Download Lecture 6

The Struggle with Infectious
Disease
Lecture 6
Emerging Diseases
Diseases of Developing Nations
Deaths due to Infectious Disease
Annual Deaths (in millions)
Disease
Deaths
Respiratory Infections
3.9
Malaria
1.3 - 3.0
HIV/AIDS
2.5
Diarrheal Diseases
1.8
Tuberculosis
1.7
Neglected Tropical Diseases
0.5
Global Situation
Vaccine Preventable Diseases
• Measles
– 91% decrease from 2000 to 2006
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Meningitis
Diphtheria
Polio
Pertussis
Yellow fever
(Rotavirus)
– causes diarrhea
Tropical Diseases
Tropical Diseases
• Diseases that thrive in a
hot, humid climate
– Sometimes extended to
hot regions e.g. sub-Sahara
• Types of infections more
common in these areas:
– More complex life forms
– Soil or water stages
– More complex stages in
insects (no over-winter
problem)
Tropical Diseases
• WHO identifies the
most common tropical
diseases as:
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Malaria,
Leishmaniasis
Schistosomiasis
Onchocerciasis
Lymphatic filariasis
Chagas disease
African trypanosomiasis
Dengue.
Tropical Diseases
• Types of disease
– Single cell parasites
– Single/multi-cell
parasites
– Nematodes
– Worms
– Virus/bacteria
Leishmaniasis
• Single cell parasite
• Transmitted by sand fly
• Person to person or
mammal to person
(dog, rodent)
• 20 species of parasites
• 30 species of sand fly
• Range:
– S America, Africa
– Occasionally Texas
• Cutaneous
– 0.7 to 1.2 mm sores
– 1.2 million cases/year
• Visceral
– Spleen, liver, kidney,
bone marrow
– 400,00 cases/year
• Life threatening
• Difficult to treat
Leishmaniasis Distribution
Schistosomiasis
• Second most devastating
parasitic disease
– 280,00 deaths/yr
• Parasitic worm
• Reservoir: freshwater
snails
• Fecal/urinary
transmission of eggs to
water
• Penetrates skin &
reproduces in blood
stream
• Symptoms are due to the
reaction to the eggs
– Inflammation/scaring in
bladder and small intestine
– 1-2 months following
infection
– Skin reaction within days
• Chronic symptoms:
– Enlarged liver, abdominal
pain, intestinal/urinary,
growth, mental capacity
• Medication is available (12 day treatment)
Schistosomiasis Distribution
Onchocerciasis (River Blindness)
• Parasitic worm
(nematode)
• Transmitted by black flies:
• Larvae develop in black fly
37 million infected
• Two stages:
– Transmissible 200-400µ
– Resident 30-50cm long
• Treatable with medication
– For lifetime of worm (15yr)
– New med attacks bacterial
food source
• Live in nodules under the
skin for <15yr
• May not induce immune
response
• Respond to dead larvae
– 1000/day per nematode
– Blotchy skin
– Reversible corneal/optic
nerve damage
Onchocerciasis Distribution
African trypanosomiasis (Sleeping Sickness)
• Single cell parasite
(rather like malaria)
• Spread by Tetsi fly
• Largely human reservoir
(some animals)
• Endemic in rural Africa
– 10,000 cases/yr
• Multiplies in body fluids
(blood,lymph,spinal
fluid)
Second stage crosses
blood/brain barrier
Leads to neuro problems
African Trypanosomiasis Ditribution
Cost of Tropical Diseases
• Difficult to accurately
compute
• Impact on agricultural
work (30% decrease for
some single diseases)
• Impact on school
attendance
• Estimated cost of
Trachoma $1.5
billion/yr
Cost of Tropical Diseases
• 24% of global disease
burden is accounted for
by sub-Saharan Africa
• Area represents 3% of
the world’s workforce
Cost of Tropical Diseases
• Generally
chemotherapy
medications are
inexpensive $0.50 $0.05
Malaria
• A parasitic disease
• Caused by single cell
organism plasmodium
– 4 types that infect
people (~16 total)
• Spread by Anopheles
mosquito
Malaria: why we should care
• Common in tropical and
sub-tropical regions
around the world
• Residents develop some
level of immunity
• Naive hosts react much
more severely
• Treatment options are
limited
Malaria: why we should care
• 300 to 500 million cases
per year (WHO)
• Over 1 million deaths
per year annually
• 85% of deaths are
children under the age
of 5
• 90% of deaths are in
Africa
Malaria
• Outside Africa malaria is
concentrated in 8
countries in SE Asia
Malaria
• Symptoms
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High fever
Shaking chills
Flu-like symptoms
Anemia
• Symptoms usually occur
within 10 days to 4
weeks (up to 1 year)
• Symptoms last 48 – 72
hours (recurrent)
Malaria
• Death is usually due to
anemia due to burst
blood cells
• Plasmodium falcparum
is the most serious and
can lead to death within
hours of the first
symptoms
Malaria
