Vibrio cholerae, also known as V. cholerae, is a bacterium that is associated with cholera. It can cause an acute illness leading to severe diarrhea. This results to dehydration, which is very detrimental to human health. This is because it can cause the demise of an individual that is affected within a very short while. It is a gram negative bacterium (Faruque & Nair, 2008, p 9). Vibrio cholerae are comma-shaped, and they have a flagellum at one end. A flagellum is a protrusion at one end of a cell body. The main function of the flagellum is to help the cell in locomotion. It also acts as a sensory organ. It is also facultatively anaerobic. The V. cholerae can be observed in two categories. These are: Vibrio cholerae Serogroup 01 and Vibrio cholerae serogroup non-01. The former is the most common cause of cholera. There are many species of V. Cholerae that belong to the later. These species do not cause diarrhea apart from Vibrio cholerae Serogroup 01 (Schoenstadt, 2012, para 2).
Vibrio cholerae is a lethal organism to human beings. This organism is lethal because it causes many deaths across the world. The bacteria kill many people especially those who live in poor conditions. People in slums and displaced persons are at a high risk of contracting the disease. In addition, poor basic infrastructure also increases the risk of the disease. Across the world, there are an approximated 3 5 million people who are infected by V. cholerae. Out of these, about 100,000-120,000 people will die from the illness (WHO, 2012 para 1). The disease is rare in the industrialized nations. However, the rest of the nations still experience cholera pandemics. Since the year 1817, only 7 cholera pandemics have occurred.
In America, there are rare cases of cholera if at all they are there. The bacteria are commonly found in the Ganges delta of India. It is also common in Bangladesh. Currently, there is an ongoing pandemic of the bacteria across Africa, Asia and Latin America. These pandemics have been reported within the last forty years. Of these pandemics, 80 per cent were reported in Africa (Schoenstadt, 2012 para 3-4).
The following is an image of Vibrio cholerae:
Source: Thaker, (2012 para, 1).
Mechanisms of Pathogenesis
The Vibrio cholerae pathogen is associated with the disease cholera as previously mentioned. The disease can be in a mild form or it can be asymptomatic. There are also severe forms of cholera that cause serious diarrhea and death.
Cholera is a disease that is very virulent. It can affect individuals across all ages, and this includes children and adults. This disease causes death within a very short time. Symptoms are developing depending on the severity of the disease. Severe forms of the disease will hardly show any symptoms. The bacteria can live within the human body for close to a week before death occurs, but no signs will be seen. In fact, 75 per cent of the people who are infected by the disease do not show any signs. In case of any symptoms, 80% of the people will show mild signs or they will show moderate symptoms. The main symptoms of cholera are diarrhea and dehydration. The diarrhea can be watery and profuse. Other symptoms that are specific to cholera include muscle cramps and vomiting. In addition, a change is observed in the appearance of the stool. The stool appears greyish in color, and it has some mucus. In addition, the stool characteristically becomes rice- water . Watery diarrhea follows suit. The diarrhea is usually painless. As fluid is lost from the body through vomiting and diarrhea, the person becomes weak and thirsty. Urine production decreases. At the final stages of the disease, the rate of heartbeat increases. Consequently, coma and death occur (Schoenstadt, 2012, para 5).
The microorganisms affect the intestines. This is where they start to multiply. The organism is said to be an environmental, as well as a human intestinal pathogen. The bacteria cause toxins in the intestines. This toxin that is produced by V. cholerae can stimulate the enzyme referred to as the adenylate cyclase. This enzyme facilitates the production of cyclic adenosine monophosphate also known as the cyclic AMP. Cyclic AMP is produced from adenosine triphosphate (ATP). The toxin, which is a prototypical enterotoxin, is the one that causes a profuse diarrhea. It causes the intestines to produce fluid that contains sodium bicarbonate and potassium. This content is too much for the intestines to absorb and hence the occurrence of diarrhea (Sack, Sack, Nair and Siddique, 2004 para 1). Encoding virulence genetic aspects can be categorized in two chromosomal sections. One is on the pathogenicity island, and the other one is on a filamentous bacteriophage. As a result of the clustering of the genes, it means that a horizontal gene transfer is likely to result to new endemic problems. It is important to note that the environmental conditions are responsible for regulating and coordinating multiple virulence genes (Butterton 2012 para 4).
For the organism to reach the intestine, it has to get through the body defensive mechanisms that are on the gastro intestinal tract. The mechanism contains acids. However, the organisms do not have the ability to resist acids. Therefore, for them to get through the tract, they must be in large numbers so as to withstand the acidity (Thaker, 2011, para 3). The bacteria are transmitted through consumption of contaminated water. The other mode of transmission is when an individual consumes contaminated food.
Methods of Growth in the Lab
Cultivation
Vibrio cholerae can strictly be classified as water borne pathogen. In addition, the pathogens are facultatively anaerobic. Therefore, they would require sodium chloride (NaCl) for their growth. Sodium chloride usually stimulates their growth. These pathogens are said to reduce nitrates into nitrites. They cannot grow in a broth that does not contain sodium chloride. Sodium chloride has to be added to the broth for the pathogens to grow. The V. cholerae can be studied in the laboratory. It has the ability to grow in a defined culture medium. One of the cultures that have been identified to support the growth of the pathogen was proposed by Nakashi back in the year 1962. It was later modified by Kobayashi and his colleagues in the year 1963. The culture is referred to as Thiosulfate Citrate Bile Sucrose Agar or simply the TCBS Agar. The culture is the best recommended for distinguished and selective cultivation of the cholera causing pathogen, as well as other forms of vibrios known to be enteropahtogenic. The culture provides conditions for rapid growth of the pathogen and other Vibrio spp (Merck, 2002 para 1). Other cultures such as the heart infusion agar, triple sugar iron agar and Kliglers iron agar can be used (CDC, n.d., p 42).
In case of a negative reaction, no color change will be observed on the culture. It is important to note that the incubation period for the pathogen in the culture will be about 48 hours. The specimen will be taken from a stool sample or from a food sample that is contaminated. The culture is very selective such that it has the capability to suppress non vibrios that might be part of the contaminant. In addition, it has all the nutritional requirements that the Vibrio spp requires for its growth. The nutrients that are contained in the culture include yeast extracts that have nitrogenous compounds, amino acids, and vitamin B complex. All these are essential for growth of the microorganism. The culture also has oxbile and sodium citrate. These aspects are important since they help to block the development of gram positive bacteria that cause contamination such as the enterococci. Sulphur in combination with ferric citrate can detect any hydrogen sulfide that might be produced. These two compounds are contained in sodium thiosulfate. Sucrose provides carbohydrates required by Vibrios for growth while NaCl is essential to stimulate growth. The indicators bromothymol blue together with the thymol blue are responsible for color change (Sigma-Aldrich Inc, p 1).
The Vibrio spp will produce a color change to form a yellow colony. This has been demonstrated in the following diagram:
Source: Merck (2002 para 6).
Laboratory Test
Tests can be carried out in the laboratory to detect V. cholerae in a specimen. Lab test are used as a confirmatory diagnosis since there are other diseases that have similar symptoms as those of cholera. The V. cholerae can be identified in the laboratory simply by carrying out a serological test on a stool specimen. This is just a simple test, and it can be confirmed further by carrying out more tests such as the biochemical tests. These tests should aim at establishing the microorganisms characteristics from those of others with similar characteristics. Tests such as bio-typing, hemolysis antimicrobial sensitivity assays, and molecular subtyping can be used to confirm the presence of V. cholerae 01. However, the use of antisera is regarded as the most rapid, as well as the most specific means of identifying the presence of V. cholerae. Identification of the enterotoxins produced by the V. cholerae and biochemical identification can fully confirm the presence of the bacteria (CDC, n.d, p 42).
Disease Treatment and Prevention
Cholera is a condition whose treatment can be attained through the use of oral rehydration salts. According to WHO (2012 para 17), more than 80 per cent cases of cholera have been treated successfully. Since the disease causes so much loss of body fluids, constant replacement of the fluids is important. In fact, in case of severe diarrhea that causes severe dehydration, the fluids are replaced intravenously. In order to reduce the duration of diarrhea, administration of antibiotics is important. This will help in reducing the volume of rehydration fluids required. In addition, antibiotics will help to reduce the duration for removing the V. cholerae from the body. Notably, antibiotics should not be administered in large amounts. There are two reasons behind this. The first one is the fact that large amounts of antibiotics do not have any effect on the spread of V. cholerae. The second reason behind the restriction of antibiotics is that they will likely increase antimicrobial resistance. Timely access to treatment is of utmost importance for effectiveness. With effective treatment, death rate is almost insignificant.
Prevention
Vibrio cholerae pathogen is associated with contaminated water. However, it can be found in contaminated food. Therefore, the first step that can be taken to prevent cholera is to ensure that the water available for consumption is clean. Multidisciplinary approach should be used in preventing the occurrence and spread of the disease. Surveillance systems can be established in order to prevent the spread of the disease through travel. They should be effective. They will be important in controlling the disease in endemic areas. In addition, they will help to mitigate cholera outbreaks. These measures will reduce the spread of cholera. Cholera outbreaks will also be reduced, as well as the number of deaths caused by cholera (WHO, 2012, para 16).
Conclusion
Cholera is a disease that is very common in crowded places and in slums where the infrastructure is poor. It is rarely found in industrialized countries. It is caused by bacteria Vibrio cholerae whose main habitat is water. The disease is important in human beings in that it causes deaths among those affected. It can also lead to death within a very short time. However, this disease can be treated. The effectiveness of treatment will depend on timely and early intervention. Its symptoms might not be noted hence increasing the risk. Prevention measures can thus be adapted to reduce its incidences.
