lectures+67 68+emerging+infections+handouts

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Emerging Infectious Diseases

Fall 2012 1

A work in continuous progress

Monday, October 22nd, 2012

A Modern Myth

In 1899 the Commissioner of the US Patent

Office supposedly said: “… everythingalready has been invented..." and then hewent on to suggest that the Patent Office was

Fall 2012 2

.

…. Close investigation has debunked this; it isnot true. In 1899 there were 3,000 morepatent applications than there were in 1898!

A More Modern Myth

By the mid-1970s, the discovery of newantibiotics had already sharply declined, butPhysicians were confident that all knownbacterial diseases were treatable withexistin antibiotics. The bulk of microbiolo

Fall 2012 3

.research had already gravitated towardViruses, against which there was no knowntherapy.

Physicians were openly talking about a “Post-Infectious Disease Era”

-But this one is true!

Forty years ago bacterial pathogens were aproblem of the past…….. In 1969, at the height of antibiotic development, the

U. S. Surgeon General publicly declared “Victoryover infectious disease”

However, bacterial diseases had persisted, andcontinue to reemerge across the globe.

Fall 2012 4

ra seases suc as e u an pose aneven more challenging threat.

Emerging diseases such as Ebola and CJD continueto perplex scientists.

Perhaps most frighteningly, antibiotic resistantbacteria lurk in the very places that people go to getwell – hospitals

.

The end of the dream…

July 04, 1976: Bellvue-Strafford Hotel, Philadelphia

Pa. The Bicentennial Year at the Bicentennial place.

A terrorist incident (perhaps the Weather

Underground?) caused many members of the

Fall 2012 5

mer can egon o ge s c urng e r conven on

there, and some died of pulmonary complications

Intense investigation eventually turned up a

previously unknown bacterium which we now know

as Legionella pneumophilia

It was not a deliberate act, after all.

Definition

“There is no simple definition of an emerging

infectious disease. In general, it can be a

completely new disease or an old disease

occurrin in new laces or new eo les; with

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new presentations; or is newly resistant to

available treatments. There are many recent

and historical examples of emerging

infectious diseases.”

http://www.geis.fhp.osd.mil/GEIS/aboutGEIS/FAQs/FAQ3.asp



Patterns of Emergence

1. Altogether New Disease:

2. Old Disease, New Place:3. Old Disease Reintroduced:

Fall 2012 7

. ,

5. Increased Virulence:

6. Drug Resistance:


1. New Disease: AIDS, Ebola, Legionnaire’s, Nipah virusinfection

2. Old Disease, New Place: Smallpox, the New World, 16thCentury, Black death (plague), Europe, 14th Century Hepatitis

E, Haiti West Nile fever, NY, 1999

3. Reintroduced: Dengue fever, Texas : Plague, India:Measles, United States: Malaria, Korea: Adenovirus, USMilitary training camps

Fall 2012 8

4. New Population: Malaria, US soldiers in Somalia: Marburgvirus, lab workers in Germany: Cholera, Peru

5. Increased Virulence: Influenza, 1918 worldwide pandemicH5N1 influenza, Hong Kong E. coli O157:H7, United States

6. Drug Resistance: Campylobacter, Malaria, Strep


Altogether New Diseases

Meaning “new” to humans: These diseases

existed in animal populations (somewhere)

previously

Le ionnaire’s Disease 1976

Fall 2012 9

HIV early 1980s

Marburg and Ebola 1960s and 1970s

Hantavirus 1990s

SARS 2000s

More “New” Diseases:Ehrlichiosis and Anaplasmosis

2008 Case Definition

CSTE Position Statement Number: 09-ID-15

Ehrlichia chaffeensis infection (formerly Human

Monocytic Ehrlichiosis [HME])

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Ehrlichia ewingii infection (formerly Ehrlichiosis

[unspecified, or other agent])

Anaplasma phagocytophilum infection (formerly

Human Granulocytic Ehrlichiosis [HGE])

Ehrlichiosis/Anaplasmosis, human, undetermined

http://www.cdc.gov/ncphi/disss/nndss/casedef/ehrlichiosis_2008.htm

Ehrlichiosis and AnaplasmosisClinical Description

Clinical presentation:

A tick-borne illness characterized by acute onset of fever

and one or more of the following symptoms or signs:

headache, myalgia, malaise, anemia, leukopenia,

thrombocytopenia, or elevated hepatic transaminases.

