, Washington, DC, pp 782–830
George CM, Burrowes V, Perin J et al (2018) Enteric infections in young children are associated with environmental enteropathy and impaired growth. Trop Med Int Health 23(1):26–33. https://doi.org/10.1111/tmi.13002
Girish S, Kumar S, Aminudin N, Ali T (2015) (Eurycoma longifolia): a possible therapeutic candidate against Blastocystis sp. Parasit Vectors 8:332. https://doi.org/10.1186/s13071-015-0942-y
Haisma SM, van Rheenen PF, Wagenmakers L, Kobold AM (2019) Calprotectin instability may lead to undertreatment in children with IBD. Arch Dis Child. https://doi.org/10.1136/archdischild-2018-316584
Hanevik K, Hausken T, Morken MH et al (2007) Persisting symptoms and duodenal inflammation related to Giardia duodenalis infection. J Infect 55(6):524–530. https://doi.org/10.1016/j.jinf.2007.09.004
Harhay MO, Horton J, Olliaro PL (2010) Epidemiology and control of human gastrointestinal parasites in children. Expert Rev Anti Infect Ther 8(2):219–234. https://doi.org/10.1586/eri.09.119
Henderson P, Anderson NH, Wilson DC (2014) The diagnostic accuracy of fecal calprotectin during the investigation of suspected pediatric inflammatory bowel disease: a systematic review and meta-analysis. Am J Gastroenterol 109(5):637–645. https://doi.org/10.1038/ajg.2013.131
Kohli A, Bushen OY, Pinkerton RC et al (2008) Giardia duodenalis assemblage, clinical presentation and markers of intestinal inflammation in Brazilian children. Trans R Soc Trop Med Hyg 102(7):718–725. https://doi.org/10.1016/j.trstmh.2008.03.002
Lam YA, Warouw SM, Wahani AMI, Manoppo JIC, Salendu PM (2014) Correlation between gut pathogens and fecal calprotectin levels in young children with acute diarrhea. Paediatr Indones 54(4):193–197
McCormick BJJ, Lee GO, Seidman JC et al (2017) Dynamics and trends in fecal biomarkers of gut function in children from 1–24 months in the MAL-ED study. Am J Trop Med Hyg 96(2):465–472. https://doi.org/10.4269/ajtmh.16-0496
Moe KT, Singh M, Howe J et al (1997) Experimental Blastocystis hominis infection in laboratory mice. Parasitol Res 83(4):319–325. https://doi.org/10.1007/s004360050256
Nieves-Ramírez ME, Partida-Rodríguez O, Laforest-Lapointe I et al (2018) Asymptomatic intestinal colonization with protist Blastocystis is strongly associated with distinct microbiome ecological patterns. mSystems 3(3):e00007–18. https://doi.org/10.1128/mSystems.00007-18
Oberhuber G, Kastner N, Stolte M (1997) Giardiasis: a histologic analysis of 567 cases. Scand J Gastroenterol 32(1):48–51. https://doi.org/10.3109/00365529709025062
Omaran EK, Hamed AF, Yousef MA (2013) Common parasitic infection among rural population Sohag Governorate. Egypt J Am Sci 9(4):596–601
Ordóñez-Mena JM, McCarthy ND, Fanshawe TR (2018) Comparative efficacy of drugs for treating giardiasis: a systematic update of the literature and network meta-analysis of randomized clinical trials. J Antimicrob Chemother 73(3):596–606. https://doi.org/10.1093/jac/dkx430
Pathirana WGW, Chubb SP, Gillett MJ, Vasikaran SD (2018) Faecal calprotectin. Clin Biochem Rev 39(3):77–90
Podewils LJ, Mintz ED, Nataro JP, Parashar UD (2004) Acute, infectious diarrhea among children in developing countries. Semin Pediatr Infect Dis 15(3):155–168. https://doi.org/10.1053/j.spid.2004.05.008
Rossignol JF, Kabil SM, Said M, Samir H, Younis AM (2005) Effect of nitazoxanide in persistent diarrhea and enteritis associated with Blastocystis hominis. Clin Gastroenterol Hepatol 3(10):987–991. https://doi.org/10.1016/s1542-3565(05)00427-1
