This once private forum for discussion about the Griffith University Infectious Disease End of Semester (EoS) exam is now closed and open to the public for general viewing.
This project is an extension of the GU-BioMed Wiki-site http://griffithbiomed.wikispaces.com/
This collaboration was created under the Creative Commons Act (see the Wiki-Site for more information). It can't be guaranteed that all content on this site is factually valid, therefore we ask that readers think critically about what they are reading and research the topic thoroughly to get a better understanding of the topics discussed.
Enjoy!
Saturday, November 22, 2008
Sunday, November 16, 2008
Q15 Discuss the following (fictional) press release... (ver 4)
15. Discuss the following (fictional) press release... "The world is a safer [place with the advent of a new vaccine against tuberculosis announced the Health Minister during a 4visit to Gambia. The vaccine should be available to treat disease caused by the tubercle virus within two years, but travelers are warned to continue boiling water and avoiding contact with mosquito-infested water".
By Tracey Archer
The first reported case of Mycobacterium tuberculosis (TB) can be dated back to as early as 2400BC, but it was not until 1991 that the first global efforts to reduce TB were implemented. Tubercle bacilli is responsible for 1.7 million global deaths per yearIn 1991 the world health advocacy (WHA) declared TB a global health issue and and1994 the world health organization placed together a strategy called DOTS (direct observation therapy short-course), 184 countries participated in the DOTS program. By 2003, treatment goals were almost at the target range set by WHO which were detection of 70% of all smear-positive cases and cure of 85% of these casesstatistics showed that the DOTS program was yielding results a good 20% lower than the anticipated cure goal of 85%. This lead to an expansion of DOTS strategy in 2005 which went hand in hand with the 2006 implementation of a new strategy named the “Stop TB” strategy which focused on the expansion of DOTS as well as ‘substantial financing’ which would boost global treatment efforts
Both strategies’ involved the cooperation of Global bodies, the use of the BCG vaccine as well as antibiotics specific for the treatment of tuberculosis and an understanding of the disease states, both infectious and non infectious, latent TB and active Tb as well as MDR-TB ( multi-drug resistant TB ) and XDR- TB, (strains of TB resistant to more then one of the second line of TB medicationThe Stop TB strategy also takes into account financing, outreach programs thus increasing the number of people that access the programs and research opportunities that can lead to future developmentsThe efficiency of these strategies was examined by the global impact of vaccines old and new as well as antibiotic treatment for each strain of TB. Past and present global efforts to reduce TB were only effective when working as one and looking into the future possibilities. For over 80 years the BCG vaccine has been used as a preventative measure against tuberculosis. BCG itself is only produced in a few laboratories around the worldthen the vaccine must be transported to other countries raising the cost of the treatment. BCG can be stored in a powder form but upon preparation sterile water is required, in some instances water must be transported with the vaccine. BCG must be then used within 2-3 hours post preparation and all BCG vaccines need to be kept in a climate of at least 6-8 degrees Celsius in freezers’or fridges BCG vaccine has proven to be effective against the spread of childhood tuberculosis by providing children with an acquired immunitythis immunity can last about 15years however does not protect from Adult tuberculosis. Future possible vaccines for TB as at 2001.
vaccine
Advances in a new TB vaccine is most likely going to come from studies into the Culture filtrates, Individual proteins, Protein mixtures and Fusion proteins. In 2001 the biggest problem in the development of new vaccines was funding. Treatment for TB infected patients depends on the strain of the diseaseAntibiotics is both a past and present treatment as Mycobacterium tuberculosis. In 1945 the development of streptomycin (SM) proved to be the first break through in therapy followed by Ioniazid (INH) in 1952. Other modern day antibiotics that are used include rifampin (Rifadin, Rimactane), ethambutol (Myambutol) and pyrazinamide. Different types of TB require different medicationsLatent TB (LTB) is an area that must be addressed if reduction in TB globally is going to be achieved. Latent TB is not symptomatic but affects around 9 billon people world widetreatment requires one primary Antibiotic over 4-9 monthsActive TB requires the administration of a mixture of antibiotics usually four at once the most commonly prescribed meds are Isoniazid, rifampin (Rifadin, Rimactane, ethambutol (Myambutol)and pyrazinamide however these drugs sometimes can have no effect suggesting that the strain of TB present in the patient is resistant to the antibiotics these patients are then recognized as having MDR-TB( multi drug resistant TB).
MDR-TB( multi drug resistant TB).is defined when two or more of the first line drugs have no effect. Physicians then prescribe 2nd line defence drug such as rifapine, streptomycin, ethionamide and cyclosserine as well as new Antituberculosis drugs such as the fluoroquinolones, PA 824 and the diarylquinoline R207910in addition other treatments may be required such as Pulmonary resection, this treatment has been proven to be effectiveThere are about 300.000 cases of muti drug resistant Tb reported annuallyand 10% of these cases have been resistant to 3 or more antibiotics from the second line of defence. This resistant Tb strain is known as XDR-TB(Extensively Drug-resistant Tuberculosis)
XDR-TB has emerged due to inadequate treatment and or non compliance to treatment. It is defined by its resistance to 1st line Tb antibiotics and injectable 2nd line Antibiotics. Treatment usually consists of a mixture of 2nd line antibiotics, and possible surgery
Some strains of TB have developed that can not be matched with the XDR-TB definition indicating that new antibiotics must be developed if the Global eradication of TB is likely to succeed). XDR-TB accounts for about 10% of MDR-TB cases and when associated with the ever rising HIV epidemic some patients with XDR-TB have no options left , unfortunately if new drugs are no produced to fight this XDR-TB then the world may be on the edge of an untreatable epidemic therefore the statement that The world is a safer [place with the advent of a new vaccine against tuberculosis is indeed a needed state mment and the fact that travelers are warned to continue boiling water and avoiding contact with mosquito-infested water” is always good advice especially with the every changing strains of TB and the past ineffectiveness of current vaccines.
By Tracey Archer
The first reported case of Mycobacterium tuberculosis (TB) can be dated back to as early as 2400BC, but it was not until 1991 that the first global efforts to reduce TB were implemented. Tubercle bacilli is responsible for 1.7 million global deaths per yearIn 1991 the world health advocacy (WHA) declared TB a global health issue and and1994 the world health organization placed together a strategy called DOTS (direct observation therapy short-course), 184 countries participated in the DOTS program. By 2003, treatment goals were almost at the target range set by WHO which were detection of 70% of all smear-positive cases and cure of 85% of these casesstatistics showed that the DOTS program was yielding results a good 20% lower than the anticipated cure goal of 85%. This lead to an expansion of DOTS strategy in 2005 which went hand in hand with the 2006 implementation of a new strategy named the “Stop TB” strategy which focused on the expansion of DOTS as well as ‘substantial financing’ which would boost global treatment efforts
Both strategies’ involved the cooperation of Global bodies, the use of the BCG vaccine as well as antibiotics specific for the treatment of tuberculosis and an understanding of the disease states, both infectious and non infectious, latent TB and active Tb as well as MDR-TB ( multi-drug resistant TB ) and XDR- TB, (strains of TB resistant to more then one of the second line of TB medicationThe Stop TB strategy also takes into account financing, outreach programs thus increasing the number of people that access the programs and research opportunities that can lead to future developmentsThe efficiency of these strategies was examined by the global impact of vaccines old and new as well as antibiotic treatment for each strain of TB. Past and present global efforts to reduce TB were only effective when working as one and looking into the future possibilities. For over 80 years the BCG vaccine has been used as a preventative measure against tuberculosis. BCG itself is only produced in a few laboratories around the worldthen the vaccine must be transported to other countries raising the cost of the treatment. BCG can be stored in a powder form but upon preparation sterile water is required, in some instances water must be transported with the vaccine. BCG must be then used within 2-3 hours post preparation and all BCG vaccines need to be kept in a climate of at least 6-8 degrees Celsius in freezers’or fridges BCG vaccine has proven to be effective against the spread of childhood tuberculosis by providing children with an acquired immunitythis immunity can last about 15years however does not protect from Adult tuberculosis. Future possible vaccines for TB as at 2001.
vaccine
| vaccine | Number of cases | example |
| Avirulent sapro-phytes | 4 5 | myobacterium vaccae myobacterium microti |
| Autotrophs | 9 | Mycobacterium smegmatis Mycobacterium tuberculosis |
| Recombinants | 20 | BCG |
| Subunits | 83 | Culture filtrates,Individual proteins,Protein mixtures Fusion proteins |
| DNA vaccine | 33 | Ag 85 HSP60 |
| Mutantsans others/ fusions | 5/11 |
|
Advances in a new TB vaccine is most likely going to come from studies into the Culture filtrates, Individual proteins, Protein mixtures and Fusion proteins. In 2001 the biggest problem in the development of new vaccines was funding. Treatment for TB infected patients depends on the strain of the diseaseAntibiotics is both a past and present treatment as Mycobacterium tuberculosis. In 1945 the development of streptomycin (SM) proved to be the first break through in therapy followed by Ioniazid (INH) in 1952. Other modern day antibiotics that are used include rifampin (Rifadin, Rimactane), ethambutol (Myambutol) and pyrazinamide. Different types of TB require different medicationsLatent TB (LTB) is an area that must be addressed if reduction in TB globally is going to be achieved. Latent TB is not symptomatic but affects around 9 billon people world widetreatment requires one primary Antibiotic over 4-9 monthsActive TB requires the administration of a mixture of antibiotics usually four at once the most commonly prescribed meds are Isoniazid, rifampin (Rifadin, Rimactane, ethambutol (Myambutol)and pyrazinamide however these drugs sometimes can have no effect suggesting that the strain of TB present in the patient is resistant to the antibiotics these patients are then recognized as having MDR-TB( multi drug resistant TB).
MDR-TB( multi drug resistant TB).is defined when two or more of the first line drugs have no effect. Physicians then prescribe 2nd line defence drug such as rifapine, streptomycin, ethionamide and cyclosserine as well as new Antituberculosis drugs such as the fluoroquinolones, PA 824 and the diarylquinoline R207910in addition other treatments may be required such as Pulmonary resection, this treatment has been proven to be effectiveThere are about 300.000 cases of muti drug resistant Tb reported annuallyand 10% of these cases have been resistant to 3 or more antibiotics from the second line of defence. This resistant Tb strain is known as XDR-TB(Extensively Drug-resistant Tuberculosis)
XDR-TB has emerged due to inadequate treatment and or non compliance to treatment. It is defined by its resistance to 1st line Tb antibiotics and injectable 2nd line Antibiotics. Treatment usually consists of a mixture of 2nd line antibiotics, and possible surgery
Some strains of TB have developed that can not be matched with the XDR-TB definition indicating that new antibiotics must be developed if the Global eradication of TB is likely to succeed). XDR-TB accounts for about 10% of MDR-TB cases and when associated with the ever rising HIV epidemic some patients with XDR-TB have no options left , unfortunately if new drugs are no produced to fight this XDR-TB then the world may be on the edge of an untreatable epidemic therefore the statement that The world is a safer [place with the advent of a new vaccine against tuberculosis is indeed a needed state mment and the fact that travelers are warned to continue boiling water and avoiding contact with mosquito-infested water” is always good advice especially with the every changing strains of TB and the past ineffectiveness of current vaccines.
15.Discuss the following (fictional) press release... (version 3)
15.Discuss the following (fictional) press release... "The world is a safer [place with the advent of a new vaccine against tuberculosis announced the Health Minister during a visit to Gambia. The vaccine should be available to treat disease caused by the tubercle virus within two years, but travelers are warned to continue boiling water and avoiding contact with mosquito-infested water".
By Matthew Cozier
Mycobacterium Tuberculosis affects approximately 1/3 of the worlds population and is the single greatest threat to impoverished nations. The current vaccine available is the Bacillus_Calmette-Guérin (BCG) vaccine which is prepared from a live attenuated strain of mycobacterium bovine tuberculosis bacillus. However the current vaccine is controversial, with efficacy ranging from 20 – 80% depending on which country the vaccine is being used in. World Health Organisation estimates that the overall average total efficacy is around 50%. In many parts of the world, any improvement on the current vaccine will help to improve health and potentially erradicate tuberculosis in some countries.
The fictional press release by the Health Minister of Gambia was factually inacurate on the grounds that he referred to the infectious microbial pathogen that causes tuberculosis as a virus. Tuberculosis is a chronic bacterial infection often inhaled. It has evolved it's own ecological 'sweet spot' or niche, where the immune system may have an increasingly difficult time trying to prevent spread and proliferation of the bacteria. Upon primary infection, most of the lungs are affected, where the individual begins to cough up blood and redistribute it around the alveoli. Over time, tubercules form to contain the bacteria, where inside the mycobacterium remains dormant. When the patient is immunocompromised, these tubercules may rupture facilitating for the widespread systemic spread of the bacteria. This secondary infection is moften fatal, since the patient suffers from an extreme inflammatory reaction leading to cardiovascular shock, compounded by the fact that the lungs become inflammed, causing low pO2 to circulate the body, and some amounts of blood to be lost while the patient coughs in prolonged fits.
The nature of the health ministers advice to continue boiling water and avoiding contact with mosquito infested water is sound and complies with most good health practices in the prevention of numerous water boune and mosquito bourne diseases such as malaria or cholera ect. However the advice does not relate specifically to an even greater threat concerning the spread of tuberculosis via the respiratory route. The government warning should have featured something along the lines of “cover your mouth when coughing/sneezing” not to spit, seek urgent medical attention, use antibiotics responsibly and comply with the prescribed dosage, continue vaccinating with the current BCG vaccines and perhaps wear a mask.
The very nature of this press release may furhter be questioned on the grounds that we should be skeptical of the new vaccines safety, efficacy, cost and ease of administration. With the prevalance of tuberculosis on the upsurge in many areas of europe, africa and india, there has been new range of antibiotic resistant and vaccine resistant tuberculosis. The development of new vaccines has been one priority of the WHO for years. Some of the new forms of vaccine include a live recombinant form of the vaccine that express some antigens presented on the surface of the M.tuberculosis. While efficacy is said to be slightly higher, the survival rates are significantly improved since it does not promote such a huge immune response.
Vaccines are among the most effective and economically viable way of erradicating tuberculosis however this will not be possibnle without continued development and clinical application of post-exposure prophylaxis treatments featuring new powerful antibiotics. These treatments may be futher facilitated with improved methods of detection and clinical diagnosis. Current techniques may involve an ELISA diagnositcs test of the sputum which may be unreliable on the grounds that they return both false positives and negatives. Subsequent serum analysis may also be helpful and provide additional confirmation to the sputum test; however this may be more expensive and take longer to have the results.
This press release does highlight one aspect of the campaign against TB that concerns the combined efforts of the public, the scientific community, aid workers and the government to help erradicate this disease. Tackling these diseases requires an enormous collaborative effort, involving time, money and co-operation. Many campaigns have been hosted over the years that use advertising and public media announcements to spread the word.
Conclusion;
By Matthew Cozier
Mycobacterium Tuberculosis affects approximately 1/3 of the worlds population and is the single greatest threat to impoverished nations. The current vaccine available is the Bacillus_Calmette-Guérin (BCG) vaccine which is prepared from a live attenuated strain of mycobacterium bovine tuberculosis bacillus. However the current vaccine is controversial, with efficacy ranging from 20 – 80% depending on which country the vaccine is being used in. World Health Organisation estimates that the overall average total efficacy is around 50%. In many parts of the world, any improvement on the current vaccine will help to improve health and potentially erradicate tuberculosis in some countries.
The fictional press release by the Health Minister of Gambia was factually inacurate on the grounds that he referred to the infectious microbial pathogen that causes tuberculosis as a virus. Tuberculosis is a chronic bacterial infection often inhaled. It has evolved it's own ecological 'sweet spot' or niche, where the immune system may have an increasingly difficult time trying to prevent spread and proliferation of the bacteria. Upon primary infection, most of the lungs are affected, where the individual begins to cough up blood and redistribute it around the alveoli. Over time, tubercules form to contain the bacteria, where inside the mycobacterium remains dormant. When the patient is immunocompromised, these tubercules may rupture facilitating for the widespread systemic spread of the bacteria. This secondary infection is moften fatal, since the patient suffers from an extreme inflammatory reaction leading to cardiovascular shock, compounded by the fact that the lungs become inflammed, causing low pO2 to circulate the body, and some amounts of blood to be lost while the patient coughs in prolonged fits.
