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331 Cards in this Set
- Front
- Back
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What does infectious disease result from? |
The infection or presence and growth of biological agents in a host organism |
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What is infectious disease also known as? |
Communicable, contagious, or transmissible disease |
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How are communicable pathogens transmitted |
From host to host, cannot live outside a host |
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Non-communicable pathogens normally live in |
an abiotic environment |
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How much of the deaths worldwide are doe to infectious disease |
25% |
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Who are particularly affected by infectious disease? |
Elderly, children, debilitated |
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What are some infectious agents of disease |
1. prions (infectious protein) 2. Viruses 3. Bacteria 4. Fungi 5. Protozoa 6. Helminthes 7. Ectoparasites and disease vectors |
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What are prions? |
1.Misfolded proteins that form aggregates or plaques called amyloid 2. Leads to more misfolded protein and amyloid accumulates
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What diseases prions cause? |
chronic degenerative brain disease 1. bovine spongiform encephalopathy 2. Creutzfeldt-Jakob disease in humans - Currently untreatable and universally fatal - arise in three different ways: acquired, familial, or sporadic. |
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What are viruses |
-A set of genes packaged in a protein coat (DNA OR RNA) -May be enveloped by a membrane derived from the host cell -classified according to type of nucleic acid +- evelope |
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How does virus replication occur? |
-Strictly intracellular obligate pathogen -entry via receptor/ligand interactions -replication dependent on host machinery -transcription and translation carried out totally or in part by host cell -viral proteins and nucleic acid assembled into viral particles and released from cell
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What are some RNA Viruses? |
-rotaviruses (diarrhea) -influenza -rhinovirus -hep a and c -HIV
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What are some DNA viruses? |
-herpes viruses -papilloma viruses -hep b |
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How does bacterial growth and reproduction occurr? |
-most replicate via binary fission -genome usually single circular DNA -abundant nutrients-->rapid replication -spores to survive harsh environments |
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obligate pathogens |
bacteria that always cause disease
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What are some types of bacterial pathogenesis? |
1. conditional or opportunistic pathogens 2. pathogenesis usually due to tissue destruction, inflammation, or toxins
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Degree of pathology due to |
ability of pathogen to gain access and to replicate in host |
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Protozoa |
-Large and diverse group -many pathogenic and commensal species -infect all major tissues and organs |
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Fungi |
-yeasts and mold -most are free-living saprobes -few pathogens -many opportunisitc |
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Human Mycoses |
-superficial (hair shaft, dead layer of skin) -cutaneous (epidermis, nails)-->ringworm, athlete's foot -subcutaneous (dermis, subcutis) -systemic (internal organs), histoplasma -opportunistic (internal organs) candida
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Helminthes |
-parasitic worms -most common form of pathogen (1/3 worlds pop infected) -major cause of morbidity (DALYs) -many have complex life cycles
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Blood-feeding arthropods |
-ectoparasites (ticks and lice) -vectors for other pathogens (especially mosquitos and ticks) |
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What are the modes of transmisssion |
person to person animals: zoonosis or immediate host environmental sources |
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What are modes of transmission within person to person contact |
-direct physical contact -indirect physical contact via fomites -respiratory droplet or airborne -fecal-oral transmission via ingestion of contaminated food or water -via biological vectors |
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What are the infectivity factors and their requirements |
1. attachment and/or entry: break host barriers to initiate 2. local or general spread: evade host defenses and establish infections 3. multiplication: increase numbers and continue evading host defesnses 4. shedding or exit: release sufficient numbers to ensure transmission 5. Host damage (pathogenesis): not strictly necessary, unless needed for exit
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Diagnostic Methods for infections |
1. microscopy=direct observation in clinical specimens 2. culture=propagation of pathogen in vitro 3. serology= measure immune response against pathogen 4. antigen detection=use antibody to detect antigen 5. Molecular=analyze DNA or RNA |
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Treatment and Chemotherapy for infections |
-selective toxicity against pathogens -fewer options for anti-virals -drug resistance rapidly develops |
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Prevention and Control |
-personal protection (hand washing, mosquito nets) -prophylaxis and chemotherapy -immunization -improved health and nutrition -environmental improvements (water treatment, sanitation) |
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What is the second leading cause of infectious disease mortality |
HIV/AIDS |
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What does AIDS stand for? |
Acquired Immunodeficiency Syndrome |
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When was AIDS first recognized? |
In 1981.
