M16: Emerging Infectious Diseases

Question 1

Definitions in Epidemiology:

Incubation period

Infectious period

Latent period

Answer 1

time from exposure to development of disease

length of time a person can transmit disease

period of infection without being infectious. This may occur right after exposure or late in the disease

Question 2

Definitions in Epidemiology:

Epidemic

Endemic

Pandemic

Answer 2

occurrence of cases of illness in excess of expectancy.

An epidemic whose incidence remains stable for a long period

a global outbreak

Question 3

Definitions in Epidemiology:

Incidence

Incidence rate

Denominators can be expressed _

Answer 3

number of new cases in a given time period in a given population
Example: 93 new cases of HIV infection in Allegheny County in 2008

number of new cases per population at risk for the disease over time
Example: 23 cases of C. difficile acquired at hospital A (500 beds) over a month with full occupancy = 23 / (500 x 30) = 0.00153 cases / patient-day

as any population at risk:
• Ventilator-days
• Central-line days

Question 4

Definitions in Epidemiology:

Prevalence

This is of little interest if an infection is of (short / long) duration (ex) but more important if an infection is of (short / long) duration (ex)

Answer 4

total number of disease cases / # individuals in the population of concern.

short
Ex. measles

long
Ex. chronic hepatitis B, HIV

Question 5

Definitions in Epidemiology:

Attack rate

Primary cases

Secondary cases:

Answer 5

proportion of exposed individuals who become ill

The person who infects a population

Those who subsequently contract the infection

Question 6

Definitions in Epidemiology:

Case fatality

This is a function of the _ of the infection and is heavily influenced by _

Virulence
- indicated by _

• Rabies: (very / not very) virulent
• Hepatitis A: (more / less) virulent

Answer 6

proportion of infected individuals who die of the infection.

severity
how many mild cases are not diagnosed

the degree of pathogenicity within a group or species of microorganisms or viruses
- case fatality rates (CFR) and/or the ability of the organism to invade the tissues of the host

very
less

Question 7

Definitions in Epidemiology:

Reservoir

Vector

Zoonosis

Answer 7

ecological niche (vs source which is the actual object).

any organism (usually an arthropod like a mosquito or tick) which harbors infectious agent and transmits it to susceptible individuals (e.g. Lyme disease, malaria)

infections that can spread from vertebrate animals to man.

Question 8

Definitions in Epidemiology:

Formula: Ro =

Ro: The basic reproductive rate is _

b is the attack rate: _

k is the number of _

D is the duration of _

Answer 8

b x k x D

the number of secondary cases following a single introduction into a fully susceptible population

how infectious

potentially infectious contacts the average person in the population has per unit time

infectivity of an infected person

Question 9

Ro = the basic reproductive rate

If Ro < 1, then _
A population that is _ or became _ affects disease spread

If Ro = 1 then _

If Ro > 1 then _

Answer 9

every new generation of infection will affect fewer individuals and the disease will die out.

vaccinated (polio)
naturally immune (hepatitis A)

approximately the same number of individuals are infected with every new generation causing endemicity (West Nile virus)

there is an ever increasing number of infected individuals causing epidemic or pandemic (Influenza)

Question 10

Definitions in Epidemiology:

Herd immunity threshold

The higher the Ro of infection, the (larger / smaller) the number of immune people is required to confer herd immunity.

For example: measles has a Ro of 15; the need of herd immunity (vaccination coverage) to interrupt transmission of measles is (high / low) in a population

Answer 10

the fraction of a population that must be immune to a given microorganism to prevent an outbreak beyond one index case.

larger

high

Question 11

Outbreak

You should suspect an outbreak when there are (#) cases of an illness with similar characteristics linked by _, _, or _.

When investigating an outbreak it is important to first decide about a case definition, and then collect data to determine (4)

Answer 11

2 or more
time, location or contacts

1. Reservoir
2. Transmission route
3. Incubation time
4. Value of Ro (limited outbreak, epidemic or endemic)

Question 12

Different causes of acute pneumonia:

Bacterial (4)

Viral (6)

Answer 12

Streptococcus pneumoniae
Legionella
Chlamydia
Mycoplasma

Influenza, Avian Influenza
Para-influenza virus 
Adenovirus
Respiratory Syncitial virus (RSV) 
Metapneumovirus
Coronaviruses (SARS)

Question 13

Severe Acute Respiratory Syndrome (SARS):

The spread of SARS could be linked to a primary (_) case and the infectivity was very (high / low). Transmission was mainly _, but also by _.

