Bringing diagnostics to developing countries: an interview with Rosanna Peeling

Abstract

Interview with Professor Rosanna Peeling, PhD by Claire Raison (Commissioning Editor)

Professor Rosanna Peeling is Chair of Diagnostic Research at the London School of Hygiene and Tropical Medicine (London, UK) and founded the International Diagnostics Centre at the institution. Professor Peeling previously worked for the WHO in Geneva, Switzerland, and continues to work on innovations for molecular diagnostics for point-of-care use in developing countries, addressing challenges posed by lack of funding and resources, regulatory issues and under-developed healthcare systems in these locations. Here, she discusses her career, recent progress in the field and how connectivity will affect global healthcare.

•	What is the biggest challenge in your field of work at present?

The focus of our work is to try and increase access to diagnostics in the developing world. In the last 10–15 years, we all thought that point-of-care (POC) diagnostics would allow us to really increase access. But now that we do have some really good POC tests (POCTs), what we’ve found is that when you suddenly decentralize testing from a few central labs to hundreds of POC testing sites, the healthcare system in those countries is really strained.

Ironically, we are trying to improve access in those countries because their healthcare systems are not strong, and they don’t have a lot of laboratories. What we underestimated was to what extent this would stress the system in terms of human resources, supply-chain management, being able to ensure the quality of a test while it is stored in the field and the quality of the testing. We are now trying to address the issue of to what extent we can introduce diagnostics that are not only much more user-friendly, simple and informative to guide treatment and management decisions, but to use that opportunity to strengthen healthcare systems. This might be addressed by using connectivity.

•	What are your opinions on the integration of digital technology into diagnostics?

Nowadays there are a lot of devices that POCTs can use to transmit data to a central database, so the ministry of health in that country has up-to-the-hour information on what’s happening across the country. We can complement that with proficiency testing information, for example, if the results from a center that hasn’t passed its proficiency testing are turning out to be incorrect and something should be done about it. Or if we found one center doing a lot of testing and another center doing very little, we know that those tests are going to expire at the latter site, so we can quickly move the tests to a site where they are doing a lot of testing. The supply chain can be informed in this way, which is an opportunity to strengthen the healthcare system. Another example is, if suddenly you have no information coming in from a particular site for a few days, you know you should call them and ask what happened.

The ministry of health in that country has up-to-the-hour information.

In South Africa, they’re thinking about bi-directional connectivity, where not only the healthcare sites send information to the central database, but the database can report back to the site operators on the trends. Information about the devices can also be tracked, such as frequency of failure; how often they break down; if there were errors, were they user errors or machine errors. The companies that make these devices store the information in a data cloud. The company wants the data on machine errors and breakdowns, and all the locations are known via GPS, so they know exactly what to do. A lot of countries, once the POC devices are deployed, have no idea what happened to them, because there isn’t a good enough tracking system.

It’s quite exciting. We’re piloting a project in one of the African countries just to understand these middleware solutions: whether they could extract the same set of data from different clouds; what kind of IT knowledge would be needed to manage a system like that in the field; what advice countries would need about human resources and training. This would all make the system a lot more efficient and the information would be very useful for designing control programs.

•	Do you think that this connectivity could be used to manage future disease outbreaks?

Absolutely. As soon as the Ebola crisis became a problem, within a couple of months, there were Ebola tests available. So if the system is already in place to extract the data, it’s a natural surveillance system that could be used. I think the health sector has been very slow to embrace connectivity and it’s about time they do.

The health sector has been very slow to embrace connectivity and it’s about time they do.

•	How close are we to eliminating mother-to-child transmission of HIV and syphilis? What needs to happen next for this to be achieved?

According to a recent update from the Pan American Health Organization, there are seven countries and territories in the Americas that report data compatible with the dual elimination of mother-to-child transmission (MTCT) of HIV and syphilis [1]. Cuba is the first country to ask the WHO to certify them.

Other than in the Americas, some countries in Asia are close to eliminating MTCT of HIV and syphilis; however, if they don’t have the diagnostic test, they can’t tell. Or if the country is using a diagnostic that is not very sensitive, it may appear that transmission has been eliminated but actually it hasn’t been. We therefore need to make the health ministries in these countries aware of the quality indicators that they need to show in terms of confirming the quality of the test and the quality of the testing. We’re working on that.

In Africa, maybe the first country to eliminate MTCT of HIV and syphilis will be Botswana, but other countries will be very far behind. I think in Africa, we will actually achieve the elimination of MTCT of HIV sooner than we will of syphilis, even though the former is more complicated. For HIV, the WHO recommended ‘Option B+’, which is to put all pregnant women who are HIV positive on treatment, regardless of their CD4 count, in recognition of the fact that we don’t want any transmission.

The result we’ve seen in Africa is a dramatic drop in the number of infants who test HIV-positive, to the extent that we have three POCTs for early infant diagnosis, and we really can’t find HIV-positive infants, which is a great thing. For example, in a region of South Africa that traditionally has very high rates of HIV-positive infants, when we first engaged that site for the evaluation of the POC tests for early infant diagnosis of HIV, around 18% of infants tested were HIV positive. Now, 2 years later, it is less than 3%, which is a really dramatic improvement. We should try to do that with syphilis.

The result we’ve seen in Africa is a dramatic drop in the number of infants who test HIV-positive.

•	What changes would you like to see in the approval and regulation of in vitro diagnostics?

