Botulism is an acute neurologic disorder with potentially life-threatening neuroparalysis that is caused by a neurotoxin produced by Clostridium botulinum (CB). The toxin binds irreversibly to the presynaptic membranes of peripheral neuromuscular and autonomic nerve junctions. Toxin binding blocks acetylcholine release, resulting in weakness, flaccid paralysis, and (often) respiratory arrest. Cure occurs following sprouting of new nerve terminals.
The 3 main clinical presentations of botulism include infant, food-borne, and wound. Additionally, because of the potency of the toxin, the possibility of botulism as a bioterrorism agent or biological weapon is a great concern.
Infant botulism (IB) arises from ingested botulism spores that germinate in the intestine and produce toxin. These spores typically come from bee honey or the environment. Most infants fully recover with supportive treatment; the infant mortality rate is less than 1%. Improperly canned or home-prepared foods are common sources of the toxin that can result in food-borne botulism (FBB). Wound botulism (WB) results from contamination of the wound with toxin-producing CB. FBB and WB occur predominantly in adults and are the focus of this article.
CB is an anaerobic gram-positive rod that survives in soil and marine sediment by forming spores. Under anaerobic conditions that permit germination, it synthesizes and releases a potent exotoxin. Microbiologically, the organism stains gram-positive in cultures less than 18 hours old. The organism may stain gram-negative after 18 hours of incubation, potentially complicating attempts at diagnosis. On a molecular weight basis, botulinum toxins are the most potent toxins known.
Eight antigenically distinct CB toxins are known, including A, B, C (alpha), C (beta), D, E, F, and G. Each strain of CB is limited to producing a single toxin type. Types A, B, E, and (rarely) F cause human disease. Toxins A and B are the most potent, and the consumption of small amounts of food contaminated with them has resulted in full-blown disease. During the last 20 years, toxin A has been the most frequent cause of food-borne outbreaks; toxins B and E follow in frequency. In 15% of CB outbreaks, the toxin type is not determined. Toxins C and D cause disease in a variety of animals. Type G toxin has been associated with sudden death but not with neuroparalytic illness. It was isolated from autopsy material from 5 patients in Switzerland in 1977.
Pathophysiology
The mechanism of action involves toxin-mediated blockade of neuromuscular transmission in cholinergic nerve fibers. This is accomplished by either inhibiting acetylcholine release at the presynaptic clefts of the myoneural junctions or by binding acetylcholine itself. Toxins are absorbed from the stomach and small intestine where they are not denatured by digestive enzymes. Subsequently, they are hematogenously disseminated and block neuromuscular transmission in cholinergic nerve fibers. The nervous, gastrointestinal, endocrine, and metabolic systems are predominantly affected. Because the motor end plate responds to acetylcholine, botulinum toxin ingestion results in hypotonia that manifests as descending symmetric flaccid paralysis and is usually associated with gastrointestinal symptoms of nausea, vomiting, and diarrhea. Cranial nerves are affected early in the course of disease. Later complications include paralytic ileus, severe constipation, and urinary retention.
WB results when wounds are contaminated with CB spores. It has occurred (1) after traumatic injury that involved soil contamination, (2) among injection drug users, particularly those who use black-tar heroin, and (3) after cesarean delivery. The wound may appear deceptively benign. Traumatized and devitalized tissue provides an anaerobic medium for the spores to germinate into vegetative organisms and produce neurotoxin, which then disseminates hematogenously. The nervous, endocrine, and metabolic systems are predominantly affected. Symptoms develop after an incubation period of 4-14 days, with a mean of 10 days. The clinical symptoms of WB are similar to those of FBB except that gastrointestinal symptoms (including nausea, vomiting, diarrhea) are uncommon.
Frequency
United States
The frequency is 0.034 cases out of 100,000 population, of which nearly 75% are associated with IB.
FBB incidences total 24 cases per year. WB incidences total 3 cases per year and 3 cases per year from the young adult cohort (aged 18-25 y). IB incidences total 71 cases per year, with a mean age of 3 months. FBB incidence totals 24 cases per year drawn from all age cohorts.
