8 Inspiring women who work in infection
By Natasha Khaleeq, Ruth Ntumba and Meesha Patel
International Women’s Day (IWD) takes place on the 8th of March every year as a day of global activism and celebration of forging women’s equality. The first IWD took place in 1911, so it has over a century of history and change. This year’s campaign theme is Inspire Inclusion.
The UK healthcare system isn’t inclusive; too much has been designed around the needs of half of the population: men. Men have frequently been treated as the default patient in clinical practice and medical research, and women’s health and healthcare needs have often been marginalised. However, researchers at Imperial are trying to change this.
In an opinion piece for the BMA, Professor Neena Modi, Professor of Neonatal Medicine at Imperial College London’s School of Public Health, points out that although many health issues have disadvantaged women globally, in 2021, the UK had the widest gender health gap in the G20. In general, women do worse than men in disease prevalence, access to healthcare, and outcomes after treatment. And pregnancy is associated with specific risks of infection. “Over 70% of medicines used in pregnancy have no, or insufficient, safety information, and in the last 30 years, only one medicine has been developed explicitly for use in pregnancy,” said Professor Modi. Pregnant and breast-feeding women were also excluded from the first wave of COVID-19 vaccine trials, which led to inconsistency in the advice issued by governments around the world. Professor Modi said: “This contributed to vaccine hesitancy, and the unvaccinated status of pregnant women substantially increased their likelihood of adverse outcomes following COVID-19 infection.”
Women’s health also directly affects the well-being of future generations. If a woman has an infection, she can pass it on through pregnancy or to her newborn baby. This is another aspect of women’s health that needs more research.
Imperial’s focus on improving women’s health is exemplified by the recent establishment of the Women's Health Network of Excellence, which promotes interdisciplinary research in women’s health and gender-based health equity.
“The lack of integration of sex and gender perspectives in infectious disease studies hinders our comprehensive understanding of how these factors influence infectious disease acquisition, progression and treatment. In the Women’s Health Network of Excellence, we aim to raise awareness of the importance of sex and gender considerations across all areas of research, including infectious disease, to foster more inclusive and impactful advancements in healthcare.”
To mark International Women’s Day, we highlight some of the work now underway in Imperial to understand challenges and gaps in knowledge on infection in women and what can be done to combat them. This includes vaccine research, diagnostics, human challenge studies, engagement, and policy.
HIV Diagnostics
In 2022, in Sub-Saharan Africa, adolescent girls and young women accounted for more than 77% of new infections among young people aged 15-24 years. “I think socio-behavioral research and interventions designed specifically to tackle these inequalities in specific populations definitely come into play and need to championed if we are to have significant impact,” says Dr Catherine Kibirige, a Senior Research Associate at the Department of Infectious Disease. After completing her first degree at the University of Bath, she volunteered with the Ugandan Ministry of Health at the Rakai Health Sciences program and began her career in HIV research, which has now lasted for over 20 years.
After gaining her PhD, Dr Kibirige earned a postdoctoral position with the Henry M. Jackson Foundation for the Advancement of Military Medicine in the US. At this institute, she developed an HIV quantification assay. “The assay has a very broad cross-subtype specificity and has various formats, including an ultra-sensitive format that can be used for cure-related research,” she says.
She joined Imperial and formed the HIVQuant Project, which aims to develop the assay into an ambient-temperature kit for use in early diagnosis, particularly for infants and for treatment monitoring of HIV patients. She says: “The kit is designed specifically for resource-constrained settings where the need is greatest, and there is a lack of access to early diagnosis and convenient timely treatment monitoring in areas or countries that do not have the infrastructure to support cold requirements for current viral load tests.
“I am also optimizing the kits to run on portable instruments that can be powered by a car battery or solar panel and can, therefore, be used in rural clinics or health centres that do not have reliable electricity.”
The impact of developing the HIVQuant kit would ensure that people with HIV are detected early, leading to a better quality of life. The kit could potentially also monitor the effects of new experimental treatments in areas where the HIV burden is the greatest, as Dr Kibirige goes on to explain:
Diagnosing HIV as soon as possible after infection and getting people into treatment quickly improves disease outcomes and allows people to live a long, productive life. Intracellular HIV DNA quantification is also a proxy for the latent HIV reservoir and can be used to monitor the effects of experimental cure therapies. A more accessible HIV DNA detection kit will allow cure research to become accessible in areas most affected by the epidemic.”
A key challenge around HIV diagnosis and treatment is the development of drug-resistant strains, which can develop due to people using treatments inconsistently. Dr Kibirige describes that new medications may offer hope. “New long-lasting injectable treatments will help solve the problem of inconsistent use of drugs, which is the main drive of drug-resistance development.”
