1
Q
changes brought about by Pasteur’s germ theoryni
A
antisepsis (the practice of using antiseptics to eliminate the microorganisms that cause disease) antibiotics immunization sanitation public health
2
Q
impact of germ theory
A
reduced childhood mortality
life expectancy increased- elderly pop is 13% of US population
3
Q
current top causes for dealth in US, and world wide threats
A
US:
1) Heart disease
2) cancer
3) stroke
4) pneumonia
worldwide: infections acocunt for 30-35% of all dealths
ex: TB infects 30% of world population
4
Q
definiction of emerging infections
A
new, re-emerging or drug resistant infections whose incidence in humans has increased within the past two decades or whose incidence threatens to increase in the near future
5
Q
factors leading to infectious disease emergence
A
- microbial adaptation and change
- human demographics and behavior
- international travel and commerce
- economic development and land use
- technology and industry
- breakdown of public health measures
- human susceptibility to infection
- climate and weather
- changing ecosystems
- poverty and social inequality
- war and famine
- lack of political will
- intent to harm
6
Q
microbial adapatation and change mechanisms/reasons
A
a number of microbes utilize different genetic mechanisms
- genome sequencing shows lateral transfer is common
- high mutation rates in RNA viruses=rapid adaptation
- quick reproduction so rare mutations build up rapidly
antimicrobials for livestock growth enhancement and over prescription of antimicrobials by doctors for convenience
-evolve modifying enzymes and “drug pumps”
superbugs ex: streptococcus and penicillin staphylococcus and vancomycin tuberculosis and isoiazid malaria and choloroquinone
7
Q
human demographics and behavior leading to emerging infections
A
-increases in human population
urbanization-more people in concentrated cities-often without adequate infrastructure
increases in the elderly population
increases in children in daycare, working women with kids= easy spread
fast paced lifestyles- which lead to increase in convenience items and more stress
high risk behavior- drug use and unprotected sex
international travel and commerce- easier and faster to travel the globe, transportation of products is rapid (fresh produce with diseases) and transport of livestock facilitates movements of viruses and arthropods (esp ticks)
increases in cruise ship travel
8
Q
economic development and land use leading to emerging diseases
A
consumption of natural resources, deforestation and dam building
logging in the rainforest has exposed people to new viruses
new standing water from dam building, canalization and irrigation
reforestation in some parts of north american has caused the emergence of lyme disease in those arease
9
Q
tech and industry relationship to emerging diseases
A
advances in technology are positive but medical technology has lead to people living longer but with weaker immune systems, blood tranfusions and organ transplants save lives but can cause infections
transportation technology- the ability to rapidly move people and goods
industrial changes- mass production of food so now we all get our water and food from same sources= easy to make many people sick from one source
industrial pollution increases incidence of TB
10
Q
breakdown of public health worldwide and increase in emerging infectious diseases
A
world wide breakdown of public health measures like adequate sanitation, immunizations, tb control have increased EID
IMF and world bank reducing public sector investments led to nagative impacts such as immunization levels, nuitrition and medical supplies to drop
similar reduction in public health funding in US caused reduction in programs for disease prevention and surveillance
lack of diagnosis and treatment in many areas of the world
11
Q
human susceptibility to infection
A
caused by:
impaired host immunity: AIDS and increases in the older population
genetic polymorphisms, malnutrition-host susceptibility is aggravated
12
Q
climate and weather and emerging infectious diseases
A
global warming will continue to cause temps to increase
elevated rainfall
-is a breading habitat for mosquitos
-decreases in salinity can increase toxic bacteria
-increases vegitation increases rodents
-increase runoff into drinking reservoirs
hgiher ocean temps increase vibrio parahaemolyticus (Shellfish)
some soil pathogens are carried by dry dusty winds
13
Q
changing ecosystems impact on infectious diseases
