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Jin Liqun Department of Parasitology Shantou University Medical College email@example.com
Plasmodium (Malarial Parasites)
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What is malaria?
Malaria is a serious and sometimes fatal disease caused by a parasite. Patients with malaria typically are very sick with high fevers, shaking chills, and flu-like illness. Four kinds of malaria parasites can infect humans: Plasmodium falciparum, P. vivax, P. ovale, and P. malariae.
Infection with any of the malaria species can make a person feel very ill; infection with P. falciparum, if not promptly treated, may be fatal. Although malaria can be a fatal disease, illness and death from malaria are largely preventable.
Is malaria a common disease?
Yes. The World Health Organization estimates that each year 300-500 million cases of malaria occur and more than 1 million people die of malaria.
Is malaria a serious disease?
Yes. Malaria is a leading cause of death and disease worldwide, especially in developing countries. Most deaths occur in young children. For example, in Africa, a child dies from malaria every 30 seconds.
• Blood parasites of the genus Plasmodium. • There are 156 named species of Plasmodium which infect various species of vertebrates.
These are P. falciparum （恶性疟原虫 ） P. vivax （间日疟原虫） P. malariae （三日疟原虫） and P. ovale （卵形疟原虫 ）
Four Plasmodium species are responsible for human malaria
Sporozoa （孢子虫） (without conspicuous locomotory organelles) Complicated life cycle: 1) Two types of hosts 2) Multiple stages 3) Human infection is caused by bite of an infected female mosquito.
In Human body
1 Exoerythrocytic stage （ schizogony 红外期裂体 生殖 ) (in liver) 2 Erythrocytic stage （ schizogony 红内期裂体生 殖） (in blood) 3 Formation of gametocytes （配子体）
1 Completion of gametogony （配子生殖） 2 Sporogony （孢子生殖）
• The malaria parasite life cycle involves two hosts. • During a blood meal, a malariainfected female Anopheles mosquito （按蚊） inoculates sporozoites( 子孢子 ) into the human host
• Sporozoites （子孢子） infect liver cells and mature into schizonts （裂殖体） , which rupture and release merozoites （裂殖子）
• Merozoites （裂殖子） infect red blood cells . • The ring stage trophozoites mature into schizonts, which rupture releasing merozoites
• Some parasites differentiate into sexual erythrocytic stages (gametocytes)
• Blood stage parasites are responsible for the clinical manifestations of the disease.
• The gametocytes （配子体） , male (microgametocytes) and female (macrogametocytes), are ingested by an Anopheles mosquito during a blood meal
• The parasites’ multiplication in the mosquito is known as the sporogony( 孢子生殖 ). • In the mosquito‘s stomach, the microgametes （雄配子，小配子） penetrate the macrogametes （雌 配子，大配子） generating zygotes
• The zygotes in turn become motile and elongated (ookinetes 动合子 ) • which invade the midgut wall of the mosquito where they develop into oocysts （卵囊）
• The oocysts grow, rupture, and release sporozoites （子孢子） , which make their way to the mosquito‘s salivary glands （唾腺）
• Inoculation of the sporozoites into a new human host perpetuates the malaria life cycle .
• 1* The sporozoite is infective stage. • 2* There are two kinds of sporozoites, tachysporozoite( 速发型子孢子 ) and brady-sporozoite ( 迟发型子孢子 ) • 3* When the brady-sporozoites get into the liver cells , they undergo dormancy （休眠期） and called hypnozoites( 休眠子 )
Exflagellation( 出丝现象 )
• The process of • male gametocyte to • form male gamete.
• Malarial parasite trophozoites are generally ring shaped, 1-2 microns in size, although other forms (ameboid and band) may also exist. • The sexual forms of the parasite (gametocytes) are much larger and 7-14 microns in size. • P. falciparum is the largest and is banana shaped, while others are
Ring form: (Plasmodium vivax ) a ring of bluish cytoplasm with a dot-like nucleus
Trophzoite of Plasmodium vivax
• irregular cytoplasm and enlarged nucleus with malarial pigment • ( hemozoin)
Schizont of P.vivax
• multiple masses of nuclear chromatin
Note: compact cytoplasm and absence of nuclear division.
Ring form of P. falciparum
Ring with double nuclei
Gametocyte of P. falciparum
banana shaped gametocyte ( P. falciparum)
Trophozoites of P.malariae
band-like or elliptic
• • In peripheral blood, every erythrocytic stages can be found in P. vivax and P. malariae infections. • Only ring forms and gametocytes can be found in P. falciparum infection. • Other stages of P. falciparum do not appear in the blood. (they hide in deep tissues)
Malaria occurs in over 100 countries and territories. More than 40% of the world’s population is at risk. Large areas of Central and South America, the Caribbean island (that is divided between Haiti and the Dominican Republic), Africa, the Indian subcontinent, Southeast Asia, the Middle East, and Oceania are considered malaria-risk areas.
