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International Development Research @ Cambridge

 

Surviving birth

Thu, 10/12/2020 - 09:00
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Surviving birth

Valente Inziku, whose wife Jennifer died in childbirth in Arua, Uganda (photography: Tadej Znidarcic)

Valente Inziku, whose wife Jennifer died in childbirth in Arua, Uganda (photography: Tadej Znidarcic)

Researchers at one of the busiest maternity hospitals in the world aim to help more women survive complications giving birth.

Obstetrician Dr Annettee Nakimuli and colleagues look after up to 28,000 births a year at Mulago Hospital in Kampala, Uganda.

Every day, 300 pregnant women visit the hospital antenatal clinic. Around 100 women are on the labour ward, and 40 of these will have complications – obstructed labour, haemorrhage, sepsis or pre-eclampsia – requiring up to 25 emergency caesarean sections to be carried out.

“When women come to the labour ward they hope to come out with the best of it – they hope to come out with a live baby, and come out alive themselves. But women go to hospital with mixed feelings – they’ve seen others die before them, so there’s a tendency to think of maternal death as something inevitable rather than avoidable,” says Nakimuli, who is also Chair of the Department of Obstetrics and Gynaecology at Makerere University in Kampala.

“In a bad month, we can have up to 15 mothers dying. For babies, the number is usually double or three times that figure.”

Part of the challenge is the sheer number of patients compared with the number of doctors and midwives.

“We are a national referral hospital so we receive everybody... we can’t deny admission because we are full,” says Nakimuli. “In fact we’re not even sure what full means – we’ve always worked above 100% capacity.”

Nevertheless, Nakimuli is convinced that, even with these difficulties, something can be done to reduce the mortality rate. Despite an astonishing workload, she and others are questioning why the level of maternal deaths is so high in sub-Saharan Africa.

IN NUMBERS...

Level of maternal deaths are nearly 50 times higher for women in sub-Saharan Africa and their babies are 10 times more likely to die in their first month of life compared with high-income countries.

Women in sub-Saharan Africa face a 1 in 37 lifetime risk of dying during pregnancy or childbirth. By comparison, the lifetime risk for a woman in Europe is 1 in 6,500.


Child and maternal mortality estimates released September 2019 by UNICEF and the World Health Organization.

Silent killer

Ten years ago, Nakimuli arrived in Cambridge as part of the Cambridge-Africa Programme, a University-wide initiative to make its expertise and resources available to support ‘African researchers working in Africa on African priorities’.

She was embarking on a PhD with Professor Ashley Moffett, an expert on the life-threatening condition pre-eclampsia that results from the placenta developing abnormally.

Pre-eclampsia occurs more commonly in women of African ancestry compared with Europeans, and happens earlier in pregnancy and is more severe, says Moffett: “What makes the disease a ‘silent killer’ is that it’s impossible to predict or prevent. The only course of action is careful monitoring and emergency delivery.”

Over the past decade, Nakimuli has travelled back and forth between her research lab at Makerere University in Kampala and Cambridge’s Department of Pathology to learn techniques, analyse samples and spend time with Moffett examining why this complex disease is so much more of a problem in Africa.

Their collaboration led to the discovery of particular genes found only in women of African descent that are linked with risk and protection in pre-eclampsia.

Professor Ashley Moffett and Dr Annettee Nakimuli (photography: Lloyd Mann)

Professor Ashley Moffett and Dr Annettee Nakimuli (photography: Lloyd Mann)

Moffett is now hopeful that recent work on ‘mini-placentas’ with Cambridge colleagues Dr Margherita Turco (see panel below) and Professor Graham Burton will provide a much-needed experimental tool to understand this mysterious disease – and the role of the placenta in general.

But even with these major steps forward, the researchers know they are still a long way off being able to offer early diagnosis and treatment, as Nakimuli explains: “I’ve really worked on trying to understand pre-eclampsia and we’ve made discoveries that will help us to understand the basic disease, but sometimes the endpoint of being able to help the patients is not easy to reach. In the meantime, it’s very obvious that we need to find other ways of helping women right now.”

Stories to books

Ugandan obstetrician Dr Imelda Namagembe is also trying to improve maternal health by, as she explains, “learning from the stories of the women who have died.”

In the UK, if a woman dies during or after pregnancy, the circumstances of her death are collected anonymously by a national service called MBRRACE (Mothers and Babies; Reducing Risks through Audits & Confidential Enquiries across the UK), which then makes national recommendations to improve future care.

Namagembe would like to see a similar system in Uganda, where the level of systematic processing and reviewing of reasons for maternal death is low.

The first step is to identify the barriers to this process, which she is doing for her PhD as part of the Cambridge-Africa Programme, co-supervised by Nakimuli and Dr Catherine Aiken from Cambridge’s Department of Obstetrics and Gynaecology.

“One of the things that makes an enormous difference to women surviving is somebody systematically collecting the reasons why mothers have died, reviewing them, understanding what’s happening, and then learning from it, and no one has done this in Uganda,” says Aiken.

She adds: “Given the pressure that doctors like Imelda and Annettee are under, it’s amazing that there’s also the will and the determination to say look we can do something about this.”

It’s a sentiment echoed by Aiken’s colleague, Dr Charlotte Patient, a Consultant Obstetrician at the Rosie Maternity Hospital in Cambridge, part of Cambridge University Hospitals NHS Foundation Trust. Patient also visits Kampala each year with a volunteer team of NHS clinicians and midwives from the Rosie organised by Cambridge Global Health Partnerships.

