Translating research into an STI diagnostic designed for African women
In this series, we are highlighting some of our Africa-Oxford Health Innovation Platform (AfOx-HIP) Fellows. Each one is an outstanding African innovator building a high-growth, science-based venture to address pressing health challenges in Africa. We spotlight how they are developing bioscience start-ups in nascent deep science ecosystems, and how nurturing translational research on the continent is central to offering commercialisation pathways for these impact-led solutions.
The Context
Fezile Khumalo (PhD) is a Carnegie Junior Research Fellow in the Faculty of Health Sciences’ Institute of Infectious Disease and Molecular Medicine and Department of Pathology: Division of Virology at the University of Cape Town (UCT) and was an Africa Oxford Health Innovation Fellow in 2023. She is establishing a translational platform within UCT to move more discoveries towards specific diagnostic applications. She is organising resources and expertise to build appropriate prototypes, ensure appropriate use of diagnostic platforms and capture clinical know-how to ensure the diagnostics are appropriate for healthcare settings across Africa. She has experience in the advancement of proof-of-concept studies for potential commercial application of diagnostic tools.
As part of the GIFT team, Fezile is developing a point-of-care lateral flow test to enable screening of BV and STI in asymptomatic women in Low- and Middle- Income Countries (LMICs).
The Problem
Approximately 377 million new cases of the four most common Sexually Transmitted Infections (STIs) were documented in 2020. Over 70% occurred in low- and middle-income countries (LMICs). Existing initiatives are not reducing the number of new infections. Due to anatomical and immunological differences, women are more susceptible to STIs than men and endure longer-lasting consequences.
The composition of the vaginal microbiome plays a crucial role in women’s sexual and reproductive health. Various genetic, behavioural, and environmental factors alter the composition and can lead to bacterial vaginosis (BV). In Sub-Saharan African populations, prevalences of BV are notably high at around 33%.
Both STIs and BV are also associated with other serious sexual and reproductive health complications, especially higher risk of HIV acquisition, and can lead to infertility, ectopic pregnancy, preterm delivery, maternal and neonatal sepsis, and pneumonia. Prompt diagnosis and accurate treatment reduces both STI transmission and infection progression, but currently only symptomatic patients receive care.
The Solution
Nearly 2000 combinations of antibodies were tested to choose the final six which are used in the prototype point-of-care lateral flow test to enable diagnosis of BV and STI in asymptomatic women.
The GIFT test is being developed in line with the ASSURED criteria set out by World Health Organization (that point-of-care diagnostic tests should be affordable, sensitive, specific, user-friendly, rapid, robust, equipment-free, and deliverable to end-users). To develop the prototypes, GIFT worked with a commercial partner, who are likely to become the manufacturing partner.
The Funding
The South African Medical Research Council has financially supported this work since the beginning and continues to support the next phase of the project. The Technology Innovation Agency (TIA) are funding the pre-commercialisation work to get a diagnostic into the market, including the upcoming registration trial. This is part of the Bio-economy Strategy, a national initiative in South Africa which aims to promote and harness bio-innovation for economic growth and social development.
The first-in-field study is supported by the EDCTP, a public-public partnership between countries in Europe and sub-Saharan Africa, funding clinical research for medical tools to detect, treat and prevent poverty-related infectious diseases in sub-Saharan Africa.
Four of the five work package leads are women, meaning this project is an opportunity for women passionate about improving women’s health to develop their technical, commercial and leadership skills. This team illustrates the power of collaborative research and venture building within Africa to advance scientific research for the benefit African populations.
The Clinical Evidence
In June to December 2023, GIFT conducted a study in three African countries (South Africa, Zimbabwe, and Madagascar) to evaluate the performance of the first-in-field GIFT prototype devices. The study assessed the sensitivity and specificity of the GIFT devices at the point-of-care for non-pregnant, sexually active women aged 18–35 years accessing family planning services. 675 women were enrolled in the study. ELISA analysis of the 800 swabs for comparison to the point-of-care tests is still ongoing in South Africa, so the results are not yet known.
Prior to study initiation, advice was sought from local Community Advisory Boards on the material to be shared with potential study participants, especially regarding the language to use on the questionnaires for behavioural and other sensitive questions.
The Technology
The GIFT device is based on a method for using cytokines patented by Dr Lindi Masson and Professor Jo-Ann Passmore (Principal Investigator in the HIV Mucosal Immunology group at University of Cape Town, Institute of Infectious Disease and Molecular Medicine and National Health Labortaory Service) as a “Method for diagnosing an inflammatory condition in the female genital tract” in October 2014.
For ten years, Dr Lindi Masson (now Senior Researcher at the Burnet Institute in Melbourne, Australia) has been studying the factors that contribute to higher acquisition of HIV, especially in women. People are 2-3x more likely to contract HIV if they have genital inflammation caused by STIs and BV. Through study of proteomics and the microbiome, she found that genital inflammation is marked by increased local production of pro-inflammatory cytokines and chemokines, irrespective of whether the patient displays symptoms. With her colleagues, she identified 10 possible biomarkers and has since studied three clinical cohorts looking for the same signals, leading to the founding of GIFT.
The Future
The GIFT team is now developing the Target Product Profile (TPP) of its diagnostic. The World Health Organisation does not have a TPP for inflammation, so GIFT must develop their own.
The device works brilliantly under lab conditions, but it needs to work as efficiently in the healthcare ecosystem. One of the aims of the clinical study was to assess how healthcare workers and patients interact with the devices. AfOx-HIP has encouraged Fezile to use design thinking approaches to identify possible routes for integration into routine care. GIFT aims for the test to become standard-of-care for all women seeking family planning services, so they can reach and treat a large number of asymptomatic women.
GIFT is working with the South African regulatory authority and preparing for a registration trial. To build enough prototype devices for this trial, GIFT need access to commercial antibodies, but the cost per device is significant. The antibodies must be stable enough not to degrade during transportation to rural areas and storage in medical facilities before they are used. Fezile is considering alternatives to their current suppliers of traditional antibodies but also considering alternative technologies for biologicals required for POC immunoassay development and hopes to discuss her ideas on this topic with collaborators in the AfOx network.
Learn more about other successful AfOx Innovation Fellows here