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Original Title
Malaria / orthodontic courses by Indian dental academy
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and offering a wide range of dental certified courses in different formats.
Indian dental academy provides dental crown & Bridge,rotary endodontics,fixed orthodontics,
Dental implants courses. For details pls visit www.indiandentalacademy.com ,or call
0091-9248678078
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and offering a wide range of dental certified courses in different formats.
Indian dental academy provides dental crown & Bridge,rotary endodontics,fixed orthodontics,
Dental implants courses. For details pls visit www.indiandentalacademy.com ,or call
0091-9248678078
www.indiandentalacademy.com Phylum Apicomplexa Chapters 8 & 9 Phylum Apicomplexa consists of 4 groups of protozoan parasites:
1.
2.
3.
4.
We will examine the first 3 groups, as they contain many parasites of medical and veterinary importance.
We will omit the gregarines as they are parasites of invertebrates and are not important.
www.indiandentalacademy.com Characteristics of the Phylum Apicomplexa 1. ______________________________________________________________
2. Possess _______________________________________________________ - these organelles are concentrated at _______________________________ - function? ____________________________________ - see diagram in text p. 124
3. _______________________________________
4. _______________________________________ - alternation of _____________________________ - hosts?
www.indiandentalacademy.com Plasmodium and Malaria Chapter 9 Malaria is one of the most important diseases of mankind. It has played an important part in the rise and fall of nations and has killed untold millions of persons. Today, __________________________are infected with malaria 1.5 billion people (2/3 of the world's population) live in endemic areas and are potential hosts. Malaria kills _____________________ people each year. In areas of Africa with high malaria transmission, an estimated ________________ people die of malaria each year over 2700 deaths per day, or 2 deaths per minute.
www.indiandentalacademy.com Plasmodium and Malaria Chapter 9 In areas of Africa with high malaria transmission, an estimated ________________people die of malaria each year over 2700 deaths per day or 1 death every 30 seconds. Uganda 12 million infections/population 31 million Tanzania 11 million infections/population 40 million Ethiopia 9 million infections/population 78 million www.indiandentalacademy.com Species of Plasmodium The genus Plasmodium contains 127 species in lizards, birds, and mammals. life cycle worked out in a bird species (Plasmodium relictum) rodent species (P. berghei) important in research (we will do an experimental infection of this parasite in lab) several species in monkeys and apes are similar to human species - important in drug studies four species infect humans they are: P. vivax, P. falciparum, P. malariae, P. ovale
www.indiandentalacademy.com Species of Plasmodium VECTOR ____________________________________________ several species can serve as vectors ___________________feed on blood and vector malaria
SURVIVAL OF MALARIA is dependent upon: 1. Many infected humans 2. Many Anopheles mosquitoes 3. Good contact between these 2 hosts
www.indiandentalacademy.com Life Cycle of Plasmodium The life cycle is complex, so we will go through it step by step to understand it. www.indiandentalacademy.com Life Cycle of Plasmodium Human Cycle 1. An infected Anopheles mosquito bites a human and _______________________________ into the bloodstream 2. Within 30 minutes, the sporozoites enter _________________________ and begin the PRE- ERYTHROCYTIC INCUBATION (lasts for about a week). 3. Within the liver cell, the sporozoite becomes a trophozoite divides by schizogony to form a multinucleate form called a ____________________________ individual nuclei will form ____________________________
www.indiandentalacademy.com Life Cycle of Plasmodium Human Cycle 4. Liver cell ruptures to release the merozoites In 2 species of malaria, some of these merozoites will re-invade liver cells to begin a new cycle in the liver - called the EXO-ERYTHROCYTIC CYCLE. Cryptozoites in these liver cells become dormant and are called _________________________________ Merozoites may break out of hypnozoites years later and enter rbc's causing a _________________________________ In all species, most or all of the merozoites leave the liver and enter the bloodstream
www.indiandentalacademy.com Life Cycle of Plasmodium Human Cycle
5. In the ERYTHROCYTIC CYCLE, a merozoite penetrates a rbc and transforms into a uninucleate _______________________________ 6. Trophozoite undergoes schizogony and becomes a multinucleate ______________________________ 7. Schizont ruptures rbc to release ______________________________ - This coincides with the onset of a fever followed by a period of chills. - Length of time of fever/chill cycle varies by species 8. Merozoites re-invade erythrocytes initiating a new erythrocytic cycle. This process is repeated over and over again resulting in the destruction of rbc's.