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Nausea, vomiting, or rash may be present in some cases .

Clinical evidence:

Any reported fever and one or more of the following:

headache, myalgia, anemia, leukopenia,

thrombocytopenia, or any hepatic transaminase elevation.


Ehrlichia chaffiensisLab Diagnosis Supportive:

Serological evidence of elevated IgG or IgM antibody reactive with E.chaffeensis antigen by IFA, enzyme-linked immunosorbent assay (ELISA),dot-ELISA, or assays in other formats (CDC uses an IFA IgG cutoff of ≥1:64and does not use IgM test results independently as diagnostic supportcriteria.), OR

Identification of morulae in the cytoplasm of monocytes or macrophages bymicroscopic examination

Fall 2012 12

Confirmed: Serological evidence of a fourfold change in immunoglobulin G (IgG)-specific

antibody titer to E. chaffeensis antigen by indirect immunofluorescenceassay (IFA) between paired serum samples (one taken in first week of illnessand a second 2-4 weeks later), OR

Detection of E. chaffeensis DNA in a clinical specimen via amplification of aspecific target by polymerase chain reaction (PCR) assay, OR

Demonstration of ehrlichial antigen in a biopsy or autopsy sample byimmunohistochemical methods, OR

Isolation of E. chaffeensis from a clinical specimen in cell culture




Ehrlichia ewingii infection (formerly Ehrlichiosis [unspecified, or other agent])

Lab Diagnosis

Laboratory criteria for diagnosis

Confirmed:

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Because the organism has never been cultured,

antigens are not available. Thus, Ehrlichia ewingii

infections may only be diagnosed by molecular

detection methods: E. ewingii DNA detected in a

clinical specimen via amplification of a specific

target by polymerase chain reaction (PCR) assay.http://www.cdc.gov/ncphi/disss/nndss/casedef/ehrlichiosis_2008.htm

Anaplasma phagocytophilum infection (formerly

Human Granulocytic Ehrlichiosis [HGE])

Lab Diagnosis Supportive:

Serological evidence of elevated IgG or IgM antibody reactive with A.

phagocytophilum antigen by IFA, enzyme-linked immunosorbent Assay(ELISA), dot-ELISA, or assays in other formats (CDC uses an IFA IgG cutoff of ≥1:64 and does not use IgM test results independently as diagnosticsupport criteria.), OR

Identification of morulae in the cytoplasm of neutrophils or eosinophils by

Fall 2012 14

Confirmed: Serological evidence of a fourfold change in IgG-specific antibody titer to A.

phagocytophilum antigen by indirect immunofluorescence assay (IFA) inpaired serum samples (one taken in first week of illness and a second 2-4weeks later), OR

Detection of A. phago cyto phil um DNA in a clinical specimen viaamplification of a specific target by polymerase chain reaction (PCR) assay,OR

Demonstration of anaplasmal antigen in a biopsy/autopsy sample byimmunohistochemical methods, OR

Isolation of A. phago cytop hilu m from a clinical specimen in cell culture


Ehrlichiosis/Anaplasmosis, human,

undeterminedCase Classification

Exposure History of having been in potential tick habitat in the 14 days prior to the

onset of illness or history of tick bite or history of tick bite.

Case Classification1. Sus ected: A casewithlaborator evidenceof ast or resentinfection but

Fall 2012 15

. no clinical information available (e.g. a laboratory report).

2. Probable: A clinically compatible case (meets clinical evidence criteria) thathas supportive laboratory results. For ehrlichiosis/anaplasmosis – anundetermined case can only be classified as probable. This occurs when acase has compatible clinical criteria with laboratory evidence to supportEhrlichia/Anaplasma infection, but not with sufficient clarity to definitivelyplace it in one of the categories previously described. This may include theidentification of morulae in white cells by microscopic examination in theabsence of other supportive laboratory results.