In 1984 Human Immunodeficiency Virus (HIV) was described as the causative agent. |
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What were the populations in which HIV/AIDS was identified |
Homosexual men in the U.S. and Sweden IV drug users Hemophiliacs Heterosexuals in Tanzania and Haiti |
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What is a similar virus compared to HIV |
SIV= simian immunodeficiency virus - found in many non-human primates -evidence indicates that HIV is derived from SIV |
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HIV Group M |
massive radiation after introduction to humans
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T/F There are no regional differences in subtype prevalence |
False |
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Factors contributing to the recognition of AIDS epidemic
Africa Pre-1981 |
-HIV infected individuals likely poor and rural -rarely consulted physicians -physicians would likely attribute disease symptoms to many other tropical diseases |
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Factors Contributing to the recognition of AIDS epidemic
U.S. Gay Community pre-1981 |
-largely upper middle class caucasians -had health insurance and regularly consulted physicians -increasing number of rare opportunistic infections and cancers |
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How is HIV trasmitted |
-intimate sexual conduct -mother to child transmission -intravenous drug use -health care workers -blood or blood product transfusion and transplanted tissue (before routine testing) |
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Genital ulcers increase |
HIV acquisition risk, by barrier breakdown |
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Increased inflammatory cells in the genital mucosa serve as |
host cells for HIV
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Higher levels of HIV are secreted with |
co-infection |
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Treating STI's lead to how much of a decrease in HIV transmission? |
42% |
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Mother to child transmission causes what percent of HIV infections in children <15 years old |
>90% |
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How much of infants will be infected with HIV without intervention |
15-45% |
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How is HIV transmitted from mother to child and what percent of children will become infected by each mode of transmission. |
-during pregnancy 5-10% -during labor/delivery 10-20% -through breastfeeding 5-20%
half of infected infants die within 2 years |
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HIV replication |
1. Enveloped RNA virus binds receptor 2. Membrane fusion with host 3. Reverse transcription (RNA-->DNA) (retrovirus) 4. Viral DNA integrated into host genome 5. viral genes and genome expresses 6. virus particles assembled and bud from host cell |
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What kinds of cells are may be infected by HIV first |
dendritic cells in skin and genital mucosa |
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What protein is the receptor for HIV |
CD4 |
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The HIV virus alters |
t-cell and macrophage function-->immune depression |
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Pathway from HIV to AIDS |
1. Tropism for immune cells 2. depressed immune response 3. loss of helper t-cells 4. immunodeficiency 5. AIDS |
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What are the 3 stages of HIV infection? |
Acute infection Asymptomatic latent phase symptomatic AIDS |
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What occurs during acute infection of HIV |
-virus replication with viremia -symptoms include: fever, enlarged lymph nodes, muscle aches, rash, tiredness |
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What occurs during asymptomatic latent phase of HIV |
-low viremia and decline in helper t-cells (CD4+) -seropositive -can last for years (avg 8)
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What occurs during symptomatic AIDS |
-CD4+ cells fall below 200/uL of blood -susceptibility to opportunistic pathogens |
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Opportunistic pathogens and what do they include |
organisms that normally do not cause disease in persons with an intact immune system
-included non-pathogenic organisms -increased disease severity and duration -dissemination throughout body or to other organs not normally affected |
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Clinical features associated with AIDS |
presence of opportunistic disease cd4+ cell counts <200uL presence of HIV antibodies (latent) Presence of viral RNA (PCR) |
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Major signs of AIDS |
weight loss >10% chronic diarrhea >1 month prolonged fever >1 month
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Minor signs of AIDS |
persistent cough >1 month generalized dermatitis candidiasis of mouth and throat (thrush) disseminated herpes simplex generalized lymphadenopathy
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Major targets for anti-hiv drug development |
integrase inhibitors reverse transcriptase inhibitors protease inhibitors fusion/entry inhibitors |
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CCombination HIV drugs are more beneficial than |
single drugs |
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Highly active antiretroviral therapy |
-improves efficacy -slows development of drug resistance -reduced viremia -side effects and compliance |
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What is the average age group most affected by HIV |
25-49 |
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What are the leading causes of death for infectious diseases |
1. respiratory infections 2. TB 3. Diarrheal Diseases 4. Malaria 5. HIV/AIDS |
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Upper vs. Lower Respiratory Tract Infections |
-upper less severe, but more easily transmitted -lower more severe, less easily transmitted
-less virulent pathogens associated with upper resp tract -more pathology associated with lower tract |
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What are the types of viruses that cause the common cold |
rhinovirus, coronavirus
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Where do the common cold viruses infect? |
Nasopharnyx (nose and throat) |
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How is the common cold transmitted |
by aerosols or contaminated hands
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What are the types of lower respiratory tract manifestations |
bronchitis bronchiolitis Pneumonia
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Acute Bronchitis |
-inflammation of the bronchi and trachea -90% viral etiology and ~10% bacterial etiology -cough with or without sputum -usually self-limiting -recurrent injuries or exposure to irritants leads to chronic bronchitis |
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Respiratory Syncytial Virus |
Causes epithelial cells to fuse localized to respiratory tract nearly all children infected by 4 years strong seasonal transmission 1% of infections require hospitalization |
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Bronchitis, pneumonia or both affects who |
children < 1 year
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Febrile rhinitis and pharyngitis affects who |
children |
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the common cold affects who |
older children and adults |
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What is pneumonia and what are the symptoms |
inflammation of the lungs, especially alveoli (air sacs)
symptoms include cough, chest pain, fever, and difficulty breathing
xrays: lack of air space |
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Can pneumonia be easily diagnosed? |
yes |
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Establishing etiology can be difficult for what respiratory infection |
pneumonia |
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How is pneumonia caused? |
-Infections (viruses, bacteria, fungi, parasites) -viruses in children common -bacteria in adults common -secondary infection following viral infection common historically major cause of death (still in developing countries |
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Influenza, symptoms, recovery, cause |
-generally more severe than common cold -high levels of cytokines (Increased inflammation, and associated with increased pathology) -recovery=1-2 weeks -symptoms: chills, fever, sore throat, muscle pains, severe headache, coughing, and weakness/fatigue -caused by influenza virus |
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How is the influenza virus transmitted? |
-by aerosols and direct contract |
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Cycle of the influenza virus |
-endemic, seasonal epidemics, and pandemic transmission cycles |
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How many types of influenza virus are there and what is it based on? |
3 types, A, B, C, based on gene structure |
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T/F Influenza virus does not exhibit different host ranges and clinical manifestations |
False |
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What does Type A influenza virus exhinit |
antigenic shift and it can cause pandemics |
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Virulence of Influenza A |
wider host range and more virulent in humans than B and C |
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In what animal is influenza virus found |
aquatic birds |
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The serotypes of influenza virus are based on
and defined by |
hemagglutinin (H) and neuraminidase (N)
which are surface proteins on the virus defined by reactivity of antibodies to virus |
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Influenza:
H mediates what |
binding of virus to host cell
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Influenza:
N releases... |
progeny virus from infected cells |
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What are the known serotypes |
16H, 9N
H1, 2, 3 and N1, 2 are common in humans |
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What is antigenic shift? |