Toxin A is found predominantly west of the Mississippi River. Toxin B is found most commonly in the eastern United States. Toxin E is found in northern latitudes, such as the Pacific Northwest, the Great Lakes region, and Alaska. The native peoples have some of the highest rates of botulism in the world. Toxin E outbreaks frequently are associated with fish products.
International
Human botulism is found worldwide. Spores from organisms producing type A or B toxins are distributed widely in the soil and have been found throughout the world. Toxin type B commonly is found in Europe. Toxin G originally was isolated in Switzerland.
Mortality/Morbidity
Mortality rates vary according to age of the patient and the type of botulism observed. In FBB, a 25% mortality rate exists overall; however, the rate is 10% in patients younger than 20 years. In WB, the mortality rate varies (15-17%); in IB, the mortality rate usually is less than 1%.
The recovery period from botulism often is quite long (30-100 d). Some patients demonstrate residual weakness or autonomic dysfunction for 1 year after the onset of the illness. However, full neurologic recovery is usual. Permanent deficits may occur in those who sustain significant hypoxic insults.
Sex
Males present more frequently with WB than females. Males and females present with FBB in equal numbers.
Age
FBB and WB predominately occur in adults.
Read more HERE
Showing posts with label Infectious Disease. Show all posts
Showing posts with label Infectious Disease. Show all posts
Friday, 1 August 2008
Tuesday, 29 July 2008
Cholera
The word cholera is derived from a Greek term that means "flow of bile." Cholera is caused by Vibrio cholerae, the most feared epidemic diarrheal disease because of its severity. Dehydration and death can occur within hours of infection.
Robert Koch discovered V cholerae in 1883 during an outbreak in Egypt. The organism is a comma-shaped, gram-negative aerobic bacillus whose size varies from 1-3 µm in length by 0.5-0.8 µm in diameter. Its antigenic structure consists of a flagellar H antigen and a somatic O antigen. The differentiation of the latter allows for separation into pathogenic and nonpathogenic strains. V cholerae O1 and V cholerae O139 are associated with epidemic cholera. V cholerae O1 is classified into 2 major biotypes: classic and El Tor. Currently, El Tor is the predominant cholera pathogen. Organisms in both biotypes are subdivided into serotypes according to the structure of the O antigen, as follows:
Serotype Inaba - O antigens A and C
Serotype Ogawa - O antigens A and B
Serotype Hikojima - O antigens A, B, and C
Pathophysiology
The infectious dose of bacteria required to cause clinical disease varies by the mode of administration. If ingested with water, the infectious dose is 103-106 organisms. When ingested with food, fewer organisms (102-104 organisms) are required to produce disease.
The use of antacids, histamine receptor blockers, and proton pump inhibitors increases the risk of cholera infection and predisposes patients to more severe disease as a result of reduced gastric acidity. The same applies to patients with chronic gastritis secondary to Helicobacter pylori infection or those who have undergone a gastrectomy.
V cholerae O1 and V cholerae O139 cause clinical disease by producing an enterotoxin that promotes the secretion of fluid and electrolytes into the lumen of the small intestine. The enterotoxin is a protein molecule composed of 5 B subunits and 2 A subunits. The B subunits are responsible for binding to a ganglioside (monosialosyl ganglioside, GM1) receptor located on the surface of the cells that line the intestinal mucosa.
The activation of the A1 subunit by adenylate cyclase is responsible for the net increase in cyclic adenosine monophosphate (cAMP). cAMP blocks the absorption of sodium and chloride by the microvilli and promotes the secretion of chloride and water by the crypt cells. The result is watery diarrhea with electrolyte concentrations isotonic to those of plasma.
Fluid loss originates in the duodenum and upper jejunum; the ileum is less affected. The colon is usually in a state of absorption because it is relatively insensitive to the toxin. However, the large volume of fluid produced in the upper intestine overwhelms the absorptive capacity of the lower bowel, resulting in severe diarrhea.
The enterotoxin acts locally and does not invade the intestinal wall. As a result, few neutrophils are found in the stool.