Although gender doesn’t change how the virus affects the body, Dr Kibirige is interested in how it impacts service delivery or implementation. So, she is hoping to "become more involved in translational research and public health implementation work as I specifically develop my ambient-temperature early HIV detection and treatment-monitoring kit and hope to study and design interventions that specifically promote the utilization of the tools within this group and improve their outcomes.”
However, there is still more to be done as the UN recognises through the 95-95-95 goals, which aim to get 95% of those on HIV treatment successfully suppressed by 2030. To be successfully suppressed, you must be HIV ‘undetectable’ and cannot spread the infection to others.
Dr Kibirige says: “This UN goal cannot be achieved unless we provide more efficient point-of-care testing to resource-limited settings that are affected by the virus and reduce the development and spread of drug-resistant strains of the virus." The HIVQuant project is currently close to completing its pilot study with its first prototype kit being tested in Malawi.
Antenatal screening policy
After completing a PhD in her home country of Brazil, Dr Carolina Rosadas, a Research Fellow in the Section of Virology, joined Imperial to further her research in Human T-lymphotropic virus 1 (HTLV-1), a viral infection that demonstrates differences in men and women. For example, HTLV-1 sexual transmission is more effective from male to female, and the progressive neurological disease caused by HTLV-1, HTLV-1-associated myelopathy (HAM), is also more frequently observed in women compared to men. “I am passionate about HTLV-1 and am excited to be able to use my research to help improve the life of those living with the virus and particularly to support preventing new infections,” she says.
HTLV-1 is also an infection that can spread from mother to child, primarily through breastfeeding. Dr Rosadas has shown that a high number of new HTLV-1 infections in Brazil are due to mother-to-child transmission and that replacing breastfeeding with exclusive formula feeding in mothers who are infected can prevent 80% of infant infections. However, antenatal screening is not routinely performed to identify which mothers are infected. Lack of antenatal screening data also impairs the development and implementation of government policies at home and abroad.
Since 2017, Dr Rosadas, alongside Professor Graham Taylor, has been working on a collaboration with the Ministry of Health in Brazil to support their HTLV-1 response. This February, she helped Brazil’s Ministry of Health implement universal HTLV-1 antenatal screening, which will prevent more than 1,000 infant infections and benefit about 2.5 million families annually.
Her recent work in collaboration with 15 institutions from Brazil and the UK has also shown that HTLV-1 antenatal screening is cost-effective. The UK National Screening Committee is assessing whether the HTLV-1 antenatal screening policy should be implemented.
“I was delighted that Brazil decided to offer screening to all pregnant women and that now they set a goal to eliminate HTLV-1 vertical transmission as a public health problem. But the work begins now. The challenge is to implement this policy in such a continental and diverse country as Brazil.”
Dr Rosadas aims to continue supporting the government in different aspects, such as preparing guidance, training in healthcare, and setting tools and targets for the elimination program. She will also use her research to answer upcoming questions and has an ongoing research collaboration to improve diagnostics and increase awareness through her HTLV social media channel. Dr Rosadas feels “the secret behind the Brazilian success is the great collaborative environment between different stakeholders: civil society, policymakers, and academia. So, I do hope to be able to keep contributing to this group.”
Dr Rosadas has also been working with the Pan American Health Organization/World Health Organization, and she’s excited about including HTLV-1 in their initiative to eliminate mother-to-child transmission of HIV, syphilis, hepatitis and Chagas Disease. “This will certainly drive a more effective response to HTLV-1 globally,” she says.
MMR vaccines combating the outbreak
Dr Helen Skirrow (Child Health Unit, School of Public Health) works on pregnancy and childhood vaccinations. She researches which pregnant women and children under five years don’t get vaccinated or get vaccinated late and why. This is a significant public health concern because it risks the health of the individual and the wider population. For example, not enough children in the UK have had their two recommended doses of Measles, Mumps and Rubella (MMR) vaccines. This has resulted in recent measles outbreaks in areas such as London and the West Midlands. Dr Skirrow also focuses on how to make it easier for pregnant women and children to be vaccinated to improve uptake.
In the UK, pregnant women are recommended to be vaccinated against seasonal influenza, whooping cough and COVID-19. These vaccines protect pregnant women and their babies as antibodies transfer through the placenta. Newborn babies can be vulnerable to infection before they get their first vaccinations at eight weeks old.