A
ecological changes can increase the risk of infection by altering human exposure or pathogen distribution
rainforest destruction- forests reduce while cropping increases humidity
urban development increases atmospheric particles and increases air temperatures
14
Q
poverty and social inequality and EID
A
mortality from infectious diseases closely correlated with income- developing and former communist bloc communiites
factors: malnutrition, lack of clean water and sanitation, poor housing, ignorance of risky behaviors and lack of social agenices to teach these things, lack of transportation, lack of funds
population of the poorest is increasing the fastest
15
Q
war and famine and EID
A
war refuges- 1% of global pop
war refugees are forced into new areas where they are exposed to new microbes from vectors and people
war and famine are closely linked
famine is also caused by social, economic and political forces. Weather and HIV/AIDS
16
Q
Lack of political will and EID
A
a global commitment is rather vague
developing world diseases don’t matter to politicians
need donors, healthcare professionals, country authorities and patients
17
Q
intent to harm and EID
A
recognized as threat, even before 2001
countries- US versus Russia
18
Q
The big 3
and diseases beyond the big 3
A
The big 3 Malaria TB HIV Diseases beyond the big 3 Respiratory infections Enteric infections STDs Vector-borne diseases
19
Q
Emerging infectious diseases
A
Emerging infectious diseases are those whose incidence in humans has increased within the past two decades or whose incidence threatens to increase in the near future
May be due to:
Spread of a new agent
Recognition of a previously undetected agent
Finding that an established disease has an infectious origin
Reappearance of an agent after decline
20
Q
Emerging Infectious Diseases
and CDC
A
Targets Surveillance and Response Applied Research Infrastructure and Training Prevention and Control
The Early Outcomes:
Raised awareness of public health deficiencies
We understood what needed to be done; however, minimal funding to do it
21
Q
Addressing the EID Threat-2018
A
Increased awareness of EIDs
Increased public health workforce Improved surveillance systems State-of-art PHL diagnostic technologies Effective laboratory networks LRN, WCLN, PHL reference centers Much improved outbreak response More and improved vaccines
22
Q
current EID threat
A
is global
high priority in high-income countries, top priority in low-income countries
23
Q
definitive host
A
: Host in which the sexual stage of a parasite life cycle occurs
e.g. humans / Schistosoma
mosquitoes / malaria
24
Q
intermediate host
A
Host in which asexual reproduction or development occurs
e.g. snails / Schistosoma
humans / malaria
25
incidental
accidental
): Is not an obligate part of the parasite life cycle
e.g. humans / Toxoplasma
often humans
26
Reservoir
Long-term hosts that maintain the natural cycle in the wild
- often are not really harmed be the carriage
e. g. mice / Toxoplasma
27
Vector
A host species that transmits an infectious form of the parasite to another host species
e.g. mosquitoes / malaria
snails / Schistosoma
28
What makes an animal a good reservoir for human infectious diseases?
Commonly infected and carries the infection for a long time
Wide geographic range
Common contact with humans
Not sick, does not show signs of disease
A reservoir does not have to be a vector, but vector such as tick or mosquito can be a reservoir
ex: bats are a reservoir for Ebola
29
Geographic distribution
: the maximum global extent of a disease regardless of intensity
30
Prevalence
disease intensity in a given area (% susceptible population)
| sporadic vs endemic vs epidemic
31
Colonization
: microbial infection where the infected person has no signs, symptoms, or damage of infection while still having the potential to infect others
32
Virulence
Virulence: severity or harmfulness of the pathogen
33
zoonoses
transmission of the infectious agent
to humans from an ongoing reservoir life cycle
in animals, without the permanent establishment
of a new life cycle in humans
ex: rabies, ebola, bird flu
just need good public health measures to control this
34
Species jumping
the infectious agent derives
from an ancient reservoir life cycle in animals,
but they have established a new life cycle in
humans that no longer involves the animals
35
Why it is important to understand the difference
| between zoonoses and species jumping?