The nature of the health ministers advice to continue boiling water and avoiding contact with mosquito infested water is sound and complies with most good health practices in the prevention of numerous water boune and mosquito bourne diseases such as malaria or cholera ect. However the advice does not relate specifically to an even greater threat concerning the spread of tuberculosis via the respiratory route. The government warning should have featured something along the lines of “cover your mouth when coughing/sneezing” not to spit, seek urgent medical attention, use antibiotics responsibly and comply with the prescribed dosage, continue vaccinating with the current BCG vaccines and perhaps wear a mask.
The very nature of this press release may furhter be questioned on the grounds that we should be skeptical of the new vaccines safety, efficacy, cost and ease of administration. With the prevalance of tuberculosis on the upsurge in many areas of europe, africa and india, there has been new range of antibiotic resistant and vaccine resistant tuberculosis. The development of new vaccines has been one priority of the WHO for years. Some of the new forms of vaccine include a live recombinant form of the vaccine that express some antigens presented on the surface of the M.tuberculosis. While efficacy is said to be slightly higher, the survival rates are significantly improved since it does not promote such a huge immune response.
Vaccines are among the most effective and economically viable way of erradicating tuberculosis however this will not be possibnle without continued development and clinical application of post-exposure prophylaxis treatments featuring new powerful antibiotics. These treatments may be futher facilitated with improved methods of detection and clinical diagnosis. Current techniques may involve an ELISA diagnositcs test of the sputum which may be unreliable on the grounds that they return both false positives and negatives. Subsequent serum analysis may also be helpful and provide additional confirmation to the sputum test; however this may be more expensive and take longer to have the results.
This press release does highlight one aspect of the campaign against TB that concerns the combined efforts of the public, the scientific community, aid workers and the government to help erradicate this disease. Tackling these diseases requires an enormous collaborative effort, involving time, money and co-operation. Many campaigns have been hosted over the years that use advertising and public media announcements to spread the word.
Conclusion;
Question 14 if you were the scientific advisor to a friendly government, fighting Dr Evil (fictional leader with plans fir world domination)...
Q14 if you were the scientific advisor to a friendly government, fighting Dr Evil (fictional leader with plans for world domination), which single bioweapon would you recommend your government be most worried about?
Answered by Tracey Archer
Clostridium botulinium and botulism has incredible potency can be injested by contaminated food or water
- not always able to detect
- c.botulinim spores in soil or marine sediments contaminate meats, vegetables and fish
- spores are relatively heat resistant, they survive food processing abd acturally germinate when placed in canned foods and with the growing economic crisis who is to say that the furure wont be a bunch of canned foods
- lethal dose can be as little as a nibble can descise itself in food without effecting smell or taste the natural defence systems of the human body,
- it would only take 0.4kg could kill the earthly population.
- the toxin given off causes neurotoxins the toxin prevents the release of the neurotransmitter acetylcholine therby interfering with neurotransmission at the peripheral cholinergic synapse. Therefore stop smuscle contractingresulting in faccid peralysis even thopugh bioweapons are not that common today the use of such weapons is increasing and the children of the futire face some rough times if this is the kind of bioweapon that may be used in the future, patients generally come to paralysis and respiratory failure. Effective against everyone even babies therefore would be easy to wipe out an entire population or race.
- Seven types (A, B, C, D, E, F and G) of botulism are recognized, based on the antigenic specificity of the toxin produced by each strain. Types A, B, E and F cause human botulism. Types C and D cause most cases of botulism in animals
- The organism and its spores are widely distributed in nature. They occur in both cultivated and forest soils, bottom sediments of streams, lakes, and coastal waters, and in the intestinal tracts of fish and mammals, and in the gills and viscera of crabs and other shellfish.
- The incidence of the disease is low, but the mortality rate is high if not treated immediately and properly. There are generally between 10 to 30 outbreaks a year in the United States. Some cases of botulism may go undiagnosed because symptoms are transient or mild, or misdiagnosed as Guillain-Barre syndrome.therefore would be a good bioweapon
Answered by Tracey Archer
Clostridium botulinium and botulism has incredible potency can be injested by contaminated food or water
- not always able to detect
- c.botulinim spores in soil or marine sediments contaminate meats, vegetables and fish
- spores are relatively heat resistant, they survive food processing abd acturally germinate when placed in canned foods and with the growing economic crisis who is to say that the furure wont be a bunch of canned foods
- lethal dose can be as little as a nibble can descise itself in food without effecting smell or taste the natural defence systems of the human body,
- it would only take 0.4kg could kill the earthly population.
- the toxin given off causes neurotoxins the toxin prevents the release of the neurotransmitter acetylcholine therby interfering with neurotransmission at the peripheral cholinergic synapse. Therefore stop smuscle contractingresulting in faccid peralysis even thopugh bioweapons are not that common today the use of such weapons is increasing and the children of the futire face some rough times if this is the kind of bioweapon that may be used in the future, patients generally come to paralysis and respiratory failure. Effective against everyone even babies therefore would be easy to wipe out an entire population or race.
- Seven types (A, B, C, D, E, F and G) of botulism are recognized, based on the antigenic specificity of the toxin produced by each strain. Types A, B, E and F cause human botulism. Types C and D cause most cases of botulism in animals
- The organism and its spores are widely distributed in nature. They occur in both cultivated and forest soils, bottom sediments of streams, lakes, and coastal waters, and in the intestinal tracts of fish and mammals, and in the gills and viscera of crabs and other shellfish.
- The incidence of the disease is low, but the mortality rate is high if not treated immediately and properly. There are generally between 10 to 30 outbreaks a year in the United States. Some cases of botulism may go undiagnosed because symptoms are transient or mild, or misdiagnosed as Guillain-Barre syndrome.therefore would be a good bioweapon
Saturday, November 15, 2008
1. A microbial pathogen can be defined as: "An organism capable of causing disease". How good is this definition?
1. A microbial pathogen can be defined as: "An organism capable of causing disease". How good is this definition?
(Answered by Tracey Archer)
microbial pathogen is an organism capable of causing disease however The word organisms in this text must include pathogenic bacteria that contributes to causing diseases such as plague, tuberculosis and anthrax for example protozoa, causing diseases such as malaria, sleeping sickness and toxoplasmosis; and also fungi causing diseases such as ringworm, candidiasis or histoplasmosis. However, other diseases such as influenza, yellow fever or AIDS are caused by pathogenic viruses, which are not living organisms and are not therefore microorganisms. So it could be said that the definition itself is not correct but only one aspect of the correct definition. A microbial pathogen can be defined as: "An organism capable of causing disease" however it is not the only and maybe not the most important disease causing factor.As of 2007, no clear examples of archaean pathogens are known although a relationship has been proposed between the presence of some methanogens and human periodontal disease.so how good is this definition following are 4 disease that are considered extremely relevent to the human species by looking at each example we can deside weather or not each disease falls into this category.
Malaria is one of the most common infectious diseases and an enormous public health problem. is a vector-borne infectious disease caused by protozoan parasites. It is widespread in tropical and subtropical regions, including parts of the Americas, Asia, and Africa. Each year, there are approximately 515 million cases of malaria, killing between one and three million people, the majority of whom are young children in Sub-Saharan Africa the most serious forms of the disease are caused by Plasmodium falciparum and Plasmodium vivax, but other related species (Plasmodium ovale, Plasmodium malariae) can also affect humans. This group of human-pathogenic Plasmodium species is usually referred to as malaria parasites. Only Anopheles mosquitoes can transmit malaria and they must have been infected through a previous blood meal taken on an infected person. When a mosquito bites an infected person, a small amount of blood is taken which contains microscopic malaria parasites. About 1 week later, when the mosquito takes its next blood meal, these parasites mix with the mosquito's saliva and are injected into the person being bitten. The parasites multiply within red blood cells, causing symptoms that include symptoms of anemia (light headedness, shortness of breath, tachycardia etc.), as well as other general symptoms such as fever, chills, nausea, flu-like illness, and, in severe cases, coma and death Although some are under development, no vaccine is currently available for malaria; preventive drugs must be taken continuously to reduce the risk of infection. These prophylactic drug treatments are often too expensive for most people living in endemic areas. Most adults from endemic areas have a degree of long-term infection which tends to recur, and also possess partial immunity (resistance); the resistance reduces with time and such adults may become susceptible to severe malaria if they have spent a significant amount of time in non-endemic areas. They are strongly recommended to take full precautions if they return to an endemic area. Malaria infections are treated through the use of antimalarial drugs, such as quinine or artemisinin derivatives, although drug resistance is increasingly common.
Sleeping sickness or human African trypanosomiasis is a parasitic disease of people and animals, caused by protozoa of species Trypanosoma brucei and transmitted by the tsetse flySymptoms begin with fever, headaches, and joint pains. As the parasites enter through both the blood and lymph systems, lymph nodes often swell up to tremendous sizes. Winterbottom's sign, the telltale swollen lymph nodes along the back of the neck may appear. If untreated, the disease slowly overcomes the defenses of the infected person, and symptoms spread to include anemia, endocrine, cardiac, and kidney diseases and disorders. The disease then enters a neurological phase when the parasite passes through the blood-brain barrier. The symptoms of the second phase give the disease its name; besides confusion and reduced coordination, the sleep cycle is disturbed with bouts of fatigue punctuated with manic periods progressing to daytime slumber and nighttime insomnia. Without treatment, the disease is invariably fatal, with progressive mental deterioration leading to coma and death. Damage caused in the neurological phase can be irreversible. In addition to the bite of the tsetse fly, the disease is contractible in the following ways:
* Mother to child infection: the trypanosome can cross the placenta and infect the fetus, causing prenatal death.
* Laboratories: accidental infections, for example, through the handling of blood of an infected person and organ transplantation, although this is uncommon.
* Blood transfusion
The disease is found in two forms, depending on the parasite, either Trypanosoma brucei gambiense or Trypanosoma brucei rhodesiense. T. b. gambiense is found in central and western Africa; it causes a chronic condition that can extend in a passive phase for months or years before symptoms emerge. T. b. rhodesiense, is the acute form of the disease but has a much more limited range. It is found in southern and eastern Africa; its infection emerges in a few weeks and is more virulent and faster developing. According to recent estimates, the disability adjusted life years (9 to 10 years) (DALYs) lost due to sleeping sickness are 2.0 milliondiagnosis rests upon demonstrating trypanosomes by microscopic examination of chancre fluid, lymph node aspirates, blood, bone marrow, or, in the late stages of infection, cerebrospinal fluid. A wet preparation should be examined for the motile trypanosomes, and in addition a smear should be fixed, stained with Giemsa (or Field), Concentration techniques can be used prior to microscopic examinationblood samples, include centrifugation followed by examination of the buffy coat; mini anion-exchange/centrifugation; and the Quantitative Buffy Coat (QBC) technique. For other samples such as spinal fluid, concentration techniques include centrifugation followed by examination of the sediment. Isolation of the parasite by inoculation of rats or mice is a sensitive method, but its use is limited to T. b. rhodesiense. Antibody detection has sensitivity and specificity that are too variable for clinical decisions. In addition, in infections with T. b. rhodesiense, seroconversion occurs after the onset of clinical symptoms and thus is of limited use.
influenza Influenza, commonly known as the flu, is an infectious disease of birds and mammals caused by RNA viruses of the family Orthomyxoviridae (the influenza viruses). The name influenza comes from the Italian: influenza, meaning "influence", (Latin: influentia). In humans, common symptoms of the disease are chills and fever, sore throat, muscle pains, severe headache, coughing, weakness and general discomfort. In more serious cases, influenza causes pneumonia, which can be fatal, particularly in young children and the elderly. Although it is sometimes confused with the common cold, influenza is a much more severe disease and is caused by a different type of virus.[2] Influenza can produce nausea and vomiting, especially in children,[1] but these symptoms are more characteristic of the unrelated gastroenteritis, which is sometimes called "stomach flu" or "24-hour flu"
Typically, influenza is transmitted from infected mammals through the air by coughs or sneezes, creating aerosols containing the virus, and from infected birds through their droppings. Influenza can also be transmitted by saliva, nasal secretions, feces and blood. Infections also occur through contact with these body fluids or with contaminated surfaces. Flu viruses can remain infectious for about one week at human body temperature, over 30 days at 0 °C (32 °F), and for much longer periods at very low temperatures. Most influenza strains can be inactivated easily by disinfectants and detergents
Flu spreads around the world in seasonal epidemics, resulting in the deaths of hundreds of thousands annually — millions in pandemic years . Three influenza pandemics occurred in the 20th century and killed tens of millions of people, with each of these pandemics being caused by the appearance of a new strain of the virus in humans. Often, these new strains result from the spread of an existing flu virus to humans from other animal species. A deadly avian strain named H5N1 has posed the greatest risk for a new influenza pandemic since it first killed humans in Asia in the 1990s. Fortunately, this virus has not mutated to a form that spreads easily between people.
Vaccinations against influenza are usually given to people in developed countries with a high risk of contracting the disease and to farmed poultry. The most common human vaccine is the trivalent influenza vaccine that contains purified and inactivated material from three viral strains. Typically, this vaccine includes material from two influenza A virus subtypes and one influenza B virus strain. A vaccine formulated for one year may be ineffective in the following year, since the influenza virus changes rapidly over time, and different strains become dominant. Antiviral drugs can be used to treat influenza, with neuraminidase inhibitors being particularly effective.
The first significant step towards preventing influenza was the development in 1944 of a killed-virus vaccine for influenza by Thomas Francis, Jr.. This built on work by Frank Macfarlane Burnet, who showed that the virus lost virulence when it was cultured in fertilized hen's eggs Application of this observation by Francis allowed his group of researchers at the University of Michigan to develop the first influenza vaccine, with support from the U.S. Army.[27] The Army was deeply involved in this research due to its experience of influenza in World War I, when thousands of troops were killed by the virus in a matter of months.
AIDS Acquired immune deficiency syndrome or acquired immunodeficiency syndrome (AIDS or Aids) is a set of symptoms and infections resulting from the damage to the human immune system caused by the human immunodeficiency virus (HIV).[1] This condition progressively reduces the effectiveness of the immune system and leaves individuals susceptible to opportunistic infections and tumors. HIV is transmitted through direct contact of a mucous membrane or the bloodstream with a bodily fluid containing HIV, such as blood, semen, vaginal fluid, preseminal fluid, and breast milk.[2][3] This transmission can involve anal, vaginal or oral sex, blood transfusion, contaminated hypodermic needles, exchange between mother and baby during pregnancy, childbirth, or breastfeeding, or other exposure to one of the above bodily fluids.
AIDS is now a pandemic.[4] In 2007, an estimated 33.2 million people lived with the disease worldwide, and it killed an estimated 2.1 million people, including 330,000 children.[5] Over three-quarters of these deaths occurred in sub-Saharan Africa,[5] retarding economic growth and destroying human capital.[6] Most researchers believe that HIV originated in sub-Saharan Africa during the twentieth century.[7] AIDS was first recognized by the U.S. Centers for Disease Control and Prevention in 1981 and its cause, HIV, identified by American and French scientists in the early 1980s.[8]
Although treatments for AIDS and HIV can slow the course of the disease, there is currently no vaccine or cure. Antiretroviral treatment reduces both the mortality and the morbidity of HIV infection, but these drugs are expensive and routine access to antiretroviral medication is not available in all countries.[9] Due to the difficulty in treating HIV infection, preventing infection is a key aim in controlling the AIDS epidemic, with health organizations promoting safe sex and needle-exchange programmes in attempts to slow the spread of the virus.
The symptoms of AIDS are primarily the result of conditions that do not normally develop in individuals with healthy immune systems. Most of these conditions are infections caused by bacteria, viruses, fungi and parasites that are normally controlled by the elements of the immune system that HIV damages. Opportunistic infections are common in people with AIDS. HIV affects nearly every organ system. People with AIDS also have an increased risk of developing various cancers such as Kaposi's sarcoma, cervical cancer and cancers of the immune system known as lymphomas. Additionally, people with AIDS often have systemic symptoms of infection like fevers, sweats (particularly at night), swollen glands, chills, weakness, and weight loss. The specific opportunistic infections that AIDS patients develop depend in part on the prevalence of these infections in the geographic area in which the patient lives
The first two diseases acturally fit into the discription quite well however the 2nd two do not as they are infact pathogenic viruses.Where as you could say that microbial pathogens can be defined as “an organism that can cause disease this infact is not a good definition because noty all pathogens that cause disease are micriobes , not all microes cause disease and some pathogenic microes do not cause disease at all.
(Answered by Tracey Archer)
microbial pathogen is an organism capable of causing disease however The word organisms in this text must include pathogenic bacteria that contributes to causing diseases such as plague, tuberculosis and anthrax for example protozoa, causing diseases such as malaria, sleeping sickness and toxoplasmosis; and also fungi causing diseases such as ringworm, candidiasis or histoplasmosis. However, other diseases such as influenza, yellow fever or AIDS are caused by pathogenic viruses, which are not living organisms and are not therefore microorganisms. So it could be said that the definition itself is not correct but only one aspect of the correct definition. A microbial pathogen can be defined as: "An organism capable of causing disease" however it is not the only and maybe not the most important disease causing factor.As of 2007, no clear examples of archaean pathogens are known although a relationship has been proposed between the presence of some methanogens and human periodontal disease.so how good is this definition following are 4 disease that are considered extremely relevent to the human species by looking at each example we can deside weather or not each disease falls into this category.
Malaria is one of the most common infectious diseases and an enormous public health problem. is a vector-borne infectious disease caused by protozoan parasites. It is widespread in tropical and subtropical regions, including parts of the Americas, Asia, and Africa. Each year, there are approximately 515 million cases of malaria, killing between one and three million people, the majority of whom are young children in Sub-Saharan Africa the most serious forms of the disease are caused by Plasmodium falciparum and Plasmodium vivax, but other related species (Plasmodium ovale, Plasmodium malariae) can also affect humans. This group of human-pathogenic Plasmodium species is usually referred to as malaria parasites. Only Anopheles mosquitoes can transmit malaria and they must have been infected through a previous blood meal taken on an infected person. When a mosquito bites an infected person, a small amount of blood is taken which contains microscopic malaria parasites. About 1 week later, when the mosquito takes its next blood meal, these parasites mix with the mosquito's saliva and are injected into the person being bitten. The parasites multiply within red blood cells, causing symptoms that include symptoms of anemia (light headedness, shortness of breath, tachycardia etc.), as well as other general symptoms such as fever, chills, nausea, flu-like illness, and, in severe cases, coma and death Although some are under development, no vaccine is currently available for malaria; preventive drugs must be taken continuously to reduce the risk of infection. These prophylactic drug treatments are often too expensive for most people living in endemic areas. Most adults from endemic areas have a degree of long-term infection which tends to recur, and also possess partial immunity (resistance); the resistance reduces with time and such adults may become susceptible to severe malaria if they have spent a significant amount of time in non-endemic areas. They are strongly recommended to take full precautions if they return to an endemic area. Malaria infections are treated through the use of antimalarial drugs, such as quinine or artemisinin derivatives, although drug resistance is increasingly common.
Sleeping sickness or human African trypanosomiasis is a parasitic disease of people and animals, caused by protozoa of species Trypanosoma brucei and transmitted by the tsetse flySymptoms begin with fever, headaches, and joint pains. As the parasites enter through both the blood and lymph systems, lymph nodes often swell up to tremendous sizes. Winterbottom's sign, the telltale swollen lymph nodes along the back of the neck may appear. If untreated, the disease slowly overcomes the defenses of the infected person, and symptoms spread to include anemia, endocrine, cardiac, and kidney diseases and disorders. The disease then enters a neurological phase when the parasite passes through the blood-brain barrier. The symptoms of the second phase give the disease its name; besides confusion and reduced coordination, the sleep cycle is disturbed with bouts of fatigue punctuated with manic periods progressing to daytime slumber and nighttime insomnia. Without treatment, the disease is invariably fatal, with progressive mental deterioration leading to coma and death. Damage caused in the neurological phase can be irreversible. In addition to the bite of the tsetse fly, the disease is contractible in the following ways:
* Mother to child infection: the trypanosome can cross the placenta and infect the fetus, causing prenatal death.
* Laboratories: accidental infections, for example, through the handling of blood of an infected person and organ transplantation, although this is uncommon.
* Blood transfusion
The disease is found in two forms, depending on the parasite, either Trypanosoma brucei gambiense or Trypanosoma brucei rhodesiense. T. b. gambiense is found in central and western Africa; it causes a chronic condition that can extend in a passive phase for months or years before symptoms emerge. T. b. rhodesiense, is the acute form of the disease but has a much more limited range. It is found in southern and eastern Africa; its infection emerges in a few weeks and is more virulent and faster developing. According to recent estimates, the disability adjusted life years (9 to 10 years) (DALYs) lost due to sleeping sickness are 2.0 milliondiagnosis rests upon demonstrating trypanosomes by microscopic examination of chancre fluid, lymph node aspirates, blood, bone marrow, or, in the late stages of infection, cerebrospinal fluid. A wet preparation should be examined for the motile trypanosomes, and in addition a smear should be fixed, stained with Giemsa (or Field), Concentration techniques can be used prior to microscopic examinationblood samples, include centrifugation followed by examination of the buffy coat; mini anion-exchange/centrifugation; and the Quantitative Buffy Coat (QBC) technique. For other samples such as spinal fluid, concentration techniques include centrifugation followed by examination of the sediment. Isolation of the parasite by inoculation of rats or mice is a sensitive method, but its use is limited to T. b. rhodesiense. Antibody detection has sensitivity and specificity that are too variable for clinical decisions. In addition, in infections with T. b. rhodesiense, seroconversion occurs after the onset of clinical symptoms and thus is of limited use.
influenza Influenza, commonly known as the flu, is an infectious disease of birds and mammals caused by RNA viruses of the family Orthomyxoviridae (the influenza viruses). The name influenza comes from the Italian: influenza, meaning "influence", (Latin: influentia). In humans, common symptoms of the disease are chills and fever, sore throat, muscle pains, severe headache, coughing, weakness and general discomfort. In more serious cases, influenza causes pneumonia, which can be fatal, particularly in young children and the elderly. Although it is sometimes confused with the common cold, influenza is a much more severe disease and is caused by a different type of virus.[2] Influenza can produce nausea and vomiting, especially in children,[1] but these symptoms are more characteristic of the unrelated gastroenteritis, which is sometimes called "stomach flu" or "24-hour flu"
Typically, influenza is transmitted from infected mammals through the air by coughs or sneezes, creating aerosols containing the virus, and from infected birds through their droppings. Influenza can also be transmitted by saliva, nasal secretions, feces and blood. Infections also occur through contact with these body fluids or with contaminated surfaces. Flu viruses can remain infectious for about one week at human body temperature, over 30 days at 0 °C (32 °F), and for much longer periods at very low temperatures. Most influenza strains can be inactivated easily by disinfectants and detergents
Flu spreads around the world in seasonal epidemics, resulting in the deaths of hundreds of thousands annually — millions in pandemic years . Three influenza pandemics occurred in the 20th century and killed tens of millions of people, with each of these pandemics being caused by the appearance of a new strain of the virus in humans. Often, these new strains result from the spread of an existing flu virus to humans from other animal species. A deadly avian strain named H5N1 has posed the greatest risk for a new influenza pandemic since it first killed humans in Asia in the 1990s. Fortunately, this virus has not mutated to a form that spreads easily between people.
Vaccinations against influenza are usually given to people in developed countries with a high risk of contracting the disease and to farmed poultry. The most common human vaccine is the trivalent influenza vaccine that contains purified and inactivated material from three viral strains. Typically, this vaccine includes material from two influenza A virus subtypes and one influenza B virus strain. A vaccine formulated for one year may be ineffective in the following year, since the influenza virus changes rapidly over time, and different strains become dominant. Antiviral drugs can be used to treat influenza, with neuraminidase inhibitors being particularly effective.
The first significant step towards preventing influenza was the development in 1944 of a killed-virus vaccine for influenza by Thomas Francis, Jr.. This built on work by Frank Macfarlane Burnet, who showed that the virus lost virulence when it was cultured in fertilized hen's eggs Application of this observation by Francis allowed his group of researchers at the University of Michigan to develop the first influenza vaccine, with support from the U.S. Army.[27] The Army was deeply involved in this research due to its experience of influenza in World War I, when thousands of troops were killed by the virus in a matter of months.
AIDS Acquired immune deficiency syndrome or acquired immunodeficiency syndrome (AIDS or Aids) is a set of symptoms and infections resulting from the damage to the human immune system caused by the human immunodeficiency virus (HIV).[1] This condition progressively reduces the effectiveness of the immune system and leaves individuals susceptible to opportunistic infections and tumors. HIV is transmitted through direct contact of a mucous membrane or the bloodstream with a bodily fluid containing HIV, such as blood, semen, vaginal fluid, preseminal fluid, and breast milk.[2][3] This transmission can involve anal, vaginal or oral sex, blood transfusion, contaminated hypodermic needles, exchange between mother and baby during pregnancy, childbirth, or breastfeeding, or other exposure to one of the above bodily fluids.
AIDS is now a pandemic.[4] In 2007, an estimated 33.2 million people lived with the disease worldwide, and it killed an estimated 2.1 million people, including 330,000 children.[5] Over three-quarters of these deaths occurred in sub-Saharan Africa,[5] retarding economic growth and destroying human capital.[6] Most researchers believe that HIV originated in sub-Saharan Africa during the twentieth century.[7] AIDS was first recognized by the U.S. Centers for Disease Control and Prevention in 1981 and its cause, HIV, identified by American and French scientists in the early 1980s.[8]
Although treatments for AIDS and HIV can slow the course of the disease, there is currently no vaccine or cure. Antiretroviral treatment reduces both the mortality and the morbidity of HIV infection, but these drugs are expensive and routine access to antiretroviral medication is not available in all countries.[9] Due to the difficulty in treating HIV infection, preventing infection is a key aim in controlling the AIDS epidemic, with health organizations promoting safe sex and needle-exchange programmes in attempts to slow the spread of the virus.
The symptoms of AIDS are primarily the result of conditions that do not normally develop in individuals with healthy immune systems. Most of these conditions are infections caused by bacteria, viruses, fungi and parasites that are normally controlled by the elements of the immune system that HIV damages. Opportunistic infections are common in people with AIDS. HIV affects nearly every organ system. People with AIDS also have an increased risk of developing various cancers such as Kaposi's sarcoma, cervical cancer and cancers of the immune system known as lymphomas. Additionally, people with AIDS often have systemic symptoms of infection like fevers, sweats (particularly at night), swollen glands, chills, weakness, and weight loss. The specific opportunistic infections that AIDS patients develop depend in part on the prevalence of these infections in the geographic area in which the patient lives
The first two diseases acturally fit into the discription quite well however the 2nd two do not as they are infact pathogenic viruses.Where as you could say that microbial pathogens can be defined as “an organism that can cause disease this infact is not a good definition because noty all pathogens that cause disease are micriobes , not all microes cause disease and some pathogenic microes do not cause disease at all.
Question 1 A microbial pathogen can be defined as: "An organism capable of causing disease". How good is this definition? (ver 2)
A microbial pathogen can be defined as: "An organism capable of causing disease". How good is this definition?
The word "pathogen" is derived from a greek context confering meaning of "suffering" and "to give birth to". Currently this word refers to a biological agent that causes diseases or illness to its host. Microbial lifeforms constitute the most abundant and richly diverse group of organisms that inhabit Earth. They have adapted to environments of all extreemes, evolved in complexity and capacity to evolve. They play a key role in many aspects of life for other organisms, and are almost certainly capable of causing disease.
Various bacterial, viral, fungal, helminth and protozoan organisms have been linked to causing disease in humans. The discovery of these microbial lifeforms was first made when microscopes were invented by Robert Hooke. However for a while, many people continued to believe that human disease and suffering was considered punishment by their gods for sin and disobediance. This continued even throughout periods where disease such as the 'plague' was among the most dreaded and feared phenomenon. Finally Louis Pasteur developed the germ theory of disease, a theory that proposes that microorganisms are the cause of many diseases, and experiments conducted by Robert Koch solidified this theory in the development of Koch's Postulates.
This definition of a microbial pathogen is currently challenged by today's current understanding of molecular biology, the bodies immune system and the mechanism of a microbial infection. On what grounds does this argument hold true? What are the flaws in this argument, and can it be improved?
Most microbes found on the human body have evolved in co-evolution as commensal organisms. Microbes found on our skin create a balanced ecology forming another barrier against unwanted colonisation. Microbes found in the gut may play a similar role but may also assist in digestion and the and absorption of macro and micro-nutrients facilitating for better health through immunological protection and nutrition. However these bacteria may also present a challenge to the body when the host is immunocompromised, the ecological balance is upset or the bacteria have access to a new compartments in the body. For this reason these relatively harmless commensal microbial organisms become opportunistic pathogens. Since bacteria are the most abundant microbe that inhabits our bodies they are most frequently involved in opportunistic infections. Staphylococcus epidermidis is a relatively innocuous bacteria that lives on the epidermal layers of the skin presenting no harm to the individual. However they are commonly implicated in post-surgical complications whereby catheters have been inserted in the skin and these bacteria have a free ride into the body; subverting the need to penetrate the skin by its own mechanisms. Once in the body, the bacteria can cause many a stapylococcal infection that can lead to significant fever and potentially death.
One distinct difference among commensal microbes, opportunist microbes, and pathogens is that pathogens have evolved the genetic ability to breach the cellular and anatomic barriers that ordinarily restrict other microorganisms (Stanley Falkow). One particular bacteria of the gut; Salmonella enterica may become particularly infectious when it acquires the ability to penetrate the gut walls. Servoar 'Typhi', have been the cause of the disease typhoid fever. The organism can be transmitted by the fecal-oral route—it is excreted by humans in feces and may be transmitted by contaminated water, food, or by person-to-person contact (with inadequate attention to personal hygiene).
Viruses are especially adapted at penetrating the host, replicating and spreading throughout a host. There are countless examples including HIV, a virus renoun for its ability to reduce the immune systems' capabilities. HIV is an RNA retrovirus that has a high affinity for the CD4 antigens of T lymphocytes and antigen presentinc cells such as dedrocytes and macrophages via the gp120 protein. Once attached, the virus penetrates these cells via a complex mechanism that manipulates the cells cytoskeletal structure and leads to insertion of the viral capsid protein contents. The DS RNA genome is unwound and integrated into the host cell's DNA via a process that requires RNA dependent reverse transcriptase. The virus may reassemble many times by expressing the newly integrated genome (consisting of gag and env genes). Viruses are obligate intracellular organisms, which make an immune response difficult because the reputable antigenic proteins are rarely able to be presented to the immune system. In addition, the HIV virus is highly mutagenic, with a rate of 3 x 10-5mutations per base per cycle generating up to 10^9 to 10^10 new virons each day. This is made possible by the recombinogenic properties of reverse transcriptase. And finally, since HIV affects the CD4 cell population, mounting an immune response is made increasingly difficult with where the entire population of effector T cells are reduced.
Fungal organisms are also capable of causing disease, however more associated with localised, topical infections rather than a systemic immune attack. Candiasis is a common fungal 'yeast' infection caused by Candida Albigans that may affect regions such as the mouth or vagina where conditions are moist, tissue is soft and the cells are columnar epithelial. These fungal infections may persist where the host is either immunocompromised, or the microflora of that region has been previously disrupted by the actions of antibiotics that kill off the protective commensal bacteria.
Finally protozoan life forms such as the Plasmodium spp. have been reputably associated with Malarial diseases. These species have established a complex lifestyle that features both the Anopheles mosquito and humans for survival and proliferation.
- Can go into detail about this;
In summary of the aforementioned microbes - essentially all are somewhat capable of causing disease; either because the host's natural defense mechanisms are in decline, or that they are specifically adapted pathogenic factors that enable them to penetrate the hosts defenses.
In spite of the previous evidence; there are many aspects that may challenge the hypothesis that microbial pathogens are specifically organisms that cause disease.
Prions are a new class of disease causing entities recently discovered. Prions by definition are 'infectious proteins', that have been linked to numerous neurodegenerative disorders such as bovine sporangiform encephalopathy (BSE), crautsford jakobs disease and curarie (in humans). Analytical studies have identified whole families of these 'misfolded' proteins that are observed in nature; two major isoforms exist - PrPC and PrPSC. In humans however, prions have also been attributed as highly carcinogenic proteins. Prions can also be transfered from host to host, as notes among canibals, where eating the brain and the spinal cord have been linked to such degenerative diseases. Recently, however studies have suggested that prions may simply play a part in the normal cell function of long term memory and even stem cell renewal. However prions cannot be considered organisms, while they may self-replicate, they do not specifcally evolve and adapt to their environment as would a typical organism.
