Preparing for Maternal GBS Vaccine Trials in Africa

NCT06833957 | Recruiting

• 1 other identifier: 101145724
• Study Type: observational
• Target: 18,100
• Locations: 4 countries
• Sites: 9

Brief Summary

Infections are one of the key causes of newborn deaths. Among them, Group B Streptococcus (GBS) is the leading cause of sepsis and bacterial meningitis in the first 90 days of life. Fortunately, GBS vaccines for pregnant women, a powerful tool for fighting infections, are currently in development. Once vaccine trials are completed, these vaccines can stop preventable newborn deaths. The PReparing for Optimal Phase III/IV maTErnal Group B StreptococCal vaccine Trials in Africa (PROTECT) project, funded by the European \& Developing Countries Clinical Trials Partnership (EDCTP) and European Commission, is supporting medical sites in Kenya, Malawi, Mozambique, and Uganda to establish uniform pregnancy and infant health data collection processes. It is also establishing surveillance of GBS in newborns to determine incidence rates and measure the burden of disease. With better reporting systems, medical sites can participate in vaccine trials and monitor vaccine safety. At the same time, the consortium is working to understand the drivers of vaccine hesitancy and to develop culturally appropriate communication tools to facilitate engagement with vaccines. The end goal is to set up a network of sites that can monitor vaccine safety for current and future vaccines.

Conditions

Invasive Bacterial Diseases (IBD); Maternal Immunization; Group B Streptococcus

Keywords

Child health; Clinical research; Clinical trials; Infectious diseases; Group B Streptococcus; vaccines; maternal immunisation; maternal health

Outcome Measures

Primary Outcomes (8)

• Pregnancy exposure registries outcome 1.1

  To establish pregnancy episode registries at sentinel site locations, at least 1 site per country.

  01.03.2026 - 28.02.2027

• Pregnancy exposure registries outcome 1.2

  To generate longitudinal cohort data on pregnancies, deliveries and infant outcomes for maternal vaccine safety assessment, specifically rates of obstetric and neonatal outcomes as defined by the GAIA project.

  01.03.2026 - 28.02.2027

• Pregnancy exposure registries outcomes 1.3

  To generate comparable essential data across Kenya, Malawi, Mozambique and Uganda on adverse pregnancy, neonatal and infant outcomes using consensus definitions for maternal vaccine safety assessment.

  01.03.2026 - 28.02.2027

• Sentinel site GBS disease surveillance outcome 2.1

  To develop and strengthen capacities for GBS disease surveillance in infants less than 90 days old at sentinel sites in four African countries, using microbiological and molecular detection methods.

  01.01.2025 - 01.09.2025

• Sentinel site GBS disease surveillance outcome 2.2

  To determine the incidence rates of early and late onset iGBS disease among infants less than 90 days old admitted across established sentinel sites (at least 1 site per country).

  01.03.2026 - 28.02.2027

• Vaccine confidence outcome 3.1

  To enhance understanding of the importance of vaccination in pregnancy.

  01.03.2025 - 28.02.2027

• Vaccine confidence outcome 3.2

  To understand contextual facilitators and barriers to maternal vaccination and willingness to participate in maternal vaccine trials in the four countries.

  01.03.2025 - 28.02.2027

• Vaccine confidence outcome 3.3

  To co-develop an educational/communication toolkit with key stakeholders to enhance understanding of the importance of maternal vaccines in pregnancy and to support engagement with maternal vaccine trials in the four countries.

  01.11.2025 - 20.08.2026

Secondary Outcomes (2)

• Sentinel site GBS disease surveillance outcome 2.3

  01.09.2025 - 28.02.2027

• Sentinel site GBS disease surveillance outcome 2.4

  01.09.2025 - 28.02.2027

Study Arms (3)

WP2: Pregnancy Episode Registries

This work package (WP2) will develop systems to determine background pregnancy and infancy outcomes, as defined by Global Alignment of Immunization Safety Assessment in Pregnancy (GAIA), in preparation for maternal vaccine clinical trials and post-implementation studies. WP2 will assess the utility of existing medical records data to accurately determine pregnancy events following immunisation and, using patient data related to atleast 4000 pregnancies in each country, to establish an easy to use pregnancy episodes registry (PER) that can be used for future Phase III/IV trials. The PER will be developed using freely available code developed under EDCTP2 so that it can be used in other African settings in the future. The WP2 group consists of pregnant women and their infants up to hospital discharge at the chosen health facilities in Uganda, Malawi, Mozambique, and Kenya.