www.indiandentalacademy.com Life Cycle of Plasmodium Human Cycle
9. Not all the merozoites re-entering rbc's become trophozoites - some transform into gametocytes. _____________________________ are female _____________________________ are male. 10. Rbc's containing gametocytes are infective to an Anopheles mosquito when she bites and takes another blood meal.
www.indiandentalacademy.com Life Cycle of Plasmodium Mosquito Cycle
11. In the mosquito stomach: macrogametocyte undergoes meiosis to become a __________________________ microgametocyte undergoes meiosis to form 6 - 8 elongate ___________________________ in a process called ___________________________ 12. The microgametes detach. Each swims to find a macrogamete, penetrates it, and syngamy occurs to form a ____________________ 13. Zygote elongates to form an ___________________________ which penetrates the stomach wall and comes to lie on the outside of the stomach.
www.indiandentalacademy.com Life Cycle of Plasmodium Mosquito Cycle
14. Ookinete rounds up to form the _________________________ 15. Within the oocyst, sporogony (a type of asexual multiple fission) occurs, resulting in an enlarged oocyst containing thousands of __________________________ 16. Oocyst bursts releasing the sporozoites into the body cavity. 17. Sporozoites migrate to the __________________________ __________________________ and are injected into the human bloodstream with the next blood meal.
www.indiandentalacademy.com Life Cycle of Plasmodium Review of Human Cycle from text page 150
www.indiandentalacademy.com Life Cycle of Plasmodium Review of Mosquito Cycle from text page 150
www.indiandentalacademy.com Some Stages of Malaria in Anopheles Feeding female Anopheles Exflagellation showing microgametes Oocysts on outside of mosquito stomach Sporozoites from salivary gland www.indiandentalacademy.com Some Stages of Malaria in the human Cryptozoite in liver cell it will burst releasing merozoites Schizont multinucleate form in rbc Trophozoite uninucleate form in rbc Gametocyte uninucleate form in rbc www.indiandentalacademy.com Plasmodium vivax Disease is ________________________________________________________ "tertian" indicates that the parasite undergoes a ____________ erythrocytic cycle in human rbc's (parasites invade rbc's every third day, hence tertian) "benign" indicates that the species is ____________________________ Has an exo-erythrocytic cycle resulting in ____________________________ occurring every 2-3 years up to 8 years. Was once the most common and widely distributed species - occurred throughout tropical and temperate regions of the world. once occurred in Wisconsin Habitat now - ____________________________________ ___________________________________ This species is responsible for ____________ of malaria in the world.
www.indiandentalacademy.com Plasmodium falciparum distribution (2005) Plasmodium vivax distribution (2005) www.indiandentalacademy.com Plasmodium vivax stages in human blood Ring-stage Trophozoite 1.
2.
Mature Trophozoite 1.
2.
3. www.indiandentalacademy.com Plasmodium vivax stages in human blood Schizont 1. 2. 3. 4.
Gametocyte (we will not distinguish between macro- and microgametocytes) 1. 2. 3. 4. www.indiandentalacademy.com Plasmodium ovale Disease is _____________________________________________________ produces mild disease 48 hour erythrocytic cycle _______________________________________ - occurs in scattered areas of western Africa, India, and islands of the western Pacific (Philippines, New Guinea) Nearly identical to P. vivax and is difficult to differentiate from this species from P. vivax we will not distinguish between P. vivax and P. ovale in human blood smears examined in lab Is responsible for ___________________ % of world malaria.
www.indiandentalacademy.com Plasmodium ovale stages in human blood Ring-stage Trophozoite 1.
2.
Mature Trophozoite 1.
2.
3. www.indiandentalacademy.com Plasmodium ovale stages in human blood Schizont 1. 2. 3. 4.
Gametocyte 1. 2. 3. 4. www.indiandentalacademy.com Plasmodium malariae Causes _________________________________ - quartan indicates a ______________________ erythrocytic cycle Occurs throughout the tropics but has a discontinuous distribution Also occurs in chimpanzees but is not considered a zoonosis as wild chimps and humans do not live together in nature for disease transmission to occur between them Relapse? ______________________________________________________ A human can be infected for many years with no apparent symptoms, and the parasite can suddenly become pathogenic. This phenomenon is called __________________________________. Fatalities are not uncommon. Is responsible for ___________% of world's malaria.
www.indiandentalacademy.com Plasmodium malariae stages in human blood Ring-stage Trophozoite 1.