Rossignol JF, Lopez-Chegne N, Julcamoro LM, Carrion ME, Bardin MC (2012) Nitazoxanide for the empiric treatment of pediatric infectious diarrhea. Trans R Soc Trop Med Hyg 106(3):167–173. https://doi.org/10.1016/j.trstmh.2011.11.007
Roxström-Lindquist K, Palm D, Reiner D, Ringqvist E, Svärd SG (2006) Giardia immunity—an update. Trends Parasitol 22(1):26–31. https://doi.org/10.1016/j.pt.2005.11.005
Salman YJ, Ali CA, Razaq AAA (2017) Fecal calprotectin among patients infected with some protozoan infections. Int J Curr Microbiol App Sci 6(6):3258–3274. https://doi.org/10.20546/ijcmas.2017.606.384
Schoepfer AM, Trummler M, Seeholzer P, Seibold-Schmid B, Seibold F (2008) Discriminating IBD from IBS: comparison of the test performance of fecal markers, blood leukocytes, CRP, and IBD antibodies. Inflamm Bowel Dis 14(1):32–39. https://doi.org/10.1002/ibd.20275
Soto-Méndez MJ, Aguilera CM, Mesa MD et al (2016) Interaction of Giardia intestinalis and systemic oxidation in preschool children in the western highlands of Guatemala. J Pediatr Gastroenterol Nutr 63(1):118–122. https://doi.org/10.1097/MPG.0000000000000891
Sulekova LF, De Angelis M, Milardi G et al (2018) Clinical and epidemiological profile of patients with Blastocystis spp and evaluation of faecal calprotectin as potential surrogate marker of pathogenicity. In: 28th ECCMID European congress of clinical microbiology and infectious diseases. Madrid, Spain, 21–24 April, P1328
Tibble JA, Sigthorsson G, Foster R, Forgacs I, Bjarnason I (2002) Use of surrogate markers of inflammation and Rome criteria to distinguish organic from nonorganic intestinal disease. Gastroenterology 123(2):450–460. https://doi.org/10.1053/gast.2002.34755
Torgerson PR, de Silva NR, Fèvre EM et al (2014) The global burden of foodborne parasitic diseases: an update. Trends Parasitol 30(1):20–26. https://doi.org/10.1016/j.pt.2013.11.002
van Rheenen PF, Van de Vijver E, Fidler V (2010) Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis. BMJ 341:c3369. https://doi.org/10.1136/bmj.c3369
Yakoob J, Jafri W, Beg MA et al (2010) Irritable bowel syndrome: is it associated with genotypes of Blastocystis hominis [published correction appears in Parasitol Res 2011 Dec;109(6):1745]. Parasitol Res 106(5):1033–1038. https://doi.org/10.1007/s00436-010-1761-x
Yakoob J, Abbas Z, Usman MW et al (2014) Cytokine changes in colonic mucosa associated with Blastocystis spp. subtypes 1 and 3 in diarrhoea-predominant irritable bowel syndrome. Parasitology 141(7):957–969. https://doi.org/10.1017/S003118201300173X
Zhang X, Qiao J, Wu X, Da R, Zhao L, Wei Z (2012) In vitro culture of blastocystis hominis in three liquid media and its usefulness in the diagnosis of blastocystosis. Int J Infect Dis 16(1):e23–e28. https://doi.org/10.1016/j.ijid.2011.09.012
Funding
No fund was obtained for the execution of the study.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
No conflict of interest to declare.
Consent to participate
Verbal consent was obtained from all participants (parents /guardians of children).
Consent for publication
All authors agree for publication.
Ethical approval
The study was approved by the Research Ethics Committee of the Medical Research Institute (MRI), Alexandria University (IORG 0008812). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Ibrahim, H.S., Salem, A.I., Ahmed, N.M.A.ER. et al. Pre-and post-treatment evaluation of intestinal inflammation in Giardia and Blastocystis infected children: a community-based study. J Parasit Dis 45, 1026–1033 (2021). https://doi.org/10.1007/s12639-021-01398-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12639-021-01398-7