“The staff in Kampala don’t need clinical expertise – they’re very good,” says Patient. “What they asked us for help with was in building clinical guidelines that could be used everywhere and updated easily. They’d had no breathing space to take a step back and develop standardised approaches.”

As the Ugandan and Cambridge teams worked together to develop guidelines for the major causes of maternal mortality, there were some unexpected successes, says Nakimuli: “Our midwives gained confidence. We saw, for example, Charlotte the doctor and Kimberley the midwife discuss matters as equal partners. It showed us how interdisciplinary teams work well. Around 80% of our deliveries are in the hands of midwives, and so the more empowered they are, the better.”

Back in the UK, Patient says she has a new perspective on her own work: “You come back with a completely different appreciation for the NHS. I really think about use of resources and how we don’t always make best use of what we have. The experience has made me a better doctor.”

“Given the pressure that doctors like Imelda and Annettee are under, it’s amazing that there’s also the will and the determination to say look we can do something about this.”

Dr Catherine Aiken, Department of Obstetrics and Gynaecology

Another success is on the way to being born: the first contemporary textbook of obstetrics written by African doctors for African women. Nakimuli and her Ugandan colleagues are currently writing the contents planned for publication in print and online by Cambridge University Press in 2021. Meanwhile, her Cambridge colleagues are providing advice and have raised funds for the book to be available as open access.

Predicting outcomes

Nakimuli is also starting a new study to understand how to predict a complicated pregnancy. Her Pregnancy Outcome Prediction Study (or POPs), funded by the Royal Society and the African Academy of Sciences, and thought to be the first of its kind in Africa, is based on a model designed by Professor Gordon Smith in Cambridge’s Department of Obstetrics and Gynaecology.

Smith’s study followed 4,212 UK women for five years from early pregnancy through to delivery in order to identify predictors of adverse pregnancy outcomes.

“In the UK, although some women are identified as high risk for pregnancy complications from their medical history, most complications occur in women with no known risk factors,” he explains.

Smith’s unique data-rich approach looks for the ‘biological signature’ of an unhealthy pregnancy using regular ultrasound scans and blood sampling, DNA sequencing, analysis of samples of placenta, fetal membranes and umbilical cord, and details of the delivery and outcome.

The huge volume of data is already providing health benefits: for instance, his team discovered that offering universal late pregnancy ultrasounds at 36 weeks’ gestation eliminates undiagnosed breech presentations of babies, lowers the rate of emergency caesarean sections, improves the health of mothers and babies, and could actually save the NHS money.

“Practice only changes when guidelines change, and guidelines only change when the evidence to support change is strong,” adds Smith.

“What motivates me is the belief that I will see preventable maternal death being talked about as a thing of the past.” (Photography: Lloyd Mann)

“What motivates me is the belief that I will see preventable maternal death being talked about as a thing of the past.” (Photography: Lloyd Mann)

Nakimuli’s goal is to look specifically at the ‘signature’ for pre-eclampsia: “Until now we have been studying the women who have developed the disease,” she says. “We need to move a stage earlier and do prospective studies that will help us to understand which women we should pay special attention to when they become pregnant.

Because African women have more severe forms of the disease, we think this is an opportunity to understand  the disease as never before.”

Moffett believes that Nakimuli has the passion and ability to make a difference: “She’s a leader. She’s not only established and maintained these wonderful collaborations between Makerere University and Cambridge but she’s been a role model for all the other collaborations that now exist in areas like sepsis, placental malaria, hypertension, anaesthesia and infection control.

“For change to happen it needs to be led by Africans like Annettee.”

Professor Ashley Moffett, Department of Pathology

Nakimuli herself is optimistic that the small successes in reducing the rate of maternal mortality in Africa will become bigger successes: “Globally, maternal and neonatal health has become a high priority among the international community, and there is more awareness in Africa that we should not accept that it is normal to die during childbirth. We are seeing small successes so, when they announce every few years there is a bit of decline, I think: yes… we will finally get there.

“What motivates me every day is the belief that, in my lifetime, I will see preventable maternal death being talked about as a thing of the past, even within sub-Saharan Africa.”

Snapshot: The placenta grower

Pregnancy complications are often the result of defective placental development and function. But how and why this should happen is a ‘black box’. These are particularly human problems and it’s not possible to study the organ inside the mother.

So Dr Margherita Turco working with Professors Ashley Moffett and Graham Burton came up with a transformative solution: she grew a uterus and a placenta in a dish. “Without a reliable experimental model that mimics how placental cells interact with the maternal tissues, it was impossible to ask even basic questions,” says Turco, from the Department of Pathology and Centre for Trophoblast Research.

“We can now grow miniature functional ‘organoids’ that so closely resemble first-trimester placentas that the cells record a positive response using a pregnancy test, showing they are secreting hormones.

“Our mini-placentas will help to shed light on the mysteries surrounding the relationships between the placenta, uterus and fetus. They could be used to understand the role of the placenta to protect the baby and how chromosomal abnormalities perturb normal development, as well as to screen the safety of drugs to be used in early pregnancy.

“To me, one of the most exciting aspects is that the events when a mother and her fetus first physically interact through the uterus and placenta have been impossible to capture. Now we can see exactly what happens when the two sides ‘talk’ to each other, and if that dialogue is perturbed in women who suffer an early pregnancy loss.”

Image: Trophoblast organoid (Margherita Turco).

Read more about our research into all aspects of reproduction in Horizons (PDF), the University of Cambridge's research magazine, and find related articles online.

Cambridge Reproduction Strategic Research Initiative

From understanding ancient ideas of generation to exploring new frontiers in fertility, Cambridge researchers are working across disciplines to study reproduction from multiple perspectives. For more information, visit the Cambridge Reproduction Strategic Research Initiative website.

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Researchers at one of the busiest maternity hospitals in the world aim to help more women survive complications giving birth.

Image: Affiliation (schools and institutions): Department of PathologyCentre for Trophoblast ResearchSchool of the Biological SciencesDepartment of Obstetrics and GynaecologySchool of Clinical MedicineCambridge-Africa ProgrammeCambridge University PressPeople (our academics and staff): Ashley MoffettCatherine AikenGordon SmithCharlotte PatientGraham BurtonMargherita TurcoSubject (including Spotlight on ... where applicable): ReproductionbirthbabiesAfricamaternal mortalitypre-eclampsiahospitalplacentaGlobal SouthStoriesSection: ResearchNews type: News
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Open-source toolkit helps developing countries meet demand for COVID-19 research and diagnostics

Tue, 08/12/2020 - 00:22

High demand for millions of COVID-19 tests per day combined with a disrupted global supply chain has left many countries facing diagnostic shortages. In a recent Nature commentary, John Nkengasong, Director of the Africa Centres for Disease Control and Prevention, said, “the collapse of global cooperation [has] shoved Africa out of the diagnostics market....African countries have funds to pay for reagents but cannot buy them.”

Scientists across the world are therefore developing new tests that are faster, cheaper, adapted to needs of local health systems and easy to manufacture in order to overcome this challenge.

To enable scientists to access the research tools they need for their work, researchers from the Open Bioeconomy Lab at the University of Cambridge, the Lab de Tecnología Libre at iBio/PUC Chile and the FreeGenes Project at Stanford University teamed up with synthetic biology company Ginkgo Bioworks to design an open source toolkit that enables researchers to produce 16 of the most useful enzymes for a number of diagnostic techniques used to detect SARS-CoV-2, the virus which causes COVID-19.

“Designing the collections was a great collaborative effort between researchers with diverse expertise and different local needs for fighting the pandemic,” said Dr Chiara Gandini from Cambridge’s Department of Chemical Engineering and Biotechnology. “We designed it with other biologists in mind, making it as easy as possible for them to reconfigure the toolkit for their requirements.”

The ‘Molecular Diagnostic Toolkit’ comprises ready-to-use DNA to produce enzymes including DNA polymerases and reverse transcriptases – the enzymes used in gold standard RT-qPCR tests. These enzymes are also useful for tests like LAMP, which is faster and simpler than RT-qPCR and is rapidly being adopted by more labs. Control DNA is also included in the toolkit to validate that tests will specifically detect SARS-CoV-2 but not closely related viruses.

The Molecular Diagnostic Toolkit uses standard laboratory techniques to produce and purify the enzymes, but many researchers in the Global South work under challenging resource constraints and may need to adapt their work to the local availability of materials. They can therefore make use of the ‘E. coli Protein Expression Toolkit’: a collection of over 100 DNA parts that can be assembled in thousands of combinations to tailor the whole production process. For example, modules are included to bind enzymes to cellulose to develop paper-based tests or to activate enzyme production in cells using light from LEDs instead of expensive chemicals.

The toolkit has been pre-ordered by over 34 labs from 16 countries, including Brazil, Chile, Peru, Colombia, Costa Rica, Mexico, Cameroon, Ethiopia, India and Vietnam.

“Having access to this palette of molecular tools is crucial for our region to fight any reagent supply shortages in the short-term, and to leverage technological autonomy in diagnostics and viral monitoring in the long term,” said Tamara Matute from the Pontificia Universidad Católica de Chile and iBio, who participated in the design of the collection. Matute’s colleague Isaac Núñez added that mechanisms like the open online community, Reclone Network, are also needed to enhance the usefulness of the collection through peer support including fostering “a collaborative community, crowd-sourced protocols and openly-shared resources.”

While the initial focus of the toolkit is to support research and development, the same DNA could be used to manufacture diagnostic kits with the correct processes and regulatory approvals in place. As it is open source, any company or institution is able to produce and commercialise enzymes from the toolkit. For example, LAMP enzymes will be manufactured at the Ethiopian Biotechnology Institute in a collaboration with the University of Cambridge supported by the Cambridge-Africa Alborada Fund.

Dr Brook Esseye of the EBTi LAMP Initiative said, “this initiative will enhance local capacity for bio-manufacturing and strengthen partnerships among researchers in various countries so we can join hands to fight this global pandemic.”

Looking beyond COVID-19, local bio-manufacturing capacity could underpin other advances in biotechnology research, education and innovation.

“A resilient local supply chain for diagnostics is vital to future health security and pandemic preparedness,” said Dr Jenny Molloy, Shuttleworth Fellow at Cambridge’s Department of Chemical Engineering and Biotechnology. “The same enzymes used to detect COVID-19 can also detect malaria, typhoid and many other diseases. They can be applied in lots of other ways to make positive social and economic impact, including research to breed better crops, measuring the effect of conservation initiatives on biodiversity and tracking antibiotic resistance. This flexibility is why it is so important that key tools for biotechnology are accessible, used and useful for all researchers around the world.”

The toolkit has been made freely available under the Open Material Transfer Agreement (OpenMTA), which gives explicit permission for recipients to distribute to other labs and to use the toolkit for commercial purposes, and can be ordered online via Stanford University’s Free Genes project.

Researchers and users of the toolkit are invited to share protocols, resources and advice via the Reclone Forum.

Researchers have developed a free, open-source toolkit that allows laboratories in developing countries to produce their own tools for COVID-19 research and diagnosis, without relying on an increasingly fractured global supply chain.

COVID-19CoronavirusPublic healthdiagnosticAfricaInnovationGlobal SouthChiara GandiniJenny MolloyStanford UniversityDepartment of Chemical Engineering and BiotechnologySchool of TechnologyA resilient local supply chain for diagnostics is vital to future health security and pandemic preparednessJenny MolloyNIAIDNovel Coronavirus SARS-CoV-2


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In Ethiopia, schools still lack basic means to contain COVID-19, as pupils return after months of interrupted learning

Mon, 07/12/2020 - 11:24

The two new research and policy reports, compiled by academics at the University of Cambridge in collaboration with partners in Ethiopia, draw attention to the combined educational and practical challenges facing the country’s schools as pupils return. The authors suggest that these converging problems, while more severe than those affecting schools in wealthy countries such as the UK, are typical of those confronting millions of parents and teachers across sub-Saharan Africa as the pandemic continues to exact a far less-visible toll on their lives and communities.

The findings are based on telephone interviews with more than 900 teachers and caregivers which were carried out in August. Schools in Ethiopia are currently reopening on a staggered basis for the first time since March, with priority given to schools in rural areas. Since the study was completed, many of the issues it documents will have been compounded by the crisis in Tigray.

Overall, the researchers found that, despite significant efforts by the Ethiopian government to support remote learning, many pupils are likely to have had little or no education during the closure period. Disadvantaged groups – such as poorer children, those in remote areas, and girls – are likely to need specific attention having missed out the most.

But while it is therefore vital that schools reopen, the reports also highlight the huge challenges of making schools COVID-safe at a time when access to a vaccine is still, in all likelihood, months away for many teachers and pupils. They point to cases where schools lack soap and running water, for example, and to concerns about the practicalities of social-distancing in overcrowded classrooms.

The surveys were undertaken by members of the Research for Equitable Access and Learning (REAL) Centre at the Faculty of Education, University of Cambridge, in partnership with colleagues at Addis Ababa University and the Ethiopian Policy Studies Institute, as part of the RISE Ethiopia and Early Learning Partnership projects.

School closures are widely understood to have deepened a long-term ‘learning crisis’ in low- and middle-income countries in which many of the least-advantaged children already struggle to attain basic levels of literacy and numeracy. Professor Pauline Rose, Director of the REAL Centre, said: “These reports describe the situation in Ethiopia, but highlight interlocking problems that apply much more widely.”

“In many parts of the world, COVID-19 has not just made it harder to keep children learning: it also makes it harder to keep them in school. There are multiple constraints affecting low- and middle-income countries which mean that the very poorest and most marginalised children are even greater risk of dropping out of the system altogether than they already were.”

Professor Tassew Woldehanna, President at Addis Ababa University, said: “With schools reopening it is essential that policy-makers have access to the sort of clear, robust evidence presented here. It is critical to targeting those pupils who need the most support, and limiting the effects of lost learning for millions of children.”

The team interviewed 443 primary school teachers and principals and 480 parents and caregivers. They also co-ordinated with surveys by the Oxford-based Young Lives programme, who spoke to a further 64 principals.

Their results show that while many teachers have been quick to adapt to remote teaching and learning, students’ access to education has clearly been uneven. In some rural regions, for example, none of the teachers interviewed had internet access and only around half of households had electricity. The researchers estimate that around two-thirds of the teachers they surveyed had reached fewer than half of their students during the closures.

The uneven provision that this implies is likely to have affected disadvantaged groups, such as poorer children, those in rural areas, and girls (whose education is often considered lower-priority than that of boys), most severely. Many teachers fear that, because these groups’ parents often have low literacy, low regard for education, and recruit their children to support the generation of family income; such children are especially at risk of dropping out of school, or of never returning.

The research also draws attention to COVID-19’s impact on pre-primary education in Ethiopia: a sector which has been neglected by many governments during the pandemic. Only 53% of parents or caregivers with young children had been able to engage in learning activities with pre-primary children during school closures. Just 10% reported any contact with pre-primary teachers.

At the same time, however, the reports highlight significant infrastructure and resource challenges within schools themselves. 38% of parents said that their children’s schools were only ‘somewhat equipped’ with handwashing facilities; 22% said that they were ‘not equipped at all’. About 15% said that they did not have facemasks for their children to wear at school, and 46% could not provide their children with hand sanitiser. A majority of teachers and principals, especially those in rural areas, expressed similar concerns about both hygiene, and a lack of adequate classroom space to maintain social distancing.

The researchers stress that despite the efforts made by the government so far, ongoing interventions will therefore be needed to help all children benefit as schools reopen. Their main recommendations are:

  • A targeted, national campaign by government, school management committees and local authorities to keep children in school.
  • Extra support (and, if viable, time in school) for students who need to recover lost learning.
  • The construction of new classrooms or sheltered areas where possible, as well as the targeted supply of extra hygiene resources such as sanitisers, facemasks and handwashing facilities to those most in need.
  • Additional investment in resources and strategies to support remote learning, particularly in the context of further possible outbreaks in schools before the effective delivery of a vaccine.

Both reports are available from the REAL Centre website.

Many schools in Ethiopia lack the hygiene facilities and infrastructure to control COVID-19 effectively, as they reopen for the first time after months of disrupted learning, new research indicates.

COVID-19educationInternational developmentdeveloping worldGlobal SouthAfricaPauline RoseFaculty of EducationSchool of the Humanities and Social SciencesCOVID-19 has not just made it harder to keep children learning: it also makes it harder to keep them in schoolPauline RoseUNICEF EthiopiaAn empty classroom in Haro Huba school, in Oromia region, central Ethiopia.


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Scientists identify warning signs over effectiveness of HIV ‘wonder drug’ in sub-Saharan Africa

Tue, 01/12/2020 - 10:00

As HIV copies itself and replicates, it can develop errors, or ‘mutations’, in its genetic code (its RNA). While a drug may initially be able to suppress or even kill the virus, certain mutations can allow the virus to develop resistance to its effects. If a mutated strain begins to spread within a population, it can mean once-effective drugs are no longer able to treat people.

HIV treatment usually consists of a cocktail of drugs that includes a type of drug known as a non-nucleoside reverse-transcriptase inhibitor (NNRTI). However, in recent years, HIV has begun to develop resistance to NNRTIs. Between 10% and 15% of patients in much of sub-Saharan Africa are infected by a strain of HIV resistant to these drugs. If a patient is infected with an NNRTI-resistant strain, they are at a two- to three-fold increased risk of the drug regimen failing.

In 2019, the World Health Organization began to recommend dolutegravir as the preferred first-line treatment for HIV in most populations. Dolutegravir was dubbed a ‘wonder drug’ because it was safe, potent and cost-effective and scientists had seen no drug resistance against it in clinical trials. However, there is little data on the success of dolutegravir against circulating strains of HIV in sub-Saharan Africa.

In a study published today in Nature Communications, an international team of researchers from South Africa, the UK and the USA examined the genetic code of HIV to determine if drug resistance mutations in 874 volunteers living with HIV affected their treatment success. The individuals were enrolled in a clinical trial for people initiating HIV treatment to compare two drug regimens: efavirenz, an NNRTI and prior first-line therapy in the region, and dolutegravir.

The goal of this study was to determine whether drug resistance to efavirenz prior to starting treatment affected treatment success (suppression of the virus in the blood) over the first two years of therapy with both of these two regimens.

As expected, the presence of drug resistance substantially reduced the chances of treatment success in people taking efavirenz, successfully suppressing the virus over 96 weeks in 65% of participants, compared to 85% of non-resistant individuals. However, unexpectedly, the same pattern was true for individuals taking dolutegravir-based treatments: 66% of those with efavirenz resistance mutations remained suppressed over 96 weeks, compared to 84% of those without the mutations. These relationships held true after accounting for other factors, such as treatment adherence.

“We fully expected efavirenz to be less effective among patients HIV strains resistant to NNRTIs,” said Dr Mark Siedner, faculty member at the Africa Health Research Institute in KwaZulu-Natal, South Africa and Massachusetts General Hospital in Boston, Massachusetts. “What took us completely by surprise was that dolutegravir – a different class of drug which is generally effective in the face of drug resistance – would also be less effective in people with these resistant strains.

“We are working now to tease out if this was due to the virus or the participants – for instance, if people with resistance are less likely to take their pills regularly. Either way, if this pattern holds true, it could have far reaching impacts on our predictions of long-term treatment control for millions of people taking dolutegravir in the region.”

Professor Ravi Gupta from the Department of Medicine at the University of Cambridge said: “This a huge concern. Dolutegravir was very much seen as a ‘wonder drug’, but our study suggests it might not be as effective in a significant number of patients who are resistant to another important class of antiretroviral drugs.”

The researchers say it is not clear why efavirenz-resistant mutations should affect susceptibility of dolutegravir, though one hypothesis is that integrase inhibitors such as dolutegravir push the virus to replicate and mutate faster, in turn developing resistance to the new drug in an evolutionary arms race. Alternatively, it could be due to poor adherence to treatment regimens, even though the analysis accounted for adherence by two independent methods. Further research is needed to find out why.

Professor Gupta added: “What this shows is that we urgently need to prioritise point of care tests to identify people with drug resistance HIV, particularly against efavirenz, and to more closely and accurately monitor treatment adherence. The development of such tests is at an advanced stage, but there a lack of investment from funders and philanthropic donors. We urgently need agencies and individuals to step forward and help support these programmes.

“In addition, we need to provide widespread access to viral load monitoring so that we can find those who are struggling, get them on more appropriate regimens, and limit the emergence of resistance when patients are failing therapy.”

The study was carried out by researchers at: the Africa Health Research Institute, University of KwaZulu-Natal, University of Witwatersrand, KwaZulu-Natal Research Innovation and Sequencing Platform, and the Centre for the AIDS Programme of Research in South Africa (CAPRISA), in South Africa; the University of Cambridge, University of Liverpool, and Imperial College London in the UK; and Massachusetts General Hospital and Harvard Medical School, USA.

The research was supported by USAID, Unitaid, the South African Medical Research Council (SAMRC), with investigational drug donated by ViiV Healthcare and Gilead Sciences, and by Wellcome and the National Institutes of Health.

Reference
Siedner, MJ et al. Reduced efficacy of HIV-1 integrase inhibitors in patients with drug resistance mutations in reverse transcriptase. Nat Comms; 1 Dec 2020; DOI: 10.1038/s41467-020-19801-x

Dolutegravir, the current first-line treatment for HIV, may not be as effective as hoped in sub-Saharan Africa, suggests new research published on World AIDS Day. The study finds that this so-called ‘wonder drug’ may be less effective in patients resistant to older drugs.

Infectious diseasesdrug resistanceGlobal SouthRavindra GuptaUSAIDWellcomeSouth African Medical Research CouncilUnitaidNational Institutes of HealthSchool of Clinical MedicineDepartment of MedicineCambridge Infectious DiseasesDolutegravir was very much seen as a ‘wonder drug’, but our study suggests it might not be as effective in a significant number of patients who are resistant to another important class of antiretroviral drugsRavi GuptaJon RawlinsonKnow your HIV status sign in Africa


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‘Spill-over’ effects show hidden value of prioritising education of poorest children and marginalised girls

Fri, 20/11/2020 - 10:11

The newly-reported study, by academics at the University of Cambridge, is one of the first to measure the complete value that interventions targeting poor and marginalised children also have for many of their peers, principally through ‘spill-over’ effects which improve the wider education system.

The team tested their model by analysing a programme by CAMFED (the Campaign for Female Education) in Tanzania, which supports the education of disadvantaged girls. They took into account its impact not just on those girls, but on other children at schools where their programme operates. Strikingly, for every $100 spent per girl, per year, the programme resulted in learning gains equivalent to an additional two years of education for all girls and boys at those schools.

The study was carried out by members of the Research for Equitable Access and Learning (REAL) Centre at the Faculty of Education, University of Cambridge.

Professor Ricardo Sabates, the co-lead researcher, said: “Helping the most marginalised children inevitably costs more, and most cost-effectiveness measures only consider that expense against the impact on those specific pupils. But programmes like CAMFED’s also have spill-over benefits and critically are keeping girls in school who would otherwise have dropped out. We can, and should, factor in those considerations when assessing cost-effectiveness.”

Professor Pauline Rose, Director of the REAL Centre, added: “While it may cost more to reach the most marginalised pupils, the impact of those efforts is far more impressive than we tend to imagine. This research explains why system reforms should focus on those who need the most support. Education systems that function for the most marginalised children function for everyone.”

CAMFED is a non-governmental organisation which improves the education of marginalised girls in Africa and was recently awarded the 2020 Yidan Prize for Education Development. In Tanzania, its bursaries enable thousands of girls to attend secondary school, in tandem with interventions aimed at improving participation and learning among all children in partner schools.

Because most cost-effectiveness analyses only measure the impact of a programme on its direct beneficiaries (in this case marginalised girls), interventions such as CAMFED’s often seem to have limited reach while at the same time appearing more expensive than those targeting a broader demographic. The Cambridge study examined how best to measure the wider impact of CAMFED’s work in Tanzania, and then used this to refine the cost-effectiveness analysis.

The researchers analysed data from CAMFED’s programme over two years. To calculate per-head costs, they distinguished between the different components of the intervention and their assorted beneficiaries. For example, the cost of bursaries was divided by the number of marginalised girls who received them, but the cost of delivering extra-curricular courses in CAMFED-supported schools was divided by the number of all participating students. This provided a basis for identifying average annual unit costs for individual categories of beneficiaries.

Impact was calculated by comparing the English test scores of children from 81 randomly-selected CAMFED-supported schools with children from 60 control schools that received no support. Scores were collected at the start and end of the two years, and the team used data about the children’s socio-economic background to make direct comparisons between pupils from similar settings.

They also compared the dropout rates at both groups of schools, and used this to weight the final cost-effectiveness analysis. This reflected the fact that CAMFED’s programme not only improves learning, but also supports girls who might otherwise have dropped out of school, or never attended at all.

The cost of the programme, when only the most marginalised girls targeted by the bursaries were considered, was apparently steep: at $130.41 per year for each girl receiving financial support. However, the researchers also found that the per-head cost for other boys and girls at the same schools was just $15.40, demonstrating far greater value for money overall. The additional cost of the bursaries was also found to be vital for enabling the most disadvantaged girls to stay in school.

Pupils attending CAMFED-supported schools made significant academic improvements compared with their peers. The improvement in English test scores among girls receiving financial support was about 35% better than comparable girls in the control group. But other girls also performed similarly, while the boys did about 25% better. Girls who received financial support were 25% less likely to drop out of school than those in the control group.

The researchers then calculated the learning gains of pupils on the CAMFED programme per unit cost. When this measure was converted into equivalent years of learning, they found that for every $100 spent on each of the marginalised girls targeted, English learning outcomes improved by the equivalent of an extra 1.45 years of schooling for all pupils. When the increased proportion of marginalised girls remaining in school was factored in, the improvement in both access and learning for all girls and boys across the CAMFED schools was actually equivalent to an additional two years of schooling per $100.

While it is difficult to compare these results with other programmes, the study suggests that the cost-effectiveness of CAMFED’s work in Tanzania is at least commensurate with similar interventions in sub-Saharan Africa that do not target marginalised groups. But the findings may also be conservative. For example, CAMFED’s programme may also have further benefits outside the school system, for example among the siblings and communities of the young women it supports.

“Even though we probably underestimated its impact, this intervention is still extremely cost-effective,” Sabates added. “It shows real improvements in learning are best enabled when we invest in the children at greatest risk of being left behind.”

The research is published in the Journal of Development Effectiveness.