SARS elicited the first global response to an outbreak. In a record time of 6 weeks after recognition of the new disease _ was isolated and identified as a new pathogen. Koch’s postulates were fulfilled in monkeys in 8 weeks and the genome sequence was available in 10 weeks. All advances were instantly available through the internet and published online in a matter of days.

Answer 13

index
high
respiratory
aerosolized feces (fomites)

SARS-CoronaVirus (SARS-CoV)

Question 14

Severe Acute Respiratory Syndrome (SARS):

There were 8000 cases of SARS identified, causing 775 deaths (mortality 10%). SARS-CoV is an (enveloped / unenveloped) RNA virus and is stable in _ and _ (1-4 days). It is killed by _ and _.

The latest serology data on SARS suggests it was not previously endemic in people. Reservoir consists of _ (civet cats, fruit bats) that can carry _ that are homologous to SARS.

Early transmission from animals to humans was inefficient, but then CoV adapted to human-human transmission through mutations (_ virus). Ongoing introduction from the reservoir to humans was demonstrated by a repeat mini-epidemic in Dec 2003-Jan 2004. This was associated with the re-opening of “wet” markets in China where live animals were sold.

Answer 14

enveloped
feces and urine
disinfectants and heat

healthy animals
coronaviruses (CoV)

RNA

Question 15

Severe Acute Respiratory Syndrome (SARS):

_ are now thought to be the natural reservoir for many viruses, including SARS-CoV, rabies, Nipah & Hendravirus and Ebola & Marburgvirus.

They chew, suck and then regurgitate _ and _, remnants tainted by _ containing these viruses are dropped under the trees that they live in and contaminate the surrounding area.

Animals (pigs, civet cats) or humans come in contact with _ and can get infected. Adaptation to the host is facilitated by the high mutation rate of _ viruses.

Proximity of humans to _ (_) and easiness of _ increase the chance of rapid dissemination causing epidemics or pandemics.

Answer 15

Bats

fruits and insects
bat saliva

bat droppings
RNA

animal reservoirs (animal husbandry)
travel

Question 16

Avian Influenza:

Avian Influenza in birds is caused by _, _, and _ strains.

Most are of (high / low) pathogenicity (_) and are carried (symptomatically / asymptomatically) in the respiratory and GI tract of birds.

(High / Low) pathogenicity (_) strains cause disseminated disease and death.

The _ strain is predominant since 2004 and continues to cause illness and death mainly in birds but also in other animal species including humans: Over 648 human cases and 384 deaths (59% mortality) have been reported as of August 10th 2012.

Until now no efficient transmission to humans has been documented due to a different _.

Conditions for a pandemic exist when a new virus subtype emerges (H5N1 or next) and _ takes place; genetic material is exchanged between _ and _ viruses - facilitating the gradual process of adaptive mutation resulting in an increased ability to bind to human cells in subsequent infections.

The virus can then infect _, spreading easily between humans (Ro>1) causing an epidemic or pandemic.

Answer 16

H5, H7 and H9

low (LPAI)
asymptomatically

High (HPAI)

H5N1

tissue tropism (interspecies barrier)

reassortment
human and avian

humans

Question 17

Avian Influenza:

1) The currently circulating _ has an expanding host range including humans, tigers and cats while some new reservoirs excrete the virus without becoming _. H5N1 viruses are now endemic in _ and spread by migrating wild birds as well as by illegal fowl trading.
2) Severe consequences are anticipated since there the mortality is (high / low) while there is no pre-existing _ to the strain unless a vaccine is developed and administered widely throughout the world.
3) In addition, this avian influenza is resistant to _ and _ possibly caused by using these antivirals in birdfeed. Resistance to _ has also been reported.

Answer 17

H5N1
ill
Asian domestic fowl

high
immunity

amantadine and rimantadine
oseltamivir

Question 18

Metapneumovirus:

Was first described in 2000. It was discovered by “fishing” with PCR primers in a cohort of children with _.

