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Case study: Early diagnosis of lymphoma in children and young adults in sub-Saharan Africa

 

Two innovative tools to speed-up diagnosis

Over 90% of children in the world with lymphomas are from sub-Saharan Africa, with these cancers caused by Epstein-Barr virus (EBV) infections, malaria and HIV. 

Although lymphomas are easy to treat and the therapy is free of charge, most patients are either diagnosed late, at which point the cancer is more difficult to treat, or remain undiagnosed. This is due primarily to the lack of reliable diagnostics services with enough surgeons and pathologists to establish the precise diagnosis fast enough.

With their NIHR Research and Innovation for Global Health Transformation award, Professor Anna Schuh from the University of Oxford, with teams in Tanzania and Uganda led by Dr Clara Chamba (Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam), Dr Faraja Chiwanga and Dr Hadija Mwamtem (Muhimbili National Hospital (MNH), Dar es Salaam), Dr Mkwizu (Kilimanjaro Christian Medical Centre (KCMC), Moshi) and Dr Ogwang (St Mary’s Hospital, Lacor), are testing two new diagnostic technologies that can help provide a fast and reliable diagnosis of lymphoma in sub-Saharan Africa

The aim of this programme is to improve and speed-up the diagnosis of a particular form of childhood cancer that is very common in sub-Saharan Africa, because it’s caused by a combination of malaria and EBV infections very early in childhood
Professor Anna Schuh, University of Oxford

The first diagnostic technology takes pictures of tissue biopsies with a small and affordable mobile camera that can be attached to any microscope. These pictures can then be sent anywhere in the world for a diagnosis. It means that fewer local pathologists would be required for diagnosis, which would make a huge difference in remote places. 

The team are now in the process of validating this low-cost and low-maintenance technology, and enhancing local pathology services by making sure they have the immunostaining technology they need for the biopsy process, and that they can do second reviews.

The second diagnostic technique is a liquid biopsy, a simple blood test that can measure circulating tumour DNA (ctDNA) to make the diagnosis of cancer. The team has now developed this non-invasive technology specifically for the EBV-related lymphomas in sub-Saharan Africa, but plan to use it for other cancer screenings across Africa in the future. 

They’ve started to engage with representatives of the Ministry of Health in Tanzania and Uganda and with the director of the Central Public Health Laboratory in Kampala. This will open a path to offering the test to all children in Uganda, thereby introducing testing of ctDNA for the first time to Africa.

This research will provide a sound basis to expand the application of this innovative technology to other cancer screenings. So the aim is not just to improve the diagnosis for these children, but also to build capacity so that DNA-based cancer diagnostics can be used across the board in sub-Saharan Africa.
Professor Anna Schuh

Building clinical research capacity

As part of their project, the team have built up existing pathology services at MNH, St Mary’s Lacor Hospital and at KCMC with automated equipment for immunohistochemistry and second-generation digital image analysis to increase speed and improve reproducibility and quality of testing.

In close collaboration with MUHAS, they equipped a DNA laboratory for local DNA sequencing, cloud-based data analysis and clinical data collection. And efforts are underway to build additional capacity for a DNA sequencing laboratory in Uganda, in partnership with the Central Public Health Laboratory. This will further expand in-country capacity to analyse blood samples for ctDNA, but also to create capacity for other genomic research and diagnostics, for example of infectious or inherited diseases.

The project is one of the first to perform human-genome sequencing in East Africa and to analyse samples in the country. 

Previously we’ve been forced to ship samples abroad for sequencing because we did not have the capacity.  Being able to generate our own sequence data from our samples and being able to analyse them is one of the things I consider as a major achievement in this project
Dr Clara Chamba, Principal Investigator, MUHAS

In the last year, the teams from Oxford and MUHAS have been busy training staff in different disciplines, from bioinformatics to quality control, both with online workshops, and face-to-face sessions in Dar es Salaam in Tanzania.

Ismail Legason, Laboratory Scientist at St Mary’s Hospital Lacor, recognises the learnings from the project: “This study has built my capacity in molecular diagnostics. I’ve had the opportunity to learn Omics techniques, including DNA extraction, library preparation, sequencing and analysis of genomic data.”

Dr Faraja Chiwanga, Head of Training and Research at MNH, has been designated as Research Capacity Strengthening Lead for the team. 

I’ve managed to properly maintain site files for this project, and I’m now training other Principal Investigators about it. I’ve started developing a Quality Assurance Plan, which didn’t exist before, and I’m being mentored on how to improve infrastructure for clinical trials including establishing a Clinical Trial Unit”. 

The project has created about 30 jobs, including for doctors, nurses, bioinformaticians, students, PhDs and MScs in health economics, biology and oncology, who are all based locally. The team also aims to develop online teaching material and support for an MSc in bioinformatics that will be open to students across East Africa.

Raising awareness and providing a cost-effective treatment

The main research site in Northern Uganda is based at the border with South Sudan, where there is one of the biggest refugee camps world-wide. Here, diseases such as malaria and EBV-virus infections are much more common, and therefore lymphomas are more likely to present themselves. 

Since healthcare workers don’t know about our research site and about our programme, I spent 2 weeks in Northern Uganda going around the refugee camps, the various health centres, to raise awareness, and we’re continuing to do this work so everybody knows that we can treat children with lymphomas” says Professor Schuh.  

They have recruited 137 patients with suspected lymphoma so far. These are all receiving a precise pathology diagnosis, and patients with Burkitt’s lymphoma or other types of B-cell lymphoma have received state-of-the-art treatment with chemotherapy and a more targeted therapy called rituximab.

We’ve managed to negotiate the price for rituximab with Roche to a GDP-adjusted value, so we’re able to provide the treatment to all our patients. Now we’re at the point where we’re already giving rituximab to children at MNH and KCMC, and we’ll start very soon in Uganda
Professor Anna Schuh

They’re also working with local charities, Tumaina la Maisha, Solitere and Prev-A Camp, to raise awareness about cancer early diagnosis. 

Thanks to these collaborations, they’ve been able to reach out to over 5,000 people and many more through social media feeds, radio announcements and a song.

Professor Schuh is confident that by enhancing the local capacity, but also by creating a strong sense of collaboration, and with the right support from local governments, they’ll be able to secure sustainability for genetic diagnostics that will save the lives of thousands of children and young adults in the region.

“We have created a spirit of collaboration and equality that goes beyond research for EBV-driven lymphoma”, she says. “Clinicians, oncologists, bio-informaticians, health economists, lab researchers, diagnosticians, pathologists, we’re all working together and we’re sharing knowledge everywhere we’re working, and that touches every cancer patient, children and adult, the whole ecosystem of cancer services across two countries.”