2.
Mature Trophozoite 1.
2.
3.
www.indiandentalacademy.com Plasmodium malariae stages in human blood Schizont 1. 2. 3. 4.
Gametocyte 1. 2. 3. 4. www.indiandentalacademy.com Plasmodium falciparum Disease is __________________________________________________________ "tertian" indicates a 40-48 hr. cycle in rbc's "malignant" indicates it is the most virulent of the 4 human species P. falciparum is the greatest killer of humanity in the tropics. it was responsible for the decline of the Greek civilization, the destruction of the Crusades, and caused more death in the Pacific in WWII than battles. it is the most dangerous because more rbc's are infected and destroyed - death occurs commonly 8-10 months after infection. Relapse? __________________________________________________________ Occurs today throughout the tropics and is responsible for ___________ % of the world's malaria.
www.indiandentalacademy.com Plasmodium falciparum stages in human blood Ring-stage Trophozoite 1.
2.
Mature Trophozoites and Schizonts disappear from peripheral blood and are not seen
Gametocyte 1. 2 3.
www.indiandentalacademy.com Plasmodium falciparum distribution (2005) Plasmodium vivax distribution (2005) www.indiandentalacademy.com History of Malaria Disease has been known since antiquity - one of first reports described fevers in 1550 BC. Malaria was commonly found in swampy areas and was thought to be contracted by breathing in "bad air" (= mal aria) in the swamps. Much effort was directed towards finding a causative agent in the water or air of these swamps. We now know that the mosquitoes that vector the disease lived in these swamps. www.indiandentalacademy.com History of Malaria First breakthrough - French physician _______________________ identified the parasites in the rbc's of malaria patients in 1880. Laveran also witnessed an unusual step in the life cycle called exflagellation.
_____________________ (1885) differentiated some species of Plasmodium and noted changes in the parasites associated with the fever - chill cycle.
www.indiandentalacademy.com History of Malaria Next breakthrough involved the mode of transmission. In the 1890's a famous British scientist ___________________________________ ___ theorized that mosquitoes may be involved in malaria transmission. Manson had recently found that mosquitoes could vector filarial worms that caused elephantiasis So why couldn't they also vector malaria?
www.indiandentalacademy.com History of Malaria Manson convinced one of his students ________________________, a physician on leave from the Indian Medical Service, to test his hypothesis. Ross went back to India and began dissecting mosquitoes. After 2 years of dissecting mosquitoes, _____________ ___________________________________________________ In 1897 ___________________________________________ __________________________________by feeding Anopheles mosquitoes on infected birds. Before Ross could prove transmission to humans, he was transferred to work on kala azar. He was awarded a Nobel Prize in Medicine in 1902.
www.indiandentalacademy.com History of Malaria Two Italians ____________________________________(1898) experimentally transmitted malaria from mosquitoes to humans.
It was not until 1948 that the complete life cycle was known when the pre-erythrocytic and exo-erythrocytic stages were found in the liver of infected humans by ________________________________.
www.indiandentalacademy.com History of Malaria Last name important in the history of malaria is that of ________________________________, a sanitation officer (ENPH!) in the Panama Canal Zone. In 1906, he used the knowledge of mosquito transmission of malaria and yellow fever (a viral disease) to begin a ______________________________ _______________. By 1913, the number of malaria cases had been greatly reduced and the building of the Panama Canal was undertaken.
www.indiandentalacademy.com Pathology of Malaria Infections During the pre-erythrocytic and exo-erythocytic cycles in the liver, there is ___________________________________________. Pathology of all 4 species occurs during the erythrocytic cycle by the synchronous rupture of schizonts and release of merozoites which destroy erythrocytes. www.indiandentalacademy.com Pathology of Malaria Infections All 4 species show the following 3 pathological effects: 1. ____________________________________ - as the rbc's are invaded and destroyed, there is a _______________________ _________________________________________________. 2. __________________________________________________ - shown by a low hematocrit 3. ___________________________________ - liver and spleen are overwhelmed in the breakdown and recycling of these destroyed rbc's results? ___________________________________________
www.indiandentalacademy.com Pathological Differences among the 4 species
Plasmodium vivax and Plasmodium ovale
Paroxysm lasts ________________ and represents the time from invasion of rbcs by merozoites until new merozoites are produced (length of erythrocytic cycle) www.indiandentalacademy.com Plasmodium vivax and Plasmodium ovale pathology
These malarias cause a long-term disease because they have the ability to ___________________________. Relapse involves the ability of cryptozoites in the liver cells during the exo-erythrocytic cycle to become dormant for long periods. The dormant cryptozoites are called _________________________________. Drug treatment or the immune system will effectively remove the erythrocytic forms, and the symptoms of malaria disappear - often for 2-3 years. For some reason (we do not know why), the hypnozoites become active and release new merozoites to invade the rbcs - the person has a malarial relapse. www.indiandentalacademy.com Plasmodium vivax and Plasmodium ovale pathology
Most individuals recover from these infections and the parasites are __________________________. Generally, the immune system totally eliminates the parasites after about 8 years.