WP3: GBS disease sentinel site surveillance

WP3 will conduct a prospective observational GBS surveillance study among infants less than 90 days old who are admitted with laboratory confirmed GBS at sentinel sites in Kenya, Uganda, Malawi and Mozambique. The WP3 study team will develop and strengthen IBD surveillance, with a focus on GBS in each site. All of the proposed sites have access to microbiological capacity that will be leveraged to monitor microbiologically confirmed neonatal sepsis burden. In doing so, WP3 will improve the nations' ability to participate in late phase clinical trials and post-licensure effectiveness studies in preparation for phase III/IV GBS maternal vaccine clinical trials and vaccine decision making. The WP3 group consists of all infants less than 90 days old admitted with GBS infection detected in blood or cerebrospinal fluid (CSF) by culture, or GBS detected in CSF by quantitative polymerase chain reaction, at the health facilities in the four countries during a period of at least 12 months.

WP4: Vaccine confidence

Many low- and middle-income countries face significant challenges regarding vaccine implementation including vaccine confidence and participation in vaccine clinical trials, especially for vaccines targeting pregnant women. Through a mixed-methods study, WP4 will assess the knowledge, attitudes and practices of pregnant women, health care providers, community members and other relevant stakeholders towards maternal vaccines, and assess the understanding and willingness to participate in maternal vaccine trials in Kenya, Malawi, Mozambique and Uganda. WP4 will also co-create a communication/education toolkit to enhance understanding of the importance of maternal vaccines and participation in maternal vaccine trials. The WP4 group therefore consists of pregnant women and health care workers at the identified health facilities at the time of fieldwork. It will also consist of stakeholders such as Ministries of Health, community leaders, religious, political, or cultural leaders.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

WP2 Pregnancy Exposure Registries study population: Pregnant women and their infants up to hospital discharge at the chosen health facilities in Uganda, Malawi, Mozambique, and Kenya. WP3 GBS surveillance study population: All infants less than 90 days old admitted with GBS infection detected in blood or CSF by culture, or GBS detected in CSF by qPCR, at referral health facilities in the four countries during a period of at least 12 months. WP4 study population: All pregnant women attending the identified health facilities at the time of fieldwork and the health care workers who provide services to these women. It will also consist of stakeholders including, but not limited to, health workers from each country's Ministry of Health, head of facilities, community leaders (community gatekeepers and influencers), older women who give support in the community, male leaders, religious, political, administrative or cultural leaders.

You may qualify if:

• All women and their infants attending for antenatal and/or delivery and postpartum services at the study sites in Uganda, Malawi, Mozambique, and Kenya.
• Infants aged less than 90 days old with laboratory-confirmed GBS infection admitted at participating health facilities in Uganda, Malawi, Mozambique, and Kenya.
• Infants whose parents or guardians provided written informed consent for their participation.
• Residents in the catchment area of participating health facilities.
• In Uganda, Kenya and Mozambique, pregnant women at any gestation period aged 18 years and above (reproductive age).
• In Malawi, pregnant women aged 16 years are eligible to be included in the study because they are considered emancipated minors.
• Pregnant women who consent to the study and give written consent.
• Stakeholders who include pregnant women, health workers, women leaders, community leaders, national stakeholders, cultural and religious leaders who are willing to take part and can give written informed consent.

You may not qualify if:

• Pregnant women who are visiting/non-resident in the research area.
• Those who may be unwell and unable to consent to take part in the study.

Sponsors & Collaborators

• Barcelona Institute for Global Health: lead
• Fundação Manhiça: collaborator
• Universiteit Antwerpen: collaborator
• LINQ Management GMBH: collaborator
• Aga Khan University: collaborator
• University of Liverpool: collaborator
• Kamuzu University of Health Sciences: collaborator
• MU-JHU CARE: collaborator
• St George's, University of London: collaborator
• University of Oxford: collaborator

Study Sites (9)

Mariakani Sub-County Hospital

Mariakani, Coast, 80108, Kenya

RECRUITING

Rabai Sub County Hospital

Rabai, Kilifi County, Kenya

RECRUITING

Queen Elizabeth Central Hospital

Blantyre, Blantyre District, Box 95, Malawi

RECRUITING

Lirangwe Health Centre

Blantyre, Blantyre District, Malawi

RECRUITING

Ndirande Health Centre

Blantyre, Blantyre, Malawi

RECRUITING

Hospital Geral De Mavalane

Maputo, Cidade de Maputo, 1100, Mozambique

RECRUITING

Manhiça District Hospital

Manhiça, Manhiça, Mozambique

RECRUITING

Kawempe National Referral Hospital

Kampala, Kampala, P. O Box 3253, Uganda

RECRUITING

Komamboga Health Centre III

Kampala, Komamboga, 4126, Uganda

RECRUITING

Related Publications (17)

• Bramugy J, Mucasse H, Massora S, Vitorino P, Aerts C, Mandomando I, Paul P, Chandna J, Seedat F, Lawn JE, Bardaji A, Bassat Q. Short- and Long-term Outcomes of Group B Streptococcus Invasive Disease in Mozambican Children: Results of a Matched Cohort and Retrospective Observational Study and Implications for Future Vaccine Introduction. Clin Infect Dis. 2022 Jan 20;74(Suppl_1):S14-S23. doi: 10.1093/cid/ciab793.

