Disease and Contemporary Society

Disease and Contemporary Society Alan Mortimer PhD Lecture 1

The notes to accompany this lecture series are provided for the educational use of the course participants. It is believed that images may be used for educational purposes and are sighted where necessary. Full lecture notes have been provided due to limited sight lines in the classroom. Please note: These notes provide the background material. The actual lectures will include content and explanations which may or may not be represented in detail in the notes provided. Expect the material to evolve throughout the course based on interests of the participants. Alan Mortimer PhD

About Me

Course Objective To discuss issues related to diseases and their treatment in the 21 st Century. We will focus on the causes progression and treatmen of these diseases We will use specific diseases as examples of broader issues The approach will be based on understanding some of the biology (and other sciences) of the disease

Don t Panic

Course Overview Week 1: Infectious agents Vaccine preventable diseases Week 2: Bacterial infections Bacterial proliferation Antibiotics Week 3: Autoimmune diseases The body s immune system Diagnosis and treatment of autoimmune diseases

Course Overview Week 4: Viral Infections of the 21 st Century How viruses change Treatment of viral infections Week 5: Cancer Cell division and proliferation Cancer treatment and the concept of a cure Week 6: Emerging and re-emerging diseases Factors influencing emergent diseases

About You

Course Format Lecture and Discussion Please hold questions until there is a natural break (write them down) Time will be set aside for answering questions and for discussion Break at mid point May vary slightly depending upon material Other topics/critical issues If there are specific questions or topics related to the course material you wish to discuss or cover please let me know today. I will try to work them in.

Supplementary Material As topics described in this course current, a great deal of the material has been developed from varied technical sources There are few books that relate directly to the course material The reading list provides interesting background material

Infectious Agents Parasites Bacteria Viruses Prions

Parasites Single or multicellular Multiply either within a cell (malaria) or within tissue (shistosomiasis) Some can be treated with antibiotics Malaria Parasite

Bacteria Generally single cell organism Do not contain a nucleus Can reproduce May have several different forms throughout their life cycle Most can live outside the body Antibiotics generally prevent reproduction Cholera Bacteria

Virus 10 to 100 times smaller than a bacteria No cell nucleus Must enter another cell to reproduce Infective agent (viron) contains only RNA or DNA (sometimes a few enzymes) Surrounded by a virus membrane Influenza Virus

Virus Examples: DNA Virus: Influenza RNA Virus: HIV Antibiotics are ineffective

Relative Sizes

Vaccine Preventable Diseases

Of Interest It is interesting to note that for many diseases which are no longer a concern in developed countries, there is incomplete understanding Sometimes little molecular biology is available Mechanism of action is not always well understood If it isn t killing people now it is of lower priority for funding

Some Vaccine Preventable Childhood Diseases Currently Vaccinated Measles, Mumps, Rubella Pertussis, Meningitis Chicken Pox (Shingles) Diphtheria, Tetanus, Pertussis (polio) Pneumonia Meningitis Rotavirus HIB (Haemophilus Influenza b) No Longer Vaccinated Polio Smallpox

Routine Publicly Funded Immunization Schedule in Ontario Tetanus, diphtheria, polio, pertussis, Haemophilus influenzae type b Pediacel 2 Month 4 Month 6 Month 12 Month 15 Month 18 Month 4-6 years Grade 7 Grade 8 girls 14-16 years Every 10 years 65 years Annually Pneumococcal conjugate healthy Prevnar 13 Pneumococcal conjugate high risk Prevnar 13 1 2 2 Rotavirus Rotarix Measles, Mumps, Rubella (MMR) M-M-R ll, Priorix Meningococcal C Conjugate Menjugate, Meningitec, NeisVac-C 3 3 4 Varicella Varivax lll, Varilrix 5 Tetanus, diphtheria, polio, pertussis Adacel-Polio 6 Measles, mumps, rubella, varicella (MMRV) Priorix-Tetra Meningococcal quadrivalent conjugate A, C, Y, W135 Menactra, Menveo Hepatitis B Recombivax, Engerix 7 8 9 Human papillomavirus (HPV) Gardasil Tetanus, diphtheria, pertussis (Tdap) Adacel, Boostrix 10 11 One adult dose 11 Tetanus, diphtheria (Td) 12 Pneumococcal polysaccharide 23 13 Influenza 14

