Team:Aberdeen Scotland/Project/Methods

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<li><a href="https://2014.igem.org/Team:Aberdeen_Scotland/Safety">Safety</a></li>
<li><a href="https://2014.igem.org/Team:Aberdeen_Scotland/Safety">Safety</a></li>
<li><a href="https://2014.igem.org/Team:Aberdeen_Scotland/Attributions">Attributions</a></li>
<li><a href="https://2014.igem.org/Team:Aberdeen_Scotland/Attributions">Attributions</a></li>
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<li><a href="https://2014.igem.org/Team:Aberdeen_Scotland/Ethics">Ethics & Outreach</a></li>
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<h1><i>E. coli</i>-based Trypanosomiasis Diagnostic System</h1>
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<h1>Current Methods</h1>
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<p>Getting back at the Sleeping sickness by detecting it early.</p>
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<p>The goal of our project is to to develop a novel method for diagnosing Trypanosomiasis. Our aim is to provide a simpler, cheaper alternative to current methods that would be more versatile in developing countries and their remote regions. We wish to create a test that would be portable, endure harsh environmental conditions and most importantly be sensitive to the early stages of the disease.</p>
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<h4>Diagnosis</h4>
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<p>Due to unspecific symptoms, clinical presentation of the disease does not allow a certain diagnosis. Differential diagnosis often includes other infections such as Malaria, Leishmanaiasis, Toxoplasmosis or Typhoid fever, as well as HIV and common Influenza. Extensive laboratory tests are needed in order to confirm the infection. The most common are serological tests based on the detection of trypanosome-specific antibodies such as CATT (card agglutination test) and LATEX/IgM test. Their sensitivity and specificity is limited and is often hard to decide whether the result of a test is positive or negative since agglutination is the output. The golden standard for Trypanosomiasis diagnosis is identification of the parasite in bodily fluids. Either live and motile or dried and stained parasites can be observed under the microscope, usually obtained from blood or bone marrow. Since the parasite often exists in low abundance, the sample needs to be concentrated prior to analysis, which requires additional equipment such as centrifuges.</p>
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<p>All current forms of diagnosis require access to electricity for microscopes, rockers, centrifuges and refrigeration. Most sufferers are living in poor and remote areas with limited access to adequate health services, which complicates the surveillance and therefore the diagnosis and treatment of cases. In addition, displacement of populations, war and poverty are important factors that facilitate transmission. This means that villagers are effectively given a death sentence once infected.</p>
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<h4>Treatment</h4>
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<p>Microscopic examination of blood as well as cerebrospinal fluid is needed in order to determine the stage of the disease, which is crucial since each stage requires a different medication regime. Stage I of Trypanosomiasis  is usually treated with Pentamidine or Suramin. Stage II requires administration of infusions with Eflornithine. The treatment is toxic, expensive and requires trained personnel to administer. Infusions are administered 4 times a day for a period of 14 days, each infusion lasting for 2 hours. Another alternative is Melasoprol, arsenic derivative, although it has severe side effects and is lethal in approximately 10% of the cases.</p>
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<h4>Novel Treatment - Link to Our Project</h4>
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<p>Nowadays, a paradigm shift in the treatment of African Trypanosomiasis takes place. Fexinidazole, currently in stage II/III clinical trials, is one of the largest advance in HAT therapy in 30 years. It is effective for both stage I and II of the disease and less toxic than currently employed therapies. A huge advantage of this medicine is that it is in a form of a pill. This eliminates the need of a trained personnel and hospital facilities, allows easier transport and storage and is less invasive for the patient.</p>
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<p>With this advancement, we feel that diagnostic methods need a make-over in order to allow mass screening of the people in Africa. A new, sensitive, inexpensive, thermostable and portable system is required, which coupled with the possibility of treating the sufferers locally has a potential to make a significant difference in the prevalence of the disease.</p>
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<p>Our IGEM team decided to tackle this major challenge and offer a platform system for diagnosis of neglected tropical diseases that is tailor made for use in remote of parts of Africa.</p>
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Latest revision as of 16:56, 17 October 2014

Team:Aberdeen Scotland/Project/Methods - 2014.ogem.org



Current Methods


Diagnosis

Due to unspecific symptoms, clinical presentation of the disease does not allow a certain diagnosis. Differential diagnosis often includes other infections such as Malaria, Leishmanaiasis, Toxoplasmosis or Typhoid fever, as well as HIV and common Influenza. Extensive laboratory tests are needed in order to confirm the infection. The most common are serological tests based on the detection of trypanosome-specific antibodies such as CATT (card agglutination test) and LATEX/IgM test. Their sensitivity and specificity is limited and is often hard to decide whether the result of a test is positive or negative since agglutination is the output. The golden standard for Trypanosomiasis diagnosis is identification of the parasite in bodily fluids. Either live and motile or dried and stained parasites can be observed under the microscope, usually obtained from blood or bone marrow. Since the parasite often exists in low abundance, the sample needs to be concentrated prior to analysis, which requires additional equipment such as centrifuges.

All current forms of diagnosis require access to electricity for microscopes, rockers, centrifuges and refrigeration. Most sufferers are living in poor and remote areas with limited access to adequate health services, which complicates the surveillance and therefore the diagnosis and treatment of cases. In addition, displacement of populations, war and poverty are important factors that facilitate transmission. This means that villagers are effectively given a death sentence once infected.

Treatment

Microscopic examination of blood as well as cerebrospinal fluid is needed in order to determine the stage of the disease, which is crucial since each stage requires a different medication regime. Stage I of Trypanosomiasis is usually treated with Pentamidine or Suramin. Stage II requires administration of infusions with Eflornithine. The treatment is toxic, expensive and requires trained personnel to administer. Infusions are administered 4 times a day for a period of 14 days, each infusion lasting for 2 hours. Another alternative is Melasoprol, arsenic derivative, although it has severe side effects and is lethal in approximately 10% of the cases.

Novel Treatment - Link to Our Project

Nowadays, a paradigm shift in the treatment of African Trypanosomiasis takes place. Fexinidazole, currently in stage II/III clinical trials, is one of the largest advance in HAT therapy in 30 years. It is effective for both stage I and II of the disease and less toxic than currently employed therapies. A huge advantage of this medicine is that it is in a form of a pill. This eliminates the need of a trained personnel and hospital facilities, allows easier transport and storage and is less invasive for the patient.

With this advancement, we feel that diagnostic methods need a make-over in order to allow mass screening of the people in Africa. A new, sensitive, inexpensive, thermostable and portable system is required, which coupled with the possibility of treating the sufferers locally has a potential to make a significant difference in the prevalence of the disease.

Our IGEM team decided to tackle this major challenge and offer a platform system for diagnosis of neglected tropical diseases that is tailor made for use in remote of parts of Africa.