In quartan malaria, merozoites of Plasmodium malariae primarily invade _________________________. There is no exo-erythrocytic cycle, so all the merozoites formed from cryptozoites invade rbcs after the pre-erythrocytic incubation (no relapse). Malarial paroxysms occur every __________________ and represent the time from merozoite invasion of rbcs to the formation of new merozoites (length of erythrocytic cycle).
This parasite produces a phenonomen called a _____________________________________. Numbers of infected rbc's can become very low that a person shows no signs of the disease. This period may last for years and the person believes he/she is free of the disease. For some unknown reason, the parasites increase their numbers, invade many new rbcs, destroy them, and cause severe anemia. Longest lasting recrudescence was 53 years. recent problem in __________________________________ How dangerous?____________________________________
Falciparum malaria is the most serious of the 4 species, usually resulting in a fatality. Remember that only the ring-stage trophozoites and gametocytes are found in peripheral blood mature trophozoites and schizonts are in rbcs of the spleen and bone marrow. There is _____________________________________, so all merozoites from the liver enter rbcs - ______________________
The erythrocytic cycle lasts from ______________ hours. Malarial paroxysm is unusual: ____________________________ _____________________________________________________
Falciparum malaria is the most pathogenic for the following reasons: 1. Merozoites invades _______________________________ - thus, more rbc's are infected and destroyed. 2. More destroyed rbcs leads to serious _____________________. 3. With more destroyed rbcs to recycle, liver and spleen enlarge - _______________________________- and often fail. 4. Infected blood becomes viscous, often plugging capillaries in the brain causing ______________________________________
5. Massive rbc destruction results in high levels of hemoglobin removed by the kidneys. Urine often becomes dark. Result? _________________________________________ 6. ______________________________________ occurs when plasma fills the lungs 7. ______________________________________occurs failure of many organs leads to shock
A combination of any of these pathologies leads to death in 8-10 months.
www.indiandentalacademy.com Sickle Cell Anemia
Presence of falciparum malaria has resulted in the maintenance of another disease which affects black persons in Africa. Cause:
www.indiandentalacademy.com Sickle Cell Anemia
Persons who are ___________________________ have rbcs that are sickle shaped, and die of other factors by age 30. However, if a person is ___________________________ for the sickle-cell anemia, rbcs are normal shaped but are protected from invasion of merozoites of P. falciparum; thus, the person is protected from falciparum malaria.
Selective pressure of malaria in Africa has led to the maintenance of an otherwise undesirable gene in the population. Problem today?
www.indiandentalacademy.com Diagnosis and Treatment of Malaria
DIAGNOSIS - identify parasites within human erythrocytes in a s stained blood smear (this is what we are doing in lab)
www.indiandentalacademy.com Treatment of Malaria
TREATMENT 1. _________________________ used from 1640 WWII; ____________________________________ from _____________________; used as final resort now.
2. Qinqhaosu used to make new drug from SE Asia called Artemisinin; commercially available in SE Asia and Africa; not in North America & Europe drugs from plant extracts work by ___________________________________ use? __________________________________
www.indiandentalacademy.com 3. ____________________________________________________ - synthetic drugs developed in WWII and used today
chloroquine (=Aralen) and mefloquine (=Lariam) destroys __________________________________________________
used in mixtures of chloroquine-primaquine or mefloquine- primaquine for P. vivax and P. ovale; chloroquine or mefloquine used individually for P. malariae
www.indiandentalacademy.com Treatment of Malaria
Chloroquine and mefloquine can be taken as a preventative - ______________________________ - by anyone travelling into a malarious area to reduce risk of infection. See Health Information for International Travelers from CDC or on the web at http://www.cdc.gov/travel/
Chloroquine is effective against vivax, ovale, and most malariae
www.indiandentalacademy.com Chloroquine resistant P. falciparum common
Chloroquine resistant P. malariae in _______________________ www.indiandentalacademy.com Treatment of Malaria
Mefloquine (Lariam) was developed in 1993 to combat chloroquine-resistant P. falciparum; it is effective against all 4 species
used as both a preventative and a treatment Works by _____________________________________ side effects include sunburning, nausea, diarrhea, and vaginal yeast infections in women. Not for pregnant women and children under 8 used as in areas of chloroquine and mefloquine resistance to P. falciparum used as an alternative for travelers who cannot or choose not to take mefloquine or Malarone.
