Keywords: Chapter 9b, Infectious and Parasitic Diseases I

acid fast

Certain classes of organisms resist decolorization when exposed to mild acid. These organisms are called "acid fast". The mycobacteria are the most common class of acid fast organisms. Some organisms are partially acid fast. These include the Nocardia spp.
anergy
The lack of a type IV hypersensitivity response (78), often seen in patients with immunodeficiency syndromes, is known as anergy. This presents a difficult clinical problem when skin testing for tuberculosis, since the physician is then unsure whether a patient has been exposed to tuberculosis. Some clinical guidelines on this problem are available from the CDC.

References

  1. MMWR 40 (RR-5) 27-33, 1991. CDC Prevention Guidelines. Purified protein derivative (PPD)-tuberculin anergy and HIV infection.

antitoxin
An immunoglobulin product, raised in animals (often horses), that binds to bacterial toxins and inactivates them (e.g., tetanus anti-toxin).
auromine-rhodamine stain
A fluorescent dye that intercalates in DNA. It is used to detect mycobacteria in sputum, or other patient samples. It is much more sensitive than the usual acid fast stains, such as the Kinyoun stain. All clinical laboratories should offer this test to screen for tuberculosis, and results should be available within 24 hours. Until such time, suspected Tb patients must be isolated in negative air pressure rooms.
Bacillus of Calmette-Guerin (BCG)
This strain of Mycobacterium tuberculosis is utilized as a tuberculosis vaccine in many countries. It is not commonly utilized in the United States, because most of the population is tuberculin-negative, and skin testing remains a useful means of identifying those at risk for developing tuberculosis. A person with a history of BCG vaccination will be skin test positive, but treatment is not indicated. Theoretically, children would benefit from BCG administration, because it confers a modicum of immunity and therefore converts the devastating childhood form of Tb into the milder adult form. This has caused CDC to recently modify its stance on the use of BCG in exposed children.

References


  1. BCG in the USA, CDC Recommendations
    bacteremia
    Bacteremia is the presence of bacteria in the blood. Bacteremia may be transient, intermittent, or continuous.
    Transient bacteremia
    occurs after such minor events as brushing or cleaning the teeth, defecation, or surgical manipulation of infected wounds. In a patient with a working reticulo-endothelial system (functioning liver and spleen), such bacteremia is of little clinical consequence.

    Intermittent bacteremia

    Most often associated with an undrained abscess.

    Continuous bacteremia

    The cardinal feature of acute endocarditis and sepsis associated with indwelling intravenous or arterial catheters.

    broth microdilution
    An automated method of determining a breakpoint MIC. KUMC uses the Vitek system (BioMerieux, Hazelwood, MO). The breakpoints for susceptibility (S), intermediate (I), and resistant (R), are different for each organism. The breakpoints are established by the National Committee for Clinical Laboratory Standards (NCCLS).
    carrier
    A person or animal that harbors a specific infectious agent in the absence of clinical disease and may serve as a potential source of infection. The carrier state may exist in an individual with an infection that is inapparent throughout its course (commonly known as a healthy or asymptomatic carrier), or during the incubation period, convalescence, and post-convalescence of an individual with a clinically recognizable disease (commonly known as incubatory carrier or convalescent carrier). Under either circumstance the carrier state may be of short or long duration (temporary or transient carrier, or chronic carrier).
    cold agglutinin
    An agglutinin is an antibody that causes the agglutination of plasma. A cold agglutinin can cause agglutination of plasma within vessels if the patient is in a cold environment. This can be serious enough to cause infarction and gangrene of extremities. Mycoplasma pneumonia is notorious for the production of such cold agglutinins.
    drug resistance
    Bacterial resistance to antimicrobials can be intrinsic or acquired. Resistance to antimicrobial agents is now common in many species of bacteria, and is beginning to emerge in several viral species, protozoa, and even helminths. In bacteria, resistance depends essentially upon 4 mechanisms. The first 3 may be due to chromosomal changes or plasmids; the fourth is always acquired from a plasmid or transposon.

    The most common method of resistance is the chemical inactivation of the antimicrobial; for example, the inactivation of penicillin by a penicillinase carried on a plasmid or chromosome. Second, the organism may change its target; for example, a mutation in a penicillin binding protein may prevent the antimicrobial from attaching to the organism. Third, organisms may decrease the amount of drug accumulation by altering their porins, or channels through their cell membranes. This is seen most often in Gram-negatives, particularly the Pseudomonas spp.

