Download CHAPTER 8 EMERGING AND RE

EMERGING AND RE-EMERGING INFECTIOUS
DISEASES
© National Museum of Health and Medicine, Washington, D.C., United States
INFECTIOUS DISEASE
• Infectious disease has played a prominent role in world history.
– The Black Death in the Middle Ages killed 1/3 Europe’s population.
– Measles destroyed the South American Aztec civilization.
– Smallpox destroyed indigenous peoples of North and South America, facilitating
the conquest of the New World.
"Triumph of Death"
(Black Plague)
Painted in 1562
Infectious Disease- Trends
• Receded in Western countries 20th century
• Urban sanitation, improved housing,
personal hygiene, antisepsis & vaccination
• Antibiotics further suppressed Morb/Mort.
• Since last quarter of 20th century- New &
Resurgent infectious diseases
• December 1967, Surgeon General William H.
Stewart declared victory over infectious diseases
Definition
• Emerging infectious disease
Newly identified & previously unknown infectious agents
that cause public health problems either locally or
internationally
• Re-emerging infectious disease
Infectious agents that have been known for some time,
had fallen to such low levels that they were no longer
considered public health problems & are now showing
upward trends in incidence or prevalence worldwide
JITMM, Bangkok, 12-14 December 2012
Infectious Diseases: A World in Transition
AIDS
Avian Influenza
Ebola
Marburg
Cholera
Rift Valley Fever
Typhoid
Tuberculosis
Leptospirosis
Malaria
Chikungunya
Zika
Dengue
JE
Antimicrobial resistance
UP
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DOWN
Guinea worm Smallpox
Yaws
Poliomyelitis
Measles
Leprosy
Neonatal tetanus
Eradicated--smallpox
EMERGING INFECTIOUS DISEASES
• First transition (also referred to as crowd transition)
– Occurs when people begin to live in much closer proximity
to one another
– Higher population density
– Proximity between populations allows for easy
transmission of disease
EMERGING INFECTIOUS
DISEASES
• Second transition
– Neighboring civilizations made contact with each
other through war or trade
– Contact allowed the exchange of pools of
infectious organisms and vectors between
populations.
EMERGING INFECTIOUS
DISEASES
• Third transition
– Worldwide exploration and
colonization led to the identification of
new populations
– Newly identified populations came into
contact with pathogens never seen
before within their cultures.
– Immunologically naïve and susceptible
populations.(Alaska-measles/Native
Americans smallpox)
EMERGING INFECTIOUS DISEASES
• Fourth transition – this is
happening today. The ongoing
causes are:
– Globalization
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Global urbanization
Increase in population density
Poverty
Social upheaval
Travel
New behaviours (medical /
sexual tourism)
Long distance trade
Technology development
Land clearance
Weather / Climate
Geographical Distribution of West Nile Virus
Origin: Uganda
Global Distribution of Cholera
Origin: India
Factors Contributing To Emergence
AGENT
• Evolution of pathogenic infectious agents
(microbial adaptation & change)
• Development of resistance to drugs
• Resistance of vectors to pesticides
• Environment
• Climate & changing ecosystems
• Economic development & Land use (urbanization,
deforestation)
• Technology & industry (food processing & handling)
• International travel & commerce
• Breakdown of public health measure (war, unrest,
overcrowding)
Summary of Climate Trends
Temperature
• Maine will warm statewide
by 1.0 to 1.5˚C by 2060
– Warmer winters
– Warmer summers
• Warmer temperatures will
be attained earlier in the
year
• Overall by 2050, Maine’s
temperatures will
resemble those seen
today in Massachusetts
Precipitation
• Statewide precipitation
will increase by 10cm
by 2060
• Summer rainfall will
remain steady in all parts
of Maine except the
central mountains
Meaning for Vector-borne Diseases in Maine
Factors Contributing To Emergence
HOST
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Human demographic change (inhabiting new areas)
Human behaviur (sexual & drug use)
Unsafe sexual practices (HIV, Gonorrhoea, Syphilis)
Changes in agricultural & food production patterns- foodborne infectious agents (E. coli)
Increased international travel (Influenza)
Outdoor activity
Human susceptibility to infection (Immunosuppression)
Poverty & social inequality
Uncontrolled Urbanization &
Population Displacement
• Growth of densely populated cities- substandard
housing, unsafe water, poor sanitation,
overcrowding, indoor air pollution
• Problem of refugees & displaced persons
• Diarrheal & Intestinal parasitic diseases, ARI
Lyme disease (B. burgdorferi)- Changes in
ecology, increasing deer populations, suburban
migration of population
The global air network
Sudden Acute Respiratory
Syndrome (SARS)
Emerged in 2003 – hotel in Hong Kong
Rapid spread worldwide – 8098 persons within 3-4
months
Last case in 2004
Person-to-person respiratory spread – droplets
Source – wet markets (live animals)
Reservoir – ferrets
Agent – corona virus
Severe Acute Respiratory Syndrome: SARS
• SARS became readily transmissible in the 1990s.