Conclusions; Since the discovery of microbes and their association with pathogenesis numerous examples of viral, fungal, bacterial, protozoan and helminth infections have been recorded somehow associated with the onset and progression of disease. The definition of a microbial pathogen has been challenged over the years on religious and ethical principals, symbiotic theories and the paradox concerning the new discovery of infectious proteins. Despite these, the theory holds true, and remains robust.
The word "pathogen" is derived from a greek context confering meaning of "suffering" and "to give birth to". Currently this word refers to a biological agent that causes diseases or illness to its host. Microbial lifeforms constitute the most abundant and richly diverse group of organisms that inhabit Earth. They have adapted to environments of all extreemes, evolved in complexity and capacity to evolve. They play a key role in many aspects of life for other organisms, and are almost certainly capable of causing disease.
Various bacterial, viral, fungal, helminth and protozoan organisms have been linked to causing disease in humans. The discovery of these microbial lifeforms was first made when microscopes were invented by Robert Hooke. However for a while, many people continued to believe that human disease and suffering was considered punishment by their gods for sin and disobediance. This continued even throughout periods where disease such as the 'plague' was among the most dreaded and feared phenomenon. Finally Louis Pasteur developed the germ theory of disease, a theory that proposes that microorganisms are the cause of many diseases, and experiments conducted by Robert Koch solidified this theory in the development of Koch's Postulates.
This definition of a microbial pathogen is currently challenged by today's current understanding of molecular biology, the bodies immune system and the mechanism of a microbial infection. On what grounds does this argument hold true? What are the flaws in this argument, and can it be improved?
Most microbes found on the human body have evolved in co-evolution as commensal organisms. Microbes found on our skin create a balanced ecology forming another barrier against unwanted colonisation. Microbes found in the gut may play a similar role but may also assist in digestion and the and absorption of macro and micro-nutrients facilitating for better health through immunological protection and nutrition. However these bacteria may also present a challenge to the body when the host is immunocompromised, the ecological balance is upset or the bacteria have access to a new compartments in the body. For this reason these relatively harmless commensal microbial organisms become opportunistic pathogens. Since bacteria are the most abundant microbe that inhabits our bodies they are most frequently involved in opportunistic infections. Staphylococcus epidermidis is a relatively innocuous bacteria that lives on the epidermal layers of the skin presenting no harm to the individual. However they are commonly implicated in post-surgical complications whereby catheters have been inserted in the skin and these bacteria have a free ride into the body; subverting the need to penetrate the skin by its own mechanisms. Once in the body, the bacteria can cause many a stapylococcal infection that can lead to significant fever and potentially death.
One distinct difference among commensal microbes, opportunist microbes, and pathogens is that pathogens have evolved the genetic ability to breach the cellular and anatomic barriers that ordinarily restrict other microorganisms (Stanley Falkow). One particular bacteria of the gut; Salmonella enterica may become particularly infectious when it acquires the ability to penetrate the gut walls. Servoar 'Typhi', have been the cause of the disease typhoid fever. The organism can be transmitted by the fecal-oral route—it is excreted by humans in feces and may be transmitted by contaminated water, food, or by person-to-person contact (with inadequate attention to personal hygiene).
Viruses are especially adapted at penetrating the host, replicating and spreading throughout a host. There are countless examples including HIV, a virus renoun for its ability to reduce the immune systems' capabilities. HIV is an RNA retrovirus that has a high affinity for the CD4 antigens of T lymphocytes and antigen presentinc cells such as dedrocytes and macrophages via the gp120 protein. Once attached, the virus penetrates these cells via a complex mechanism that manipulates the cells cytoskeletal structure and leads to insertion of the viral capsid protein contents. The DS RNA genome is unwound and integrated into the host cell's DNA via a process that requires RNA dependent reverse transcriptase. The virus may reassemble many times by expressing the newly integrated genome (consisting of gag and env genes). Viruses are obligate intracellular organisms, which make an immune response difficult because the reputable antigenic proteins are rarely able to be presented to the immune system. In addition, the HIV virus is highly mutagenic, with a rate of 3 x 10-5mutations per base per cycle generating up to 10^9 to 10^10 new virons each day. This is made possible by the recombinogenic properties of reverse transcriptase. And finally, since HIV affects the CD4 cell population, mounting an immune response is made increasingly difficult with where the entire population of effector T cells are reduced.
Fungal organisms are also capable of causing disease, however more associated with localised, topical infections rather than a systemic immune attack. Candiasis is a common fungal 'yeast' infection caused by Candida Albigans that may affect regions such as the mouth or vagina where conditions are moist, tissue is soft and the cells are columnar epithelial. These fungal infections may persist where the host is either immunocompromised, or the microflora of that region has been previously disrupted by the actions of antibiotics that kill off the protective commensal bacteria.
Finally protozoan life forms such as the Plasmodium spp. have been reputably associated with Malarial diseases. These species have established a complex lifestyle that features both the Anopheles mosquito and humans for survival and proliferation.
- Can go into detail about this;
In summary of the aforementioned microbes - essentially all are somewhat capable of causing disease; either because the host's natural defense mechanisms are in decline, or that they are specifically adapted pathogenic factors that enable them to penetrate the hosts defenses.
In spite of the previous evidence; there are many aspects that may challenge the hypothesis that microbial pathogens are specifically organisms that cause disease.
Prions are a new class of disease causing entities recently discovered. Prions by definition are 'infectious proteins', that have been linked to numerous neurodegenerative disorders such as bovine sporangiform encephalopathy (BSE), crautsford jakobs disease and curarie (in humans). Analytical studies have identified whole families of these 'misfolded' proteins that are observed in nature; two major isoforms exist - PrPC and PrPSC. In humans however, prions have also been attributed as highly carcinogenic proteins. Prions can also be transfered from host to host, as notes among canibals, where eating the brain and the spinal cord have been linked to such degenerative diseases. Recently, however studies have suggested that prions may simply play a part in the normal cell function of long term memory and even stem cell renewal. However prions cannot be considered organisms, while they may self-replicate, they do not specifcally evolve and adapt to their environment as would a typical organism.
Conclusions; Since the discovery of microbes and their association with pathogenesis numerous examples of viral, fungal, bacterial, protozoan and helminth infections have been recorded somehow associated with the onset and progression of disease. The definition of a microbial pathogen has been challenged over the years on religious and ethical principals, symbiotic theories and the paradox concerning the new discovery of infectious proteins. Despite these, the theory holds true, and remains robust.
Friday, November 14, 2008
Question 18. (2nd post) Which virus do you consider most important?
Q18. Which virus do you consider most important?
By Anna Shirley
In regards to this question, I chose influenza virus – this seems like an odd choice because its not something too many people worry about because it is both preventable and treatable. However, it has been documented throughout history and in 1918 it infected more than 2 billion people worldwide and killed 40 million – there has never been a greater loss of life in a comparable period in the history of the world, nor has there been since. In addition, it has the ability to continually mutate and reinfect people with different strains – our complacency about this seemingly harmless virus has probably contributed to its spread. However, another outbreak could be just around the corner, which was briefly seen with the avian influenza outbreak in 2006; and in today’s modern society where there is a high level of global traffic and transport, it could soon become a pandemic. Not only are there porcine influenza, avian influenza and human influenza to worry about, but an avian influenza could combine with a human influenza to create a new influenza virus. Therefore, for all these reasons, influenza is of great importance and also concern.
Essay
The influenza virus has continued to plague humanity for centuries – from ancient Greece to modern day, influenza has been documented throughout history and has killed people in their millions. In ancient times it may have been difficult to treat those affected, but in today’s society we have access to a vast array of information and vaccines to target influenza - yet people still become infected by it and can even die because of it. In 1918 the influenza pandemic was at a magnitude never seen before. It started in the USA but soon spread to Europe during World War I, affecting France, England, Spain, Germany, and Russia, before continuing onto other parts of the world such as India, China, Japan, Africa, South America and even Alaska. It then eventually returned to the USA to cause complete devastation to the population. By the end of its reign it had infected more than 2 billion individuals and killed up to 40 million people. There has never been a greater loss of life in a comparable period in the history of the world, nor has there been since. Then by 1919, it seemed to disappear as enigmatically as it had appeared.
So why is influenza still a problem? In comparison to HIV, there are vaccines against the flu so it shouldn’t be as much of a problem - yet the total mortality of the 1918–1919 pandemic killed as many as 25 million in the first 25 weeks, but HIV/AIDS only killed 25 million in its first 25 years. In contrast to the common cold (another recurring viral disease) which has hundreds of different viruses, influenza only has 3 serotypes of influenza virus (A, B and C – of which A causes most illnesses), so it should be easier to contain. Yet, we have still not been able to control or eradicate this persistant virus that is both preventable and treatable. Why is it so hard to get this one virus under control?
The influenza virus is a single stranded RNA virus that consists of 2 main proteins, haemagglutinin and neuraminidase, which are arguably the most important determinants of virulence in the influenza virus.
These proteins are usually important for attaching to host cells and also detaching once they have replicated, but these proteins are also capable of continually changing through mutation (random point mutations during RNA translation), which produces new strains of the virus. This technique is called antigenic drift, and it is the ability of the virus to exploit this process that allows influenza to constantly adapt to avoid the immune system and no longer be recognised – the host has to now mount a new response to get rid of the new strain of influenza virus. Therefore, every winter we see a different strain of influenza which brings about a different vaccine every season – no one vaccine can eradicate influenza.
However, the influenza virus is also capable of antigenic shift – the exchange of genetic information. This occurs when there is co-infection of 2 different strains of influenza virus which exchange their RNA, creating a mixture of RNA which is packaged into new virions and creates new viruses with different antigens. The virus can even potentially infect other host species. More alarmingly, if a person is co-infected with both avian and human forms of influenza, antigenic shift can allow the formation of a new influenza virus, of which the human population has no immunity against, causing a pandemic.
Influenza is also of great concern because it is easily transmissible. It is spread from person to person by talking, coughing and sneezing via airborne droplets that enter the respiratory tract, allowing the virus to penetrate the host cell and replicate. In addition, the virus tends to emerge during winter when people are more likely to be indoors and in confined spaces – both of which facilitate the spread of the virus between people. For these reasons, the virus is easily capable of spreading and potentially exploding into a pandemic.
The economic cost of influenza is also of concern. In the US alone, it is estimated that influenza is responsible for costing the economy $10 billion dollars annually, and a potential threat of an influenza pandemic in the future could cost the world close to hundreds of billions of dollars in both direct and indirect costs – and in today’s volatile economic climate, we have to ask ourselves whether we could even afford an influenza pandemic. But a global pandemic is not out of the question in today’s modern world. Overcrowding, urbanisation, global transport, simultaneous outbreaks of animal influenza and insufficient supply of influenza vaccines could all contribute to an outbreak any time soon. The WHO even estimates that if a pandemic were to occur today, influenza would cause 2-7.4 million deaths globally – health-care systems would be rapidly overburdened, economies strained, and social order disrupted. All it would take is for the influenza virus to mutate into a strain no one has any immunity towards, which in combination with these modern-day conditions would facilitate the spread of the influenza pandemic.
Conclusion
Currently, the world is not equipped to deal with a influenza pandemic, and if it were to occur we would see devastating results. Even though a person can ‘protect’ themselves with an influenza vaccine and prevent themselves from becoming infected, the high mutation rate and incidence of antigenic shift allows new strains of influenza virus to constantly emerge and threaten to infect the population. This seemingly harmless virus is currently both treatable and preventable, but if we remain complacent about it for much longer, it might soon be uncontrollable like HIV.
By Anna Shirley
In regards to this question, I chose influenza virus – this seems like an odd choice because its not something too many people worry about because it is both preventable and treatable. However, it has been documented throughout history and in 1918 it infected more than 2 billion people worldwide and killed 40 million – there has never been a greater loss of life in a comparable period in the history of the world, nor has there been since. In addition, it has the ability to continually mutate and reinfect people with different strains – our complacency about this seemingly harmless virus has probably contributed to its spread. However, another outbreak could be just around the corner, which was briefly seen with the avian influenza outbreak in 2006; and in today’s modern society where there is a high level of global traffic and transport, it could soon become a pandemic. Not only are there porcine influenza, avian influenza and human influenza to worry about, but an avian influenza could combine with a human influenza to create a new influenza virus. Therefore, for all these reasons, influenza is of great importance and also concern.
Essay
The influenza virus has continued to plague humanity for centuries – from ancient Greece to modern day, influenza has been documented throughout history and has killed people in their millions. In ancient times it may have been difficult to treat those affected, but in today’s society we have access to a vast array of information and vaccines to target influenza - yet people still become infected by it and can even die because of it. In 1918 the influenza pandemic was at a magnitude never seen before. It started in the USA but soon spread to Europe during World War I, affecting France, England, Spain, Germany, and Russia, before continuing onto other parts of the world such as India, China, Japan, Africa, South America and even Alaska. It then eventually returned to the USA to cause complete devastation to the population. By the end of its reign it had infected more than 2 billion individuals and killed up to 40 million people. There has never been a greater loss of life in a comparable period in the history of the world, nor has there been since. Then by 1919, it seemed to disappear as enigmatically as it had appeared.
So why is influenza still a problem? In comparison to HIV, there are vaccines against the flu so it shouldn’t be as much of a problem - yet the total mortality of the 1918–1919 pandemic killed as many as 25 million in the first 25 weeks, but HIV/AIDS only killed 25 million in its first 25 years. In contrast to the common cold (another recurring viral disease) which has hundreds of different viruses, influenza only has 3 serotypes of influenza virus (A, B and C – of which A causes most illnesses), so it should be easier to contain. Yet, we have still not been able to control or eradicate this persistant virus that is both preventable and treatable. Why is it so hard to get this one virus under control?
The influenza virus is a single stranded RNA virus that consists of 2 main proteins, haemagglutinin and neuraminidase, which are arguably the most important determinants of virulence in the influenza virus.
These proteins are usually important for attaching to host cells and also detaching once they have replicated, but these proteins are also capable of continually changing through mutation (random point mutations during RNA translation), which produces new strains of the virus. This technique is called antigenic drift, and it is the ability of the virus to exploit this process that allows influenza to constantly adapt to avoid the immune system and no longer be recognised – the host has to now mount a new response to get rid of the new strain of influenza virus. Therefore, every winter we see a different strain of influenza which brings about a different vaccine every season – no one vaccine can eradicate influenza.
However, the influenza virus is also capable of antigenic shift – the exchange of genetic information. This occurs when there is co-infection of 2 different strains of influenza virus which exchange their RNA, creating a mixture of RNA which is packaged into new virions and creates new viruses with different antigens. The virus can even potentially infect other host species. More alarmingly, if a person is co-infected with both avian and human forms of influenza, antigenic shift can allow the formation of a new influenza virus, of which the human population has no immunity against, causing a pandemic.
Influenza is also of great concern because it is easily transmissible. It is spread from person to person by talking, coughing and sneezing via airborne droplets that enter the respiratory tract, allowing the virus to penetrate the host cell and replicate. In addition, the virus tends to emerge during winter when people are more likely to be indoors and in confined spaces – both of which facilitate the spread of the virus between people. For these reasons, the virus is easily capable of spreading and potentially exploding into a pandemic.
The economic cost of influenza is also of concern. In the US alone, it is estimated that influenza is responsible for costing the economy $10 billion dollars annually, and a potential threat of an influenza pandemic in the future could cost the world close to hundreds of billions of dollars in both direct and indirect costs – and in today’s volatile economic climate, we have to ask ourselves whether we could even afford an influenza pandemic. But a global pandemic is not out of the question in today’s modern world. Overcrowding, urbanisation, global transport, simultaneous outbreaks of animal influenza and insufficient supply of influenza vaccines could all contribute to an outbreak any time soon. The WHO even estimates that if a pandemic were to occur today, influenza would cause 2-7.4 million deaths globally – health-care systems would be rapidly overburdened, economies strained, and social order disrupted. All it would take is for the influenza virus to mutate into a strain no one has any immunity towards, which in combination with these modern-day conditions would facilitate the spread of the influenza pandemic.
Conclusion
Currently, the world is not equipped to deal with a influenza pandemic, and if it were to occur we would see devastating results. Even though a person can ‘protect’ themselves with an influenza vaccine and prevent themselves from becoming infected, the high mutation rate and incidence of antigenic shift allows new strains of influenza virus to constantly emerge and threaten to infect the population. This seemingly harmless virus is currently both treatable and preventable, but if we remain complacent about it for much longer, it might soon be uncontrollable like HIV.
Question 20 (2nd post) Design a program to eradicate rabies as a human disease, based on your understanding of the virus’ life cycle
Rabies is a single strand RNA virus belongs to the lyssavirus family which most always results encelphaltis and death. Symptoms may occur in the host within two days of contraction or lay dominant for up to several years although the average dormancy is around 30 to 50 days which causes problem with diagnosis. It’s a zoonotic disease which can only survive briefly in the environment due to its sensitivity; therefore needing constant host interaction. The rabies virus life cycle of replication occurs in an animal host such as a canine, bat or racoon, once the virus infects a non human host it then replicates in the salivary glands, although it also infects other organs and tissues. For effective eradication of rabies as a human disease wild animal numbers need to be regulated along with domestic animals interaction with these wild animals. This virus is seldom past via human to human due to its inability to affectivity replicate in human saliva glands although it has occurred. The further spread to humans occurs when the rabies virus penetrates the skin. Infected patients have to follow treatment protocol to increase the likelihood of the patient’s survival.
The first and foremost important step in stoping rabies as a human disease is to stop human and animal interaction, although this have proven more difficult than it sounds. With modern day farming techniques and the ever expanding urban sprawls, there is more and more animal-human interaction. Animals are successfully adapting to living closely with humans. This interaction with animals increases the likelihood of contraction and transmission of this debilitating disease. Stopping human-animal interaction it is almost impossible although wild animal interaction can be decreased by making domestic properties unattractive for wild animals. Therefore by implicated more effect waste removal systems, not leaving food scraps open and outside. Educating general public and young child on what to do when they come across wild animals, for example do not provoke or feed, will decrease the likelihood of animal attacks and overall incidence rates of rabies. Also any strange activities in animals including bats should be reported so information on areas with high incidence of rabies is accurate and made known to the public. Rabies becomes an increasing problem when humans feel the need to invite animal into their homes and domesticate then, resulting in increased contact with a potential host of the rabies virus and therefore potential increase human contraction of this dreadful disease.
Just because humans imply an animal is domesticated does not mean it cannot be infected with rabies. Simple measures for common house hold pet, should be taking to reduce rabies infections in house hold pets. Fencing back yards potentially stops infected animals contact with domestic pets, fencing also reduces domestic pets roaming free. It have been documented that an increase in wild and stray dogs increases rabies in a population. By simply knowing where your pet is decreases rabies via stoping wild animal and domestic animal interactions. Routine vaccinations for domestic pets should be made mandatory where it is economically feasible. Livestock also need to be protected against rabies whether this is via vaccination or by decreasing the animal likelihood of contact with infected animals. This is done by vaccination or elimination of other animal around the livestock and making farms less attractive to wild animal. It should be noted that current vaccines are and can be rendered inactive due to viral mutations and adaption increase likelihood of humane infections.
The invention of the human vaccine for rabies has been effective in the vaccination of people in high-risk jobs, such as veterinarians, wildlife personnel, and animal control officers. Once a human has contracted the disease it is rare for human to human spread due to the virus’ inability to replicate effectively in the salivary glands of humans, although human-human spread has occurred. Theoretically humans could transmit the disease via a bite or non-bite exposure (eg kiss). Human-to-human transmission has occurred among eight recipients of transplanted corneas, in a number of countries, this was due to the donors unknowingly being previously infected with rabies. If treatment is given promptly after being exposed to or bitten by an animal that could have rabies, human illness can be prevented. Treatment consists of immediately wash the wound or exposed surface with soap and water, removal of contaminated clothing, and seed medical advice where adherences to hospital protocol is crucial therefore decreasing infection and further human-human spread.
Conclusion
The eradication of rabies virus in humans is possible if interaction with animals is highly regulated and documented. Regulation and documentation of animal interaction is very difficult especially with children, people that are constantly working with animals and in general people who love animals. With the increase in pollutions and decrease in a number of natural habitats there is going to be increase incidences of human-animal contact. Therefore if humans are educated on what to do when they are in close vicinity to a wild or domestic animal the prevalence of the rabies virus will decrease in human pollution and eventually it will be eradicated. If humans where not increasingly taking native habitats from these animals, the rabies virus would not be so common. So really humans like in many other cases are the problem in this equation.
The first and foremost important step in stoping rabies as a human disease is to stop human and animal interaction, although this have proven more difficult than it sounds. With modern day farming techniques and the ever expanding urban sprawls, there is more and more animal-human interaction. Animals are successfully adapting to living closely with humans. This interaction with animals increases the likelihood of contraction and transmission of this debilitating disease. Stopping human-animal interaction it is almost impossible although wild animal interaction can be decreased by making domestic properties unattractive for wild animals. Therefore by implicated more effect waste removal systems, not leaving food scraps open and outside. Educating general public and young child on what to do when they come across wild animals, for example do not provoke or feed, will decrease the likelihood of animal attacks and overall incidence rates of rabies. Also any strange activities in animals including bats should be reported so information on areas with high incidence of rabies is accurate and made known to the public. Rabies becomes an increasing problem when humans feel the need to invite animal into their homes and domesticate then, resulting in increased contact with a potential host of the rabies virus and therefore potential increase human contraction of this dreadful disease.
Just because humans imply an animal is domesticated does not mean it cannot be infected with rabies. Simple measures for common house hold pet, should be taking to reduce rabies infections in house hold pets. Fencing back yards potentially stops infected animals contact with domestic pets, fencing also reduces domestic pets roaming free. It have been documented that an increase in wild and stray dogs increases rabies in a population. By simply knowing where your pet is decreases rabies via stoping wild animal and domestic animal interactions. Routine vaccinations for domestic pets should be made mandatory where it is economically feasible. Livestock also need to be protected against rabies whether this is via vaccination or by decreasing the animal likelihood of contact with infected animals. This is done by vaccination or elimination of other animal around the livestock and making farms less attractive to wild animal. It should be noted that current vaccines are and can be rendered inactive due to viral mutations and adaption increase likelihood of humane infections.
The invention of the human vaccine for rabies has been effective in the vaccination of people in high-risk jobs, such as veterinarians, wildlife personnel, and animal control officers. Once a human has contracted the disease it is rare for human to human spread due to the virus’ inability to replicate effectively in the salivary glands of humans, although human-human spread has occurred. Theoretically humans could transmit the disease via a bite or non-bite exposure (eg kiss). Human-to-human transmission has occurred among eight recipients of transplanted corneas, in a number of countries, this was due to the donors unknowingly being previously infected with rabies. If treatment is given promptly after being exposed to or bitten by an animal that could have rabies, human illness can be prevented. Treatment consists of immediately wash the wound or exposed surface with soap and water, removal of contaminated clothing, and seed medical advice where adherences to hospital protocol is crucial therefore decreasing infection and further human-human spread.
Conclusion
The eradication of rabies virus in humans is possible if interaction with animals is highly regulated and documented. Regulation and documentation of animal interaction is very difficult especially with children, people that are constantly working with animals and in general people who love animals. With the increase in pollutions and decrease in a number of natural habitats there is going to be increase incidences of human-animal contact. Therefore if humans are educated on what to do when they are in close vicinity to a wild or domestic animal the prevalence of the rabies virus will decrease in human pollution and eventually it will be eradicated. If humans where not increasingly taking native habitats from these animals, the rabies virus would not be so common. So really humans like in many other cases are the problem in this equation.
Question 9:Discuss factors that have led to the global HIV pandemic (2nd Post)
QUESTION: 9
By Kaitlyn Watson
Within the global pandemic of HIV infection there are many different epidemics, each with its own dynamics and each influenced by many factors including time of introduction of the virus, population density, and cultural and social issues. Effective management strategies depend on knowledge of all these factors. The following points aim look at how the HIV virus has spread and become a pandemic killing hundreds of millions of people.
1) The contagiousness and means of transmission has lead to the spread of the disease. HIV has been detected in a number of body fluids including peripheral blood, semen, cervical secretions, breast milk, urine, cerebrospinal fluid ,saliva and tears
The three main means of infection occurs via;
· sexual contact
· intravenous drug usage
· mother-to-child transmission
Transmission via sexual contact and intravenous drug use are difficult to control. Sexual transmission of the disease and prevention means such as the use of a condom is often a difficult subject to breach due to its personal nature. Whereas intravenous drug usage is a high risk taking behaviour and therefore the additional risk of HIV infection to a drug is often not a significant factor associated with their drug usage.
2) The most important variable that has accounted for the rapid global spread of HIV-1 is increasing travel, which presented the virus an opportunity to become established in the human population and be transmitted widely by sexual intercourse and mother to infant spread. This increase in globalisation, and the improvement of transport technology, has enabled people to become more mobile. This has implications for HIV in that people who are infected can travel to and from their countries having unprotected sex, or participating in IV drug use and sharing needles, increasing the risk of HIV contraction for a number of people, globally. Global sex tourism also increases the risk of people contracting HIV, as often in these activities safer sex is not practised.
3) The spread of HIV can also be attributed in the past to blood transfusions. Although it has been rare since March 1985 when routine screen of blood products was initiated, in the past it was a great risk factor associated with blood transfusions. As a result Haemophilliacs were identified as a high risk group for contracting the disease, and consequently many of those receiving frequent blood transfusion were subsequently infected with and died of the AIDS.
4) Heterosexual transmission is now the most common means of spreading the disease in the current world. It was once thought to be exclusively a homosexual male disease however as the disease has spread to the underdeveloped world heterosexual is the most common sexual means of contracting the disease. The lack of public health messages in the past has lead to its spread.
5) Where the effects of AIDS are most predominately felt and where the greatest amounts of people are infected lie in the populations of the underdeveloped world i.e. Sub-Saharan Africa. The following issues are:
a. poor education- with a low level of education, individuals are more likely to transmit and become infected by the disease... i.e. without knowledge that condom usage can protect against sexual transmitted HIV
b. poor public health messages regarding safe sex and HIV spread
c. low income areas- in areas of low income women are more likely to engage in the sex industry where safe sex is not often practiced and the rates of IV drug usage are higher
d. poor nutrition- This can be seen in increased transmission rates from mother to child, via vertical transmission. When the mother is depleted of micronutrients in particular vitamin A, there is a significant increase in the transmission of HIV/AIDS
6) Medical transmission of HIV/AIDS is extremely rare and the documented cases do not occur frequently, however before safe practice procedures were established this means of transmission and spread was much more prevalent
7) Mother-to-child-transmission
This form of transmission parentally from mother to child can occur in the 2nd and 3rd trimester of a pregnancy, also via blood exposure during birth and subsequently through breast milk from the infected mother. This is currently preventable by the administration of antiretroviral medication to the mother from the 2nd trimester to till after the baby’s birth. Although this means of transmission is preventable, transmission in the underdeveloped world due to insufficient access to the antiretroviral drugs. Also, in the past this means of transmission has lead to millions of children being born with HIV infection and therefore has facilitated it spread throughout the underdeveloped world
Will the AIDS epidemic ever come to an end ... the biological basis for the abatement of the AIDS epidemic cannot depend on evolutionary changes in either the host or the virus, but it will require effective antiretroviral vaccination or chemotherapy to therefore end this pandemic infection.
By Kaitlyn Watson
Within the global pandemic of HIV infection there are many different epidemics, each with its own dynamics and each influenced by many factors including time of introduction of the virus, population density, and cultural and social issues. Effective management strategies depend on knowledge of all these factors. The following points aim look at how the HIV virus has spread and become a pandemic killing hundreds of millions of people.
1) The contagiousness and means of transmission has lead to the spread of the disease. HIV has been detected in a number of body fluids including peripheral blood, semen, cervical secretions, breast milk, urine, cerebrospinal fluid ,saliva and tears
The three main means of infection occurs via;
· sexual contact
· intravenous drug usage
· mother-to-child transmission
Transmission via sexual contact and intravenous drug use are difficult to control. Sexual transmission of the disease and prevention means such as the use of a condom is often a difficult subject to breach due to its personal nature. Whereas intravenous drug usage is a high risk taking behaviour and therefore the additional risk of HIV infection to a drug is often not a significant factor associated with their drug usage.
2) The most important variable that has accounted for the rapid global spread of HIV-1 is increasing travel, which presented the virus an opportunity to become established in the human population and be transmitted widely by sexual intercourse and mother to infant spread. This increase in globalisation, and the improvement of transport technology, has enabled people to become more mobile. This has implications for HIV in that people who are infected can travel to and from their countries having unprotected sex, or participating in IV drug use and sharing needles, increasing the risk of HIV contraction for a number of people, globally. Global sex tourism also increases the risk of people contracting HIV, as often in these activities safer sex is not practised.
3) The spread of HIV can also be attributed in the past to blood transfusions. Although it has been rare since March 1985 when routine screen of blood products was initiated, in the past it was a great risk factor associated with blood transfusions. As a result Haemophilliacs were identified as a high risk group for contracting the disease, and consequently many of those receiving frequent blood transfusion were subsequently infected with and died of the AIDS.
4) Heterosexual transmission is now the most common means of spreading the disease in the current world. It was once thought to be exclusively a homosexual male disease however as the disease has spread to the underdeveloped world heterosexual is the most common sexual means of contracting the disease. The lack of public health messages in the past has lead to its spread.
5) Where the effects of AIDS are most predominately felt and where the greatest amounts of people are infected lie in the populations of the underdeveloped world i.e. Sub-Saharan Africa. The following issues are:
a. poor education- with a low level of education, individuals are more likely to transmit and become infected by the disease... i.e. without knowledge that condom usage can protect against sexual transmitted HIV
b. poor public health messages regarding safe sex and HIV spread
c. low income areas- in areas of low income women are more likely to engage in the sex industry where safe sex is not often practiced and the rates of IV drug usage are higher
d. poor nutrition- This can be seen in increased transmission rates from mother to child, via vertical transmission. When the mother is depleted of micronutrients in particular vitamin A, there is a significant increase in the transmission of HIV/AIDS
6) Medical transmission of HIV/AIDS is extremely rare and the documented cases do not occur frequently, however before safe practice procedures were established this means of transmission and spread was much more prevalent
7) Mother-to-child-transmission
This form of transmission parentally from mother to child can occur in the 2nd and 3rd trimester of a pregnancy, also via blood exposure during birth and subsequently through breast milk from the infected mother. This is currently preventable by the administration of antiretroviral medication to the mother from the 2nd trimester to till after the baby’s birth. Although this means of transmission is preventable, transmission in the underdeveloped world due to insufficient access to the antiretroviral drugs. Also, in the past this means of transmission has lead to millions of children being born with HIV infection and therefore has facilitated it spread throughout the underdeveloped world
Will the AIDS epidemic ever come to an end ... the biological basis for the abatement of the AIDS epidemic cannot depend on evolutionary changes in either the host or the virus, but it will require effective antiretroviral vaccination or chemotherapy to therefore end this pandemic infection.
Question 10 Discuss drug treatments against malaria
#10 - Discuss drug treatments against malaria.
By Russell Allen
Malaria is the leading cause of death in developing countries. WHO estimates around 300-500 million people are infected with malaria each year, resulting in nearly 3 million deaths annually. Around 90% of these deaths occur in sub-Saharan Africa. Around 2.24 billion people, over 40% of the worlds population, are at a daily risk of contracting the potentially fatal disease. These statistics are staggering, considering the prophylactic and effective treatments available from the local pharmacy.
There are four different Plasmodium species of capable of causing malaria: P. ovale, P. malariae, P. vivax, and the most common P. falciparum, to which its current prevalence owes its success. P. falciparum exploits the capacity of antigenic variation to evade the attempts so far tried to eradicate the disease. In 1955 the World Health Organisation launched the Global Malaria Eradication Program, emphasizing vector control through the use of DDT spraying and national surveillance. Due to the enormous malarial reservoir present in sub-Saharan Africa, and the poor economic status of the countries which harboured the disease, it was determined that this region could not support the infrastructure required for an effective eradication program, and was largely ignored throughout the campaign. Countries involved in the campaign, including most of Europe and the United States, saw great success with a rapid decline in malaria cases. However in 1965 the project had begun to fall apart in countries like India, where political unrest and population movements contributed to the rise of the deadly disease. In 1969 the campaign was declared a failure, doomed by the inflexibility of the control measures required to sustain its success. But the biggest failure was yet to be seen. Drug resistance developed by P. falciparum meant a new form of the plasmodium had emerged, deadlier than ever. Resistance to chloroquine compounded the already devastating pathogenicity of the disease, and its effects continue to be apparent in todays endemic regions.
Many synthetic quinine analogues have since been produced to treat malaria. Chloroquine is still a highly effective initial therapy for all four human malarias, except of course the chlorquine-resistant strains of P. falciparum. Quinine, the original botanic treatment for malaria isolated from chincona bark in the 17th century, given intravenously remains an effective choice for severe malaria infections.
Regimens are often implemented to completely eradicate the parasite from the blood, and from exo-erythrocytic stages of the plasmodium life cycle, primarily in the liver. For such regimens, pyrimethamine/sulfadoxine combinations are used. Pyrimethamine inhibits the enzyme dihydrofolate reductase (DHFR), blocking the production of nucleic acids, with a much higher affinity to protozoal organisms than that of the mammalian host. Sulfadoxine works synergistically to block the same substrates, and sequentially inhibit the protozoans ability to utilize folate, essential for nucleic acid synthesis.
Doxycycline is indicated for the prevention of recurring malaria due to dormant hypnozoites in the liver. Again, this treatment follows initial therapy with quinine to eliminate both blood and tissue etiologies.
There are a range of prophylactic treatments, determined by the area destined for travel. These areas are categorized by their resistance or sensitivity to malarial drugs chloroquine and mefloquine. Other factors include length of stay, activities planned, availability of healthcare, and age. The prophylactic regimens often initiate treatment in the week leading up to the travel date, as well as one tablet daily whilst in affected areas, and completed with a daily dose up to 4 weeks after leaving such areas.
People travelling to areas where malaria is endemic are highly susceptible to being infected with malaria, even with prophylactic treatment. The goal of the treatment is not to prevent malaria infection, but rather prevent its progression into the debilitating stages of its complex life cycle. Initiatives such as the Roll-back Malaria Partnership and The Global Fund aim to provide leadership, guidance and funding to an effective eradication campaign. Much promise is resting on a new clinical trial beginning later this year in Africa, hosted by the Malaria Vaccine Initiative PATH, and funded by the Bill and Melinda Gates Foundation, it will be the biggest trial conducted on children in Africa, and will determine the safety and efficacy of the latest advances in malarial vaccines.
By Russell Allen
Malaria is the leading cause of death in developing countries. WHO estimates around 300-500 million people are infected with malaria each year, resulting in nearly 3 million deaths annually. Around 90% of these deaths occur in sub-Saharan Africa. Around 2.24 billion people, over 40% of the worlds population, are at a daily risk of contracting the potentially fatal disease. These statistics are staggering, considering the prophylactic and effective treatments available from the local pharmacy.
There are four different Plasmodium species of capable of causing malaria: P. ovale, P. malariae, P. vivax, and the most common P. falciparum, to which its current prevalence owes its success. P. falciparum exploits the capacity of antigenic variation to evade the attempts so far tried to eradicate the disease. In 1955 the World Health Organisation launched the Global Malaria Eradication Program, emphasizing vector control through the use of DDT spraying and national surveillance. Due to the enormous malarial reservoir present in sub-Saharan Africa, and the poor economic status of the countries which harboured the disease, it was determined that this region could not support the infrastructure required for an effective eradication program, and was largely ignored throughout the campaign. Countries involved in the campaign, including most of Europe and the United States, saw great success with a rapid decline in malaria cases. However in 1965 the project had begun to fall apart in countries like India, where political unrest and population movements contributed to the rise of the deadly disease. In 1969 the campaign was declared a failure, doomed by the inflexibility of the control measures required to sustain its success. But the biggest failure was yet to be seen. Drug resistance developed by P. falciparum meant a new form of the plasmodium had emerged, deadlier than ever. Resistance to chloroquine compounded the already devastating pathogenicity of the disease, and its effects continue to be apparent in todays endemic regions.
Many synthetic quinine analogues have since been produced to treat malaria. Chloroquine is still a highly effective initial therapy for all four human malarias, except of course the chlorquine-resistant strains of P. falciparum. Quinine, the original botanic treatment for malaria isolated from chincona bark in the 17th century, given intravenously remains an effective choice for severe malaria infections.
Regimens are often implemented to completely eradicate the parasite from the blood, and from exo-erythrocytic stages of the plasmodium life cycle, primarily in the liver. For such regimens, pyrimethamine/sulfadoxine combinations are used. Pyrimethamine inhibits the enzyme dihydrofolate reductase (DHFR), blocking the production of nucleic acids, with a much higher affinity to protozoal organisms than that of the mammalian host. Sulfadoxine works synergistically to block the same substrates, and sequentially inhibit the protozoans ability to utilize folate, essential for nucleic acid synthesis.
Doxycycline is indicated for the prevention of recurring malaria due to dormant hypnozoites in the liver. Again, this treatment follows initial therapy with quinine to eliminate both blood and tissue etiologies.
There are a range of prophylactic treatments, determined by the area destined for travel. These areas are categorized by their resistance or sensitivity to malarial drugs chloroquine and mefloquine. Other factors include length of stay, activities planned, availability of healthcare, and age. The prophylactic regimens often initiate treatment in the week leading up to the travel date, as well as one tablet daily whilst in affected areas, and completed with a daily dose up to 4 weeks after leaving such areas.
People travelling to areas where malaria is endemic are highly susceptible to being infected with malaria, even with prophylactic treatment. The goal of the treatment is not to prevent malaria infection, but rather prevent its progression into the debilitating stages of its complex life cycle. Initiatives such as the Roll-back Malaria Partnership and The Global Fund aim to provide leadership, guidance and funding to an effective eradication campaign. Much promise is resting on a new clinical trial beginning later this year in Africa, hosted by the Malaria Vaccine Initiative PATH, and funded by the Bill and Melinda Gates Foundation, it will be the biggest trial conducted on children in Africa, and will determine the safety and efficacy of the latest advances in malarial vaccines.
Thursday, November 13, 2008
5) Discuss progress towards vaccines to prevent the common cold
Discuss the progress towards vaccines to prevent common cold
Important note:common cold not a single disease but a conventional term for a host of dieases characterized (whats significance for vaccine development?? (from here-on the acronym will be refered to as 'dvt')) by a mild upper respiratory illness. Symptoms include nasal stuffiness, discharge (rhinorrhea), sneezing and sore throat.
Caused by numerous viruses that belong to several families (also significance to efforts to develop vaccine??), e.gs are adenovirus, parainfluenza virus, rhinovirus, respiratory synctial virus (RSV), enterovirus and coronavirus.
Some 20 to 30 percent of colds without proven viral cause (prob cant develop vaccine against unknown causative agent???)
some causative agents might still be undisvovered. Recent discovery of new causative agent , human metapneumonic virus as cause of common cold.
About 5 peercent of common cold infections characterised by more than two or more causative agents
Why develop vaccine???
common cold most common infection in humans.
Main cause of consultations with primary health care providers in the developed world (absenteeism at work etc, all take financial toll)
vaccine thought to be potentially the most effective way of controlling common cold.
Vaccine progress
One of the pertinet questions has always been whether its possible to develop a single or combined effective vaccine to combat all or most of the numerous agents against the cold.
Enormous number of organisms a big problem when it comes to vaccine development.
Possible alternative: dvt of vaccine against the more common viral causative agents ,eg during autumn up to 80 percent of infections due to rhinovirus (at least in the united states anyway).
One possible :vaccine derived from killed or split virus.works for influenza. Not an avenue explored much coz of incident with RSV vaccine trials.
RSV (respiratory synctial virus): once a potential candidate for vaccine dvt. In 1960's formalin inactivated RSV vaccine was associated with increased morbidity and mortality. When vaccine recipients were naturally exposed to RSV virus, 80 percent of RSV vaccines were hospitalized, compared to 5 percent of the control. Two fatalities resulted.
Rhinovirus: most common causative viral agent in all age groups,accounts for most of all resp illnesses. Good candidate for vaccine dvt.
Problems: more than 100 serotypes of rhinovirus have been identified as causing the common cold.
All the different serotypes induce neutralizing antibodies in their own specific way.
Absence of a suitable common antigen across the spectrum of rhinoviruses.
Current avenues of research
vaccine effect through mediated T-cell response.T cell response might be preserved through different viral strains.
Generation of T cell response normally requires endogenous expression of antigen.
Plasmid DNA encoding nucleocapsid protein of influenza known to evoke T cell response after injection into muscle. Protects not only from injected strain but other strains as well. Same appraoch used for common cold???
for parainfluenza virus: evaluation of recombinant bovine (PIV3) and human PIV3 attenuated vaccines in animal models.
11. Drugs to treat Influenza
11. Drugs to treat Influenza
Answered by Lyndsee
There are three serotypes of Influenza virus, A, B and C. Type B and C cause relatively few cases of flu (B will cause Reye’s disease in children) so the majority of flus are caused by type A. The flu is particularly dangerous because of antigenic drift and shift. Antigenic drift is point mutations that occur randomly in the RNA during transcription. Antigenic shift is the exchange of genetic information. While a vaccine has been developed against influenza, it is only able to provide immunity from three strains (if it is a multivalent vaccine), and only for a limited time period. In most cases immunity will last for no more than three years for that particular strain. However, due to constant antigenic drift and antigenic shift, the vaccine often becomes obsolete. A major problem with vaccines is that they’re difficult to culture using egged embryos. Also the strains of virus that kill poultry will also kill the egg embryo. A new technology developed to cope with these issues uses ‘reverse genetics’, whereby the viral RNA genome is converted back to DNA where manipulation to remove the pathogenic genes occurs. The genome is then converted back to RNA for vaccine production, which makes a safer non-pathogenic version of the virus that also grows more effectively in culture or egg embryo.
Amanatadine is an available, relatively cheap drug effective in the prophylaxis and also treatment of Influenza A virus. Its mechanism of action is to prevent viral uncoating of the virus upon entry into the cell. This prevents further replication of the virus due to the inhibition of viral RNA release. The process is carried out by altering the activity of the M2 protein on the membrane of influenza infected cells. This blocks the M2 ion channel. Amantadine is directed at individuals at greater risk of influenza (the elderly etc), as a prophylactic treatment. Amanatadine is also useful for those for whom the influenza vaccine is contraindicated. Amanatadine can also be given in conjunction with the vaccine, as it does not alter the vaccine’s efficacy. However amantadine is not effective against influenza-B virus or parainfluenza virus.
Amantadine is administered as a capsule, tablet or syrup. It has been shown to be 70-90% effective but adverse reactions include confusion, anxiety, insomnia, dry mouth, blurred vision, urinary retention, constipation and hallucinations. These side effects are more common in the elderly. These effects can disappear after the first week of therapy. Caution should be exercised when administering the drug to patients already taking anticholinergic medications as it may exacerbate the anticholinergic effects leading to seizures. There is also a risk of resistance developing and those taking amantadine should be kept separate from high risk contacts.
Rimantadine is another available drug similar to amantadine, however produces less side effects. Rimantadine cannot be administered to children. Rimantadine is only a little more expensive than amantadine.
Zanamivir is a selective neuraminidase inhibitor. Neuraminidase normally cleaves salicylic acid from host and viral cell surfaces facilitating the release of progeny virus from the infected host cell. Zanamivir prevents this cleavage, causing nascent viruses to clump at the host cell surface, causing a reduction in numbers of active virus. Neuraminidase is found in all strains of virus and thus is effective against all strains, unlike amantadine. It can be administered via oral inhalation which delivers the drug directly into the pulmonary site of influenza infection and minimizes systemic exposure. Risk of resistance developing is also minimal, due to the specific binding of Zanamivir onto highly conserves portions of the influenza A and B neuraminidase. No significant side effects have been experienced with Zanamivir; however the drug should be given with caution to patients with chronic obstructive pulmonary disease because of bronchospasm or lung function decline risk.
Tamiflu, another neuraminidase inhibitor is available in pill form. It is also proposed to alter virus particle aggregation and release. While very similar to Zanamivir, its side effects include nausea, vomiting, abdominal pain, dizziness, cough and fatigue. It’s also contraindicated in patients with an oseltamivir phosphate allergy.
Influenza often increases the risk of the development of a bacterial infection (opportunistic). Thus treatment often includes antibiotics.
Answered by Lyndsee
There are three serotypes of Influenza virus, A, B and C. Type B and C cause relatively few cases of flu (B will cause Reye’s disease in children) so the majority of flus are caused by type A. The flu is particularly dangerous because of antigenic drift and shift. Antigenic drift is point mutations that occur randomly in the RNA during transcription. Antigenic shift is the exchange of genetic information. While a vaccine has been developed against influenza, it is only able to provide immunity from three strains (if it is a multivalent vaccine), and only for a limited time period. In most cases immunity will last for no more than three years for that particular strain. However, due to constant antigenic drift and antigenic shift, the vaccine often becomes obsolete. A major problem with vaccines is that they’re difficult to culture using egged embryos. Also the strains of virus that kill poultry will also kill the egg embryo. A new technology developed to cope with these issues uses ‘reverse genetics’, whereby the viral RNA genome is converted back to DNA where manipulation to remove the pathogenic genes occurs. The genome is then converted back to RNA for vaccine production, which makes a safer non-pathogenic version of the virus that also grows more effectively in culture or egg embryo.
Amanatadine is an available, relatively cheap drug effective in the prophylaxis and also treatment of Influenza A virus. Its mechanism of action is to prevent viral uncoating of the virus upon entry into the cell. This prevents further replication of the virus due to the inhibition of viral RNA release. The process is carried out by altering the activity of the M2 protein on the membrane of influenza infected cells. This blocks the M2 ion channel. Amantadine is directed at individuals at greater risk of influenza (the elderly etc), as a prophylactic treatment. Amanatadine is also useful for those for whom the influenza vaccine is contraindicated. Amanatadine can also be given in conjunction with the vaccine, as it does not alter the vaccine’s efficacy. However amantadine is not effective against influenza-B virus or parainfluenza virus.
Amantadine is administered as a capsule, tablet or syrup. It has been shown to be 70-90% effective but adverse reactions include confusion, anxiety, insomnia, dry mouth, blurred vision, urinary retention, constipation and hallucinations. These side effects are more common in the elderly. These effects can disappear after the first week of therapy. Caution should be exercised when administering the drug to patients already taking anticholinergic medications as it may exacerbate the anticholinergic effects leading to seizures. There is also a risk of resistance developing and those taking amantadine should be kept separate from high risk contacts.
Rimantadine is another available drug similar to amantadine, however produces less side effects. Rimantadine cannot be administered to children. Rimantadine is only a little more expensive than amantadine.
Zanamivir is a selective neuraminidase inhibitor. Neuraminidase normally cleaves salicylic acid from host and viral cell surfaces facilitating the release of progeny virus from the infected host cell. Zanamivir prevents this cleavage, causing nascent viruses to clump at the host cell surface, causing a reduction in numbers of active virus. Neuraminidase is found in all strains of virus and thus is effective against all strains, unlike amantadine. It can be administered via oral inhalation which delivers the drug directly into the pulmonary site of influenza infection and minimizes systemic exposure. Risk of resistance developing is also minimal, due to the specific binding of Zanamivir onto highly conserves portions of the influenza A and B neuraminidase. No significant side effects have been experienced with Zanamivir; however the drug should be given with caution to patients with chronic obstructive pulmonary disease because of bronchospasm or lung function decline risk.
Tamiflu, another neuraminidase inhibitor is available in pill form. It is also proposed to alter virus particle aggregation and release. While very similar to Zanamivir, its side effects include nausea, vomiting, abdominal pain, dizziness, cough and fatigue. It’s also contraindicated in patients with an oseltamivir phosphate allergy.
Influenza often increases the risk of the development of a bacterial infection (opportunistic). Thus treatment often includes antibiotics.
Question 12: In the context of infectious disease, which bacterium do you consider most important?
