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Introduction to Environmentally Transmitted Pathogens, Part 2 Envr 421 Mark D. Sobsey Spring, 2008 Some Important Pathogens of Aquatic and Terrestrial Environments • 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, especially the respiratory tract IMPORTANT HUMAN ENTERIC VIRUSES Viruses/Groups Enteroviruses: (polios, echos*, coxsackies*, etc.) Hepatitis A virus Hepatitis E virus Reoviruses Rotaviruses Adenoviruses* Noroviruses*: Norwalk, Snow Mountain, etc. Astroviruses Zoonotic (Animal)? no no (primates) pigs, rats, others yes yes, maybe** unlikely** maybe** unknown *On EPA’s candidate contaminants list (CCL) **Usually different ones infect humans & animals; but maybe not always IMPORTANT HUMAN ENTERIC BACTERIAL PATHOGENS AND OTHER SOURCES OF THEM Bacterium/Group Zoonotic? Other Sources? Salmonella spp. (except S. typhi) Campylobacter spp. Escherichia coli Helicobacter pylori* Aeromonas hydrophila* Yersinia enterocolitica Vibrio cholerae; other Vibrio spp. Leptospira Mycobacteria spp. (non-tubercular) Shigella spp. yes no yes yes unknown yes yes yes yes very rare no no no yes maybe unknown yes yes yes no yes no *On EPA’s candidate contaminants list (CCL). Important Human Enteric Protozoan Pathogens Protozoan Cryptosporidium parvum Cyclospora cayetanensis* Giardia lamblia Entamoeba histolytica Balantidium coli Microsporidia* (Enterocytozoon and Septata) Toxoplasma gondii* *On EPA’s candidate contaminants list (CCL). Zoonotic? yes unknown yes rare yes (pigs) yes unknown yes Helminths (Worms): Some of the Important Ones in Developed (Western) Countries Most acquired from ingestion of or contact with fecescontaminated 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 Some Non-fecal Bacterial Pathogens Bacteria: Legionella spp. L. pneumophila, etc. Mycobacterium spp. M. tuberculosis 1 M. avium-intracellulare Other bacteria >20 Pneumonia; febrile illness Legionnaires’ disease many Upper respiratory illness tuberculosis several Upper respiratory illness many Variable; "opportunistic" or "conditional pathogens Some Non-fecal Protozoan Pathogens Free living amebas: Naegleria fowleri 1 Acanthamoeba spp. few Primary amebic meninoencephalitis eye infections; encephalitis Some Non-fecal Helminths Agent: • Dracunculus medinensis (N) No. 1 • Schistosoma (T; blood fluke) S. haematobium, S. mansoni and S. japonicum 3 • Schistosoma spp. (T). birds and fish few N = Nematode; T = Trematode Illness and Sites Tissue infections (subcutaneous & deep; esp. foot and/or leg Liver, intestine, colon bladder & rectum from colonization of venous vessels. swimmers itch: larvae penetrate skin; not in bloodstream; no maturation in human Occurrence of Microbial Pathogens in Humans • Microbial pathogens usually are not “normal flora” of humans; – But, opportunities for pathogenicity are possible; e.g., trauma – 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” visitor illness from local E. coli strains – “Some “normal flora” are pathogenic for sensitive populations, such as immunocompromised persons: • Example: Pneumocystis carinii (a protozoan or fungus) – causes fatal pneumonia in AIDS patients – immunocompetent people get asymptomatic infections 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 in the developed world: – Annual illness rates are higher in infants, children, the elderly, child caregivers, health professionals, the poor, male homosexuals and other high risk groups & in developing countries • Not all enteric infections produce illness (asymptomatic or sub-clinical infections) – 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. 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 108/gram • Low infectious dose; perhaps as few as 10-100 virus particles – Virus has not been cultured in laboratory animals or cell cultures Response of Human Volunteers to Norwalk Virus Infection via the Oral Route 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. 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 for many strains 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 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 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. Life Cycle of Cryptosporidium parvum • Oocysts ingestion from water and food • Reach target site of infection in intestine • Attach to and enter cell (sub-membraneous compartment) • Complex asexual/sexual multiplication sequence of events, leading to oocysts • Mature oocysts produced • Oocysts shed in feces Examples of Pathogen Encounters and Prevention Considerations Type of contact Example Type of Agent Source Strategy for Preventive Aim Prevention Inhalation Common cold Virus None Difficult to avoid contact Ingestion Coccidiodomycosis Typhoid fever Salmonella food poisoning Gonorrhea Fungus Aerosol from infected persons Soil None Hard to avoid contact Lower infecting dose Surgical infections Bacterium Normal flora Aseptic Avoid contact surroundings techniques Sexual contact Wound Insect Bite Malaria Bacterium Water, food Bacterium Food Sanitation Sanitation Bacterium Person Social Behavior Protozoan Mosquito Insect control Avoid contact Eliminate vector Constitutive Defenses: Physical Barriers to Infection System or Organ Skin Mucous membranes Cell Type Clearing Mechanism Squamous Columnar nonciliated (e.g., gastrointestinal tract) Desquamation Perstalsis Columnar ciliated (e.g., trachea) Mucociliary movement Tears, saliva, mucus, sweat Cuboidal ciliated (e.g., nasopharynx) Secretory Flow of liquids Constitutive Defenses: Chemical Barriers to Infection System or Organ Source Skin Mucous membranes Sweat, sebaceous glands Parietal cells of stomach Secretions Neutrophils Lung A cells Salivary glands Neutrophils Small bowel and below Liver via biliary tree Gut flora Substances Organic acids Hydrochloric acid, Low pH Antimicrobial compounds Lysozyme, peroxidase, lactoferrin Pulmonary surfactant Thiocyanate Myeloperoxidase Cationic proteins Lactoferrin Lysozyme Bile acids Low molecular weight fatty acids