It is a common cause of _ infections in children and adults and has been prevalent for decades. New techniques can discover “new” diseases.

Answer 18

undiagnosed pneumonias

respiratory

Question 19

Different causes of meningitis, encephalitis, encephalopathy in the USA:

Bacterial (3)

Viral (4)

Fungus (1)

Prion (2)

Answer 19

Streptococcus pneumoniae
Neisseria meningitidis
Listeria

Enterovirus
West Nile virus
Herpes Simplex virus
Arboviruses

Cryptococcus

CJD
vCJD

Question 20

West Nile Virus:

Several cases of _ occur.

An outbreak of a communicable disease was investigated when this illness was previously absent and when >2 of these cases were associated in time and place. The investigation yielded 8 human cases that met the case definition of which 3 died. They all were active outdoors and lived in a 2-by-2 mile area in northern Queens.

Serology was positive for _ against _ species. In the meantime, an excess of dead crows in the NYC parks was observed. Brain tissue from dead crows was collected and viral cultures on eggs were positive.

Nucleic acid analysis of the cultured virus was analogous to West Nile Virus (WNV) in the flavivirus family, linking the cause of the death of the crows to the observed illness in humans. Antibodies for WNV have since been found in many _ and _ species The incidence of WNV+ mosquito pools coincided with ill humans and horse and infected birds.

Answer 20

encephalitis

IgM
flavivirus

bird and mosquito

Question 21

West Nile Virus:

WNV infection is (symptomatic / asymptomatic) in only 1:5 people infected (by serology).

It causes a _ only in 1:150 people. WNV is widespread in Africa, Middle East, Eastern Europe and now endemic in the USA.

The reservoir is _ and transmission occurs per _ that are viremic for life.

Preventive measure are mosquito control by spraying and eliminating water pools (tires), by personal protection against mosquito bites (DEET/clothing) and screening of organ and blood donations during the period of endemicity (summer and fall).

Answer 21

symptomatic

meningo-encephalitis

birds
mosquitoes

Question 22

New variant Creutzfeldt Jacob Disease (vCJD):

_ are diseases of humans and other animals.

Some of these are _ and some are _ by either inherited or spontaneous mutations.

Although the cause of some of these encephalopathies are _ and thus infectious, they are not caused by live micro-organisms but by _.

Answer 22

Spongiform encephalopathies

transmissible
genetic

transmissible

abnormal (dead) proteins or prions

Question 23

• Transmissable and genetic spongiform encephalopathies in humans (5)
• Spongiform encephalopathies in animals (3)

Answer 23

-Sporadic Creutzfeldt-Jakob disease (sCJD)
-New variant Creutzfeldt-Jakob disease (vCJD)
–Kuru (Fore tribe members in New Guinea eating human brains)
–Gerstmann-Straussler-Scheinker disease (GSS)
–Fatal familial insomnia (FFI)

–Scrapie (sheep)
–Bovine spongiform encephalopathy (BSE)
–Chronic wasting disease (CWD) in elk and deer

Question 24

New variant Creutzfeldt Jacob Disease (vCJD):

The cause of spongiform encephalopathy is a protein found in high quantities in the _ (and much lower levels in other tissues). This protein, called _ is present in all brains without _, but when the protein takes on an abnormal shape it accumulates unless _ by normal pathways.

In susceptible individuals with the 129 MM genotype, elevated levels of this abnormal protein kill _ and cause the clinical symptoms of the disease.

Human to human transmission of prion disease has been documented by (4)

Answer 24

brain
prion (PrP)
any harmful effects
destroyed

brain cells

cannibalism, use of corneal transplants, contaminated neurosurgical devices and blood transfusions

Question 25

New variant Creutzfeldt Jacob Disease (vCJD):

Abnormal prions are _ proteins and survive the rendering process (highly resistant to _ and _).

_ spread between cows in the UK when left-over bovine carcasses (bone meal) were used as animal feed. The emergence of _ was noted and changing feed practices have decreased the incidence.

When patients were reported with unusual presentations of _ (younger age at onset and causing rapid death) a link with BSE suspected. Named “variant Creutzfeldt-Jakob Disease (vCJD)” caused clinical symptoms in humans that were very similar to BSE symptoms in cattle. The disease is uniformly _ and has been casually linked to the consumption of either _ or _. Cumulatively ~230 human cases have been reported (mainly in the UK) as of 2013.

