Today. Emerging Diseases. The concept of anti-ideas. Why new diseases appear Some specific examples. Vaccines

Size: px

Start display at page:

Download "Today. Emerging Diseases. The concept of anti-ideas. Why new diseases appear Some specific examples. Vaccines"

Tyler O’Brien’
5 years ago
Views:

1 Emerging Diseases

2 Today Emerging Diseases Why new diseases appear Some specific examples The concept of anti-ideas Vaccines

3 Ecology of Disease In most cases epidemics and plagues are caused by an infectious agent entering (finding?) an new ecological niche

4 Emerging Diseases Changes that can lead to an emerging disease 1. Changes in the local environment 2. Relocation to a new environment 3. Genetic changes in the infectious agent

5 Changes in the Local Environment Changes in population distribution Usually (but not always) urbanization Plague, TB in Indigenous populations Global Warming Vector borne diseases Lyme disease, Dengue Fever, Chikungunya Physical Environment Changes Catastrophic Changes (e.g. flooding) Human intervention Cholera, Ebola

6 Relocation to a New Environment Transport from an endemic region to naïve region Historically Smallpox A greater hazard with increased international travel Spanish Flu SARS MERS Zika

7 Genetic Changes in the Infectious Agent Mutations within the genetic material of a virus can make a relatively benign infection highly virulent. Zika

8 Species Jump Transfer of infectious agent from animal to human SARS Ebola HIV Innfluenza

9 We have discussed impacts of urbanization

10 With increasing temperatures the range of disease vectors changes Mosquitoes Ticks Global Warming

11 Dengue Fever Also know as Breakbone Fever Viral infection with 4 serotypes Transmission by mosquito Aedes aegypti Widely distributed throughout the world Also spread Yellow Fever, Zika and Chikungunya

Dengue Fever Developed in monkeys Jumped to humans in Africa/SW Asia 100-800 years ago

12 Dengue Fever Developed in monkeys Jumped to humans in Africa/SW Asia years ago Second world war transported mosquito and disease around the world 100 million infected annually

Dengue Fever Symptoms Symptoms start 3-10 days after bite Skin rash High fever: 104-105 for 4-7 days

13 Dengue Fever Symptoms Symptoms start 3-10 days after bite Skin rash High fever: for 4-7 days Febrile seizures: can be extremely severe hence the name breakbone fever Usually resolves after 10 days

14 Dengue Fever No vaccine available No treatment Prevention has been partially successful

15 Dengue Hemorrhagic Fever 4 Serotypes of Dengue Infection with one serotype does not provide immunity to other three In fact infection with a second serotype is much more serious

develop Crisis period lasts 1 day Bleeding occurs in

16 Dengue Hemorrhagic Fever Symptoms: Similar course to Dengue Fever But with fever shocklike symptoms develop Crisis period lasts 1 day Bleeding occurs in patches under the skin Sometimes bleeding from nose & mouth

17 Dengue Hemorrhagic Fever Shock-like symptoms develop Can cause death 100,000 deaths each year due to Dengue and Dengue Hemorrhagic Fever Increased capillary permeability and reduced clotting ability are believed to be due to over-reaction of the immune system Antibody-dependent Enhancement (ADE)

18 Dengue Fever Dengue Fever is one of the fastest spreading (geographically) vector borne infectious diseases Cases have been reported in Southern Texas (2005) Endemic throughout Caribbean

19 Dengue Fever Range could be impacted by climate change Dengue seems to be more ubiquitous than yellow fever

21 Physical Environment Change Ebola is caused by a virus (Ebolavirus) which is endemic in certain fruit bat colonies in central Africa

22 Ebola Virus Fruit bats are considered the natural host Contact with blood, secretions, organs or other body fluids Chimps, gorillas, monkeys, forest antelope, porcupines

23 Ebola Virus 5 known Ebola viruses 4 infect humans Clinically almost identical to Marburg virus First recorded epidemic: August 26, 1976 in Yambuku on the Ebola River DRC Zaire EBOV

24 Ebola Virus May have the highest case mortality of any known disease: 90% in some epidemics; 83% overall With treatment as low as 50% Sporadic outbreaks in remote villages usually in or near to rainforest

25 Ebola Virus Human to human transmission through infected tissue of fluids Family members Funerals Health care workers (poorly protected) Transmission via infected serum can occur up to 7 weeks

26 Ebola Virus Symptoms 2 21 days following infection Stage 1: fever, intense weakness, muscle pain, headache, sore throat Stage 2: vomiting, diarrhoea, rash impaired kidney function, internal & external bleeding Infectious up to 61 days

inflammation) Endothelial cells, hepatocytes are targets

27 Ebola Virus Virus enters monocytes in the blood stream and multiplies Breakup of cells causes cytokine response (fever, inflammation) Endothelial cells, hepatocytes are targets Death of endothelial cells causes blood leakage ad clotting problems