Pregnancy offers an excellent opportunity for healthcare professionals to talk to families and pregnant women about vaccinations and answer any questions or concerns they may have. They can also discuss the routine childhood vaccination programme and check if any other children in the family are up to date with their vaccines. The second dose of MMR vaccine is usually offered to children as part of the preschool vaccinations at three years and four months. Dr Skirrow describes this as a problem with “concerningly low uptake in some areas of London”. However, “it is not too late if you think your child may have missed a dose” as GPs can be contacted. Women should also check they’re up to date with their vaccines; if they’re not, they can be vaccinated after their baby is born. This will help manage the current measles outbreaks in the UK and prevent future outbreaks.
Five years ago, Dr Skirrow started working with The Mosaic Community Trust - an organisation based in an ethnically diverse area of London with historically low childhood vaccine uptake. They first collaborated on an NIHR Imperial Biomedical Research Centre (BRC)-funded public involvement project to discover why some pregnant women in North West London don’t get vaccinated.
Following this, Dr Skirrow and Lena Choudary-Salter (Head of The Mosaic Community Trust) co-produced an NIHR-funded project called ‘Why did nobody ask us?!’.
Our collaboration has really helped us to understand the voices of families and women who live very close to Imperial’s St Mary’s campus, but whose voice haven’t often been heard in research. Their perspective is very important in terms of vaccine uptake research because we know children from minority ethnic backgrounds or who live in more deprived areas are less likely to get vaccinated, and we need to understand why. For example, we have found that we need to make it really easy for parents to speak to healthcare professionals about their children's vaccines and make sure getting their children vaccinated is convenient and easily accessible.”
Dr Skirrow’s research and interests have been informed by her own experiences (she is currently on maternity leave with her third child), including during her pregnancy with her first child in early 2013 when the whooping cough vaccine had just been introduced due to an increase in cases amongst newborn babies in the UK. She explains: “I had the whooping cough vaccine because I felt very clearly as a doctor that that was the right thing to do. But lots of my non-medical pregnant friends were asking, ‘Why are we being offered this?’ which made me realise how many questions you have when pregnant about vaccines.”
Further interest in vaccine uptake was informed by Dr Skirrow’s experience managing measles outbreaks as a public health registrar. This led her to want to research which children don’t get vaccinated and how outbreaks can be prevented. Later, during the COVID-19 pandemic, she focused on pregnant women’s attitudes towards COVID-19 vaccines and how routine vaccine services were affected by the pandemic. “New vaccinations need to be communicated really clearly to pregnant women with information tailored specifically to address pregnant women’s questions,” she says.
Covid vaccine and the menstrual cycle
Dr Victoria Male, from the Department of Metabolism, Digestion and Reproduction, is a Senior Lecturer in Reproductive Immunology. She is a prominent voice on SARS-CoV-2 and its effects on fertility in both men and women, as well as its implications for pregnancy, breastfeeding, newborns, and the menstrual cycle.
Throughout the COVID-19 pandemic, Dr Male played a crucial role in providing evidence-based guidance to the public, addressing widespread speculation about the COVID-19 vaccine's negative influence on fertility. She felt a sense of “responsibility to tackle these rumours.” In December 2020, vaccine trials showed that people became (unintentionally) pregnant at the same rate as placebo groups. Several studies in fertility clinics and one large study with more than 2,000 couples confirm this to be accurate. The same studies show that COVID-19 vaccination doesn’t affect male fertility. In contrast, COVID-19 infection in a male partner reduces the chance of conception for a couple of months due to decreased sperm count and quality.
Dr Male also worked on issues around the safety and risks associated with COVID-19 and vaccination in pregnant women. During the pandemic, pregnant women who were unvaccinated and caught the virus for the first time faced higher risks of preterm birth and stillbirth and were more likely to suffer from the most severe form of the virus. In the face of these risks, COVID-19 vaccination in pregnancy seemed a desirable proposition; however, to begin with, there was very little data on the safety and effectiveness of COVID-19 in this population. By Spring 2021, data from the USA suggested that COVID-19 vaccination was safe and effective in pregnant individuals, so the UK began offering COVID-19 vaccination during pregnancy. Further studies, including more than half a million people, confirmed the safety and effectiveness of vaccination and show that pregnancy vaccination offers babies protection against severe COVID-19 for three to six months after they’re born.
While vaccination reduces risks of complications during pregnancy, pregnancy remains a COVID risk factor, which is why boosters are still being offered to pregnant women.
Dr Male also advocates for "better consideration of sex in vaccine research", highlighting the importance of including data on female reproductive health to assist decision-making. She notes that while COVID-19 vaccine trials had equal male and female participation, gathering more information on menstrual cycles could have provided valuable insights. Because of this knowledge gap and in response to reports that some women experienced changes to their periods shortly after COVID-19 vaccination, Dr Male has focused efforts on assessing the impact of the COVID-19 vaccine on the menstrual cycle. She was part of a team that used Natural Cycles tracking app data to tackle this issue. The app allowed researchers to compare the menstrual cycles of thousands of vaccinated and unvaccinated individuals.