    Lastly, some organisms are capable of bypassing an anti-microbial-sensitive step. For example, the vancomycin resistance only now emerging in the members of the genus Enterococcus is due to a transposable gene encoding an alanine ligase. This new ligase replaces the physiologic one, and the transposable alanine ligase has a thousand-fold less affinity for vancomycin. Thus, vancomycin cannot inhibit peptidoglycan synthesis in the cell wall of such organisms.


    E test
    The E test (AB Biodisk NA, Piscataway, NJ) is a recently developed quantitative method of determining the minimum inhibitory concentration (MIC), wherein a plastic strip with a calibrated gradient of antimicrobial is placed upon an agar plate with a standardized concentration of the microbial isolate. The MIC is read directly off the strip where the colonies cross the calibrated strip.
    emerging infection
    Any infectious disease which has come to medical attention within the last two decades. Many times, such diseases exist in nature as zoonoses, and only emerge as human pathogens when humans come in contact with a formally isolated animal population, such as monkeys in a rain forest due to deforestation. Drug-resistant organisms could also be included as emerging infections, since they exist because of human influence. Some recent examples of emerging infections include human immunodeficiency virus, Ebola virus, and multi-drug resistant tuberculosis. The Centers for Disease Control (CDC) has recently compiled a monograph on

    Emerging Infections.
    endemic
    The constant presence of a disease or infectious agent within a given geographic area; may also refer to the usual prevalence of a given disease within such area. Hyper-endemic expresses a persistent intense transmission and holoendemic a high level of infection beginning early in life and affecting most of the population, e.g., malaria in some places. (see zoonosis).
    epizootic
    An epidemic in a population of wild animals.
    fastidious organisms
    Some organisms, particularly a small group of Gram-negative organisms, often require the clinical microbiology laboratory to use special media in order to grow them. If you suspect one of these organisms, you must notify the lab so that they will use the proper growth medium. Also, some of these organisms represent a danger to laboratory personnel, so notification of the laboratory that one of them might be involved in a patient you are treating is only politic, and may save you a savage brow-beating. These organisms include: the HACEK group (see below), Brucella spp., Pasteurella multicida (dog or cat bites), Capnocytophaga canimorsus (dog bites), Streptobacillus moniliformis (gerbil or rat bites), Bordetella pertussis (whooping cough), Brucella spp. (Bang's disease, undulant fever), and Francisella tularensis (rabbit fever, tularemia).
    germ tube
    A test used in the clinical microbiology laboratory to quickly speciate a yeast isolate. For all practical purposes, if a yeast germinates (produces a germ tube) in calf serum within 20 minutes, it may be identified as Candida albicans.
    HACEK organisms
    An acronym for a group of fastidious Gram-negative organisms that are sometimes capable of causing endocarditis, and that may not grow in the standard amount of time that blood cultures are incubated (5 days). If you suspect that a patient has endocarditis due to a fastidious organism, you must request that the lab keep the blood culture for at least 2 weeks. Enriched media is also required for growth upon subculture, although they will grow in the blood culture broth. The HACEK organisms are: Hemophilus aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominus, Eikenella corrodens, and Kingella spp.
    herd immunity
    The immunity of a group or community (the herd). The resistance of a group to invasion and spread of an infectious agent is based upon the resistance to infection of a high proportion of individual members of the group. If the infectious agent can't find a susceptible host to infect, then an epidemic would die out. The Sabin vaccine took advantage of herd immunity to more or less eliminate polio from North America. The vaccine strain of the polio virus could infect other members of the household, even if they had not been vaccinated.
    host
    A person or other living animal, including birds and arthropods, that affords subsistence or lodgment to an infectious agent under natural (as opposed to experimental) conditions. Some protozoa and helminths pass successive stages in alternate hosts of different species. Hosts in which the parasite attains maturity or passes in sexual stage are primary or definitive hosts; those in which the parasite is in a larval or asexual state are secondary or intermediate hosts. A transport host is a carrier in which the organism remains alive but does not undergo development.
    immunization
    Immunization is a deliberate attempt to protect against a specific disease by innoculation of the respective microbe into the human or animal to be protected. The Chinese apparently immunized against smallpox by innoculation from the skin pox of a surviving patient as early as the 6th century. However, it was Edward Jenner in 1796 who conducted the first scientific experiments with cowpox, in order to confer protection against smallpox. This use of a similar virus, or attenuated virus, was a new innovation. It is now routine to use dead or attenuated organisms to immunize humans or animals. Cloned proteins may even be used, as with the current Hepatitis B vaccine. Indeed, live attenuated preparations are now considered somewhat dangerous, because of increasing numbers of immunocompromised people who might acquire overwhelming infection, even with an attenuated vaccine strain of the organism. However, live vaccines generally give excellent immunity, may infect other hosts, thus giving rise to herd immunity, and have allowed the complete elimination of one disease, smallpox, from the face of the earth. Eradication of other diseases may be possible via worldwide immunization efforts.

