Policy & Practices Journal

Week 5: June 2nd - June 6th

Human practices sub-team was formed to focus on the purpose of the project and the positive impact it could have globally. This week was focussed mainly on brainstorming potential ideas for application of a rapid diagnostic test for infectious tropical diseases. One of the most prominent ideas was that of misdiagnosis and overdiagnosis for malaria and the lack of resources to provide an accurate and rapid diagnosis of these other dangerous diseases. Throughout this brainstorming we indicated that we wanted to further look into Dengue Fever, Meningococcal Meningitis and pneumonia that are often misdiagnosed as malaria. In regards to these diseases, we looked into their symptoms and misdiagnosis statistics and existing technologies of diagnosis. We began to look into potential contacts and experts that would be able to assist us with their expertise on the subject of misdiagnosis.

Week 6: June 9th - June 13th

Throughout this week we continued researching the various diseases, specifically focusing on misdiagnosis of malaria in developing countries and specifically the social and economic effects of this issue. We continued researching diseases that mimic malaria including dengue fever, meningitis, and pneumonia. On June 9th, we met with one of our experts Dr. Abebe Bayih who worked in the hospital setting in Ethiopia Through our meeting he was able to confirm that misdiagnosis is a major issue in developing countries due to lack of facilities and resources. We then discovered that typhoid fever has very similar symptoms to malaria such as high fever, headache, stomach pain, and loss of appetite and is often confused in diagnosis due to lack of lab resources and high rates of co-infection. Due to regular cases of this co-infection of malaria and typhoid fever, patients are often given antimalarial drugs with antibiotics to treat the typhoid fever. This presents two issues of both increasing unnecessary economic costs as well as the issue of antibiotic resistant bacteria. If lab resources are not available, physicians often diagnose based on clinical symptoms and the location the patient is coming from. Additionally we discussed the existing diagnostic technologies and both the economic aspects of the device as well as the accuracy of implementation. A rapid diagnostic tests for malaria cost less than $1, and in order to ensure economic success of mass production of a diagnostic device for another infectious disease, it is incredibly important to factor in cost. The device needs to be able to withstand room temperature as freezers and other lab conditions for storage might be unavailable. This device needs to be robust and able to withstand transport and storage before the test itself is administered. The time it takes to administer the test and receive in a result was advised to be approximately an hour for multiple diseases. Although the potential for overnight diagnosis for multiple diseases would be useful, Dr. Bayih presented the scenario in which immediate decisions must be made without time for any test to be administered. Dr. Bayih was very receptive and enthusiastic regarding the idea of having an inexpensive version of the diagnostic test for home-use, field use, and for use in the hospitals with no lab equipment available as well as a digitalized more expensive version for the hospitals with available lab equipment . This meeting confirmed that the issue of misdiagnosis combined with overdiagnosis are a pressing issue in developing countries and multi diagnostic device with different cost models would be extremely useful and provide early diagnosis reducing the mortality rate for these diseases. We continued to research statistics regarding misdiagnosis and finalize our target diseases for the project. Infectious diseases such as typhoid, malaria and meningitis are commonly misdiagnosed due to overlap in clinical manifestations. A recent study done in Tanzania examined the hospitalization of 500 children with fever. 62% of the patients were treated for Malaria, while only 2% were actually tested positive (Duke Global Health, 2012). A study from Afghanistan showed that 413 of 414 patients tested negative for malaria, yet 412 of 414 were treated for it regardless (Nader, Chandler, Whitty, & Rowland, 2012)