3. Confirmed: A clinically compatible case (meets clinical evidence criteria)that is laboratory confirmed.


Re-emerging Diseases

Well-known “old” infectious diseases which we once

thought to have beaten, but which are resurgent due

to shifts in our environment or in our behavior

This happens often when, for one reason or the

Fall 2012 16

o er, peope s op prac c ng vacc na on or a g ven

disease because the risk of vaccine complications

rises over the risk of the disease itself

Or it can happen as an unintended consequence

when other health or environmental practices

change

Re-emerging Disease

Potential Candidates

Di htheria Discontinuation of

Any infectious disease which is endemic in a human Any infectious disease which is endemic in a humanpopulation and which is held in check by organizedpopulation and which is held in check by organized vaccination programmes vaccination programmes

Fall 2012 17

Pertussis

Herpes Zoster

Measles

Polio

etc

vaccination for any

reason will allow a

susceptible population

to develop, and the

disease will shortly re-

emerge

Fall 2012 18



Re-Emerging Diseasesdue to

Changes in Social or Environmental Practices

Tuberculosis Re-emerged after being effectively beaten

because it was able to persist in the homeless, prison and IV drugusing communities, until it got a timely boost from the emergence

of HIV

Fall 2012 19

Prisons throughout the world have historically been

incubators for TB. When governments fall and the care (if

any) of prisoners deteriorates, TB can re-emerged with a

vengeance

After the collapse of the Soviet Union from the Gulags

Release of prisoners after fall of the Apartheid government in

South Africa.

Re-Emerging Diseasesdue to

Changes in Social or Environmental Practices

Malaria was brought well under control

throughout the world by the late 1950s, after

10 to 15 years of DDT use.

Fall 2012 20

Since DDT was discontinued, malaria has re-

emerged as the #1 infectious disease killer in

the world

More recent insecticides have failed to “dent”

the mosquito vector population

Old Diseases in new PlacesNew Host Populations

Many examples in the past 500+ years of history

Plague Europe from Asia 14th Centuryth

Fall 2012 21

Syphilis New world to the Old 16th Century

Plague again ? 17th Century

Cholera World from India 18th Century

Measles Pacific Islanders 19th Century

Polio Inuit (Eskimo) Peoples 20th Century

Old Diseases in new Orificesthe “New” STIs

Certain “Safe Sex ”1 Anal-Oral practices2 haveenabled some of the traditionallyGastrointestinal pathogens to recently “makethe jump” to become real STDs

Fall 2012 22

ar a am a - ro ozoan

Amoeba sp. - Protozoan

Shigella sp. – True Bacteria

E. coli – True Bacteria

Others? – Hepatitis A, B. and C ?

1

“Safe Sex” is a classic oxymoron

2 Sometimes called “Rimming”

Old bugs withIncreased Virulence

H1N1 Influenza, 1918 worldwide pandemic

H5N1 influenza, 1967 Hong Kong

Staph aureus Exotoxin TSST-1 -1980s USA

Fall 2012 23

The “Flesh Eating” Strep – 1990s USA

E. coli O157:H7, 1990s USA

Drug Resistance

PPNG Penicillinase positive Neisseria

gonorrhoea

MDR TB Multiple-Drug resistant

Mycobacterium tuberculosis

Fall 2012 24

u u

Emergence of Drug Resistance plasmids which

are spreading through the Enterobacteriaceae and

even to non-related bacteria



Patterns of Emergence

1. Altogether New Disease:

2. Old Disease, New Place:3. Old Disease Reintroduced:

Fall 2012 25

. ,

5. Increased Virulence:

6. Drug Resistance:

7. Old Disease which we are onlyslowly realizing is infectious innature


The Classic:Helicobacter pylori First seen in the human stomach in 1875

Role in gastric disease first suggested in 1899

Experiments in New York’s Bellview Hospital in1947 showed that some ulcers could be cured withantibiotics

Fall 2012 26

Barry Marshall and Robin Warren first cultured theorganism in 1981-1982

Marshall infected himself with the organism in thelate 1980s and proved its pathogenicity

Marshall and Warren won the 2005 Nobel Prize for this work.