Vibrio cholerae, also known as V. cholerae, is a bacterium that is associated with cholera. It can cause an acute illness leading to severe diarrhea. This results to dehydration, which is very detrimental to human health. This is because it can cause the demise of an individual that is affected within a very short while. It is a gram negative bacterium (Faruque & Nair, 2008, p 9). Vibrio cholerae are comma-shaped, and they have a flagellum at one end. A flagellum is a protrusion at one end of a cell body. The main function of the flagellum is to help the cell in locomotion. It also acts as a sensory organ. It is also facultatively anaerobic. The V. cholerae can be observed in two categories. These are: Vibrio cholerae Serogroup 01 and Vibrio cholerae serogroup non-01. The former is the most common cause of cholera. There are many species of V. Cholerae that belong to the later. These species do not cause diarrhea apart from Vibrio cholerae Serogroup 01 (Schoenstadt, 2012, para 2).
Vibrio cholerae is a lethal organism to human beings. This organism is lethal because it causes many deaths across the world. The bacteria kill many people especially those who live in poor conditions. People in slums and displaced persons are at a high risk of contracting the disease. In addition, poor basic infrastructure also increases the risk of the disease. Across the world, there are an approximated 3 – 5 million people who are infected by V. cholerae. Out of these, about 100,000-120,000 people will die from the illness (WHO, 2012 para 1). The disease is rare in the industrialized nations. However, the rest of the nations still experience cholera pandemics. Since the year 1817, only 7 cholera pandemics have occurred.
In America, there are rare cases of cholera if at all they are there. The bacteria are commonly found in the Ganges delta of India. It is also common in Bangladesh. Currently, there is an ongoing pandemic of the bacteria across Africa, Asia and Latin America. These pandemics have been reported within the last forty years. Of these pandemics, 80 per cent were reported in Africa (Schoenstadt, 2012 para 3-4).
The following is an image of Vibrio cholerae:
Source: Thaker, (2012 para, 1).
Mechanisms of Pathogenesis
The Vibrio cholerae pathogen is associated with the disease cholera as previously mentioned. The disease can be in a mild form or it can be asymptomatic. There are also severe forms of cholera that cause serious diarrhea and death.
Cholera is a disease that is very virulent. It can affect individuals across all ages, and this includes children and adults. This disease causes death within a very short time. Symptoms are developing depending on the severity of the disease. Severe forms of the disease will hardly show any symptoms. The bacteria can live within the human body for close to a week before death occurs, but no signs will be seen. In fact, 75 per cent of the people who are infected by the disease do not show any signs. In case of any symptoms, 80% of the people will show mild signs or they will show moderate symptoms. The main symptoms of cholera are diarrhea and dehydration. The diarrhea can be watery and profuse. Other symptoms that are specific to cholera include muscle cramps and vomiting. In addition, a change is observed in the appearance of the stool. The stool appears greyish in color, and it has some mucus. In addition, the stool characteristically becomes “rice- water”. Watery diarrhea follows suit. The diarrhea is usually painless. As fluid is lost from the body through vomiting and diarrhea, the person becomes weak and thirsty. Urine production decreases. At the final stages of the disease, the rate of heartbeat increases. Consequently, coma and death occur (Schoenstadt, 2012, para 5).
The microorganisms affect the intestines. This is where they start to multiply. The organism is said to be an environmental, as well as a human intestinal pathogen. The bacteria cause toxins in the intestines. This toxin that is produced by V. cholerae can stimulate the enzyme referred to as the adenylate cyclase. This enzyme facilitates the production of cyclic adenosine monophosphate also known as the cyclic AMP. Cyclic AMP is produced from adenosine triphosphate (ATP). The toxin, which is a prototypical enterotoxin, is the one that causes a profuse diarrhea. It causes the intestines to produce fluid that contains sodium bicarbonate and potassium. This content is too much for the intestines to absorb and hence the occurrence of diarrhea (Sack, Sack, Nair and Siddique, 2004 para 1). Encoding virulence genetic aspects can be categorized in two chromosomal sections. One is on the pathogenicity island, and the other one is on a filamentous bacteriophage. As a result of the clustering of the genes, it means that a horizontal gene transfer is likely to result to new endemic problems. It is important to note that the environmental conditions are responsible for regulating and coordinating multiple virulence genes (Butterton 2012 para 4).
For the organism to reach the intestine, it has to get through the body defensive mechanisms that are on the gastro intestinal tract. The mechanism contains acids. However, the organisms do not have the ability to resist acids. Therefore, for them to get through the tract, they must be in large numbers so as to withstand the acidity (Thaker, 2011, para 3). The bacteria are transmitted through consumption of contaminated water. The other mode of transmission is when an individual consumes contaminated food.
Methods of Growth in the Lab
Cultivation
Vibrio cholerae can strictly be classified as water borne pathogen. In addition, the pathogens are facultatively anaerobic. Therefore, they would require sodium chloride (NaCl) for their growth. Sodium chloride usually stimulates their growth. These pathogens are said to reduce nitrates into nitrites. They cannot grow in a broth that does not contain sodium chloride. Sodium chloride has to be added to the broth for the pathogens to grow. The V. cholerae can be studied in the laboratory. It has the ability to grow in a defined culture medium. One of the cultures that have been identified to support the growth of the pathogen was proposed by Nakashi back in the year 1962. It was later modified by Kobayashi and his colleagues in the year 1963. The culture is referred to as “Thiosulfate Citrate Bile Sucrose Agar” or simply the TCBS Agar. The culture is the best recommended for distinguished and selective cultivation of the cholera causing pathogen, as well as other forms of vibrios known to be enteropahtogenic. The culture provides conditions for rapid growth of the pathogen and other Vibrio spp (Merck, 2002 para 1). Other cultures such as the heart infusion agar, triple sugar iron agar and Kligler’s iron agar can be used (CDC, n.d., p 42).
In case of a negative reaction, no color change will be observed on the culture. It is important to note that the incubation period for the pathogen in the culture will be about 48 hours. The specimen will be taken from a stool sample or from a food sample that is contaminated. The culture is very selective such that it has the capability to suppress non vibrios that might be part of the contaminant. In addition, it has all the nutritional requirements that the Vibrio spp requires for its growth. The nutrients that are contained in the culture include yeast extracts that have nitrogenous compounds, amino acids, and vitamin B complex. All these are essential for growth of the microorganism. The culture also has oxbile and sodium citrate. These aspects are important since they help to block the development of gram positive bacteria that cause contamination such as the enterococci. Sulphur in combination with ferric citrate can detect any hydrogen sulfide that might be produced. These two compounds are contained in sodium thiosulfate. Sucrose provides carbohydrates required by Vibrios for growth while NaCl is essential to stimulate growth. The indicators bromothymol blue together with the thymol blue are responsible for color change (Sigma-Aldrich Inc, p 1).
The Vibrio spp will produce a color change to form a yellow colony. This has been demonstrated in the following diagram:
Source: Merck (2002 para 6).
Laboratory Test
Tests can be carried out in the laboratory to detect V. cholerae in a specimen. Lab test are used as a confirmatory diagnosis since there are other diseases that have similar symptoms as those of cholera. The V. cholerae can be identified in the laboratory simply by carrying out a serological test on a stool specimen. This is just a simple test, and it can be confirmed further by carrying out more tests such as the biochemical tests. These tests should aim at establishing the microorganisms’ characteristics from those of others with similar characteristics. Tests such as bio-typing, hemolysis antimicrobial sensitivity assays, and molecular subtyping can be used to confirm the presence of V. cholerae 01. However, the use of antisera is regarded as the most rapid, as well as the most specific means of identifying the presence of V. cholerae. Identification of the enterotoxins produced by the V. cholerae and biochemical identification can fully confirm the presence of the bacteria (CDC, n.d, p 42).
Disease Treatment and Prevention
Cholera is a condition whose treatment can be attained through the use of oral rehydration salts. According to WHO (2012 para 17), more than 80 per cent cases of cholera have been treated successfully. Since the disease causes so much loss of body fluids, constant replacement of the fluids is important. In fact, in case of severe diarrhea that causes severe dehydration, the fluids are replaced intravenously. In order to reduce the duration of diarrhea, administration of antibiotics is important. This will help in reducing the volume of rehydration fluids required. In addition, antibiotics will help to reduce the duration for removing the V. cholerae from the body. Notably, antibiotics should not be administered in large amounts. There are two reasons behind this. The first one is the fact that large amounts of antibiotics do not have any effect on the spread of V. cholerae. The second reason behind the restriction of antibiotics is that they will likely increase antimicrobial resistance. Timely access to treatment is of utmost importance for effectiveness. With effective treatment, death rate is almost insignificant.
Prevention
Vibrio cholerae pathogen is associated with contaminated water. However, it can be found in contaminated food. Therefore, the first step that can be taken to prevent cholera is to ensure that the water available for consumption is clean. Multidisciplinary approach should be used in preventing the occurrence and spread of the disease. Surveillance systems can be established in order to prevent the spread of the disease through travel. They should be effective. They will be important in controlling the disease in endemic areas. In addition, they will help to mitigate cholera outbreaks. These measures will reduce the spread of cholera. Cholera outbreaks will also be reduced, as well as the number of deaths caused by cholera (WHO, 2012, para 16).
Conclusion
Cholera is a disease that is very common in crowded places and in slums where the infrastructure is poor. It is rarely found in industrialized countries. It is caused by bacteria Vibrio cholerae whose main habitat is water. The disease is important in human beings in that it causes deaths among those affected. It can also lead to death within a very short time. However, this disease can be treated. The effectiveness of treatment will depend on timely and early intervention. Its symptoms might not be noted hence increasing the risk. Prevention measures can thus be adapted to reduce its incidences.