1 Prevnar 13: Healthy children receive Prevnar 13 at 2, 4, and 12 months of age. 2 Prevnar 13: High risk schedule for children with underlying medical conditions who receive Prevnar 13 at 2, 4, 6 and 15 months of age. Rotarix is given orally at 2 and 4 months. The National Advisory Committee on Immunization (NACI) recommends 3 that the first dose be given only between 6 week and up to 15 weeks (no later than 14 weeks and 6 days). The product monograph recommends that the second dose be given no later than 24 weeks, while NACI advised that it can be given up to less than 8 months. MMR should be given on or after the first birthday. A second dose is given at 4 to 6 years of age combined with 4 varicella in the MMRV vaccine Priorix-Tetra. For additional information, refer to the document entitled MMR, Varicella and MMRV Schedules. Varicella: A 2-dose schedule of varicella is now recommended. The first dose is given at 15 months as single 5 varicella; the second dose is given at 4 to 6 years of age combined with MMR in the MMRV vaccine Priorix-Tetra. For additional information, refer to the document entitled MMR, Varicella and MMRV Schedules. Diphtheria, tetanus, pertussis, and polio (Adacel-Polio) is the vaccine given at 4 to 6 years of age; can also be given 6 if 7 years of age or older and missed 4-6 year booster. Quadracel and Pediacel (if Hib is needed) should be given if the child requires a primary 3 dose series. MMRV (Priorix-Tetra) contains measles, mumps, rubella and varicella and is the recommended product for the 7 second dose of MMR and varicella which is given at 4 to 6 years of age. In Ontario, it is only recommended from 4 to 12 years of age inclusive. 8 Meningococcal quadrivalent conjugate (A, C, Y, W135) is offered free to Grade 7 students at school. Hepatitis B is offered free to Grade 7 students at school. It is a 2-dose series for those 11 to 15 years of age (0 9 and 4-6 months, depending on the product) and a 3-dose series for anyone outside this age range (0, 1 and 6 months). 10 Human papillomavirus (HPV) is offered free to Grade 8 female students at school. It is given as 3 doses (0, 2 and 6 months). Diphtheria, tetanus, and pertussis (Tdap) is the vaccine recommended for 14 to 16 year olds. This vaccine is 11 now publicly funded for adults. All adults should receive one dose of this vaccine even if they had a Tdap booster at age 14-16 years. 12 Tetanus, diphtheria (Td) boosters are recommended every 10 years for adults who have already received one dose of pertussis containing vaccine (Tdap). Pneumococcal polysaccharide 23 is recommended for people 65 years of age and older, people with high-risk 13 medical conditions and residents of long-term care facilities. One lifetime dose except for people with very high- risk medical conditions who receive two lifetime doses. 14 Influenza: Children 6 months to less than 9 years of age who have not been previously immunized with a seasonal influenza vaccine should receive 2 doses at least 4 weeks apart. For more information, contact the Middlesex-London Health Unit

Vaccine Preventable Childhood Diseases Today we will examine several as examples Mumps Measles Rubella We will also discuss (of interest to the present population) Chickenpox & Shingles All these are caused by viruses

Vaccine Preventable Diseases We will also examine the vaccine debate

Mumps Viral Infection Paramyxovirus Transmission by respiratory droplets Replicates in nasopharynx and lymph nodes Spreads to multiple tissues Meninges Glands such as salivary Pancreas, testes, ovaries

Mumps Complications Death 1/5000 Deafness 1/20,000 Pancreatitis 3.5% Orchitis/Oophoritis ~40% men ~5% in women In Canada Peak before vaccine was ~46,000/yr Peak since vaccine is 202/yr

Good Source of Information Good source of information and everybody s go to: CDC Pink Book Available on line

Measles Highly infectious viral infection First described in 7 th century Described by Persian physician Rhazes as more to be dreaded than smallpox First isolated in 1954 (Enders and Peebles) Per-vaccination 90% immune by age 15 Still endemic and fatal in developing countries

Measles WHO estimates 145,700 deaths in 2013 In 2000 estimate was ~450,000 deaths Reduction is due to global elimination strategy Led by WHO