• First documented case was identified in mainland China.
• It is transmitted by droplet aerosol and fomites deposited on
the respiratory mucosal epithelium.
• Pneumonia like disease.
• 2002-2003 outbreak infected 8400+ with
916 confirmed dead.
WEST NILE VIRUS
• West Nile virus is caused by an arbovirus (arthropod borne,
RNA viruses).
• The virus is carried in the saliva of mosquitoes and is
transmitted through bites.
• Birds are the primary hosts (Crow and Cardinals)
• Infection is spread from bird to bird by mosquitoes.
WEST NILE VIRUS: Pathogenesis
• Most infected people are asymptomatic unless
the infection causes an invasive neurological
disease called West Nile Fever.
– Symptoms include fever, headache, myalgia, and
anorexia.
– Severe infection can cause profound fatigue,
myocarditis, pancreatitis, and hepatitis.
– Particularly severe cases can result in encephalitis
or meningitis and death.
– The illness can also be transferred through blood
transfusions and transplantation.
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Imported Arboviral Illnesses
• Exotic Arboviruses are important public health risks for the
United States
– Competent vectors are present in parts of the United States
– These arboviruses include
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Dengue
Yellow fever
Chikungunya
Tick-borne encephalitis
Japanese encephalitis
Venezuelan equine encephalitis
Rift Valley fever
Zika
• Dengue and Yellow Fever are nationally reportable illnesses
• Travel history is extremely important in the diagnosis of
arboviral illnesses
Aedes aegypti mosquito
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Distribution of mosquito
Maine Center for Disease Control
and Prevention
ZIKA Virus
• The latest plague (geographic spread due to
global travel)
• What we do and do Not know (is
it more virulent due to mutations now)
• Look at other viruses (rubella,CMV)
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History
• First isolated in 1947 from a rhesus monkey in
the Zika forest of Uganda
• First isolated from humans in 1968 in Nigeria
• Outbreaks occurred in Africa, Southeast Asia,
the Pacific Islands and the Americas
• Americas
– Chile (Easter Island), March 2014
– Brazil, May 2015
– Puerto Rico, December 2015
Maine Center for Disease Control
and Prevention
Transmission
• Through mosquito bites
– Primarily Aedes aegypti species(albopictus)
– Humans are the reservoir
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From mother to child--intrauterine
– No reports from breastfeeding to date
• Possibly through infected blood- and sexual contact
– No reports from transfusions
– 36 probable reports of spread through sexual
contact
Maine Center for Disease Control and Prevention
Symptoms
• About 1 in 5 people will become ill
• Symptoms include:
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Fever
Rash
Joint Pain
Conjunctivitis
Muscle pain, headache, pain behind the eyes,
vomiting
• Clinical illness is usually mild and lasts for several
days to a week
• Incubation typically 2-14 days
Maine Center for Disease Control
and Prevention
Diagnosis/Treatment
• Single-stranded RNA virus, genus Flavivirus
• Differential diagnosis is broad and includes:
dengue,
leptospirosis, malaria, rickettsia, group A strep, rubella, measles, parvovirus,
enterovirus, adenovirus, chikungunya
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Diagnosis by PCR in first 4 days—IgM 4-7 days
Urine + PCR up to 14 days
• Positive PCR suggests infectivity (not entirely clear)
• Cross reaction with Dengue + Chik. Igm
• There is no specific treatment
Maine Center for Disease Control
and Prevention
Countries with past or current evidence of
Zika virus transmission
Maine Center for Disease Control
and Prevention
Map courtesy of
ZIKA Virus in Pregnancy – Limited Information
• No evidence of increased susceptibility
• Infection may occur in any trimesterneurologic damage likely in first trimester
• Incidence in pregnancy not known
• No evidence that ZIKA is more severe
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Latest Information on ZIKA
• Enough evidence – ZIKA virus during pregnancy
causes microcephaly—also other brain defects,
eye defects, hearing loss, impaired growth
• Birth defects most likely in first trimester
• Women with ZIKA virus infection - wait 8 weeks
after symptoms before attempting conception
• A man infected with ZIKA can transmit – avoid
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sex during pregnancy(condoms)