Multiple sclerosis is a neurological disease that affects the brain and spinal cord. This paper tries to present what is multiple sclerosis, the anatomy on which this disease is affected, etiology, pathogenesis, and the risk factors, differential diagnosis, natural diagnosis, and the various treatment options of the disease.
The problem
Multiple sclerosis is a disease that damages the myelin sheath of neurons in our brain and spinal cord. It is also called disseminated sclerosis and encephalomyelitis. Myelin sheath is a material that exists as the protector and cover of the axons in the neurons. Nerves cells help transmit electric signals between the spinal cord and brain in order to communicate with each other. Multiple sclerosis is a nervous system disease that affects the nerve cells in the brain and spine. The cause of the disease is more or less unknown to us and it is considered as our autoimmune system attacks myelin and causes the disease. The absolute cure is not possible for this disease but pharmacological therapy, occupational therapy will help reduce and control the symptoms. Even though MS is regarded to be a mild disease, sometimes the affected may lose the ability for writing, walk, and speak.
The physiology that is being attacked by the disease
Multiple Sclerosis is a nerve disorder. It means that it affects the brain and spinal cord. There are numerous neurons in our brain. Electric wave helps the brain to communicate with the spinal cord. This disease affects the myelin which is the protector of the axon through which the electric wave passes. When the myelin sheath of a neuron is damaged, the communication between the brain and spinal cord becomes irregular. “Demyelination is the term used for a loss of myelin, a substance in the white matter that insulates nerve endings. Myelin helps the nerves receive and interpret messages from the brain at maximum speed. When nerve endings lose this substance they can not function properly, leading to patches of scarring, or ‘sclerosis’, occurring where nerve endings have lost myelin. It is these areas of scarring that give multiple sclerosis its name.” (Demyelination para.1).
Epidemiology of Multiple Sclerosis
More cases affected by multiple sclerosis are reported among women and the age group of 20 to 40 is a higher risk group of the disease. Around 300000 patients are affected by this disease in North America and 70 percent of the patients belong to the age group from 21 to 40. “The most notable “epidemic” was described on the Faroe Islands after they were occupied by British troops in W.W.II. Similar increases in the incidence of the disease were seen on Shetland and Orkney Islands, in Iceland, and in Sardinia. A specific “point agent” for these “epidemics” never was identified.” (Rose, et al). Even though there are inconsistencies in the estimate of the distribution of the disease, it is considered that white people have a higher risk of getting the disease than Asian and African origins.
Etiology, pathogenesis, and risk factors
It is because the reaction of the immune system and blood-brain barrier penetrates into the central nervous system. The immune system attacks the basic protein which is myelin and then eventually it leads to the formation of plagues. These plaques are found in the nervous system especially more in white matter, brain stem, spinal cord, and cerebellum. The plague causes the reduction of axons and thereby it results in neuro-cognitive impairment. Studies show that genetics plays a vital role in the development of the disease. If a person suffers from multiple sclerosis, his relative, parents, and siblings have 1-3 percent of higher risks of affecting the disease. Women have more vulnerability of affecting the disease. So also, the Caucasian race, Native Americans who live in the northern part of America, Australian Aborigines, and Maoris of New Zealand are the main races that would be easily affected by this disease. More case of Multiple Sclerosis is reported in temperate climate than in the tropical region. “The risk factors for multiple sclerosis are female; age 20-40; family history of multiple sclerosis; Caucasians of Anglo-Scandinavian or North Sea ancestry; living in a geographical area with increased incidence of the disease: above the 37th parallel.” (Who is at the Risk of Multiple Sclerosis? para. 6).
The signs and symptoms of Multiple sclerosis
The signs of Multiple sclerosis are the following “visual disturbances, muscle weakness, trouble with coordination and balance, sensations such as numbness, prickling, or “pins and needles and thinking and memory problems.” (Other Health Topics: Multiple Sclerosis, para. 2). The common symptoms of multiple sclerosis are tiredness, numbness, dysfunction of bladder system, bowel dysfunction, dizziness, sexual dysfunction, cognitive and emotional problems, feeling of pain, depression, bowel dysfunction, speech disorganization, difficulty in swallowing, headache, loss of hearing, problems in breathing and itching. Sometimes multiple sclerosis becomes complicated resulting in blindness and paralysis.
Differential diagnosis
Post-infectious encephalomyelitis which is the result of the response of the autoimmune system to viral infection can be one of the differential diagnoses. Central Nervous System Vasculitis, Lyme disease, Systemic Lupus Erythematosus, Tropical spastic Paraparesis, Behcet syndrome, Sarcoidosis and Sjogren’s syndrome, Vitamin B-12 deficiency, and Tertiary syphilis, leukodystrophies of adulthood, hereditary degenerative disorder, progressive multifocal Leukoencephalopathy are the major differential diagnosis of multiple sclerosis. “inflammatory (systemic lupus erythematosus, Sjögren’s syndrome, vasculitis, sarcoidosis, Behçet’s disease), infectious (Lyme disease, syphilis, progressive multifocal leukoencephalopathy, HTLV-1 infection, herpes zoster), genetic (lysosomal disorders, adrenoleukodystrophy, mitochondrial disorders, CADASIL), metabolic (vitamin B12 deficiency), neoplastic (CNS lymphoma) and spinal (degenerative and vascular malformations) diseases.” (Trojano & Paolicelli para.1).
Natural history of Multiple sclerosis
It becomes a neurological disease and studies show that around sixty percent of people who have multiple sclerosis lead to the neurological illness. There is no alteration in the life expectancy of multiple sclerosis patients in the beginning stages of the disease. “The rate of suicide has been reported to be increased sevenfold in MS patients. Up to 40% of patients with attacks severe enough to render them nonambulatory may not recover. At 15 years from MS onset, 50% of patients are disabled to the point at which they at least require a cane to walk a half block. Early age at onset, female sex, the relapsing-remitting course at onset, and perhaps optic neuritis or sensory symptoms at onset and relatively few attacks in the first two years are associated with a favorable course.” (Neurol para.1).
Treatment for multiple sclerosis
No treatment can result in the complete cure out of multiple sclerosis. But there are a number of treatment options to slow down the effects of the disease. They are pharmacological therapy, chemotherapy, deep brain stimulation, plasmapheresis, and alternative therapy.
Chemotherapy
It is used in the treatment of multiple sclerosis in a way that it makes damages white blood cells. White blood cells attack the myelin in the nervous system that protects the axon. When the white blood cells are destroyed, it would help slow down the reaction of the immune system. Therefore chemotherapy is useful to halt the severity of multiple sclerosis.
Deep brain stimulation
It has three components in the treatment. This process includes a thin wire of electrodes implanted in the brain. The insulated wire connects the lead to the internal pulse generator. IPG is a neuron-stimulator that is implanted in the chest. This treatment for multiple sclerosis will not cure completely but it can slow down the progress. It usually helps to control the tremor in the head and body.
Pharmacological therapy
A number of medicines are used in the management and control of multiple sclerosis. The most used medicines are Antivert, Bonamine, Atarax, Avonex, Cymbalta, Dantruim, Detrol, Elavil, and Paxil.
Plasmapheresis
This treatment involves the process of withdrawing whole blood from the person, removal of liquid portion plasma from the blood and its replacement, and the blood that contains white cells is transfused back into the person and this is very effective in dealing with the patient of multiple sclerosis. It removes all the antibodies from the blood that would lead to the severity of the problem.
Rehabilitation
Rehabilitation is very effective in the treatment of MS patients. Rehabilitation includes a set of therapies. They are physical therapy, occupational therapy, speech therapy, cognitive therapy, and vocational therapy.
Alternative medicine
There are a number of factors that precipitate the disease such as environmental factors, genital factors, and dietary factors. So, it includes various interventions such as adequate exercise, schedule of diet, strategies for stress management, biofeedback, acupuncture, and various therapies. There can be the integration of all these various treatments that would reduce the severity of the problem. Patients respond variously to different treatments. So the best treatment for multiple sclerosis is according to the reaction of the patients towards the different treatment methods.
Conclusion
Even though there are a number of treatment options for Multiple sclerosis, there is no absolute cure. Some parts of the world and some races are higher-risk groups. There are environmental factors, genetic factors, and dietary factors that lead to the problem. The treatment can slow down the hardness of the problem. This paper gives a glance at multiple sclerosis and its different aspects.
Works Cited
Demyelination. Multiple Sclerosis International Federation. 2009. Web.
Contrast-induced nephropathy has become an important basis of hospital acquired morbidities due to high utility of iodinated contrast agents. The cases are rapidly growing in the area of diagnostic imaging and strategies that involve angiography in patients at risk (1). It is considered as the third important cause of renal failure which is next to surgery and hypotension (1). The administration of CM contributes to immediate renal vasodilatation and a continued vasoconstriction which in turn leads to high intrarenal vascular resistances, a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR) (2). These alterations in the renal circulation may lead to ischaemia which serves as the vital component for nephropathy (2). This also contributes to increasing in the levels of metabolite adenosine which in turn is crucial for hemodynamic renal biphasic reaction (2). Adenosine is a nucleoside and a plays role in ATP hydrolysis by acting as a vasoactive substance (3). It influences renal circulation by exerting its effects on vasoconstriction and vasodilatation through Adenosine receptors (3). The outcome of this effect also leads to high diuresis and natriuresis which in turn is having connection with endothelin (2). Next in CIN pathogenesis, the aberrations in endothelial function cause the generation of free radicals after ischemic reperfusion which leads to medullary vasoconstriction (3). Here, NO undergoes reaction with free radicals to generate peroxynitrite (3). This leads to inactivation of NO causing hemodynamic changes in the outer medulla which further worsens ischemic harm (3). Further, the pathogenesis of CIN is thought to involve hypoxic renal medullary injury (5). Here, nitric oxide, adenosine and prostaglandins participate in the medullary transport activity (5). This process when gets altered would lead to insufficient oxygen demand and thereafter acute tubular necrosis (ATN) (5). CM administration affects renal parenchymal oxygenation leading to medullary hypoxaemia as also revealed from non-invasive blood oxygenation level dependent magnetic resonance imaging (BOLD MRI) (5). Therefore, a fall in renal parenchymal oxygenation causes an alteration in the renal microcirculation (5). The ultimate effect is that there would not be any motility of red blood corpuscles in the blood vessels which results in cellular aggregation (5).