The answer to this question is of course a matter of personal opinion and there is obviously no right or wrong answer. The following essay is only an example of how it may be answered.
The bacterium I have chosen to talk about may not necessarily cause the most number of deaths or have the fastest rate of infection nor is it usually the first bacterium thought of when considering the ‘most scary of bacteria causing infectious disease’ but I feel it is a good example of a class of bacterium that is going to pose a great threat in the future. This class is the SUPERBUG and the bacterium is Staphylococcus aureas, or to be more accurate vancomycin resistant Staphylococcus aureas (VRSA).
S. aureas is a spherical bacterium that is frequently found in the nose and skin of a third of the human population and usually does not cause infection. However it is an opportunistic pathogen and given the chance can cause skin infections such as pimples and carbuncles, scalded skin syndrome or life threatening diseases such as pneumoni, meningitis, osteomyelitis, endocarditis, Toxic shock syndrome (TSS) and septicemia. This organism is also considered to be the cause of the most nosocomial infections reported.
S. aureus was the first bacterium in which penicillin resistance was found—in 1947, just four years after the drug started being mass-produced. When microbes began resisting penicillin, medical researchers fought back with chemical cousins, such as methicillin and oxacillin. By 1953, the antibiotic armamentarium included chloramphenicol, neomycin, terramycin, tetracycline, and cephalosporins. Methicillin was then the antibiotic of choice, but has since been replaced by oxacillin due to significant kidney toxicity. MRSA (methicillin-resistant Staphyloccus aureus) was first detected in Britain in 1961 and is now "quite common" in hospitals. MRSA was responsible for 37% of fatal cases of blood poisoning in the UK in 1999, up from 4% in 1991. Half of all S. aureus infections in the US are resistant to penicillin, methicillin, tetracycline and erythromycin and researchers fear that we may be nearing an end to the seemingly endless flow of antimicrobial drug largely due to the major pharmaceutical companies losing interest in the antibiotics market because of these drugs no longer being as profitable as drugs that treat chronic (long-term) conditions and lifestyle issues
The epidemiology of infections caused by MRSA is rapidly changing. In the past 10 years, infections caused by this organism have emerged in the community and is now an epidemic that is responsible for rapidly progressive, fatal diseases including necrotizing pneumonia, severe sepsis and necrotizing fasciitis. The 2 MRSA clones in the United States most closely associated with community outbreaks, USA400 (MW2 strain, ST1 lineage) and USA300, often contain Panton-Valentine leukocidin (PVL) genes and, more frequently, have been associated with skin and soft tissue infections. Outbreaks of community-associated (CA)-MRSA infections have been reported in correctional facilities, among athletic teams, among military recruits, in newborn nurseries, and among active homosexual men. CA-MRSA infections now appear to be endemic in many urban regions and cause most CA-S. aureus infections
For a long period of time the antibiotic vancomycin was literally considered the drug of last resort however, strains with intermediate (4-8 ug/ml) levels of resistance, termed GISA (glycopeptide intermediate Staphylococcus aureus) or VISA (vancomycin intermediate Staphylococcus aureus), began appearing in the late 1990s. The first identified case was in Japan in 1996, and strains have since been found in hospitals in England, France and the US. In 2002, a newly reported VRSA was isolated from the catheter tip of a renal dialysis patient in Michigan. The isolate contained both the mecA gene (methicillin resistance) and the vanA gene (vancomycin resistance). The presence of the vanA gene was confirmed by polymerase chain reaction and was located on a 60-kb plasmid. The DNA sequence of the VRSA vanA gene was identical to that of a vancomycin-resistant strain of Enterococcus faecalis recovered from the same catheter tip culture. This VRSA was, thus, the first likely transfer in vivo of high-level vancomycin resistance from E faecalis to S aureus. Should this plasmid, or another one like it, be transferred from one S aureus strain to another as rapidly as was the plasmid containing the beta-lactamase gene, this may herald the demise of vancomycin as a clinically useful agent.
When asked to think about the most important bacterium in the context of infectious disease S. aureus may not be the first one that comes to mind, however it is this bacterium and others like it that are at the forefront of the ‘superbug’ emergence. It may be other superbugs such as antibiotic resistant TB that may cause the greater medical challenges in the future but at this moment in time it is bacterium like VRSA that are leading the way in gaining and spreading of antibiotic resistant genes (and have been since the introduction of antibiotics) and therefore they are the most important bacterium in the context of infectious disease at present.
The bacterium I have chosen to talk about may not necessarily cause the most number of deaths or have the fastest rate of infection nor is it usually the first bacterium thought of when considering the ‘most scary of bacteria causing infectious disease’ but I feel it is a good example of a class of bacterium that is going to pose a great threat in the future. This class is the SUPERBUG and the bacterium is Staphylococcus aureas, or to be more accurate vancomycin resistant Staphylococcus aureas (VRSA).
S. aureas is a spherical bacterium that is frequently found in the nose and skin of a third of the human population and usually does not cause infection. However it is an opportunistic pathogen and given the chance can cause skin infections such as pimples and carbuncles, scalded skin syndrome or life threatening diseases such as pneumoni, meningitis, osteomyelitis, endocarditis, Toxic shock syndrome (TSS) and septicemia. This organism is also considered to be the cause of the most nosocomial infections reported.
S. aureus was the first bacterium in which penicillin resistance was found—in 1947, just four years after the drug started being mass-produced. When microbes began resisting penicillin, medical researchers fought back with chemical cousins, such as methicillin and oxacillin. By 1953, the antibiotic armamentarium included chloramphenicol, neomycin, terramycin, tetracycline, and cephalosporins. Methicillin was then the antibiotic of choice, but has since been replaced by oxacillin due to significant kidney toxicity. MRSA (methicillin-resistant Staphyloccus aureus) was first detected in Britain in 1961 and is now "quite common" in hospitals. MRSA was responsible for 37% of fatal cases of blood poisoning in the UK in 1999, up from 4% in 1991. Half of all S. aureus infections in the US are resistant to penicillin, methicillin, tetracycline and erythromycin and researchers fear that we may be nearing an end to the seemingly endless flow of antimicrobial drug largely due to the major pharmaceutical companies losing interest in the antibiotics market because of these drugs no longer being as profitable as drugs that treat chronic (long-term) conditions and lifestyle issues
The epidemiology of infections caused by MRSA is rapidly changing. In the past 10 years, infections caused by this organism have emerged in the community and is now an epidemic that is responsible for rapidly progressive, fatal diseases including necrotizing pneumonia, severe sepsis and necrotizing fasciitis. The 2 MRSA clones in the United States most closely associated with community outbreaks, USA400 (MW2 strain, ST1 lineage) and USA300, often contain Panton-Valentine leukocidin (PVL) genes and, more frequently, have been associated with skin and soft tissue infections. Outbreaks of community-associated (CA)-MRSA infections have been reported in correctional facilities, among athletic teams, among military recruits, in newborn nurseries, and among active homosexual men. CA-MRSA infections now appear to be endemic in many urban regions and cause most CA-S. aureus infections
For a long period of time the antibiotic vancomycin was literally considered the drug of last resort however, strains with intermediate (4-8 ug/ml) levels of resistance, termed GISA (glycopeptide intermediate Staphylococcus aureus) or VISA (vancomycin intermediate Staphylococcus aureus), began appearing in the late 1990s. The first identified case was in Japan in 1996, and strains have since been found in hospitals in England, France and the US. In 2002, a newly reported VRSA was isolated from the catheter tip of a renal dialysis patient in Michigan. The isolate contained both the mecA gene (methicillin resistance) and the vanA gene (vancomycin resistance). The presence of the vanA gene was confirmed by polymerase chain reaction and was located on a 60-kb plasmid. The DNA sequence of the VRSA vanA gene was identical to that of a vancomycin-resistant strain of Enterococcus faecalis recovered from the same catheter tip culture. This VRSA was, thus, the first likely transfer in vivo of high-level vancomycin resistance from E faecalis to S aureus. Should this plasmid, or another one like it, be transferred from one S aureus strain to another as rapidly as was the plasmid containing the beta-lactamase gene, this may herald the demise of vancomycin as a clinically useful agent.
When asked to think about the most important bacterium in the context of infectious disease S. aureus may not be the first one that comes to mind, however it is this bacterium and others like it that are at the forefront of the ‘superbug’ emergence. It may be other superbugs such as antibiotic resistant TB that may cause the greater medical challenges in the future but at this moment in time it is bacterium like VRSA that are leading the way in gaining and spreading of antibiotic resistant genes (and have been since the introduction of antibiotics) and therefore they are the most important bacterium in the context of infectious disease at present.
Q19 Discuss the molecular interactions between HIV and host cells, and how these interactions almost never lead to eradication of HIV from a person
Q19 Discuss the molecular interactions between HIV and host cells, and how these interactions almost never lead to eradication of HIV from a person
Answered by: Kara-Lee.Mepstead@student.
HIV interaction Host cell never lead to eradication
HIV persists and lives in the human body as a reterovirus. HIV utilizes the cells of the immune system for survival. This enables destruction of the immune system providing a safe guard for survival of HIV.
The HIV viral capsid contains 2x single stranded RNA molecules each joined to a reverse transcriptase molecule.
- high affinity CD4 antigen
- HIV: gp120 on envelope bind CD4 antigen of T lymphocytes & APC
- gp41 attatches co-reeptor fuse with cell & enter
- reverse transcriptase: RNA—transcribed DNA
- DNA dbStrand DNA Intergrase intergrate into host DNA
- 10 billion virions/day OR dormant
Initial: CD4 death
Latency period: escape detection, remain dormant lymphoid tissues, CD4 normal, peripheral viral burden low
Exhaust the immune system avoid eradication
- virus kill infected T4 cells
- killer T-cells destroy virus infected T-cells
- Detached gp120 & 41 bind & block CD4 receptors prevent T cells responding to foreign antigens
- soluable suppressor factor released by T4
- infect/disrupt/kill CD4 receptor containing cells (esp. APC)
- Virus-initiated auto-immune response to CD4 receptors destruction cells with receptors
AIDS development
- selection viral varients resistant to neutralizing Ab.
Late stage:
- significant loss immune function
- ↑ infection, cancer death
Variability: no 1 person infected with same coated HIV hard to treat
Question 11. Answered by Samantha.
11. Drugs to treat influenza:
The main form of treatment is prevention, in the form of vaccines. The currently available vaccines are based on killed virus, and induce an immune response (mainly Ab response) to the hemagglutinin and neurimidase proteins. While the vaccines are relatively efficacious towards the virus strain/s on which they are based, the immunity they induce is short-lived and they quickly become obsolete due to the antigenic drift of the influenza virus. Newer types of vaccines include: cold-adapted attenuated live virus vaccines and “subunit” vaccines, consisting of virus proteins/peptides produced by recombinant DNA technology.
While everyone can have a bad dose of the ‘flu’, persons who are particularly at risk and should get vaccinated are diabetics, severe asthmatics, persons with heart disease/chronic lung disease, children with cyanotic congenital heart disease, persons undergoing immune-suppressive therapies and those over 65 years of age.
Various treatments are available, from the time-proven ones (rest, hydration and acetaminophen) to various antiviral agents (ribavirin and rimantadine). Ribavirin is a purine nucleoside analog with relatively broad antiviral spectrum in cell culture. It inhibits some DNA viruses and many RNA viruses, including Influenza A and B viruses, as it appears to inhibit virus replication by several different mechanisms, perhaps explaining its range of activity. The triphosphate form of ribavirin inhibits virus encoded, DNA-dependent DNA polymerases and possibly RNA-dependent RNA polymerases as well. Ribavirin monophosphate inhibits inosine monophosphate dehydrogenase, leading to an overall reduction in cellular pools of GTP, which in turn resistricts viral (and cellular) nucleic acid synthesis. In addition it impairs capping of virus-specific messenger RNA (by the addition of methylated guanine nucleotides to the 5’ end of RNA molecules). The relatively broad spectrum of ribavirin is accompanied by a concomitant lack of potency at nontoxic doses, probably because the mechanisms by which it inhibits viruses are nonspecific and also inhibit cellular enzymes. Lack of specificity translates into poor clinical activity for most viral infections.
The anti-influenza drugs Amantadine and Rimantadine target the entry of the influenza virus into host cells, specifically the A strain. The primary mechanism of action involves disrupting virus entry by preventing virion disassembly. The influenza A virion contains a transmembrane protein M2, that is well conserved among human and avian strains. The M2 protein functions as an H+ ion channel. Influenza virus enters cells through endosomes, and the M2 protein allows H+ ions to move from endosomes into the virion interior during the entry process. The flux of H+ ions decreases the pH in the virion, which is necessary for conformational changes in the influenza virus nucleocapsid protein that allow movement of the viral ribonucleoproteins (containing the viral genome segments) into the cell nucleus to establish infection. Amantadine and Rimantadine inhibit the ion channel function of M2, presumably by their large structures blocking the channel through which the ions flow. They effect impedes influenza virion disassembly after internalization through endosomes. Resistance to Amantadine and Rimantadine occurs with a single amino acid substitutions at particular points in the transmembrane region of M2 that prevent drug binding within the channel. When treatment is initiated before exposure to the virus, the drugs prevent clinical disease in more than 75% of cases. About 3-5% of amantadine recipients report mild CNS reactions, including anxiety, insomnia, and difficulty concentrating. The main use has been prophylaxis in individuals who are at increased risk of severe infection during suspected influenza A virus epidemics. A major limitation of the drugs is that they are not active against influenza B strains; drug disruption of M2 function is specific for influenza A strains.
Question 10. Answered by Samantha
10. Discuss drug therapies against malaria.
Malaria: Is the most important of all protozoan diseases, perhaps the most important infectious disease (except maybe mycobacterium), causes 2.3% of global disease, caused by P.falciparum, P.vivax, P. malariae and P.ovale. Reemerging disease is falciparum. Natural immunity to malaria is imperfect – the fact which also translates into a major impediment for vaccine development. Even persons who have lived all their lives in endemic areas, and have evidence of strong humoral and cellular immunity may get infected. The difference is that clinical manifestations tend to be less severe that in non-immune persons. Chloriquine is the most widely used (and misused) drug for antimalarial chemoprophylaxis and treatment. Chloriquine, and other quinine-based drugs, enter the parasite’s food vacuole, where RBC hemoglobin is degraded for the nutrition of the parasite. Normally, toxic heme released by this degradation is detoxified and converted to harmless malarial pigment. Chloriquine blocks heme detoxification and kills the parasite. Chloriquine resistance occurs by mutation of a vacuolar membrane protein that causes Chloriquine to be pumped out of the food vacuole and permits heme detoxification to resume.
While Chloriquine originally was effective against all four species of Plasmodium infecting humans, most P.falciparum strains circulating in Africa, SE Asia, and South-America have developed resistance to this drug. The alternative drug-of-choice for Chloriquine-resistant P.falciparum used to be Fancidar (trade name for a combination drug). However, any of the malaria strains are now double resistant. In addition, Fansidar has potential unwanted side-effects. Currently, if an infection with P.falciparum is acquired in a geographic area known to host Chloriquine/Fancidar resistant malaria, a combination-therapy with newer alternative drugs is applied. However, the best preventative measure is not to be bitten by a mosquito in the first place. So apart from schemes of applying environmental insecticides and drainage to floodways (expensive), as a visitor to malaria-endemic areas can protect yourself by simply measures such as mosquito nets, insect-repellants and protective clothing. Many experimental vaccines are under development.
Patients infected with Chloriquine-resistant P.falciparum can be treated with other agents, such as Malarone (a fixed combination of atovaquone and proguanil), mefloquine, quinine, quinidine, halofantrine or artesunate. At present, P.falciparum cases acquired in areas where drug resistance is prevalent are usually treated in the United States with a combination of doxycycline and quinine, Malarone, or quinidine. Mefloquine, a quinine derivative, is also active against Chloriquine-resistant strains but is often toxic at treatment doses. However, it is a mainstay for chemoprophylaxis in travelers to most areas with Chloriquine-resistant malaria. Unfortunately, resistance to mefloquine has also been detected in parts of SE Asia, and travelers to that area are now being advised to take daily doxycycline to prevent infection. Although all of the antimalarials mentioned are effective in controlling acute infection caused by P.vivax or P.ovale, none is effective against the liver (hypnozoite/exo-erythrocytic) stages of those species. Primaquine, a derivative of quinine, is effective against the hypnozoite stages. It is used with Chloriquine to prevent late relapses associated with maturation of the hypnozoite to the tissue schizont stage and the subsequent release of infectious merozoites. However, Primaquine is more toxic than Chloriquine and causes nausea, vomiting and diarrhea. In patients with G6P deficiency, Primaquine induces hemolysis. Primaquine is not indicated for either P.falciparum or P.malariae infections because those parasites do not produce a dormant (hypnozoite) stage in the liver.
