IVI and Madagascar

 

Official Relations

 

In 2018, H.E. Prof. Yoёl Rantomalala, then Minister for Public Health of the Republic of Madagascar, submitted a letter to the IVI Board of Trustees (BOT) requesting its approval of Madagascar’s accession as an IVI member state. The IVI BOT approved Madagascar’s accession in December 2018. The government of Madagascar has still not deposited an instrument of accession to the IVI Establishment Agreement with the United Nations. 

 

Ongoing Collaboration

 

Madagascar Institute for Vaccine Research

On December 2021, IVI and the University of Antananarivo opened the Madagascar Institute for Vaccine Research, also known as the “the University of Antananarivo – International Vaccine Institute Collaborating Center” with a ceremony held at the University of Antananarivo.

 

The Madagascar Institute for Vaccine Research is housed in a new facility constructed on the University of Antananarivo campus using overhead cost funding from ongoing and upcoming projects with IVI. This newly constructed Collaborating Center will bolster the University with additional educational capacity and help Madagascar establish a center of excellence for vaccine research capable of conducting vaccine clinical trials.

 

Implementing a Health and Demographic Surveillance System (HDSS)

HDSS seeks to collect accurate longitudinal demographic, socio-economic, health related data and geolocation information from the population living in the surveillance catchment area in D.R. Congo and Madagascar. HDSS runs from 2022 through 2026 with funding from the IVI European Regional Office, in collaboration with the Heidelberg Institute of Global Health, The Hong Kong Jockey Club Global Health Institute, the Ghana FDA, and the Madagascar Institute for Vaccine Research. 

 

Implementing an HDSS will facilitate a better understanding of the basic demographic and health characteristics underlying the population within the study area. It will provide reliable up-to-date denominators calculating vital rates and analyses requiring ‘at risk’ populations, demographically characterized sampling frame for epidemiological studies. HDSS will also serve as a real platform for conducting surveys, demonstration projects, implementing and evaluating interventions, carrying out effectiveness studies and investigational trials with potential public health value. 

 

Expanding COVID-19 Vaccine Access and Delivery in Africa (ECOVA) 

ECOVA-01 is a Phase 3 randomized, observer-blind, controlled trial to assess the efficacy, immunogenicity, and safety of BBIBP-CorV vaccine against SARS-CoV-2 infection.

 

This was the first COVID-19 vaccine clinical trial conducted in Africa and significantly contributed to building capacity for the subsequent Vaccine Against Schistosomiasis for Africa (VASA) project.

 

ECOVA-02 is a phase 2, observer-blind, randomized study to assess the safety, tolerability and immunogenicity of heterologous prime-boost COVID-19 vaccines regimens in healthy adults aged 18 to 65 years. ECOVA-02 is a mix and match study using the Sinopharm and Johnson & Johnson vaccines. 

 

Data analysis on clinical vaccine effectiveness has been completed, and a manuscript summarizing results has been submitted. The study’s closeout and stakeholder engagement are planned for 2025.

 

ECOVA 01 and 02 are conducted in cooperation with INS, with funding from the Coalition for Epidemic Preparedness Innovations (CEPI).

 

Surveillance for Typhoid Conjugate Vaccine Impact Assessment in Africa (STIA)

Since SETA Plus ended in June 2023, typhoid fever and iNTS surveillance have continued through the STIA program, alongside the THECA project. STIA operates facility-based surveillance sites in Burkina Faso, DRC, Ghana, Madagascar, and Nigeria, running until the end of 2025. It collects data from patients with fever or intestinal perforation to assess the incidence, severity, and antimicrobial resistance of Salmonella Typhi and iNTS, and to help countries track disease trends before and after TCV introduction. Regional typhoid and iNTS meetings in Cape Town (Dec 2022) and Kinshasa (Dec 2024) have strengthened policy development and collaboration across the continent.

 

The objectives are to: (1) generate data on typhoid and iNTS disease burden, (2) detect changes after TCV introduction, (3) monitor antimicrobial resistance, and (4) build laboratory and surveillance capacity.

 

Typhoid Conjugate Vaccine Introduction in Madagascar (TyMA)

The Typhoid Conjugate Vaccine Introduction in Madagascar (TyMA) project aims to curb the spread of typhoid fever in the country by vaccinating at-risk groups and supporting the development of a national typhoid fever control plan. The vaccine effectiveness study, which utilizes the TYPHIBEV® typhoid conjugate vaccine, includes a geographic information system-supported census, vaccination, and surveillance. 

 

As of November 2024, more than 36,500 people have been vaccinated with the typhoid conjugate vaccine, including 33,000 children. Both passive and active surveillance activities are underway, identifying typhoid-positive cases among fever patients and conducting monthly household visits to improve fever detection and better estimate the true burden of Salmonella Typhi. Among the project’s funders are: European and Developing Countries Clinical Trials Partnership and the Government of Sweden.

 

COVID-19 Research in African Settings (COVIA)

In response to the disproportionate lack of disease burden data in low- and middle- income countries, COVIA aims to support local institutions in Madagascar and Burkina Faso to detect COVID-19 cases by implementing health care facility-based disease surveillance, vaccine hesitancy surveys, and the study of febrile samples collected in the typhoid programs. In Madagascar, COVIA is operating in health clinics across three rural districts of Antananarivo. COVIA is supported by funding from Sweden’s Sida.