• Disease is transmitted
from person to person
by mosquito
• Separate life stages in
people and insect
• Three distinct life stages
– First: Injected by
mosquito into blood
stream and migrate to
liver and multiply
Malaria
• Rupture liver cell and
enter blood stream
• Second: parasite infects
red blood cell
(erythrocyte) and
multiplies over ~ 48
hours
• Red cell ruptures
releasing further
parasites
Malaria
• Two types of
reproduction take place
– Asexual (more efficient)
– Gametes (evolutionary)
• Parasites are returned
to mosquito through a
blood meal
• Third: parasite
reproduces in mosquito
Malaria
• Treatment:
– Drug treatments can
only be effective when
parasite in not hiding in
another cell
– Drug resistance has
developed
• In part due to incomplete
treatment of infection
– Multi-drug treatments
are currently being used
successfully
Malaria Prevention
• Prevention becomes
key strategy
• Mosquito control
– Mosquitos have become
insecticide resistant
– Mosquito habitat control
• Mosquito bite control
– Bed net programs
• Vaccines have been
unsuccessful
Malaria Prevention
• Mosquito control
– Mosquitos have become
insecticide resistant
– Mosquito habitat control
Malaria Prevention
• Mosquito bite control
– Bed net programs
Malaria Prevention
• Reduction in deaths
since 2000 by 25%
worldwide and 33% in
Africa
Malaria Vaccine Development
Possibilities (Pro)
• Plasmodium is in the size
range where the immune
system functions well
• It is a single cell organism in
all stages
Issues (Con)
• Plasmodium more complex
than bacteria or virus
• Life cycle complex, many
stages and forms
– Sexual & asexual
• Reproduction rate in blood
borne stage greatly exceeds
the need for survival
– Have to kill off nearly all
Malaria Vaccine Development
• Potential targets for
vaccine:
– Pre-erythrocyte
– Blood stage
– Transmission blocking
• Currently 41 vaccines
under development
Malaria Vaccine Development
• One vaccine has made it
to phase 3 clinical trial
• Has proved “somewhat
effective” ~30% - 50%
• Less effective in young
children (where it is
most needed) than in
older children
• We are not there yet
Dengue Fever
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
and Chikungunya
Dengue Fever
• Developed in monkeys
• Jumped to humans in
Africa/SW Asia 100-800
years ago
• Second world war
transported mosquito
and disease around the
world
• 100 million infected
annually
Dengue Fever
Dengue Fever Symptoms
• Symptoms start 3-10
days after bite
– Skin rash
– High fever: 104°-105° for
4-7 days
– Febrile seizures: can be
extremely severe …
hence the name
“breakbone fever”
– Usually resolves after 10
days
Dengue Fever
Dengue Fever
• No vaccine available
• No treatment
• Prevention has been
partially successful
Dengue Fever Prevention
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
Dengue Hemorrhagic Fever
• Symptoms:
– Similar course to Dengue
Fever
– But with fever shock-like
symptoms develop
– Crisis period lasts 1 day
• Bleeding occurs in
patches under the skin
• Sometimes bleeding
from nose & mouth
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)
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
Dengue Fever
• Range could be
impacted by climate
change
– Dengue seems to be
more ubiquitous than
yellow fever
Impacts of Climate Change
• Diseases transmitted by
Asus Egyptus :
Dengue
Yellow Fever
Zika
Impacts of Climate Change
• Other mosquito borne
infections
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West Nile
Chikungunya
Filariasis
Japanese encephalitis
• More species of
mosquitoes are
infective
Asian Tiger Mosquito
Impacts of Climate Change
• Other impacts of climate change:
– Severe weather
• Impacts mosquito populations
• Impacts areas for waterborne diseases
• Impacts costal areas
– Change in habitat
• Change is range of species
• Change in ecological habitat
– Deforestation
Ebola
Early Epidemiology
Ebola Outbreak 2014
Key Factors in Disease Reduction
• 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
SARS
SARS
• Outbreak started
November 2002 in
Hong Kong
• Jumped from wild
animal (civet cat)
• Case fatality 9.6%
• High transmission rate
person to person
• First serious coronavirus
SARS
• Spread to 37 countries
• 8,237 cases
• 775 deaths
Supplementary Material
• Ebola
• SARS
• Chagas
Ebola Virus
•
Ebola, previously known as Ebola hemorrhagic fever, is a rare and deadly disease
caused by infection with one of the Ebola virus strains. Ebola can cause disease in
humans and nonhuman primates (monkeys, gorillas, and chimpanzees).