Therefore, human radiocontrast nephrotoxicity is better assessed by several risk contributing agents that affect a hygienic renal circulation (6). A defect in the production of vasoactive substances in renal/vascular diseases increases the risk of radiocontrast nephropathy (6). Substances like prostanoids and nitric oxide provide resistance against the radiocontrast agents (6). This was revealed when rats received pretreatment with indomethacin and N omega-nitro-L-arginine methyl ester (L-NAME) developed acute renal failure (6). As Nitric oxide synthesis gets inhibited by L-NAME, its significance was considered important in minimizing the risk of radiocontrast nephropathy (6). Further, as renal ischemia is associated with nephropathy, as discussed earlier, it may predispose the patients to transient azotemia (7). This occurs because of restricted trauma to the nephron which is similar to complicated forms of acute renal failure (8). Here, parameters like GFR, renal plasma flow, transmembrane hydraulic pressure difference need to be assessed as their levels are important to understand the pathogenesis contrast induced nephrotoxicity (8). However, further studies are required for concrete information. Earlier, Russo and his co workers (9) described the role of several parameters in the pathophysiology of contrast media (CM)-induced nephropathy. These include endothelin-1 (ET-1) levels, urinary sodium concentration, sodium levels and glomerular filtration rate (GFR), and RPF (9). This was revealed when patients who developed chronic renal failure were checked for the levels of above mentioned clinical indicators of CRF (9). A sudden decrease in GFR, tubular functional defect related to the proximal nephron, protection offered with treatment on acute and short-term GFR variations have indicated the influence of CM on CRF patients (9). Therefore, the patients having CRF need to be assessed for clinical markers to assess the severity of CM-induced nephropathy. The other aspects in the pathogenesis are the function of adenosine. It was reported that renal adenosine when gets stimulated and produced in high levels would predispose individuals to acquire CM-ARF (10). Diabetic subjects and those with a history of renal disease serve as good targets for CM-ARF (9).
This could be due to increased sensitivity to adenosine by the renal vasculature as many animal investigations reported high vasoconstriction driven by adenosine in kidneys of diabetic model animals (7). But this adverse event in the pathogenesis could be overcome by the supply of antagonists specific of adenosine receptors, in patients with diabetes and without diabetes (7). Therefore, the metabolite adenosine plays important role in modulating the CM-ARF especially, in patients with diabetes (9). This could indicate that antagonists developed for adenosine receptors may have therapeutic efficacy in lessening the incidence of CM-ARF in susceptible diabetic patients and those with low renal functional defects. It is reasonable to mention that in the present case, the old woman who developed acute renal failure 48 hours may be having Diabetes Mellitus as an underlying complication. Probably, this might have aggravated the problem. This may indicate that the diagnostic evaluation of the patient suspected for CM-ARF could be made feasible by employing markers related to adenosine metabolism. Next, nephropathy is better connected with conventional high-osmolality contrast media (HOM) (11). This condition develops due to intravascular dose of HOM (11).
Research work by Lautin and his group indicated that LOM (lower-osmolality contrast media) is related to decreased risk of nephropathy indicating its reduced nephrotoxic effect (11). The other aspects in the pathogenesis of CIN are that proximal tubular cells are susceptible to cytotoxicity induced by contrast media (3). However, in vitro studies emphasizing on cell cultures and tubular segments are under investigation (3). Mainly, cell vacuolization is the frequent problem indicating cellular injury (3). Loss of proteins like cytochrome C of mitochondria, sodium-potassium ATPase pump, enhanced susceptibility of cell membrane to phospholipase A2(3). These conditions result due to the direct effect of contrast media on tubular cells (3). In addition, cytotoxicity also occurs because of low resistance in the transepithelial region, inulin infiltration and dislocation of membrane proteins after the induction of radio contrast materials (3). Contrast media induces N-acetyl-beta-D-glucosaminidase (NAG) driven enzymuria alanine aminopeptidase (AAP) and microproteinuria where alpha1-and beta2- microglobulin participate (3). Both these conditions contribute to tubular damage (3). Similarly, immunological alterations include complement system activation in contrast to the endothelial cell activation through the alternate pathway. Infiltration of neutrophils and macrophages into the mesangial region causes low GFR and contraction (3). These pathogenic mechanism contributing to CIN are believed to be associated with many hyperosmolar agents like, hypertonic saline and mannitol as they induce related alterations in enzymatic pathways and structural integrity (3). Therefore the pathogenesis of radiocontrast nephropathy may be influenced by several parameters, like vasoactive substances, nonionic low-osmolarity, High or low osmolality, RPF, GFR, renal plasma flow, transmembrane hydraulic pressure, endothelin-1, serum and creatinine etc. To better assess the magnitude of nephrotoxicity, the above mentioned parameters need to be thoroughly evaluated for their diagnostic relevance.
This could be better done by screening programs. It would be an added advantage to select patients especially with ischemia, azotemia, diabetes, obesity and cardiovascular problems.
Gentamycin Nephrotoxicity
The next aspect of the description is on the Nephrotoxic Effect of Gentamicin. This drug was earlier utilized to study toxic events keeping in view of enzyme activities excluding the cellular abnormalities at the gross morphology level (12). The pathogenic changes to note were inhibition of protein synthesis specific to cellular and brush border membrane (BBM) (12). There were high phosphatidylinositol and phosphatidylcholine levels, low levels of sphingomyelin (SPH), in BBM (12). The research group has observed differences in control and treated group of animals (12). It was found that in treated animals the levels of phospholipids in cortical homogenates and BBM were high compared to low amount in control animals (12). Therefore, gentamycin mostly serves to affect phospholipid metabolism by preventing phospholipid degradation (12). The presence of gentamycin was reported to be high on basal structures and cell organelles like lysosomes Golgi complex, and mitochondria (12). Hence, gentamicin-induced nephrotoxicity was reported to involve a kind of long-established trafficking (12). Gentamicin facilitates increased production of plasma creatinine and urea, protein, copper and zinc excretion in the urine, decreased creatinine production and activity of cortical alkaline phosphatase, in diabetic animal models (13). Proximal renal damage was high and further it also contributed to fatal conditions in about one third of the old animals compared to younger ones (13). This may indicate that severity of gentamicin induced nephrotoxicity develops with age. In the present case, the old woman seems to be more likely to have been affected by or susceptible to gentamicin.
Hence, gentamicin effects may be more prominent in old individuals those with diabetes mellitus (13). Therefore, the present case seems to support the literature in this context of nephrotoxicity. Further, gentamicin-induces nephrotoxicity through the aid of platelet-activating factor (PAF) (14). It was revealed that rats when treated with PAF antagonist BN-52021 showed a marked elevation of plasma creatinine level decreased creatinine clearance and high amounts of N-acetyl-beta-D-glucosaminidase (NAG) and alkaline phosphatase (AP) in urine (14). In addition, histopathology indicated necrosis of cortical tubules. The generation of Glomeruli PAF in gentamicin-treated rats was high compared to control groups (14). These findings have indicated the importance of PAF in the nephrotoxicity driven by gentamicin. Gentamicin was reported to exert its effects through reactive oxygen metabolites (15). This was revealed in models of acute renal failure (15). Gentamicin was reported to produce iron from the renal cortical mitochondria (15). The role of iron is central in models of tissue injury, as it able to catalyze the production of free radicals (15). However, certain agents offer protection against gentamicin-induced nephrotoxicity by guarding iron chelators and reactive oxygen metabolites (15). Therefore, acute renal failure in humans could be avoided by better understanding the mechanism of reactive oxygen metabolites. (15).
The association between hydrogen peroxide and superoxide anion in the presence of iron contributes to the formation of hydroxyl radicals (16). This interaction probably emphasizes the role of gentamicin they may exert its effects in a cascade manner starting from generation of superoxide anion, hydrogen peroxide, hydroxyl radical, and water(16). This may indicate decrease of oxygen species along the single pathway which may be vital for Acute renal failure (16). Large number of studies have provided a clearcut description on the gentamicin as nephrotoxicity with regard to the mediators and reduced oxygen metabolites (16). Hence, the role free radicals may also become an important aspect in the pathogenesis of gentamicin induced nephrotoxicity. The role of mitochondria needs to be understood to gain further insights in the pathogenesis of gentamicin induced nephrotoxicity (17). This is because mitochondrial respiration was reported to increase the production of reactive oxygen metabolites (17). Gentamicin could induce changes in mitochondrial respiration by acting stimulating state 4 and inhibiting state 3(17). It was revealed in a fluorescence technique that gentamicin induced formation of hydrogen peroxide was increased in a great amount from 0.17 +/- 0.02 nmol (17). This activity has indicated the important role of mitochondria in the production of hydrogen peroxide (17). This aspect of drug toxicity may need an evaluation. To his end, it was reported that by employing instruments like gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS), nephrotoxicity can be better assessed(18). It was found that polyamines and amino acids were high in urine samples of animals exposed to gentamicin after a single dose (18). This event occurred before the histological examination of kidney damage and clinical manifestations of nephrotoxicity(18). But when the dose level was increased, the variations induced by nephrotoxicity led to more severe loss of amino acids in urine, accompanied with low nucleosides amino acids in kidney tissue (19). This had indicated that depending on the levels of amino acids when present in the branched chain manner in urine, a model was developed for studying and assessing nephrotoxin-treated samples with various proportions of accuracy for several days since the beginning of the experiment to the end (18). Therefore, the degree of acute renal failure which has a damaging effect on kidney could be assessed by range of clinical markers in a noninvasive approach (18).
