Dried Blood Spot Test to Assess TB in Pregnancy

NCT04871230 | Completed

• 2 other identifiers: 2021-01TTS-2008-25933
• Study Type: observational
• Target: 1,424
• Locations: 1 country
• Sites: 12

Brief Summary

Despite being a key contributor to maternal mortality in high-burden regions, TB in pregnancy is a hugely neglected area of global public health. During pregnancy, the symptoms of TB are often overlooked and undiagnosed because they are vague, non-specific, and can be very similar to common complaints during pregnancy. Women with TB in pregnancy are at an increased risk of anemia and perinatal death. The DROP-TB project aims to expand the tuberculosis (TB) detection testing in pregnancy by creating a system where blood samples are collected from women at their local healthcare clinics instead of/or at national-level TB diagnostic centres where visits can require substantial travel and cost. Blood samples collected in specific RNA stabilizing tubes and on specific storing paper filters are collected from pregnant women with presumptive TB and transported to a central TB testing facility and analyzed by real-time polymerase chain reaction (qPCR). The DROP-TB method measures the mRNA expressions known to be markers of TB infection and disease. Based on veinous blood sampling, those signatures have showed high sensitivity (93%) and specificity (97%), can differentiate between active and latent infection, and performs well in the presence of other infections such as HIV. The DROP-TB program was specifically designed to increase the coverage of TB testing in pregnancy to improve health outcomes for women and their unborn children. The evidence generated from this program will demonstrate the feasibility of this program in providing TB diagnosis to women in rural and remote regions of LMIC with the example of Madagascar. Evidence will be presented to policy makers as a case to support the national scale up of the program in LMICs.

Conditions

Tuberculosis

Keywords

Pregnant women; Tuberculosis; Diagnostic; Genes signature; Dried Blood Spot

Outcome Measures

Primary Outcomes (2)

• diagnostic feature of test 3 G q-PCR capillary blood compared to gold stantard test

  The diagnostic performance are estimated by the sensitivity and specificity of the 3G q-PCR test with capillary blood compared to the sputum test as gold standard

  at inclusion

• diagnostic feature of test 3 G q-PCR capillary blood compared to 3 G q-PCR veinous blood

  The diagnostic performance are estimated by the sensitivity and specificity of the 3G q-PCR test with capillary blood compared to the 3 G q-PCR veinous blood as a reference test

  at inclusion

Study Arms (2)

Pregnant women suspected TB

This group enrolled as cases

Diagnostic Test: 3G DBS; Diagnostic Test: Sputum Test; Diagnostic Test: 3G Veinous Blood

Pregnant women without signs suspected TB

This group enrolled as controls

Diagnostic Test: 3G DBS; Diagnostic Test: 3G Veinous Blood

Interventions

3G DBS DIAGNOSTIC_TEST

Collection of capillary blood samples for the 3G q-PCR test

Also known as: 3G qPCR test with Dried Blot Spot Samples

Pregnant women suspected TB; Pregnant women without signs suspected TB

Sputum Test DIAGNOSTIC_TEST

Collection of sputum for test culture, microscopy, GeneXpert

Also known as: Culture sputum, GeneXpert Sputum, Microscopy Sputum

Pregnant women suspected TB

3G Veinous Blood DIAGNOSTIC_TEST

Collection liquid veinous blood for the 3G q-PCR test

Pregnant women suspected TB; Pregnant women without signs suspected TB

Eligibility Criteria

• Age: 15 Years+
• Gender Eligibility Details: Pregnant women
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All pregnant women addressed to 101 TB diagnostic and treatment centers of Madagascar

You may qualify if:

• Group cases:
• pregnant women aged over 15 adressed to TB diagnostic and treatment centers for a bacteriological diagnosis of pulmonary TB
• Or with one or more symptoms of presumptive TB: cough, fatigue, weight loss, fever, chills, night sweats, shortness of breath, loss of appetite
• agreed to participate in the study with full knowledge of the facts and signed an informed consent
• Group control:
• pregnant women over 15 years referred to a prenatal health center,
• without known or clinically observed pathology associated with pregnancy
• agreed to participate in the study with full knowledge of the facts and signed an informed consent

You may not qualify if:

• Group cases :
• Patients undergoing TB treatment for more than 2 weeks
• Treatments with immunosuppressive drugs (≥ 14 consecutive days);
• Progressive disease which does not allow venous blood sampling and venous capillary sampling;
• All other clinical manifestations deemed incompatible for the study
• Group Control :
• No clinical signs of TB, no history of previous TB
• No other known or clinically observed pathologies

Sponsors & Collaborators

• Institut Pasteur de Madagascar: lead
• National Tuberculosis Program, Madagascar: collaborator
• Analakely Hospital University Care and Public Health, Madagascar: collaborator
• Virginia-Maryland College Veterinary Medecine, Blacksburg: collaborator
• Johns Hopkins Bloomberg School of Public Health: collaborator

Study Sites (12)

