Genetic Diversity of Toxoplasma Gondii in Cancer Patients

• ClinicalTrials.gov Identifier: NCT04834076
• Recruitment Status: Unknown
• First Posted: April 6, 2021
• Last Update Posted: January 13, 2022
• Sponsor: Sohag University
• Information provided by (Responsible Party): Eman Fathi Fadel Mohammed, Sohag University

Tracking Information

• First Submitted Date: April 4, 2021
• First Posted Date: April 6, 2021
• Last Update Posted Date: January 13, 2022
• Actual Study Start Date: June 1, 2020
• Actual Primary Completion Date: January 30, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 5, 2021)

• Isolation and genotyping of T. gondii from blood of Cancer patients in Sohag Governorate, Egypt using PCR and DNA sequencing of Toxoplasma gondii B1 & RE genes. [ Time Frame: up to 1 year ]
  Using PCR and DNA sequencing
• Evaluation of T. gondii infection in cancer patients using ELISA. [ Time Frame: up to 1 year ]
  IgG, IgM.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Genetic Diversity of Toxoplasma Gondii in Cancer Patients
• Official Title: Genetic Diversity of Toxoplasma Gondii in Cancer Patients

Brief Summary

I. Evaluation of T. gondii infection in cancer patients using different serological markers.

II. Studying genetic lineages infecting cancer patients in Sohag Governorate to predict clinical course and therapeutic needs using B1 and RE genes.

Detailed Description

The global cancer burden is estimated to have risen to 18.1 million new cases and 9.6 million deaths in 2018. Patients with cancer have deficient cellular immunity and are potentially susceptible to opportunistic infections including Toxoplasma gondii (T. gondii). Few reports are available about toxoplasmosis in this group of patients. In recent years, it has emerged as an important life-threatening opportunistic pathogen in immunocompromised patients.

T. gondii is a ubiquitous obligate intracellular protozoan parasite that can infect virtually any nucleated vertebrate cell. T. gondii is one of the most successful parasites worldwide, with upwards of 30% of the human population infected.

While T. gondii infection in immunocompetent individuals is usually asymptomatic, it is more detrimental in immunocompromised individuals, such as those with HIV, patients receiving organ transplants or undergoing cancer treatment. A variety of malignancies, including lymphoma, leukemia, and myeloma, can reactivate toxoplasmosis. Moreover, T. gondii is incriminated to be responsible for the progression of malignant diseases.

Screening of toxoplasmosis in cancer patients is mandatory to guard against life-threatening disseminated disease. Diagnosis rely mainly on serology. A study in 2018 was performed to assess the prevalence of anti-T. gondii antibody among cancer patients in Cairo-Egypt. Among 180 cancer patients, a total of 110 patients (61.1%) were positive for anti-T. gondii antibodies. Till now there is no screening program in Egypt for toxoplasmosis in cancer patients although recently demonstrated to be at high risk for acquiring the infection with life-threatening sequelae.

Despite the significant improvements in serological methods, there are still unresolvable limitations such as inability of these methods to confirm the presence of parasite in immunocompromised patients. To overcome these limitations, different molecular methods including conventional PCR (cn PCR), nested PCR, real-time PCR (qPCR) and also loop-mediated isothermal amplification (LAMP) techniques have been developed to detect T. gondii DNA in biological samples.

As molecular diagnosis is not depending on the immunological condition of the host, it would be ideal for cancer patients. The ability of molecular methods to detect low amounts of parasites in fluids or tissues is a key issue, as Toxoplasma can circulate at low concentrations, or inconstantly.

T. gondii has been considered a single species in the genus Toxoplasma. Early studies on the parasite strains from North America and Europe identified limited genetic diversity, which were classified into three clonal lineages I, II, and III.

Genotyping of isolates from all continents revealed a complex population structure. Recent research supports the notion that T. gondii genotype may be associated with disease severity. The outcome of toxoplasmosis is related primarily to host and parasite genetics.

The first PCR technique for T. gondii detection was established by Burg and colleagues in which the 35-repeat B1 gene of T. gondii genome was amplified. Following it, several multi-copy targeting genes including 18S rRNA-, P30-,529-bp repeat fragment or the AF146527 element have been used for the detection of T. gondii in different biological samples.

In spite of the growing data concerning T. gondii genotypes and its role in epidemiological and biological studies,very few studies have been reported in Egypt until now. It is essential to genetically define and characterize T. gondii strains isolated from cancer patients to understand the population genetic structure, population biology, and pathogenesis of this important pathogen in our locality using the highly sensitive molecular techniques.

To the best of our knowledge, this is the first study in Egypt to reveal the population structure of T. gondii in patients with cancer.

• Study Type: Observational
• Study Design: Observational Model: Case-Control; Time Perspective: Retrospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Blood samples in EDTA tubes for molecular detection of Toxoplasma gondii gene then for sequencing.

• Sampling Method: Probability Sample

Study Population

50 cancer patients referred to the Oncology Department, Faculty of medicine, Sohag University and 20 healthy controls will be recruited in the study.

Relevant demographic and clinical data will be obtained from all participants. Written consents will be obtained from each participant after clear full explanation about the procedures and their significance.

Condition

• Toxoplasma Gondii Infection
• Cancer

Intervention

• Diagnostic Test: ELISA
  ELISA is is a test that detects and measures toxoplasma IgG and IgM antibodies in blood.
• Diagnostic Test: PCR
  Polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it to a large enough amount to study in detail.
• Diagnostic Test: Sequencing
  DNA sequencing is a laboratory technique used to determine the exact sequence of bases (A, C, G, and T) in a DNA molecule. The DNA base sequence carries the information a cell needs to assemble protein and RNA molecules. DNA sequence information is important to scientists investigating the functions of genes.

Study Groups/Cohorts

• Cancer patients
  50 cancer patients referred to the Oncology Department, Faculty of medicine, Sohag University.
  Interventions:

  • Diagnostic Test: ELISA
  • Diagnostic Test: PCR
  • Diagnostic Test: Sequencing
• Healthy controls
  50 healthy controls will be recruited in the study.
  Interventions:

  • Diagnostic Test: ELISA
  • Diagnostic Test: PCR
  • Diagnostic Test: Sequencing

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: April 5, 2021): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2022
• Actual Primary Completion Date: January 30, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Hematologic cancers on treatment
• Solid Cancers on treatment

Exclusion Criteria:

• Patients with other immune compromise states eg. DM, autoimmune diseases
• Patients who are HIV positive

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Egypt

Administrative Information

• NCT Number: NCT04834076
• Other Study ID Numbers: Toxoplasma gondii genomics
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Eman Fathi Fadel Mohammed, Sohag University
• Original Responsible Party: Same as current
• Current Study Sponsor: Sohag University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Eman FF Mohammed, Ass lecturer; Sohag University

• PRS Account: Sohag University
• Verification Date: January 2022