Answer 25

denatured
heat and chemicals

BSE
Mad Cow Disease (BSE)

sporadic CJD
fatal
BSE meat contaminated with brain tissue or the consumption of brain tissue itself

Question 26

Different causes of acute gastroenteritis:

Bacterial (6)

Viral (2)

Parasites (2)

Toxins (5)

Answer 26

E. coli 
Salmonella
Campylobacter
Yersinia
Vibrio cholera
Bacteroides fragilis 

Norovirus
Rotavirus

Giardia
Cryptosporidium

Staphylococcal toxin
Bacillus cereus
Botulism
Ciguatara
Scombroid

Question 27

Norovirus:

(formerly named Norwalk virus) was first described as the cause of an outbreak of _ in Norwalk, Ohio (1968). As part of the investigation bacterial cultures of feces were negative. Then a human experiment was conducted to test Koch’s postulates:

1) Feces was _ (bacteria and parasites were _)
2) Filtrate was fed to volunteers who all developed _, this was suggestive of a viral etiology.
3) Pre-treatment of the filtrate with _ did not destroy infectivity: The virus did not contain a _ which would have made it environmentally unstable. Viruses with lipid membranes need _ such as wet hands, snot, or genital tract but typically do not survive harsher environments such as the _ or .
4) Electron microscopy showed viral particles (1972), confirming it was a virus with a _ that offers the unstable inside protection against (4). These viruses flourish in the _.

Answer 27

gastro-enteritis

filtrated
removed

gastro-enteritis

soap
lipid envelop
moisture

gastro-intestinal tract or dry surfaces

capsid
RNA genome
high temperatures, drying, acid and detergents
GI-tract

Question 28

Norovirus:

Norovirus causes a self-limited _ (24-48 hours) with nausea, vomiting, abdominal pain and diarrhea. It is very _ and has caused many outbreaks in schools, cruise ships and hospitals. Diagnosis can be made by PCR and EM of _, and by serum testing for _ by ELISA.

Reservoir is _ and transmission is indirect by _ (hands/food/door handles) and _ with viruses (vomiting). There is no available _ or _

Preventive measures are:

1. _ after touching contaminated surfaces and prior to eating
2. harsh chemical _ of environment

Answer 28

acute gastro-enteritis
contagious
stool
antibodies

humans
oral-fecal route
airborne fomites
treatment or vaccination

washing hands
cleaning

Question 29

Re-emerging Infections:
Tuberculosis:

Tuberculosis was previously thought to be nearly _ in the resource rich world but is now resurging due to _ and the increasing pool of _ hosts (HIV).

In addition, the spread of _ and _ TB is causing great concern, especially in Sub-Saharan Africa and the former Russian Republics.

Answer 29

eradicated
immigration
immunocompromized

Multi Drug resistant (MDR)
Extreme Drug resistant (XRD)

Question 30

Re-emerging Infections:
Polio:

Polio has re-emerged in _ and _ in areas where it had been eradicated.

Most of the outbreaks have been due to re-introductions of polio from _ areas to people with low herd immunity - _ because religious beliefs.

Some outbreaks have occurred due to reverting of _ polio vaccine strains back to _ poliovirus.

Answer 30

Africa and Asia

endemic
not vaccinated

attenuated
wild-type

Question 31

Re-emerging Infections:
Measles and Pertussis:

Other vaccine-_ diseases such as measles and pertussis have re-emerged due to _ with immunization recommendations.

This is mainly driven by some parents who are more concerned about potential rare _ of vaccinations rather than maintaining the herd immunity against these devastating illnesses.

Answer 31

preventable
non-compliance

side effects

Question 32

Re-emerging Infections:
Salmonellosis:

Salmonellosis which nearly disappeared from the first world with improved _ and treatment is now re-emerging with wider distribution of _ and more _.

Answer 32

hygiene
food supply
antibiotic resistance

Question 33

Re-emerging Infections:

Because re-emerging infections are per definition not from _ microorganisms, the real challenge in preventing them is constant public health surveillance.

