Sponsored symposia (19 October)

On Tuesday 19 October, sponsored symposia were organised by Merck, Medicines for Malaria Venture (MMV), European Global Health Research Institutes Network (EGHRIN) and Instituto de Salud Carlos III (ISCIII).

By Paul Chinnock

Merck | Female genital schistosomiasis (FGS) – a major challenge for women’s health in sub-Saharan Africa

Kindly sponsored by Gold level sponsor Merck – within the track Advancing biomedical interventions towards improved and equitable health – there was a session on ‘Female genital schistosomiasis (FGS) – a major challenge for women’s health in sub-Saharan Africa

The Chair, Jutta Reinhard-Rupp who leads Merck’s Global Health Institute, said that FGS is now recognised as a major challenge for women’s health in sub-Saharan Africa. To tackle this major neglected tropical disease (NTD) and major gynaecological disease we will need policy changes, diagnostic tools and treatment. She introduced each of the three contributors to the session.

FGS Accelerated Scale-up Together (FAST): The FAST Programme in Ghana and Madagascar

Presenter Julie Jacobsen of Bridges to Development (United States) stressed that FGS is not a new problem. Schistosoma parasites affect the genital tract as well as the urinary tract. To act against it, we must collaborate with those who work in sexual and reproductive health programmes. FAST is not trying to create new interventions; it aims to use existing tools but seeks to combine them in a single holistic approach. These tools are:

  • Diagnosis and treatment through integrated health services
  • Training to recognise, treat and record FGS within the health system (it is not currently included within most medical training)
  • Ensuring the community is aware of its risk and impact
  • Annual mass administration of praziquantel, which is safe and already in widespread use in Africa, donated by Merck.

The FAST Package is supported by Grand Challenges Canada, with matching support from other partners. This programme in Ghana and Madagascar started in March 2020 and is set to run till March 2022. Strong national commitment will be required from the NTD, sexual health and HIV programmes to integrate FGS diagnosis and treatment within the health system. In each country there are two focus districts where intensified activities will take place.

The programme has been held back by the pandemic but progress in training has been made. To establish training competencies, a virtual workshop was held in four sessions held over three weeks with 65 participants from 24 countries (including 14 endemic countries) and this allowed a curriculum to be developed. After this, an online interactive competency training course was established. Interest level was high (1527 applied) and exceeded the number that could be accommodated; 318 attended and 198 completed (91 took the course in English, 107 in French). A diverse range of health professionals attended. Following their attendance, 73% said they felt more confident to diagnose and treat FGS. Attendees said they would find ways of creating locally appropriate action plans. The FAST team were impressed with what they were able to achieve online, utilising the support of the Geneva Learning Foundation. However, connectivity is still an issue in some areas and more on-the-ground support will be needed. More info on www.fastpackage.org.

Concerted action on FGS in Cameroon: Integrating precision mapping of urogenital schistosomiasis with rapid assessment of FGS for better community management of gynaecological diseases

Sandrine Nyotue of the Centre International de Recherches, d’Enseignements et de Soins (CIRES, Cameroon) gave this presentation. She noted that in sub-Saharan Africa, many diseases (communicable and non-communicable) have a disproportionately high impact on women. This is particularly the case for NTDs such as FGS. Globally, 93% of urogenital schistosomiasis is in sub-Saharan Africa, with up to 40 million women suffering from the condition, which also increases risks of cervical cancer and HIV infection. There is also a social impact.

This study aimed to take stock of the situation in two areas of high endemicity for schistosomiasis in Cameroon. The objectives were to assess the feasibility and acceptability by health workers for testing and treatment, for the use of telemedicine to provide them with remote support, and the use of telemedicine for diagnosis. The work was carried out within the HIV service. In the study women aged 13-50 were given a colposcopic examination and given praziquantel if found to have FGS. Over 600 women were made aware of the problem, of whom 40% chose to participate further. 48% of these were found to be FGS positive. 40% were also found to be HPV positive. Cervical cancer screening was also carried out. Lessons have been learned and several difficulties have now been defined but the study has provided valuable information on the FGS situation.