-A sudden major change in the virus -may also confer increased pathogenicity, virulence, transmissibility, in addition to new antigenic variant -occurs less frequently than antigenic drift
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What is antigenic shift due to |
recombination and re-assortment of virus genomes -multiple variants in same host cell -segmented genomes allow for re-assortment -often occurs in pigs since both avian and human viruses can infect |
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Pandemics are believed to involve |
recombination between avian viruses and human viruses |
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Influenza Vaccine |
Type A H1N1 H2N2 and Type B
exact strains reviews annually (drift)
recommended for high risk individuals, elderly or compromised. |
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Influenza Treatment |
2 classes of anti-virals -viral rep (M2) inhibitors (rimantadine amantadine) against type A -neuraminidase inhibitors (zanamivir oseltamivir) agaisnt types A and B -both decrease severity if given within 1-2 days of disease onset (symptoms) -effective for prophylaxis |
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alveoli |
small air sacs of the lungs, sing (alveolus)
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antigenic drift |
slow changes in the antigenic properties of a pathogen due to the constant and steady changes in the gene sequence, resulting in a minor change in antibody reactivity with the antigen |
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antigenic shift |
a rapid and sudden change in antigenic and or other properties of a pathogen due to genetic recomb between different strains of pathogen |
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bronchiolitis bronchitis |
inflammation of bronchioles " " bronchi
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pharyngitis |
inflammation of the pharynx |
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rhinitis |
inflammation of the mucous membranes of those nose and nasal passages |
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RSV |
respiratory syncytial virus, very common virus primarily found in children |
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serotype |
refers to the immunological variations between strains of infectious organisms such as bacteria and viruses. determines by reactivity to well characterized defined antibodies
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sputim |
mucus that is coughed up |
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bacteria
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diverse prokaryotic organisms that can cause a wide variety of diseases in humans and other organisms
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Bactericidal
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drugs that kill bacteria
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bacterostatic
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drugs that slow or stop the replication of bacteria but do not necessarily kill bacteria
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communicable disease
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disease caused by pathogens that are transmitted from host-to-host and generally cannot live for extended periods outside a host
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contagious disease
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communicable diseases that are easily transmitted between hosts
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convalescence
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the stage of recovery following a disease or injury
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ecto-parasite
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an organism, generally and arthropod, that attached or lives on the skin of its host and derives nutrients
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fomite
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an object that can harbor infectious agents and thus may serve as means of transmission
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fungus
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saprobic eukaryotic organism which yields yeast and mold. Some are opportunistic pathogens
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helminth
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a worm, some are parasitic
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in vitro culture
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growth of an organism in and artificial medium, can be used in the diagnosis of some micro-organism and viruses
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incubation period
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the amount of time between the start of infection and the appearance of symptoms
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infection
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invasion and multiplication of pathogens in a body tissue
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infectious
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refers to the relative ease of transmission
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infectivity
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ability of an organism to enter, survive, and replicate within a host
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mycosis
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an infection caused by a fungus
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opportunistic pathogen
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an organism that is normally not pathogenic, but can become pathogenic in immunocompromised or debilitated hosts
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parasite
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An organism that lives on a host organism and causes disease. Generally refers to protozoa, helminthes, and anthropods
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pathogen
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an organism or biological entity that is capable of causing disease
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prion
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infectious protein
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prodromal
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the period characterized by non-specific or mild symptoms indicating the onset of disease
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protozoan
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an eukaryotic microbe, some of which can cause disease (protozoa=plural)
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systemic
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affects the body as a whole
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tropism
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the tendency to be associated with a particular organ or attracted to a particular substance
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vector
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and organism that transmits infectious diseases
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virulence
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degree of damage or disease caused by a pathogen, can be conditional
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zoonosis
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a disease that is normally found in animals that can be transmitted to humans
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CD4 protein
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A cell-surface protein found on some t-cells, monocytes, macrophages, and dendritic cells. Serves as a receptor fo rHIV
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CD4+ cells
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cells that express the cd4 protein on their surface. Predominately helper t-cells, macrophages, and dendritic cells
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HAART
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Highly Active Antiretroviral Therapy. A combo of drugs used in the treatment of HIV infections
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Immunodeficiency
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a condition in which some components of the immune system are missing or defective
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opportunistic infection
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micro-organisms that normally do not cuase disease except in individuals with compromised immune system
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retrovirus
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a class of viruses characterized by having a RNA dependent DNA polymerase which copies the RNA genome into DNA
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reverse transcriptase
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an RNA dependent DNA polymerase found in retroviruses that converts the RNA genome of the virus into a DNA molecule
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SIV
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Simian Immunodeficiency Virus, related to HIV but in non-human primates
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tropism
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having an affinity for a particular organ or tissue, or moving towards or away from a particular stimulus
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viremia
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refers to the presence or level of virus infection (i.e. the number of virus particles present)
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What is tuberculosis primarily caused by
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myobacterium tuberculosis
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What part of the body does tuberculosis primarily affect?
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The lungs
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Tuberculosis can be active or
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latent
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T/F tuberculosis does not spread to other orgrans
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False
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How common is tuberculosis?