Further, the biomarkers must get thoroughly verified for their efficacy with regard to the diagnostic application. It is reasonable to describe that the toxic effects of gentamicin have a long cascade system that needs to be deciphered at the molecular, biochemical and cellular level. From the above mentioned literature, it was learnt that the enzymes catalyzing the generation of oxygen metabolites may be controlled by feed back mechanism. Genes acting at this level may need to be studied to determine their downstream or upstream effects. Cell organelles like mitochondria play important role in the generation of energy through a cycle of events that involve oxygen species. The generation of free radicals may be another important source to modify the gentamicin driven nephrotoxicity. As such markers that reflect the activity of free radicals may provide insights on the gentamicin induced pathogenesis. In the present case, it can be assumed the old lady might have received gentamycin therapy before hospitalization. This could have resulted in the development of nephrotoxicity.
IgA Nephropathy
The final aspect to be focused in the description is Pathophysiology and Pathogenesis of IgA Nephropathy. The most frequent cause of glomerulonephritis was considered globally to be of IgA nephropathy (IgAN) (19). This condition is presented by microhematuria and/or proteinuria, recurrent gross hematuria, and diffuse mesangial IgA deposits in glomeruli. Initially, IgAN was thought to be less harmful, but it has potential to contribute to end-stage renal disease as found in nearly in 20-40% of patients who are susceptible to renal disease (19). IgAN occurs in patients diagnosed late after 5 to 25 years (19).
The indicators of this disease are high serum creatinine levels, high systemic blood pressure, and continuous protein excretion (19). The histopathological indicators are extension of immune deposits to the perivascular space and crescent formation, glomerulosclerosis and tubular atrophy/interstitial fibrosis (19).
Rauta and his co workers described that various parameters determine the effect of IgAN (20). These include histopathological findings, proteinuria, serum cholesterol, level of Ccr, and hypertension (20). In addition, certain indicators could assess the disease progression like lack of episodes of macroscopic hematuria, male sex, magnitude of tubular atrophy and serum urate level (20). These factors need to be assessed in combination to gain insights on IgAN. But, several parameters are independently related to the disease progression like the level of glomerular score, presence of hypertension and in histopathology arteriolosclerosis and urinary erythrocytes. (20). These parameters have provided a paradigm for assessing the risk as far as the outcome is concerned. Therefore, IgAN relies on the renal function which is largely influenced by the connection between parameters and outcome (20). As there is an existence of independent parameters that reflect the early and evident form of disease, predicting IgAN at an earlier stage is warranted (20). In view of the growing research importance, there is need to be considered primary IgA nephropathy (IgAN) with regard to its natural history(21). This is because there are concerns in characterizing this disease while considering patients for renal biopsy, in the utility of various classifying criteria for the renal lesions, statistics which lead to misinterpretation (21). It was further described that prolonged progression from 5 to 25 years and remission, geographic fluctuations are well known features that reflect a good natural history of IgAN(21).
Similarly, the random cases that demonstrate severe forms renal damage, high creatinine concentrations, arterial hypertension and nephrotic range proteinuria have been well implicated as predictors. In contrast, the independent predictors are Mean blood pressure value (MAP) and proteinuria during follow-up period (21). Histopathologic observations include severity of interstitial fibrosis and glomerular sclerosis (21). The other risk factors were the connection between crescents and tuft adhesions which occur due to segmental necrosis (21). It was further reported that parameters that serve as independent prognostic markers are age and mean proteinuria during follow-up period (21). Therefore, these factors need to be considered to better assess the severity of progression IgAN. In the present case, there may be a defect in the evaluation of the patient with regard to the IgAN.Although serum creatinine levels and age were measured, certain independent factors could have helped the patient to survive.
It is reasonable to connect this part of description with Henoch-Schoenlein purpura (HSP). HSP is a kind of systemic vasculitis represented by vascular wall deposits of IgA (22). This encompasses arthralgia or arthritis, haematuria, gut and glomeruli and is associated with purpura, colic, small vessels in skin and gut (22). This condition contributes to chronic renal failure mostly in 20 % of pediatric cases and is evident by the manifestation of glomeruli with epithelial crescents (22). HSPN is associated with high generation of aberrant glycosylated IgA, which is not metabolized by the liver (22). This result in the production of IgA macromolecules, that reside in the blood stream with further deposits stored in vessel walls and the glomerular mesangium (22). HSPN is also represented by the clinical signs of skin, and joint disorders (23). Immunofluorescent investigations revealed that HSPN and IgA nephropathy are similar due to the existence of IgA deposits in the glomeruli and the vessel walls (23).
This has indicated the immunologic form of pathologic lesions (23). Therefore, HSPN may play vital role in the overall pathogenesis of contrast induced nephropathy. Relationships and differences do exist between IgAN and HSPN as these disorders could occur in the same patient with the manifestation of more or less similar clinical defects (24). The age could vary from 15 to 30 years as seen in IgAN whereas HSPN was reported to occur in childhood (22). Manifestations specific to Nephritic and/or nephrotic syndromes commonly occur in HSPN (24). On contrary to IgAN, hypersensitivity is associated with HSPN (24). Further, inflammations of extracapillary and endocapillary regions and that of fibrin deposits in the glomerulus are also common in HSP (24). Although, there were no wide differences between the two disorders, the only exemption is for an increased frequency of high plasma IgE levels in HSPN and for a superior mass of circulating IgA-containing complexes (IgA-CC) (24). Leukocytes get largely infiltrated at tissue level in HSPN vasculitis, whereas these cells are activated at a higher degree by HSP induced IgA-CC and/or circulating chemokines (24).
Pankhurst and his associates have reported that vasculitic glomerulonephritis occurs in both IgAN and HSP (25). This was revealed in large group of patients presented with IgAN, HSP (25). The clinical characteristics include median glomerular filtration rate at 45.56 ml/min arterial blood pressure 104.67 mm Hg and proteinuria 1.19 g/24 h. Similarly, biopsy studies revealed a median chronic damage of 10% (25). The immune system of study patients was tuned to a compromised state (25). This has indicated the reliability of the biopsy studies in assessing the extent of chronic damage, renal function and blood pressure at presentation (25). Therefore biopsy studies seem to furnish insights on the pathogenesis of vasculitic IgA nephropathy. In the present case, the old woman may be having a compromised immune system compromised. This probably could have made her susceptible to advanced stages acute renal failure or nephrotoxicity and associated problems. Here, the important point to note is that although HSPN occurs in childhood, it could also develop in adult individuals. A large population study has been carried out in adults having HSP and they were also followed up for nearly 14 years (26). Biopsy investigations were in agreement with mesangial deposits characteristic of HSP and this is connected to abdominal pain, purpura and bowel angina (26). Significant proportion of patients presented palpable purpura, arthritis and gut association (26). Similarly, renal insufficiency related to proteinuria and hematuria were also noted (26). The follow up period also revealed the significant survival of patients (26). Few death cases were attributed to gastric discomfort and few patients were close to end-stage renal failure, serious renal failure and temperate renal insufficiency in various proportions. This was revealed from the levels of CrCl (26). In addition, the degree of altered renal function and proteinuria presented, the extent of interstitial fibrosis, proportion of sclerotic glomeruli and occurrence of glomeruli with fibrinoid necrosis were reported to correlate with reduced weak renal prognosis (24). This reported has strongly indicated that the outcome of HSPN pathogenesis in adult population is serious and weak compared to that found in children (26). Biopsy investigations were in agreement with mesangial deposits characteristic of HSP and this is connected to abdominal pain, purpura and bowel angina. It has further emphasized on the need of biopsy investigations to better understand the pathogenesis with regard to that of renal function and associated symptoms.
Appropriate scientific intervention would enable to understand pathogenesis of IgA and/ or its association with HSPN. This study has strongly favored the present case of old women who is having similar clinical characteristics like abdominal pain, urine dipstick turning out was positive for ketones and proteins etc. She could have been thoroughly evaluated for the mentioned parameters that were covered in the cited literature. This may indicate that there is a need of evidence based approach. The health care professionals must consider the available literature extensively, retrieve the needful information and do best for the betterment of the patient.
References
Tadhg, G. Gleeson and Sudi Bulugahapitiya. AJR. 2004.183
Simian Detrenis, Michele Meschi, Sabrina Musini, Giorgio Savazzi. Lights and shadows on the pathogenesis of contrast-induced nephropathy: state of the art. Nephrol Dial Transplant. 2005 20: 1542–1550.
Efstratiadis, G, Pateinakis, P, Tambakoudis, G, Pantzaki, A, Economidou, P, Memmos, D Contrast media-induced nephropathy: case report and review of the literature focusing on pathogenesis. Hippokratia. 2008; 12(2): 87–93.