New dosage of praziquantel to treat FGS: first results from the PoC/Phase II clinical trial in Madagascar

Presenter Bodo Sahondra Randrianasolo, of the Association K’OLO VANONA (Madagascar), said that FGS prevalence in the country had been estimated to be in the range 15-75% and proceeded to describe the clinical features of FGS.

The objectives of the study she presented were to assess the efficacy of a new dosage of praziquantel, and to assess the degree of inflammation of the cervix before and after treatment (using immunological markers). She described the two study sites. The study was a non-blinded randomised controlled trial. Participants were women aged 15-35 who had been diagnosed with FGS. 381 women were screened but only 116 met the inclusion criteria. Details on methods were provided. Half the participants received a single 40mg/kg dose and half got five doses. There were significant declines in the CLS marker in both groups and a disappearance of lesions in many cases. The percentage with urogenital complaints decreased significantly in both groups. There was no significant difference in treatment effectiveness between the groups. Adverse effects were also similar in both groups. While this is a small study, it supports the view that single-dose praziquantel can be an effective treatment for FGS.

MMV | Main post-approval and real-life studies conducted and ongoing in parallel with the launch and scale-up of Pyramax in Africa

This symposium was kindly sponsored by the Medicines for Malaria Venture (MMV) chaired by Isabelle Borghini of MMV and co-chaired by Kassoum Kayentao (University of Bamako).

Efficacy and safety results from the post-registration WANECAM 1 and CANTAM studies

Stephan Duparc (Chief Medical Officer at MMV) presented data on the development of pyronaridine-artesunate (Pyramax) and from two post-registration studies. A robust package of clinical trials supports the efficacy of Pyramax. Over 12,700 children (including 2,600 under-fives) have received the drug in Phase I-III trials. There have also been trials in adults. There have been 30 sites in 21 malaria-endemic countries in Asia and Africa. Cure rates have been in the range 97-99% and non-inferiority to artemether-lumefantrine has been demonstrated. Successful results have also been achieved against Plasmodium vivax malaria. A review of reported liver test abnormalities concluded that there was a very low risk of progressive liver injury. This led to a European Medicines Agency (EMA) decision that Pyramax should be registered for use only in areas of low malaria transmission with evidence of artemisinin resistance, with further restrictions on its use also required (including a requirement that liver function tests should always be performed before and after treatment).

Following this decision, a Phase IIIb/IV trial was conducted (funded by EDCTP) involving the West African Network for Clinical Trials of Antimalarial Drugs (WANECAM) to assess safety and efficacy in children and adults over a two-year period. In this study there was no significant difference in efficacy between Pyramax and the three other regimens with which it was compared. (The longer half-life of Pyramax may have some advantage for treatment efficacy but might also increase the likelihood of the development of resistance.) Liver function changes were minor, returned to normal quite quickly, and were no different from the changes seen with the other regimens. Cardiac changes were minor and fewer than with the other regimens.

Based on the WANECAM study data, EMA lifted the restrictions it imposed on Pyramax use. But EMA still had some concerns and required a further real-world study to be done primarily to study safety in patients who already had liver function tests abnormality. There were sites in five countries, where health workers were trained to recognise specific hepatic events. Again, efficacy rates were high. (Results were published in PLOS Medicine this June.) No hepatic events were reported in the study. Dr Duparc said that this is very reassuring, and there is no need to test patients for liver function abnormalities before or after treatment. The studies therefore support the wider use of Pyramax as first or second-line therapy for the treatment of acute, uncomplicated malaria in endemic areas.