28 Ebola Outbreak 2014

29 Chronology Index Case: 18 month boy in Meliandou Sparsely populated area Only 31 households Located in the forest district (Gueckedou) Largely deforested (up to 80%) for resource development Brings animals in closer contact with people -Seen playing near a hollow tree infested with bats

30 Chronology Died December 26, 2013 Vomiting, black stools, fever Early January family members, traditional healers, midwives in village had died Spread to 4 other sub districts First report January 24, 2014 district health clinic investigated by MSF 5 cases of severe diarrhoea: rapidly fatal outcome

31 Chronology Ebola had never been seen in East Africa General belief put area at low risk Cholera and Lassa Fever are widespread Based on symptoms only Cholera would be expected Cholera bacteria were found in post mortem samples Probably endemic infection

32 Chronology Carried to capital city Conakry by member of boy s extended family Died in hospital Feb 5 Doctors had no reason to suspect Ebola No measures were taken Disease spread to 4 cities and along routes

33 Chronology Ministry of Health issued alert on unidentified disease March 13, 2015 WHO/AFRO, WHO, MSF investigation March Epidemiology and Outbreak tracing Laboratory analysis 21 March Pasture Institute identified flavivirus 22 Identified Zaire strain of Ebola virus

34 Chronology March 23, 2015 outbreak was announced by WHO 49 cases 29 deaths reported Under control April 13, 2016 Cases 28,633 Total of 11,325 deaths

35 Early Epidemiology

37 Fighting Ebola Support the patient so that the immune system can fight the virus Improve the immune system convalescent serum Anti-viral Vaccines Possibly

38 Above All Education: Cultural practices, particularly funeral practices Identification of symptoms Reducing stigma Seeking medical care Reduction in spread can be related directly to: Community driven education programs Availability of medical care

43 Genetic Changes Mutations can make a relatively benign virus highly pathogenic

44 Zika Virus

45 Zika Virus Zika virus is an arbovirus transmitted by mosquito Aedes family Aedes Aegypti (principally) Same mosquitos transmit: Dengue fever Yellow Fever Japanese Encephalitis

46 Zika Virus Flavivirus family Includes Dengue, Yellow Fever, Japanese Encephalitis RNA virus Capsid enclosed Surrounded by membrane Primate intermediate host Monkey primary

47 Zika Virus Incubation time in mosquito is about 10 days Incubation time in humans 2 to 7 days 25% show symptoms Remains in blood for typically for about 1 week (unclear as yet) Appears to remain longer in semen (limited data)

48 Zika Virus History First isolated from rhesus monkeys in Zika forest Uganda in 1947 First evidence in humans was 1952 in Nigeria A significant number of Indians tested showed an immune response (1952) Indicates it had been present there for some time Case reports from Africa and South East Asia Only a total of 14 confirmed cases up to 2007

49 Zika Virus History First outbreak outside Asia and Africa was in 2007 Yap Islands Micronesia 49 confirmed cases No hospitalizations, no deaths French Polynesia confirmed cases 8750suspected cases 47 presented with neurological symptoms

51 Zika Virus History Zika outbreak identified in Bahai State NE Brazil in early 2015 Identified in neighbouring countries, in particular Columbia Now identified in most countries in South and Central America within range of Aedes mosquito

52 Link to Microcephaly First cases (35) of microcephaly were identified in October 2015 in women who reported having rash (no confirmed disease) To end of January 2016 ~3500 cases have been reported Recently Zika virus RNA has been found in several infants who died at childbirth

53 What Happened? Chinese scientists sequenced the RNA genome of the virus Compared samples from 2010 outbreak in Cambodia to 2015 samples Disease had been transported by travelers potentially Confederations Cup 2013 from Polynesia to Brazil Scientists found 8 mutations in the RNA They made clones with only one of each of the mutations Seven were relatively benign when tested in mice One (S139N) caused nerve tissue damage and brain damage

54 What Happened?

55 Treatment and Prevention Treatments for viral infections are difficult and expensive to develop (think AIDS) Vaccine development is possible but will take time Potential concerns

56 The number of cases of microcephaly has dropped drastically from a peak in 2016 Genetic sequencing is not yet available Is it education or virus change?

