Where are the Ebola diagnoses of the last time?

The Democratic Republic of Congo (DRC) is in the midst of the worst Ebola outbreak since 1976. It is the second largest epidemic in the world and could escalate into an even deeper crisis due to conflict, political instability and poor infrastructure. and socio-economic weaknesses.

The largest epidemic to date (from 2014 to 2016, in West Africa) has prompted companies, including Cepheid in California^1,2 and Altona in Germany³, to develop new diagnoses. And 14 tests have been approved by the United States Food and Drug Administration (FDA) and the World Health Organization (WHO), or both.

However, health workers and organizations trying to stem the current epidemic can not get diagnostic tests quickly enough. Even when funds from international donors are available to pay for them, laboratory or health center staff take two to eight weeks to get the tests.

There are two types of diagnostic tests for Ebola. Rapid diagnostic tests detect a viral protein; those based on polymerase chain reaction (PCR) identify the genomic material of the virus. By filling out business application forms, sending an email to manufacturers and searching their websites, we have established that of the recently approved tests provided by companies, only four are readily available to buyers (see "What products are available?"). All these tests are based on PCR. OraSure Technologies in Bethlehem, Pennsylvania, has made its OraQuick rapid diagnostic test available to WHO and the US Centers for Disease Control and Prevention (CDC), which distributes the test to health workers at the facility. current epidemic. But it is not available for other buyers.

Our badysis reveals that research and increase in production were maintained for only a few of the tests provided by the company developed and approved during the 2014-2016 emergency. Indeed, we were co-developers of a diagnostic test for Ebola⁴ this is no longer available as the manufacturer has decided to focus exclusively on oncology.

Diagnoses are essential to contain epidemics. Without these tests, it is impossible to determine whether the infected people have infected other people, whether the virus persists among survivors or to search for the cause of death. In our opinion, the different methods of diagnosing the Ebola virus must be evaluated and the best ones chosen in order of priority. More importantly, developers need to be encouraged to maintain their investments in diagnostics during and after outbreaks so that health workers do not scramble for testing at the onset of the next outbreak.

Emergency medicine

In August 2014, nearly six months after the start of the Ebola outbreak in West Africa (which killed more than 11,000 people), the FDA created a "user authorization" procedure. emergency "for Ebola diagnostic tests. This allows medical products that the agency has not yet approved to be used in an emergency – to diagnose, treat or prevent serious diseases or conditions in the absence of alternatives (see go.nature.com / 2vbkhhd).

The following month, WHO launched an emergency use badessment and enumeration procedure to enable more rapid review of diagnoses in the event of a public health emergency (see go.nature.com/2vcgjjd) . He also called on manufacturers to develop easy-to-use diagnostics and quick results on sites where people are tested and in countries lacking health infrastructure and skilled personnel.

While the epidemic was raging, researchers, manufacturers and other organizations, such as the Foundation for New Innovative Diagnostics (FIND) and Médecins Sans Frontières (MSF, also known as Doctors Without Borders) Borders), both based in Geneva, Switzerland, have striven to accelerate the development, evaluation, production and deployment of Ebola diagnostics. Over the next two years, the FDA has approved 11 tests and the WHO, 7 (see "Success Story").

Health workers in the DRC do not need 14 different tests for the Ebola virus. What they need is a handful of quick, reliable, easy-to-use and PCR-based diagnostic tests that are always available. Why are there so few diagnostics provided by the company approved in stock and on sale?

Developing diagnoses for unpredictable infectious diseases such as Ebola is a high-risk strategy for manufacturers. Compared to the millions of tests routinely required for diseases such as malaria and tuberculosis, it takes relatively little for viral haemorrhagic fevers such as Ebola – even during outbreaks that typically affect hundreds or even thousands of people. This means that the costs of manufacturing a test, storing raw materials and final product, and logistics and distribution issues for field deployment, far outweigh the gains made on sales.