Development projects that target the education of the world’s very poorest girls also significantly improve other young people’s attainment, according to new research that suggests such initiatives should become a priority for international aid.

Africaeducationdeveloping worldGlobal SouthRicardo SabatesPauline RoseCamfedSchool of the Humanities and Social SciencesFaculty of EducationReal improvements in learning are best enabled when we invest in the children at greatest risk of being left behindRicardo SabatesCAMFED/Eliza PowellSophia (right), a CAMFED Learner Guide, with secondary student Hanipha, who she supports at school in Morogoro, Tanzania


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Enterprising researchers: Making a difference in Southern Africa

Thu, 15/10/2020 - 11:50
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Making a difference in
Southern Africa

Gaborone, Botswana. Credit: Eddie Chuan-Shun Ho, Wikimedia Commons

Gaborone, Botswana. Credit: Eddie Chuan-Shun Ho, Wikimedia Commons

Around 20,000 people in Botswana are hearing impaired. With little support, they struggle to access critical services such as healthcare and banking. Many are unable to cast their vote. Children, who account for more than half of the deaf population, often fail to receive even a basic education and thus have their life chances limited from the start.

This is something aspiring tech entrepreneur and ICT Associate at the Botswana Institute for Technology Research and Innovation (BITRI), Lucia Otsetswe-Moapare wants to change. Her solution is a mobile app which both teaches sign language and translates it and which she hopes will be adopted by schools, banks and hospitals to deliver services to this disenfranchised community.

In 2019, Otsetswe-Moapare was one of 17 entrepreneurial researchers from three southern African universities taking part in a knowledge exchange programme with the University of Cambridge.

Supporting entrepreneurship

Tech entrepreneur Lucia Otsetswe-Moapare

Tech entrepreneur Lucia Otsetswe-Moapare

In 2018, six of the world's top 10 fastest growing economies were in Africa. 2019 saw an 11 per cent increase in foreign investment across the continent.

An article in The Economist, published at the end of March, gave further (pre-COVID) grounds for optimism about the continent's economic trajectory pointing, amongst other things, to "the emergence of a start-up culture. Last year [2019] venture-capital funds invested about $1.3bn in new African firms, an increase of more than 600% over the $200m invested in 2015."

The pandemic has brought an abrupt and devastating halt to any further progress, with the UN warning that it will disproportionately affect the world's poorest nations.

But back in 2019, when what The Economist was calling a "start-up boom" had started to gain ground and coronavirus was on no one's radar, researchers and knowledge exchange professionals from Cambridge and three southern African universities took part in a remarkable back-and-forth set of visits.  

According to BITRI’s Director of Partnerships, Bathsheba Mbongwe, the idea for this programme germinated when Cambridge researchers visited BITRI in 2018. They started to talk about "the need for universities to work in partnership with local industry in order to achieve societal impact" and about how best "to establish academia-industry innovation ecosystems."

At around the same time, the University of Namibia was developing its vision for the future, with innovation, enterprise and community engagement firmly at its heart. Lúrio University (Unilurio), a technical university in the north of Mozambique, was similarly tasked with increasing the number of entrepreneurs emerging from its portals.

From these converging conversations an ambitious knowledge-exchange programme emerged, involving more than 50 participants and 10 institutions.

What do we mean by “knowledge exchange”?

Definitions vary, but in essence, it is about sharing knowledge developed inside universities with communities outside those universities. “Knowledge” is broadly defined to include ideas, information, skills and experiences. The “exchange” part is critical: this is not a one-way process, but is designed to bring insights from outside the university back in. Its goal is to create or expand the impact university-devised knowledge has on the world.

This particular programme had three main aims. The first was to share Cambridge's experience and expertise with the three Southern African universities as they build their capabilities to commercialise their own intellectual property.

The second was to identify areas for ongoing research collaboration between the universities in areas which will have significant and lasting impact. And the third was to help Cambridge evolve the support it offers to other universities looking to maximise the impact of their research.

“It was a fantastic opportunity for us to work closely with our knowledge exchange and technology transfer counterparts in Southern Africa.

The insights we gained from the experience will inform our training and capability development activities so that we can continue to offer targeted and effective support to our many university partners."Iain Thomas, Head of Life Sciences, Cambridge Enterprise Exchanging knowledge

At the heart of the programme were the 17 impressive examples of entrepreneurship - including Otsetswe-Moapare's - already underway in Botswana, Mozambique and Namibia.

They were presented at the first workshop in Botswana where Cambridge experts were on hand to share their knowledge of research commercialisation. Alongside researchers in topics such as innovation management, intellectual property and industrial sustainability were a team from Cambridge Enterprise, the University’s technology transfer arm, with a wealth of experience in commercialising intellectual property.  

As well as looking at how each of the entrepreneurs could improve their own chances of success, the group also considered the “innovation ecosystem” and the critical role policymakers, universities and businesses need to play in it in order to create a thriving entrepreneurial community.

Although the Cambridge context is clearly very different to the African one, hearing how the Cambridge Cluster has evolved into one of the world’s most successful innovation ecosystems offered some useful insights.

For João Salavessa, founding Director of the Faculty of Social Sciences and Humanities at Unilurio in Mozambique, the Cambridge story gave them, “lots of new ideas which is important for us right now. We need more entrepreneurs and we have a lot of opportunities. If our students can develop their ideas and work for themselves, it is a benefit both for them and for the whole country."