Prevention
Eradication
Virulence
36
Factors that Contribute to the Emergence of a New Zoonoses
Microbial/viral (e.g. mutations and evolution)
Individual host (lack of immune surveillance (AIDS)
Population host (e.g. transportation and urban crowding)
Environmental (e.g. ecological and climate influences)
Global human and livestock populations continue to grow
-this brings people and animals in closer contact
Advanced transportation makes long distance travel
possible in less than the incubation period
of most infectious agents
Massive ecological and environmental changes brought
about by humans
Zoonotic agents may be the choice for many
bioterrorist activities
37
Trypanosomiasis
Called Sleeping Sickness, vector is the tsetse fly
Classical example of an emerging infection, 1890-1930
-re-emerged in 60s,
Leading public health problem in Africa during that time,
colonialism brought it to new areas
Nearly eliminated by 1960 using population screening,
case treatment, chemoprophylaxis
Re-emerging infection in central Africa
-1960s was a time of turmoil and political upheaval because colonization was ending+ civil unrest due to the cold war
38
types of African trypanosomiasis
west african: humans are the reservoir, diseases is chronic (since we are the reservoir it takes a long time to kill us), mortalilty is 100%,
East Africans: reservoirs are antelopes and cattle- so direct zoonosis to humand, disease has rapid progression in humans since we arent the reservoir and pathogen doesnt care if it kills us, mortality is 100%
has waves of pasasitemia- same thing as plasmodium
10 days is about how long it takes adaptive immune response, so the pathogen changes its surface coat so immune repsonse can't detect it, every 10 days, so can't be detected= no way to make a vaccine
39
problems estimating t trypanosomiasis
60 million people at risk, but <2 million screened
No health facilities in many areas at risk
Conflict or insecurity in epidemic foci
Clinical diagnosis is difficult until late in disease
- intermittent fever
- lymph node swelling
- headaches and sleep disturbance
- weight lose (they look like AIDS)
- lab diagnosis is hard (antigenic variation)
40
Management of Trypanosomias
Disease management in three steps:
1) Screening for potential infection. Serological tests and/or checking for swollen cervical glands.
2) Diagnosis shows whether the parasite is present.
3) Staging to determine the disease progression. -examination of cerebro-spinal fluid by lumbar puncture
41
Treatments for Trypanosomias
First stage treatments: early drugs are good
| Second stage treatments: late drugs must cross BBB
42
Hantavirus
Enveloped negative strand RNA virus
-now named the Sin Nombre virus
Chronic, asymptomatic infection of rodents
Excreted in fresh rodent urine, saliva, feces
-breathed in by humans
Worldwide distribution
No insect vectors
Susceptible to many disinfectants
43
hantavirus in humans
Incubation period is not really known…1-5 weeks?
First symptoms include fever, fatigue, and muscle aches
After a few days: shortness of breath (lungs fill with fluid)
and sometimes headaches, dizziness, nausea, vomiting,
diarrhea, and stomach pain.
RAPID progression-short time to death
Treatment: only intubation, the earlier the better
more common in rural dry areas
4 species of mice that carry it in US
44
SARS (severe acute respiratory syndrome)
first surfaced in china but China didn;t divulge this info,
it spread world wide by travellers
Symptoms are initially flu-like illness: rapid onset of high fever followed by muscle aches, headache and sore throat.
Early laboratory findings may include:
thrombocytopenia (low platelet count)
leucopenia (low white blood cell count)
followed by bilateral pneumonia
progressing to acute respiratory distress
Mortality rate for younger people is between 3-6%, but about 50% for persons over 65.
45
SARS origing
S. east asia makets- easier for zoonosis to occur from fresh market for meat has animals and humans crammed together so not surprising it broke out
civets are most likely reservoir- probs picked it up from a more exotic species and then were brought to market
it is a novel RNA sequence so the virus probs evolved in isolation for a long time before jumping to humans.
zoonotic disease
46
Ebola virus
negative strand RNA virus, enveloped
broke out in Africa, public health measures were not fast enough to control it
symptoms:Fever, Severe headache, Muscle pain, Weakness, Fatigue, Diarrhea, Vomiting, Abdominal (stomach) pain, Unexplained hemorrhage (bleeding or bruising)
Symptoms may appear anywhere from 2 to 21 days after exposure to Ebola, but the average is 8 to 10 days.