Efficacy and safety of 4 ACTs (pyronaridineartesunate, artemether-lumefantrine, artesunate-amodiaquine and dihydroartemisinin-piperaquine) for the treatment of falciparum malaria in African pregnant women (the PYRAPREG study)

Kassoum Kayentao of the Malaria Research Training Centre, University of Bamako, Mali described the study. He reminded us that malaria in pregnancy is an overwhelming public health problem in Africa. Currently artemether-lumefantrine (AL) and dihydrartemisin-piperaquine (DP) are the most widely used treatments for malaria in pregnancy and for intermittent preventive treatment in pregnancy (IPTp). The long post-therapeutic effect of DP makes it more suitable for use in IPTp but would limit it use in curative treatment in pregnancy. There is a need for alternative therapeutic options and Pyramax could have the potential to fulfill that role.

Nine institutions in three European and five African countries are involved in study, which seeks to compare the efficacy of Pyramax to AL or DP, to describe the safety profile of all three regimens, and to explore the pharmacokinetics of pyronaridine in HIV-infected and uninfected women. Study recruitment began in January 2021 and is still under way. Dr Kayentao reported data up to August this year. So far, 473 potential participants have been screened and 219 enrolled. Recruitment will continue till the end of the year. Five suspected adverse drug reactions have been reported to date but none of them involving Pyramax.

Comparative efficacy and safety of pyronaridine-artesunate versus artemether-lumefantrine in the treatment of acute, uncomplicated malaria among children in south-west Nigeria

This study was presented by Catherine Falade of Pharmacology and Therapeutics, University of Ibadan, Nigeria. In Nigeria, which has the highest national malaria burden, the drugs of choice for malaria are AL and artesunate-amodiaquine (ASAQ).

Comparison of AL and Pyramax efficacy in acute, uncomplicated malaria was the main objective. Other objectives were to compare parasite clearance time and other haematological indicators of treatment success. There were two study sites, both in southwest Nigeria. Most such studies have been limited to children under five years, but the epidemiology of malaria in Africa is changing with older children more likely than previously to be infected. This study therefore included children of 3-144 months. 87 children received AL and 85 Pyramax. There was a very extensive investigation of adverse events, particularly serious adverse events.

Adequate clinical and parasitological response was significantly higher with Pyramax (92% v 72%) but cure rate was the same in both groups, as was parasite and fever clearance. However, haematological recovery was significantly better with Pyramax. Cure rate in children under six months was also higher with Pyramax. There were more instances of treatment failure with AL, including two failures within the first 14 days. (None were seen in that period with Pyramax.)

Adverse effects were mild in both groups, with no significant changes in liver function tests. In conclusion, both treatments were safe and efficacious but there were more issues with treatment failure with AL.

EGHRIN | Equal Voices: Addressing Inequities in Global Health Research Participation

Equity in agenda definition in global health research between Europe and partner countries – a view from the European Commission

Barbara Kerstiëns is head of the unit responsible for combatting disease in the PEOPLE Directorate of the Directorate-General for Research and Innovation at the European Commission. She noted that, with global support, progress has been made against poverty-related diseases but the burden remains high and the pandemic has increased inequalities in every domain, including access to medicines and the gap between men and women. She referred to the importance of the work of EDCTP.

In working to fight poverty-related diseases, we must also tackle underlying issues including inequalities between men and women. EDCTP’s policy is to promote equality from a gender perspective. This policy has been put into practice, for example through the Outstanding Female Scientist Prize, and the support given to efforts to include a gender perspective within the activities of regulatory authorities in Senegal. EDCTP encourages good gender-related practices in clinical research.

A complex set of factors leads to gender imbalance within medical research. Women are substantially under-represented in research institutes.

EDCTP is supporting a study of the gender-related impact of the COVID-19 pandemic. This is a step towards addressing gender issues and their socioeconomic consequences; and towards a recovery that it is fair, gender-responsive and leaves no one behind.

Work is now progressing towards the launch of the Global Health EDCTP3 Joint Undertaking. Governance will be key and a strong role will be played by African governments. Research priorities will be set, additional partners will become involved, including more from industry which is seen as crucial. Access to new technologies and addressing unmet needs will remain important considerations. Priorities will include emerging diseases and the spread of antimicrobial resistance. Links will be established with the new European Health Emergency preparedness and Response Authority (HERA). First calls for proposals under the new programme are hoped to be made next year.