  PMID: 34725690 BACKGROUND

• Paul P, Chandna J, Procter SR, Dangor Z, Leahy S, Santhanam S, John HB, Bassat Q, Bramugy J, Bardaji A, Abubakar A, Nasambu C, Libster R, Yanotti CS, Seedat F, Horvath-Puho E, Hossain AKMT, Sadeq-Ur Rahman Q, Jit M, Newton CR, Milner K, Goncalves BP, Lawn JE; GBS long term outcomes LMIC collaborative group. Neurodevelopmental and growth outcomes after invasive Group B Streptococcus in early infancy: A multi-country matched cohort study in South Africa, Mozambique, India, Kenya, and Argentina. EClinicalMedicine. 2022 Apr 28;47:101358. doi: 10.1016/j.eclinm.2022.101358. eCollection 2022 May.

  PMID: 35747160 BACKGROUND

• Aerts C, Leahy S, Mucasse H, Lala S, Bramugy J, Tann CJ, Madhi SA, Bardaji A, Bassat Q, Dangor Z, Lawn JE, Jit M, Procter SR. Quantifying the Acute Care Costs of Neonatal Bacterial Sepsis and Meningitis in Mozambique and South Africa. Clin Infect Dis. 2022 Jan 20;74(Suppl_1):S64-S69. doi: 10.1093/cid/ciab815.

  PMID: 34725702 BACKGROUND

• Goncalves BP, Procter SR, Paul P, Chandna J, Lewin A, Seedat F, Koukounari A, Dangor Z, Leahy S, Santhanam S, John HB, Bramugy J, Bardaji A, Abubakar A, Nasambu C, Libster R, Sanchez Yanotti C, Horvath-Puho E, Sorensen HT, van de Beek D, Bijlsma MW, Gardner WM, Kassebaum N, Trotter C, Bassat Q, Madhi SA, Lambach P, Jit M, Lawn JE; GBS Danish and Dutch collaborative group for long term outcomes; GBS Low and Middle Income Countries collaborative group for long term outcomes; GBS Scientific Advisory Group, epidemiological sub-group; CHAMPS team. Group B streptococcus infection during pregnancy and infancy: estimates of regional and global burden. Lancet Glob Health. 2022 Jun;10(6):e807-e819. doi: 10.1016/S2214-109X(22)00093-6. Epub 2022 Apr 28.

  PMID: 35490693 BACKGROUND

• Absalon J, Simon R, Radley D, Giardina PC, Koury K, Jansen KU, Anderson AS. Advances towards licensure of a maternal vaccine for the prevention of invasive group B streptococcus disease in infants: a discussion of different approaches. Hum Vaccin Immunother. 2022 Dec 31;18(1):2037350. doi: 10.1080/21645515.2022.2037350. Epub 2022 Mar 3.

  PMID: 35240933 BACKGROUND

• Moon S, Bermudez J, 't Hoen E. Innovation and access to medicines for neglected populations: could a treaty address a broken pharmaceutical R&D system? PLoS Med. 2012;9(5):e1001218. doi: 10.1371/journal.pmed.1001218. Epub 2012 May 15.

  PMID: 22615544 BACKGROUND

• Rottingen JA, Chamas C, Goyal LC, Harb H, Lagrada L, Mayosi BM. Securing the public good of health research and development for developing countries. Bull World Health Organ. 2012 May 1;90(5):398-400. doi: 10.2471/BLT.12.105460. No abstract available.

  PMID: 22589577 BACKGROUND

• Philip RK, Shapiro M, Paterson P, Glismann S, Van Damme P. Is It Time for Vaccination to "Go Viral"? Pediatr Infect Dis J. 2016 Dec;35(12):1343-1349. doi: 10.1097/INF.0000000000001321.

  PMID: 27626913 BACKGROUND

• Mehta U, Clerk C, Allen E, Yore M, Sevene E, Singlovic J, Petzold M, Mangiaterra V, Elefant E, Sullivan FM, Holmes LB, Gomes M. Protocol for a drugs exposure pregnancy registry for implementation in resource-limited settings. BMC Pregnancy Childbirth. 2012 Sep 3;12:89. doi: 10.1186/1471-2393-12-89.

