Hematological and biochemical effects of Toxoplasma gondii, Entamoeba histolytica, and Schistosoma infection among Hepatitis C virus patients from Menoufia Province, Egypt

Hany M Ibrahim; Azza H Mohamed; Hend S Mabrook

doi:10.4103/bbrj.bbrj_69_21

ORIGINAL ARTICLE

Year : 2021 | Volume : 5 | Issue : 3 | Page : 295-301

Hematological and biochemical effects of Toxoplasma gondii, Entamoeba histolytica, and Schistosoma infection among Hepatitis C virus patients from Menoufia Province, Egypt

Hany M Ibrahim, Azza H Mohamed, Hend S Mabrook
Department of Zoology, Faculty of Science, Menoufia University, Shibin El Kom, Egypt

Date of Submission	02-May-2021
Date of Acceptance	29-Jun-2021
Date of Web Publication	7-Sep-2021

Correspondence Address:
Prof. Hany M Ibrahim
Department of Zoology, Immunology and Physiology Unit, Faculty of Science, Menoufia University, Shibin El Kom
Egypt

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/bbrj.bbrj_69_21

Abstract

Background: Hepatitis C virus (HCV) is highly distributed in Egypt. Moreover, parasitic diseases such as schistosomiasis, toxoplasmosis, or amebiasis are frequent in Egypt. Dual infections of HCV and each of these parasitic diseases are possible and associated with bad clinical consequences. The present study was done to monitor the clinical, biochemical, and hematological changes in Toxoplasma gondii, Entamoeba histolytica, and/or Schistosoma co-infection in the HCV-infected patients from Menoufia Province, Egypt. Methods: One hundred and nine blood samples, HCV monoinfected patients and co-infected with T. gondii, E. histolytica, and/or Schistosoma, were monitored and subjected to clinical chemistry and hematological examinations Results: Liver cirrhosis in patients with concomitant multiple parasites during chronic HCV infections showed a high percentage compared to HCV mono-infected patients. Moreover, significant increases in the level of alpha-fetoprotein, aspartate transaminase, prothrombin time, and the relative monocyte count were demonstrated in patients with concomitant multiple parasites during chronic HCV infections compared to HCV mono-infected patients. Changes in the levels of platelets and relative lymphocytes/neutrophils count were detected during dual or multiple infections. Conclusions: Schistosomiasis, toxoplasmosis, or amebiasis had unpropitious effects on HCV-infected patients and it is recommended to screen these parasitic diseases among HCV patients to reduce the HCV clinical outcome.

Keywords: Amebiasis, biochemical, Egypt, hematological, hepatitis C virus, schistosomiasis, toxoplasmosis

How to cite this article:
Ibrahim HM, Mohamed AH, Mabrook HS. Hematological and biochemical effects of Toxoplasma gondii, Entamoeba histolytica, and Schistosoma infection among Hepatitis C virus patients from Menoufia Province, Egypt. Biomed Biotechnol Res J 2021;5:295-301

How to cite this URL:
Ibrahim HM, Mohamed AH, Mabrook HS. Hematological and biochemical effects of Toxoplasma gondii, Entamoeba histolytica, and Schistosoma infection among Hepatitis C virus patients from Menoufia Province, Egypt. Biomed Biotechnol Res J [serial online] 2021 [cited 2023 Jun 9];5:295-301. Available from: https://www.bmbtrj.org/text.asp?2021/5/3/295/325614

Introduction

All over the world, the highest prevalence of hepatitis C virus (HCV) is reported in Egypt.^[1] In 2015, the detected HCV seroprevalence was 10% among the same age Egyptian patients.^[2] Among the Egyptian provinces, the highest prevalence of active HCV infection was detected in Menoufia province at 8%.^[3]