We have learned the need for coordination between researchers, funders, policy makers, public health authorities and other key players. Only through global collaboration will we be able to improve our response to new infectious threats. The end of the current crisis must be used as an opportunity to build back better. We must continue to invest in research, and capacity and resources must be available to all.

How to better achieve gender balance

Jolene Skordis, economist at the University College London Centre for Global Health Economics, began by calling for ‘equal voices for equal genders’ and asked why very few women make it to positions of leadership in global health.

Gender, she said, is a social construct influenced by the distribution of power and resources. Work, education and opportunities (including career opportunities) continue to be defined by gender. A 2019 Lancet series found evidence that globally 70% of health workers are female but 70% of health leaders are male. There is a difference between who does and who decides! Women are undervalued, discriminated against and experience gender violence. Many calls have been made to address this situation but today Prof. Skordis said she would focus on individual inequalities and make use of a personal perspective.

Many women have the potential to be leaders but most do not make it to senior positions. Fewer girls enrol in secondary school and many do not complete it. They are more likely to face harassment and often don’t have access to adequate toilet facilities – challenging if you’re trying to study while menstruating. Girls will probably have caring responsibilities at home, which often take priority. Education for girls is not valued and many families are reluctant to pay school fees.

For those who complete school, opportunities narrow sharply. Further study is often not possible. Family expectations are that a girl will marry and have children at this age, and not continue with an expensive education. Some may be lucky and make it to university but it will be understood that this will not take priority over the woman’s primary role as wife, mother and carer. Financial support for higher education must usually be obtained through men.

When Professor Skordis did her PhD, she could not find a supervisor in her own country. She left the country (and her husband followed her). She is one of the lucky ones. But a PhD is only the start. Women are more likely to have to take career breaks, even though both men and women become parents. Travel and working commitments interfere with a parenting role. Her own daughter has found this difficult and her marriage has not survived. This is not unusual. Women often have to make impossible choices. We must stop expecting women to make such choices.

She stressed that she is amongst the most privileged of women. Some girls are not even born because of their gender, some are denied schooling or married off against their will, or used as domestic slaves and silenced within their own homes. We need an equal voice for women in global health so that all these issues can be addressed.

Achieving equity in global health research between the Global North and South

Catherine Kyobutungi is the Executive Director of the African Population and Health Research Center (APHRC). She said she would speak as the leader of a research organisation in Kenya and the leader of a capacity strengthening initiative for universities in Africa. She also would adopt a personal, not an academic perspective.

Her lived experience has been working within an unequal power system characterised by monopoly over knowledge, expertise and influence, but also by disregard for many forms of knowledge. She spoke of ‘unilateral learning’ where implicit assumptions are made over who knows what and whose knowledge needs to be upgraded. Few, she said, are ‘Willing to learn from people like me’.

Those who know the system can take more advantage of funding mechanisms. The system seems to be rigged so that those who have get more and those who don’t get less. So much is skewed towards one set of partners, who have more leadership opportunities. Unequal practices persist over time.

There are blind spots in the system – some voices are never heard and some things are left unsaid. Capacity building often happens in a vacuum because some individuals are unable to function within the systems that have been created.

What can be done by funding agencies and by all of us? Agencies must define what is equitable. We need to develop metrics that go beyond traditional measures of what is good. We have good measures on what is regarded as good study design – sample size, good ethics etc. But we need to define what is good capacity strengthening and what equitable partnerships look like. How will voices be heard and not just the voices of the authors of the paper? A study is more likely to be funded if it has good design but no importance is attached to equitable partnership and capacity building. We must find a way of measuring these other factors.

There should be diverse people on the panels of agencies. Success should be measured, horizontally and longitudinally, on the basis of system change and transformation. For example, there should be expectations as to composition of a research team after five and after ten years.

However, the issue goes beyond funding agencies. We need to hear the voices of more people. Knowledge is hard to quantify – it is often measured in terms of how many papers you have published. But what else have you learned in conducting the study and how do we measure that? What skills are you learning beyond discovering how to get a paper published? We need to define which skills are actually useful.