For the 17 entrepreneurs the next stage was a visit to Cambridge for some practical workshops covering topics such as how to develop a business plan, how to carry out and benefit from market research and how to make a compelling pitch to potential investors.

"The partnership with Cambridge was an eye-opener in how to engage with industry." Dr Bathsheba Mbongwe, Director of Partnerships, BITRI

For Otsetswe-Moapare, currently exploring partnerships with Botswana’s Ministry of Education, banks and hospitals to support the take-up of her app, "the programme was perfect timing for me as I was just at the commercialisation stage. I learnt a huge amount but the two things that really changed my approach were understanding the importance of market research and that negotiations are all about building long-term relationships."

Food security and pigeon peas in Mozambique

Pigeon peas. Credit: www.uniprot.org/

Pigeon peas. Credit: www.uniprot.org/

In Mozambique, Ramula Issa, a researcher at Unilurio, is also committed to making a difference to people's lives.

Food security remains one of the most pressing challenges in sub-Saharan Africa. Pigeon peas (Cajanus cajan) could be part of the solution. They are already an important source of protein and micro-nutrients for many Mozambicans but a lack of processing technologies means that much of the harvest is often wasted.

Until her project was put on hold by the coronavirus, Issa had been exploring how to turn her PhD in nutrition into a business. Her goal is both to help farmers better preserve the harvest and its nutritional composition using new technologies, processes and packaging and also to create a new range of pigeon pea-based products - such as cookies - which would be affordable and appetising, have a long shelf-life and a high nutritional value.

Her trip to Cambridge proved to be an important catalyst: "When I was researching, I was only thinking about the research. Experts from Cambridge not only showed me it was possible to create a business but gave me the skills to go about it."

There's still much to be done and Issa is looking forward to restarting the project as soon as she can. "Food security is such a big problem. We need to make sure that the research we do makes a difference."

The importance of listening

Dr Bathsheba Mbongwe, Botswana Institute for Technology Research and Innovation (left) and Dr Sara Serradas Duarte, Cambridge Global Challenges

Dr Bathsheba Mbongwe, Botswana Institute for Technology Research and Innovation (left) and Dr Sara Serradas Duarte, Cambridge Global Challenges

The success of the programme has been recognised by the UK's leading professional body for knowledge exchange practitioners. Earlier this year, it was awarded the prestigious PraxisAuril UKRI Team of the Year 2020 Award.

Dr Sara Serradas Duarte from Cambridge Global Challenges, the driving force behind the initiative, said: "The two aspects of this programme that were fundamental to its success were listening and jointly learning.

"The starting point was the needs of the institutions in southern Africa but as a result of the projects all of us in Africa and the UK have become better equipped to deliver knowledge exchange and to collaborate on new research."

But winning an award is by no means the end of the story. Research collaborations between the universities are progressing in areas such as microbial and electrochemical energy production systems and medical sterilization and water remediation.

The participating universities are putting in place mechanisms to support research commercialisation. Unilurio, for example, has set up CADI, the Centre for Academic Development and Innovation, to deliver its own entrepreneurship training and a knowledge-exchange Agribusiness Unit in conjunction with the Mozambique government and with funding from the African Development Bank.

Unilurio is also using its new expertise to forge stronger connections with big business - an important component in any successful ecoysystem.

"There is currently a gap between the universities and companies, mostly because of a lack of trust and a lack of awareness about what we are doing. We need to change that and find ways of working with each other. It's really important that the big companies hire local people," said Salavessa.

In November 2019, in partnership with the Cambridge Global Challenges team, Unilurio delivered three workshops designed to persuade industry and government that they need to work with their local universities which, said Salavessa, "were an important starting point in making that happen."

As all countries face the daunting task of rebuilding their COVID-ravaged economies, it is now more important than ever that universities are able to turn their research into economic and social value. In Botswana, Mozambique and Namibia, that means supporting inspiring young entrepreneurs like Issa and Otsetswe-Moapare as they pursue their dreams of improving the lives of the people around them.

This pioneering programme has helped to strengthen the entrepeneurial capabilities of three southern African universities. It has also helped Cambridge develop the support it is able to give to other universities wanting to do the same. That sounds like a productive exchange of knowledge.

Cambridge Global Challenges is the Strategic Research Initiative of the University of Cambridge that advances the contribution of its research towards addressing the United Nations' Sustainable Development Goals in the Global South. 

Cambridge Enterprise, part of the University of Cambridge, supports academics, researchers, staff and students in achieving knowledge transfer and research impact. Liaising with organisations both locally and globally, its offer expert advice and support in commercialisation and social enterprise. 

TopBuilt with Shorthand Summary: 

An award-winning team from Cambridge, Botswana, Mozambique and Namibia has been bolstering entrepreneurship in Southern Africa and supporting some exciting new ventures along the way.

Image: Affiliation (schools and institutions): Cambridge Global ChallengesCambridge EnterprisePeople (our academics and staff): Sara Serradas DuarteIain ThomasSubject (including Spotlight on ... where applicable): AfricaBotswanaMozambiqueNamibiaGlobal SouthSection: ResearchNews type: Features
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Welcome to Cambridge Global Challenges

Cambridge Global Challenges is the Strategic Research Initiative (SRI) of the University of Cambridge that aims to enhance the contribution of its research towards addressing the Sustainable Development Goals (SDGs) by 2030, with a particular focus on the poorest half of the world’s population.

 

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Research Strategy Manager (Dr Sara Serradas Duarte): coordinator@gci.cam.ac.uk​.