Frequency
United States
Among the millions of Americans who travel to endemic areas in foreign countries, only 42 imported cases of cholera were reported from 1965-1991. However, in August 1986, 4 cases of cholera were acquired in Louisiana and 1 case was acquired in Florida. These patients were hospitalized with severe diarrhea and had stool cultures that yielded toxigenic V cholerae O1 Inaba. Although the vehicle of transmission was not specifically identified, the patients had consumed seafood within 5 days prior to symptom onset. Toxigenic V cholerae O1 El Tor Inaba appears to have an environmental reservoir on the US Gulf Coast.
Sixty-one cases of cholera were reported from January 1, 1995, through December 31, 2000, in 18 states and 2 US territories. Thirty-seven were travel-associated cases; the other 24 cases were acquired in the United States.1 Individuals living in the United States most often acquire cholera through travel to cholera-endemic areas or through consumption of undercooked seafood from the Gulf Coast or foreign waters.
In 2005, 12 cases were reported to the World Health Organization (WHO) and, of these, 8 were imported.
International
Since 1817, 7 cholera pandemics have occurred. The first 6 occurred from 1817-1923 and were probably the result of V cholerae O1 of the classic biotype. The pandemics originated in Asia, with subsequent spread to Europe and the Americas.
The seventh pandemic was caused by V cholerae O1 El Tor, which was first isolated in Egypt in 1905. The pandemic originated from the Celebes Islands, Indonesia, in 1961; this pandemic affected more countries and continents than the previous 6 pandemics. The last extension of this pandemic was into Latin America. The total number of cases officially reported from 1997 through March 26, 1998, was 120,867; 89% of these cases were reported in Africa.
In 2002, all regions of the world continued to report cholera caused by V cholerae O1 El Tor; that year, 142,311 cases and 4564 deaths were reported to the WHO by 52 countries. Compared with 2001, the number of reported cases almost doubled.
Between 2002 and 2004, the number of cases reported to the WHO decreased worldwide. In 2005, however, the number reported increased 30% to a total of 131,943 cases in 52 countries.
In October 1992, an epidemic of cholera emerged from Madras, India, as a result of a new serogroup, O139 (also known as Bengal). This Bengal strain has now spread throughout Bangladesh and India and into neighboring countries in Asia. Some experts regard this as an eighth pandemic. Thus far, 11 countries in Southeast Asia have reported isolation of this Vibrio serogroup.
Mortality/Morbidity
If untreated, the disease rapidly results in dehydration and can result in death in more than 50% of infected individuals. The mortality rate is increased in pregnant women and children.
Age
People of all ages are susceptible, although infants are protected through maternally transmitted antibodies during breastfeeding. An attack of the classic biotype of V cholerae usually protects against recurrent infection by either biotype, but El Tor cholera does not protect against further attacks.
Read further HERE
Robert Koch discovered V cholerae in 1883 during an outbreak in Egypt. The organism is a comma-shaped, gram-negative aerobic bacillus whose size varies from 1-3 µm in length by 0.5-0.8 µm in diameter. Its antigenic structure consists of a flagellar H antigen and a somatic O antigen. The differentiation of the latter allows for separation into pathogenic and nonpathogenic strains. V cholerae O1 and V cholerae O139 are associated with epidemic cholera. V cholerae O1 is classified into 2 major biotypes: classic and El Tor. Currently, El Tor is the predominant cholera pathogen. Organisms in both biotypes are subdivided into serotypes according to the structure of the O antigen, as follows:
Serotype Inaba - O antigens A and C
Serotype Ogawa - O antigens A and B
Serotype Hikojima - O antigens A, B, and C
Pathophysiology
The infectious dose of bacteria required to cause clinical disease varies by the mode of administration. If ingested with water, the infectious dose is 103-106 organisms. When ingested with food, fewer organisms (102-104 organisms) are required to produce disease.
The use of antacids, histamine receptor blockers, and proton pump inhibitors increases the risk of cholera infection and predisposes patients to more severe disease as a result of reduced gastric acidity. The same applies to patients with chronic gastritis secondary to Helicobacter pylori infection or those who have undergone a gastrectomy.
