2. Epidemiology: some basic concepts and definitions
Virulence can be defined as a measure of the severity of a disease caused The relationships between infection and disease are frequently dynamic in nature. Here we examine the evolution of infectious disease in empirical and the evolution of pathogen virulence both in theoretical and experimental investigations. . Our goal is to understand the specific network properties that cause relationship between network heterogeneity and fixation probability for . analysis of host adaptation and its relationship with virulence in. Cucumber mosaic . infectivity but not of host-associated differential accumulation, and suggest that A major goal of our work was to analyze the relationship be- tween virus.
This means it is relative to a time, a place and a population all of which, technically, should be precisely specified but often aren't. Two cases of a cold aren't an epidemic but two cases of rabies in the same place might be one case is never an epidemic, however. When something is called an epidemic might differ between two health officials and it is a plastic word that is loaded with other meanings so is liable to be manipulated in either direction.
Epidemics refer to human populations, strictly speaking it comes from Greek roots, meaning "upon the people". The same thing in animals is an epizootic. The technical word for this in birds is an epornithic, but in all the things I've read bout H5N1 in birds I've never seen this word used.
A pandemic crosses many international borders so that it involves large portions of the global population although not necessarily all of it. Log in to post comments By revere on 13 Jun permalink Randy: I'm sure someone has done it and maybe a reader who follows this can tell us who and where.
Log in to post comments By revere on 13 Jun permalink Thanks again, Revere - that did it. His most recent post explores implications of one possible scenario while pointing out that no one knows which scenario will actually come to pass, if any. Log in to post comments By name not verified on 13 Jun permalink Thank you very much, Revere, for this very helpful post.
These distinctions are something I've been wondering about for a while, and it doesn't help that these terms are often used incorrectly or interchangeably. I learn something valuable every day that I read your blog.
I think its starting to weight in on people outside of the blog as to the enormity of what could happen. Thi s request was made as the wife of a VP at a brokerage firm joined my just the facts email list. She read what was being posted and then started printing it off for her husband to read when he got home. I got the call today for the "economics" question.
I only deal with actualities when they happen. On the other hand predictives I am really big into.
My ex-commander once told me that if you prepare for the worst case you were just that If something happens you didnt think of, you were underprepared. If something happens that is bigger than the worst case projected, you are just screwed. Revere, I say again I wish you would prepare. You are going to be needed to balance things if it comes.
The adaptive evolution of virulence: a review of theoretical predictions and empirical tests
Log in to post comments By M. Randolph Kruger not verified on 13 Jun permalink Dr Gleeson's "moderate" scenario, by the way, is based on a pandemic far less severe thanas are the scenarios being used by many planners. Worst case is downright paralyzing.
Log in to post comments By Name not verified on 13 Jun permalink Reveres, Is it my computer settings or are the letters and lines squished together on this blog? It doesn't appear the same near the top with the wording under "profiles" or "recent posts" I enjoy reading and learning from reading your posts. On this site, I will have to make sure I am very rested and very awake to unscramble the lines.
I do not want to misinterpret what I am reading. Log in to post comments By Floridagirl not verified on 13 Jun permalink Floridagirl: What browser are you using? Older versions of Internet Explorere IE seem to be having a problem with this and other sites, too.
You'll get used to it fast and like it a lot more. Yo can import allyour IE bookmarks quickly and be ready to go in a flash. If you are not using IE, let me know what you are using and I'll try to solve your problem with some help from the hivemind and Sb tech support. Log in to post comments By revere on 13 Jun permalink I totally agree with the comment about the 'planning scenarios' that planners are using. In my interview last week with Dr. By Healthbizz not verified on 13 Jun permalink Reveres, If you don't mind my asking Why do you choose not to prepare?
Is it because you believe the likelihood is so remote that you do not? I am basing this question on MRK alluding to this. Possibly it was covered earlier in a post I missed?
Log in to post comments By Scorsbee not verified on 14 Jun permalink Scorsbee: We do prepare but we spend all our energy where we think it is invested best, at the community level. We are public health people and those are the terms we think in. We just haven't done it on the individual level.
We could have prescribed Tamiflu for ourselves but we had ethical qualms about it since we knew it would be rationed and we believed we should take whatever share the community eventually decided we should get. Everybody copes in different ways. Some people do individual prepping. We do community prepping. I have downloaded firefox and made you the home page. I cannot get rid of IE. I sometimes work form home and many of my programs rely on IE But, this is a solution, and I thank you for it.
