Global dealings in disease – the importance of diagnostic technology

Although viruses like Zika and Ebola have demonstrated the importance of good diagnostic technology, the field remains undervalued and underfunded. Practical Patient Care asks Rosanna Peeling, professor and chair of diagnostics research at the London School of Hygiene and Tropical Medicine, what the implications are for developing-world countries where the disease burden is highest, and whether technology transfer could be the solution.

Those that follow the news for public health stories, or watch the odd flick from Hollywood's conveyor belt of pandemic disaster movies, will know that however scary a disease might seem, there is almost always some kind of solution in the pipeline. Whether it is avian flu, swine flu or older diseases like tuberculosis (TB), medical professionals can usually be relied upon to find and produce drugs to keep people alive.

But while the search for these new medicines is crucial and gripping, one area that is often overlooked is how the virus is diagnosed in the first place. Not only does diagnostic equipment rarely make the news when it comes to fighting a disease, it is often undervalued and underfunded by governments and donors.

Diagnostics underfunding

According to the Lewin Report, diagnostics comprise less than 5% of hospital spending, despite influencing 60-70% of healthcare decision-making.

"Diagnostics is not valued as a commodity for funding," says Rosanna Peeling, professor and chair of diagnostics research at the London School of Hygiene and Tropical Medicine, and a former researcher with the World Health Organisation (WHO). "Most people think that diagnostics does not save lives. Compared with funding levels for drug and vaccine development, funding for diagnostics is really pitiful."

To understand the importance of diagnostics, look no further than Zika, the viral disease transmitted by the Aedes mosquito, which is currently sweeping through Brazil. Zika was first isolated in monkeys in 1947, but it wasn't until a major outbreak in French Polynesia in 2013, and its recent association with babies born with neurological disorders, that people began taking it seriously. The hunt for a vaccination is, unsurprisingly, dominating the news - but without appropriate diagnostics, attempts to contain and prevent the disease are being hampered.

"As things stand, the only way to diagnose Zika is with a molecular test that is largely inaccessible to the population," Peeling says. "So we can't establish the causality of the infection and we have no idea how extensive the outbreaks have been. All of the efforts to understand the correlation have been compromised by the fact that we do not have good diagnostics to put to use."

The commercial conundrum

Thankfully, Zika is being treated with the seriousness it deserves: governments and donor agencies have set aside money for diagnostic development on top of medicine and vaccines. According to Peeling, at least 20 companies from around the world are currently developing a diagnostic for the disease. Sadly, though, this isn't the norm. According to Financial Times journalist Andrew Jack, access to diagnostic technology in the developing world is "among the most important gaps in medicine - and among the most challenging to fill".

In many countries where the disease burden is highest, diagnostic equipment remains desperately lacking. Entire diseases can be neglected by companies that do not see any commercial value in them. And even with diseases like TB, for which high-quality diagnostic technology already exists, the cost of importing equipment - and the lack of any adequate laboratory infrastructure in developing countries - means governments and vulnerable populations often go without the tools they need.

"Companies are reluctant to develop products they don't think people could afford in the developing world," Peeling says. "Even with donor funding, there must be very clear commitments to purchase these diagnostics before companies will spend time and effort on it. The pipeline for developing diagnostics isn't very efficient, either. It usually takes eight to ten years to develop a new diagnostic platform. You have to put it together with a technological platform, the prototype has to be evaluated, you need good specimens to perform the evaluations, and you need to get the regulatory approval. It is a long investment in terms of time and effort. If a company invests in a product that only has a life cycle of five years or so, it's really difficult to generate return on investment."

In the absence of appropriate diagnostic equipment, many developing countries rely upon syndromic management to diagnose infectious diseases: a strategy promoted by WHO by which presumptive treatment is offered for patients that present with the major causes of a particular syndrome. According to Peeling, it is ineffective, has low specificity and, in the case of malaria, leads directly to drug resistance.

"Take the example of a child presenting with fever in Africa," she says. "In instances like this in the past, it has been presumed to be malaria, and all children with fever were given presumptive treatment using antimalarial drugs. Eventually, the malaria parasite developed resistance to chloroquine. The new generation of antimalarials were so expensive that giving them out syndromically wasn't an option, so there was an incentive to develop diagnostics. That's when they found out that a lot of so-called malaria was not actually malaria.

"The same thing happens with sexually transmitted diseases. WHO has syndromic management guidelines for how to manage people presenting with genital discharge, for example: the idea is to just treat all of the major causes of the syndrome without resorting to the use of any diagnostic tools.

"Advocating syndromic management means companies are not motivated to develop diagnostics until the treatment is so expensive that they cannot afford to just give it out to everyone."

Global partnerships in action

Identifying the problems associated with syndromic management is important, but it doesn't solve the existing mismatch between commercial interests and patient need over access to diagnostic technology. One solution, identified by Peeling in a report she prepared for WHO in 2011, is technology transfer, defined by the report as "the sharing of knowledge from those who own the know-how to those who do not".

"There are different methods of technology transfer," Peeling says. "One example we cite is a US company that has patented technology for the detection of HIV and syphilis antibodies in blood. They decided to partner with the Brazilian Government, which has a big manufacturing and research facility; the government paid $4 million for the company to transfer the patented technology, so it could expand the technology's use to all the tropical diseases that are endemic in the Americas. I think that's a very beneficial kind of technology transfer: the company had no other real interest in a lot of the topical diseases, because they had no US market. It was a good partnership."

And this is not the only example of technology transfer and local production in action. Peeling's report cites a number of different arrangements involving a range of nonprofit, governmental and commercial organisations. In 2010, for example, the Oswaldo Cruz Foundation (Fiocruz), a Brazilian research and development institution, signed a major technology transfer agreement with US company Chembio Diagnostics. The agreement enabled Fiocruz to market Chembio's Dual Path Platform, a rapid test for HIV infection; it also included access to exchange, personnel training and technical product documentation.

In another instance, the diagnostics division of multinational company Roche recently agreed to do research and development work within South Africa - the goal being to develop a molecular test for mycobacteria that could meet the needs of the local population. And finally, in India, various commercial companies have collaborated with the Programme for Appropriate Technology in Health - an international nonprofit that helps develops diagnostic technologies - to procure lateral-flow point-of-care technology.

A worldwide way forward

When it works, the benefits of these technology transfer agreements are clear: not only is access to diagnostics increased, but it is often also tailored to the needs of local populations in developing countries. But problems do remain. Test developers are often blocked by issues around intellectual property, financial return, external funding being withdrawn and the technology produced lacking real quality. In one case in Kenya, an initiative between the Kenyan Medical Research Institute and the Japanese International Cooperation Agency broke down after Kenya's own government wouldn't buy the HIV tests that had been produced.

"The idea is great, but the execution of it has been fraught with legal problems around intellectual property, mistrust and tough negotiations on profits and returns," Peeling says. "There aren't that many good examples of technology transfer around, but I think what we need to do is incentivise countries in the developing world to create their own technology sectors with donor help and partnerships."

Is Peeling being optimistic? Though many of the obstacles to technology transfer and local production remain, she senses that a more favourable climate for diagnostics is finally beginning to emerge.

"If you look at recent developments with Ebola and Zika, I think we're now seeing a lot of international cooperation," she says. "I think people increasingly realise that without good diagnostics, you cannot do anything. People are saying we should have this pathway from bench to bedside. Right now, it's fragmented and full of duplication - but there's a way to make it more efficient, and there's nothing like an outbreak to make that happen."