Zika and Pregnant Women-DX
• Pregnant women with symptoms—PCR1-4
days—urine up to 14 days
• Pregnant Women IgM after 4 days
• Ultasonography may be indicated
• Amniocentesis guidelines
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ZIKA and Guillain-Barre
• New case control studies proves a link
• Rates may be .24/1000 cases
• Other neurologic syndromes under
investigation
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ZIKA in US as of November, 2016
• Travel associated ZIKA – 4496
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Pregnant – 1114(18 cases microcephaly)
Sexually transmitted 36
Guillain-Barre – 13
Locally Acquired ZIKA – 14(Miami and Texas)
Maine -12 cases—all travel
• US Territories – 33,258
• Pregnant – 2561
• Guillain-Barre - 48
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Updates on ZIKA
• The virus is present longer in semen than
blood(up to 62 days)
• After ZIKA a man should wait 6 months before
attempting conception
• Natural infection likely gives long term immunity
• FDA is developing a screening test for blood—
defer donation if recent travel
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Who should be tested for ZIKA
• Symptomatic individuals with travel history
to a Zika affected country
• Pregnant women with travel history to Zika
affected country
• Partners of pregnant women with travel
history to a Zika affected country
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Public Health
• Notify providers of Zika virus and how to test
• Warn residents when traveling to ZIKA areas
to avoid mosquito bites- use DEET/bed nets
• Cruise ship destinations – Zika
• Monitor for locally acquired transmission - in
US – Miami
Maine Center for Disease Control and Prevention
What is new with ZIKA
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WHO downgraded Zika from PH emergency to threat
ZIKA identified in Texas
Zika epidemic may have peaked
Severity of Zika in SA may be Due to coinfections
Vaccine testing in full swing
Zika funding passed by congress
Zika may persist in vaginal fluid for weeks
Female to male transmission documented
ZIKA – The Future
• Vaccine—active research now—
phase I trials
• Sterile mosquitoes - trials
• Mosquito control – now---Brazil
• Anti-virals- nothing yet available
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Chikungunya (that which bends you over)- Epidemiology
• Transmitted by Aedes aegypti and less
albopictus
• Monkeys, apes and rodents act as reservoirs
• 3 genotypes – West Africa – East Africa –
Asia
• Described first in 1955 – Makonde plateau
• 2013 first cases in Caribbean
• 2014 cases transmitted
in Florida
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Chikungunya – Signs and Symptoms
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Incubation – 1-12 days, typically 2-3
Majority infected get symptoms
Fever to 104° - petechial rash on trunk
Systemic symptoms – headache, nausea,
conjunctivitis, loss of taste, pedal edema
• Fever resolves 2-3 days – joint pains
persists weeks to years
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Chikungunya - Diagnosis and Prevention
• Diagnosis – RT-PCR, virus isolation –
serology
• Prevention – mosquito control – personal
protection
• Vaccine – not available – phase II trials
• Treatment – symptomatic – NSAIDS
• Chronic arthritis – Ribavirin might help –
maybe Chloroquine - steroids not useful
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Prevention of Arboviral Illnesses
• At Home:
– EPA approved repellents: DEET, Picaridin, oil of lemon of
eucalyptus, or IR3535
– Wear protective clothing Permethrin-treated clothing
– Limit outdoor activities in high-risk areas
– Screens on windows and doors
– Household source reduction
• Abroad:
– Use bed nets
– Receive the YF vaccine
– Use the same practices that you would use to prevent
mosquito-borne illnesses at home
Mosquito Protection
Control Directed at the Immature Stages
• Biological Control
– Predators
– Pathogens and Parasites
– Genetic Control
• Mechanical (Environmental) Control
– Source Reduction
– Environmental Manipulation
• Chemical Control
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Oils
Paris Green
Insecticides
Insect Growth Regulators (IGRs)
Control
Directed at the Adult Stages
• Aerosols, Mists and Fogs
• Ultra-low-volume applications
• Residual house-spraying
Ebola Virus Disease (EVD)
Outbreak 2014
2014 West Africa Outbreak
• The 2014 Ebola
outbreak is the largest
Ebola outbreak in history
and the first in West
Africa.