Moreover, many parasitic infections are prevalent in Egypt and present a threat. In particular, Schistosoma infection has been endemic in Egypt. During the first five decades of the 20^th century, about 80% of the Egyptian village's residents were suffering from schistosomiasis.^[4] Many global complications are associated with Schistosoma infection such as anemia, retard child growth, and chronic liver inflammation.^[5] The protozoan parasites such as Toxoplasma gondii and Entamoeba histolytica infection resulted in common foodborne worldwide diseases such as toxoplasmosis and amebiasis, respectively. Toxoplasmosis is associated with abortion or neonatal mortalities and life-threatening for immunodeficient and immunocompromised patients.^{[6],[7],[8],[9]} El-Sayed et al. observed the association between toxoplasmosis and chronic liver disease.^[10] In the intestine, amebiasis is accompanied by increased diarrhea, gas, abdominal pain, and fever. Through the blood, the parasite can enter another organ like the liver and cause liver abscesses. In the developing world, amebiasis causes many thousands deaths annually and its mortality is commonly rendered to an amoebic liver abscess.^[11]

In Egypt, both diseases such as toxoplasmosis and amebiasis are frequent among human beings.^{[12],[13],[14],[15],[16]} A recent study concluded that although praziquantel as chemotherapy works well through the downregulation of the intensity of Schistosoma infection in Egyptian Delta villages, re-infection seems to be continued due to difficulties to avoid contaminated water contact.^[17]

Dual infections of HCV and parasitic diseases such as schistosomiasis, toxoplasmosis, and/or amebiasis are possible and have been previously reported.^{[10],[18],[19]} HCV patients with single or multiple infections of such parasitic diseases may have developed bad clinical consequences in comparison with mono-infected HCV patients. A previous report concluded that Schistosoma co-infection elevates severity and persistence of HCV infection through the reduction of interferon-gamma (IFN-γ), interleukin (IL)-4, and IL-10 secreting HCV-specific T-cell responses.^[19] Moreover, a significant association between T. gondii positivity and higher HCV viral load was demonstrated.^[10] Therefore, the current study was done to assess the clinical chemistry and hematological changes in T. gondii, E. histolytica, and/or Schistosoma co-infection in the chronic HCV infected patients from Menoufia Province, Egypt.

Methods

Ethical statement

The present study was conducted in accordance with the Declaration of Helsinki and the Guidelines for Good Clinical Practice and approved by the Institutional Review Board, Faculty of Medicine, Menoufia University, Menoufia Province, Egypt. The purpose and procedures involved in the current study were explained and written informed consent was obtained from all participants.

Exclusion criteria

Patients with malignancy including hepatocellular carcinoma (HCC) or renal, cardiopulmonary, or autoimmune disorders or HBV-positive and pregnant women were excluded from the current study.

Detection of hepatitis C virus antibodies and RNA

HCV antibodies were determined by enzyme-linked immunoassay (ELISA) test using (Atlas Medical GmbH, Germany). Qualitative assessment of HCV-RNA by polymerase chain reaction was done using the commercial kit (GeneProof diagnostic kit, India) according to the manufacturer's instructions.

Serological detection of parasites infection

Schistosoma-specific antibodies were determined by indirect hemagglutination test using the commercial kit (Fumouze Diagnostics Co., France). T. gondii-specific antibodies (IgG and IgM) were detected using ELISA commercial kit (Pishtaz Teb Zaman Diagnostics, Iran). Finally, E. histolytica-specific antibodies (IgG) were demonstrated using ELISA commercial kit (Creative Diagnostics, NY, USA). All tests were done according to the manufacturer's instructions.

Stool examination

Stool samples were collected in a 25 ml dry, clean plastic container. Gross examination was done for color, mucus, blood, consistency, and adult parasites. Each sample was utilized to prepare slides for direct wet smear examination and formalin-ethyl acetate sedimentation concentration method according to Garcia et al. (2018).^[20]

Blood samples

Out of one hundred and eighty examined HCV-positive patient's samples, 109 blood samples were collected and examined, including HCV mono-infected patients, and co-infected with T. gondii, E. histolytica, and/or Schistosoma. The patient's samples and data collected from private medical laboratories, Menoufia province, Egypt, during the period between October 2017 and December 2018 were enrolled in this study. To evaluate the clinical, hematological, and biochemical alteration, the study population was divided into nine groups:

Group-I: 18 patients with chronic HCV mono-infection
Group-II: 3 patients with concomitant acutely infected T. gondii (IgM positive) and chronic HCV infections
Group-III: 31 patients with concomitant chronically infected T. gondii (IgG positive) and chronic HCV infections
Group-IV: 6 patients with concomitant E. histolytica (IgG positive and cyst detected) and chronic HCV infections
Group-V: 7 patients with concomitant Schistosoma (Ig positive) and chronic HCV infections
Group-VI: 6 patients with concomitant T. gondii (IgG positive) plus E. histolytica (IgG positive) and chronic HCV infections
Group-VII: 27 patients with concomitant T. gondii (IgG positive) plus Schistosoma (Ig positive) and chronic HCV infections
Group-VIII: 7 patients with concomitant E. histolytica (IgG positive) plus Schistosoma (Ig positive) and chronic HCV infections
Group-VIIII: 4 patients with concomitant T. gondii (IgG positive) plus E. histolytica (IgG positive) plus Schistosoma (Ig positive) and chronic HCV infections.

Clinical, hematological, and biochemical analysis

Complete blood count was determined using an automated hematology analyzer Dirui (BF-6500, China). Direct, total bilirubin, alanine transaminase (ALT), aspartate transaminase (AST), albumin, fasting sugar, and creatinine were run on using CHEM-7 (Erba Diagnostics Mannheim GmbH, Germany). Antinuclear antibody and alpha-fetoprotein (AFP) were determined using Human HumaReader single plus (GmbH D-65205, Germany). Thyroid-stimulating hormone (TSH) was assayed by the commercial kit (Bioactiva Diagnostica, Germany). The prothrombin time (PT) was done using the commercially available kit (Biomed Diagnostics, Germany). In patients, compensated cirrhosis was determined by Fibro-scan TM with reading values more than 12.5 kPa.

Statistical analysis

For statistical analysis, the SPSS (IBM SPSS Statistics for Windows, Armonk, NY, USA) computer program was used. Hematological, biochemical, and scan changes were evaluated using an analysis of variance test, followed by post hoc analysis of group differences that was accomplished by the least significant differences test; P < 0.05 were considered to be statistically significant.

Results

Higher percentage of liver cirrhosis in patients with concomitant Schistosoma and chronic HCV infections was detected compared to those patients with HCV mono-infection. Moreover, a high percentage of liver cirrhosis in patients with concomitant (T. gondii plus E. histolytica, T. gondii plus Schistosoma or E. histolytica plus Schistosoma) and chronic HCV infections were detected, respectively, as follows 33.3%, 96.3%, or 85.7%, when compared to those patients with HCV mono-infection. The highest percentage of liver cirrhosis 100% was recorded in patients with concomitant T. gondii plus E. histolytica plus Schistosoma and chronic HCV infections [Table 1]. Although the increase in the HCV RNA load in the patients with concomitant mono-parasitic infection ofT. gondii, E. histolytica, or Schistosoma among the HCV infected patients compared to those patients with HCV mono-infection, no significant difference (P > 0.05) was demonstrated at the level of HCV RNA load among the studied populations. Furthermore, among HCV-infected patients, multi-parasitic infections of (T. gondii plus E. histolytica), or (E. histolytica plus Schistosoma) and (T. gondii plus E. histolytica plus Schistosoma) showed a non-significant elevation in the HCV RNA load compared to those patients with HCV mono-infection. A significant elevation (P < 0.05) in the level of AFP in patients with concomitant (T. gondii plus E. histolytica or T. gondii plus Schistosoma) and chronic HCV infections was detected compared to those patients with HCV mono-infection [Table 1].

Table 1: Characteristics of cirrhosis, hepatitis C virus load, and alpha-fetoprotein data of the study population

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In [Table 2], significant elevation (P < 0.05) in PT was detected in patients with concomitant (T. gondii plus E. histolytica) among the chronic HCV infected patients were detected compared to those patients with HCV mono-infection. Moreover, a significant increase (P < 0.05) in the levels of AST was detected in patients with concomitant (T. gondii plus Schistosoma) and chronic HCV infections as compared to those patients with HCV mono-infection or those patients with concomitant (T. gondii, E. histolytica, or Schistosoma) and chronic HCV infections, while no significant differences (P > 0.05) were determined on the levels of TSH, glucose, ALT, albumin, total bilirubin, direct bilirubin, or creatinine [Table 2].