Measles Paramyxovirus 1 antigenic types Hemagglutinin is an important surface antigen H glycoprotein does change but not important Respiratory transmission (as with rubella) Two stages Day 3 reticuloendothelial system (skin rash) Day 5-7 respiratory tract and other organs

Measles Complications are most common in those: 5 years of age and younger Age Distribution of Measles Complications. CDC Pink Book http://www.cdc.gov/vaccines/pubs/pinkb ook/meas.html 20 years of age and older

Measles Fatalities are usually due to pneumonia (60%) Primarily in children Second largest cause of death is encephalitis Usually in adults US mortality rate (1985-1992) 0.2% That is 1 in 500 cases

Vaccine Preventable Diseases We will also examine the vaccine debate

From: Historical Comparisons of Morbidity and Mortality for Vaccine-Preventable Diseases in the United States JAMA. 2007;298(18):2155-2163. doi:10.1001/jama.298.18.2155 Date of download: 11/19/2015 Copyright 2015 American Medical Association. All rights reserved.

MMR Vaccine Coverage in UK 1992-2012 Source UK National Health Service http://www.pbs.org/wgbh/nova/body/autism-vaccinemyth.html

Note to Participants Lecture slides will contain less information (words) I have provided greater detail for reference

Chicken Pox and Shingles Infectious agent is a Herpes virus VZV Varicella-Zoster Virus Varicella: chicken pox Zoster: shingles Three subfamilies of Herpes virus: Alphaherpesviruses - HSV-1, HSV-2, VZV Betaherpesviruses - CMV, HHV-6, HHV-7 Gammaherpesviruses - EBV, HHV-8

Chicken Pox and Shingles All look the same under electron microscope Enveloped double stranded DNA viruses. Genome consists of long and short fragments which may be orientated in either direction, giving a total of 4 isomers

Varicella-Zoster Virus Properties Belong to the alphaherpesvirus subfamily of herpesviruses Double stranded DNA enveloped virus Genome size 125 kbp, long and short fragments with a total of 4 isometric forms. One antigenic serotype only, although there is some cross reaction with HSV.

Epidemiology Primary varicella is an endemic disease. Varicella is one of the classic diseases of childhood, with the highest prevalence occurring in the 4-10 years old age group. Varicella is highly communicable, with an attack rate of 90% in close contacts. Most people become infected before adulthood but 10% of young adults remain susceptible. Herpes zoster, in contrast, occurs sporadically and evenly throughout the year.

Pathogenesis The virus is thought to gain entry via the respiratory tract and spreads shortly after to the lymphoid system. After an incubation period of 14 days, the virus arrives at its main target organ, the skin. Following the primary infection, the virus remains latent in the cerebral or posterior root ganglia. In 10-20% of individuals, a single recurrent infection occurs after several decades. The virus reactivates in the ganglion and tracks down the sensory nerve to the area of the skin innervated by the nerve, producing a varicella form rash in the distribution of a dermatome.

Varicella Primary infection results in varicella (chickenpox) Incubation period of 14-21 days Presents fever, lymphadadenopathy. a widespread vesicular rash. The features are so characteristic that a diagnosis can usually be made on clinical grounds alone. Complications are rare but occurs more frequently and with greater severity in adults and immunocompromised patients. Most common complication is secondary bacterial infection of the vesicles. Severe complications which may be life threatening include viral pneumonia, encephalititis, and haemorrhagic chickenpox.

Rash of Chickenpox

Herpes Zoster (Shingles) Herpes Zoster mainly affect a single dermatome of the skin. It may occur at any age but the vast majority of patients are more than 50 years of age. The latent virus reactivates in a sensory ganglion and tracks down the sensory nerve to the appropriate segment. There is a characteristic eruption of vesicles in the dermatome which is often accompanied by intensive pain which may last for months (postherpetic neuralgia)

Herpes Zoster (Shingles) Herpes zoster affecting the eye and face may pose great problems. As with varicella, herpes zoster in a far greater problem in immunocompromised patients in whom the reactivation occurs earlier in life and multiple attacks occur as well as complications. Complications are rare and include encephalitis and disseminated herpes zoster.

Shingles