• The current outbreak is
affecting 3 countries in
West Africa.
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Current as of 10/2/2014
Ebola
• Previously known as Ebola hemorrhagic fever
• Ebola Virus Disease (EVD) is caused by infection
with a virus of the family Filoviridae, genus
Ebolavirus
• Natural reservoir of Ebola virus remains unknown
• Researchers believe that the virus is animal-borne
and that bats are the most likely reservoir.
General EVD Background
• Ebola Virus Disease (EVD) is one of numerous viral
hemorrhagic fevers (VHFs).
• The first Ebola virus species was discovered in 1976 in what
is now the Democratic Republic of the Congo near the Ebola
River.
• EVD is often severe in humans, with case fatality rates
reaching 50-90% in developing countries.
• After an incubation period of a few days, symptoms usually
begin abruptly.
• The natural reservoir host of Ebolaviruses remains unknown.
However, evidence suggests it is a zoonosis (animal-borne)
with bats being the most likely reservoir..
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Ebolavirus species
• Ebola virus (Zaire ebolavirus)
• Sudan virus (Sudan ebolavirus)
• Taï Forest virus (Taï Forest ebolavirus,
formerly Côte d’Ivoire ebolavirus)
• Bundibugyo virus (Bundibugyo ebolavirus)
• Reston virus (Reston ebolavirus) nonhuman primates
EBOLA -Outbreak History--1976
• 1976 Zaire (Congo)
• 318 Reported Cases
• 280 Deaths (88%)
• 1976 – South Sudan
• 284 reported cases
• 151 deaths(38%)
• 1976 – England
• 1 Case(no deaths)
Outbreak History -1976-2013
• 33 Previous Outbreaks
• 2,361 Reported Case
• 1,548 Deaths (66%)
2014- 2015 Outbreak
• 27,580 Reported Cases
• 11,297 Deaths -probable, confirmed and
suspected
Impact on United States
• On September 30, CDC confirmed the first travelassociated case of Ebola to be diagnosed in the United
States in a person who had traveled to Dallas, Texas from
Liberia. The patient did not have symptoms when leaving
West Africa, but developed symptoms approximately five
days after arriving in the U.S. (arrived Sept. 20).
• Contact tracing, a standard public health procedure, is
immediately employed in order to identify and monitor those
who may have been potentially exposed to a sick patient.
• Even with the first U.S. confirmed case, Ebola does not
pose a significant risk to the United States.
• Fear level very high.
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General EVD Transmission
• Ebola virus is spread from one person to another
through direct contact with:
o Ebola-infected blood or body fluids, such as, but not
limited to, urine, saliva, feces, vomit, and semen
o Objects, such as needles, that have been
contaminated with infected body fluids
• Healthcare workers, family and friends, and others who
come into close contact with Ebola-infected patients
(including corpses of those who expired due to EVD)
have the highest risk of exposure.
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General EVD Transmission
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General EVD
Presentation
• Symptoms may appear
anywhere from 2 to 21 days
after exposure to Ebola
virus, although 8-10 days is
most common.
• Only symptomatic Ebolainfected patients are able to
transmit EVD; Patients
without symptoms who are
infected with Ebola virus
are not contagious.
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General EVD
Assessment
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Timely diagnosis and treatment of EVD is
important but challenging because the
disease is difficult to diagnose clinically
in the early stages of infection.
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Because early symptoms, such as
headache and fever, are nonspecific to
EVD, cases of EVD may be initially
misdiagnosed.
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It is important to obtain an accurate and
complete history of travel or potential
contact with an Ebola case from a patient
exhibiting Ebola-like symptoms.
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Excerpt from CDC checklist for Patients Being Evaluated for EVD in US
General EVD Treatment
• There is no specific cure for Ebola virus infection.
