Disease Informatics: How to handle diseases associated with viruses?

1. R. P. Deolankar Sudhatai Murthy Information specialist Ranitai Bang Disease specialist Disease Informatics:How to handle diseases associated with viruses?

2. Prerequisite • Lecture no. 37141: Assessment of Holistic (Wholistic) Health and Fitness, Disease Informatics. February 17, 2010 • Lecture no. 36261: Disease Informatics: Living in the Toxic World, November 6, 2009 • Lecture no. 35791: Disease Informatics: The burden of disease, September 11, 2009 • Lecture no. 34141: Disease Informatics: Brush up the terms describing techniques and resources, February 19, 2009 • Lecture no. 34011: Disease Informatics: Terms and Jargon to begin with, February 1, 2009 • Lecture number -31981: Disease Informatics: ICD-11 at the doorstep, February 26, 2008 • Lecture number-30331: Disease Informatics: Phytates driving from the back-end to Influenza, Encephalitis, Hepatitis, Anemia at the front-end, July 10, 2007 • Lecture number-28921: Disease Informatics: Host factors simplified, February 07, 2007 • Lecture number-25381: DIG for Disease Informatics group; Part-II, November 07, 2006 • Lecture number-25371: DIG for Disease Informatics group; Part-I, November 07, 2006

3. Viral Outbreaks • Viral outbreaks make sensational news • Where the bug comes from? Is it testing of biological warfare? Which company harvests most of the profit as a result of an outbreak? • There is also confusion between virus and disease

4. Interesting People • 1st type will provide you minutiae of information on virus and will get you convinced that bug is really difficult to win over • 2nd type will provide you simple solutions like taking sunbath for prevention of flu and will give you adequate explanation • 3rd type will give you solutions but shall confess that to explain the science of cure in modern terms is beyond their capacity

5. Common Cold Story b4tea.com • It is said that “Common Cold” will be relieved within one week if treated, and within seven days if not treated • On the other hand people in various parts of the world experienced that spicy Indian curries could relieve common cold • What is the truth? Let us discuss and find it out

6. (W) Holistic Thinking • Virological approach to treat the disease means to eliminate the virus. In terms of cricket, you must clean bowled the batsman (disease) and see the wickets (virus) dropped. But this is incomplete cricket • Catch, run-out, lbw etc (modulating host and environmental factors) are permitted in complete cricket

7. Disease is a process • The disease causing factors (component causes) summarized as host factors, environmental factors and etiologies interact or work together • The process results in providing sets of disease causal mechanisms known as sufficient cause or causes

8. Pathogenesis Prof. David Kriebel Prof. Paolo Vineis • The mechanisms drive the individual from a state of health to the disease through a series of events typically described as Disease Causal Chain (DiCC) or web • Picture of DiCC comprising of events and driving factors, depicting past, present and prediction is the complete definition of disease Definition of a disease based on a single component cause is not an accurate one. Better definition of disease is provided by knowing more number of component causes

9. One cause one effect! • “Common cold” is a definition of a disease based on a single component cause that is virus • The school that believes in one cause one effect has no alternative but to believe that virus causes the disease • The disease can be diagnosed by detecting the virus or viral forensics and can be treated by antiviral drugs or prevented by vaccination

10. Viruses and Disease • Viruses infect susceptible individuals • Replicate only inside the living cells • Can be seen through electron microscope • Specific as compared to other pathogens due to limited genetic information • Although several diseases have been defined after viruses, and several viruses have been named after diseases, in reality, viruses could only be component causes of the disease

11. Virus Exposure • On getting exposure to virus, some individuals get infection • Most of those who get infections get better without treatment • This is the reason why doctor usually does not need to have a laboratory identify the specific virus involved

12. Continued… • Many viral infections are so distinctive that a doctor can diagnose them based on their symptoms • Sometimes infection of one virus builds paraspecific immunity to several other viruses. It is understood that pox viruses are good paraspecific immunity builders