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1.7 billion people infected
1.3 Million deaths 2012 |
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Emergence of tuberculosis possibly associated with
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agricultural revolution urbanization
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What reduced the prevalence of tuberculosis
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Public Health Measures and antibiotics
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Characteristics of mycobacterium tuberculosis
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-slow growing
-complex lipid-rich cell wall |
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Role of mycolic acid/lipid shell as a virulence factor
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-resistance to desiccation (better transmission)
-low permeability contributes to: resistance to many common antibiotics resistance to disinfectants and detergents slow growth -protects from host defenses complement resistance survival within macrophages |
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Mycobacteria replicate within macrophages
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active phagocytosis-->block fusion of phagosome with lysosome and resist killing activities of macrophage-->breakdown phagosome and replication-->lysis of infected macrophages-->long-term chronic infections
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Transmission of Tuberculosis
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-primarily airborne via droplet nuclei
-produced during coughing, sneezing, shouting, singing -remain airborne for several hours -inhale and infection reach aveoli |
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An active TB case infects how many persons per one year on average
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10-15
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Infectiousness determinants of TB
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only active (not latent pulmonary cases)
number of bacteria expelled |
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Environment of TB transmission
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Small enclosed spaces favored
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Exposure Transmission Factors of TB
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duration, freq, physical proximity
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Susceptibility transmission factors
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-immune status of exposed individual
-genetic predisposition |
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What percent of newly infected individuals develop an active infection within 2 years, most develop what..
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~5%, asymptomatic latent infection
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Primary Progressive TB
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-generally children, elderly, debilitated, immunodeficient
-generally confined to the lungs -numerous AFB found in sputum -can disseminate to other organs (miliary TB) -50% mortality within 2 years |
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In TB, activation and recruitment of lymphocytes leads to
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granuloma formation and latent infection
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In TB localized inflammation leads to
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recruitment of lymphocytes and other immune effector cells
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In TB, cellular mass forms and
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encapsulates the mycobacteria, which allows the mycobacteria to persist for life of the patient =latent tb infection, asymptomatic, non-infectious, contained by granuloma
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TB reactivation factors
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age, diabetes, steroids, chronic poor health, HIV
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Secondary Progressive TB
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-Due to reactivation of latent infection
-aka, post primary TB -center of granuloma becomes necrotic and soft -rupture releases mycobacteria into airways (highly infectious, formation of pulmonary cavities, dissemination also possible..miliary TB) |
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Pathophysiology of Pulmonary TB
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-mycobacteria are highly immunogenic
-inflammation-->tissue damage -granuloma formation -Rupture of larger granulomas -cavities (up to 15cm) -Fibrosis and scarring associated with healing |
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Clinical Manifestations of TB
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-low-grade fever
-night sweats -fatigue -weight loss -cough (initially dry, later productive and purulent, blood tinged) -organ specific for extra-pulmonary |
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Diagnosis of TB
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1. identify mycobacteria in sputum
-acid fast stained smear -culture (8-12 weeks) -molecular tests 2. Chest x-ray/other imaging 3.TB skin test -hypersentivity rxn -primarily LTBI |
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Mantoux TB skin test
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-t-cells recognizing PPD migrate to injection site
-localized inflammatory response -size or induration and risk factors determine diagnosis -high false positive rate |
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Treatment of TB, what is the typical treatment
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-TB is curable
-Drug resistance is a major problem -requires multiple drugs for a long duration -typical treatment protocol: (isoniazid, rifampicin, pyrazinamide, ethambutol, then INH) -compliance is problematic |
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Directly observed therapy Short course (DOTS)
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-person observes patient swallowing tablet
-prevents relapse and spread of TB -slows development of drug resistance |
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Multidrug Resistant (MDR) TB
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-resistance to INH and RFP
-requires treatment with second line drugs (more expensive, longer treatment duration, more AE's) -higher mortality rate -MDR-TB-->XDR-TB -resistance to 1st and 2nd line of drugs -first recognized in 2006
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TB vaccine
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-bacili calmetter-guerin (BCG) developed in 1921
-questionable efficacy (appears to protect children against miliary TB or TB meningitis) -0-80% effective in preventing pulmonary TB -WHO recommends vaccination of children in highly endemic countries |
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droplet nuclei
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particles 1-5 micrometers in diameter, implicated in spread of airborne infections
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LTBI
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Latent TB infection
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MDR-TB
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multi-drug resistant tuberculosis. Resistance to at lease isoniazid
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mycolic acid
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a fatty acid found in the cell wall of mycobacteria
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PPD
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purified protein derivative. An extract of mycobacterium tuberculosis protein used for the skin test
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primary TB
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a case of active TB which develops within 2 years after acquiring the infections
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secondary TB
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a case of active TB due to activation of a latent infection
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tubercle
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a small nodule (i.e. granuloma) due to encapsulation of mycobacterium tuberculosis bu immune effector cells
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XDR-TB
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extensively drug resistant TB, includes resistance to second line drugs
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active TB
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an infectious disease primarily infecting the lungs caused primarily by mycobacterium tuberculosis. Generally refers to a symptomatic state that is contagious
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granuloma
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tumor-like mass or nodule due to chronic inflammation associated with an infectious disease
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latent
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refers to a dormant form of an infection that can later reactivate
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How many estimated cases of diarrheal diseases occur each year, where is the highest incidence
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1.7 billion, developing countries
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Who has the greatest impact of diarrheal diseases