Week 7: June 16th - 20th

On the 16th the human practices team met with Dr. Lisa Allen who has a biomedical background and a PhD in Public and Global Health. She has had direct international experience with misdiagnosis of malaria, working in a rural hospital in Tanzania since 2008. After discussing potential priorities of their impact with the hospital and the community, it was determined that malaria was perceived as the biggest issue. The medical officer in charge thought malaria diagnosis was ineffective, so the main task of their presence was to improve the situation. 95% of patients were diagnosed with malaria based on microscopy; however pregnant women and children under 5 malaria had a default diagnosis of malaria for a fever. In the region in which Dr. Allen worked, actual malaria cases were declining due to high altitude and the temperature drop to 4∘ Celsius during the night. Despite this decline the diagnosed cases of malaria were showing no decrease, despite the low potential for infection. Citizens of this area would automatically assume that that fever is malaria, culturally using this inclusive term to describe any similar illness, similar to how our society using the term “flu” to describe what is potentially different health issues. Dr. Allen emphasized that awareness and education of other neglected infectious diseases was imperative, as this mindset of clinicians was part of the problem. Missing a case of malaria is considered “unforgivable” therefore overdiagnosis is present. Clinicians are aware of the algorithms for diagnosis of other diseases, but usually do not have lab capacity for bacterial infections. Having “safer than sorry” mindset, patients often receive both antimalarial drugs and antibiotics in the hopes it will treat malaria, and whatever other diseases exist if it happens not be malaria. Overdiagnosis and treatment with both antimalarial drugs and antibiotics result in a great economic impact on institutions and patients, shortage of antimalarial drugs, and increasing drug resistance. Patients pay for their prescription drugs, and if the diagnosis is not accurate and treatment is unsuccessful, patients waste their personal resources. Dr. Allen also looked into rapid diagnostic tests (RDT) what clinicians think of them. Many seems to criticize them because RDT can’t quantify infections which might be important in determining the most effective type of treatment. The cultural mind set also plays a role. Microscopy slides come back positive, so malaria is diagnosed. A lot of RDTs come back negative and clinicians do not trust it. However, RDTs were only created to target malaria, so a multidiagnostic test might solve the problem in terms of mistrust because the big question asked when malaria tests come back negative is “If it is not malaria, then what is it?” Dr. Allen felt that an important aspect of success of the project would be to analyze the limitations that are presented in the developing world setting. We need to consider mind for our design include storage space (no freezers), shelf life, price (ideally the device needs to be under $1; microscopy only costs about 34), diagnosis time. Overnight tests were classified as an option that is not ideal as many patients have to work several hours to arrive at the hospital, and to commute again the next day would be discouraging for use of such testing. Dr. Allen recommended that we check the Foundation for Innovative New Diagnostics (FIND) and other organizations that are working on similar ideas for hopes of potential collaboration. We also discussed the potential for quantification of infection, and will look into this option however the PCR of DNA might affect this aspect.

We have also introduced weekly policy and practice meetings to further discuss this subject with the Policy and Practices team. This week we are also planning on contacting Kirsten Jacobsen of Public Health Canada that was interested in this years iGEM team doing a video conference with a committee dedicated to looking at emerging technologies through Public Health Agency of Canada. This relationship could be a valuable resource to learning and impacting policy through our project and our policy and practices team. Additionally we are looking into contacting additional perspectives from experts in the field of malaria misdiagnosis to gather a broad view of perspectives from various individuals, occupations and respective regions of work. The team also broke up the weekly tasks into contacting additional experts and research on diseases in different regions as well as policy in Canada and developing countries.

Week 8: June 23rd - 27th

This week we began to work on the delegated tasks that each member of this subteam receive. We concentrated on looking at two regions: Tanzania and Ethiopia. One of the topics that was researched is the organization and management structure of the National Health System in Tanzania. The National Health System in Tanzania has central-district government structure. There are several layers in the Health Services Structure: village health service, dispensary services, Health Centre Services, District Hospitals, Regional Hospitals, and Referral/Consultant Hospitals. Village health service is the lowest level. Usually each village has two health workers who received short training before starting. Dispensary services supervise all the village health posts in its ward. Health Centre Services provide care for about 50,000 people. Each district then has a district hospital. Regional hospitals are similar to district hospitals, but they offer additional services and have specialists in certain fields. Referral/Consultant Hospitals represent the highest level in the country. There also are private health facilities that are often owned by government health care workers which creates a conflict of interest. In Ethiopia, on the other hand, the core of the health policy is accessibility of healthcare for all parts of the population, and encouraging private and non government organization participation in the health sector. Some of the priorities of the health policy include health information, education, communication, development of health service management systems, and provision of essential medicines, medical supplies, and equipment. We also found a paper on National Drug Policy of The Transitional Government of Ethiopia (Nov. 1993). The following is the summary of the relevant sections: 1. Selection of Drugs This section states that National Drug list will be formulated considering safety, efficiency, quality and cost and based on health problems in the country, infrastructure, and fundings. National Drugs Advisory Committee will be established to evaluate and decide upon drugs and to create lists of drugs used in the country. 2. Drug Supply The country plans to establish drug manufacturing facilities with the possible help from private investments. Pharmacists would be responsible for compounding drugs in hospitals, pharmacies and drugs while maintaining required standards. The government will also establish an enterprise to distribute the drugs on the national and regional levels. Both public and private sectors will be involved in the production of drugs. 3. Stock Management and Distribution Storage facilities will be created to ensure proper conditions for drug storage. 4. Drug Administration and Control The National Drug Advisory Committee will be responsible to evaluating drugs based on safety, quality, price, and other criterias. Drugs that satisfy the requirements will be issued certificated and existing drugs will go through regular evaluations. Information about harmful and beneficial effects of drugs will be collected. 5. Manpower Training and Utilization All professionals and biotechnologists will receive proper training. 6. Drug Information and Promotion Accurate information and reference materials will be distributed to the workers in the field. 7. Trading Agencies and Scientific Bureaus 8. Drug Use A list of prescription and nonprescription drugs will be created. Drug dispensing will be monitored by licensed professionals. 9. Traditional Drugs 10. Research and Development Research facilities will be established to carry out drug-related research. Research will strengthen the quality of pharmaceutical services. 11. Drug Pricing The government will make an effort to ensure that public gets affordable pricing for drugs. Additionally we continued to reach out to experts in the area of misdiagnosis and are waiting on the responses of two individuals to give us another perspective on this global issue.

