Why study parasites?
The weird and bizarre
House, M.D. Episodes
The superb diagnostician everyone loves to hate Hugh Laurie
7 (1-07) "Fidelity" December 28, 2004 African trypanosomiasis
29 (2-07) "Hunting" November 22, 2005 Echinococcosis
32 (2-10) "Failure to January 10, 2006 Cerebral malaria Communicate"
43 (2-21) "Euphoria, Part 2" May 3, 2006 Primary amoebic meningoencephalitis by Naegleria fowleri
50 (3-04) "Lines in the Sand” September 26, 2006 Baylisascaris
60 (3-14) "Insensitive" February 13, 2007 Diphyllobothrium latum causing Vitamin B12 deficiency
73 (4-03) "97 Seconds" October 9, 2007 Strongyloidiasis
83 (4-13) “No More Mr. Nice Guy" April 28, 2008 Chagas disease
Why study parasites?
The weird and bizarre Infectious diseases: Emerging and re-emerging diseases Biodefense/bioterrorism links
1 Why study parasites?
NIAID Biodefense Research: Category A, B & C Priority Pathogens Infectious diseases: Emerging and re-emerging diseases Biodefense/bioterrorism links
Why study parasites?
The weird and bizarre Infectious diseases: Emerging and re-emerging diseases Biodefense/bioterrorism links Interesting Biology Unique eukaryotic biological properties
Unique Eukaryotic Biology
• Antigenic variation • Apicoplast • GPI-anchored proteins • Glycosomes • Bent DNA helices • Hydrogenosomes • Polycistronic transcription • Kinetoplast DNA (kDNA)(kDNA) • Trans-splicing of RNAs • Mitosomes • Mitochondrial RNA editing
2 Why study parasites?
The weird and bizarre Infectious diseases: Emerging and re-emerging diseases Biodefense/bioterrorism links Interesting Biology Unique eukaryotic biological properties Global Public Health Tropical diseases affecting some of the worlds poorest populations Diverse group of organisms ranging from microscopic to large multicellular organisms. Protozoa - unicellular eukaryotes Platyhelminthes - flatworms Nematodes - roundworms Arthropods - insects and ticks (parasitic or that transmit parasites)
Number of people infected/affected by parasitic diseases
Disease with HIGH mortality: Disease with morbidity and QL losses:
Malaria - 489 M
Sleeping Sickness 0.5 M Schistosomiasis - 200 M
Chagas disease - 18 M Onchocerciasis - 18 M Visceral Leishmaniasis - 4 M Filiariasis - 650 M
Ascariasis - 1.4 B
** Calculated World Pop Hookworm diseases - 1.3 B 1/26/09: Cutaneous leishmaniasis - 8 M 6.88 Billion Food and waterborne
Note: statistics from ~2004 protozoan - 1.5 B
Why study parasites?
The weird and bizarre Infectious diseases: Emerging and re-emerging diseases Biodefense/bioterrorism links Interesting Biology Unique eukaryotic biological properties Global Public Health Tropical diseases affecting some of the worlds poorest populations Diverse group of organisms ranging from microscopic to large multicellular organisms. Protozoa - unicellular eukaryotes Platyhelminthes - flatworms Nematodes - roundworms Arthropods - insects and ticks (parasitic or that transmit parasites)
3 MICROBIO590S Parasitology
More Concepts and Terms
“…no matter how we set ourselves off from nature we remain a part of it, and thus we invariably share parasites with the other species in which we live.” Julius P. Kreier PARASITIC PROTOZOA
Ecto- vs. Endoparasite
Ectoparasites live on, but not in their hosts. Protozoan Ichthyophthirius that causes fish “Ick”
Endoparasites live within the body and tissue of their hosts. The majority of parasites to be discussed. Protozoan Trypanosoma that causes African Sleeping sickness.
4 Facultative vs. Obligate
Facultative - usually a free-living organism but can invade host under certain conditions. Can cause severe disease. Naegleria fowleri
Obligate - most parasites Trypanosoma cruzi require a host for at least one stage of its life cycle. Some parasitic worms have free-living larval stages.