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Children, major cause of death/contributes ot malnutrition in <5 years old
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Viscous cycle of diarrhea and malnutrition
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diarrhea-->decreased nutrient absorption-->malnutrition-->impaired immunity-->increased infections and durations-->diarrhea
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The vast majority of diarrhea caused by
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infectious agents
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Types of Pathogens that cause gastrointestinal disease
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viruses, bacteria, protozoa, helminthes
disease involves ingestion of pathogen or toxin produced by pathogen |
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3 common transmission mechanisms for diarrheal diseases
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1. fecal-oral transmission
2. food-borne transmission 3. Water-borne transmission |
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Fecal-oral transmission
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-infectious stage of pathogen excreted in feces
-direct or indirect (eg, soil transmission) contact -ingestion of contaminated food or water |
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Food-borne intransmission
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-contamination of food with pathogen (ie, fecal-oral transmission)
-bacterial growth in food |
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Water-borne transmission
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infectious agents associated with water
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Water-borne transmission factors
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-life cycle stage or intermediate host associated with water
-deficiencies in sewerage and water treatment infrastructure (high levels of endemicity in developing countries, traveler's diarrhea) -water treatment failures -diaster situations-->outbreaks -occupational or recreational contact with water |
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gastroenteritis & symptoms
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inflammation of the stomach and small intestine. symptoms include nausea, vomiting, diarrhea, and abdominal discomfort
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colitis and symptoms
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inflammation of the colon. symptoms include pain, abdominal cramps, dysentary
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enterocolitis
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inflammation of the small and large intestines
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diarrhea
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frequent and or watery stools usually resulting from disease of the small intestines
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dysentery
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blood and mucus in the feces often associated with colitis
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endogenous flora can only cause disease under what special circumstances
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migration to other parts of the body, immune supression
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symbiotic realtions
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commensalism (microbe benefits)
mutualism (both benefit) parasitism (host is harmed) |
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functions of the gut microbia
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-normal flora is more mutualistic than commensal
-digesting unused carb substrates -vitamin production -training the immune system -preventing growth of pathogens (competing for space and resources, metabolic wasted and anti-bacterial activities) |
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Pathogenic bacteria express
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virulence factors
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What are virulence factors
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-pathogen products
-associated with any aspect of disease process -adhesins -immune system avoidance -invasins (promote penetration of host barriers) -toxins -type III secretion (toxin secretion) |
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What leads to osmotic diarrhea
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superficial damage to mucosa due to microbial by-products or adherence
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what leads to inflammatory diarrhea
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destruction of mucosal epithelium due to invasion or cytoxicity
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for diarrheal diseases local inflammation is a result of
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microbial adherence or invasion of mucosa
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What happens if there is a deeper invasion into sub-mucosa
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dissemination via blood and lymphatics
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peritonitis
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perforation of intestinal wall
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Can bacterial toxins cause disease independent of the bacterium?
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Yes
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Main two types of bacterial toxins
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exotoxin-secreted prodcut
endotoxin-lipid A of lipopolysaccharide (LPS) |
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Effects of Endotoxin
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Low concentrations
-activated innate immunity -cytokines, fever, vasodilation High concentrations -hypotension-->endotoxic shock-->death |
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Exotoxins
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-secreted proteins or peptides
-many types and mechanisms -generally heat labile, but some are heat stable -target specific host pathways -many are enzymatic (Increase potency) |
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Examples of exotoxins
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neurotoxins: interfere with nerve transmission
cytotoxins: kill or lyse host cells enterotoxins: affect intestinal epithelium |
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AB toxins
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-a subunit=activity (responsible for toxicity, interferes with cellular physiology)
-b subunit= binding (binds to receptor of target cell, facilitates entry of A-subunit into target cell) -vaccine possibility (generally neither subunit is toxic by itself) |
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Cholera Toxin
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-high affinity binding to ganglioside (lipid)
-entry activates cAMP/protein kinase signal transduction pathway -phosphorylation of CFTR leads to increase CI secretion and Na+ absorption -massive loss of electrolytes and water dehydration-->electrolyte imbalance-->muscle cramps-->shock |
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How enterotoxins lead to secretory diarrhea
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1. necrosis of intestinal epithelium
(small intestine-->bloody diarrhea, large intestine-->dysentery, inflammatory diarrhea) 2. 2 mechanism: cytotoxins, epithelial cell invasion and bacterial replication 3. may disseminate to other organs |
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salmonella enterica
serotype typhi |
-only human sources
-typhoid (=enteric) fever -systemic spread via infected macrophages, especially liver, spleen, bone marrow -fever headache, muscle ache, etc -exacerbated by LPS |
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salmonella enterica
other serotypes |
-human and animal sources
-gastroenteritis -generally restricted to intestinal mucosa -usually self-limiting |
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Viral pathogens of the GI tract
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-fecal-oral transmission
-gastro-enteritis (specific diagnosis difficult) -oral rehydration used to treat sever cases -rotavirus (common in infants and children, higher mortality in developing countries) -caliciivirus |
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Treatment of Diarrhea
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-generally mild and self-limiting
-oral rehydration therapy (ORT) in severe cases (e.g. cholera, small children) -antibiotics rarely used (drug resistance, prolongs symptoms b/c disrupts normal flora) -specific drugs for protozoa -probiotics as adjunct therapy to replace normal GI flora |
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Campylobacter
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A genus of bacterial that is major cause of foodborne illness in humans.
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cholera
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An acute infectious disease of the small intestine caused by the bacterium Vibrio cholerae and characterized by profuse watery diarrhea, vomiting, muscle cramps, severe dehydration, and depletion of electrolytes.
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cholera toxin
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An A-B enterotoxin secreted by the bacterium Vibrio cholerae which is responsible for the massive, watery diarrhea characteristic of cholera.