We found that 1% of people experienced a clinically significant (greater than 8-day) delay to the period after they were vaccinated, and 4% experienced a heavier than usual period. Importantly, we found that cycles returned to normal in one to two months.”
Dr Male and her team are still uncertain about how the vaccine triggers these temporary changes in some menstrual cycles. They believe it could be due to COVID-19 infection and some vaccinations activating a response in the immune system. Scientists already know that when the body produces immune proteins, known as cytokines, they can affect the hypothalamus, which regulates body temperature and the menstrual cycle. Thus, there is a potential link between vaccination, immune response, and menstrual changes.
The COVID-19 Human Challenge study
Dr Anika Singanayagam is an NIHR Academic Clinical Lecturer in the Section of Adult Infectious Disease. Her research aims to improve strategies to control the transmission of respiratory viruses using vaccines, antivirals, or diagnostic testing.
She is Principal Investigator in the UK’s second SARS-CoV-2 ‘human challenge’ study. Human experimental infection challenge studies recruit young, healthy volunteers who are intentionally inoculated with an infectious agent in a safe and controlled way. Samples from volunteers are collected before and after the participants are challenged, which allows investigators to study an infection in great detail. For Dr Singanayagam and colleagues' study, the collected samples allowed them to examine how the virus replicates, how immune responses can control it, and how infectious people are to others. Another aim was to identify the number of viruses that cause mild infections in more than half of the infected participants. “Following this, we can go on to test novel vaccines using the challenge model, for example, those that can reduce or block transmission or provide cross-variant protection.”
Gender is an integral component to consider when conducting the human challenge. It influences how patients are monitored and what is regarded as the “normal range”, as these vary for men and women. Gender differences may also influence immune responses. Thus, gender is essential not only in determining how studies are conducted but also in analysing the data that is generated.
Dr Singanayagam also noted other impacts of infectious disease epidemics or pandemics disproportionally experienced by women. A report by the IFS found that mothers in the UK were more likely than fathers to have quit or lost their jobs during lockdown, so would contribute a large share of childcare and household responsibilities. It’s also worth noting that maternal and foetal infection risks are unknown when a new pathogen emerges, making decision-making around the best care difficult. This includes potential delays in using new treatments because of a lack of data during development. More research is also required to investigate further the differences in biology between men and women, such as their immune response to vaccines.
“Having equal representation of women and men in clinical trials is something healthcare professionals should strive for. And, in my view, having strong representation of women at the forefront of Infection research and decision-making – leading research grants, acting as PIs on clinical trials, and contributing to national task forces and advisory committees, is key to ensuring women’s health needs are given due attention.”
Blood in Action
Alison Perry, originally from Canada, is a British-trained midwife. “Midwifery has been my main lens into women’s health, and in some ways, the profession's challenges mirror the issues in women’s health,” she says. She’s supported by the Parasol Foundation to do her PhD and is an honorary research fellow in the Women’s Health Research Programme at the George Institute for Global Health. Patient and public involvement and engagement (PPIE) are now commonly featured in our expectations of women’s health research.
Alison’s research is related to improving our understanding of community engagement mechanisms so that it can be reflected in the quality of research and improve outcomes in women’s health. Alison’s research is concerned with the equitable inclusion of people in research and health, which requires critiquing entrenched structures and assumptions within health systems. “Involvement in the midwifery profession has featured some of the same considerations," she says. "More directly, though, midwifery gives me first-hand knowledge of maternity, which is the setting of the Blood in Action Project.”
The Blood in Action (Bia) Project (funded by the Parasol Foundation) is a research project looking to better utilise routinely collected samples in maternity. Blood samples are collected to screen for a range of viruses in pregnant women, and the research team is keen to put these samples to an even better effect to inform population-level issues such as the current rising level of measles in the UK. The team are aware that health policy and care are built upon research that has excluded the experience and anatomical/ biological reality of women, which is an unacceptable bias that affects the quality of life. The Bia Project stands to contribute to redressing the systemic exclusion of women by harnessing the potential of everyday NHS pathways already in place.
Alison’s doctoral work alongside the Bia Project provides more creative methods and modes of engagement at the intersection of arts and health, including storytelling and mosaic arts. “In general, if we focus more on the creation of relationships versus exclusively on outcomes, we will begin to get things right,” she says.