CHRR Ambositra, CDT Ivato

Ambositra, Amoron'i Mania Region, Madagascar

Location

CSBII Ivato, AMIT Behoririka, OSTIE Behoririka, CSB II Tanjombato, CSB II Analamahitsy

Antananarivo, Analamanga Region, 101, Madagascar

Location

CSB II Isotry Central, Dispensaire SALFA 67 ha, Centre Hospitalier d'Ambohidroa

Antananarivo, Analamanga Region, Madagascar

Location

CSBII Ambohimanarina, CSB II Anosipatrana, CSB II Ambohipo, CHRD Itaosy

Antananarivo, Analamanga Region, Madagascar

Location

Dispensaire SALFA Ambohibao, Centre Hospitalier de Soavinandriana, Dispensaire ECAR Anatihazo Isotry,

Antananarivo, Analamanga Region, Madagascar

Location

Service de Pneumo-phtisio CHU Befelatanana, CHU de Soins et Santé Publique Analakely (CHUSSPA)

Antananarivo, Analamanga Region, Madagascar

Location

CHU Fenoarivo

Fenoarivo, Analamanga Region, Madagascar

Location

DAT Toliara, SALFA Betela Toliara, Service Pneumo du CHU Toliara, Clinique Saint Luc

Toliara, Atsimo-Andrefana Region, Madagascar

Location

DAT Toamasina, CHU PPH Toamasina, SALFA Toamasina, CSBII Foulpointe

Toamasina, Atsinanana Region, Madagascar

Location

DAT Mahabibo, SALFA Antanimalandy, Service de Pneumologie CHU Androva

Mahajanga, Boeny Region, Madagascar

Location

Service Pneumo du CHU Fianarantsoa, SALFA Ivory Atsimo, CHRD1 Ambohimahasoa, CHRD1 Ambalavao

Fianarantsoa, Upper Matsiatra, Madagascar

Location

CHRR Antsirabe, SALFA Andranomadio, CSB II Mandoto, CSB II Ambohibary , CSB II Ambohibary

Antsirabe, Vakinankaratra Region, Madagascar

Location

Related Publications (6)

• Sweeney TE, Braviak L, Tato CM, Khatri P. Genome-wide expression for diagnosis of pulmonary tuberculosis: a multicohort analysis. Lancet Respir Med. 2016 Mar;4(3):213-24. doi: 10.1016/S2213-2600(16)00048-5. Epub 2016 Feb 20.

  PMID: 26907218 BACKGROUND

• Sharma A, Jaiswal S, Shukla M, Lal J. Dried blood spots: concepts, present status, and future perspectives in bioanalysis. Drug Test Anal. 2014 May;6(5):399-414. doi: 10.1002/dta.1646. Epub 2014 Apr 1.

  PMID: 24692095 BACKGROUND

• McAllister G, Shepherd S, Templeton K, Aitken C, Gunson R. Long term stability of HBsAg, anti-HBc and anti-HCV in dried blood spot samples and eluates. J Clin Virol. 2015 Oct;71:10-7. doi: 10.1016/j.jcv.2015.07.303. Epub 2015 Jul 29.

  PMID: 26370308 BACKGROUND

• Rakotosamimanana N, Raharimanga V, Andriamandimby SF, Soares JL, Doherty TM, Ratsitorahina M, Ramarokoto H, Zumla A, Huggett J, Rook G, Richard V, Gicquel B, Rasolofo-Razanamparany V; VACSEL/VACSIS Study Group. Variation in gamma interferon responses to different infecting strains of Mycobacterium tuberculosis in acid-fast bacillus smear-positive patients and household contacts in Antananarivo, Madagascar. Clin Vaccine Immunol. 2010 Jul;17(7):1094-103. doi: 10.1128/CVI.00049-10. Epub 2010 May 12.

  PMID: 20463103 RESULT

• Ostler MW, Porter JH, Buxton OM. Dried blood spot collection of health biomarkers to maximize participation in population studies. J Vis Exp. 2014 Jan 28;(83):e50973. doi: 10.3791/50973.

  PMID: 24513728 RESULT

• Gruner N, Stambouli O, Ross RS. Dried blood spots--preparing and processing for use in immunoassays and in molecular techniques. J Vis Exp. 2015 Mar 13;(97):52619. doi: 10.3791/52619.

  PMID: 25867233 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

The novel test is based on measurements of relative amounts of mRNA expression associated with 3 target genes identified through a genome-wide multicohort analysis using genetic sequencing data from confirmed pulmonary TB patients. The 3-gene mRNA-based q-PCR test (3G q-PCR) is able to detect infection in 93% of patients, can differentiate between active pulmonary disease and latent infection with good sensitivity (i.e. 88%)

MeSH Terms

Conditions

Tuberculosis; Disease

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Niaina RAKOTOSAMIMANANA, PhD

  Institut Pasteur Madagascar

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2021
• First Posted: May 4, 2021
• Study Start: October 27, 2021
• Primary Completion: September 30, 2022
• Study Completion: September 30, 2022
• Last Updated: September 28, 2023

Record last verified: 2023-09

Locations

MA (12)