Some Diseases which we are just now beginning to recognize as being infectious

Cervical Carcinoma HPV

Prostate Cancer XMRV*

Head and Neck Cancers HPV

Fall 2012 27

Diabetes Mellitis Mycoplasma sp.

Atherosclerosis Chlamydophila pneumoniae

Schizophrenia Toxoplasma gondii

Alzheimer’s Prions?

* = Xenotropic Murine Leukemia Related Virus, a gamma-

retrovirus. Disproven ??

Not our Usual Suspects…

ALS (Lou Gehrig’s Disease) Prions

Multiple Sclerosis Epstein-Barr Virus

Chronic Fatigue Syndrome “

Fall 2012 28

OCD (PANDAS)* Streptococcus sp.

* PANDAS = Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection

Even the current epidemic of

Obesitymay be an infectious disease!

MINIREVIEW: “Adipocyte, Adipose Tissue, and

Infectious Disease” 2007, Mahalia S. Desruisseaux,

Fall 2012 29

agayo , ara . ru o, er er . anow z, an

Philipp E. Scherer ( Albert Einstein College of Medicine

and the Montefiore Medical Center, Bronx, New York)

in: INFECTION AND IMMUNITY, Mar. 2007, p. 1066–1078

Vol. 75, No. 3Copyright © 2007, American Society for Microbiology. All Rights Reserved

http://iai.highwire.org/cgi/reprint/75/3/1066

The National Institute for Allergy and

Infectious Disease

Fall 2012 30

Has a lot to say on this subjectSee

http://www3.niaid.nih.gov/topics/emerging/



List of NIAID Emerging and Re-emerging Diseases

Group I—Pathogens Newly Recognized in the Past

Two Decades

Acanthamebiasis

Australian bat lyssavirusBabesia, atypical

Helicobacter pylori

Hendra or equinemorbilli virus

Fall 2012 31

Ehrlichiosis

Encephalitozooncuniculi

Encephalitozoon hellem

Enterocytozoonbieneusi

Hepatitis E

Human herpesvirus 8

Human herpesvirus 6

Lyme borreliosis

Parvovirus B19


Group II—Re-emerging Pathogens

Enterovirus 71

Clostridium difficile

Fall 2012 32

Mumps virus

Streptococcus, Group A

Staphylococcus aureus


Group III—Agents with Bioterrorism Potential

Category A

Bacillus anthracis (anthrax)

Clostridium botulinum toxin (botulism)

Fall 2012 33

Yersinia pestis (plague)

Variola major (smallpox) and other related pox viruses

Francisella tularensis (tularemia)



Category A (continued)

Viral hemorrhagic fevers Arenaviruses

LCM, Junin virus, Machupo virus, Guanarito virus

Lassa Fever

Fall 2012 34

unyav ruses Hantaviruses

Rift Valley Fever

Flaviruses Dengue

Filoviruses Ebola

Marburg



Category B (part 1 of 3) Burkholderia pseudomallei

Coxiella burnetii (Q fever)

Brucella species (brucellosis)

Fall 2012 35

Burkholderia mallei (glanders)

Chlamydia psittaci (Psittacosis)

Ricin toxin (from Ricinus communis)

Epsilon toxin of Clostridium perfringens

Staphylococcus enterotoxin B

Typhus fever (Rickettsia prowazekii)



NIAID—Category B (part 2 of 3):

Food- and waterborne pathogens Bacteria

Diarrheagenic E.coli

Patho enic Vibrios

Viruses (Caliciviruses, Hepatitis

A)

Fall 2012 36

Shigella species

Salmonella

Listeria monocytogenes

Campylobacter jejuni

Yersinia enterocolitica

Cryptosporidium parvum

Cyclospora cayatanensis

Giardia lamblia

Entamoeba histolytica

Toxoplasma

Fungi

Microsporidia





Category B – (part 3 of 3) Additional viral encephalitides

West Nile virus

LaCrosse

Fall 2012 37

California encephalitis

VEE

EEE

WEE

Japanese Encephalitis virus

Kyasanur Forest virus



Category C:

Emerging infectious disease threats suchas Nipah virus and additional hantaviruses.

