Docstoc

Emerging infectious diseases EID

Document Sample
Emerging infectious diseases  EID Powered By Docstoc
					Emerging infectious diseases 新興的感染疾病
交通大學生物科技學系 彭慧玲 hlpeng@mail.nctu.edu.tw

International Conference on Emerging Infectious Diseases (EID)

   

Which infectious diseases are emerging ? Whom are they affecting? Why are they emerging now? What can we do control them?

Definition






A new microbe The invasion of a new host by a known microbe The increase of clinical severity caused by an existing microbe

Causes of the diseasesa reflection of human and microbial ecology


Changes in human practices


Legionnaires’ disease > 60 y, 10% (2000) 21% (2050) Vector-borne, food-borne, water borne, and nosocomial infections zoonotic infections Bio-terrorism



An aging planet




Large outbreak


 

Legionnaries’disease 退伍軍人症


1977, an outbreak of Legionella pneumophila lung infection in the legionnaires attending the conference


“ ventilator pneumonia” – associated with contamination of air-conditioning water towers
Long-term care facilities- nursing homes 2~15% community acquired pneumonia



cause 10~ 40% of the nosocomial pneumonia
 

Lyme disease 萊姆症


1982, Lyme disease and spirochete


Borrelia burgdorferi transmitted by deer tick  Autoimmune reactivity
long-term neurological damage  CDC report in 2003~2005, 300 cases per 100,000 population in New York (2 counties) and Dukes county in Massachusetts
 irreversible

Geographic origins of EID (1940-2004)

Socioeconomic drivers

- Population density
- Agriculture practice

- Antibiotic drug use
Category of EID event - Zoonotic wildlife

Nature (2008) Feb

Rapid changes of microbial genetic makeup


Drug resistant Microbes Nature (2008) Feb  Global trends in EID: Virus and Bacteria

The microbes- Virus (病毒) and Bacteria (細菌)
- differentiated on the basis of size?
Nano-bio

The giant virus- Mimivirus


mimicking microbe virus
A DNA virus ~ 800 nm diameter No ribosome machinery
Science 306 (October 2004)



 

Giant bacteria
 

1985, isolated from the intestinal tract of the Red Sea brown surgeonfish 200 mm ~ 500 mm
Namibia Sulfur Pearl



Epulopiscium fishelsoni








1997, isolated from ocean sediment off the coast Namibia spherical g-proteobacteria bacteria 100~750 mm diameter vacuole rich in sulfur granules occupies about 98% of the cell a whale of a bug!
Thiomargarita namibiensis

Viruses versus bacteria
Viruses

  

Bacteria

  

simple organization DNA or RNA viruses reproduce by assembly obligate intracellular parasites

cellular organization both DNA and RNA reproduce by division some are obligate intracellular parasites

- A novel virus


Hepatitis virus A (1960~), hepatitis B
(1970), hepatitis E virus (enteric-, 1988), hepatitis C virus (1989), hepatitis G viruses (1995~1996)  Hepatitis E in England and Wales
2005, 329 cases were confirmed  ~ 100 cases Indigenous infections



Zoonotic infections? EID (2008) 14:165-7

Human immunodeficiency virus (HIV)


1983, HIV was correlated with AIDS (acquired immunodeficiency
syndrome)  A retrovirus (an RNA virus) believed to have evolved in Africa from a monkey virus  2006 CDC estimation:




~ 1 million HIV infections in USA Converging HIV and MDR-TB (multidrug resistance tuberculosis) Outbreaks Worsen

Glycodendrons- PNAS(2008)

- Increase of clinical severity

SARS- epidemic of 2003


severe acute respiratory syndrome
Infected more than 8500 people and killed ~800 patients in 29 countries




3 groups coronaviruses:  groups 1 and 2: mammalian virus  human coronaviruses  HCoV-229E and HCoV-OC43  group 3: avian viruses

Coronavirus (crown-like) - an RNA virus

The origin of SARS-CoV- a zoonosis?