• There are no specific medications (e.g., antiviral drug)
that have been proven to be effective against Ebola.
• Symptoms of Ebola are treated supportively, as they
appear. The following basic interventions, when used
early, can increase the chances of survival.
– Providing intravenous fluids and balancing
electrolytes (body salts)
– Maintaining oxygen status and blood pressure
– Treating other infections if they occur
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Infection Prevention and Control Recommendations
• CDC recommends protection with gowns,
gloves, boots, masks to prevent any contact with
infectious materials with known or suspected
Ebola Viral Disease (EVD).
• Though these recommendations focus on the
hospital setting, the recommendations for
personal protective equipment (PPE) and
environmental infection control measures are
applicable to any healthcare setting.
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Vaccines
• Human trials of experimental Ebola
vaccines have begun in U.S.
• Canada is to ship 800 vials of its Ebola
vaccine to the World Health
Organization
• Recent data shows some success
What is New With Ebola
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Chronic ocular disease identified
Persistence of ebola in seminal fluid(500 Days)
Treatment with Favipiravir an anti-viral
Persistence of Ebola in West Africa
Public concerns minimal (despite ebola cases)
• Infectious brain disease confirmed in
patient treated at Maine Med
• The Portland hospital took the precaution this week of
suspending elective surgeries in order to sterilize its
surgical equipment and facilities
PRIONS AND PRION DISEASES
• These infectious diseases are not caused by
microorganisms.
• They are caused by infectious proteins called prions.
• Diseases are called transmissible spongiform
encephalopathies (TSE).
PRION HYPOTHESIS
• Prions are proteins normally found on nerve cells
and are known as PrPc (prion protein cellular).
• Infectious prions are folded improperly and are
known as PrPsc (prion protein scrapie).
– They are routinely found in scrapie (a neurological
disease of sheep).
PRION HYPOTHESIS
• Prions are practically indestructible.
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They can withstand cooking.
They can withstand autoclaving.
They are resistant to strong alkali treatment.
They are resistant to disinfectants.
They can survive in soil for years.
• Inactivation requires autoclaving in an alkali
solution (bleach containing 2% chlorine) for one
hour.
TSE
• Infective prions can be ingested with prioncontaining material.
• These prions can move through the intestinal wall
rapidly and enter lymph nodes where they
incubate
– They are picked up by peripheral nerves and moved to
the spinal cord and brain.
• Infectious prions can be transmitted between
species
– Incubation time is significantly longer when they cross
between species.
TSE
• Prions produce transmissible spongiform
encephalitis (TSE).
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It is a neurodegenerative disease.
It can affect cattle and humans.
There is no test for it in live organisms.
There is no treatment.
There is no cure.
TSE
• Symptoms include:
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Lack of coordination
Staggering
Slurred speech
Dramatic mood swings
Paralysis
Death within one year of symptom onset
TSE
• “Mad cow” disease was first seen in Britain in 1984
– By the year 2000, there were 180,000 confirmed cases in
cattle in Britain.
• The infection in cattle has been attributed to sheep brain
supplement included in cattle feed.
• First human case documented in Britain
was in 1996.
– To date, there have been more than
120 cases documented in humans.
• Estimates of the number of new cases
in the next few decades vary from a few
hundred to 150,000.
SUPERBUGS
An intro to bacteria, infectious
diseases, and antibiotic resistance
How abundant are bacteria?
Bacterial Abundance
Total bacteria on Earth
Number of stars in the universe
Age of the universe in seconds
Bacteria in the human gut
5 x 1030
7 x 1022
4.4 x 1017
1 x 1014
Cells in the human body
Texts sent in 2009
People on Earth
1 x 1013
1.5 x 1012
6.9 x 109
Introduction
• Since the first use of antibiotics in the 1930s
and 1940s, bacteria quickly adapted and
developed mechanisms to escape their effects
• Over the following decades, new antibiotics
were developed to overcome resistance
• Since the 1990s, new antibiotic development
has fallen sharply while bacterial resistance
continues to increase
• Antibiotic resistance is responsible for
countless human deaths and billions of dollars
in healthcare expenses
Introduction
Resistance Beyond Typical Bacteria
• Imidazole-resistant Candida spp.