Table 2: Characteristics of biochemical data of the study population

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On the level of hematological findings, a significant increase (P < 0.05) was detected at the level of MCV in patients with concomitant Schistosoma and chronic HCV infections compared to those patients with HCV mono-infection. On the other hand, a significant decrease (P < 0.05) was detected in the level of platelet count in patients with concomitant mono-parasitic infection of T. gondii, E. histolytica, and multi-parasitic infections of (T. gondii plus E. histolytica), or (T. gondii plus Schistosoma) among the chronic HCV infected patients compared to those patients with HCV mono-infection. On the level of the relative differential leukocyte count, a significant increase (P < 0.05) was detected in the percentage of the relative lymphocyte count accompanied by a significant decrease (P < 0.05) in the relative neutrophil count in patients with concomitant E. histolytica or T. gondii plus Schistosoma and chronic HCV infections compared to those patients with HCV mono-infection. Finally, a significant increase (P < 0.05) was detected in the percentage of the relative monocyte count in patients with concomitant (T. gondii plus E. histolytica) and chronic HCV infections compared to those patients with HCV mono-infection. No significant changes were demonstrated on the levels of the other examined hematological parameters [Table 3].

Table 3: Hematological findings of different groups

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Discussion

In the present study, liver cirrhosis in patients with quadrate concomitant T. gondii, E. histolytica, Schistosoma, and HCV infections recorded 100%. Triple concomitant infection or even concomitant Schistosoma and chronic HCV infections showed a higher percentage than HCV mono-infected patients. Furthermore, without any significant change, higher HCV RNA load was demonstrated in multi-parasitic infected patients of (T. gondii, E. histolytica), or (E. histolytica, Schistosoma) and (T. gondii, E. histolytica, Schistosoma) compared to those patients with chronic HCV mono-infection. mono-infection. Patients with concomitant (T. gondii plus E. histolytica or T. gondii plus Schistosoma) and chronic HCV infections showed a significant increase in the level of AFP, a tumor-associated marker, compared to those patients with HCV mono-infection. Kamal et al. reported that concomitant Schistosoma and HCV infections have a higher incidence of HCC and cirrhosis than patients mono-infected with chronic HCV.^[21] Previous reports showed an obvious reduction in T-cell IL-4, IFN-γ, and IL-10 production and inhibition in the intrahepatic T-lymphocyte responses against HCV infection in Egyptian patients infected with HCV and Schistosoma which consequently promoted persistent HCV infection and fastened the clinical course of the viral disease.^{[19],[21],[22]} On the other side, toxoplasmosis represents a potential risk for HCV patients, where significant associations between Toxoplasma infection and liver cirrhosis or HCV viral load were demonstrated.^{[10],[23],[24]} Moreover, a previous report concluded that liver cirrhosis is a major risk factor for pyogenic liver abscesses,^[25] which also might be enhanced by E. histolytica infection. Finally, the association between AFP level and parasitic diseases such as schistosomiasis, toxoplasmosis, or amebiasis was established.^{[26],[27],[28]}

Concerning liver function, in the current study, although patients with concomitant T. gondii or E. histolytica or Schistosoma and HCV did not show any significant difference when compared to HCV mono-infected patients, multiple infections such as T. gondii plus E. histolytica or T. gondii plus Schistosoma in HCV-infected patients resulted in a significant elevation in the PT and AST, respectively. In humans and big mammals, schistosomiasis, toxoplasmosis, or amebiasis significantly increased the liver enzymes: ALT, AST, ALP, and PT in the sera compared to these parasites noninfected subjects.^{[10],[26],[29],[30],[31],[32]} Moreover, several studies detected that schistosomiasis, toxoplasmosis, or amebiasis resulted in extensive liver cells damage.^{[10],[33],[34],[35],[36]}