Knowledge gained from research usually stays with professors and the technocrats of health ministries. Often it does not reach those working on the ground. Knowledge is not there just to be cited in other papers!

We should make a deliberate effort to invest in institutions that are the drivers of change. Capacity strengthening must be seen as an end in itself, not just an add-on to a research project.

ISCIII | Fostering a stronger collaboration in personalised medicine: The EU-Africa PerMed project

Within the track of ‘Capacity strengthening, collaborations, enhancing the research environment, knowledge translation’, the Instituto de Salud Carlos III (ISCIII, Spain) has sponsored a session on Fostering a stronger collaboration in personalised medicine: The EU-Africa PerMed project.

Joaquín Guinea of InnovaTec (Spain) began explaining the concept of personalised medicine (PM). The term refers to a medical model which uses the characterisation of individual phenotypes and genotypes to tailor the right therapeutic strategy for the right person at the right time. It uses multiple sources of information about a person to improve prevention as well as treatment.

The EU-Africa PerMed project seeks to build links between Europe and Africa in personalised medicine. It is a four-year project that started in February 2021. Its final objective is to integrate African countries into the International Consortium for Personalised Medicine (www.icpermed.eu). He described in more detail the six specific objectives of this programme, which all focus on engagement with relevant health-related organisations in Africa. A consortium has already been established that includes six European and six African countries. The programme has an external advisory board. He laid out the six ‘work packages’ of which the programme is comprised – their objectives, activities and deliverables. A carefully planned ‘Journey’ for the project was also described.

In the short-term, the aim is to facilitate the integration of African organisations into the project, to support a wider adoption of PM standards, and to support EU-AU policy dialogue on PM. In the medium-long term, it is intended to reduce global inequalities in PM research and use PM to contribute towards the Sustainable Development Goal 3: Ensure healthy lives and promote wellbeing for all.

The Personalised Medicine research and innovation landscape in Africa: results of the EUAfrica PerMed scientific and policy mapping work

A presentation followed from Erika Sela, InnovaTec (Spain) and Amr Radwan, Egyptian Center of Innovation and Technology Development (ECITD, Egypt).

A mapping programme has been conducted to gain knowledge of the health research and innovation policy landscape in Africa, with a focus on PM. This has included a bibliometric analysis of recent research publications to establish who is already working in this area, what is their main focus, who they are collaborating with and other relevant issues.

Amr Radwan outlined some of the results of the bibliometric analysis, which identified institutions, areas of research and trends, all of which were assessed against 25 key indicators. 4340 publications from Africa relating to PM were found, from 3205 institutions and authored by over 39,000 researchers. 70% of reported studies were based on international collaborations but 60% had African first authors. 13 disease categories account for 80% of the publications, mainly infectious. The trend is growing rapidly.

Full results are available on the project website (www.euafrica-permed.eu/) and will be discussed and validated with stakeholders at a meeting in Nairobi next February.

Challenges and opportunities of personalised medicine for Africa

Rizwana Mia, South African Medical Research Centre, said that her intention was to make her audience think more about the potential for PM use in Africa.

Modern technology means we can now shift toward precise healthcare. Africa, which has the highest underlying disease burden in the world, needs to go further and address its burden more sustainably. Africa needs to catch up! Africa is known to have a large genetic diversity, but more research is needed on the African genome to make possible the introduction of PM.

PM introduction poses many challenges to African governments and other institutions. These include meeting the need for improved public health care. Africa does have effective private care and we must close the gap between the two sectors. There is also limited core infrastructure and poor data infrastructure (public health records are rarely held electronically). There are only a few biobanks and genomic sequencing is not widely available. There is a lack of skills and poor access to drugs.

Genomic scientists have poor data from Africa available to them. One result is that medicines are not really made with African populations in mind.

But PM offers a feasible long-term approach to improving heath in Africa. There are many opportunities, if we find out more about the African genome, work with the private sector, and foster intercontinental linkages. She left the meeting with other issues relevant to PM to think about.