To determine the relative infectivity of these 2 routes, an infectivity titration of a standard challenge pool of virulent HAV was performed in tamarins and chimpanzees. In both species, 1 oral dose of HAV was equivalent to These findings have relevance for attempts to develop live, attenuated HAV vaccines that can be administered orally.
HepatitisA virus HAVa pathogen that is transmitted by the fecal-oral route, continues to have significant impact on human health worldwide. Effective inactivated hepatitisA vaccines have been licensed, but an orally administered, live, attenuated vaccine would bemore practical for use in developing countries.
Attempts to develop such vaccines have not been successful, however, and the only licensed in China live, attenuated hepatitis A vaccine must be administered by injection [ 1 ]. This and other candidate live, attenuated hepatitisA vaccines have required parenteral administration because of difficulties in achieving consistent infection by the oral route with the titers of virus available from cell culture.
The purpose of the present study was to characterize further the biology of HAV infection by determining the relative infectivity of a wild-type HAV strain when administered by the oral versus the intravenous iv route. The relationship between the infectious dose of virus and markers of infection was also studied.
Materials and Methods Animals. This study was performed with tamarins Saguinus mystax and chimpanzees Pan troglodytes because previous studies demonstrated comparable sensitivity of these 2 species to iv infection with HAV [ 2 ]. Eighteen wild-caught tamarins and 10 domestically raised chimpanzees were housed at Bioqual Rockville, MD.
Blood samples were obtained weekly, and serum was tested for the following liver enzyme activities: The tests were performedwith commercial reagents atMetpath Rockville, MD. Although the results obtained for the 3 enzymes paralleled each other in both species, tamarins were evaluated with the ICD test and chimpanzees were evaluatedwith the ALT test because of greater respective sensitivity.
Tominimize the number of animals used, chimpanzees and tamarins thatwere not infectedwith 1 dose of HAV were reinoculated with a larger dose and reevaluated.
The SD strain of HAV was recovered from a naval recruit, 1 of persons who contracted hepatitis A from a cook who prepared salads and desserts in a navy galley during the prodromal period of his HAV infection [ 3 ].
Bacterial Pathogenesis - Medical Microbiology - NCBI Bookshelf
The inoculum was free of other viruses, as determined by inoculation of primary African green monkey kidney cells [ 4 ] and by electron microscopy authors' unpublished data.
Although it is difficult to comprehend the mechanisms of all the cell responses and the myriad sequelae of the cell mediators released rather indiscriminately in the host following exposure to endotoxin, it does seem clear that the host cellular response to endotoxin, rather than a direct toxic effect of endotoxin, plays the major role in causing tissue damage Fig.
Detection of Endotoxin in Medical Solutions Endotoxin is omnipresent in the environment. It is found in most deionized-water lines in hospitals and laboratories, for example, and affects virtually every biologic assay system ever examined. It tends to be a scapegoat for all biologic problems encountered in the laboratory, and, many times, this reputation is deserved. Because of its pyrogenic and destructive properties, extreme care must be taken to avoid exposing patients to medical solutions containing endotoxin.
Even though all supplies should be sterile, solutions for intravenous administration can become contaminated with endotoxin-containing bacteria after sterilization as a result of improper handling. Furthermore, water used in the preparation of such solutions must be filtered through ion exchange resins to remove endotoxin, because it is not removed by either autoclave sterilization or filtration through bacterial membrane filters.
If endotoxin-containing solutions were used in such medical procedures as renal dialysis, heart bypass machines, blood transfusions, or surgical lavage, the patient would suffer immediate fever accompanied by a rapid and possibly lethal alterations in blood pressure.
Solutions for human or veterinary use are prepared under carefully controlled conditions to ensure sterility and to remove endotoxin. Representative samples of every manufacturing batch are checked for endotoxin by one of two procedures: The rabbit pyrogenicity test is based on the exquisite sensitivity of rabbits to the pyrogenic effects of endotoxin.
A sample of the solution to be tested usually is injected intravenously into the ear veins of adult rabbits while the rectal temperature of the animal is monitored. Careful monitoring of the temperature responses provides a sensitive and reliable indicator of the presence of endotoxin and, importantly, one measure of the safety of the solution for use in patients. The Limulus lysate test is more common and less expensive. It is so sensitive, however, that trace quantities of endotoxin in regular deionized water often obscure the results.