Christiane M. Erley, Heyne, N, Rossmeier, S, Vogel, T, Teut Risler, Hartmut Osswald. Adenosine and extracellular volume in radiocontrast media-induced nephropathy. Kidney International 1998 54 (67): S-192–S-194.
Samuel N. Heyman, Christian Rosenberger and Seymour Rosen. Regional alterations in renal haemodynamics and oxygenation: a role in contrast medium-induced nephropathy.Nephrol Dial Transplant.2005 20 (1): i6–i11
Agmon, Y Peleg, H, Greenfeld, Z, Rosen, S, Brezis, M. Nitric oxide and prostanoids protect the renal outer medulla from radiocontrast toxicity in the rat. J Clin Invest 1994;94(3):1069-75.
Cigarroa, R, G, Lange, R,A, Williams, R,H, Hillis ,L,D. Dosing of contrast material to prevent contrast nephropathy in patients with renal disease. Am J Med. 1989;86(6 Pt 1):649-52.
Myers, B,D, Miller, D,C, Mehigan, J,T, Olcott, C,O, 4th, Golbetz, H, Robertson, C,R, Derby, G, Spencer, R, Friedman ,S. Nature of the renal injury following total renal ischemia in man. J Clin Invest 1984; 73(2):329-41.
Russo, D, Minutolo, R, Cianciaruso, B, Memoli, B, Conte, G, De Nicola, L. Early effects of contrast media on renal hemodynamics and tubular function in chronic renal failure. J Am Soc Nephrol 1995;6(5):1451-8.
Pflueger, A, Larson ,T,S, Nath, K,A, King ,B,F, Gross, J,M, Knox, F,G. Role of adenosine in contrast media-induced acute renal failure in diabetes mellitus. Mayo Clin Proc. 2000;75(12):1275-83
Lautin, E,M, Freeman, N,J, Schoenfeld, A,H, Bakal ,C,W, Haramati, N, Friedman, A,C, Lautin, J,L, Braha ,S, Kadish, E,G, et al. Radiocontrast-associated renal dysfunction: a comparison of lower-osmolality and conventional high-osmolality contrast media. AJR Am J Roentgenol. 1991; 157(1):59-65.
David, P. Sundin, Ruben Sandoval and Bruce A. Molitoris. Gentamicin Inhibits Renal Protein and Phospholipid Metabolism in Rats: Implications Involving Intracellular Trafficking. J Am Soc Nephrol. 2001 12:114-123.
Ali, B, H, Bashir, A, K, Mugamer, I,T, Tanira, M,O. Gentamicin nephrotoxicity in the rat: influence of age and diabetes mellitus. Hum Exp Toxicol. 1996;15(1):51-55.
Rodriguez-Barbero ,A, López-Novoa, J,M, Arévalo, M. Involvement of platelet-activating factor in gentamicin nephrotoxicity in rats. Exp Nephrol. 1997 ;5(1):47-54.
Baliga, R, Ueda, N, Walker, P,D, Shah, S,V. Oxidant mechanisms in toxic acute renal failure. Am J Kidney Dis. 1997; 29(3):465-77.
Walker, P,D, Barri, Y, Shah, S,V. Oxidant mechanisms in gentamicin nephrotoxicity. Ren Fail. 1999; 21(3-4):433-42.
Walker, P,D, Shah, S,V. Gentamicin enhanced production of hydrogen peroxide by renal cortical mitochondria. Am J Physiol. 1987; 253(4 Pt 1):C495-9.
Boudonck ,K,J, Mitchell ,M,W, Német, L, Keresztes, L, Nyska, A, Shinar, D, Rosenstock, M. Discovery of metabolomics biomarkers for early detection of nephrotoxicity. Toxicol Pathol. 2009;37(3):280-92.
Rychlik, I, Andrassy, K, Waldherr, R, Zuna, I, Tesar, V, Jancová, E, Stejskalová ,A, Ritz, E. Clinical features and natural history of IgA nephropathy. Ann Med Interne (Paris). 1999;150(2):117-26.
Rauta, V, Finne, P, Fagerudd, J, Rosenlöf ,K, Törnroth, T, Grönhagen-Riska , C. Factors associated with progression of IgA nephropathy are related to renal function–a model for estimating risk of progression in mild disease. Clin Nephrol 2002;58(2):85-94.
Coppo, R, D’Amico, G. Factors predicting progression of IgA nephropathies. J Nephrol. 2005;18(5):503-12.
Davin, J, C, Ten Berge, I, J, Weening ,J,J.. What is the difference between IgA nephropathy and Henoch-Schönlein purpura nephritis? Kidney Int. 2001 Mar;59(3):823-34
Pankhurst, T, Lepenies, J, Nightingale, P, Howie, A,J, Adu, D, Harper, L. Vasculitic IgA nephropathy: prognosis and outcome. Nephron Clin Pract. 2009;112(1):c16-24.
Chacko, B, John, G,T, Neelakantan, N, Korula ,A, Balakrishnan, N, Kirubakaran ,M,G, Jacob, C,K. Presentation, prognosis and outcome of IgA nephropathy in Indian adults. Nephrology (Carlton). 2005;10(5):496-503.
Vibrio cholera is the causative agent of Cholera, a severe epidemic diarrheal disease that attacks both children and adults. Infection results from the consumption of food or water contaminated by the bacterium Vibrio cholera (3). The disease is treatable but can cause death within just a few hours if no intervention is taken. Cholera remains a serious public health concern. The World Health Organization estimates 3-5 million cholera cases every year with a reported 100 000- 120 000 deaths (9).
However, there is a marked disparity in prevalence rates between developed and developing countries with poor sanitation in the later having been cited as the main cause (9). In the United States, cholera cases remain extremely low and this has been attributed to improved hygiene and sanitation over the year (8). Cholera cases reported in the United States are those that result from travel to endemic areas and the consumption of undercooked seafood.
Incidence rates remain low with 0.50 cases per 100,000 population from 2003-2008 recorded for people older than 50 years (8, 9). Worldwide Cholera statistics are not accurate as many cases/incidences are not reported (8, 9). Many countries fear the negative impact Cholera outbreak reports may have on local economic activities such as trade and tourism (8, 9). Recent epidemics have been reported in Zimbabwe (2008-2009) and in Haiti (2010).
Electron microscopic image of Vibrio cholera Thaker, V.V. (2011).
Vibrio cholera is a comma-shaped, anaerobic bacterium whose size ranges from 1-3 µm in length and 0.5 – 0.8 µm in diameter (8, 3). Its major proteinous building blocks are a flagellin H antigen and a somatic O antigen (8). The bacterium belongs to the genus Vibrio and shares the characteristic features of these members such as facultative anaerobism, asporogenosity, motility, and being gram-negative (5).
These bacteria are also predominantly aquatic, inhabiting areas such as estuaries and brackish water with algal bloom (5, 9). In such an aquatic environment, the bacterium thrives in association with zooplankton and phytoplankton where they exist as free-swimming cells, attached to plants, algae, copepods and other sea animals (4). Apart from water sources eating raw or undercooked seafood has also been associated with the development of the disease (5).
This is one of the main sources of transmission in the United States (1). The bacterium has the ability to ferment glucose, sucrose and mannitol and this feature has been utilized in many laboratory tests (5). The main reservoirs of Vibrio cholera are humans and water. Animals do not play any role in transmission (8). Infection is high in communities with poor hygiene standards. Other etiological factors cited are human migration and seasonal climatic warming along the coastlines.
These conditions enable Vibrio members to thrive. Interestingly, studies have shown that people with type O blood group have a higher than normal susceptibility to cholera (8). Although there are many subgroups of the bacterium only the O1 and O139 serogroups have been known to cause epidemic and pandemic Cholera(5). There are three serogroups of Vibrio O1 namely: Inaba(O antigen A and C), Ogawa (O antigen A and B) and Hikojima (O antigen A, B and C) (8).
Lifecycle of V.cholerae (Butler & Camilli, 2005)
Mechanism of pathogenesis
There are about 200 strains of Vibrio Cholerae bacterium but only two strains, O1 and S139 are associated with pandemic and endemic cholera(8). The S139 strain (Bengal) is endemic in Asia (8, 5). A person gets infected from ingesting water or food contaminated with Vibrio cholera. Infection dose for the manifestation of clinical symptoms varies depending on the mode of infection but is higher from water compared to food (8).
Nevertheless, infection requires a very high ingestion dose. Once ingested the bacteria migrate to the small intestines and begin to multiply (6). The incubation period may last 18h to 5 days (5). However, large quantities of ingested Vibrio cholera are needed in order to develop symptoms (6). Cholera is highly virulent (9). Signs of Cholera get noticeable 18h to 5 days after ingestion (5). General symptoms are akin to those of gastrointestinal diarrhea and include sudden weight loss, excessive thirst, postural hypotension, fatigue, dry mouth, sunken eyes, wrinkled skin, somnolence and comma in advanced stage (8). Children may experience hypoglycemia (8).
Children and adults normally experience similar signs although extreme drowsiness, convulsions and coma are rare in adults (8). Most Vibrio cholera infections are asymptomatic. In fact, mild to moderate infections may not be distinguishable from other causes of gastroenteritis (8). Symptomatic cholera is distinctively characterized by voluminous watery diarrhea at the peak of infection often with vomiting (8).
A bucket with typical rice stool from a cholera patient (Sack, D.A. Sack, R.B., Nair, G.B. and Siddique, A.K. (2004)).