In the United States, this occurs largely at the local and state level. Each US state decides which infectious diseases are _ for the purposes of counting cases, a system of passive surveillance for organisms of public health significance.

Physicians are legally required as a condition of licensure to _, but in practice few actually do this.

Most reporting occurs via _ and _, which automatically report notifiable diseases. In most states, they also forward bacterial and viral isolates to state reference typing laboratories on a standing or as-requested basis, depending on the pathogen.

Answer 33

novel

reportable

report suspected cases of these notifiable diseases to the local/state health department

hospital and outpatient microbiology laboratories

Question 34

Re-emerging Infections:

At the national level, the Centers for Disease Control, a division of the US Public Health Service, coordinates national outbreak investigations between state _ and _ (MDs, veterinarians, and epidemiologists) in the Epidemic Intelligence Service (EIS) to investigate outbreaks of foodborne and other reportable illnesses that cross state lines.

The entire system is voluntary, and CDC must coordinate with _ (FDA, USDA) if control measures must be taken.

Answer 34

health departments
field officers

food safety enforcement agencies

Question 35

Foodborne Illnesses:

Foodborne illnesses sicken more than 4,000,000 people per year in the U.S. alone. Detection of outbreaks of foodborne illness can be (easy / difficult) given modern large-scale agriculture and widespread food distribution networks. A significant number of cases of cases can occur nationwide from a single point source without _.

The genus Salmonella is a Gram (positive / negative) bacterium which is a _ without much host specificity.

It ends up in meat products where _ comes in contact with said foods, and eggs can be internally contaminated as well. The virulent serotype of _ causes typhoid fever, a potentially fatal infection in humans, but this disease has become rare with improved sanitation in the America’s and Europe. Infections by other foodborne serotypes (S. enterica serotypes Typhimurium, Enteriditis, Cholerasuis etc.), however, are on the rise.

These cause disease states ranging from self-limited _ in the normal host to _ in the elderly and immunocompromised. The usual case fatality rate for non-typhoidal Salmonella is ~ 0.03-0.06%.

Answer 35

difficult
attracting the notice of a local or state health department

negative
zoonosis

animal fecal contamination
Salmonella enterica Typhi

gastroenteritis
septicemia/death

Question 36

Foodborne Illnesses:

To monitor for foodborne outbreaks of Salmonella that would escape local detection, the CDC uses a voluntary molecular epidemiology program called _, part of CDCs FoodNet safety research arm.

State health departments collect Salmonella bacterial isolates from all diagnosed cases and type them using _, a visual band-based typing system for bacteria based on the unique patterns that result when genomic DNA from a strain of Salmonella is digested by a restriction enzyme and run on a high-resolution agarose gel.

The banding pattern for each Salmonella tested by a health department is uploaded to a CDC website. Epidemiologists can then monitor for _ and assist local health departments in tracing outbreaks to suspect foods.

Once a food has been implicated as the source in an outbreak, the CDC’s only role is to continue _ the success of any interventions that other enforcement agencies take (USDA, FDA, and state agricultural regulators); CDC has no legal enforcement authority over the _.

Answer 36

PulseNet

pulsed field gel electrophoresis (PFGE)

unique PFGE types

monitoring
food supply

Question 37

Important factors in emerging infections (5)

Answer 37

Interspecies crossing
Adaptation of a virus
Susceptible hosts
Global warming
Improved diagnostic tests

Question 38

Important factors in emerging infections:

1. Interspecies crossing
   Close human proximity to (3)
   Encroachment to new _ (humans handling jungle meat-Ebola)
2. Adaptation of a virus to the human host
   Change (human) as incidental _ to reservoir (SARS)
   Improved human-human _ (HIV)
   _ can determine pathogenicity (diarrhea in SARS)
3. Susceptible hosts
   International _ increases the size of population at risk (SARS)
   _ exposes non immune humans to a “new” disease (H5N1)
   Decreased _ rates due to concerned parents (measles)
4. Global warming
   Expansion of _ habitats (Dengue, chikungunya)
5. Improved diagnostic tests
   Reveal new _ of existing syndromes (Metapneumovirus)

Answer 38

birds, pigs (Influenza) and bats
reservoirs

host
transmission
Tissue tropism

travel
Antigenic shift
childhood vaccination

mosquito

pathogens