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Self-Destructive Defenses
Sickle Cell Anemia * Common in sub-Saharan Africa * Moderately common in the Mediterranean, India and the Persian Gulf Thalassemias - characterized by unusually small RBCs that aggregate and disintegrate * Alpha Thal - SE Asia, Malaysia, Southern China * Beta Thal - SE Asia, S Asia, Middle East and the Mediterranean and Africa Hemoglobin E (SE Asia) + Hemoglobin C (sub-Saharan Africa) ddd TERM 2
Self-Destructive Defenses Continued
DEFINITION 2 Ovalcytosis - Oval shaped RBC * Common in Southeast Asia, Indonesia, New Guinea * Glucose-6-Phosphate-Dehydrogenase deficiency - More sensitive to toxins that enter the system, affects people who eated Fava beans, giving it the name favism * G6PD is a nutrient required by P. Falciparum * X chromosome * Mediteranean and subsaharan Africa Cystic Fibrosis - defense against S. typhi TERM 3
Benign Genetic Defenses
DEFINITION 3 Defective Duffy Antigen - absense confers resistance to the moderatly virulent malaria organism, Plasmodium vivax * Duffy antigen presense is rare among west Africans in the malaria belt The Health disadvantage of not having Duffy antigen is unknown Defective CCR5 - a membrane receptor on T cells for receiving cytokine messages * provides a defense against some strains of HIV * Couldn't have been evolved to provide resistance against HIV, because it didn't exist. Plague + S. Pox S + E Europe TERM 4
Rare and Deadly Diseases
DEFINITION 4 Generally do not occur often because they reduce the fitness of the person to 0% and thus making it impossible to pass on the genetic trait. Often only occur at a rate of less than 1/10,000. The same chance as if it were a random genetic mutation Examples: - Duchenne's Muscular Distorphy - (Higher because X-Linked) - Huntington's Disease (Does not develop until older age) TERM 5
Possible Self-Destructive Defenses (Ashkenazi
Jews)
DEFINITION 5 Genetic Diseases that seem to have higher occurance rates than should be expected in some populations but do not appear to give any kind of benefit Founder Effect - High frequency is due to the chance presense in an ancestor, who then was successful for other reasons - Diseases are caused by different mutations; founder effect fails to explain ** Self-Destructive Defense - the alterations of lip[id metabolism may provide some unknown protections against some servere urban or quasiurban disease common in NE Europe, Smallpox ect
Examples of Possible-Self Destructive
Defenses
Tay-Sachs Disease - lipid deposition in the brain; fitness - 0%
- Ashkenazi jews - US non-Jews: 1.7-2.6:100,000 - Sephardic Jews TERM 7
Generalizations About Genetic Diseases
DEFINITION 7
- Genetic diseases have extremely high monozygotic twin concordances - Genetic diseases that occur at too high a frequency to be maintained by mutation without compensating benefits are shown to be or are likely to be defenses against infectious agents - When twin concordance is moderate or low, genetic association with disease may reflect genetic association with disease may reflect genetic susceptibility to infectious agents TERM 8
Examples of Generalizations about Genetic
Diseases
DEFINITION 8 The epsilon 4 allese of the apolipoprotein E gene inscreases vulnerability to infection with C. pnemoniae, with is a leading candidate as infectious cause of diseases to which the E allele has been linked Different composistions of MHC complexes between populations TERM 9
Genetic Load
DEFINITION 9 In population genetics, genetic load or genetic burden is a measure of the cost of lost alleles due to selection (selectional load) or mutation (mutational load). - the human genome project will probably not fulfill one of its central goals (cure of human disease) - It will probably help us facilitate the recognition of foreign genetic material - Will eventually help identify numerous slightly deliterious mutations that contribute to genetic load TERM 10
Virulence
DEFINITION 10 The harmfulness of an infection
Sit-and-wait transmission
Parasites that are durable in the external environment are predicted to be more virulent than parasites that are labile in the external environment because durable parasites can rely on the mobility of the uninfected hosts to facilitate transmission TERM 17
Vertical Transmission
DEFINITION 17 Transmission from parent to offspring - Vertical transmission is expected to favor extreme benignity, because success at vertical transmission depends directly on the reproductive success of the host - the mildness leads to better reproductive success of the host and hence better transmission of the host's offspring Example
- Microsporidans in mosquitos (Nosema, Thelohania, Pleistophora) TERM 18
Virulence Management
DEFINITION 18 Vector-proof housing should favor evolution of reduced virulence among arthropod-borne pathogens by disfavoring transmission from ill immobile hosts - Plasmodium falciparum -- Seasonal rarity of mosquitos - Plasmodium vivax exists because of seasonal rarity P. vivax hibernans (korea) extremely mild - Infrastructural inhibition of mosquito-borne diseases - Water purification in order to control Shigella -- S. dysenteriae (severe) S. flexeri (next most severe) S. sonnei (b) TERM 19
