Target Diseases

A trend of misdiagnosis

Febrile illnesses that pose symptoms similar to malaria are of particular concern in malaria-endemic countries. Patients who present symptoms such as fever, nausea, and headache are often suspected to have malaria before a diagnosis is even made, due predominantly to malaria's high prevalence in these regions. The tragedy lies in the fact that patients who test negative for malaria but show its clinical signs and symptoms are often given antimalarial drugs and considered to have malaria despite their diagnosis (Mabey, Peeling, Ustianowski, & Perkins, 2004). The over-prescription of antimalarials fosters an environment for the continued emergence of drug resistance, unnecessarily taxes healthcare systems, and most importantly, worsens the patient's condition. Clinicians in malaria-endemic countries are presented with a dilemma when patients with symptoms identical to that of malaria are tested negative with commonly used malarial diagnostics such as Rapid Diagnostic Tests (RDTs) and microscopic blood smears. On one hand, they know that their patient most likely does not have malaria based on the tests, however they do not have the diagnostic means to explore the possibility of other diseases and know that missing a case of malaria is considered unforgivable.

Clinicians must make an important decision at this junction based on limited information, the consequences of which could have severe effects on the patient. Some clinicians will opt to treat all cases of fever, nausea, and headache as malaria and indiscriminately prescribe anti-malarial drugs, consequently ensuring that no case of malaria goes unaddressed. The ramifications of such practice can be tremendous, as we have seen in countries such as Uganda, Tanzania, and Sudan (Mabey, Peeling, Ustianowski, & Perkins, 2004). Others must ask themselves the question, "if it's not malaria, then what is it?". Unfortunately, clinicians who fear the consequences of over-prescription and wish to consider alternative diagnoses are left with very few diagnostic options due to limited time and resources.

We at iGEM Calgary built our summer project around developing a solution to this problem. We propose a diagnostic test capable of evaluating the presence of several diseases in parallel, thus opening the door to more routes of treatment and allowing the clinician to make an informed decision regarding treatment plans. Additionally, in cases of a patient being co-infected with both malaria and different febrile illnesses - a common occurrence in malaria-endemic countries - our device will facilitate the diagnosis of all diseases instead of just one. Current malaria diagnostic methods do not offer this feature, which has the potential to lead to dangerous situations. For example, if a co-infected patient is given a malaria RDT and tests positive, the clinician may make the false assumption that the patient only has malaria and remain unaware of other infections. Our device was not designed to replace existing gold standard diagnostics that are being used in these regions. Instead, our objective was to offer a comprehensive and affordable diagnostic option that tests for multiple diseases as economically as possible. We researched a wide spectrum of infectious diseases and decided to target the following:

• Typhoid Fever
• Dengue Fever
• Meningitis
• Visceral Leishmaniasis
• Schistosomiasis

Our rationale behind choosing these diseases was the fact that they shared many signs and symptoms strikingly similar to those of malaria. Additionally, these diseases are present in high numbers within malaria-endemic countries (Uganda, Tanzania, Sudan, etc.) making co-infection a significant concern.

This is not to say, however, that our device is limited specifically to these diseases. Our device was designed with modularity and customization in mind. By simply switching a few DNA sequences within our genetically engineered B. subtilis our device has the potential to detect virtually any pathogen present in a blood sample whose genome has been sequenced and made available in public repositories. Based on which diseases are common within certain regions of the world, we can modify our device to detect those diseases of interest before shipping it to the end-user. The true strength of our device lies it ability to adapt to different geographic areas and offer a diagnostic assay that is tailored to a specific medical landscape.

Think of our device as the utility knife of diagnostic tools: affordable, handy, and ready for use in any situation it may encounter.