V cholerae O1 and V cholerae O139 cause clinical disease by producing an enterotoxin that promotes the secretion of fluid and electrolytes into the lumen of the small intestine. The enterotoxin is a protein molecule composed of 5 B subunits and 2 A subunits. The B subunits are responsible for binding to a ganglioside (monosialosyl ganglioside, GM1) receptor located on the surface of the cells that line the intestinal mucosa.
The activation of the A1 subunit by adenylate cyclase is responsible for the net increase in cyclic adenosine monophosphate (cAMP). cAMP blocks the absorption of sodium and chloride by the microvilli and promotes the secretion of chloride and water by the crypt cells. The result is watery diarrhea with electrolyte concentrations isotonic to those of plasma.
Fluid loss originates in the duodenum and upper jejunum; the ileum is less affected. The colon is usually in a state of absorption because it is relatively insensitive to the toxin. However, the large volume of fluid produced in the upper intestine overwhelms the absorptive capacity of the lower bowel, resulting in severe diarrhea.
The enterotoxin acts locally and does not invade the intestinal wall. As a result, few neutrophils are found in the stool.
Frequency
United States
Among the millions of Americans who travel to endemic areas in foreign countries, only 42 imported cases of cholera were reported from 1965-1991. However, in August 1986, 4 cases of cholera were acquired in Louisiana and 1 case was acquired in Florida. These patients were hospitalized with severe diarrhea and had stool cultures that yielded toxigenic V cholerae O1 Inaba. Although the vehicle of transmission was not specifically identified, the patients had consumed seafood within 5 days prior to symptom onset. Toxigenic V cholerae O1 El Tor Inaba appears to have an environmental reservoir on the US Gulf Coast.
Sixty-one cases of cholera were reported from January 1, 1995, through December 31, 2000, in 18 states and 2 US territories. Thirty-seven were travel-associated cases; the other 24 cases were acquired in the United States.1 Individuals living in the United States most often acquire cholera through travel to cholera-endemic areas or through consumption of undercooked seafood from the Gulf Coast or foreign waters.
In 2005, 12 cases were reported to the World Health Organization (WHO) and, of these, 8 were imported.
International
Since 1817, 7 cholera pandemics have occurred. The first 6 occurred from 1817-1923 and were probably the result of V cholerae O1 of the classic biotype. The pandemics originated in Asia, with subsequent spread to Europe and the Americas.
The seventh pandemic was caused by V cholerae O1 El Tor, which was first isolated in Egypt in 1905. The pandemic originated from the Celebes Islands, Indonesia, in 1961; this pandemic affected more countries and continents than the previous 6 pandemics. The last extension of this pandemic was into Latin America. The total number of cases officially reported from 1997 through March 26, 1998, was 120,867; 89% of these cases were reported in Africa.
In 2002, all regions of the world continued to report cholera caused by V cholerae O1 El Tor; that year, 142,311 cases and 4564 deaths were reported to the WHO by 52 countries. Compared with 2001, the number of reported cases almost doubled.
Between 2002 and 2004, the number of cases reported to the WHO decreased worldwide. In 2005, however, the number reported increased 30% to a total of 131,943 cases in 52 countries.
In October 1992, an epidemic of cholera emerged from Madras, India, as a result of a new serogroup, O139 (also known as Bengal). This Bengal strain has now spread throughout Bangladesh and India and into neighboring countries in Asia. Some experts regard this as an eighth pandemic. Thus far, 11 countries in Southeast Asia have reported isolation of this Vibrio serogroup.
Mortality/Morbidity
If untreated, the disease rapidly results in dehydration and can result in death in more than 50% of infected individuals. The mortality rate is increased in pregnant women and children.
Age
People of all ages are susceptible, although infants are protected through maternally transmitted antibodies during breastfeeding. An attack of the classic biotype of V cholerae usually protects against recurrent infection by either biotype, but El Tor cholera does not protect against further attacks.
Read further HERE
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