13. HIV; a chronic infection and AIDS • A person carrying HIV virus is HIV+ve • CDC definition: AIDS is CD4+ T cell count below 200 per µL of blood or 14% of all lymphocytes in HIV+ve individuals; (reversed whenever the count goes up the limits) • World Health Organization defines AIDS in terms of conditions in HIV+ve individual; (reversed if conditions are reversed although HIV+ve status might not turn HIV-ve)

14. Malnutrition induced by HIV (also by other viral infections) • Sulphur metabolism is disturbed as evidenced by loss of sulfur (Cysteine and glutathione) in AIDS patients • Could be due to virus or drug • However, some simple solution to the AIDS treatment, through nutraceutical or functional food, could arise if this aspect is investigated • Malnutrition concept applies to several other viral diseases

15. Nutraceuticals for AIDS [PMID: 19857540]. Prof. Ethan Will Taylor • The nutrient-related metabolic abnormalities in HIV infection regarding antioxidants, selenium, sulfur, tryptophan and niacin are interrelated • The OSINS (oxidative stress-induced niacin sink) model: guide the design of nutraceutical regimens for HIV/AIDS

16. Lifestyle also matters • Systematic review suggests that massage therapy may have a positive effect on immunological function of people with HIV/AIDS • Aerobic exercise also appears to be safe and may be beneficial for adults living with HIV/AIDS • Apparently, there are various tools available to reverse AIDS [PMID: 20091636], [PMID: 15846623]

17. Popular view on HIV/ AIDS • HIV is not the sufficient cause of AIDS • Nobel laureate Prof. Luc Montagnier, who discovered the Human Immunodeficiency Virus (HIV) also held this view • In this case viral as well as non-viral targets are appreciated Prof. Luc Montagnier

18. HIV and AIDS hypothesis • HIV is the sole cause of AIDS: vaccine and antiviral drugs are the only solutions • Hypothesis is profitable for pharmaceutical and vaccine companies • Companies promote the social, educational and research projects in this direction, talk least about alternative/ complementary strategies Robert Gallo

19. Michael Latham, Cornell University says…in his article ‘The great vitamin A fiasco’ • Just as there is big business and big science, there is big aid. International aid programmes are not driven simply by science. With any politically-influenced policy, evidence is part of the mix, but it may be interpreted recklessly • The main aid policy drivers are first of all, the national interests of the major bilateral donors, mainly governments of Northern countries Latham M. The great vitamin A fiasco. World Nutrition May 2010; 1, 1: 12-45. Also available at: www.wphna.org Prof. Michael Latham

20. Continued… • In the case of overseas development assistance, the biggest donor in absolute terms is, far and away, the USA, particularly thorough the US Agency for International Development (USAID). • By federal law, USAID programmes, however beneficial to recipients, must further the interests of the USA, as interpreted by the US governments of the day.

21. Continued… • The second driving force is industry, which in the case of food aid is the big agriculture and food companies, and in the case of VAC is Big Pharma – the giant pharmaceutical companies that manufacture synthetic nutrients • The third influence is culture. However sympathetic nationals of rich countries are with nationals of impoverished countries, without extensive field experience and residence in the community in such countries, they are unlikely to understand their needs

22. Denial of HIV and AIDS hypothesis • Third view is denial of the hypothesis wherein vaccine and antiviral drugs could harm rather than help • The drugs themselves could be contributing cause • AIDS like disease can be seen in HIV-ve persons also • The proponents feel that the focus of treatment should be non-viral targets only Peter Duesberg

23. Denials continued… • Denialists believe that organizations funded liberally cannot solve the real problem because their policy is corrupted by the commercial people • The personnel from health departments have been provided perks to fulfill their personal ambition to make policy in favor of some commercial organizations

24. Coming back to Indian curry • Indian curry is a functional food • May have antiviral chemical or may not have • Shows beneficial effect in common cold-like disease • Some people think that it has value in prevention and treatment of flu If one understands the disease process completely then he or she would also modulate some factor lying within the sphere of host factors or environmental factors to treat the disease

25. Public Health Approach • Definitions of diseases for public health purpose are usually component cause definitions • Big figures are produced in favor of a component cause • This is also convenient for commercial firms; get a patent for one factor and turn it to big business However, two patients may have same disease as per public health approach of defining a disease could be treated differently by the intelligent doctor depending on individual features