Intermittent vs. Permanent
Intermittent/ temporary - micropredation - “parasite” feeds on the host and then leaves.
Permanent - parasite that lives its entire adult life on or within the host. Most of the parasites we discuss are permanent.
Life cycles
Entamoeba histolytica Direct Life Cycle - parasite passes from one host to the next through contaminated food/water, air, or sexual intercourse.
Indirect Life Cycle - parasite passes from one host to the next through a vector and/or intermediate host. Diphyllobothrium latum Many parasites have complex indirect life cycles.
5 Vectors - Actively transmit parasites
Mechanical Vector - no multiplication or development of parasite takes place. Horse fly
Biological Vector - Tsetse fly either multiplication or development takes place.
Transmission of 2 related protozoa
Tsetse fly
Horse fly
Feeds often moving Proboscus used for front legs and mouth blood meal - longer parts vigorously. feeding period. Trypanosoma brucei Trypanosoma evansi bloodstream form is remains on the mouth ingested - develop to parts - no biological procyclic form - migrate development occurs. and develop to infective epimastigotes (new form).
Hosts
Definitive host - where sexual reproduction occurs. If there is no sexual reproduction documented, then it is the host that is most important to humans.
Typically a vertebrate. Exception - Plasmodium Intermediate host - where asexual replication or parasite development occurs. Paratenic host - transport host, but parasites do not develop in this host. Reservoir host - any animal that carries an infection that can serve as a source of infection to human and other animals. Accidental host - parasite enters or attaches to other than the normal host. Parasites usually do not survive in the wrong host, but can cause serious disease (Toxocara).
6 Example
Intermediate Paratenic Bridging the gap between human Host Host And small fish/copepod.
Copepod Monoecious Intermediate Hermaphroditic Host Definitive Diphyllobothrium Host latum Free-swimming stage
Summary
Ecto- vs. Endparasite
Facultative vs. Obligate
Intermittent vs. Permanent
Vectors
Hosts
Life Cycles
Know these definitions
Be able to compare/contrast using specific examples
Infectious Diseases
Emerging Infectious Diseases
New diseases (mainly viral agents) Re-emerging Infectious Diseases
Tuberculosis, Poliomyelitis Neglected Diseases
AIDS, Malaria, Tuberculosis
Typically called the big 3. Most (“The Great”) Neglected Diseases
Many tropical parasitic diseases
7 Emerging Infectious Disease
Infectious diseases whose incidence in humans has increased in the past 2 decades or threatens to increase in the near future have been defined as "emerging." These diseases respect no national boundaries include:
New infections resulting from changes or evolution of existing organisms (host and/or pathogen)
Known infections spreading to new geographic areas or populations Previously unrecognized infections appearing in areas undergoing ecologic transformation
Old infections re-emerging as a result of antimicrobial resistance for known agents or breakdowns in public health measures.
Emerging(re) Infectious Diseases
Nearly all are zoonotic or species jumping agents -HIV Species Jumping -Influenza -Hepatitis C and E
-E. coli 0157:H7 -Cryptosporidium -Ebola -Hantavirus Zoonoses -Lyme disease -nvCJD -Trypanosomiasis -West Nile Virus
Zoonoses
Zoonoses - transmission of the infectious agent to humans from an animal reservoir. No establishment of a permanent new life cycle solely in humans (still requires animals).
Species jumping - the infectious agent derives from an ancient animal reservoir, but has established a new life cycle in humans that DOES NOT require an animal transmission phase any longer.
8 Contributing Factors for Zoonoses
Pathogen evolution (adaptation)
Mutations
Host condition
Vaccination
Immunological disorders
Host population
Urban crowding (land use)
Host demographics & behavior
Global travel
Environmental
Climate
Destruction
Public Health breakdown
Dealing with Zoonoses
Why are the pathogens jumping? Can we predict this?
Who will be the world’s doctor? WHO, UN - need to get rid of political links?