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enterotoxin
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A toxin produced by bacteria that specifically affects intestinal cells and causes the vomiting and diarrhea associated with food poisoning.
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Escherichia coli
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A bacterium that normally resides in the human colon. Some strains can cause disease.
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exotoxin
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A toxin produced by a micro-organism and secreted into the environment.
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inflammatory diarrhea
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A diarrhea associated with pathogen invasion of the intestinal mucosa characterized by dysentery.
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(intestinal) flora
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Microorganisms that normally inhabit the lumen of the intestinal tract.
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LPS (lipopolysaccharide)
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A molecule consisting of lipids and polysaccharide moieties that is a major component of the cell wall of gram negative bacteria.
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oral rehydration therapy (ORT)
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Treatment for diarrhea-related dehydration in which an electrolyte solution containing fluids and vital salts is administered.
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osmotic diarrhea
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Diarrhea associated with damage to the intestinal mucosa resulting in increased secretion of water and decreased absorption of water.
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probiotic
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A dietary supplement containing live bacteria or yeast that supplements normal gastrointestinal flora, given especially after depletion of flora caused by infection or ingestion of an antibiotic drug.
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Salmonella
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A genus of bacteria which includes many pathogenic species, causing food poisoning, typhoid, and paratyphoid fever in humans and other infectious diseases in domestic animals.
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secretory diarrhea
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A watery diarrhea generally caused by bacterial toxins.
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typhoid fever
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An acute, highly infectious disease caused by Salmonella enterica serotype typhi and primarily transmitted by contaminated food or water.
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waterborne
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Referring to infectious or toxic agents acquired by ingesting contaminated water.
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What are protozoa
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-single-celled eukaryotic organisms
-proto(=first)+zoa(=animal) |
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Protozoan Motility Mechanism and subgroup
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flagella-flagellates
cilia-ciliates ameboid movement-amebas gliding motility-apicomplexa |
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Fecal-oral transmission factors
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-poor personal hygiene
-developing countries -water-borne epidemics -zoonosis` entamoeba=no cyrptosporidium=yes giardia=relatively rare |
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Control/Prevention for fecal oral transmission
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1. improve personal hygiene
2. treat asymptomatic carriers 3. health education 4. protect water supply 5. treat water if questionable. |
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Entamoeba histolytica
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1. no animal reservoirs
2. cosmopolitan distribution 3. worldwide incidence= .2-50% (10% of the world may be infected) 4. faculative pathogen (most clear the infectious spotaneous in 6-12 months with no or mild symptoms, can cause a serious invasive disease) |
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Pathogenesis of Amebiasis, Non-invasive
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-ameba colony on intestinal mucosa of colon
-asymptomatic cyst passer -non-dysenteric diarrhea, abdominal cramps, other GI symptoms |
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Pathogenesis of Amebiasis,Invasive
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-necrosis of mucosa-->ulcers, dysentery
-ulcer enlargement-->severe dystentery, colitis, peritonitis -metastasis-->extraintestinal amebiasis (primarily liver) |
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Severe Pathogenesis
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1. ulcer enlargement-->severe dysentery
2. perforation of intestinal wall-->peritonitis 3. abscesses with secondary bacterial infections 4. metastasis to other organs (liver) 5. Direct spread vis fistula to organs -from liver to lung -from skin to genitalia 6. cessation of cyst production |
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Giardia lamblia
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-worldwide distribution
-higher prevalence in developing countries (20-60%) -2-5% in industrial countries -most common protozoa found in stools -~200 mil clinical cases/year -giadiasis often symptomatic, acute/chronic diarrhea -typical fecal-oral life cycle |
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protozoa cysts play what role in infection
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infective stage, passed in feces
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protozoa trophozoite play what role in infection
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replicative stage, small intestine
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Range of outcomes for giardia infections
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-asymptomatic/latent
-acute short-lasting diarrhea -chronic/nutritional disorders |
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Subacute/chronic features of giardia infections
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-recurrent diarrheal episodes
-cramps uncommon -sulfuric belching, anorexia, nausea frequent -can lead to weight loss and failure to thrive |
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Acute symptoms of giardia infectious
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-1-2 week incubation
-sudden explosive, watery diarrhea -bulky, frothy, greasy, foul-smelling stools -no blood or mucus -upper gastro-intestinal uneasiness, bloating, flatulence, belching, cramps, nausea, vomiting, anorexia -usually clears spontaneously (undiagnosed), but can persist or become chronic |
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Cryptosporidium
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-two species infecting humans
-fecal-oral transmission -first human cases 1976 -self-limiting diarrhea in immunocompetent persons -profuse, watery diarrhea associated with AIDS |
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cyrptosporidiosis and aids
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1. disease more severe in aids patients, malnourished children, etc
2. diarrhea persists for months or years 3. more profuse 4. correlated with low CD4+ counts 5. Parasite primarily found in small intestine of immunocompetent 6. More extensive in AIDS patients-often includes stomach, small and large intestines, and biliary tract |
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2 major genotypes identified for cyrptosporidium
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1. genotype 1(C. hominis)
-only human sources -non-infective mice or calves -anthroponotic transmission 2. genotype 2(C.Parvum) -human and bovine sources -infective mice and calves -zoonotic and anthroponotic transmission 3. Other genotypes rare, isoloated only from AIDS patients |
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Milwaukee Outbreak
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-massive cryptosporidiosis outbreak following spring thaw
->400, 000 people -~100 fold higher prevalence -treated water had high levels of turbidity -oocysts identified in ice made -broken pipe-->sewage mixing with clean water? |
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osmotic diarrhea
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enterocyte malfunction, impaired absorption, enhanced secretion , excessive solutes
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inflammatory diarrhea
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-mucosal invasion
-leukocytes in stools |
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secretory
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-toxin associated
-excessively watery |
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Diagnosis of protozoa
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-in feces by microscopy (staining)
-detection of antigens in feces -extra-intestinal amebiasis (history of dysentery, organ specific symptoms, imaging, serology) |
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Treatment for giardia and e. histolytica
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-metronidazole (flagyl)
-generally good prognosis with no sequelae |
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Treatment for crytosporidium
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-no extremely effective drugs, especially AIDS patients
-nitazoxanide for immunocompetent patients -supportive care in severe cases (re-hydration and nutritional support, anti-motility agents) -extra preventive measures recommended for AIDS patients |
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ameba
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A single-cell protozoan characterized by itsability to change shape and move via pseudopodia (i.e., ameboid movement).