The stool resembles ‘rice water’ and may have a characteristic ‘fishy’ smell (5). However, victims infected may not necessarily exhibit the hallmark watery diarrhea but mild diarrhea without serious debilitating symptoms (5). Vomiting is caused by reduced motility in the gastric and intestines (8). Vomiting may not always be present (5). The vomitus is normally a clear alkaline fluid (5). This causes the body to lose so much water that patients develop severe dehydration and shock and entire vascular collapse within just a few hours(8). If unchecked, death commonly results in less than 24 hours (8). Dehydration is proportional at the intracellular, intravascular and interstitial levels (8). The WHO has classified dehydration as severe, moderate or mild and specifies appropriate interventions for each (8). Severely dehydrated children and adults may suffer from tachycardia, extremely low pulse and hypotension (8). Without early interventions measures Cholera fatalities can be a high of over 50 %( 5).
Development of the disease is brought about by the colonization of the proximal small intestine upon which the bacterium produces a cholera toxin that accelerates diarrhea. The fluid and electrolytes (K+ and bicarbonates) loss is confined to the duodenum and upper jejunum (8). The major salts lost are bicarbonates and potassium ions (8). The endotoxin of the O1 type is made up of proteinous subunits 5B and 2A that confers virulence (3). The O139 strain produces a similar endotoxin except that its virulence is enhanced by lipopolysaccharide and a novel O-antigen capsule (8).
Methods for growth in the Lab
Vibrio members can grow at high PH or bile salts, conditions which inhibit the growth of potential confounders such as Enterobacteriaceae (8). Lab cultures are used to confirm cholera outbreaks. TCBS (Thiosulphate Citrate Bile Sucrose Agar) is one of the selective agars used in the isolation and rapid cultivation of Vibrio cholera (7). This medium is highly selective and is able to provide nutritional sustenance for the vibrio species while eliminating non-vibrio micro-organisms.
Growth of Vibrio Cholerae on TBSC culture (Merck, K.G.A. (2002). TCBS Agar).
For culturing, sample fresh feces is placed onto a TCBS (Thiosulphate Citrate Bile Salts Sucrose) agar (5). TCBS agar is composed of nutrients, salts and coloring agents namely: mixed peptone, yeast extract, sucrose, sodium citrate, ferric citrate, sodium chloride, sodium thiosulphate, oxbile, sodium cholate, Thymol blue, Bromothymol blue and agar. The PH of this growth medium is around 8.6 at room temperature and pressure (7).
These ingredients set up conditions that inhibit the growth of Enterobacteriaceae (4). Oxbile and bile salts suppress enterococci (4). The Thymol- Bromothymol blue mixture changes to an indicative yellow color when acid is formed from sucrose fermentation by Vibrio cholera (4).
Following 6-12h of incubation, a second inoculation in the same plate is done and incubated for 18-24hours. Growth is evident from the appearance of large smooth and round yellow colonies and is interpreted as a positive identification (7, 8). Yellow coloration is due to the fermentation of sucrose by the Vibrio members (4). No color change indicates a negative reaction. Specific strains of Vibrio known to produce the yellow color include Vibrio alginolyticus, Vibrio cholera and Vibrio fluvialis (7). However, the yellow color can also be attributed to non-vibrio members such as Enterococcus faecalis, E.coli as a well as Proteaus mirabilis (7).
Appearance of Colonies
Microorganisms
Flat, 2-3 mm in diameter, yellow
Vibrio cholerae, Vibrio cholerae type El Tor
Small, blue-green center
Vibrio parahaemolyticus
Large, yellow
Vibrio alginolyticus
Blue
Pseudomonas, Aeromonas and others
Very small, translucent
Enterobacteriaceae and others
Positive identification can be confirmed from agglutination on a non-selective medium with O1 or O139 antiserum (5). Notable rapid tests include dark-field microscopy in which the effect of O1 or O139 antiserum is observed on a wet mount of a liquid stool sample(5). Rapid tests are recommended for monitoring the disease in remote areas where cultures are not viable (5).
Serological tests such as slide agglutination can be used to identify Vibrio cholerae O1 serotype antigen on suspect samples (2). However, additional characterization may be necessary to ascertain the cholera toxin (2). Positive serotype identification is based on agglutination on anti-sera to type-specific O antigen(2). Other tests used to reveal important public health information include hemolysis, molecular subtyping, and antimicrobial sensitivity assays (2).
Biochemical tests used to confirm isolates of Vibrio cholera include oxidase tests, String test, Klinger’s Iron agar test, Triple sugar, Iron Agar, salt broth as well as Voges, Poskaver test. Hemolysis tests are based on the ability of certain Vibrio members ability to lyse erythrocytes (2). Although many such strains are now non-hemolytic, it is still used to differentiate various continental strains (2). Specific tests include Plate Hemolysis, Tube and Hemolysis Assay (2). Modern methods with high sensitivity and specificity such as Polymerase Chain Reaction (PCR) have also been developed. PCR has been used to screen food samples (8).
Disease treatment and prevention
Cholera is a treatable disease. Cholera patients lose a high amount of body fluids and electrolytes and the primary treatment regimens seek to first rehydrate the patient to restore the body hydration status in the shortest time possible(8). Rehydration may include Lactated Ringer solution, isotonic sodium chloride solution, or oral rehydration solution (ORS) (8). Intravenous rehydration is performed on severely rehydrated patients (9, 3). The WHO recommends oral rehydration solution for moderately dehydrated patients and replacement of 10% of the bodyweight within 2-4h in severely dehydrated patients (8, 5). The hydration is maintained until diarrhea ceases. Insufficient rehydration may lead to temporary survival only for patients to succumb later (5). For severely dehydrated patients, antibiotics (e.g. doxycycline) can also be used to reduce vomiting and the volume of rehydration solutions needed (8). For extremely debilitated patients a cholera cot may be used to monitor excretion and body hydration.
A child, lying on a cholera cot, showing typical signs of severe dehydration from cholera (Sack, D.A. Sack, R.B., Nair, G.B. and Siddique, A.K. (2004)
Patients with cholera are not able to feed but food should be provided as soon as they are able to eat (5). Health authorities are also required to set up accessible treatment centers in the affected areas. Cholera reporting standards and guidelines are periodically reviewed by the WHO (9). Inappropriate treatment has been known to cause complications such as acute renal failure, and miscarriage or premature delivery in pregnant women (8, 5). Painful muscle crumps in legs and limbs are common (5). However, with prompt and proper treatment the high fatalities and adverse effects associated with cholera can be significantly reduced.
Prevention of Cholera outbreak is aimed at hindering the transmission of Vibrio cholera from its source (5). In this case, greater emphasis is laid on improving sanitation and supply of drinking water, thorough cooking of food and mass health education (5,8). During Cholera outbreaks health authorities normally stress purification of water, food preparation, identifying signs of infection and locations for early treatment (9, 5, and 8).
Since its discovery, a number of vaccines against Vibrio cholera have been developed. These vaccines consist of killed V. cholerae and subunits that serve to stimulate immunity against future attacks. Some of them include the Oral ones such as Dukoral, Shancol and Orochol (5). Shancol confers longer protection against V.cholerae in children less than 5 years (5). The quality of these vaccines has improved overtime though some countries such as the US have to date not licensed their use or even recommended them (5). Some vaccines have also not been recommended by WHO due to their low protective efficacy and adverse side effects (1).
Conclusion
Vibrio cholera causes Cholera, a potentially pandemic disease estimated by WHO to claim over 120 000 lives yearly. Many of the bacterium strains are innocuous except for the O1 and S139 types which cause the disease. Infection is brought about by the ingestion of contaminated food and water. Pathogenicity is as a result of the bacterium colonizing the small intestine and releasing an endotoxin leading to development of major symptoms such as voluminous diarrhea and vomiting. Vibrio Cholerae can be cultivated in the laboratory using the TCBS Agar whereby positive growth is evident from development of yellow colonies. Further confirmatory tests can be performed by a number of serological and biochemical tests. The primary intervention for Cholera is rehydration. Vaccines have also been developed although they have only gained acceptance in some countries.
Butler, S. M., & Camilli, A. (2005). Going against the grain: chemotaxis and infection in Vibrio Cholerae. Nature Reviews Microbiology, 3, 611-620. Web.
Shigellosis is a diarrheal disease caused by a group of bacteria called Shigella.
Types:
Shigella sonnei (the most common in the US);
Shigella flexneri;
Shigella boydii;
Shigella dysenteriae.
Shigella germs are found in infected stools of individuals.
Shigella is highly contagious – exposure to a minute contaminated fecal matter causes infection.
Transmitted when infected objects come into contact with the mouth or is swallowed:
Contaminated hands touch food or mouth;
Consuming food contaminated with Shigella;
Swallowing recreational during swimming from any water source;
Contact with feces through sexual contact.
(Centers for Disease Control and Prevention, 2015b).
Shigellosis: Signs/Symptoms
Symptoms of shigellosis are generally noted 1 to 2 days after exposure.
Causes gastroenteritis manifested through:
Diarrhea (may be bloody);
Fever;
Abdominal pain;
Tenesmus (a painful urge to pass stool but the bowel is empty).
For healthy persons, symptoms last about 5 to 7 days.
Reinfection with the similar types of Shigella is usually difficult and can take several years.
Shigellosis: Prevalence
Estimates
About 500,000 cases of shigellosis reported the US annually;
5,400 hospitalizations and 38 deaths;
Lacks definite seasonality thus reflects the significance of person-to-person transmission.
Incidence
In 2013, the US reported 4.82 cases per 100,000 individuals.
Trends
No significance decline in the last 10 years;
Shigella sonnei infection rate declined between 2008 and 2011, but increased in 2012 (Centers for Disease Control and Prevention, 2015b).