www.indiandentalacademy.com Treatment of Malaria 5. _______________________________ developed in 1980 to destroy erythrocytic forms of P. falciparum
Causes side effects as skin rash, poor healing, excessive bleeding, and diarrhea
Problem -
www.indiandentalacademy.com Treatment of Malaria
6. ________________________________ new drug that became available in July, 2000 to combat drug resistant P. falciparum
Has been shown to be 98% effective in treating P. falciparum
Kills schizonts of P. falciparum
Problem -
Question?
www.indiandentalacademy.com
7. New drug Fosmidomycin reported in journal Science in 2002
Drug shuts down enzyme in metabolic pathway of malaria; appears to be effective against drug-resistant malaria
Effective in mouse studies
Human trials just started no results yet
Will it work against Plasmodium falciparum? www.indiandentalacademy.com Distribution of Malaria in the World Extent of malaria in the world before any eradication programs were started. www.indiandentalacademy.com Distribution of Malaria in the World www.indiandentalacademy.com Malaria in the U.S. About ______________cases of malaria are diagnosed in the U.S. each year. How were Americans infected? www.indiandentalacademy.com Malaria in the U.S. Malaria was once a major problem in southern & midwestern U.S. Species present were ___________________________________. Wisconsin had both species. www.indiandentalacademy.com Malaria in the U.S. By the 1950's malaria was eradicated from the U.S. due to: 1. 2.
www.indiandentalacademy.com Malaria Eradication
Because malaria eradication was successful in the U.S., the World Health Organization began a worldwide eradication program in 1956. What did they have for eradication? 1.
2.
It was thought that this was it for malaria.
www.indiandentalacademy.com Malaria Eradication
Eradication was successful during much of the 1960's but problems began to occur in the 1970's and continue today. Example: in 1947, 7 million cases of malaria reported in India in 1966, 40,000 cases of malaria in India (height of control) in 1977, 5 million cases were diagnosed in 1990s, 3 million cases
Eradication was failing. Why?
www.indiandentalacademy.com Malaria eradication failed. Why? 1. Money was not available to combat mosquitoes or treat human cases. (Energy crisis of 1970's took alot of money away from malaria eradication) 2. Disease occurs in third-world countries where the disease is poorly understood by the masses. 3. Trained medical personnel and hospitals are few in number in these countries. 4. Resistance of P. falciparum to chloroquine, mefloquine, and Fansidar. 5. Resistance of Anopheles mosquitoes to DDT and other insecticides www.indiandentalacademy.com Malaria Prevention 1. Avoid mosquito bites use insecticides, repellents, netting 2. Chemoprophylaxis with chloroquine, mefloquine, and Fansidar but this a problem in areas with P. falciparum resistant strains New finding: In October, 2000, researchers at the US Institute of Allergy and Infectious Diseases announced they found that the mutation of a single gene in the Plasmodium parasite is responsible for the emergence of chloroquine resistance. Formerly it was believed that a number of mutations spread over a number of genes was likely responsible. If this result holds up, it should make it easier to potentially alter chloroquine in such a way as to evade the parasite's new-found resistance and make chloroquine an effective treatment for malaria once again.
www.indiandentalacademy.com Malaria Prevention 3. Malaria vaccine a circumsporozoite vaccine (called SPf66) has been developed, but human trials have not been promising (under 50% protection) A new vaccine consisting of Plasmodium genes and hepatitis antigens that works with T lymphocytes has been developed. Preliminary tests rated it as being 65% effective against P. falciparum. More extensive tests are currently underway. Recent funding available from the ____________________________Foundation Several Nobel prizes in medicine await for the development of effective malaria vaccines.
www.indiandentalacademy.com www.indiandentalacademy.com Despite all these advances, malaria will likely be with us as long as there are humans on this earth.
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