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amebiasis
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The disease caused by an ameba and especiallythat caused by Entamoeba histolytica (eg.,amebic dysentery).
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cryptosporidiosis
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The disease (i.e., diarrhea) caused by aninfection with Cryptosporidium
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Cryptosporidium
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A genus of protozoa that infects a wide variety of animals and is often the cause of severe diarrhea in AIDS patients.
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cyst
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A protozoan stage that is dormant and resistant to environment stresses that can convert into an active stage under the appropriate conditions (eg., ingestion by a host).
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Entamoeba
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A genus of ameba most noted for Entamoeba histolytica which causes amebic dysentery.
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Giardia
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A genus of flagellated protozoa that is a common cause of diarrhea in humans.
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protozoan
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A large and diverse group of eukaryotic microbes; some of which can cause human disease. (pl. = protozoa)
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trophozoite
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An actively growing and replication stage in many protozoan life cycles.
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Vector transmission requries |
1. the presence of the vector and substantial vector-host contact 2. stage of pathogen to be present in the blood 3. pathogen must be able to adapt to two relatively different hosts |
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Facts about malaria |
-207 million cases in 2012 -627,000 deaths 2012 -80% cases and 90% of deaths in africa -77% deaths in children <5 years |
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Causative agent of malaria |
-plasmodium -5 species infecting humans |
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Distribution of Malaria |
-tropical and subtropical climates -formally widespread in temperate zones -40% of the worlds's population in endemic areas |
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life cycle of malaria |
1. transmitted by anopheles mosquitos 2. sporozoites injected with saliva 3. sporozoites enter circulation 4. invade liver cells 5. undergo an asexual replication 6. 1000-10,000 merozoites 7. merozoits invade RBC 8. asexual rep 9. responsible for disease |
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Clinical features of malaria |
1. characterized by acute febrile attacks 2. manifestation and severity depend on species and host status 3. recrudescences and relapses can occur over months and years 4. can develop severe complications (especially p. falciparum) |
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Malaria Paroxysm |
1. paroxysms associated with synchrony of merozoite release (48/72 hour cycles) 2. temp is normal and patient feels well between paroxysms 3. falciparum may not exhibit classic paroxysms (continuous fever) 4. Paroxysms become less severe and irregular as infection progresses |
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Anti-malarial immunite |
-semi-immune may exhibit little or no symptoms -non-sterilizing -immunity is slow to develop and short lived -p. falciparum can be lethal in non-immune |
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Anti-parasite malarial immunite |
prevents merozoite invasion, eliminated infected erythrocyctes etc. |
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Anti-disease malarial immunity |
neutralization of released antigens or toxic effects |
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Severe Falciparum Malaria |
~10% of falciparum malaria cases-->severe disease -mortality rate of 10-50% -many different organs can be affected -several complication can occur simultaneously -complication can develop rapidly -higher parasitemias and sequestration contribute |
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3 most common complications of severe falciparum malaria |
1. cerebral malaria -consciousness ranges from stupor to coma -convulsions frequently observed 2. severe anemia -especially children -destruction and decreased RBC production 3. respiratory distress -can progress to respiratory failure -best predictor of death |
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Sequestration (malaria) |
-Pf-infected erythrocytes adhere to endothelial cells (primarily in brain, heart, lungs, and gut; immune evasion) -not seen in other species -contributes to higher parasite load and complications |
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Possible pathophysiology of sequestration (malaria) |
cytoadherence-->cerebral ischemia-->hypoxia, metabolic effects, cytokines->coma-->death |
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Treatment of malaria |
1. anti-malarials available 2. chloroquine is first choice for non-falciparum 3. artemisinin combo therapy (ACT) is first line for falciparum 4. chemoprophylaxis recommended for transient visits to endemic areas 5. drug resistance is a major problem |
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Artemisinin |
-originally identified from chinese traditional medicine -generally well tolerated -fast acting and short half-life -ACT is standard treatment for falciparum since 2006 -WHO discourages mono-therapy with artemisinin derivatives |
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mutation in drug targets or transporters lead to |
increased drug tolerance, mutations selected and spread under drug pressure |
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Factors contributing to development and spread of drug resistance |
1. self-treatment 2. poor compliance 3. long drug half-life 4. transmission intensity 5. mass administration 6. exposing parasite to sub-therapeutic levels of drug selects for increased tolerance to drug |
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Control and prevention strategies for malaria |
reduce human-mosquito contact reduce vector reduce parasite reservior |
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bed bets and malaria in africa |
treated bed nets reduce morbidity and mortality reduces exposure |
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ACT |
Artemisinin combination therapy. Generally the first line of treatment for falciparum malaria in much of the world. |
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anopheline |
Refers to the mosquito genus Anopheles. Some species transmit themalaria parasite. |
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arbovirus |
Arthropod-borne virus. Viruses transmitted by mosquitoes or other arthropods. |
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arthropod |
A group of organisms containing jointed limbs (i.e., legs) and a hard exoskeleton (eg., insects). |
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chloroquine |
A highly effective anti-malarial for non-falciparum malaria. It is of little use against falciparum malaria due to wide-spread drug resistance. |