• Multidrug-resistant tuberculosis
• Multidrug-resistant malaria
• Anti-viral resistant influenza
• Multidrug-resistant E. coli
Antibiotic Use Leads to
Antibiotic Resistance
Inpatient
Agriculture
Outpatient
Reasons for Antibiotic Overuse :
Conclusions from 8 Focus Groups
Patient Concerns
• Want clear explanation
• Green nasal discharge
• Need to return to work
Physician Concerns
• Patient expects
antibiotic
• Diagnostic uncertainty
• Time pressure
Antibiotic Prescription
Barden L.S. Clin Pediatr 1998;37:665
Antibiotic Use Leads to
Antibiotic Resistance
• Resistant bacteria or their
genetic determinates are
selected when colonizing or
infecting bacteria are exposed
to antibiotics
• Resistant bacteria can then be
transmitted between patients
• Highest risk patients:
– Immunocompromised
– Hospitalized
– Invasive devices
(central venous catheters)
Mechanisms Of Antibiotic Resistance
• Bacteria are capable of
becoming resistant through
several mechanisms
• One or many mechanisms
may exist in an organism
• Multidrug-resistant bacteria
often have multiple
mechanisms
• Genes encoding resistance
may exist on plasmid or
chromosome
Decreased
Permeability
Alteratio
n in
Target
Molecule
Community-Acquired Resistant
E. Coli
• Mostly UTIs
• Young healthy women in
addition to the elderly
• 10-20% now resistant to
fluoroquinolones
• 30-50% resistant to
trimethoprimsulfamethoxazole
• CTX-M β-lactamases
becoming more common
– Cause cephalosporin resistance
Antimicrobial Therapy
Appropriate initial
antibiotic while improving
patient outcomes and
heathcare
Unnecessary
antibiotics and adverse
patient outcomes and
increased cost
A Balancing Act
What is Antimicrobial Stewardship
• Antimicrobial stewardship involves the
optimal selection, dose and duration of an
antibiotic resulting in the cure or prevention
of infection with minimal unintended
consequences to the patient including
emergence of resistance, adverse drug
events, and cost.
Ultimate goal is improved patient care and
healthcare outcomes
Conclusion
• Inappropriate and excessive use of antibiotics
is a major factor contributing to emerging
antibiotic resistance
• Determinants of resistance are selected for by
antibiotic use
• Multiple mechanisms exist for bacteria to
become resistant to antibiotics
• Antibiotic resistance is a problem in
outpatient and inpatient settings and is a
factor in a wide variety of infections
• Antibiotic resistance continues to emerge as a
serious threat to public health
The Global Threat of Epidemic Infectious
Diseases
Projected Global Trends
• Asian countries will lead in economic growth
• Asian Cities will lead in population growth
 Circular rural to urban migration
• Increased globalization
 Increased trade
 Increased movement of people, animals and commodities
 Increased movement of pathogens
• Increased probability of epidemic disease
• Increased threat to global economic security
Examples of recent emerging
diseases
Source: NATURE; Vol
July CHATURVEDI
2004;
Dr. 430;
KANUPRIYA
www.nature.com/nature
Transmission of Infectious Agent from
Animals to Humans
• >2/3rd emerging infections originate from animalswild & domestic
• Emerging Influenza infections in Humans
associated with Geese, Chickens & Pigs
• Animal displacement in search of food after
deforestation/ climate change (Lassa fever)
• Humans themselves penetrate/ modify
unpopulated regions- come closer to animal
reservoirs/ vectors (Yellow fever, Malaria)
• Eco-Tourism
Live Animal Importation into the USA - 2002
• 47,000 mammals
 28 species of rodents
• 379,000 birds
• 2 million reptiles
& Poisonous snakes
• 49 million amphibians
• 223 million fish
Data from U.S. Fish & Wildlife Service
Exotic Infectious Diseases That Have
Recently Been Introduced to the US
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West Nile Fever
Dengue Fever
Yellow Fever
Mayaro Fever
Chikungunya
Epidemic Polyarthritis
SARS
Influenza
Lassa Fever
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Monkeypox
CJD/BSE
HIV/AIDS
Cholera
E. coli O157
E. Coli 0104:H4
Malaria
Leishmaniasis
Chagas Disease
Cyclospora
Pathogens of Tomorrow
From Whence They Will Come?
From Asia
From Animals
Mostly Viruses
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