Recovery from Ebola depends on good supportive clinical care and the patient’s immune response. People who recover from Ebola infection develop antibodies that last for at least 10 years.
reservoir most likely fruit or insectivore bats
47
Increasing Numbers of Immunocompromised Persons- why?
HIV is increasing worldwide
Older persons (aging baby boomers)
Patients with cancer, after transplants, diabetes, obesity etc.- improving tech allowing people to live with cancer etc longer
Malnutrition is still over 10% or 815 million people and major source of immune compromised people
13 Factors of Emerging Infectious Diseases:
Human Demographics and Behavior
Human Susceptibility to Infections
Technology and Industry
48
Why are the elderly at increased risk for infectious diseases?
Older persons spend more time in hospital, exposing them to infections
Older persons have more medical procedures performed
e.g. catheterization increases UTIs
Institutionalization (nursing homes) increases infections abd crowding
e.g. aspiration pneumonia, infected pressure ulcers, implants,
Physiological Changes of Aging
1) Immune changes increase infection risks (e.g. TB, influenza)
2) Age-related diseases (cancer, diabetes, dementia etc.) increase infections
3) Organ changes in older persons:
- skin (dry and crakced= bad defense)
- stomach acid reduced- first line a/ enteric pathogenes
- bladder changes increase UTIs- not as strong, so easy pathogen transfer/survival
- organ transplants or plastic and metal parts internally
49
Immune Changes with Age
Protective immunity drops with age
-poor priming to new antigens
(efficacy of immunization is decreased)
-poor recall of old antigens (i.e. antigens you saw
when you were young)
-poor affinity maturation- low IgG (i.e. not high affinity)
Poor proliferation of T cells, poor IL-2 production= can't recognize as many pathogens and poor memory of pathogens
Many changes in later cytokine production (IL-4, IFN)
T cell subsets: naïve are down and memory are up
T cell microclones-as much as 50% of T cells are clones
(5000 to 10,000 each) thus not a broad repartee
50
obesity and influenza/other diseases
direct correlation between post-op and worse influenza disease in obese people- direct correlation with body mass index and hospitalization
later
later noticed that obese people are at increased risk for hospitalization during seasonal influenza and saw this in other infections too
obesity is increasing in the US and worldwide, including in children
51
obesity and immunity connection
Adipose tissue is not just cells that store fat, there are lots of immune cells in adipose tissue- is an active endocrine organ
-it is a chronic state of inflammation= bad response to pathogens
Adipose tissue is considered an active endocrine organ
Adipocytes produce and respond to proteins
Adipocyte-produced proteins are called adipokines
Some adipokines are cytokines produced by immune cells
TNFα and IL-6 are cytokines that are “bad” adipokines
Obesity sets up a state of low-grade, chronic inflammation that results in immunodeficiency including altered lymphocyte and monocyte functionality
Both diet-induced and genetic obesity leads to increased susceptibility to bacterial and viral infection-seen in lab animals as well as some case studies
obesity affects several components of the immune response- T cells, NK, B-cells, macrophages
poor response to vaccination- showed definitive decreased response to vaccine for Hepatitis B, and not getitng as much long term immunity
but if people lost weight, response improved
52
Cryptosporidium parvum
water-borne pathogen
Increased dramatically with the AIDS epidemic, by 1986
4% of AIDS patients had cryptosporidiosis with a
61% fatality rate
Large reservoir of wild animals and livestock
Lifecycle is completed within a single
life-cycle:
intestinal parasite
intracellular-cytoplasm, but also in brush border membrane
no treatment for it-has a different life-cycle to hard to treat
oral rehydration therpay is all you can do-have to wait for our own immune cells to clear it
also hard/expensive to make vaccine
53
Cryptosporidium in Human Disease
WATER-BRONE
Transmission is fecal/oral: outbreaks associated
with faulty water purification
1-2 week incubation with PROFUSE watery diarrhea (12L/day)
We shed oocysts in stool; cysts are very robust,
resistant to chlorination must boil
Self-limiting except in immunocompromised patients
Nitazoxanide for people with healthy immune response but…
no effective drugs for immune compromised; treatment oral rehydration
54
Cryptosporidium Prevention
Existing water testing and treatment methods can fail to reliably
detect or remove it
Cryptosporidiosis has been linked to drinking and recreational
water (LAKES, GOLF COURSESE), food, person to person and farm animal contact