Shigellosis: Pathogenesis
Virulence factors
Aid adherence to epithelium of the intestine, survive stomach acid, invade host cells, evade immune responses, and introduce toxins into the body.
The pathogenesis
Bacterium enters the host cell;
Attacks the cellular machinery to evade immune responses and renew its replicative space;
Uses injectisome to inject effector proteins into the host cell, manipulates the eukaryotic cell’s cytoskeleton, mainly actin fibers;
Actin polymerization leads to pathogen uptake, intracellular motility and pass to other host cells;
Mediates the cell death of macrophages to advance and evade the immune system (Anderson, Salm, Allen, & Nester, 2015; Sansonetti, 2001).
Shigellosis: Treatment
Treatment
Diarrhea resolves alone without antibiotics after 5 to 7 days;
Mild cases may require only fluids and rest;
Bismuth subsalicylate – Pepto-Bismol® is necessary;
Avoid loperamide and diphenoxylate (antidiarrheal medicines) because they cause slow down of the gut and worsen the condition;
Severe cases require antibiotics to reduce the duration of symptoms;
Use of bacteriophage.
Antibiotic Resistance
Shigella is often resistant to antibiotics;
Stool culture is necessary for effective antibiotics;
Report outcomes within few days after antibiotics administration.
Shigellosis: Outcome
Positive treatment outcomes are expected with antibiotics.
However, antibiotic resistance often occurs:
Report outcomes within few days after treatment;
Further susceptibility tests will be conducted to determine the most effective antibiotics;
Ampicillin may be replaced with flouroquinolones and azithromycin.
No licensed vaccine available for Shigella (Centers for Disease Control and Prevention, 2015b).
Shigellosis: Prevention
No licensed vaccine is currently available for Shigella.
Reduce risks of person-to-person through:
frequent, thorough hand washing before eating and after changing diapers or helping other individuals who have defecated.
Handle infected feces carefully.
Do not drink or swallow water from ponds, lakes, rivers, or untreated swimming pools.
Adhere to strict guidelines on water and food hygiene.
Avoid sexual intercourse with persons who diarrhea or have recently recovered (Centers for Disease Control and Prevention, 2015b).
Typhoid Fever: Transmission
Life-threatening, contagious illness caused by bacterium, SalmonellaTyphi;
Salmonella Typhisurvives only in humans;
Bacteria are found in the bloodstream and intestinal tract;
Carriers usually recover from typhoid fever but still have the bacteria;
Stools of infected persons carry bacteria;
Eating food or drinking beverages contaminated by SalmonellaTyphi causes typhoid fever;
Salmonella Typhibacteria multiply and move into the bloodstream (Centers for Disease Control and Prevention, 2013).
Typhoid Fever: Signs/Symptoms
High sustained fever – as high as 103° to 104° F (39° to 40° C);
Weaknesses;
Stomach pains;
Headache;
Loss of appetite;
A rash of flat, rose-colored spots;
It is recommended to perform stool or blood test to determine the presence of Salmonella Typhi– the only sure way.
Typhoid Fever: Prevalence
Common in most parts of the underdeveloped world (about 21.5 million persons each year):
Asia;
Africa;
Latin America.
Not so common in developed countries such as:
The United States (5,700 cases occur annually, about 75% results from foreign travels);
Canada;
Western Europe;
Australia;
Japan.
Typhoid Fever: Pathogenesis
Salmonella Typhienters the mucosa of small and large bowel.
Stays intracellularly and proliferate.
Ulceration of lymphoid follicles may take place.
Initial developments occur in the second section of patches of the lower small intestine.
Systemic dissemination takes place to:
Liver;
Spleen;
Reticuloendothelial system.
Between 1 to 3 weeks, the bacteria multiply in these organs.
Infected cells rupture.
Bacteria move to the bile and infect the lymphoid tissue of the small intestine, the ileum.
Heavy infection occurs.
Invasion of mucosa occurs.
The epithelial cells release various proinflammatory cytokines (Singh, 2001).
Typhoid Fever: Treatment
Individuals experiencing high fever and feel weak should see the doctor immediately.
Antibiotics are administered in confirmed cases.
Several cases of antibiotics have been reported:
Reduced susceptibility to fluoroquinolones;
The emergence of multidrug-resistance, particularly in South Asia.
Antibiotic susceptibility testing is recommended for effective treatment.
Antibiotic therapy include:
Fluoroquinolones;
Ceftriaxone;
Azithromycin (Centers for Disease Control and Prevention, 2013).
Typhoid Fever: Outcome
Administered antibiotics should have positive outcomes;
Cases of resistance may complicate treatment;
Individuals who fail to get treatment may still have the fever for months;
About 20% die from typhoid fever complication;
Symptoms may disappear but the person may still be carrying SalmonellaTyphi;
Symptoms may recur;
Infected persons may pass the disease to other individuals;
It is recommended to complete the dose;
Stool culture is necessary to determine that no Salmonella Typhi is left in the body.
Typhoid Fever: Prevention
Do not consume risky foods and drinks.
Vaccination is highly recommended:
Ty21a (Vivotif Berna, Swiss Serum and Vaccine Institute);
ViCPS (Typhim Vi, Pasteur Merieux);
Note: Vaccines are not completely effective.
Maintain optimal hand hygiene.
Food should be:
Thoroughly cooked;
Peeled off;
Washed;
Do not consume foods and drinks from street vendors.
Cholera: Transmission
Cholera is an acute intestinal infection caused by strains of the bacteria Vibrio cholerae;
Cholera has a short incubation period and produces enterotoxin that causes watery diarrhea that lead to dehydration;
Vibrio cholerae is present in stool or other effluent of an effected person;
The bacteria seep into and contaminate waterways, soils, or sources of drinking water and food;
On drinking or using infected water for washing, a healthy person can get infected by the bacteria;
Hygiene plays a key role in cholera transmission and it is one measures of a country’s social development.
Cholera: Signs/Symptoms
Cholera symptoms may be manifested within two hours of infection.
Most cases may take 7-14 days before falling ill, although Vibrio cholerae is present in their feces.
The primary symptom is copious, painless, water rice diarrhea, that leads to dehydration manifested through:
Rapid heart rate;
Low blood pressure;
Loss of skin elasticity;
Muscle cramps;
Thirst.
Vomiting is also common among many patients.
Cholera: Prevalence
Situation
In 2013, the WHO received 129, 064 cases from 47 countries globally (World Health Organization, 2016):
Africa reported 43%;
Americas reported 47%.
Cholera annual global burden is estimated 1.4 to 4.3 million cases and 28000 to 142000 deaths.
In 2015, WHO responded to multiple Cholera out breaks, especially in the Eastern Mediterranean and African regions.
Global reporting is not accurate due to fears of negative impact on travel and trade.
Trends
Endemic countries include India, Indonesia, Zimbabwe, and other African and Southern Asia countries.
Between 2001-2009, Africa reported 93% to 98% of total global cases.
The increasing outbreak in the island of Hispaniola, Haiti and the Dominican Republic from 2010 and the decreasing cases from Africa since 2012 has drastically changed the proportion.
Cholera remains a significant public health problem, especially in Sub-Saharan Africa, Southern Asia and in Hispaniola (World Health Organization, 2016).
Cholera: Pathogenesis
Approximately 2/3 of Vibrio cholerae survive the acidic condition of the host digestive tract;
In the host small intestine, the bacteria produce long tail-like structures, flagella, that help them to propagate and move through intestinal mucus to the intestinal wall;
In the intestinal wall, the bacteria produce figure like projections, frimbriae or pili, for attachment;
The bacteria multiply necessitating more space and new hosts;
They toxic protein to propel new multiplying bacteria to external environment for new hosts.
Cholera: Treatment/Outcome
Rehydration therapy reduces fatalities to under 1% of all patients;
Antibiotic treatment is used as an adjunct to hydration treatment, especially for severely ill patients (Centers for Disease Control and Prevention, 2015a):
Severe dehydration; Doxycycline, and Tetracycline: Erythromycin recommended for children;
Moderate or severe dehydration; Doxycycline, Ciprofloxacin, Azithromycin: Erythromycin, Azithromycin for pregnant women and children.
Zinc treatment:
Zinc supplements significantly reduces duration and severity of diarrhea, especially in children.
Cholera: Prevention
Proper and regular washing of hands with soap and water, in absences of soap, sand or ash can be used;
Proper feces disposal (use of latrine or chemical toilet);
Avoiding defecating in water bodies;
Toilets should be dug 30 meters from water bodies;
Drinking and using safe water; bottled water with unbroken seals, boiled and chlorine treated water, and stored in clean covered containers;
Food should be properly cooked, covered, and eaten while hot;
Fruits must be cleaned and pealed;
Vaccination recommended;
Proper and thorough cleaning of kitchens, bathrooms and clothing.
References
Anderson, D., Salm, S., Allen, D., & Nester, E. (2015). Nester’s Microbiology: A Human Perspective (8th ed.). Whitby, ON: McGraw-Hill.
Centers for Disease Control and Prevention. (2013). Typhoid Fever. Web.
Centers for Disease Control and Prevention. (2015a). Cholera. Web.
Centers for Disease Control and Prevention. (2015b). Shigella – Shigellosis. Web.
Sansonetti, P. J. (2001). Shigellosis: from symptoms to molecular pathogenesis. American Journal of Physiology – Gastrointestinal and Liver Physiology, 280(3), G319-G323.
Singh, S. (2001). Typhoid Fever: Pathogenesis and Laboratory Diagnosis. Journal of Indian Academy of Clinical Medicine, 2(1), 17-20.
World Health Organization. (2016). Number of Reported Cholera Cases. Web.