Week 9: June 30th - July 4th

We began this week talking to Kirsten Jacobsen from the Public Health Agency of Canada. Kirsten was a Policy and Practices judge from last years iGEM competition and reached out to our team to become involved in the project and get our team to present via video conference to a committee from the public health agency of Canada regarding our project and the safety measures that we take when working on these projects. We are additionally looking into Biosafety policy of Canada and plan on using Kirsten as a resource. To learn more about the Biosafety laws in developing countries we also started looking at potential organizations that we can contact for more information.

Week 10: July 7th - July 11th

This week we also started contacting some organizations working with health care in developing countries. We contacted the Health Policy Project, the World Health Organization (WHO) and Foundation for Innovative New Diagnostics (FIND). The Health Policy Project got back to us saying they are happy to answer our questions. So this week we started preparing a list of questions that we can ask the organizations that we contact.

Week 11: July 14th - July 18th

The list of questions for the organizations was discussed with all of the members of the Policies and Practices sub-team and sent to Health Policy Project. The questions we asked are: What are the regulatory requirements to get a diagnostic device to market in Ethiopia? What safety tests must a diagnostic device pass in order to be considered approved in Ethiopia? What policies are in place in developing countries such as Ethiopia regarding synthetic biology and genetically modified organisms? Do you think there is a need for a multi-diagnostic test that provides a distinct diagnosis between malaria and diseases that present similar symptoms? In developing countries such as Ethiopia, what level of government involvement is present in the healthcare system? Is there a positive mindset regarding these initiatives of distribution of diagnostics and is there a potential for subsidization?

Throughout the week we also started working on the presentation for Geneva Conference. We started by creating an outline of important points that we want to mention in the presentation. We also started considering the possible format of the presentation and the 2 choices were a power point or a video.

Week 12: July 21st - July 25th

This week we continued working on the presentation for Geneva conference. This week Policies and Practices sub-team also presented their work to the rest of the team. We used the presentation prepared for Geneva conference because it summarized what we have done and it was a chance for us to get feedback on the presentation from the rest of the team.

This week additionally we decided to work on our human practices interviews and set up times with our three experts on Malaria misdiagnosis to ensure that we have a variety of perspectives to help us with informed design. Having the perspectives of qualified individuals that have worked in this industry all over the world will help us make choices to accurately represent any challenges we may face within our device. Everyone was very helpful and forwarded details of their research and additional resources that will help us locate the information that will assist with informed design. This assistance ensures that our project is authentic with real application in the developing world and that we will make the appropriate design considerations.

Week 13: July 28th - August 1st

This week 4 representatives from our team went to Geneva for Biological and Toxins Weapons Convention. More information on our trip can be found here. Attending the Biological Toxin and Weapon Convention gave the four representatives from our team the opportunity to showcase the iGEM competition on an international stage - and show the individuals responsible for influencing and creating policy the level of synthetic biology research and competition that occurs at the undergraduate level. This level of publicity for the iGEM foundation was noted by several Non-Governmental Organizations and guests of the meeting and appreciated by country delegations. Aspects of the convention such as the poster presentation allowed the four individuals to network and communicate ideas with individuals such as the FBI and other university researchers that were familiar with iGEM and others whom had never heard of the organization and were very interested to learn more. This level of networking with international professionals was enlightening and interested to gather a range of perspectives on both the synthetic biology industry and our project. Our representatives got the opportunity to view the discussion of current policy in place - and the process of forming this policy. Our group was invited meetings at the Canadian mission and took part in discussions that we may never have the opportunity to partake in again. This was a great opportunity to also expand our own professional development and perspective among the great opportunity to promote iGEM and our 2014 iGEM Calgary research.