26. Doctor’s Approach • Doctor who is not a family doctor has to spend either more time per patient to understand all the components of the disease and apply more of his or her clinical skills or else take public health short-cut in naming the disease • Two patients could have different set of component causes to make a sufficient cause • Hence, visit to a family doctor is strongly recommended rather than self medication based on public health disease propaganda

27. Acute Infections • An acute infection sets rapid onset of disease, has relatively brief period of symptoms, and resolves within days • It is responsible for precipitation of epidemics involving millions of individuals each year • Most of these are seasonal; and a pre-seasonal immunity building program is an appropriate solution rather than making several vaccines

28. Japanese Virus • Japanese Encephalitis Virus causes encephalitis in one case out of approximately 500 exposure cases • Hence, in this case, name of the virus should be Japanese virus and name of the disease should be Japanese Virus Encephalitis • Wrong nomenclature creates lot of confusion

29. Acute Encephalitic Syndrome • Acute Encephalitic Syndrome is current name to cover the disease as several other viruses have been associated with similar disease • Some kind of endocrine disruption is also probable in disease case • Reversing the acute inflammation is the key of treatment

30. Zinc Deficiency x Virus Interaction • Zinc deficiency is the fifth leading risk factor for disease in the developing world, aggravated due to diarrhea depleting zinc, weakens blood brain barrier, very common in Terai soils and soils of Gorakhpur • Improvement in zinc nutrition could minimize hypozincemia cases and thereby Acute Encephalitic Syndrome could be thus the additional hypothesis

31. Treatment with poxvirus factors • Some poxvirus factors initiate robust adaptive immune response • Treatment with poxvirus immuno-modulatory proteins targeting key innate pathways such as interferons, chemokines, inflammatory cytokines, complement, and the toll-like receptor (TLR) family of pattern recognition receptors could be hypothetical solution for Acute Encephalitic Syndrome

32. Adverse events due to smallpox vaccination • Smallpox vaccine is less safe than other vaccines routinely used today • The vaccine is associated with known adverse effects that range from mild to severe • Mild vaccine reactions include formation of satellite lesions, fever, muscle aches, regional lymphadenopathy, fatigue, headache, nausea, rashes, and soreness at the vaccination site • Serious adverse events included death, progressive vaccinia, eczema vaccinatum, postvaccinial encephalitis, and generalized vaccinia

33. Virus x Nutrient Interaction • Keshan disease (KD) is characterized by endemic juvenile cardiomyopathy found in China • KD is linked to the interaction of deficiency of selenium or vitamin E and Coxsackievirus B virus • Specific host nutritional deficiency alters viral genotype and makes it more virulent

34. Continued… • Antioxidant nutrients could be best preventive measures against several viral diseases • Recently, it is shown that nutrient x genome interaction could be used as therapy for Hepatitis C Virus Hepatosteatosis; beta-carotene, vitamin D2, linoleic acid, arachidonic acid (AA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) are nutrients of interest

35. Zoonotic Infections • Rabies virus is transmitted from dog (an animal) to human • The so called Japanese Encephalitis Virus is also transmitted from animal to human by mosquito • These are known as zoonotic infections • Several viruses are zoonotic

36. Reye’s Syndrome • Characterized by inflammation and swelling of the brain and degeneration of the liver attributed to Aspirin that interacts with viruses like influenza or chickenpox • It is believed by naturopaths that antipyretic treatment prolongs the illness and suppression of acute disease leads to chronic or severe disease • Asthma morbidity after the short-term use of ibuprofen in children has been reported

37. Drug x Virus Interaction • It can be hypothesized that some drugs that are used in the initial phases (like fever) to treat the ‘disease associated with virus’ could extend the disease causal chain by playing the role of component cause of the severe disease (like encephalitis) • Role of drug treatment for fever and bodyache in the initial phase of the viral infection progressing to the development of Acute Encephalitic Syndrome is not adequately studied