Fall 2012 38

Another possible Category of “emerging” infectiousdiseases:

- Well-known organisms that were once

thought to be completely harmless to

humans

…… for example….Fall 2012 39

Serratia marscesens

Between Sept. 20 and Sept. 27 of

1950, a Navy mine-laying vessel

cruised the San Francisco coast,

spraying an aerosol cocktail of Serratia

and Bacillus microbes – all believed to

be safe – over the city from giant

,

declassified Army reports. Based on

results from monitoring equipment at

43 locations around the city, the Army

determined that San Francisco had

received enough of a dose for nearly

all of the city’s 800,000 residents to

inhale at least 5,000 of the particles.

Fall 2012 40

Serratia is a Gram-negative rod, a member

of the Enterobacteriaceaef amily. It grows

aerobically on common lab media, and it is

easy to detect because it forms brightly

pigmented colonies on plain Nutrient Agar

SERRATIA MARCESCENS, CONTAMINATED SOLUTION

- USA (02): (ALABAMA)

****************************************************************

A ProMED-mail post

<http://www.promedmail.org>

ProMED-mail is a program of the

International Society for Infectious Diseases

http://www.isid.org

Date: Thu 7 Apr 2011

Source: Fox 6 News, WBRC [edited]

Fall 2012 41

. . - - -

Bacteria that affected 19 Alabama hospital patients and possibly led

to the death of 9, initiated on a faucet [tap] at the Homewood-based

Meds IV pharmacy, according to the Alabama Department of Public

Health.

Samples of the bacteria, Serratia marcescens , were identified on a

sink faucet in the pharmacy. Water from that tap was used along with

soap to clean out a container used to create an amino-acid compound

used to create TPN [total parenteral nutrition],

Finding Serratia bacterium on a faucet is not uncommon, according to State

Health Officer Dr Don Williams. What's troubling, he said, is that the filter used

to sterilize the product failed and this is where the real problem lies. W illiams

said in a press conference Thursday [7 Apr 2011] it was his department's 1st

experience dealing with an outbreak of this kind and is working with the FDA to

determine if washing containers with unsterile water is within federal guidelines.

Williams confirmed that there is no risk to any other patients going forward and

the problem is absolutely limited to the TPN obtained by Meds IV. He said the

Centers for Disease Control and Prevention [CDC] polled other states to see if

anyone else was seeing similar problems with the bacteria and TPN. The CDC

Fall 2012 42

u w , y w

received TPN from Meds IV. "There is nothing to suggest that any of the

infections were associated with any pharmacy other than Meds IV," Williams

said. "Based on everything that we know, it is clearly linked to the

compounding of TPN in that pharmacy.”



Emerging Infectious

Diseases is publishedmonthly by the Centersfor Disease Controland Prevention (CDC),

1600 Clifton Road,

Fall 2012 43

Mailstop D61, Atlanta, GA30333, USA.

Telephone 404-639-1960,fax 404-639-1954,

e-mail [email protected] .

Some Important Web Sites

US Department of Defense Global Emerging

Infections Surveillance and Response System

(DoD-GEIS)http://www.geis.fhp.osd.mil/aboutGEIS.asp

Fall 2012 44

Disease

http://www3.niaid.nih.gov/topics/emerging/

CDC National Center for Infectious Disease

http://www.cdc.gov/ncidod/diseases/eid/

Books on the Subject

Ewald, Paul, “Plague Time: the New GermTheory of Disease”, 2002, Anchor Books, NewYork. ISBN 0-385-72184-6

Levy, Elinor and Fischetti, Mark , “The New

Fall 2012 45

er seases , ree vers ress, ewYork. ISBN 1-4000-5275-0

Zuk, Marlene, “Riddled with Life” 2007,Houghton Mifflin Harcourt, Orlando, Fl. ISBN978-0-15-603468-5

END

Fall 2012 46

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