    References


    MMWR 43 (RR1), 1994. CDC General Recommendations on Immunization.


  2. MMWR 42 (RR4), 1993. Use of vaccines and immune globulins in persons with altered immunocompetence.


  3. MMWR 44(RR5), 1995. CDC Recommended Childhood Immunization Schedule, United States, 1995.

  4. Plotkin, S, and Mortimer, S. Vaccines. 2nd Edition, Saunders, 1995. A recent text discussing all available and experimental vaccines, plus an excellent history of vaccination.
    incidence rate
    A quotient (rate), with the number of new cases of a specified disease diagnosed or reported during a defined period of time as the numerator, and the number of persons in a stated population in which the cases occurred as the denominator. This is usually expressed as cases per 1,000 or 100,000 per annum. This rate may be expressed as age- or sex-specific or as specific for any other population characteristic or subdivison (see Morbidity rate and Prevalence rate).

    Attack rate, or case rate, is an incidence rate often used for particular groups, observed for limited periods and under special circumstances, as in an epidemic, usually expressed as percent (cases per 100). The secondary attack rate in communicable disease practice expresses the number of cases among familial or institutional contacts occurring within the accepted incubation period following exposure to a primary case, in relation to the total of determinable. Infection rate expresses the incidence of all infections, manifest and inapparent.


    intermediate (I)
    When the clinical microbiology laboratory indicates that an organism is intermediate in susceptibility to a particular anti-microbial, what they mean is that the infection caused by that particular organism may be inhibited by attainable concentrations of that particular drug, if higher dosages can be used or if the infection involves a body site where the antimicrobial can be physiologically concentrated (such as the urinary tract). It also serves as a no-man's land to prevent technical artifacts from causing major discrepancies in interpretation. Call the lab or your friendly infectious disease specialist for advice.
    Kirby-Bauer
    A modification of the original minimum inhibitory concentration (MIC) method, whereby a paper disk is used to diffuse a standardized amount of antimicrobial into agar plated with the microbial isolate. It generates what is called a breakpoint MIC, where standardized cutoff values break organisms into groups of susceptible (S), intermediate (I), or resistant (R).
    leukocyte esterase
    Esterase are produces by polymorphonuclear leukocytes. In a patient with pyuria (pus in the urine), a simple dipstick test may be used to determine the presence of leukocyte esterase. If positive, this greatly increases the liklihood that any organism isolated will be a true pathogen, and not a contaminant.
    minimum bacteriocidal concentration (MBC)
    The lowest concentration of an antimicrobial agent that kills 99.9 % of the test inoculum. The MBC is mainly used by infectious disease specialists in special cases, such as bacterial endocarditis or osteomyelitis, where cidal levels of antimicrobials are hard to achieve clinically.
    minimum inhibitory concentration (MIC)
    The lowest concentration of an antimicrobial agent that inhibits growth of a micro-organism. The test is performed by diluting the antimicrobial agent in broth or agar, then plating a standardized concentration of the organism. These agar or broth dilution tests are too cumbersome to perform in most clinical microbiology laboratories. The test most frequently used to estimate the MIC in most clinical laboratories is the Kirby-Bauer disk diffusion test, where paper disks containing a standardized concentration of anti-microbial are placed on a standard agar medium, and the zone of inhibition is measured. Automated machines may determine the MIC via broth microdilution. Few physicians, other than infectious disease specialists, are capable of correctly interpreting MICs, so the laboratory is obligated to interpret them to avoid risk of misinterpretation. They are usually labelled as susceptible (S), intermediate (I), and resistant (R) (see separate definitions for these classes).
    morbidity rate
    An incidence rate used to include all persons in the population under consideration who become clinically ill during the period of time stated. The population may be limited to a specific sex, age group or those with certain other characteristics.
    mortality rate
    A rate calculated in the same way as an incidence rate, using as a numerator the number of deaths occurring in the population during the stated period of time, usually a year. A total or crude mortality rate utilizes deaths from all causes, usually expressed as deaths per 1,000, while a disease-specific mortality rate includes only deaths due to one disease and is usually reported on the basis of 100,000 persons. The population base may be defined by sex, age or other characteristics. The mortality rate must not be confused with the case fatality rate.
    non-treponemal tests (for syphilis)
    These serologic tests are most useful for screening. They are very sensitive, but specificity is a problem. Patients with rheumatoid arthritis, systemic lupus, and other diseases may react positively. Such results must be confirmed by the more specifec treponemal tests for syphilis, before you tell the patient that they have syphilis!