Paroxysm( 发作 ) Cold stage Fever (39- 41degrees C ) Profuse perspiration and the temperature begins to drop. Within a few hours the patient feels exhausted but symptomless and remains symptomatic until the next paroxysm
2 Typical symptoms Chilly stage (30min – 1 hr, cold and shivering) hot stage (1-4 hr, intense heat and delirium 谵妄）
sweating and crisis stage (1-2 hr)copious perspiration （ Three successive stages ） Fever is associated with severe headache, nausea (vomiting) and convulsions
3 The mechanism of the paroxysm
Rupture of R B Cs (schizonts)
merozoites, metabolic substances, hemozoin engulfed by white cells and monocytes to produce pyrogens( 热原质 )
temperature regulating center(hypothalamus) Fever
4 Relapse （复发） : Some patients relapse back in to disease weeks, months even years after the apparent cure. (The cause of relapse is hypnozoite activation) 5 Recrudenscence （再燃）： The paroxysm appears in some patients after inadequate or incomplete treatment. ( The cause is the remained erythrocytic stage multiplication )
What are the signs and symptoms of malaria? Symptoms of malaria include fever and flulike illness, including shaking chills, headache, muscle aches, and tiredness. Nausea, vomiting, and diarrhea may also occur. Malaria may cause anemia and jaundice (yellow coloring of the skin and eyes) because of the loss of red blood cells. Infection with one type of malaria, Plasmodium falciparum, if not promptly treated, may cause kidney failure, seizures, mental confusion, coma, and death.
Incubation Period Following the infective bite by the Anopheles mosquito a period of time (the "incubation period") goes by before the first symptoms appear. The incubation period in most cases varies from 7 to 30 days. The shorter periods are observed most frequently with P. falciparum and the longer ones with P. malariae.
The classical (but rarely observed) malaria attack lasts 6-10 hours. It consists of a cold stage (sensation of cold, shivering) ; a hot stage (fever, headaches, vomiting; seizures in young children) and finally a sweating stage (sweats, return to normal temperature, tiredness)
Period (days) merozoites (No) period (hours) merozoites (No) _________________________________________________________ P. vivax 8 1200 48 16 P. malariae 11 ? 72 8 P. falciparum 6 4000 36-48 24 ________________________________________________________ Related with incubation perod Related with paroxysm
Classically (but infrequently observed) the attacks occur every second day with the "tertian" parasites (P. falciparum, P. vivax, and P. ovale) and every third day with the "quartan" parasite (P. malariae).
• More commonly, the patient presents with a combination of the following symptoms: • Fever • Chills • Sweats • Headaches • Nausea and vomiting • Body aches • General discomfort
Severe malaria occurs when P. falciparum infections are complicated by serious organ failures or abnormalities in the patient's blood or metabolism
• Cerebral malaria, with abnormal behavior, impairment of consciousness, seizures, coma, or other neurologic abnormalities • Severe anemia due to hemolysis (destruction of the red blood cells) • Hemoglobinuria (hemoglobin in the urine) due to hemolysis • Pulmonary edema (fluid buildup in the lungs) or acute respiratory distress syndrome (ARDS), which may occur even after the parasite counts have decreased in response to treatment • Abnormalities in blood coagulation and thrombocytopenia (decrease in blood platelets) • Cardiovascular collapse and shock
Acute kidney failure Hyperparasitemia, where more than 5% of the red blood cells are infected by malaria parasites Metabolic acidosis (excessive acidity in the blood and tissue fluids), often in association with hypoglycemia Hypoglycemia (low blood glucose). Hypoglycemia may also occur in pregnant women with uncomplicated malaria, or after treatment with quinine.
In P. vivax and P. ovale infections, patients having recovered from the first episode of illness may suffer several additional attacks ("relapses") after months or even years without symptoms. Relapses occur because P. vivax and P. ovale have dormant liver stage parasites (hypnozoites)that may reactivate.
Malaria during pregnancy(especially P. falciparum) may cause severe disease in the mother, and may lead to premature delivery or delivery of a low-birth-weight baby.
On rare occasions, P. vivax malaria can cause rupture of the spleen or acute respiratory distress syndrome (ARDS).
Nephrotic syndrome (a chronic, severe kidney disease) can result from chronic or repeated infections with P. malariae.
1 Anemia 2 Splenomegaly 3 Cerebral malaria 4 Malaria nephropathy (nephrosis) 5 Congenital malaria usually fatal 6 black water fever…
1 Anti-sporozoite vaccines 2 Anti-asexual blood stage vaccines 3 Transmission-blocking vaccines Vaccines are being developed and tried but none is available yet for routine use .
• Diagnosis is based on symptoms and detection of parasite in Giemsa stained blood smears. • There are also antibody tests • (left).