38. Post-viral Diseases • A post-viral cough is a cough that lingers following an infection, such as a common cold or flu • It could last for more than two months • Post viral cough could be resistant to treatment • Post-viral fatigue syndrome is characterized by fatigue following a viral infection

39. Antiviral Drug • Antiviral drugs are toxic to human cells • Only a limited number of metabolic functions can be targeted for development of antiviral drugs as viruses replicate inside cells using the cells' own machinery • Moreover, viruses are capable of developing resistance to antiviral drugs

40. Oseltamivir • CNS suppressive action of Tamiflu (oseltamivir phosphate), a drug used in influenza treatment, has been associated with sudden death and several neuropsychiatric disorders in children • Resistance to Tamiflu is also being reported

41. Bacteriotherapy • Several intestinal infections (A00 to A09 of ICD-10) as well as non-infective causes (K52 of ICD-10: colitis associated with Toxins, allergies etc.) lead to diarrhea • Bacteriotherapy reverses certain diarrhoeas associated with viruses, non-viral infections, and due to non-infectious etiologies also • So the (viral) diseases could also be named after prevailing dysbiotic conditions that could be rectified by Bacteriotherapy

42. Nervous Treatment for Diarrhoea • Several diarrheas can also be treated with anti-secretary drugs like Acetorphan (Racecadotril) that modulate the functioning of the nervous system without reducing gut motility at a prescribed dose • So the (viral) diseases could also be named after down regulation of enkephalinase or malfunctioning of nervous system.

43. Hepatitis b and Aflatoxins • Some of the cases of Hepatocellular carcinoma have been attributed to the interaction or working together of Hepatitis b virus and aflatoxins • Hepatitis b strategy (vaccination) is a way to prevent diseases associated with hepatitis b while aflatoxin strategy would prevent the cancer and several other problems created by the toxicities

44. Milwaukee Protocol • Unorthodox Coma Therapy (Milwaukee protocol) helps patient to survive rabies without a preventive vaccine • A cocktail of drugs is given to suppress brain activity • The suppressed brain provides time for immune system to produce the antibodies to fight off the virus Rodney Willoughby Jr http://graphics2.jsonline.com

45. Nonviral Targets • Protections offered by vitamin D in diseases like flu, selenium in viral cardiomyopathy, probiotics in diarrhea, spicy Indian curry in common cold or flu etc are indications that prevention and treatment of viral diseases could have nonviral targets

46. Innate immunity • Innate immunity protects the individual from several infections. It is built through proper nutrition and appropriate lifestyle. Some of the strategies to built innate immunity are taking regular exercises in fresh air and expose skin to Sun, reduce stress, maintain healthy microbiota in and on the body, consume lot of antioxidants and functional nutrients like omega-3 fatty acids obtained through food that emulates the food of a hunter gatherer.

47. Pediatrics and innate immunity • Acute viral infections are rampant in infants and children • Provide value added breast feeding and appropriate weaning • Exposure of an individual having strong innate immunity actually helps in development of specific and paraspecific immunity • Prevention of exposure to the viruses, acquiring specific immunities -- actively or passively -- through a series of vaccinations or immunoglobulins, treatment with interferons are just alternatives

48. Diagnosis provided by virologist • If comprehensive disease definitions are not provided for an individual patient then doctors are missing several targets to treat the diseases that are associated with viruses • It is very much required that virological diagnosis should not be dominated by clinician’s diagnosis • Otherwise one may miss simple solution like “Indian curry” and go for less efficacious and toxic antiviral drugs

49. Translation of Research • Performing research with incomplete disease definitions could result in outcomes that can not be translated • If translation is the mantra then comprehensive picture of the disease should be clear to the investigator • If outcome of virus research is not solution to the disease then research policy needs to be evaluated critically

50. There should be initiative to form Disease InformaticsGroup where doctors/ health workers, epidemiologists, information engineers work together to compile all the disease related information, update it regularly, and develop software tools required for defining the disease as described in this presentation. The definition of the disease for a particular patient should be with least error, should be in the form of Disease Causal Chain, should identify most of the targets – viral as well as non-viral – to combat (or prevent) a cluster of diseases and design a holistic treatment. Thank you