  PMID: 22943425 BACKGROUND

• Boytchev H. Maternal RSV vaccine: Further analysis is urged on preterm births. BMJ. 2023 May 10;381:1021. doi: 10.1136/bmj.p1021. No abstract available.

  PMID: 37164373 BACKGROUND

• Chaithongwongwatthana S, Yamasmit W, Limpongsanurak S, Lumbiganon P, Tolosa JE. Pneumococcal vaccination during pregnancy for preventing infant infection. Cochrane Database Syst Rev. 2015 Jan 23;1(1):CD004903. doi: 10.1002/14651858.CD004903.pub4.

  PMID: 25613573 BACKGROUND

• Salam RA, Das JK, Dojo Soeandy C, Lassi ZS, Bhutta ZA. Impact of Haemophilus influenzae type B (Hib) and viral influenza vaccinations in pregnancy for improving maternal, neonatal and infant health outcomes. Cochrane Database Syst Rev. 2015 Jun 9;2015(6):CD009982. doi: 10.1002/14651858.CD009982.pub2.

  PMID: 26059051 BACKGROUND

• Giles ML, Krishnaswamy S, Macartney K, Cheng A. The safety of inactivated influenza vaccines in pregnancy for birth outcomes: a systematic review. Hum Vaccin Immunother. 2019;15(3):687-699. doi: 10.1080/21645515.2018.1540807. Epub 2018 Nov 15.

  PMID: 30380986 BACKGROUND

• Ginsburg AS, Klugman KP. Vaccination to reduce antimicrobial resistance. Lancet Glob Health. 2017 Dec;5(12):e1176-e1177. doi: 10.1016/S2214-109X(17)30364-9. Epub 2017 Nov 8. No abstract available.

  PMID: 29128252 BACKGROUND

• Yusuf N, Raza AA, Chang-Blanc D, Ahmed B, Hailegebriel T, Luce RR, Tanifum P, Masresha B, Faton M, Omer MD, Farrukh S, Aung KD, Scobie HM, Tohme RA. Progress and barriers towards maternal and neonatal tetanus elimination in the remaining 12 countries: a systematic review. Lancet Glob Health. 2021 Nov;9(11):e1610-e1617. doi: 10.1016/S2214-109X(21)00338-7.

  PMID: 34678200 BACKGROUND

• Marchant A, Sadarangani M, Garand M, Dauby N, Verhasselt V, Pereira L, Bjornson G, Jones CE, Halperin SA, Edwards KM, Heath P, Openshaw PJ, Scheifele DW, Kollmann TR. Maternal immunisation: collaborating with mother nature. Lancet Infect Dis. 2017 Jul;17(7):e197-e208. doi: 10.1016/S1473-3099(17)30229-3. Epub 2017 Apr 19.

  PMID: 28433705 BACKGROUND

• Lawn JE, Bianchi-Jassir F, Russell NJ, Kohli-Lynch M, Tann CJ, Hall J, Madrid L, Baker CJ, Bartlett L, Cutland C, Gravett MG, Heath PT, Ip M, Le Doare K, Madhi SA, Rubens CE, Saha SK, Schrag S, Sobanjo-Ter Meulen A, Vekemans J, Seale AC. Group B Streptococcal Disease Worldwide for Pregnant Women, Stillbirths, and Children: Why, What, and How to Undertake Estimates? Clin Infect Dis. 2017 Nov 6;65(suppl_2):S89-S99. doi: 10.1093/cid/cix653.

  PMID: 29117323 BACKGROUND

Related Links

• PROTECT study website

Biospecimen

Retention: SAMPLES WITH DNA

Blood and cerebrospinal fluid.

MeSH Terms

Conditions

Communicable Diseases

Condition Hierarchy (Ancestors)

Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Eve Nakabembe

  MU-JHU CARE

  STUDY DIRECTOR

Central Study Contacts

Azucena Bardají

CONTACT

+34 93 2275 400; azucena.bardaji@isglobal.org

Lucy Walmsley

CONTACT

+34 93 2275 400; lucy.walmsley@isglobal.org

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Target Duration: 8 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2025
• First Posted: February 19, 2025
• Study Start: March 1, 2025
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2027
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Time Frame: Anticipated start date: 01/05/2027 No end date.
• Access Criteria: Scientists interested in the PROTECT data will be able access the IPD to view the metadata in the public research repositories and Genebank. The data collected in this project will be quantitative data generated from clinical assessments and medical records (entered onto digital clinical report forms -CRF- via the REDCap secure database); microbiological data, molecular data and whole genome sequences. Scientists interested in the PROTECT data will be able to view the metadata in the public research repositories and Genebank. Following an access request they will be able to view the associated data.

Locations

UG (2); KE (2); MO (2); MA (3)