It can be used for rapid detection of certain Gram-negative infections e. Test kits are commercially available. The amebocyte is the sole phagocytic immune cell of the horseshoe crab, and the gelation reaction is believed to be involved in sequestering invading Gram-negative bacteria. Exotoxins Exotoxins, unlike the lipopolysaccharide endotoxin, are protein toxins released from viable bacteria.
They form a class of poisons that is among the most potent, per unit weight, of all toxic substances. Most of the higher molecular-sized exotoxin proteins are heat labile; however, numerous low molecular-sized exotoxins are heat-stable peptides. Unlike endotoxin, which is a structural component of all Gram-negative cells, exotoxins are produced by some members of both Gram-positive and Gram-negative genera.
The functions of these exotoxins for the bacteria are usually unknown, and the genes for most can be deleted with no noticeable effect on bacterial growth. In contrast to the extensive systemic and immune-system effects of endotoxin on the host, the site of action of most exotoxins is more localized and is confined to particular cell types or cell receptors.
Tetanus toxin, for example, affects only internuncial neurons. In general, exotoxins are excellent antigens that elicit specific antibodies called antitoxins. Not all antibodies to exotoxins are protective, but some react with important binding sites or enzymatic sites on the exotoxin, resulting in complete inhibition of the toxic activity i. Exotoxins can be grouped into several categories e. Neurotoxins are best exemplified by the toxins produced by Clostridium spp.
This potent neurotoxin acts on motor neurons by preventing the release of acetylcholine at the myoneural junctions, thereby preventing muscle excitation and producing flaccid paralysis.
The cytotoxins constitute a larger, more heterogeneous grouping with a wide array of host cell specificities and toxic manifestations. One cytotoxin is diphtheria toxin, which is produced by Corynebacterium diphtheriae. This cytotoxin inhibits protein synthesis in many cell types by catalyzing the ADP-ribosylation of elongation factor II, which blocks elongation of the growing peptide chain.
Enterotoxins stimulate hypersecretion of water and electrolytes from the intestinal epithelium and thus produce watery diarrhea. Some enterotoxins are cytotoxic e. Enterotoxins also can disturb normal smooth muscle contraction, causing abdominal cramping and decrease transit time for water absorption in the intestine. Neither pathogen invades the body in substantial numbers, except in the case of E.
Importantly, cholera toxin and E. In contrast, the organisms responsible for shigellosis Shigella dysenteriae, S. Despite causing extensive ulceration of the mucosa, the pathogens rarely enter the bloodstream. The Shiga enterotoxin produced by Shigella species and the Shiga-like enterotoxin elaborated by many isolates of E.
It is not clear how this cytotoxic enterotoxin causes hypersecretion of water and electrolytes from the intestinal epithelium. These enterotoxins differ from those secreted by V. The latter enterotoxins cause no structural damage to cells, and are described as cytotonic. Siderophores Both animals and bacteria require iron for metabolism and growth, and the control of this limited resource is often used as a tactic in the conflict between pathogen and host.
Although blood is a rich source of iron, this iron is not readily available to bacteria since it is not free in solution. Most of the iron in blood is bound either to hemoglobin in erythrocytes or to transferrin in plasma. Similarly, the iron in milk and other secretions e. Some bacteria express receptors for eukoyotic iron-binding proteins e. Via these specialized receptors iron acquisition is facilitated, providing the esssential element for bacterial growth. Other bacteria have evolved elaborate mechanisms to extract the iron from host proteins Fig.
Siderophores are substances produced by many bacteria and some plants to capture iron from the host. The absence of iron triggers transcription of the genes coding for the enzymes that synthesize siderophores, as well as for a set of surface protein receptors that recognize siderophores carrying bound iron.
The binding constants of the siderophores for iron are so high that even iron bound to transferrin and lactoferrin is confiscated and taken up by the bacterial cells.
An example of a bacterial siderophore is enterochelin, which is produced by Escherichia and Salmonella species. Classic experiments have demonstrated that Salmonella mutants that have lost the capacity to synthesize enterochelin lose virulence in an assay of lethality in mice.
Injection of purified enterochelin along with the Salmonella mutants restores virulence to the bacteria.