    These tests take advantage of antibodies to a tissue lipids called cardiolipin. These antibodies are produced as an after-effect of treponemal infection. The most common tests are the Rapid Plasma Reagin card (RPR), and the Venereal Disease Research Laboratory test (VDRL). Both tests are quite similar. You have an example of the RPR test in your Supplemental Image Database.


    nosocomial infection
    An infection occurring in a patient in a hospital or other health care facility and in whom it was not present or incubating at the time of admission, or the residual of an infection acquired during a previous admission. Includes infections acquired in the hospital but appearing after discharge, and also such infections among the staff of the facility.
    opportunistic infection
    An infection with an organism that is not normally a pathogen for an immunocompetent host, e.g., Candida albicans. Such an opportunistic infection is a sign to evaluate the patient for immunodeficiency.
    prevalence rate
    A quotient (rate) obtained by using as the numerator the number of persons sick or portraying a certain condition in a stated population at a particular time (point prevalence), or during a stated period of time (period prevalence), regardless of when that illness or condition began, and as the denominator the number of persons in the population in which they occurred.
    prozone
    A condition of imbalance between the relative concentrations of antigen and antibody. For example, in the RPR test for syphilis, patients with a large antibody excess may have a negative test, even though they have large amounts of anti-treponemal antibody. In such a case where the patient is strongly suspected of having syphilis, the serum must be diluted and the test repeated.
    rejection criteria
    Specific rejection criteria for clinical specimens that are collected, transported or stored under improper conditions prior to receipt by the laboratory. For example, un-refrigerated urine cultures are routinely rejected, since the bacteria within multiply rapidly at room temperatures, invalidating results. Many sputum cultures are rejected after Gram-staining because they have large number of epithelial cells, suggesting mouth origin (i.e., spit), instead of an expectorated sputum.
    reservoir
    Any person, animal, arthropod, plant, soil or substance (or combination of these) in which an infectious agent normally lives and multiplies, on which it depends primarily for survival, and where it reproduces itself in such manner that it can be transmitted to a susceptible host.
    resistant
    When the clinical microbiology laboratory indicates that an organism is resistant (R) to a particular antimicrobial, what they mean is that the infection caused by that particular organism cannot be appropriately treated by achievable concentrations of that antimicrobial agent, or that resistance may be present despite the results of standardized susceptibility testing.
    Schlicter testing
    The lowest dilution of serum that kills 99.9% of the inoculum. Blood is drawn during the peak and trough of the antimicrobial being utilized, then the serum is diluted in broth and tested against the microbial isolate. This test is usually done only in tertiary centers, by infectious disease specialists, to treat difficult cases of endocarditis, osteomyelitis, or sepsis in an immunocompromised patient.
    selective media
    A medium that contains antibiotics, or other substances that inhibit the growth of certain classes of bacteria, in order to enhance the growth of the desired species. A good example would be the Thayer-Martin media used in the isolation of gonococci.
    Sodium polyanethol sulfonate (SPS)
    Most commercial blood culture systems contain SPS as an anticoagulant. SPS has several other important effects on the blood culture, however. It inactivates neutrophils and certain antibiotics, and precipitates fibrinogen and certain components of the complement cascade. These are all good effects, but it may also inhibit growth of certain organisms. These organisms include: Neisseria gonorrhoeae, Neisseria meningitidis, Gardnerella vaginalis, and Streptococcus pneumoniae. The effect can be neutralized by adding gelatin to the medium. You may want to suggest this to the lab if you have reason to suspect any of the above organisms as an etiologic agent in your patient's septic episode.
    susceptibility testing
    One of the methods mentioned in this keyword list, such as the Kirby-Bauer method, Schlicter testing, synergy testing, E test, MIC, or MBC. A direct test for beta-lactamase activity could also be considered a form of susceptibility testing. These are laboratory (in vitro) methods, designed to correlate with clinical in vivo activity. They are only guidelines. Individual patient considerations must be taken into account.
    susceptible (S)
    When the clinical microbiology laboratory indicates that an organism is susceptible (S) to a particular antimicrobial, what they mean is that the infection caused by that particular organism may be appropriately treated by standard doses of that particular antimicrobial.
    synergy testing
    A research method used to evaluate combinations of antimicrobial drugs. It is not utilized clinically, except in tertiary centers.
    Thayer-Martin media
    An agar medium containing antibiotics, useful in the isolation of Neisseria gonorrheae. Normally supplied as a biplate, with Thayer-Martin on one side and chocolate agar on the other. Due to the fastidious nature of the gonococcus, this culture medium is usually inoculated by the clinician at the bedside.
    transmission (of an infectious agent)
    Any mechanism by which an infectious agent is spread from a source or reservoir to a person. These mechanisms are:
    Direct Transmission
    Direct and essentially immediate transfer of infectious agents to a receptive portal of entry through which human or animal infection may take place. This may be by direct contact as by touching, biting, kissing or sexual intercourse, or by the direct projection (droplet spread) of droplet spray onto the conjunctiva or onto the mucous membranes of the eye, nose or mouth during sneezing, coughing, spitting, singing or talking (usually limited to a distance of about 1 meter or less).
    Indirect Transmission
    Vehicle-Borne
    Contaminated inanimate materials or object (fomites) such as toys, handkerchiefs, soiled clothes, bedding, cooking or eating utensils, surgical instruments or dressings (indirect contact); water, food, milk, biological products including bood, serum, plasma, tissues or organs; or any substance serving as an intermediate means by which an infectious agent is transported and introduced into a susceptible host through a suitable portal of entry. The agent may or may not have multiplied or developed in or on the vehicle before being transmitted.
    Vector-Borne
    (a) Mechanical: Includes simple mechanical carriage by a crawling or flying insect through soiling of its feet or proboscis, or by passage of organisms through its gastrointestinal tract. This does not require multiplication or development of the organism.
    (b) Biological: Propagation (multiplication), cyclic development, or a combination of these (cyclopropagative) is required before the arthropod can transmit the infective form of the agent to man. An incubation period (extrinsic) is required following infection before the arthropod becomes infective. The infectious agent may be passed vertically to succeeding generations (trans-ovarian transmission); trans-stadial transmission indicates its passage from one stage of life cycle to another, as nymph to adult. Transmission may be by injection of salivary gland fluid during biting, or by regurgitation or deposition on the skin of feces or vomitusl capable of penetrating through the bite wound or through an area of trauma from scratching or rubbing. This transmission is by an infected.non-vertebrate host and not simple mechanical carriage by a vector as a vehicle. However, an arthropod in either role is termed a vector.
    (c) Airborne: The dissemination of microbial aerosols to a suitable portal of entry, usually the respiratory tract. Microbial aerosols are suspensions of partially or wholly of microorganisms. They may remain suspended in the air for long periods of time, some retaining and others losing infectivity or virulence. Particles in the 1- to 5 micrometer range are easily drawn into the alveoli of the lungs and may be retained there. Not considered as airborne are droplets and other large particles which promptly settle out (see Direct Transmission, above).
    (d) Droplet nuclei: Usually the small residues which result from evaporation of fluid from droplets emitted by an infected host (see above). They also may be created purposely by a variety of atomizing devices, or accidentally as in microbiology laboratories or in abattoirs, rendering plants or autopsy rooms. They usually remain suspended in the air for long periods of time.
    (e) Dust: The small particles of widely varying size which may arise from soil (as, for example, fungus spores separated from dry soil by wind or mechanical agitation), clothes, bedding, or contaminated floors.