55
Cholera
No vaccine or natural immunity, re-infection is common (same as cryptosporidium)
very bad in refugee camps
prevalent in southern africa and southern asia
Etiological agent is Vibrio cholerae- serogroup O1, Biotype El Tor
that produce cholera toxin
Clinical features vary from asymptomatic to profuse watery
diarrhea with vomiting, circulatory collapse and shock
25-50% of cases at fatal if untreated- treatment is oral rehydration
therapy (sugar and salt mixed with clean water)
hard to deliver in remote areas and during epidemics
Risk group is persons living in poverty in the developing world,
low risk for travelers, virtually no risk for persons in the US.
Transmission is through contaminated drinking water or food
-large epidemics often related to fecal contamination of
water or street vended foods
-occasional transmission from undercooked shellfish
that have been naturally contaminated
In developing countries, population migrations into urban centers
have strained the existing water and sanitation infrastructure
56
O1- El Tor Strain
it had replaced classic cholera strain
The El Tor strain has been isolated as free-living bacteria or
with phytoplankton, zooplankton, crustacea, and mollusks
The El Tor strain can produce a “rugose” phenotype which is
exopolysaccharide production that confers chlorine
resistance and biofilm formation
The survival of El tor is decreased if the seawater is filtered
Attachment to surfaces is important for marine organisms
- surfaces absorb and concentrate scarce nutrients
- biotic surfaces (chitin) can be degraded by attached bacteria
Cholera has reemerged because it can form a biofilm to stick to surfaces= allowed it to spread
rugose form can build biofilm, but now it is susceptible to filtration
57
Cholera Prevention
Epidemics are markers for poverty and lack of basic sanitation
Need infrastructure for sanitation and safe water handling
- addition of sodium hypochlorite solution
Vaccine offers incomplete protection for a short duration:
- no multivalent vaccine for O139 strain
- O139 has changed its antigenic surface
Natural reservoir in warm costal waters makes eradication highly unlikely
- How did Bengal replace El Tor? Now they co-exist?
Travelers should “Boil it, cook it, peel it, or forget it”
- drink water that has been boiled or treated
- eat only foods that have been cooked and are still hot
- eat food that you peel yourself
58
biological basis for infectious disease epidemiology
| -the factors that make an organism capable of causing an outbreak
1) pathogenicity
2) virulence
3) infective doese
4) incubation period
5) persistence
6) communicability
59
Pathogenicity
Ability to produce disease in an organism
Not the Virulence
Either a pathogen or not
```
Ability to
enter tissue
colonize
produce toxins
spread from host to host
almost a yes/no question
```
60
virulence
how damaging the symptoms are
| virulence is the organism's degree of pathogenicity
61
infective dose
how much of the pathogen needed to cause disease
| ex: ebola, need very little
62
incubation period
how long until symptoms appear after infected
| ex: anthrax 2 days, Ebola 2 weeks
63
persistence
how long before pathogen stops being infective
| -stability in environment so it can stay and continue to cause disease
64
communicability
how fast it can spread
65
Ro
reproductive number
the average number of secondary cases a typical infectious individ will cause in a completely susceptible population
used to predict how bad an outbreak can be
needed to calc how many people to vaccinate if you are to achieve herd immunity
Ro greater than 1= out of control
R0= 1 low
Ro less than 1= what we want, under control
66
passive surveillane
dectors report diseases on the side, their main job is to treat patients
-allow recog of outbreak
67
active surveillance
poeple being paid to go and their priority is surveying and finding diseases
-allow recog of outbreak
68
syndromic surveilance
googling disease symptoms and that being reported
| -allow recog of outbreak
69
case definition
standard set of criteria for deciding whether a person should be classified as having the disease or not
Classify cases as one of the following:
Confirmed: laboratory verification
Probable: clinical features without lab verification
Possible: fewer of typical clinical features
70
cycle of poverty
poverty leads to malnutrition and poor salary since you're not able to work, leading to lower spcioeconomic status so you can't afford proper healthcare when you get sick-> so you can't work even more->leads to further lowering of socioeconomic status
71
Cerebral Malaria
Cerebral malaria-syndrome defined by an unarousable coma, not attributable to other causes, with any level of P. falciparum parasitemia.