This week we received a reply from Health Policy Project. They answered all of our questions in great details and provided useful documents that we can study. The documents included Biosafety Law in Ethiopia, and National Strategic Plan in regards to malaria. They also provided us with detailed information on what is the procedure to getting the device on market. The first step is get registered with Food, Medicine, Health Services Administration and Control Authority by submitting an application with required technical documentation and specifications details of the product. If the product is already registered with the World Health Organization (WHO) then FMHSACA usually registers the device provided all of the required documentation is submitted. Otherwise, FMHSACA might choose to run its’ own safety and quality control tests with the help from Ethiopian Public Health Institute. It is also recommended that the device has Certificate of Good Manufacturing Practice to ensure successful implementation. Upon completion of the registration process, the device might be included in health care workers’ trainings. The device would also have to be listed in National Guidelines in order for health care professionals to use the product. A representative from Health Policy Project also agreed that misdiagnosis of malaria is a problem, so a multidiagnostic device that would improve the diagnosis of malaria and diseases with similar symptoms is needed in developing countries such as Ethiopia. From Health Policy Project we also provided information on the level of government involvement in health care and reflected on the possible mindset of the government in regards to diagnostic tests like ours. Since FIND and WHO are located at Geneva, we also contacted both of these organizations to arrange an in-person meeting while the 4 representatives from the team are in Geneva for the conference.

Week 14: August 5th - August 8th

The week all of the representatives that attended the Biological Weapons Convention in Geneva Switzerland took time to reflect and review all of the information they were able to learn over the entirety of the experience. This valuable information will help us create an informed design for our device, and make adjustments based on international feedback we received from a variety of valuable perspectives. We discussed this experience and what they have learned at the conference and meeting with FIND. More information on the meeting with FIND can be found here

These team members made sure to thoroughly document this experience to ensure that this information will benefit the design and implementation of our project. The Biological Weapons Convention and the meeting with FIND both provided our team with valuable information and insight into synthetic biology on an international level.

Week 15: August 11th - August 15th

The World Health Organization responded to our email regarding our research and what feedback they have regarding our project. This is also an opportunity to gain insight in the malaria misdiagnosis information available from the World Health Organization, as the specific department of the WHO that responded to us is a part of the malaria program.

Week 16: August 18th - August 22nd

This week we created a list of all of the diseases that we previously talked about that have similar symptoms as malaria. Then we looks at the specific symptoms (other than fever) of each to see if we can group certain diseases according to similar symptoms. For example, some diseases might have neck pain as a symptom, while other have stomachache as a symptom. If a patient exhibits neck pain and fever symptoms, for example, then a doctor can administer a diagnostic test that tests for the diseases that have these two symptoms in common. So this week was spent looking into this idea and looking at the different symptoms of diseases that mimic malaria.

Week 17: August 25th - August 29th

This week we started writing summaries for different aspects we looked into as part of the Policies and Practiced research. Different components include diagnostic landscape, device implementation, and informed design. The write ups for these sections integrate the interviews with the experts and general facts about misdiagnosis of malaria that we found as part of our research. Information received from FIND during the Geneva trip was also very useful in writing up these sections.

Week 18: September 1st - September 5th

This week we worked on preparing for the aGEM presentation. We prepared content for the presentation and videos featuring our expert's interviews. We also practiced answering potential questions that can arise after our presentation at aGEM. We also started uploading policies and practices content on the wiki.

The Canadian and American governments as well as the FBI attend the Pathogen Security Partners meeting that will be taking place this fall in November. We have stayed in contact with representatives from the Public Agency of Canada and the Canadian Department of Foreign Affairs as they are interested in a presentation from our team at this event and governmental meeting. This in addition to our teams experience at the Biological Weapons Convention in Geneva will allow iGEM and its teams to create an awareness of undergraduate research in synthetic biology and the impact of iGEM on this industry. Over the next couple weeks our team plans to continue to plan this presentation with our contacts with the Canadian government, and continue to pursue our project after the Giant Jamboree in Boston. We have forwarded more information regarding our project and its potential impact and have set up several phone meetings to discuss these plans. Although this is a future direction for our project that will take place after Boston, our team is very passionate about the synthetic biology industry and scope of our project and wants to take this opportunity to showcase the potential of iGEM.

Week 19: September 8th - September 12th

We have continued discussion with the Government of Canada and the Public Health Agency of Canada over the past week and will continue for the entirety of iGEM 2014 to ensure they have the necessary background information on our project. This necessary background information will ensure that a relevant presentation can be created addressing the conferences interests in our team’s project. By staying in contact and discussion the necessary planning measures that will need to be taken to attend this event we can make this experience possible.

The remaining weeks until iGEM composed of finalizing and compiling all results of the research and perspectives we have gathered. Additionally we have continued to organize the logistics for the presentation at the Pathogen Security Partners meeting and implement this policy throughout our designs and device.