•
Ebola is caused by infection with a virus of the family Filoviridae, genus Ebolavirus.
There are five identified Ebola virus species, four of which are known to cause
disease in humans: Ebola virus (Zaire ebolavirus); Sudan virus (Sudan ebolavirus);
Taï Forest virus (Taï Forest ebolavirus, formerly Côte d’Ivoire ebolavirus); and
Bundibugyo virus (Bundibugyo ebolavirus). The fifth, Reston virus (Reston
ebolavirus), has caused disease in nonhuman primates, but not in humans.
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Ebola viruses are found in several African countries. Ebola was first discovered in
1976 near the Ebola River in what is now the Democratic Republic of the Congo.
Since then, outbreaks have appeared sporadically in Africa.
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The natural reservoir host of Ebola virus remains unknown. However, on the basis
of evidence and the nature of similar viruses, researchers believe that the virus is
animal-borne and that bats are the most likely reservoir. Four of the five virus
strains occur in an animal host native to Africa.
•
CDC Atlanta, USA
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
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
Ebola Virus
• Fruit bats are
considered the natural
host
• Contact with blood,
secretions, organs or
other body fluids
• Chimps, gorillas,
monkeys, forest
antelope, porcupines
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
Ebola Virus
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
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
Host immune responses to Ebola virus and cell damage due to direct infection of monocytes
and macrophages cause the release of cytokines associated with inflammation and fever (A).
Sullivan N et al. J. Virol. 2003;77:9733-9737
Ebola Outbreak 2014
Ebola Outbreak 2014
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
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’
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
• Bacteria were found in post mortem samples
– Probably endemic infection
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
Chronology
• Ministry of Health issued alert on
‘unidentified disease’ March 13, 2015
• WHO/AFRO, WHO, MSF investigation March
14-25
– Epidemiology and Outbreak tracing
– Laboratory analysis
• 21 March Pasture Institute identified flavivirus
• 22 Identified Zaire strain of Ebola virus
Chronology
• March 23, 2015 outbreak was announced by
WHO
– 49 cases
– 29 deaths reported
Early Epidemiology
Current Status
• Fighting Ebola
– Support the patient so that the immune system
can fight the virus
– Improve the immune system ‘convalescent serum’
– Anti-viral
• When will it work?
– Vaccines
• Why is it taking so long?
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
What Have We Learned?
• Above all
• Prevent spread of the virus
• How many times in history, how many diseases
– Increase understanding of disease transmission
• How many theories
– Education to overcome cultural beliefs
• What other cultural beliefs
Have we come so far?
Supplementary Material
Chagas
• Transmission through
feces of ‘kissing bug’
– Enters through skin or
wound
– Enters tissue near wound
and differentiates
– Gametes multiply by
binary fusion
• Does not differentiate in
blood stream
• Central and South
America
• Acute phase: immediate
to several months
– Mild/asymptomatic,
swelling
• Chronic stage
– No parasites in blood
– Asymptomatic
• Complications:
– Heart rhythm (sudden
death)
– Dilated heart,
esophogus/colon
SARS
SARS
• Severe Acute
Respiratory Syndrome
• Caused by a coronavirus
– Causes upper respiratory
tract infection and
gastrointestinal tact
infection in mammals
and birds
– 5-6 strains infect humans
SARS
• Outbreak started
November 2002 in
Hong Kong
• Jumped from wild
animal (civet cat)
• Case fatality 9.6%
• High transmission rate
person to person
• First serious coronavirus
SARS
• Spread to 37 countries
• 8,237 cases
• 775 deaths
SARS
• Feb 23, 2003 first case
in Canada: vacationing
in Hong Kong
– Died at home March 5
– Victims son reported to
hospital March 7 with
unknown illness
– Potentially infected
many health workers
and visitors
• Identified as TB and
isolated
– Patient in next bed in ER
returned to hospital
March 15 and died
• Unknown disease
• Unknown mode of
transmission
– Highly transmissable
SARS
• Only precautionary
measure was isolation
• Disease was described
March 31, 2003
• Work started on a vaccine
– There were confounding
factors noted in cats
• Convalescent serum was
considered
• Second outbreak May –
June 2003
Novel Coronavirus Infection
• A second novel
coronavirus has
appeared
– First cases early 2012 in
Saudi Arabia and Jordan
– Presents as pneumonia
but also renal failure
– Recently 3 cases have
been reported in UK
with no history of travel
Novel Coronavirus Infection
• 12 confirmed cases with
5 deaths
• Seems less contagious
than SARS
– Mode of transfer is not
known
– Fatality rate was highest
in earliest cases
• Global surveillance is
underway