1% of P. falciparum infections progress to CM and 10-20% of these cases die.
Usually seen in children >2yrs.
t-cells probs attack BBB and damage brain capillaries
72
Respiratory Distress Syndrome
almost same as cerebral malaria but in lungs instead not brain
A feature of malaria in African children and Asian adults.
RDS can be caused by injury to lung micro-vascular endothelium and aveolar epithelium via proinflammatory mechanisms.
Can be caused by heart failure, parasite sequestration, or increased requirement for respiration.
RDS often associated with metabolic acidosis, usually involving lactic acidemia
73
Variant surface antigens (VSAs)
Malaria parasites develop in RBCs lacking expression of MHC molecules.
Express parasite-encoded antigens on RBC surface.
PfEMP1 best characterized ~60 copies occur in each parasite but only 1 expressed.
Mediates binding through different domains
of parasites to different host tissues leading to pathology and the inability of the spleen to clear parasites from the blood.
also have knob proteins which cause clumping and allow pathogen to attack RBCs
74
Malaria Resurgence
Development of insecticides and anti-malarials after WWII gave the hope that malaria eradicated.
After 5 years, malaria eradication programs ended because of slow progress due to increasing insecticide and anti-malarial resistance leaving hundred of millions susceptible to disease
DRUG RESISTANCE
misuse of anti-malarials by untrained personnel and governments
lack of drug development on the part of drug companies & government
fake drugs: either little or no active drug included, leading to treatment failure or failure of prophylaxis. Est. to account for tens of thousands or as many as 200,000 deaths annually. Lack of regulatory agencies
Single use therapy….combination therapy prevents resistance
75
measures to control malaria
ANTIMALARIALS-few new drugs being developed. Those available used in combination.
VACCINES-antigenic constructs, irradiated sporozoites, gene KO sporozoites: to provide the most people with protection at the lowest costs.
VECTOR CONTROL-Obligate mosquito stages and there are many ways to kill a mosquito.
76
Malaria Vector Control
Mosquito must take 2 blood meals to transmit parasite
Barriers-insecticides or insecticide impregnated bednets, engineered mosquito pathogens- effective
Release of sterile mosquitoes- not effective since selected against
Construction & release of bio-engineered mosquitoes
77
Disadvantages of insecticide use for malaria
Resistance due to overuse and misuse of insecticides
Mutation and selection may account for resistance
Change in mosquito behavior may also achieve resistance
Possible harm to humans and wildlife
78
influenza and children
a disease of childhood
Children suffer the highest rates of infection
Influenza-associated pediatric hospitalization and mortality
Role for children in community transmission- easily spread due to daycare and pre-school
79
influenza imp features
Short incubation period: 1 to 3 days
Viral shedding (infectious) 1 day before symptom onset through 5-7 days after symptom onset
Maximum infectivity associated with fever
Highly communicable
Transmission via coughing, sneezing, close contact, contaminated surfaces
Approximately 50% of influenza-infected persons have limited or no symptoms
Potential for virus transmission
types: A, B C and D
Negative-sense segmented RNA genome
10 major proteins
Two major surface proteins of A and B viruses: Hemagglutinin (HA) and Neuraminidase (NA)
RNA-containing genome
Consequences for mutation: very prone to mutation via errors in transcription and without adequate “proof-reading” mechanisms capable of editing out the errors
Antigenic Drift
Manifests in HA and NA as a result of continuous and gradual accumulation of point mutations in the HA and NA genes within a subtype
80
influeza's affects on different age groups
children suffer the most
| mortality highest in elderly
81
influenza antivirals
Adamantanes (Amantadine & Rimantadine)
No longer effective against influenza type A,
Neuraminidase inhibitors
[Tamiflu & Zanamivir; Peramivir(i.v.)]
