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From fundamental science to practical implementation, work on diagnostics that can reliably detect diseases in the developing world is among the most important gaps in medicine — and among the most challenging to fill.
The first stumbling block is basic science. The most recent outbreak of Ebola in west Africa highlighted some of the difficulties. Despite a surge in international activity to help treat the infection, there were no practical, rapid or consistent tests to confirm the disease. There were also considerable dangers in shipping dangerous samples to remote central laboratories for study.
The latest annual survey by G-Finder, a research group, of total research and development funding for neglected diseases in 2014 shows that less than 6 per cent went to diagnostics.
Private sector research is modest, since even in richer countries diagnostic companies are often the poorer orphan to drug companies. Development can be costly, slow and uncertain, pricing is relatively low and product life cycles short. Government donors and philanthropic and product partnerships such as Path and the Foundation for Innovative New Diagnostics seek to respond with limited resources.
There has been considerable progress in diagnoses for some diseases. For HIV, simple and cheap blood tests now confirm cases of the virus in the most remote and poorest areas of the world. Yet more sophisticated tests — such as the simple amplification-based assay (or Samba) system, developed by Dr Helen Lee and a team at Cambridge university’s Diagnostics Development Unit — are needed for effective clinical management. The Samba test, for example, flags up whether newborn children of mothers with HIV are infected and tracks progress in patients who are already on treatment.
In tuberculosis, the introduction of tests — led by Cepheid’s GeneXpert molecular polymerase chain reaction system — has marked important progress. Smear microscopy, developed more than a century ago, is very slow and unreliable, notably for detection in children.
That raises a second concern: the ability to implement innovations in the field. GeneXpert remains too sophisticated and expensive to be distributed at primary healthcare centres. Access to suitably trained staff and mechanisms to share diagnoses rapidly with patients and healthcare workers remain bottlenecks.
“The problem is to have diagnostics adapted to the reality of low-income settings, where laboratory infrastructure is pretty poor,” says Martina Casenghi, TB diagnostic adviser for the access campaign of Médecins Sans Frontières, the health charity. “We need tools that are affordable and adapted to field conditions, where it is hot, humid and dusty and there is no electricity or clean water.”
A third issue is broadening the range of diseases for which diagnostics have been developed. Cheap, reliable and rapid tests for malaria have improved confirmation of the parasite radically, at least for the most dangerous falciparum type. But they have also revealed that many fevers in children previously assumed to be malaria are in fact caused by other diseases, without providing a simple way of discovering what is causing the illness.
Prof Rosanna Peeling, chairman of diagnostics research at the London School of Hygiene and Tropical Medicine, says: “We don’t have good tests for fever or pneumonia. We really need industry to come up with the holy grail of the ‘fever stick’, which could be different in each country and even within countries in different seasons. It is not that easy.”
In the absence of reliable diagnoses there is a worry that diseases will be incorrectly treated with any available drugs, such as antibiotics.
A final concern is regulation. Internationally, regulatory processes for the approval of new diagnostics remain slow and sometimes contradictory. The World Health Organisation has strengthened its “pre-qualification” system, but critics suggest approvals remain slow and duplicate previous processes by requesting additional evidence.
In many poorer countries, there is the opposite concern, as substandard or unauthorised diagnostic tests are widespread. “A lot of bad tests are being used because regulatory capacity is very weak or non-existent,” says Prof Peeling. “Many tests are sold that have no evidence behind them and no real data to show that they work properly. Nobody is really overseeing that.”