In the current study, lower platelet count (but within the normal range) was observed in patients with concomitant mono-parasitic infection of T. gondii, E. histolytica, or multi-parasitic infections of (T. gondii plus E. histolytica) or (T. gondii plus Schistosoma) among the chronic HCV infected patients compared to HCV mono-infected patients. The heavily infected Schistosoma mansoni Ethiopian adults recorded a low platelet count accompanied by high PT.^[37] Moreover, in thrombocytopenic mice, worm burdens of S. mansoni were significantly increased.^[38] Thrombocytopenia was detected in different case studies during T. gondii or E. histolytica infection.^[29],[39]

In the present study, patients co-infected with Schistosoma and HCV had a significantly higher level of MCV than HCV mono-infected patients. Patients co-infected with concomitant T. gondii plus E. histolytica and HCV had a significantly higher percentage of the relative monocyte count than HCV mono-infected patients. Significant elevation was demonstrated in monocyte count for the E. histolytica cyst stage in Iraqi patients when compared to its control group.^[40] Toxoplasma-positive women from Prague, Czech Republic, had increased monocyte counts as compared to control subjects.^[41]

In the present study, results from patients infected with concomitant E. histolytica or T. gondii plus Schistosoma and HCV showed a significant increase at the percentage of the relative lymphocyte count accompanied by a significant decrease in the relative neutrophil count when compared to HCV mono-infected patients. Al-Shaibani detected a similar pattern with an increase in the lymphocyte count associated with a decrease in the granulocyte count in E. histolytica cyst-infected patients from Najaf City, Iraq.^[40] During the acute infection with T. gondii, CD8 + CD57 + T-lymphocytes were expanded in a young immunocompetent patient.^[42] Moreover, a higher level of lymphocytes was demonstrated in Schistosoma haematobium-infected schoolchildren in Gabon.^[43]

Conclusions

In the current study, multiple parasitic infections represented serious risk factors for chronic HCV patients. Therefore, schistosomiasis, toxoplasmosis, and amebiasis should be considered in their follow-up. Further studies will be required to clarify the mechanisms behind these consequences.