Effective against influenza subtypes A and B
Both oral, inhalant and i.v. preparations available
Differ in age ranges, routes of administration, costs, and adverse events
Development of complete resistance by former seasonal H1N1; pdmH1N1 and H3N2 remains susceptible
Need to deliver within 48 h of illness onset for maximal benefit
Role of diagnostics and up-to-date surveillance information to ensure antivirals are effective
It will reduce illness severity for all individuals and lessen hospitalization and death for those at greatest risk
82
seasonal influenza vaccine
Primary strategy to reduce influenza infections and their complications
Safe and effective(?)
2 vaccine options:
Inactivated influenza vaccine
For all age groups ≥ 6 months (Universal)
Options now include high potency and adjuvented
Live attenuated influenza vaccine
Licensed for non-pregnant persons aged 2-49 years
Vaccine is matched to circulating strains of seasonal types A (2 subtypes) and B (2 lineages) influenza
Universal vaccination: Children are a priority!
Rates of usage disappointing!!!
Each year because of the changing nature of influenza the components of the vaccine must be changed to keep up with the circulating strains of flu
Very complex process
Heavy reliance on state-based virologic surveillance
83
Influenza 2014-2015
quite severe influenza
a certain strain was expected but due to antigenic drift we got a different one, so vaccines were ineffecitve and it was a difficult virus to work with and characterize
84
antigenic shift in influenza
When a new subtype of influenza A emerges in humans either directly from an avian source or possibly following a genetic reassortment event in an animal intermediate host
Can occur suddenly or evolve over time
This can occur in 3 ways highlighted in the diagram
Necessary precursor for an influenza pandemic.
antigenic shift associated with pandemics
includes acquisition of novel genes through reassortment
appearance of novel influenza A viruses bearing new HA or HA&NA
85
Pandemic Influenza
Results from a novel subtype of influenza A virus to which the overall population possess no immunity
Characteristics include:
Extremely rapid global spread
Occurrence in multiple or widespread geographic areas worldwide; locally explosive epidemics
Association with unusually high rates of morbidity and mortality
Likely all ages affected; possible unique age predilection for severe disease
Multiple waves of disease over 2 or more years
Significant social, infrastructure and economic impacts
86
Pandemic influenza prevention strategies
| National strategy
Stopping, slowing or limiting the spread of a pandemic to the U.S.