Enterovirus 71 (1998~ )
 

An RNA virus Typical cold symptoms
 

mild enteric disease hand, foot, and mouth disease



CNS (central nervous syndrome) diseases

- A new host


H 抗原; HA

Influenza virus (an RNA virus)


Specific antigens- HA, NA


Antigenic variation
HA 1~3 and NA 1~2



human flu


N 抗原; NA; 神 經胺酸 脢



  

Influenza Pandemics
1918, HswN1 (Spanish flu) 1947, H1N1 1957, H2N2 (Asian flu) 1968, H3N2 (Hong Kong flu) 1977, H1N1 (Russian flu)





Avian flu- H5N1(1997~)

Most Influenza Strains Do Not Match Current Vaccine


The predominant type A flu virus this year is the H3N2 strain; 87% are the "Brisbane" strain. And 93% of this year's type B flu bugs are from the "Yamagata" lineage.


The current flu vaccine's H3N2 component is the "Wisconsin" strain; the type B component is from the "Victoria" lineage. That means reduced protection against the Brisbane and Yamagata bugs. (CDC Feb 2008)

Generation of a reassortant virus
- broad host range and segmented genome

Reassortant virus

Avian flu virus


H9N2 (1998/1999)


China and Hong Kong Netherlands



H7N7 (2003)




H5N1 in human (1997~2003~)


Hong Kong, China, and worldwide….

Emerging Infectious Diseases (2007) October

Barry J. Marshall

- A novel bacteria


Winner of the Nobel prize in physiology or medicine 2005

1983, Helicobacter pylori (HP) is  world-wild infection rate ~ 60%  the causing agent peptic ulcers  a major risk factor for mucosaassociated lymphoid tissue (MALT) lymphoma  Classified by WHO (1994) as a class I carcinogen- gastric cancer  2~6 folds increase risk

Multi-drug resistant bacteria



Co-epidemic MDR-TB/ HIV-AIDS MRSA (methicillin resistant Staphylococcus aureus)  Increased MRSA in Dutch hospital related to animal contact (Clin Infect Dis 2008;46:261-263)  Community-Acquired MRSA Often Fatal


1 year of follow-up 21.8% of MRSA patients died in comparing with 5.0% of the non-MRSA cohort
(BMC Medicine 2008;6)



Pan-drug resistant bacteria


Alcinetobacter baumanni causes an opportunistic infections

Reemrgence of anaerobic bacteremia (Clin Infect Dis 2007, 44:895-900)
- Emergent resistance to antimicrobial agents

- Diminishing ability to provide reliable prediction of infection source

The Mayor Clinic (Rochester, MN)

Microbiota shift diseases

 

Periodontal disease Bacterial vaginosis Inflammatory bowel disease: Crohn’s disease




a wide spread granulomatous inflammation of the intestine possible etiology
 



Genetic susceptibility uncontrolled tissue injury Intestinal bacteria


an adherent-invasive E. coli (Cellular Microbiology 2007)

Prion


A small proteinaceous infectious
particle





Passes through the filter (100 nm) and still transmits disease resistant to a wide range of chemical and physical treatment


inactivated at 121oC 1 h

Scrapie- cause intense itching

Scrapie and Kuru


Scrapie: the prototype of prion
(18th century in England)  A natural progressive brain disease



Kuru: “shivering” or “ trembling”


1950, occurred in the Fore tribe of New Guinea highlands  Related to the cannibalistic practices  Blurred speech, silly smiles, and dementia

lose the ability to walk, talk, and see

The 1st Nobel Prize for prion study



1976, Carleton Gajdusek (1923~)


retired as chief of the laboratory of CNS at NIH

Demonstrated Kuru’s etiology  an infectious invisible slow (~ 30 y incubation period) virus as that of Scrapie?  Never saw any inflammation!