Acknowledgments

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Elhendawy M, Abo-Ali L, Abd-Elsalam S, Hagras MM, Kabbash I, Mansour L, et al. HCV and HEV: Two players in an Egyptian village, a study of prevalence, incidence, and co-infection. Environ Sci Pollut Res Int 2020;27:33659-67.
2.	Ahmed OA, Kaisar HH, Badawi R, Hawash N, Samir H, Shabana SS, et al. Efficacy and safety of sofosbuvir-ledipasvir for treatment of a cohort of Egyptian patients with chronic hepatitis C genotype 4 infection. Infect Drug Resist 2018;11:295-8.
3.	Ministry of Health and Population [Egypt], El-Zanaty and Associates [Egypt], and ICF International. Egypt Health Issues Survey (2015). Cairo, Egypt and Rockville, Maryland, USA: Ministry of Health and Population and ICF International; 2015.
4.	Farley J. Bilharzia: A History of Imperial Tropical Medicine. UK: Cambridge University Press; 1991. p. 359.
5.	Bahgat MM. Interaction between the neglected tropical disease human schistosomiasis and HCV infection in Egypt: A puzzling relationship. J Clin Translational Hepatol 2014;2:134-41.
6.	Chintana T, Sukthana Y, Bunyakai B, Lekkla A. Toxoplasma gondii antibody in pregnant women with and without HIV infection. Southeast Asian J Trop Med Public Health 1998;29:383-6.
7.	Aspinall TV, Guy EC, Roberts KE, Joynson DH, Hyde JE, Sims PF. Molecular evidence for multiple Toxoplasma gondii infections in individual patients in England and Wales: Public health implications. Int J Parasitol 2003;33:97-103.
8.	Frenkel JK, Escajadillo A. Cyst rupture as a pathogenic mechanism of toxoplasmic encephalitis. Am J Trop Med Hyg 1987;36:517-22.
9.	Luft BJ, Remington JS. AIDS commentary. Toxoplasmic encephalitis. J Infect Dis 1988;157:1-6.
10.	El-Sayed NM, Ramadan ME, Ramadan ME. Toxoplasma gondii infection and chronic liver diseases: evidence of an association. Trop Med Infect Dis. 2016; 1(1): 7. https://doi.org/10.3390/tropicalmed1010007.
11.	Haque R, Kabir M, Noor Z, Rahman SM, Mondal D, Alam F, et al. Diagnosis of amebic liver abscess and amebic colitis by detection of Entamoeba histolytica DNA in blood, urine, and saliva by a real-time PCR assay. J Clin Microbiol 2010;48:2798-801.
12.	Stauffer W, Abd-Alla M, Ravdin JI. Prevalence and incidence of Entamoeba histolytica infection in South Africa and Egypt. Arch Med Res 2006;37:266-9.
13.	Ibrahim HM, Huang P, Salem TA, Talaat RM, Nasr MI, Xuan X, Nishikawa Y. Prevalence of Neospora caninum and Toxoplasma gondii antibodies in northern Egypt. Am J Trop Med Hyg 2009;80:263-7.
14.	El-Shqanqery HE, Ibrahim HM, Mohamed AH, El-Sharaawy AA. Seroprevalence of Toxoplasma gondii infection and associated risk factors among asymptomatic pregnant females in Egypt. J Egypt Soc Parasitol 2017;47:93-100.
15.	Ibrahim HM, Mohamed AH, El-Sharaawy AA, El-Shqanqery HE. Molecular and serological prevalence of Toxoplasma gondii in pregnant women and sheep in Egypt. Asian Pac J Trop Med 2017;10:996-1001.
16.	Abozahra R, Mokhles M, Baraka K. Prevalence and molecular differentiation of Entamoeba histolytica, Entamoeba dispar, Entamoeba moshkovskii, and Entamoeba hartmanni in Egypt. Acta Parasitol 2020;65:929-35.
17.	Elmorshedy H, Bergquist R, Fayed A, Guirguis W, Abdel-Gawwad E, Eissa S, et al. Elimination of schistosomiasis requires multifactorial diagnostics: Evidence from high- and low-prevalence areas in the Nile Delta, Egypt. Infect Dis Poverty 2020;9:31.
18.	Matsuo T, Shinzawa H, Sugahara K, Mitsuhashi H, Watanabe H, Abe T, et al. Case report: A patient who developed an amoebic liver abscess during treatment with interferon. J Gastroenterol Hepatol 1998;13:1068-71.
19.	Farid A, Al-Sherbiny M, Osman A, Mohamed N, Saad A, Shata MT, et al. Schistosoma infection inhibits cellular immune responses to core HCV peptides. Parasite Immunol 2005;27:189-96.
20.	Garcia LS, Arrowood M, Kokoskin E, Paltridge GP, Pillai DR, Procop GW, et al. Practical guidance for clinical microbiology laboratories: Laboratory diagnosis of parasites from the gastrointestinal tract. Clin Microbiol Rev 2018; 31(1): e00025-17.