Latin Test of Virulence Management
DEFINITION 19 Vibrio cholerae entered Latin America by way of Peru in 1991 and spread throughout most of South and Central America within a year -- In Chile, water was PURE and V. cholerae evolved REDUCED --In Guatemale, Peru, and Ecuador POOR and NO REDUCED -- Ecuador water was poor and evolved INCREASED Toxgenicity TERM 20
Virulent Management Through Vaccine
DEFINITION 20 Restrict antigens to those pathogen components that make benign organisms harmful - Such vaccines should selectively disfavor the harmful varients -- Example - Corynebacteria diphtheriae and Hemophilus influenzae Both of these examples used a virulence antigen strategy inadvertently
Prophylactic (preventative) Treatment
The treatment (generally of a hospital ward) in order to prevent the outbreak of a particular pathogen (Staphylococcus aureus) --within two weeks antibiotic resistance to penicillin increased from being rare to being present in a majority of strains -- Related organism, Entercoccus, developed resistance to all available antibiotics in New York TERM 22
The Socioeconomic Problem
DEFINITION 22 Antibiotic usage is good for the patients and the physician over the short term but bad for the society over the long term - Tragedy of the Commons: Group interest does not accord with individual interst TERM 23
Long-Term Strategies to Control Antibiotic
Resistance
DEFINITION 23 Dead-ending (Taxoplasma gondii) (Lyme disease) TERM 24
Virulence Management using Antibiotics
DEFINITION 24 Reduced antibiotic resistance should favor reduced virulence - If virulent organisms are sensitive, treatment will tend to favor propagation of mild organisms, because mild organisms do not tend to cause significant illness and hence to not tend to be treated -- Therefore, leaving less virulent strains to act as live vaccines Antibiotic resistance of V. cholerae is positively correlated with virulence in Guatemale, Ecuador, and Chile (Resistance did not increase in Chili TERM 25
Applying Antibiotic Virulence Management to
Vectorborne, Hospital Acquired, and Outside
DEFINITION 25 Application to vectorborne diseases: Vectorproofing of houses should favor resudced resistance to antimalarials Application to hospital acquired diseases: reductions in attendant-borne transmission should favor reduced antibiotic resistance in hospital settings Application to antibiotic resistance in the outside community in rich countries: encouraging people to stay home when they are sick should reduce the antibiotic resistance by favoring evolution toward extreme benignity
Hemophilus
ducreyi
Chancroid: Localized but often severe soft chancres that destroy tissue substantial amounts of genital tissue Geography: generally Africa, Southeast Asia, and the CAribbean; found occasionally in the Southeastern US Bacteria TERM 32
Garnerella vaginalis
DEFINITION 32 Vaginosis: Upheaval of normal bacterial fauna of vaginal tract accompanied with malodorous dischage, often with vaginitis May induce Reiter's syndrome Geography: global Bacteria TERM 33
Ureaplasma
urealyticum
DEFINITION 33
- Urethritis -In neonates: a chronic lung disease (risk of chronic lung disease is doubled, pneumonia (inflammation of lungs coupled with and fillings of lungs with exudate), meningitis (inflammation of the meninges, which are the membranes that envelope the brain and spinal cord). Geography: global Bacteria TERM 34
Mycoplasma hominis
DEFINITION 34 Vaginitis & Urethritis Geography: Global Bacteria TERM 35
Candida albicans
DEFINITION 35 Yeast infection: itching, burning urination, altered sicharge Geography: global Fungi
Hepatitus B virus
-Liver cancer - Hepatitus $ liver cirrhosis (destruction of normal tissue structure and replacement with fibrous tissue - Geography: Global Virus TERM 37
Hepatitus C virus
DEFINITION 37 -Liver cancer -Hepatitis & liver cirrhosis -probably some type 2 (=insulin-independent, adult-onset) diabetes TERM 38
Human Immunodeficiency Virus
(HIV)
DEFINITION 38 -AIDS TERM 39
Human herpes simplex type II
(HHSVII)
DEFINITION 39 -Genital blisters -In newborns: encephalitis, blindness -HHSV II in mother is positively correlated with later development of schizophrenia in offspring, implicating prenatal infection - Geography: global Virus TERM 40
Cytomegalovirus
DEFINITION 40
- A member of the herpes virus family infects leukocytes, particularly monocytes (precursors to macrophages) - Known to be genitally transmitted -Probably transmitted by saliva, like EBV Infects 40-80% of adults in the US, usually asymptomatic -Causes severe inflammation of the retina, lung or g-i tract -Can cause blindness, neurological damage, lung infections, hepatitus in neonates infected at birth - Can cause cardiovascular disease
Exploitation Levels
- An increase in the potential for sexual transmission favors high levels of exploitation of hosts by pathogens - Highly exploitative persistent pathogens will tend to cause more long-term damage (side effects) than less exploitative persistent pathogens