Who will be the world’s expert on zoonoses?
Develop new strategies to deal specifically with emerging zoonoses.
Surveillance will be key, but also greater involvement of field and basic science research.
Infectious Diseases
Emerging Infectious Diseases
New diseases (mainly viral agents) Re-emerging Infectious Diseases
Tuberculosis, Poliomyelitis Neglected Diseases
AIDS, Malaria, Tuberculosis
Typically called the big 3. Most (“The Great”) Neglected Diseases
Many tropical parasitic diseases
9 Great Neglected Diseases
HAT is just one example.
Pharmaceutical industry is ONLY part of the problem.
Improved economic situation
Improved public health
Global alliances are extremely important
We are now on the way!
Medecins sans Frontieres
Roll back Malaria
DNDi - Drugs for Neglected Diseases initiative
Human African Trypanosomiasis (HAT)
Classical example of a zoonotic emerging infection, 1890-1930.
Leading public health problem in Africa at that time, colonialism brought the disease to new areas with a 2/3 death rate.
Nearly eliminated by 1960 using population screening, case treatment, chemoprophylaxis, and vector control.
Currently classified by WHO as a re-emerging and uncontrolled disease.
HAT Nearly Eliminated in 1962!
Human African Trypanosomiasis, central Africa, 1926-1999
HAT: re-emerging, Neglected Tropical Disease
10 HAT: More recent data
2004
Classified by WHO as a re-emerging uncontrolled disease.
How was control successful?
Then….
……..and Now.
Card agglutination Test Anion Exchange Centrifugation Technique Molecular Tools
Time consuming Sensitive Expensive Still under development Additional equipment
Large # of false +’s
11 Estimating Disease Burden
> 60 M people at risk, only about 3-6 M are screened for HAT.
Health facilities lacking in disease foci areas.
Little if any public health measures being implemented.
Huge political conflict and insecurity in epidemic foci.
Clinical diagnosis is difficult until late stage. Intermittent fever - malaria?
Weight lose - AIDS? Diagnostics - false negatives
Barriers to control HAT
Insufficient resources - developing countries
War and civil disturbances = arefugees
No vaccine = no prevention
Crisis in chemotherapeutics
Melarsoprol was 95% effective, but in 1997 resistance up to 30% was emerging in Uganda, Sudan and Angola (DRofC little data).
Arsenal of therapeutic drugs is minimal (~6)
Toxicity -drugs kill 4-10% of the patients.
Treatments for HAT
Drug Indication Status (summer 2000)
Pentamidine early stage donations phasing out Suramin early stage halt of production Melarsoprol CNS resistance and future production uncertain Eflornithine CNS not produced Nifurtimox CNS halt of production
Recent developments are that all five are being produced and donated by the WHO for five years
Eflornithine - called the “resurrection drug” May 2001 - Aventis agreement - donate eflornithine for 5 years + 25 million in support of field studies etc. 2006 - agreement ran out NOW????
12 Africa’s burden
Sub-Saharan Africa Has the Highest Prevalence of Nine Neglected Tropical Diseases
PLoS Med 2(11): e336 doi:10.1371/journal.pmed.0020336
Do you know these public health workers?
13 • World’s first peer-reviewed, open-access journal devoted to the NTDs • Launch supported by Bill and Melinda Gates Foundation • Papers on pathology, epidemiology, treatment, control, prevention • Magazine section devoted to policy and advocacy
• International editorial board—half of the Associate Editors are from endemic countries
“It is expected that the journal will be both catalytic and transformative in promoting science, policy, and advocacy for these diseases of the poor.” —Peter Hotez, Editor-in-Chief
Papers Discussion
Common features of the NTDS
• diseases that have burdened humanity for centuries • cause immense suffering
• cause life-long disabilities
• impair childhood growth & development
• poverty-promoting conditions
• disproptionate effect on the poor
• shortage of safe and effective treatments
• gap in attention for global R & D
• no commericial markets for products that target these diseases
PLoS Med 2(11): e336 doi:10.1371/journal.pmed.0020336
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