At the end of the epidemic in West Africa, fears about the Ebola virus declined, as did the public and private funds available to manufacturers. Companies have struggled to get enough samples to evaluate their tests even in the event of an emergency⁵. But with fewer people infected, it becomes even more difficult to evaluate field tests and obtain national and local authorizations to share samples and transport clinical specimens.

We believe that it is urgent to take two steps to improve the availability of diagnoses, both during the current outbreak of Ebola in the DRC and during future crises.

Evaluate and prioritize specific diagnoses.The takers must evaluate the tests and choose the winners. For the Ebola virus, health workers need two or three PCR-based tests and two or three rapid diagnostic tests that can be used in tropical environments where resources are scarce. PCR-based tests tend to be more accurate, so they are preferable if the necessary infrastructure and expertise are available. Rapid diagnostic tests are simpler to perform and therefore easier to use in the field. Competition between several manufacturers may drive down prices, and having alternatives may be a guarantee in the event of supply problems.

To maximize the chances of health workers to make a correct diagnosis during an outbreak, priority tests should include those who can simultaneously identify co-circulating pathogens that cause similar symptoms. For Ebola, it can be other Ebola virus strains, such as Sudan virus or Bundibugyo virus; the protozoan that causes malaria; or other viruses of hemorrhagic fever, such as Marburg and yellow fever.

In addition to reliability and ease of use in the field, various factors must be taken into account when selecting the most promising candidates, including the existence or not of the badociated infrastructure. Thousands of GeneXpert PCR machines needed for the Xpert Ebola test have already been installed throughout Africa – for the diagnosis of HIV and multidrug-resistant TB.⁶. Although machines are not always placed in the right places to be useful in the event of an Ebola outbreak, people are used to handling them. Indeed, their widespread installation has already made it possible to deploy the Xpert Ebola test during the two recent epidemics in the DRC.

Encourage developers.Many programs have shown that companies can be encouraged by incentives to develop diagnostics for infectious diseases that mainly affect low- and middle-income countries. In 2006, for example, the GeneXpert PCR platform was made available to middle-income countries at about half of its initial cost.⁶, thanks to FIND, mobilizing millions of dollars of donor funds. Many other such programs are needed, especially those focused on epidemics.

An increased investment in surveillance could be another way of providing markets for developers and manufacturers. The establishment of national and regional surveillance programs for viral haemorrhagic fever, for example, throughout Central and West Africa, would require thousands of diagnostic tests. In Uganda, a national surveillance program has confirmed 16 independent outbreaks of viral haemorrhagic fever since 2010, reduced response time to outbreaks by 2 to 3 weeks to 1 to 3 days, and resulted in shorter and less severe epidemics.⁷.

You can also learn a lot from the vaccine community. For example, a public health organization and a government authority may commit to buying a vaccine before it is licensed. This is an important incentive for the vaccine industry, where licensing remains the biggest bureaucratic barrier. In 2016, for example, Gavi, the Vaccine Alliance in Geneva, announced that it would donate US $ 5 million to Merck to supply 300,000 doses of its Ebola VSV vaccine to people living with HIV. West Africa. The vaccine had not yet been approved by the regulators. The same type of agreement should be made for the diagnosis.

Deployment of diagnostic and surveillance programs in LMICs requires sustained funding: international organizations and donors, such as the United Nations and the African Centers for Disease Control and Prevention; the ministries of health of the G20 countries; Public-private partnerships; and the governments of countries at risk. And, just like vaccines, we believe that a kind of global alliance is needed.

FIND's epidemic preparedness diagnostic strategy, aimed at streamlining diagnostic development, was designed in 2017 for this purpose.⁸. But in our opinion, there is a lack of financial support and the necessary burden to bring together stakeholders from the entire field of diagnosis. Since 2016, the Coalition for Innovations in Epidemic Preparedness (CEPI) in Oslo has established a list of priorities for vaccines against epidemic diseases. He also liaises with funders to help ensure that promising candidate vaccines for LMICs are integrated into clinical trials. We urge CEPI to incorporate diagnostics into its program.

Together, these steps will help prevent investments made during an epidemic from being wasted. These efforts must be continued to help citizens cope with the next crisis.