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The Iceberg Concept: As Applied to Virus Infections

The Iceberg Concept: As Applied to Virus Infections. Examples of Encounters and Disease Prevention. Constitutive Defenses: Physical Barriers to Infection. Constitutive Defenses: Chemical Barriers to Infection. Some Important Pathogens of Aquatic and Terrestrial Environments.

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The Iceberg Concept: As Applied to Virus Infections

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  1. The Iceberg Concept: As Applied to Virus Infections

  2. Examples of Encounters and Disease Prevention

  3. Constitutive Defenses: Physical Barriers to Infection

  4. Constitutive Defenses: Chemical Barriers to Infection

  5. Some Important Pathogens of Aquatic and Terrestrial Environments • The Microbial Agents: • Most are from feces or other excreta (urine, respiratory exudates, etc.) of humans and/or other animals • Some are of natural origin • either exclusively or in addition to fecal contamination • Enteric Microbial Agents: • Infect the human and/or animal gastrointestinal (GI) tract • Some enteric microbes also infect or invade other sites in the body

  6. IMPORTANT HUMAN ENTERIC VIRUSES Viruses/Groups Animal Feces Enteroviruses: no (polios, echos, coxsackies, etc.) Hepatitis A virus* no Hepatitis E virus pigs, rats Reoviruses yes Rotaviruses yes** Adenoviruses* yes** Caliciviruses*: no Norwalk, Snow Mountain, etc. *On EPA’s candidate contaminants list (CCL). **humans & animals usually infected by different ones; not always.

  7. IMPORTANT HUMAN ENTERIC BACTERIAL PATHOGENS AND OTHER SOURCES OF THEM Bacterium/Group Animals Other Sources Salmonella spp. yes no (except S. typhi) no no Campylobacter spp. yes yes Escherichia coli yes no Helicobacter pylori*unknown unknown Aeromonas hydrophila*yes yes Yersinia enterocolitica yes yes Vibriocholerae; other Vibrio spp. yes yes Leptospira yes no Mycobacteria spp. (non-tubercular) very rare yes Shigella spp. no no *On EPA’s candidate contaminants list (CCL).

  8. IMPORTANT HUMAN ENTERIC PROTOZOAN PATHOGENS Parasite Animal Feces Cryptosporidium parvum yes Cyclospora cayatenensis*unknown Giardia lamblia yes Entamoeba histolytica rare Balantidium coli yes (pigs) Microsporidia* yes (Enterocytozoon and Septata) unknown Toxoplasma gondii* yes *On EPA’s candidate contaminants list (CCL).

  9. Helminths (Worms): Some of the Important Ones Most acquired from ingestion of or contact with feces-contaminated soil or food • Nematodes (Roundworms): • Ascaris lumbricoides 1 GI illness; pneumonitis • Trichuris trichuria 1 chronic GI • Hookworms: • Ancylostoma duodenale 1 chronic anemia • Necator americanus 1 chronic anemia • Strongyloides stercoralis 1 chronic anemia • Cestodes (tapeworms): • Hymenolepis nana 1 GI illness

  10. Some Non‑fecal Bacterial Pathogens Bacteria: Legionella spp. >20 Pneumonia; febrile illness L. pneumophila, etc. Legionnaires’ disease Mycobacterium spp. many Upper respiratory illness M. tuberculosis 1 tuberculosis M. avium-intracellulare several Upper respiratory illness Other bacteria many Variable; "opportunistic" or "conditional pathogens

  11. Some Non‑fecal Protozoan Pathogens Free living amebas: Naegleria fowleri 1Primary amebic menino- encephalitis Acanthamoeba spp. few eye infections; encephalitis

  12. Some Non-fecal Helminths Agent: No. Illness and Sites • Dracunculus medenensis (N) 1 Tissue infections (subcutaneous & deep; esp. foot and/or leg • Schistosoma (T; blood fluke) 3 Liver, intestine, colon S. haematobium, S. mansoni bladder & rectum from and S. japonicum colonization of venous vessels. • Schistosoma spp. (T). few swimmers itch: larvae birds and fish penetrate skin; not in bloodstream; no maturation in human

  13. Occurrence of Microbial Pathogens in Humans • Microbial pathogens usually are not “normal flora” of humans; opportunities for pathogenicity are possible • Some are “normal flora” of animals: • Salmonella enteriditis and Campylobacter jejuni in poultry • “Normal flora” for local populations may be pathogenic for visitors and transient populations: • “Traveller’s diarrhea” due to local strains of E. coli • “Some “normal flora” are pathogenic for sensitive populations, such as immunocompromised persons: • Example: Pneumocystis carinii (a protozoan or fungus) • causes fatalpneumonia in AIDS patients • immunocompetent people get asymptomatic infections