Question 5. Answered by Samantha
5. Discuss progress towards vaccines to prevent the common cold.
Because conventional vaccine approaches do not appear feasible, current efforts are directed towards identifying effective antiviral compounds against rhinoviruses.
Following most rhinovirus infections, neutralizing antibodies develop in serum and nasal secretions. Unfortunately, those antibodies are only effective in preventing infection by the same rhinovirus serotype. Therefore, infection with a different serotype can readily occur. A vaccine to prevent rhinovirus infection does not appear feasible because it would have to comprise more than 100 serotypes. Nevertheless, several novel approaches to prophylaxis have been explored. One is the use of recombinant interferon-α administered by nasal spray. When given for 5 days before viral infection, interferon was 80% effective in preventing illness. However, when given longer than 5 days, interferon led to nasal symptoms as bothersome as those of a cold. Interferon treatment of rhinovirus infection is no longer being pursued because it is not effective in clearing an established infection. Antiviral drugs that inhibit various stages of the life cycle have been developed. They include compounds that bind the viral capsid and block uncoating of the viral RNA and inhibitors of the viral proteases. Although some of the compounds have proven safe and effective in clinical trials, their effectiveness is reduced by the emergence of resistant viral strains. Further compromising the effectiveness of antiviral drugs is the short duration of virus shedding and illness.
Wednesday, November 12, 2008
Question 3.
Discuss: “As with other infectious agents, the clinical manifestations of parasitic disease may reflect tissue damage by the parasite, the effects of the host immune system, or both.”
Cienne Morton
Parasites invade and damage their host, who retaliates by releasing a barrage of harmful factors upon the parasite or parasite-infected cells. The symptoms of infectious disease reflect these hostile exchanges between host and parasite. Clinical manifestations of the disease can be a result of parasite-mediated tissue damage (e.g. due to toxin release or cell lysis), nonspecific damage caused by the immune system (the immune system killing the body’s own cells), or not really damaging at all, but inconvenient characteristics of a heightened immune response (like a runny nose and minor headache).
Parasite-mediated damage
- Microbial damage to the host is usually in the form of toxins or other factors that degrade cells. The effect of bacterial toxins is seen in the clinical presentation of botulism, tetanus, bacterial dysentery, anthrax and cholera. The clinical presentation of parasitic diseases is similarly dictated by parasitic destruction of host tissue. Examples are given below:
Plasmodium (protozoan - malaria)
o Causes erythrocytes to display ‘sticky’ protein on cell surface, making them adhere to vessel walls. This can block some vessels and lead to lack of perfusion to blood brain barrier, leading to coma
o Haemolysis by the parasite causes anaemia and haemoglobinuria
Naegleria (protozoan - amoeboid meningoencephalitis)
o attacks brain tissue: primary amoebic meningoencephalitis
o ‘eats’ brain tissue through trogocytosis (uptake of plasma membrane constituents) and release of cytolytic molecules and protein-degrading enzymes
o Confusion
o Loss of balance, seizures, hallucination
o Altered sense of taste, smell
o Serious, less than 1% survival in later stages
Leishmania (protozoan - leishmaniasis)
o Cutaneous: skin lesions
o Visceral (infects liver, spleen) – most serious, near 100% mortality if untreated
Trypanosoma brucei (protozoan - African sleeping sickness)
o Crosses blood brain barrier, infects brain
o neurological disturbances: diurnal somnolence and nocturnal insomnia
o extrapyramidal (tremor, motor incoordination)
Ascariasis (helminth)
o Nutrional deficiency (worm feeds on food from host in intestines)
Immune system-mediated symptoms
- The clinical presentation of a disease is hardly ever due to parasitic tissue damage alone. Whenever a pathogen attacks a host, an immune response will be triggered. Infection by a microbe triggers inflammation, the protective response of the host. Many symptoms common to different infections are due to inflammation, triggered by the pathogen but facilitated by the body’s own immune system, such as a runny nose, coughing and sneezing. The immune response plays an important role in influencing the clinical presentation of parasitic diseases. Examples of immune-mediated symptoms are:
redness, swelling, pain, pus at site of skin infection
o chancre in some cases of trypanosomiasis at site of fly bite
rash
o trypanosomiasis
lymphadenopathy
o Winterbottom’s sign in trypanosomiasis
hepatomegaly, splenomegaly are signs of immune upregulation
o trypanosomiasis
o malaria
o schistosomiasis
o leishmaniasis
While damage may be caused by an invading parasite, the sensation of pain is caused by the body. Symptoms such as headache and abdominal pain are due to the body while signs like damage are due to the parasite.
o Headache in malaria, naegleria infection, trypanosomiasis
o Abdominal pain: schistosomiasis (helminthic)
Fever: caused by pyrogenic factors that are released by the nervous system in response to infection and is present in a multitude of infectious diseases.
o Malaria
o Trypanosomiasis
o Leishmaniasis
o Naegleria
o Schistosomiasis
Diarrhoea: can be pathogenic, triggered by invading pathogen or substance, or can be mediated by the host in a bid to expel gastrointestinal parasites. Present in schistosomiasis
Anaemia:
o Journals have recently reported that haemolysis by Plasmodium may only account for 10% of the red blood cell destruction associated with malaria. 90% of the destruction may actually be due to phagocytes ingesting non-infected red blood cells.
The immune-mediated symptoms above are designed to protect the host, but on occasion the immune system may inadvertently potentiate the disease. African Sleeping sickness (trypanosomiasis) is characterised by an early (haemolymphatic) and late (meningoencephalitic stage). In the latter stage, the trypanosomes have traversed the blood brain barrier and interfere with neurological function. The mechanism by which the protozoa penetrate the blood brain barrier is not fully characterised, but it has been reported that the immune response may play a part. Upon inflammation, the immune system releases inflammatory cytokines that increase the permeability of blood vessels (like prostaglandins, TNF-alpha, IFN-gamma), so that when brain-associated capillaries become inflamed, the normally impermeable endothelium becomes permeabilised. In this case, the immune system aids the progression of trypanosomiasis, and may actually facilitate the neurological stage of the disease.
In parasitic diseases discussed here, both parasite-mediated damage and the host immune response influence the clinical presentation of a disease.
Q10; Discuss drug therapies against malaria.
Q10; Discuss drug therapies against malaria.
By Matthew Cozier
Antimalarial drugs are those that are designed to prevent or cure malaria. There are two major classes of antimalarial drugs – tissue schizonticidal and blood schizonticidal drugs. This is because the malarial parasites Plasmodium spp. Live in the body in a variety of forms. There are four major subtypes of Plasmodium that cause malaria. Plasmodium vivax, Plasmodium malariae, Plasmodium falciparum & Plasmodium ovale. It is important to first understand the lifecycle of these microbes in order to discuss the current drug therapies against malaria.
Malaria presents a major challenge to economic and social development] in developing countries where approximately 515 million people are affected each year. The current strategies aimed at fighting malaria, as supported by the WHO and the Bill & Melinda Gates Foundation include developing new effective drug therapies against malaria, distributing them, decreasing the cost and providing these therapies to those in need.
Malaria is transferred from human to human by way of mosquitos enacting as vectors. If one mosquito bites a human, the exchange of saliva for blood allows the entry of a Plasmodium spp. Into the body, effectively penetrating the hosts primary defenses. At this point in the lifecycle, malarial microbes are refered to as sprozoites by which make their way to the liver through the circulatory system. Once they reach the liver, they may proliferate in numbers multiplying in numbers asexually and asymptomatically for a period of 6–15 days. Sometimes, at this stage, the malarial parasites form hypnozoites that are able to remain dormant for 6-12 months. Eventually, they move out of the liver and back into the bloodstream as Merozoites, specifically able to infect red blood cells (RBC's). The Merozoites cause the most damage to the blood reducing reducing the capacity of RBC's to carry oxygen around the body. Some Merozoites will turn into Gametocytes, that are taken up by the Mosquito in circulation. Once inside the mosquito these Gametocytes reproduce sexually and migrate to the salivary glands of the mosquito inducing salivary production and facilitating for its own spread once the mosquito bites another individual.
The immune system remains powerless against malaria since the parasites occupy the liver and erythrocytes, hiding from cells. In any case when malaria spends a relatively short period outside any cell of the body. This makes the potential use and production of a vaccine against malaria very unlikely. However the anti-malarial drugs are designed to target malaria at various stages of the lifestyle.
Blood Schizonticidal agents;
- Chloroquinine; affect on haem disposal, prevent digestion of hemoglobin and reducing supply of amino acids needed for parasite viability essentially we're starving their vital requirements to survive.
-- at high [] it prevents RNA and DNA synthesis
-- treatment of chloroquine senstivie malaria resistance with P.falciparin in most parts of the world increased expression of MDR-ABC transporters,
-- Oral IM, SC, IV forms of chloroquine available - does tend to concentrate in the affected cells
released slowly by the liver and metabolised by the liver
- Quinine dervived from cinchona bark binds malarial DNA inhibits haem polymerase works similar to chloroquininie does not affect the liver forms of malaria.
--The primary chemotherapeutic agent against falciparum, and may be used in combination with doxycycline or pyrimethamine in suladoxine.
-- Given in 7 day oral gcourses or slow IV infusion
-- Bolus dose, contraindicated due to risk of arrythmias Mefloquine;
-- Inhibits haem polymerase
-- Not generally used in australaia due to severe neuropsychotic reactions as part of their SE's. P
Proguanil and pyrimethamine
- prevents utilisation of folate
- inhibits conversion of dihydrofolate to tetrahydrofolate by dihydrofolate reductase
- High affinity for plasmodial enzyme than human form.
- Proguanil is used as an alternative to mefloquine pyrimethamine with sulphadoxine is used for the treatment of uncomplicated chlrooquinine-resitant p.falciparum with quinine.
- Few untoward effects.
Doxycyclie & tetracycline
- prevents ribosomal synthesis of proteins and hence replication of these parasites...
used in areas where methaquine and chloroquinine resistance is known...
Tissue Schozonitical agents;
- Rdical cures and attack parasties of the liver (hypnozoites)
- Effective against; P.Vivax and P.ovale
- Primaquinin
-- mechanism of action unknown
-- resistance rare
-- few unwanted SE's – only that of the GIT. Chemoprophylais;
-- start 1 week before entering area with malaria or 2-3 weeks if using mefloquinine
plus 4 weeks after leaving infected area
-- Block link between exo-erythrocytic and erythrocytic stages.
-- Prevent development of malarial attacks kill parasites as they emerge from the liver
They DON”T prevent primary infection of the liver...
Prevent transmission; destroy gametocytes primaquine, proguanil, pyrimethamine
The relative cost of these drugs is something to consider. New drugs such as Atovaquone may cost up to 5euro's for a tablet with adult doses consisting of in excess of 3 tablets per day.
These drug therapies are limited however in that they do not target the reservoir for infection which presides in the mosquito population. Non-pharmacological agents such as DDT have been used in the past to kill mosquitos. In addition, fly nets, repellants and avoiding swampy areas where these mosquitos live and breed is commonly recommended to prevent encouter with malaria.
By Matthew Cozier
Antimalarial drugs are those that are designed to prevent or cure malaria. There are two major classes of antimalarial drugs – tissue schizonticidal and blood schizonticidal drugs. This is because the malarial parasites Plasmodium spp. Live in the body in a variety of forms. There are four major subtypes of Plasmodium that cause malaria. Plasmodium vivax, Plasmodium malariae, Plasmodium falciparum & Plasmodium ovale. It is important to first understand the lifecycle of these microbes in order to discuss the current drug therapies against malaria.
Malaria presents a major challenge to economic and social development] in developing countries where approximately 515 million people are affected each year. The current strategies aimed at fighting malaria, as supported by the WHO and the Bill & Melinda Gates Foundation include developing new effective drug therapies against malaria, distributing them, decreasing the cost and providing these therapies to those in need.
Malaria is transferred from human to human by way of mosquitos enacting as vectors. If one mosquito bites a human, the exchange of saliva for blood allows the entry of a Plasmodium spp. Into the body, effectively penetrating the hosts primary defenses. At this point in the lifecycle, malarial microbes are refered to as sprozoites by which make their way to the liver through the circulatory system. Once they reach the liver, they may proliferate in numbers multiplying in numbers asexually and asymptomatically for a period of 6–15 days. Sometimes, at this stage, the malarial parasites form hypnozoites that are able to remain dormant for 6-12 months. Eventually, they move out of the liver and back into the bloodstream as Merozoites, specifically able to infect red blood cells (RBC's). The Merozoites cause the most damage to the blood reducing reducing the capacity of RBC's to carry oxygen around the body. Some Merozoites will turn into Gametocytes, that are taken up by the Mosquito in circulation. Once inside the mosquito these Gametocytes reproduce sexually and migrate to the salivary glands of the mosquito inducing salivary production and facilitating for its own spread once the mosquito bites another individual.
The immune system remains powerless against malaria since the parasites occupy the liver and erythrocytes, hiding from cells. In any case when malaria spends a relatively short period outside any cell of the body. This makes the potential use and production of a vaccine against malaria very unlikely. However the anti-malarial drugs are designed to target malaria at various stages of the lifestyle.
Blood Schizonticidal agents;
- Chloroquinine; affect on haem disposal, prevent digestion of hemoglobin and reducing supply of amino acids needed for parasite viability essentially we're starving their vital requirements to survive.
-- at high [] it prevents RNA and DNA synthesis
-- treatment of chloroquine senstivie malaria resistance with P.falciparin in most parts of the world increased expression of MDR-ABC transporters,
-- Oral IM, SC, IV forms of chloroquine available - does tend to concentrate in the affected cells
released slowly by the liver and metabolised by the liver
- Quinine dervived from cinchona bark binds malarial DNA inhibits haem polymerase works similar to chloroquininie does not affect the liver forms of malaria.
--The primary chemotherapeutic agent against falciparum, and may be used in combination with doxycycline or pyrimethamine in suladoxine.
-- Given in 7 day oral gcourses or slow IV infusion
-- Bolus dose, contraindicated due to risk of arrythmias Mefloquine;
-- Inhibits haem polymerase
-- Not generally used in australaia due to severe neuropsychotic reactions as part of their SE's. P
Proguanil and pyrimethamine
- prevents utilisation of folate
- inhibits conversion of dihydrofolate to tetrahydrofolate by dihydrofolate reductase
- High affinity for plasmodial enzyme than human form.
- Proguanil is used as an alternative to mefloquine pyrimethamine with sulphadoxine is used for the treatment of uncomplicated chlrooquinine-resitant p.falciparum with quinine.
- Few untoward effects.
Doxycyclie & tetracycline
- prevents ribosomal synthesis of proteins and hence replication of these parasites...
used in areas where methaquine and chloroquinine resistance is known...
Tissue Schozonitical agents;
- Rdical cures and attack parasties of the liver (hypnozoites)
- Effective against; P.Vivax and P.ovale
- Primaquinin
-- mechanism of action unknown
-- resistance rare
-- few unwanted SE's – only that of the GIT. Chemoprophylais;
-- start 1 week before entering area with malaria or 2-3 weeks if using mefloquinine
plus 4 weeks after leaving infected area
-- Block link between exo-erythrocytic and erythrocytic stages.
-- Prevent development of malarial attacks kill parasites as they emerge from the liver
They DON”T prevent primary infection of the liver...
Prevent transmission; destroy gametocytes primaquine, proguanil, pyrimethamine
The relative cost of these drugs is something to consider. New drugs such as Atovaquone may cost up to 5euro's for a tablet with adult doses consisting of in excess of 3 tablets per day.
These drug therapies are limited however in that they do not target the reservoir for infection which presides in the mosquito population. Non-pharmacological agents such as DDT have been used in the past to kill mosquitos. In addition, fly nets, repellants and avoiding swampy areas where these mosquitos live and breed is commonly recommended to prevent encouter with malaria.
Subscribe to:
Comments (Atom)