21.	Kamal S, Madwar M, Bianchi L, Tawil AE, Fawzy R, Peters T, et al. Clinical, virological and histopathological features: Long-term follow-up in patients with chronic hepatitis C co-infected with S. mansoni. Liver 2000;20:281-9.
22.	El-Kady IM, Lotfy M, Badra G, El-Masry S, Waked I. Interleukin (IL)-4, IL-10, IL-18 and IFN-gamma cytokines pattern in patients with combined hepatitis C virus and Schistosoma mansoni infections. Scand J Immunol 2005;61:87-91.
23.	Ustun S, Aksoy U, Dagci H, Ersoz G. Incidence of toxoplasmosis in patients with cirrhosis. World J Gastroenterol 2004;10:452-4.
24.	El-Nahas HA, El-Tantawy NL, Farag RE, Alsalem AM. Toxoplasma gondii infection among chronic hepatitis C patients: A case-control study. Asian Pac J Trop Med 2014;7:589-93.
25.	Mølle I, Thulstrup AM, Jepsen P, Sørensen HT, Vilstrup H. Liver cirrhosis is risk factor for pyogenic liver abscesses. BMJ 2001;323:52-3.
26.	Amanjee S, Kew MC, Van Staden L. The pathogenesis of raised serum alpha-fetoprotein levels in amoebic and pyogenic hepatic abscesses. Trop Gastroenterol 1990;11:99-102.
27.	Mohammed NS, Al-Saqur IM, Al-Alassie AH. Possible role for alpha- fetoprotein in Toxoplasma gondii infection among aborted Iraqi women. J Sci 2015;5:704-9.
28.	Bout D, Carlier Y, Santoro F, Masseyeff R, Capron A. Alpha-foetoprotein in Schistosoma mansoni schistosomiasis. Trans R Soc Trop Med Hyg 1982;76:40-241.
29.	Sucak GT, Yagoci M, Karakan T, Haznedar R. Unusual presentation of amebic liver abscess with thrombocytopenia and splenomegaly. Int J Infect Dis 2001;5:53-5.
30.	Ning A, Wu X, Li H, Liang J, Gao Z, Shen J, et al. Abnormal liver function in different patients with Schistosoma japonicum. Parasitol Res 2015;114:85-90.
31.	Al-Khamesi MB, Al-Sibahi ZN, Al-Obaidy LH, Hilal ZH. Studying of kidney, liver functions and some blood ions in toxoplasmosis patients. Al-Mustansiriyah J Sci 2016;27:43-6.
32.	Bishr NM, Abdel-Rahman AA, Ashour AM, Ibrahim HM. Biochemical effects of Toxoplasma gondii and Neospora caninium infection on dairy bovine models in Menoufia Province, Egypt. Adv Animal Vet Sci 2021;9:379-86.
33.	Blais J, Garneau V, Chamberland S. Inhibition of Toxoplasma gondii protein synthesis by azithromycin. Antimicrob Agents Chemother 1993;37:1701-3.
34.	Calderaro A, Peruzzi S, Piccolo G, Gorrini C, Montecchini S, Rossi S, et al. Laboratory diagnosis of Toxoplasma gondii infection. Int J Med Sci 2009;6:135-6.
35.	Gasim GI, Bella A, Adam I. Schistosomiasis, hepatitis B and hepatitis C co-infection. Virol J 2015;12:19.
36.	Nowak P, Mastalska K, Loster J. Entamoeba histolytica-Pathogenic protozoan of the large intestine in humans. J Clin Microbiol Biochem Technol 2015;1:010-7.
37.	Eyayu T, Zeleke AJ, Seyoum M, Worku L. Basic coagulation profiles and platelet count among Schistosoma mansoni-infected adults attending Sanja Primary Hospital, Northwest Ethiopia. Res Rep Trop Med 2020;11:27-36.
38.	Stanley RG, Ngaiza JR, Wambayi E, Lewis J, Doenhoff MJ. Platelets as an innate defense mechanism against Schistosoma mansoni infections in mice. Parasite Immunol 2003;25:467-73.
39.	Deutsch M, Nezi V, Kountouras D, Belegrati M, Kalmantis T, Dourakis SP. Immune-mediated thrombocytopenic purpura associated with Toxoplasma gondii infection in an immunocompetent patient. Hematol J 2004;5:538-9.
40.	Al-Shaibani SW. Infection with Entamoeba histolytica and its effect on some blood parameters in Najaf City. J Physics ISCPS Conf Ser 1660 2020; 1660:012008. [doi: 10.1088/1742-6596/1660/1/012008].
41.	Flegr J, Stříž I. Potential immunomodulatory effects of latent toxoplasmosis in humans. BMC Infect Dis 2011;11:274.
42.	García-Muñoz R, Rodríguez-Otero P, Galar A, Merino J, Beunza JJ, Páramo JA, et al. Expansion of CD8+CD57+T cells in an immunocompetent patient with acute toxoplasmosis. Adv Hematol 2009;2009:173439.
43.	Dejon-Agobé JC, Adegnika AA, Grobusch MP. Haematological changes in Schistosoma haematobium infections in school children in Gabon. Infection 2021;49(4):645-651. [doi: 10.1007/s15010-020-01575-5].