HPV policy
Cancer Research UK estimates that around 80% of people will be infected with Human papillomavirus (HPV) at some point in their lives, and the World Health Organisation state that 99% of cervical cancer cases (the most common cancer in women) are linked to infection with high-risk HPV. Paula Christen (School of Public Health), says: “Cervical cancer remains a global health issue, disproportionately affecting women in countries in the African region, where 85% of global mortality from cervical cancer occurred based on 2020 estimates.”
In many countries, women don’t have access to or can’t afford appropriate treatments. Therefore, there is a critical need for comprehensive research on HPV and the development of effective prevention strategies, including vaccination and screening programmes.
Paula is a social scientist and epidemiologist. She specialises in researching evidence-informed decision-making in infectious disease control policies and programmes. During her PhD research, she focused on how decision-makers can be integrated into modelling HPV vaccination in Mozambique for evidence to be relevant for policy and health programme development.
During her work in Mozambique, Paula developed a framework encompassing three main parts:
- Probing evidence needs of stakeholders to formulate research questions. She conducted and analysed interviews to identify key evidence needs that can be addressed using mathematical models.
- Address evidence needs with an appropriate method. Paula estimated how current policies impact vaccination programmes on health, cost savings for the healthcare system, and broader economic benefits. She showed that vaccination programmes can reduce health and financial disparities across socioeconomic populations and free up medical staff capacity.
- Science communication. Evidence for the HPV vaccination programme was summarised in an evidence brief, presented and discussed with previous interview participants.
Policies need to consider entrenched income inequalities, access to treatment and the distribution of cervical cancer within populations. Paula's research in Mozambique showed that the benefits of HPV vaccination would mainly affect wealthier women. So, policies need to focus on rural and poorer populations. For catastrophic health expenditure incidence to be reduced by 50% in Mozambique, the treatment would have to be almost entirely paid for by the government for patients in the poorest areas. Policies addressing inequalities need to be developed with stakeholders at the community level.
Thus, funding for research to identify appropriate HPV vaccination policies should be diverted to researchers based in countries most affected by HPV. They have the knowledge and understanding of the context in which policies should be introduced and are therefore in the best position to develop policy-relevant evidence.”
Globally, there is an increasing number of licensed vaccines and national vaccine introductions, so eradication of HPV types which cause cancer is becoming more feasible, significantly reducing the need for preventive measures in the future. In the past few years, studies have shown that HPV vaccination reduces the burden of cervical cancer. By 2094, immunisation of girls born between 2005 and 2014 with vaccines that target cancer-causing genotypes is estimated to prevent 8.7 million cases globally.
The future of HPV diagnostics
While highly accurate tests like PCR exist for HPV detection, the efficacy of preventive measures hinges on overcoming barriers to screening, particularly the discomfort associated with sample collection methods, such as the smear test, which poses a significant obstacle for women.
Sanziana Foia (Department of Bioengineering) is the founder of Papcup, an electrochemical device that is compact, reusable, and about the size of your fist. Unlike traditional smear tests, the device uses menstrual blood samples, and its electrochemical biosensor detects HPV efficiently and reliably.
“My inspiration for Papcup arose from my own negative experience with smear tests and the realisation of the widespread discomfort and barriers faced by women undergoing this procedure.”
Sanziana was motivated by a passion for science and commitment to social justice; she embarked on a mission to create Papcup to provide access to life-saving screenings, particularly for underprivileged and marginalised communities. With her invention, Sanziana reached the semifinals of the We Innovate competition at Imperial College London, which provided the first catalyst for Papcup’s development.
She says: “Creating a user-friendly, comfortable, and intuitive device for sample collection is crucial in encouraging more widespread participation in life-saving screenings. By developing Papcup, which offers an easier and more accessible alternative to traditional smear tests, we can empower women to take control of their health and prevent cervical cancer effectively.”
There is also potential for developing tailored diagnostic tests and screening guidelines aimed explicitly at detecting HPV infections and related complications in men.
Since March 2023, when Sanziana and her team won the Hackstarter competition, she has focused on building the business and securing funding to propel her vision forward. She has participated in the Summer Accelerator at Imperial, the Venture Builder Incubator at the University of Edinburgh and a Cancer Research Horizon programme. The team have also recently been accepted into the NHS CEP Patient Entrepreneur programme. Now, they’re directing their efforts towards validating the market and developing their Minimum Viable Product.
I believe that the future of rapid diagnostic tools for HPV is Papcup!”
Besides Sanziana’s entrepreneurial journey, her PhD research focuses on developing a microneedle biosensor for detecting anti-malarial drugs to create a diagnostic tool in regions lacking laboratory infrastructure. This will optimise drug dosages and combat drug-resistant malaria strains.