Creutzfeldt-Jakob disease (CJD)




The human form of mad cow disease  BSE (Bovine Spongiform encephalopathy) Identified by Creutzfeldt and Jakob (1920)






A progressive fatal neurodegenerative disease Usually aged between 50~75 Characterized by seizures, massive incoordination, dementia

Transmission of CJD

  

Injection with contaminated growth hormone Transplantation of contaminated corneas Contact with contaminated medical devices


brain electrodes- “Iatrogenic” 1996 in UK, causes an unusual incidence of CJD in young people (<45 yr)- new variant of CJD/ vCJD
(Emerg Infect Dis 2007)

Ingestion of infected tissue




Blood transfusion and spread of vCJD

BSE epidemic-emergence of vCJD

1,2,3- iatrogenic CJD

vCJD

Inheritable CJD- prnp
 

A Gerstmann-Straussier-Scheinker syndrome A Kuru like familial disease Inherited forms emerge earlier (~ 45 yr)




familial CJD, GSS, fatal familial insomnia (FFI)10~15% specific mutation of the gene on chromosome 20prnp

Prion protein (PrP)
  

Aggregates of a protease-resistant, hydrophobic glycoprotein- PrP PrPsc for Scrapie prion protein Human (chromosme 20) and other animals encode a PrPc (cellular prion protein)- prnp




PrPsc is protease-resistant, aggregates into fibrils (amyloid rods), is found in cytoplasmic vesicles and is secreted The normal PrPc is protease-sensitive and appears on the cell surface

The 2nd Nobel prizePrion pathogenesis




PrPsc binds to the normal PrPc on the cell surface, causing it to be processed into PrPsc - a replicating protein, to be released from the cell, and to be aggregated as amyloid-like  1997, Stanley Prusiner (1942~) for showing that plaques in the brain PrPsc is sufficient to Vacuolated neurons (loss of cause disease
function and lack of an immune response)
 Director of institute of

neurodegenerative disease UCSF

The prion hypothesis- propagation of prion protein
“X protein?”

Bio-weapon: bio-safety P4 level

生物戰劑預估的殺傷力

Biological weapon (Germ warfare)


Bio-terrorist attempts to
identify virulent pathogens suitable for aerosol delivery and industrial scale fermentation process to produce large quantities of pathogens and toxins
Cutaneous Anthraxcaused by

Bacillus anthracix

Smallpox (Variola)
 


smallpox virus A re-emerging disease:
“Biological weapon”

transmitted by aerosol or contact
 

humans are only reservoir 30% fatality

Ebola hemorrhagic fever




A severe and often fatal disease in human or nonhuman primates 1st recognition- 1976


4 subtypes:  Humans- Ebola-Zaire, EbolaSudan, and Ebola-Ivory Coast  Nonhuman Primates- EbolaReston

TRENDS in Microbiology (2007)

Hantavirus Pulmonary Syndrome
An outbreak occurred in May 1993 in the Four Corners (New Mexico, Arizona,


Colorado, and Utah)  The deer mouse- the principal carrier (climate changes)  Navajo Indian
 No person to person spread



cause hemorrhagic fever

To counter the diseases
 

Rapid diagnosis Vaccine and drug development


Functional genomics
 

gene annotation expression at mRNA level


cDNA microarray



proteomics

基因晶片

二維蛋白質電泳膠片

激脢晶片

Cyclopentadine linker

Peptide

Monolayer alkanethiolates on gold

抗體晶片

Vaccines are nontoxic antigens


A vaccine consists of a preparation of killed microorganisms; living, weakened (attenuated) microorganisms; or inactivated bacterial toxins (toxoids) that are administrated to an animal to induce immunity artificially.


Subunit vaccine and DNA vaccine (target to the major antigens)

Preparedness
- the next influenza pandemic


Priority subtypes for vaccine preparation




H5N1  the avian strain is lethal for chick embryos  Baculovirus-expression system  modified HA A surrogate nonpathogenic H5N3


low immunogenicity

Generation of a pandemic influenza vaccine strain



PLoS Pathogens (2007) March

New Solutions
 

New aspect for prevention: Surveillance- Monitoring disease
prevalence


A treatment-based approach to a variety of

surveillance programs (an early warning system)
- CDC (center of disease control) - WHO (world health organization) - NIH (national institute of health) - NHRI (national health research institute)


				
DOCUMENT INFO
Shared By:
Categories:
Stats:
views:405
posted:4/28/2008
language:English
pages:54