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31-07-2010, 04:31 PM
Scientific classification (http://en.wikipedia.org/wiki/Biological_classification)
Kingdom: Bacteria (http://en.wikipedia.org/wiki/Bacteria)
Phylum : Actinobacteria (http://en.wikipedia.org/wiki/Actinobacteria)
Order: Actinomycetales (http://en.wikipedia.org/wiki/Actinomycetales)
Family: Corynebacteriaceae (http://en.wikipedia.org/wiki/Corynebacteriaceae)
Genus: Corynebacterium (http://en.wikipedia.org/wiki/Corynebacterium)
Species: C. diphtheriae

Classification//
Four subspecies are recognized: C. diphtheriae mitis, C. diphtheriae intermedius, C. diphtheriae gravis, and C. diphtheriae belfanti. The four subspecies differ slightly in their colonial morphology and biochemical properties such as the ability to ****bolize certain nutrients, but all may be toxigenic (and therefore cause diphtheria) or non-toxigenic.
Corynebacterium diphtheria //
Corynebacteria are Gram-positive, aerobic, nonmotile, rod-shaped bacteria classified as Actinobacteria. Corynebacteria are related phylogenetically to mycobacteria and actinomycetes. They do not form spores or branch as do the actinomycetes, but they have the characteristic of forming irregular, club-shaped or V-shaped arrangements in normal growth. They undergo snapping movements just after cell division, which brings them into characteristic forms resembling Chinese letters or palisades.
The genus Corynebacterium consists of a diverse group of bacteria including animal and plant pathogens, as well as saprophytes. Some corynebacteria are part of the normal flora of humans, finding a suitable niche in virtually every anatomic site, especially the skin and nares. The best known and most widely studied species is Corynebacterium diphtheriae, the causal agent of the disease diphtheria.Diphtheria is an upper respiratory tract illness characterized by sore throat, low fever, and an adherent membrane (called a pseudomembrane on the tonsils, pharynx, and/or nasal cavity. Diphtheria toxin produced by C. diphtheriae, can cause myocarditis, polyneuritis, and other systemic toxic effects. A milder form of diphtheria can be restricted to the skin.Diphtheria is a contagious disease spread by direct physical contact or breathing aerosolized secretions of infected individuals. Once quite common, diphtheria has largely been eradicated in developed nations through wide-spread use of the DPT vaccine. For example, in the U.S., between 1980 and 2004 there were 57 reported cases of diphtheria. However, it remains somewhat of a problem worldwide (3,978 reported cases to WHO in 2006) in the face of efforts to achieve global vaccination coverage.

Diphtheria is a serious disease, with fatality rates between 5% and 10%. In children under 5 years and adults over 40 years, the fatality rate may be as much as 20%. Outbreaks, although very rare, still occur worldwide, even in developed nations. Following the breakup of the former Soviet Union in the late 1980s, vaccination rates in the constituent countries fell so low that there was a surge in diphtheria cases. In 1991 there were 2,000 cases of diphtheria in the USSR. By 1998, according to Red Cross estimates, there were as many as 200,000 cases in the Commonwealth of Independent States, with 5,000 deaths.
History and Background //
No bacterial disease of humans has been as successfully studied as diphtheria. The etiology, mode of transmission, pathogenic mechanism and molecular basis of exotoxin structure, function, and action have been clearly established. Consequently, highly effective methods of treatment and prevention of diphtheria have been developed.The study of Corynebacterium diphtheriae traces closely the development of medical microbiology, immunology and molecular biology. Many contributions to these fields, as well as to our understanding of host-bacterial interactions, have been made studying diphtheria and the diphtheria toxin. Some of the milestones along this path are given below.




RESERVOIR//
Human carriers are the reservoir for C. diphtheriae, and are usually asymptomatic. In outbreaks, high percentages of children are found to be transient carriers.
symptoms of Diphtheria//
Diphtheria is a disease which mainly occurs in the autumn and winter season and it affects all age persons, but mostly found in children. Early symptoms of the disease are inflammation of throat and mild fever. It is rare among infants up to the age of six months. According to Ayurveda, diphtheria is the result of the vitiation of the kapha. Symptoms of Diphtheria may vary from person to person.
Some of the common symptoms of diphtheria are listed below:


The disease typically causes a bad sore throat.

Drooling (suggests airway obstruction is about to occur).

Mild fever and chills.

Bloody, watery drainage from nose.

Swollen glands

Feel weakness.

Fatigue.

High pulse rate.

A hallmark sign of this disease is a thick, gray covering which develops at the back of your throat, making it very difficult to breathe.

Diphtheria can also infect your skin. Bluish coloration of the skin may be caused by lack of oxygen.

Skin lesions can be seen in cutaneous diphtheria (usually seen in the tropics).

The infection also causes the lymph glands and tissue on both sides of the neck to swell to an unusually large size.

Children which get infected from diphtheria have symptoms that include


Nausea.

Vomiting.

Chills.

A high fever



Pathogenicity //
The pathogenicity of Corynebacterium diphtheriae includes two distinct phenomena:
1. Invasion of the local tissues of the throat, which requires colonization and subsequent bacterial proliferation. Little is known about the adherence mechanisms of C. diphtheriae, but the bacteria produce several types of pili. The diphtheria toxin, as well, may be involved in colonization of the throat.
2. Toxigenesis: bacterial production of the toxin. The diphtheria toxin causes the death eucaryotic cells and tissues by inhibition protein synthesis in the cells. Although the toxin is responsible for the lethal symptoms of the disease, the virulence of C. diphtheriae cannot be attributed to toxigenicity alone, since a distinct invasive phase apparently precedes toxigenesis. However, it has not been ruled out that the diphtheria toxin plays an essential role in the colonization process due to short-range effects at the colonization site.
DEATH//
The overall case-fatality ratefor diphtheria is 5%10%, with higher death rates (up to 20%) in persons <5 and >40 years of age. Thecase-fatality rate for diphtheria has changed very little during the last 50 years
COMPLICATIONS//
Most complications of diphtheria, including death, are attributable to effects of the toxin. The severity of the disease and complications are generally related to the extent of local disease. The toxin, when absorbed, affects organs and tissues distant from the site of invasion.The most frequent complications of diphtheria are myocarditis and neuritis:
Myocarditis may present as abnormal cardiac rhythms and can occur early in the course of the illness or weeks later, and can lead to heart failure. If myocarditis occurs early, it is often fatal.
Neuritis most often affects motor nerves and usually resolves completely. Paralysis of the soft palate is most frequent during the third week of illness. Eye muscles, limbs, and diaphragm paralysis can occur after the fifth week. Secondary pneumonia and respiratory failure may result from diaphragmatic paralysis.Other complications include otitis media and respiratory insufficiency due to airway obstruction, especially in infants.



CLINICAL FEATURES//
The incubation period of diphtheria is 25 days (range, 110 days). Disease can involve almost any mucous membrane. For clinical purposes, it is convenient to classify diphtheria into a number of manifestations, depending on the site of disease.
LABORATORY DIAGNOSIS//
Diagnosis is usually made based on the clinical presentation since it is imperative to begin presumptive therapy quickly.Culture of the lesion is done to confirm the diagnosis. It is critical to swab the pharyngeal area, especially any discolored areas, ulcerations, and tonsillar crypts. Culture medium containing tellurite is preferred because it provides a selective advantage for the growth of this organism. A blood agar plate is also inoculated for the detection of hemolytic streptococcus. If diphtheria bacilli are isolated, they must be tested for toxin production.Gram stain and Kenyon stain of material from the membrane itself can be helpful when trying to confirm the clinical diagnosis. The Gram stain may show multiple club-shaped forms which look like Chinese characters. Other Corynebacterium species ("diphtheroids") that can normally inhabit the throat may confuse the interpretation of direct stain. However, treatment should be started if clinical diphtheria is suggested, even in the absence of a diagnostic Gram stain.In the event that prior antibiotic therapy may have impeded a positive culture in a suspect diphtheria case, two sources of evidence may aid in presumptive diagnosis: (1) isolation of C. diphtheriae from culturing of close contacts, and/or (2) a low nonprotective diphtheria antibody titer in sera obtained prior to antitoxin administration (less than 0.1 I.U.). This is done by commercial laboratories and requires several days. To isolate C. diphtheriae from carriers, it is best to inoculate a L&ouml;fflers or Pais slant with the throat swab. After an incubation period of 1824 hours, growth from the slant is used to inoculate a medium containing tellurite.
Treatment//
If the health care provider thinks you have diphtheria, treatment should be started immediately, even before test results are available.
Diphtheria antitoxin is given as a shot into a muscle or through an IV (intravenous (http://www.nlm.nih.gov/medlineplus/ency/article/002383.htm) line). The infection is then treated with antibiotics, such as penicillin and erythromycin.
People with diphtheria may need to stay in the hospital while the antitoxin is being received. Other treatments may include:


Fluids by IV

Oxygen

Bed rest

Heart monitoring

Insertion of a breathing tube

Correction of airway blockages

Anyone who has come into contact with the infected person should receive an immunization or booster shots against diphtheria. Protective immunity (http://www.nlm.nih.gov/medlineplus/ency/article/000821.htm) lasts only 10 years from the time of vaccination, so it is important for adults to get a booster of tetanus-diphtheria (Td) vaccine every 10 years.
Those without symptoms who carry diphtheria should be treated with antibiotics.
ANTIBIOTICS//
Treatment is with erythromycin orally or by injection (40 mg/kg/day; maximum, 2 gm/day) for 14 days, or procaine penicillin G daily, intramuscularly (300,000 U/day for those weighing 10 kg or less and 600,000 U/day for those weighing more than 10 kg) for 14 days. The disease is usually not contagious 48 hours after antibiotics are instituted. Elimination of the organism should be ********ed by two consecutive negative cultures after therapy is completed.
TRANSMISSION//
Transmission is most often person-to-person spread from the respiratory tract. Rarely, transmission may occur from skin lesions or articles soiled with discharges from lesions of infected persons (fomites).
IMMUNOGENICITY AND VACCINE EFFICACY//
After a primary series of three properly spaced diphtheria toxoid doses in adults or four doses in infants, a protective level of antitoxin (defined as greater than 0.1 international units of antitoxin/ml) is reached in more than 95% of vaccine recipients. Diphtheria toxoid has been estimated to have a clinical efficacy of 97%.




PREVENTIVE MEASURES//
For close contacts, especially household contacts, a diphtheria booster, appropriate for age, should be given. Contacts should also receive antibioticsbenzathine penicillin G (600,000 units for persons younger than 6 years old and l,200,000 units for those 65years old and older) or a 7- to 10-day course of oral erythromycin, (40 mg/kg/day for children and 1 g/day for adults). For compliance reasons, if surveillance of contacts cannot be maintained, they should receive benzathine penicillin G. Identified carriers in the community should also receive antibiotics. Maintain close surveillance and begin antitoxin at the first signs of illness. Contacts of cutaneous diphtheria should be handled as above; however, if the strain is shown to be nontoxigenic, investigation of contacts can be discontinued.
















Corynebacterium








Corynebacterium







. demonstrating "Chinese letters" formations





Gram stain of Corynebacterium spp






Corynebacterium_diph



























Stained Corynebacterium cells. The "barred" appearance is due to the presence of polyphosphate inclusions called ****chromatic granules. Note also the characteristic "Chinese-letter" arrangement of cells















Corynebacterium diphtheriae colonies on blood agar. CDC.



SELECTED REFERENCES

CDC. Diphtheria, tetanus, and pertussis: Recommendations for vaccine use and other preventive measures. MMWR 1991;40(RR- 10):128.

CDC. Pertussis vaccination: use of acellular pertussis vaccines among infants and young children. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR

1997;46(RR-7):125.

CDC. Update: Diphtheria Epidemic Newly Independent States

of the Former Soviet Union, January 1995March 1996. MMWR

1996;45:6937.

CDC. Toxigenic Corynebacterium diphtheriae Northern Plains

Indian community, AugustOctober 1996. MMWR 1993;42:8401,

847.

Chen RT, Broome CV,Weinstein RA,Weaver R, Tsai TF. Diphtheria

in the United States, 197181. Am J Public Health 1985;75: 13937.

Farizo KM, Strebel PM, Chen RT, Kimbler A, Cleary TJ, Cochi

SL. Fatal respiratory disease due to Corynebacterium diphtheria:

case report and review of guidelines for management, investigation,

and control. Clin Infect Dis 1993;16(1):5968.

Hardy IRB. Diphtheria. In: Evans AS and Brachman PS, eds.

Bacterial Infections of Humans. Epidemiology and Control. 3rd ed.

New York, NY: Plenum Medical Book Company; 1998:25368.

Orenstein WA, Hadler S,Wharton M. Trends in vaccine-preventable diseases. Semin Pediatr Infect Dis 1997;8:2333.

Vitek CR and Wharton M. Diphtheria in the former Soviet Union:

Reemergence of a pandemic disease. Emerg Infect Dis

1998;4:53950.

Wharton M and Vitek CR. Diphtheria. In Plotkin SA, Orenstein

WA, eds. Vaccines. 4th ed. Philadelphia, PA: Saunders, 2003:21128.


















References


^ (http://en.wikipedia.org/wiki/Corynebacterium_diphtheriae#cite_ref-0) Microbiology: A Human Perspective. Fourth edition. McGraw Hill


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http://www.textbookofbacteriology.net/diphtheria.html



http://www.textbookofbacteriology.net/diphtheria_2.html (http://www.textbookofbacteriology.net/diphtheria_2.html)





http://en.wikipedia.org/wiki/Corynebacterium_diphtheriae (http://en.wikipedia.org/wiki/Corynebacterium_diphtheriae)





http://www.drlera.com/bacterial_diseases/diphtheria_.htm