    treponemal tests (for syphilis)
    These serologic tests for syphilis use specific treponemal antigens. The test in the most common use is the fluorescent treponema antigen test (FTA). Cross reactivity may still occur in patients with rheumatologic diseases, but not with the frequency of non-treponemal tests.
    typhus nodule
    The characteristic histopathologic lesion seen in disease due to Rickettsiae spp. The lesion consists of a collection of chronic inflammatory cells surrounding a capillary whose endothelial cells contain rickettsial organisms.
    vaccination
    The common term for immunization. It derives from the Latin vacca, cow, since the original smallpox immunization was derived from cowpox, and vaccination consisted of passing the infection by scarification (scratching the skin) from cow to human.

    References


  5. MMWR 43 (RR1), 1994. CDC General Recommendations on Immunization.


  6. MMWR 42 (RR4), 1993. Use of vaccines and immune globulins in persons with altered immunocompetence.


  7. MMWR 44(RR5), 1995. CDC Recommended Childhood Immunization Schedule, United States, 1995.

  8. Plotkin, S, and Mortimer, S. Vaccines. 2nd Edition, Saunders, 1995. A recent text discussing all available and experimental vaccines, plus an excellent history of vaccination.
    zoonosis
    An infection or infectious disease transmissible under natural conditions from vertebrate animals to man. May be enzootic or epizootic (see Endemic and Epidemic).