Clinical trial NCT04547738: Influence of Filarial Infections on Tuberculosis Disease and Tuberculosis Vaccination in Cameroon
Official title: Mansonella Perstans Effects on BCG Vaccine-induced Protection Against Childhood Tuberculosis (TB) as Well as TB Disease Severity and Recovery in Cameroon (MAP-TB)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Tuberculosis
Keywords: filariae
tuberculosis
BCG vaccination
Lead sponsor: University Hospital, Bonn
Sponsor class: OTHER
First posted: 2020-09-14
Enrollment: 2500
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: * TB positive individuals (older than 5 years)
* TB contacts (children 5-17 years old)

Brief summary: 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?


Eligibility criteria: 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

Primary outcomes:
measure: Influence of filariae infection on TB disease outcome and BCG vaccination
timeFrame: 3 years
Secondary outcomes:
measure: Biomarkers for TB severity and BCG vaccination
timeFrame: 3 years
Other outcomes:
Locations:
city: Buea
country: Cameroon
facility: University of Buea
Study officials:
affiliation: UKB, IMMIP
name: Achim Hoerauf, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: