Acute febrile syndromes: Sabine Dittrich explains which tools are necessary

As head of this new malaria and fever program, I am in charge of developing the integrated strategy and supervising the actual delivery of the organizations work in both fields

The Foundation for Innovative New Diagnostics (FIND) faces the lack of diagnostics for the main global health challenges, as tuberculosis, malaria and non-malarial fevers, HIV and neglected tropical diseases. While developing the fever strategy, FIND focuses on the patient and in the different locations they seek treatment. The diagnostic challenges faced by the patients may vary according to where they are. For example, when arriving at health units, the clinical physicians should have simple tools able to answer who should be given anti-malaria or antibiotic drugs, who can go home and who should be forwarded to a better-equipped health center, since the disease could be severe. To know more about this matter, the Brazilian Society of Tropical Medicines Press advisory (BSTM Press) talked to the FINDs chief for the new malaria and fever program, Dr. Sabine Dittrich. Find the full interview below.

BSMT: Tell us a little about the work developed by the Foundation for Innovative New Diagnostics and your role at the foundation?

Dra. Sabine Dittrich: FIND is a Product Development and Delivery Partnership with regional access platforms in India, South Africa, Uganda and Vietnam and activities in 35 countries. FIND is working to address the lack of diagnostics for major global health challenges including tuberculosis, malaria and non-malarial fevers, HIV, and neglected tropical diseases (NTDs).  The organization’s aim is to transform diagnostic challenges into simple and holistic solutions.

Over the last decade, FIND has partnered in the delivery of 22 new diagnostic tools with 11 receiving WHO approval to date. The team has also created an enabling environment for the development of numerous others through the provision of specimen banks, reagent development and better market visibility. From early R&D to implementation, FIND focuses on global access by ensuring that the products it supports are affordable, broadly available and appropriate to patient and user needs. Generating evidence for policy approvals, both at global and national levels, and to inform implementation strategies, is also a key part of FIND’s work.

The two, previously independent programs, Malaria and Fever, will be merged in January 2018 and it will be a great opportunity for us to take a holistic, patient centered look at malaria and fever diagnostic needs. As Head of this new Malaria and Fever Program, I am responsible for determining the integrated strategy and overseeing the effective delivery of the organization’s work in both areas.

BSMT: A platform to help better diagnosing millions of people with unknown-source severe febrile diseases in low and middle-income countries is being developed. Can you tell us more about this?

Dra. Sabine Dittrich: As part of FIND’s fever portfolio , we are working with a number of partners on a variety of development projects aiming to improve fever diagnostics. For instance, projects range from better triage tests for non-severe patients at primary health care level, to simple multiplexed panel and improved blood culture at hospital level. Our partnership with Médecins Sans Frontières (MSF) includes work to develop a target product profile (TPP) for a multiplex multi-analyte diagnostic platform technology – essentially a test capable of detecting a wide array of different disease markers using a single patient sample. The idea is to support clinical decision-making at MSF facilities, as well as in district-level hospitals in resource-constrained settings. It is often very difficult for clinicians to decide on appropriate treatment in the absence of quality diagnostic tools and the envisioned device would bring such testing capacity to places that are currently underserved.

BSMT: What kind of diagnostic tools are needed for acute febrile diseases? Can you tell us about the strategies used by FIND?

Dra. Sabine Dittrich: When developing our strategy for fever we wanted to focus on the patient and the different places patients seek care. The diagnostic challenges faced by patients can depend on where they are, and this is something we wanted to account for. For example, when patients first present to health facilities, clinicians should have simple tools that tell them who should receive antimalarials or antibiotics, who can go home, and who should be referred to a better-equipped health facility as the disease might be severe. Beyond this first contact, for many pathogens it is important to further identify which specific treatment or intervention is most appropriate, particularly for pathogens that can be resistant to certain drugs or require drugs other than empirical broad-spectrum antibiotics.

To address all these different needs while remaining strongly patient-centric, we have developed a portfolio of projects that aims to help address the challenges across this spectrum of needs and we hope to be able to support the global health community soon with new and improved tests at multiple levels.

BSTM: What innovations handling acute febrile diseases can we expect for the next years?

Dra. Sabine Dittrich: Personally, I am very excited about the prospect of evaluating and developing improved triage biomarker tests to differentiate between bacterial and non-bacterial infections that will not only help to improve patient management, but also support the fight against antimicrobial resistance. To achieve this, we are working with a team at FioCruz that will help us to get data relevant to Brazil. On the multiplexed pathogen identification front, we are thrilled about our collaboration with Chembio and are very much looking forward to the completion of the development of the new 8-plex test and its use in real-life settings.

Overall it is a great time to work in this area, as we are seeing many advances in fever diagnostics as well as data suggesting the advantage of combining diagnostics with simple electronic algorithm tools. The latter has a lot of exciting potential and we are looking forward to exploring this work more in the coming years.

BSTM: Which are the populations most affected by acute febrile diseases?

Dra. Sabine Dittrich: Acute febrile illness is a universal syndrome, and fever is one of the most frequent symptoms reported by patients, particularly children, when they present at clinics – regardless of the country or level of wealth. The difference is the causative agents of fevers, particularly in areas with declining malaria incidence. We know that the causes of fever can be very different even within one country, especially one as big as Brazil. Another challenge is the seasonality of infections and the impact that many different interventions can have on the rise or fall of one disease. This makes working on fever diagnostics very challenging, but for me it is also what makes it particularly fascinating.

Many large studies in Asia, Africa and Latin America are continuing to explore this question, and we are also eagerly awaiting additional data from epidemiological projects as well as mapping projects to better target our multiplex tests towards the identified needs.

BSTM: What is your opinion about the arboviral diseases (dengue, zika, chikungunya, yellow fever, West Nile fever, Oropouche, Mayaro) that Brazil has been facing?

Dra. Sabine Dittrich: Arboviruses are challenging as many of the symptoms are very similar and clinicians can have trouble differentiating the diseases. In Brazil, all the main mosquito vectors are present in the country – allowing for co-circulation of different arboviruses – but there is still a lot of underreporting of arboviral diseases due to challenges in diagnosis. There is therefore an urgent need for diagnostic tools that can distinguish between viruses (especially to confirm flavivirus serology results), and diagnostic tests that are accessible even in remote areas, to better estimate the burden for each arboviral infection and support patient care.

It is also difficult to coordinate surveillance and outbreak response in a large country on topics where a “one health” approach is required. This shows that we should be aware of, and prepared for, (re-)emerging pathogens circulating in new areas and displaying symptoms that had not been previously linked to arbovirus infection, such as microcephaly in the babies of pregnant women exposed to Zika virus.

BSTM: Do you believe in a global scale dissemination of these diseases?

Dra. Sabine Dittrich: Yes. We have seen that prevalence of Zika, Dengue and Chikungunya in particular has gone up in many places, and this is largely due to the ease with which pathogens can travel in our modern age. We always read that pathogens don’t respect borders, and in the case of many viral vector-borne pathogens, this is certainly true as long as the vector is also present at the destination.

BSTM: In your opinion, how is the worlds health? And what can we expect in a close future regarding fevers?

Dra. Sabine Dittrich: This is a big question. There remains a lot of inequality in the world and access to healthcare is no exception. The good news is that significant research is being conducted into many different aspects of fevers, as explained above. I have high hopes for the introduction of game-changing diagnostics in the (hopefully) not too distant future. Ensuring access to these game-changers will be the next big challenge.

BSTM: To you, what is the relation between fevers and poverty?

Dra. Sabine Dittrich: Ending poverty is the first of the Sustainable Development Goals (SDGs), which explain that the manifestations of poverty include limited access to basic services such as healthcare. Children born into poverty are almost twice as likely to die before the age of five as those from wealthier families. In low-resource settings, fever is often the first sign of many infectious diseases, yet fevers are often incorrectly diagnosed, or not diagnosed at all, leading to poor surveillance data and inappropriate treatment for patients. Another worrying effect is that pathogens with outbreak potential are not identified in time to contain the outbreak – as was the case most recently with Zika and Ebola. Access to healthcare is critical in addressing the challenges of poverty.

Our goal of creating diagnostic solutions that allow recognition of the different causes  fever, and ensuring that they are treated appropriately as soon as possible, will help the world reach the SDG 2030 targets.

BSTM: Would you like to add something we didnt approach and you find important?

Dra. Sabine Dittrich: Thank you very much for this opportunity, and I very much look forward to continuing to work with many brilliant Brazilian scientists and organizations to make sure our work is relevant to the country.…