 

Vaccine against Schistosomiasis for Africa (VASA)

With funding from the EU Horizons 2020, IVI launched VASA in 2019 to conduct a Phase I clinical study of the SchistoShield® anti-schistosomiasis vaccine in Madagascar. This project includes disease surveillance and cost-effectiveness studies, the formation of a global consortium to advance schistosomiasis vaccine research, and an Integrated Product Development Plan (IPDP) for development of the vaccine backed by the Gates Foundation. In addition, VASA contributes towards a human challenge model for the vaccine which was developed in partnership with the University of Leiden.

 

Previous Collaboration

 

Schistosomiasis in Madagascar (SOMA)

In 2019 IVI established SOMA, a program which aimed to diminish the burden of schistosomiasis infections in at-risk populations in Madagascar. One component of this program included mass administration campaigns of the anti-parasite drug praziquantel (PZQ) targeting at-risk individuals. In addition, SOMA focused on water, sanitation and hygiene (WASH) education and training programs, and helped to create new water and sanitation infrastructure in Madagascar before the project concluded in 2020.

 

International Vaccinology Course

From 2012-2018, six individuals from Madagascar participated in IVI’s International Vaccinology Course.

 

Effect of a Novel Typhoid Conjugate vaccine in Africa (THECA)

The THECA program runs in parallel to the SETA and SETA Plus programs, conducting effectiveness trials and vaccination campaigns using a recently licensed typhoid conjugate vaccine (Typbar-TCV). Health economics studies are also assessing the feasibility and cost-effectiveness of TCV when administered through a mass vaccination campaigns. In Madagascar, THECA is supporting the introduction of TCV in the country. THECA is support by funding from the Bill and Melinda Gates Foundation and the EU EDCTP.

 

Severe Typhoid in Africa (SETA) Plus and COVID-19

As a follow-up to SETA (see below), the Bill and Melinda Gates Foundation granted IVI additional funding to launch SETA Plus in 2020, which extended typhoid surveillance in Madagascar.

 

With additional funding from the Cambridge-Africa ALBORADA Fund and Sida, SETA Plus expanded its diagnostics and implemented safety training and surveillance platforms to track the spread of COVID-19 in Madagascar.

 

Severe Typhoid in Africa (SETA)

The Severe Typhoid Fever in Africa (SETA) program, a multicountry surveillance study, aimed to understand the burden of severe typohid fever and the associated case fatalities, clinical characteristics, and potential host risk factors that may be related to the disease severity. The SETA program also aimed to investigate the host immune response and bacterial shedding patterns associated with invasive salmonellosis.

 

SETA conducted prospective healthcare facility–based surveillance with active screening of enteric fever and clinically suspected severe typhoid fever with complications was performed using a standardized protocol across the study sites in Burkina Faso, the Democratic Republic of Congo (DRC), Ethiopia, Ghana, Madagascar, and Nigeria.

 

The data generated by SETA will be essential in developing adequate immunization strategies and typhoid and iNTS disease control and prevention policies. The SETA study results will have a direct impact, particularly in countries eligible for support from Gavi, the Vaccine Alliance, on potential uptake of TCV in the next 10 years.

 

Typhoid Surveillance in sub-Saharan Africa Program (TSAP)

From 2010 to 2014, IVI’s The Typhoid Fever Surveillance in Africa Program (TSAP) obtained comparable incidence data on typhoid fever and invasive nontyphoidal Salmonella (iNTS) disease in sub-Saharan Africa through standardized surveillance in ten countries (Burkina Faso, Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar, Senegal, South Africa, Sudan, and Tanzania).

 

With initial funding from the Bill and Melinda Gates Foundation in 2010, a field site was established in Burkina Faso to conduct surveillance on the invasive Salmonella infections largely impacting children and rural populations. In 2013, data analyses from this program showed a high incidence of typhoid fever burden in Burkina Faso, following which IVI obtained additional funding from the Else Kroner-Fresenius-Stiftung of Germany to carry out capacity-building activities in the country. In 2013, data analyses from this program showed a high incidence of typhoid fever burden in Madagascar, following which IVI obtained additional funding from the Else Kroner-Fresenius-Stiftung of Germany to carry out capacity-building activities in the country.

 

Each TSAP site conducted passive surveillance for bloodstream infections among febrile patients to isolate and identify aerobic bacteria from the patients’ blood. Healthcare utilization surveys were conducted to adjust population denominators in incidence calculations for differing healthcare utilization patterns and improve comparability of incidence rates across sites. The results of TSAP indicated that enteric fever caused by Salmonella Typhi and non-typhoidal Salmonella are significant problems in Africa and that the prevalence of multi-drug resistance may limit appropriate treatment options.

 

Along with its new disease burden discoveries, TSAP and its collaborators strengthened local surveillance capacities at multiple sites across sub-Saharan Africa, creating a system that has improved bacterial disease diagnostics, disease surveillance, reporting, and analysis systems in the region.