I was funded by the Gates Foundation and Grand Challenges Canada to try and improve the regulatory oversight of diagnostics for the whole of the developing world in 2 years. We managed to do that in some way but it’s far from complete. We did get 23 countries in Africa committed to the harmonization of approval, which is really important if you want innovation, rather than each company having to go to every single country and do a clinical trial to get approval.

Some of the countries in Africa wanted to band together to become the East African Community, and they’re actually thinking of having a common currency, that’s how strong they are. They are very keen to jointly approve medicine and diagnostics; they have already approved three medicines jointly, so the mechanism is there.

•	What are your hopes for the next 5 years in diagnostics for infectious diseases?

We have always said that we hoped for novel technologies that could be introduced everywhere. Now the test developers have delivered, but we don’t know how to introduce the tests. I think we need innovation in the delivery of these novel technologies so that they have the right impact, in the right population. This ties in to being able to strengthen the healthcare system using these novel technologies because of their data transmission possibilities.

Most of these technologies are ‘sample in, answer out’ and they are very user-friendly and simple to use, so there’s no reason why we can’t introduce them in such a way that they would have impact. However, linkage to care after diagnosis is very important and I think we need to work at that. Instead of talking about technical innovation, we’re now talking about innovation of delivery of healthcare.

I think that there needs to be more holistic thinking about how you deliver health services, so the situation isn’t diagnosis on its own and then treatment later. It has been shown that previously, half of infant diagnoses were not ever delivered back to the carers. Before POCTs were available, dried blood spots would be taken, which were sent to a centralized lab. The mother was asked to bring the baby back to get the results, but sometimes the mother didn’t come back, or the sample took too long to process, or the results are lost, or the specimens are lost…there are all kinds of reasons why in the end, half of the results were not reported back. There needs to be better linkage there.

There needs to be more holistic thinking about how you deliver health services.

•	What are the most important changes needed to achieve better global healthcare for neglected tropical diseases?

Of the neglected tropical diseases, seven are targeted for elimination by 2020, and almost all use mass drug administration as the main control strategy. Now, after several rounds of mass treatment, countries need to assess the current situation, but there aren’t good enough diagnostics to measure this, because diagnostics were not an important consideration in the control strategy. So now we need to work out what the best diagnostic tools are to detect infections at a very low level. Normally when diseases are down to a very low prevalence, the pathogen load is very low, so you need very sensitive tests. Because you’re trying to assess elimination, you need very specific tests, which could only mean molecular testing. This can’t be done in very remote settings. The specimens could possibly be collected and taken back to be tested at a centralized lab. But the platforms are not there because the very sensitive and very specific tests for these diseases have never been a priority.

One thing that is also a big challenge for diseases that are near elimination is that the cost per case detected is high. In a country where your health budget is extremely low, there are competing priorities. If every case takes US$10,000 to detect, would you go on to allocate budget toward that? Probably not. So this has been a problem. How do you get to the end without external funding help?

A big challenge for diseases that are near elimination is that the cost per case detected is high.

•	What has been the most valuable lesson you have learnt from establishing the International Diagnostics Centre?

When I was at the WHO, we realized that the public sector by itself cannot do everything, and that we really need to work with companies. Since I’ve been funded by UNITAID, to try and lower the barriers for market entry for companies, what I’ve found is that working with companies is very difficult.

So we formed the International Diagnostics Centre to try and provide a neutral forum for interactions. It’s not been easy, because of perceived conflicts of interest. I think that in the pharmaceutical world, they are 10 years ahead of us in terms of setting up the International Conference on Harmonisation and the infrastructure needed, so that even though drug companies conduct the trials, they are considered independent because they’re monitored and they adhere to international standards and so on. But we don’t have that yet for diagnostics. I am hoping that we could. So we will keep working at this partnership and try to define how you manage the conflicts of interests and the expectations of so many countries as well as so many companies. It is useful and it’s something we need to work at if we want innovation of delivery and to have affordable goods.

•	What’s next for the Centre?

We are supporting different initiatives such as connectivity and helping countries with models of quality assurance. For example, how does a country manage thousands of sites? So we’re working at these generic models for working out what are the best, most cost-effective strategies for introduction and scale-up so that other countries can use them and adapt them for their own healthcare system. In one country maybe because of geographic distribution of sites and prevalence of infection, they may adopt different models rather than a single model for each country.

I think we also still need to work on the regulatory issues. Companies are happy that we’re working on regulatory harmonization, and when we have data from the CE evaluations, we can act as watchdogs for regulators from all different countries, who can come together to review the data. We’re not saying that all countries have to have a consensus; each country should be able to go home and make a decision about whether to approve a diagnostic or not, but at least they can see the same set of trial data together, rather than each country having separate domestic trial data. I think these things are still very important, because they’re big challenges, and it’s only when you work in a collaborative way that you can begin to address them.

•	What is your proudest achievement in your career so far?

I developed a lot of the systems of how to evaluate a test, and published a series with Nature Reviews Microbiology on how to design and conduct a diagnostics evaluation, so those are good to go towards a system like the International Conference on Harmonisation, but we’re still far from it. I was also proud to be awarded the George Macdonald medal last year and was the first woman to win the medal.

But the most interesting thing so far is that Bill Gates asked to meet me one on one. We had such an interesting discussion about a lot of the intractable problems in diagnostics. He’s been called an impatient optimist – he wants things to happen and to happen quickly – he wants to leapfrog over existing problems and so it was very interesting to talk.

Disclaimer

The opinions expressed in this interview are those of the interviewee and do not necessarily reflect the views of Expert Reviews Ltd.

Financial & competing interests disclosure

The interviewee has no relevant affiliation or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.