A South African innovation designed to detect inflammation related to HIV infections and women’s sexual and reproductive fitness has been the subject of its first clinical studies. Almost 700 women will participate in the validation of genital inflammation control (GIFT) evolved at the University of Cape Town (UCT).
Almost 700 will participate in the validation of genital inflammation control (GIFT) developed at the University of Cape Town (UCT).
GIFT is a foreign collaboration composed almost exclusively of scientists led by UCT Professor Jo-Ann Passmore and Dr. Ann Ann Passmore. Lindi Masson, from UCT but now from the Burnet Institute in Australia. The progression of the trial includes a partnership with Cape Town biotech company Medical Diagnostech under the leadership of Ashley Uys and Lyndon Mungar.
GIFT is a rapid and affordable test to detect vaginal inflammation, one of the main sources of HIV risk in young women. It is caused by sexually transmitted infections (STIs) and bacterial vaginosis.
These situations can often be treated with antibiotics, but since most women have no symptoms, they go undiagnosed and untreated. And that’s where the developers of GIFT believe the test could fundamentally change the landscape.
Clinical studies in South Africa, Zimbabwe and Madagascar are a key step in verifying the functionality of the lateral test, which uses highly sensitive antibodies to identify biomarkers of inflammation, even when given in amounts of a few trillionths of a gram (picograms).
Once the effects of the studies have been analysed, the GIFT device will be finalised and registered with an investment from the Technology Innovation Agency and the South African Medical Research Council (SAMRC). Then it will be in commercialization.
“It is essential to develop effective tactics to address the threat of HIV among women in South Africa. Given that a significant proportion of [HIV’s] threat comes from undiagnosed but treatable STIs, greater STI control through inventions like GIFT is urgently needed,” Passmore said.
inflammatory enemy
The roots of GIFT lie in finding that South African women with asymptomatic STIs and bacterial vaginosis (a disruption of healthy bacterial communities) had degrees of vaginal inflammation compared to women with symptoms.
This is concerning because inflammation facilitates HIV infection. If left untreated, it can also lead to pelvic inflammatory disease, premature birth, damage to the fallopian tubes, scarring of the reproductive tract, and infertility.
“Treatable STIs and bacterial vaginosis are very common in South Africa and other resource-limited countries, and we found that while most women have symptoms, only women with symptoms receive treatment,” Masson said. “In fact, etiological testing is too expensive to implement in those settings. “
In order to arrive at a cheap diagnosis, the GIFT team began by identifying and comparing biomarkers of inflammation. He then resorted to the progression of a device to measure biomarkers.
Dr Monalisa Manhanzva, who leads the GIFT project, and Dr Fezile Khumalo, who is building UCT’s Centre for Translational Research, contributed to the creation of the device.
“The progression of the GIFT device has been challenging because biomarkers of inflammation are provided in the vagina at very low concentrations (picograms),” Manhanzva said.
“Our project is to identify antibodies that can stumble upon those incredibly low concentrations and give a visual result with the naked eye. This led us to read meticulously about thousands of other antibody combinations.
Khumalo added: “The good thing about the innovation is its simplicity in testing for inflammation and interpreting the results. We use an undeniable approach with popular parts to keep prices low and usability. This informed our product profile, facilitating progression and production for the clinical study. .
“It’s really just a popular side test, but one that can detect very small amounts of inflammation. Once we discovered the right antibodies sensitive enough, it was relatively undeniable to do the rest and do it correctly.
Passmore said: “Measuring those biomarkers in vaginal patterns is a completely different challenge. Vaginal patterns are confusing: mucus is not our friend. We had to find cutting-edge tactics to ensure reliable detection of biomarkers, regardless of pattern matrix.
Covid to the rescue
The team’s next challenge is to create a method suitable for low-resource settings to find a way to process vaginal swab samples as simply as possible.
“We usually use a vortex for the samples in the lab and extract all the samples from the vaginal swab,” Masson said.
“For this, we have learned from the Covid-19 pandemic, which has used approaches to manually treat nasal swabs. Micaela Lurie, whose PhD co-supervised with Jo-Ann, showed that if we used flexible tubes, we could simply squeeze the “We ran a swab through the tube between our hands and wrung it out effectively, and it worked even better than our popular lab treatment methods. “
When it came time to produce theArray, the GIFT team forged what Masson called a “unique partnership” with Medical Diagnostech, a developer and manufacturer of lateral flow kits.
“The work done at UCT to identify biomarkers of GIFT allocation allowed us to optimally expand a product for clinical trials in a short period of time. These collaborations aim to maximize the commercialization of quality products, the first in the world,” said Uys of Medical Diagnostics.
This public-private partnership is due to intellectual and privacy issues, Masson said. But the company “allowed our UCT students and postdocs to work in their labs, along with their staff, for most of the device progression process. “
Khumalo said, “This meeting of minds allowed us to push the progression process forward and share our experiences. Educational and business perspectives have been invaluable to our ability to move to this stage.
Initiation of validation studies
The control kits were sent to clinical sites at the Desmond Tutu Health Foundation Youth Centre in Masiphumelele, Cape Town, the Spilhaus Clinical Research Site in Harare and the Befelatanana University Hospital of Gynecology and Obstetrics in Antananarivo.
Masson said 225 women will participate in the on-site screening, with two tests for patients: one administered by a nurse and the other by a lab technician.
“At the same time, we compare the stability of the devices under certain conditions. “
Clinical study data will measure the accuracy of the GIFT device; its functionality compared to existing popular care: syndromic control that overlooks most cases of situations causing inflammation (STIs and bacterial vaginosis); and the acceptability, feasibility and cost-effectiveness of the tests. Sensitivity research will be conducted in subgroups of patients with different disease severity.
This painting is achieved through key partnerships with GIFT team members of:
“It’s vital for us to examine the effects of GIFT on the women who helped us test the device [by participating in clinical trials] and in the broader communities where the studies were conducted,” Passmore said.
“The willingness of women in South Africa, Madagascar and Zimbabwe to marry us by donating vaginal samples to allow us to expand the device makes this a true collaboration. We co-expanded the device with the women who participate.
Next steps
The GIFT team obtained an investment from the Technology Innovation Agency to finalize and sign the device, as well as conduct pre-market testing. SAMRC’s investment will enable a simplified clinical trial for device registration.
Masson said UCT’s fitness economics unit is conducting a load effectiveness analysis of GIFT. “Our purpose is to keep the charge of the device as low as possible and we have several methods to achieve this. “
Passmore said: “Antibodies are at the expense of the device itself, so we make our own antibodies. “
Masson said previous studies on the effectiveness of charges conducted by the Health Economics Unit showed that fitness painters’ salaries had the highest implementation-related charge.
“Self-diagnosis can overcome this obstacle, so we are also exploring this approach. “
The final step will be to commercialize GIFT, and Masson and Passmore hope the device will continue to be manufactured in South Africa.
“It is vital to expand capacity and invest in human capital in Africa, to test in Africa for Africa. This has been a key point of our work,” Passmore said.
Clinical studies are a key milestone in GIFT’s journey, but Masson said they remain at the core of the mission.
“We know from previous studies that rates of STIs and bacterial vaginosis are high in South Africa if controlled (up to 70%) and yet most women go undiagnosed. The social and economic burden is enormous, but until there are cheap functions to address it, the prevalence will remain maximum.
“The progression adventure for a new controller is demanding. It takes determination, flexibility and determination to cope with the ever-changing demanding situations in the healthcare sector,” Manhanzva said.
“Success is achieved through teamwork and partnerships with experts in other fields, all working in combination to overcome barriers and promote innovation. “
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