  14. Occurrence of Enteric Microbial Pathogens in Humans and Pathogen Shedding • Enteric (gastrointestinal) illnesses are second only to respiratory illnesses in the population • Most people get 1 enteric illness per year: • Annual illness rates are even higher in infants, children, the elderly, child caregivers, health professionals, the poor, male homosexuals and other high risk groups • Not all enteric infections produce illness (asymptomatic or sub-clinical infections) • So, rates of infection are even higher (by perhaps 2 to 100 times) • People (and animals) with enteric infections fecally excrete high concentrations of pathogens for days, weeks, months or longer. • Pathogen concentrations can be >106 to >109 per gram of feces. • Community pathogen shedding is often 1-10% at any time.

  15. Disease Due to Some Important Waterborne Enteric Virus Pathogens Norwalk Virus Gastroenteritis: A Localized Infection • Fecal‑oral transmission • Localized infection of small intestine • Damage to microvilli of intestinal epithelium • “blunting” of the microvilli • Incubation period 1‑3 days • Illness 1‑3 days • Major symptoms: diarrhea, vomiting, nausea, abdominal pain and low grade fever • Fecal shedding from onset of illness for several days. • Virus concentration in feces as high as 109/gram • Low infectious dose; perhaps as few as 10-100 virus particles • Virus has not been cultured in laboratory animals or cell cultures

  16. Response of Human Volunteers to Norwalk Virus Infection via the Oral Route

  17. Disease Due to Some Important Waterborne Enteric Virus Pathogens Hepatitis A Virus and Infectious Hepatitis: A Systemic Infection • Fecal‑oral transmission • Systemic (generalized; disseminated) infection • Liver as "target organ" • Incubation period 2‑6 weeks; average 4 weeks • Illness for several weeks or months • Destruction of liver hepatocytes • Jaundice (in some but not all cases) and severe "flu‑like" symptoms, including gastrointestinal symptoms. • Virus shed fecally from 2 weeks before to a few weeks after onset of symptoms.

  18. Disease Due to Some Important Waterborne Enteric Bacterial Pathogens Salmonella gastroenteritis: (S. enteriditis): localized infection • Fecal‑oral transmission • Localized infection of intestines • Damage and inflammation to lamina propria • 0.5‑2 day incubation period • Watery diarrhea, nausea, vomiting, abdominal cramps, low grade fever, lasting several days • Bacteria shed fecally at billions per gram • Infectious dose is relatively high: >103 ID50

  19. Disease Due to Some Important Waterborne Enteric Bacterial Pathogens Typhoid fever: (S. typhi and S. paratyphi): Systemic Infection • Fecal-oral transmission • Systemic infection: • Macrophages, reticuloendothelial system (esp. liver, spleen and bone marrow), gallbladder and intestines as major sites of damage • 1.5‑2 week incubation period • Symptoms: fever, headache, malaise, anorexia, then bloody diarrhea • Mortality rate 10%, if untreated • Carrier state possible • "Typhoid Mary”: infamous food handler; infected hundreds • Fecally shed at billions/gram by ill persons and carriers

  20. Disease Due to Some Important Waterborne Enteric Protozoan Pathogens Giardiasis (Giardia lamblia): localized enteric infection • Fecal‑oral transmission; hardy cyst ~10 m diameter • Human and numerous non‑human animal reserviors • Infectious dose: low: ID50 ~10 cysts • Infection: cysts excyst in small intestine; trophozoites attach to microvilli of intestinal epithelium, tissue damage and • interference with transport processes • Profuse watery to semi‑solid, greasy, bulky, malodorous diarrhea; abdominal cramps,nausea, vomiting, anorexia, low grade fever, headache • 1‑1.5week incubation period • Duration of Illness: few days to months • Subchronic infection possible

  21. Disease Due to Some Important Waterborne Enteric Protozoan Pathogens Cryptosporidium and cryptosporidiosis • Cryptosporidium parvum: coccidian (sporozoan) parasite • Numerous animal reservoirs: feral, domestic and agricultural • Fecal-oral transmission of hardy oocyst, ~5 m diameter • Infectious at low dose: ID50 ~10 oocysts for some strains • Excysts in small intestine; trophozoites attach to epithelial cells • Complex life cycle; 6 major stages, some asexual, other sexual • Infection and illness in immunocompetent hosts: similar to giardiasis: diarrhea, nausea, vomiting, anorexia, fever, malaise • Incubation period ~1 week; duration ~1.5 weeks, range 1-4 weeks • Infection in immunocompromised hosts (ex, persons with AIDS): • Life threatening, excessive fluid loss, chronic, no drug therapy • ISpread to extra-intestinal sites: respiratory tract; pneumonia.

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