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drug pressure |
Refers to the continuous presence of a drug than leads to selection of pathogens that are increasingly tolerant of that drug. |
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falciparum |
A species of Plasmodium (i.e., malaria parasite) responsible for the most morbidity and mortality associated with malaria. |
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gametocytes |
Stages in the malaria parasite life cycle that are transmitted from humans to mosquitoes. |
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merozoite |
A stage in the malaria parasite life cycle that invades red blood cells. |
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parasitemia |
Refers to the presence or level of a parasite infection (i.e., the number of parasites present in a sample). |
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paroxysm |
A sudden re-occurrence or intensification of a symptom. In malaria refers to the periodic febrile attacks. |
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Plasmodium |
The genus of malaria parasites. |
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sequestration |
Refers to the adherence of P. falciparum infected erythrocytes to endothelial cells in tissues rather than circulating in the peripheral blood stream. |
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sporogony |
The life cycle stage of the malaria parasite that occurs in the mosquito resulting in the production of sporozoites. |
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sporozoite |
An organism, generally an arthropod, that transfers (or carries) a pathogen from host to another. |
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vector |
An organism, generally an arthropod, that transfers (or carries) a pathogen from host to another. |
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vivax |
A common and widespread species of Plasmodium (i.e., malaria parasite). |
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Neglected Tropical Diseases (NTD) |
1. primarily in low income countries 2. lower prevalence of some 3. many have low mortality 4. resources are focused on the "big three" 5. But, some have high morbidity and high prevalence |
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Importance of helminth infections |
1. under-recognized burden of disease 2. low mortality 3. high morbidity 4. significant impact on childhood development 5. frequent co-infections with other helminths or pathogens 6. complex interaction with host immune response |
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Transmission of Ascaris lumbricoides |
-poor sanitation -human feces as fertilizer -eggs: 200,000 per day, 2 weeks to mature, persist for 10 years |
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Conditions Needed for STH Transmission |
-infected persons living in the community -defecation on ground -appropriate condition for eggs to mature and larva to survive -contact with contaminated soil |
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Pathology and Disease manifestation of helminths |
1. most infections asymptomatic 2. can include diarrhea, dysentery, and chronic colitis, intestinal obstruction, weight loss, emaciation, and anemia 3. Heavy worms burdens in children impair physical and cognitive development 4. Anemia and iron deficiency associated with hookworm infections |
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Hookword Anemia |
1. infection generally asymptomatic 2. injure host during attachment to intestinal mucosa 3. loss of .2ml of blood per worm per day (anemia and iron deficiency, protein malnutrition, impaired physical and cognitive development, poor fetal outcomes, silent and insidious disease) |
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Mass Drug Administration (MDA) |
-used with albendazole widely used to control STH infections -typically admin annually in schools by teachers -improvements in catch-up growth and physical fitness -improved cognition and educational performance |
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Generalized life cycle of filariae |
human (adult worms)-->human (mf in blood)-->insect vector (microfilaria develops to infective stage)-->enters human tissues when vector feeds (infective larva)-->human (adult worms) |
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Pathology of helminths |
-ranges from asymptomatic to irreversible damage -immune response affects degree any type of disease -disease may be due to adult (LF) or microfilaria (onchocerca) stages (adult worms obstruct lymph channels-->lymph accumulation, subcutaneous mf-->inflammation) |
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MDA can |
interrupt transmission -mass treatment of at risk pop, annually for at least 5 years, plus vector control |
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Transmission factors of helminths |
-defecation/urination in surface water -presence of appropriate snail host -contact with infested water -highest infection rates generally seen in childhood and adolescence |
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Pathology and Disease helminths |
-associated with inflammatory response against eggs -s. mansoni and S. japonicum affect liver and intestines -s. haematobium affects bladder -praziquantel used for treatment and MDA |
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Cysticercosis |
-cysticerci present in tissues (muscle, subcutaneous, brain) -invasion of CNS is most problematic -neurocysticercosis -common cause of seizures and convulsions |
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anti-helminthic |
A drug use to treat helminth infections. |
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Ascaris lumbricoides |
A species of soil transmitted roundworms that infect humans. |
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cysticercosis |
Disease due to presence of cysticerci in the tissues. Referred to as neurocysticercosis if present in brain. |
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filaria |
A type of round worm characterized by vector transmission. |
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geohelminth |
Also known as soil transmitted helminth. |
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hookworm |
A type of soil transmitted helminth characterized by teeth or plates which anchor the worm to the intestinal epithelium. |
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intermediate host |
A required host in the life cycle of a parasite which is essential for larval development. |
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MDA |
Mass Drug Administration. The distribution of drugs to everyone in a defined population regardless of the presence of infection in the individuals. |
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Schistosoma |
A genus of flukes transmitted via water and a snail as the intermediate host. |
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soil-transmitted helminth (STH) |
Helminthes in which the eggs mature into larvae in the soil and then subsequently infect the human either via ingestion or penetration of the skin. |
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tape worm |
A type of flat worm. Also called cestode. |
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Trichuris trichiura |
A species of soil transmitted helminthes that infects humans (aka, whipworm) |
