Influence of Filarial Infections on Tuberculosis Disease and Tuberculosis Vaccination in Cameroon (MAP-TB)

Mansonella Perstans Effects on BCG Vaccine-induced Protection Against Childhood Tuberculosis (TB) as Well as TB Disease Severity and Recovery in Cameroon (MAP-TB)

Filarial nematodes modulate the host immune response to promote regulatory and T helper type 2 immune responses, which were shown to influence concomitant infections. Indeed, several studies showed that increased susceptibility and worsened disease course of HIV, tuberculosis (TB) and malaria in filarial endemic regions. Moreover, the investigators demonstrated that M. perstans infections polarize and suppress immune responses with likely consequences for concomitant infections and vaccine-induced protection. In addition, the investigators observed altered frequencies of natural killer and regulatory T and B cells in filarial and M. tuberculosis co-infected individuals and that M. perstans influences CD4+ T cell function and immune responses upon purified protein derivative antigen stimulation. Nevertheless, the consequences of manifestation of TB disease and influence on TB vaccination remains unknown. Thus, the trial aim to address two main questions with high clinical relevance: 1) Does filarial infection influence disease severity and recovery in tuberculosis patients? 2) Does filarial infection influence Bacille Calmette-Guérin (BCG)-induced protection against disease progression in vaccinated children?

Study Overview

• Status: Recruiting
• Conditions: Tuberculosis
• Intervention / Treatment: Drug: TB treatment according to national guidelines

• Study Type: Observational
• Enrollment (Anticipated): 2500

Contacts and Locations

• Study Contact: Name: Samuel Wanji, Prof. Dr.; Phone Number: +237 77 72 43 84; Email: swanji@yahoo.fr
• Study Contact Backup: Name: Manuel Ritter, Dr.; Phone Number: +4928828711453; Email: manuel.ritter@ukbonn.de

Study Locations

• Cameroon
  • Buea, Cameroon
    • Recruiting
    • University of Buea
    • Contact: Samuel Wanji; Phone Number: +237694727715; Email: samwandji@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

• TB positive individuals (older than 5 years)
• TB contacts (children 5-17 years old)

Description

Inclusion Criteria:

• Patient is older than 5 years old
• Patient have BCG scare or get the BCG vaccination at birth
• Patient had no previous treatment of, tuberculosis or with at least one of the study drugs i.e. isoniazid,rifampicin, pyraziamide, ethambutol
• Patient have no history of hypersensitivity to rifampicin, or any of the above mentioned drugs
• Patient is not on any medication likely to interact with the study medication
• Patient have no history of or current clinical signs of ascites, jaundice, partial or complete deafness, myasthenia gravis, renal dysfunction (known or suspected), diabetes mellitus, and severe immune compromise (e.g., immunosuppressive drugs after organ transplant), or have no evidence of (previous) tuberculosis, Buruli ulcer or leprosy and no terminal illness (e.g., metastasized cancer)
• Patient have no mental condition
• Patient is able to take oral medication
• Patient have no mental condition including addiction with substance abuse e.g. alcohol
• Patient is willing to give informed pre-consent, and consent
• In case the patient is below 18, the parents or legal guardians were informed and provide consent

Exclusion Criteria:

• Patient is younger than 5 years old
• Patient have no BCG scare or miss the BCG vaccination at birth
• Patient had previous treatment of, tuberculosis or with at least one of the study drugs i.e. isoniazid,rifampicin, pyraziamide, ethambutol
• Patient have a history of hypersensitivity to rifampicin, or any of the above mentioned drugs
• Patient is on any medication likely to interact with the study medication
• Patient have a history of or current clinical signs of ascites, jaundice, partial or complete deafness, myasthenia gravis, renal dysfunction (known or suspected), diabetes mellitus, and severe immune compromise (e.g., immunosuppressive drugs after organ transplant), or evidence of (previous) tuberculosis, Buruli ulcer or leprosy; or terminal illness (e.g., metastasized cancer)
• Patient have a mental condition including addiction with substance abuse e.g. alcohol likely to interfere with possibility to comply with study protocol
• Patient is unable to take oral medication or having gastrointestinal disease likely to interfere with drug absorption
• Patient have a mental condition including addiction with substance abuse e.g. alcohol likely to interfere with possibility to comply with study protocol
• Patient is not willing to give informed pre-consent, and consent or withdrawal or consent
• In case the patient is below 18, were the parents or legal guardians were not informed and did not provide consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Tuberculosis (TB) index patients; - Patients (older than 5 years) diagnosed with TB before initiation of TB treatment	Drug: TB treatment according to national guidelines; National clinics in Cameroon will initiate TB treatment according to national guidelines upon positive TB diagnosis
TB contacts; - Children (5-17 years old), who had contact with TB index patients	Drug: TB treatment according to national guidelines; National clinics in Cameroon will initiate TB treatment according to national guidelines upon positive TB diagnosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Influence of filariae infection on TB disease outcome and BCG vaccination	Does filarial infection influence tuberculosis disease severity and recovery under treatment and influence Bacille Calmette-Guérin (BCG)-induced protection against disease progression Parasitological diagnosis: Blood smear for microfilaria detection using microscopy; DNA isolation from urine, blood and stool for helminth detection using LAMP and PCR technology; Helminth egg detection in urine and stool using Kato Katz technique; Skin snip for detection of Onchocerca volvulus infection TB diagnosis: Chest radiography; Sputum smear and culture; GeneXpert; TST Test; Physical examination; Questionnaires to obtain medical, TB contact and treatment history	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers for TB severity and BCG vaccination	Decipher biomarker for TB disease severity and recovery under treatment and for prediction of BCG vaccine induced immune protection against development of TB Laboratory assessment: - CFP10/ESAT6 in vitro and TB-TAM assay from peripheral whole blood using flow cytometry technology	3 years

Collaborators and Investigators

• Sponsor: University Hospital, Bonn
• Investigators: Principal Investigator: Achim Hoerauf, Prof. Dr., UKB, IMMIP

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): October 1, 2023

Study Registration Dates

• First Submitted: September 4, 2020
• First Submitted That Met QC Criteria: September 10, 2020
• First Posted (Actual): September 14, 2020

Study Record Updates

• Last Update Posted (Actual): November 23, 2021
• Last Update Submitted That Met QC Criteria: November 22, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: tuberculosis; filariae; BCG vaccination
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis
• Other Study ID Numbers: HO2009/14-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No