How People Get Malaria (Transmission) Usually, people get malaria by being bitten by an infected female Anopheles mosquito. 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, a small amount of blood is taken in which contains the microscopic malaria parasites. The parasite grows and matures in the mosquito’s gut for a week or more, then travels to the mosquito’s salivary glands. When the mosquito next takes a blood meal, these parasites mix with the saliva and are injected into the bite.
Once in the blood, the parasites travel to the liver and enter liver cells to grow and multiply. During this "incubation period", the infected person has no symptoms. After as few as 8 days or as long as several months, the parasites leave the liver cells and enter red blood cells.
Once in the cells, they continue to grow and multiply. After they mature, the infected red blood cells rupture, freeing the parasites to attack and enter other red blood cells. Toxins released when the red cells burst are what cause the typical fever, chills, and flu-like malaria symptoms.
Hyperreactive malarial splenomegaly (also called "tropical splenomegaly syndrome") occurs infrequently and is attributed to an abnormal immune response to repeated malarial infections. The disease is marked by a very enlarged spleen and liver, abnormal immunologic findings, anemia, and a susceptibility to other infections (such as skin or respiratory infections).
If a mosquito bites this infected person and ingests certain types of malaria parasites ("gametocytes"), the cycle of transmission continues.
The malaria parasite life cycle involves two hosts. During a blood meal, a malaria-infected female Anopheles mosquito inoculates sporozoites into the human host . Sporozoites infect liver cells and mature into schizonts , which rupture and release merozoites . (Of note, in P. vivax and P. ovale a dormant stage [hypnozoites] can persist in the liver and cause relapses by invading the bloodstream weeks, or even years later.) After this initial replication in the liver (exo-erythrocytic schizogony ), the parasites undergo asexual multiplication in the erythrocytes (erythrocytic schizogony ). Merozoites infect red blood cells . The ring stage trophozoites mature into schizonts, which rupture releasing merozoites . Some parasites differentiate into sexual erythrocytic stages (gametocytes) . Blood stage parasites are responsible for the clinical manifestations of the disease.
The gametocytes, male (microgametocytes) and female (macrogametocytes), are ingested by an Anopheles mosquito during a blood meal . The parasites’ multiplication in the mosquito is known as the sporogonic cycle . While in the mosquito's stomach, the microgametes penetrate the macrogametes generating zygotes . The zygotes in turn become motile and elongated (ookinetes) which invade the midgut wall of the mosquito where they develop into oocysts . The oocysts grow, rupture, and release sporozoites , which make their way to the mosquito's salivary glands. Inoculation of the sporozoites into a new human host perpetuates the malaria life cycle.
Control and treatment
Treatment: 1 Cloroquine, Qinghaosu, etc. (blood cycle) 2 Primaquine, Pyrimethamine,etc.(liver stage) 3 Primaquine.(Gametocytes) Mosquito control Malaria supervision
• Toxoplasma gondii is a protozoan parasite that infects most species of warm blooded animals, including humans, causing the disease toxoplasmosis. Intracellular parasite • Final host(cat) • Intermediate host(vertebrates )
Toxoplasma gondii • Tachyzoites (Trophozoite 速殖 子 ) are typically crescent shaped with a prominent, centrally placed nucleus
• Toxoplasma gondii cyst in brain tissue
Oocysts in the feces of cat
• Toxoplasma has worldwide distribution and 20%-75% of the population is seropositive without any symptoms. • However, the infection poses a serious threat in immunosuppressed individuals and pregnant females.
* Opportunistic parasite
• Although Toxoplasma infection is common, it rarely produces symptoms in normal individuals. • Congenital infections occur in about 1-5 per 1000 pregnancies of which 5-10% result in miscarriage( 流产 )and 810% result in serious brain and
eye damage to the fetus.
• In immunocompromised individuals, infection results in damage of brain, liver lung and other organs, and often death.
• Suspected toxoplasmosis can be confirmed by isolation of the organism from tonsil( 扁桃腺 )or lymph gland biopsy.
• Acute infections benefit from pyrimethamine( 乙嘧啶 )or sulphadiazine( 磺胺嘧 啶 ). Spiramycin( 螺旋霉素 ) is a successful alternative. Pregnant women are advised to avoid cat litter and to handle uncooked and undercooked meat carefully. Prevention:
1 Avoidance of close contact with pets and of contamination of food and water. 2 Avoidance of eating poorly cooked food and milk.
Leishman Sand fly ia donovani
Kalaazar skin lesions
Plasmodi um (Four species)
Female anopheli ne mosquito .
Toxoplas ma gondii
Malarial paroxys m: chills, fever, headach e, nausea cycles. Oral from Adult: flu cat fecal like; material; congenit or meat al: abortion, neonatal blindness and
Intracellu Pentosam lar (macroph ages) leishman ial Plasmodi Quinine bodies. a in derivatives R.B.C.
Intracellu lar (in macroph ages) tachyzoit es
Sulphonamides , pyemethamine, possibly spiramycin