Limiting the domestic spread of a pandemic, and mitigating disease, suffering and death
Sustaining infrastructure and mitigating impact to the economy and the functioning of society
Awareness is raised, but no funding provided
87
novel influenza reports
are increasing
due to a combo of: ongoing contact among avian species, domestic poultry and swine and humans with continual reassortment of various flu viruses; also improved detection and surveillance
88
latest global influenza concern
Influenza A H7N9
over
Over 5 influenza seasons, almost 1567 laboratory-confirmed human cases with avian influenza A(H7N9) virus with 615 deaths
Typical flu-like illness with severe pneumonia
Most cases in older individuals with direct link to avian contact in live markets; however cases range in ages from 4-84
Difficult to track in birds since mild or no illness initially; however, there has evolved high path variant in poultry and some waterfowl
Extent of spread in wild or domestic poultry unknown
Again, no sustained human-to-human transmission
89
Recipe for a human influenza pandemic
emergence of a novel subtype of influenza
an immunologically naive population
replication in humans- leading to disease
efficient and sustained human-human transmission
-human-human transmission has not been achieved in H5N1 (avian), H7N9(latest concern) both are avain origin and swine variant, but concern is there as a 3 changes to genome in H7N9 could make it more transmissible between mammals and humans
90
US causes of foodborne illness and death
norovirus- high illness,
Salmonella- low illness, high death rate
toxoplasm and listeria- less illness, high death
91
toxoplasm
second in foodborne death
forms cycts in brain, they can re-emerge and cause death since in brain
makes things worse for HIV patients because with cysts in brain, immune system goes down and can't keep cysts in check
92
Factors that Facilitate the Spread of Foodborne Diseases
1) International Travel and Commerce- globalization of the food supply,
particularly perishable foods, like fresh produce
2) Technology and Industry- new food production industries- centralized
processing and widespread distribution of human and animal foods
3) Human Demographics and Behavior- US market for ready to eat
and “ethnic” foods
4) Microbial adaptation and change-
Can certain bacteria survive better on plants now?
5) Human susceptibility to infection- young, old, pregnant, HIV, cancer
93
cyclospora
cyclospora can't be grown in the lab
outbreaks highlight the role of internation food distribution and emergence of previously unknown pathogens
lifecycle- complex
diarrhea causing
94
E. coli 0157:H7
Identified in 1982, became famous in 1993 outbreak at
Jack in the Box, 732 cases with 4 death of children
Most often transmitted in uncooked ground beef
Young children shed the organism in their feces for 1-2 weeks
after their illness resolves (daycare centers and pools)
-July 2004 a Bronx daycare center had 26 cases linked
```
Causes bloody diarrhea, and abdominal cramping with
no fever (5-10 days).
```
2-7% have hemolytic uremic syndrome (HUS when RBCs destroyed,
Kidney failure). Blood transfusions and kidney dialysis needed
There is no evidence that antibiotics work, and the may
promote kidney problems
produces toxin almost identical to shiga toxin
new processing tech and consolidated meat processing has brought emergence
-prevention= feeding them grass
not just in meat- also in produce, unpasturized apples turned into apple juice- contaminated apples from manure
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PFGE
Pulsed-Field Gel Electrophoresis
Molecular subtyping method used to generate a “DNA fingerprint” of a bacterial isolate
Looks at the entire bacterial chromosome- cleaved by enzymes at conserved sites
Improvement in discrimination over other traditional subtyping methods
Fragments are seperated on a gel
Genetic variation in the bacterial genome creates a “fingerprint” that is specific for a given strain.
Mutations, insertions, inversions or deletions change the size of the fragments created by the restriction enzyme
Compare new isolate band patterns to others in local database
-cheap, fast
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WGS
Whole Genome Sequencing
Tool for mapping or comparing genomes of organisms thru sequencing all or most (Next Gen Sequencing-NGS) of their genomic material
Shows enhanced discrimination of organisms which appear to be indistinguishable by other subtyping methods (PFGE, serotyping, etc)
Adopted by PulseNet in 2014 as the next generation subtyping platform to replace PFGE
-can see whats actually changing so can understand/know how to better treat it
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Limitations of WGS
assembling repeats and phage elements correctly is hard
not really Not truly “whole” genome sequencing
Genome assembly occurs in multiple pieces
Short read data not conducive for complete genome assembly from multiple pieces
Very large amounts of data generated each run
Large storage capacity needed
Need to be able to set up an effective and efficient pipeline for data sharing
Upfront equipment and ongoing reagent costs
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Pulse net
surveillance systnme
| A national network of public health laboratories
emerging infectious diseases
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