57 Species Jump Some viruses can infect multiple species When in close proximity one species can infect another

58 SARS Severe Acute Respiratory Syndrome First cases in (Guangdong Province) November 2002 (atypical pneumonia) Reported by China February 2003 First case identified in Hong Kong (March 2003) and Hanoi (February 2003)

59 Spread by Travelers Doctor who treated patient in Guangdong travelled to Hong Kong for a wedding (Metropole Hotel) Spread to several dozen hotel guests within 24 hours Canadian (78 year old woman) on holiday at the same hotel contracted SARS Returned home Became Canadian Index Case

60 SARS in Canada Highly contagious Spread by reparatory droplets Spread to Family members Health care workers Outbreak attenuated rapidly 44 deaths

61 Original source was determined to be civet cats a delicacy in China Original Cause

62 Influenza

63 Influenza Virus Three types of influenza A: Rapid onset, more severe, causes death B: Longer onset, less severe C: Does not infect people Classification is based on Hemagglutinin and Neuraminidase 16 HA and 9N H1,2,3 & N1,2 common

64 Influenza virus has a lot of hosts!

66 Internal System Detects foreign cells Self identification molecules Marks foreign cells Antibodies Destroys foreign cells and removes them Variety of techniques depending on type of invader

67 Antibody Mediated Response University of Illinois at Chicago

68 Types of vaccines Killed virus Inactivated Partial protein

69 Killed Virus Grown in living cells Eggs Vero cells Rhesus cells Purified by ultracentrifugation Killed by chemicals: Formaldehyde Detergents

70 Inactivated Grown in non-human cells Grown at subphysiological temperatures 7 passages for polio

71 Oral Polio Vaccine Problems Reversion OPV diseases due to shed virus VAPP Monkey viruses (SV40) Now test for specific viruses No longer used in most countries where polio has been eradicated

72 Partial protein Usually bacterial vaccines May use only part of the bacterial cell May synthesis only key proteins

73 Adjuvants Adjuvants Materials added to vaccine to increase effectivness Stimulate the non-specific immune system Macrophages stimulate B cell and T cell production Need to be in the appropriate size range Can increase immunogenicity by a factor of 5

74 How to improve the vaccines Adjuvants: Several oil-in-water adjuvants, including MF59 and AS03, have significantly enhanced immune responses in healthy adult vaccine recipients to inactivated influenza A/H5N1 or H1N1. These adjuvants may also broaden the spectrum of immune protection (multiple subtyes of virus). The adjuvants may spare antigens: good for pandemic preparation.

75 Fact Based Decisions Naive populations Need to look at early vaccination for a specific disease Best data is for polio in North America National vaccination began in ,000 cases in ,000 cases in cases in 1961

77 Fact Based Decisions Costs can be difficult to calculate Large herd immunity Few diseases are reportable Many remaining diseases are not fatal One correlated statistic (without causation) The year after the introduction of influenza vaccine in Ontario, there was a 30% reduction in hospital emergency room visits during flu season

78 Fact Based Decisions New diseases do not have the same demographic impact as recurring diseases

79 Unusual Age Distribution Median Deaths/100k ph1n1 10 Average Deaths/100k Mortality rate per 100,000 separated by age group for 2009 H1N1 Pandemic and Average influenza related deaths for the period

80 Fact Based Decisions Rare diseases Limited sample size Difficulty getting significance Difference between raising immunity and preventing disease Surrogate Markers HPV for Cervical Cancer

81 Under-Vaccination Concerns as early as the first vaccine Smallpox: concerns about injecting cow into people Similar concern exists today: injecting foreign material into people

82 Under-Vaccination Perceived risk-benefit has changed A generation without serious infectious disease

83 The Autism Scandal Autism appears at the same developmental period when childhood vaccinations are given Andrew Wakefield published a report in Lancet linking MMR vaccine and Autism Retracted by the journal in 2010 Conflict of interest Manipulation of data Callous disregard of suffering of children

84 The Autism Scandal

85 Thymerisol Mercury based antibiotic used in some multiple dose vaccines Eliminated in 2001 No change in rates of neurological conditions before or after 2001 (NIH etc)

86 Media Recent article in Toronto Star (Feb 05, 2015) Article was focused on people who had presumed side effects from HPV vaccine The positive stuff was added as an afterthought (probably by lawyers) Really badly written Supported by media because he was award winning and respected

87 HPV vaccine Gardasil has a dark side, Star investigation finds Although hundreds of thousands of girls in Canada have safely taken Gardasil, at least 60 Canadians experienced debilitating illnesses after inoculation. By: David Bruser News Reporter, Jesse McLean Investigative News reporter, Published on Thu Feb Vaccine debate is one we shouldn t even be having: Mallick Heather Mallick Columnist, Published on Fri Feb Many hundreds of thousands of teenage girls in Canada have been safely given the three-dose vaccine but since 2008 at least 60 have suffered convulsions or disabling pain afterwards. It s not clear why but it is worth noting and investigating, as the story said repeatedly. Their suffering matters. These girls are worth listening to.

88 Great Ideas of Biology Alan Mortimer PhD

89 Dengue Fever Prevention

The Struggle with Infectious Disease. Lecture 5

The Struggle with Infectious Disease Lecture 5 Tropical Diseases Life and infectious disease began in the rift valley/rain forest of Eastern Africa Peoples migrated North to temperate regions Tropical