MALARIA
1
2
1. Mal-aria (Bad air) till 1880
2. Tropical disease due to presence of sporozoa of
plasmodium
3. Transmitted to humans by ...
•

Malaria is caused by four species of
protozoa
Plasmodium malariae.
P. falciparum. (more lethal)
P. vivax.
P. ovale (rar...
• NMEP (National Malaria Eradication Program) in India
1958.
• Nearly complete eradication in due to
powerful insecticides...
Life Cycle of Malarial Parasite
• Complex Sexual (in female mosquito) and asexual
Life cycle (in humans).
• Sexual Life Cy...
Pre-erythrocyitc
state

Zygote
Oocysts
Sporozoites

Sporozoites

Schizonts
Exo-erythrocyitc
state

Asexual
Erythrocytic
st...
Sporozoites hardly survived in blood hence get
sheltered in Liver parenchymal cell
In Liver it divide and developed into m...
9
The malaria parasite life cycle involves 2 hosts. During a blood meal, a malaria-•
infected female Anopheles mosquito inoc...
• During merozoite maturation in RBC, host’s
Hb is digested and transported to parasites
food vacuole and provides amino a...
• P. vivax causes BENIGN TERTIAN MALARIA
– Benign as it is rarely fatal
– Tertian as fever is on every 3rd day (48 h)
– Re...
13
Clinical presentation
• Early symptoms
–
–
–
–
–
–
–

Headache
Malaise
Fatigue
Nausea
Muscular pains
Slight diarrhea
Sligh...
Clinical presentation
• Acute febrile illness, may have periodic febrile
paroxysms every 48 – 72 hours with
• Afebrile asy...
Drugs used to treat Malaria-First group
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.

4-aminoquinolones: Eg. Chloroquine, Amodia...
CLOROQUINE
•
•
•
•
•
•
•

Available as Chloroquine Phosphate
p.o./i.m./slow i.v. infusion
very high volume of distribution...
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Malaria

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Malaria

  1. 1. MALARIA 1
  2. 2. 2
  3. 3. 1. Mal-aria (Bad air) till 1880 2. Tropical disease due to presence of sporozoa of plasmodium 3. Transmitted to humans by the infected female mosquito Anopheles 4. Malarial parasite is a single cell protozoa called Plasmodium. 5. 300-500 millions cases of malaria detected out of which 1.5-2.7 million death every year 6. Nine major species of anopheline mosquitoes transmit malaria in India. In urban areas, malaria is . mainly transmitted by Anopheles stephensi 3
  4. 4. • Malaria is caused by four species of protozoa Plasmodium malariae. P. falciparum. (more lethal) P. vivax. P. ovale (rare). • The plasmodium transmitted to human by the bite of an infected female anopheles mosquito. 4
  5. 5. • NMEP (National Malaria Eradication Program) in India 1958. • Nearly complete eradication in due to powerful insecticides. • In 1970’s due to emergent of drug and insecticides resistant all attempts failed. 5
  6. 6. Life Cycle of Malarial Parasite • Complex Sexual (in female mosquito) and asexual Life cycle (in humans). • Sexual Life Cycle: Fertilization takes place in mosquito gut and Oocysts liberates matured sporozoites which migrates and stay in insects salivary glands. • Asexual Life Cycle: These sporozoites then passed to blood of another human to begin asexual cycle • NO AVAILABLE DRUGS ARE LETHAL TO SPOROZOITES 6
  7. 7. Pre-erythrocyitc state Zygote Oocysts Sporozoites Sporozoites Schizonts Exo-erythrocyitc state Asexual Erythrocytic stage Schizogony Merozoites Merozoites Tropozoites Blood Schizonts Merozoites Tropozoites Pyrogen + TNF-α+ Haem 7
  8. 8. Sporozoites hardly survived in blood hence get sheltered in Liver parenchymal cell In Liver it divide and developed into multinucleated SCHIZONTS. Hosts are asymptomatic (PRE-ERHTHROCYTIC STATE) In Liver, Schizonts gets matured in 8-21 days to form mononucleated MEROZOITES liberated from liver and released in blood stream If the species is P. falciparum, merozoites bind to erythrocytes and forms TROPHOZOITES If the species is P.vivax / P.ovale, some merozoites re-enters liver cell and form dormant HYPNOZOITES (Sleeping form, which may lasts for several month and may get relapse) EXO OR PARA ERYTHROCYTIC STATE 8
  9. 9. 9
  10. 10. The malaria parasite life cycle involves 2 hosts. During a blood meal, a malaria-• infected female Anopheles mosquito inoculates sporozoites into the human host. Sporozoites infect liver cells. There, the sporozoites mature into schizonts. The schizonts rupture and release merozoites. This initial replication in the liver is called the exoerythrocytic cycle. Merozoites infect RBCs. There, the parasite multiplies asexually (called the erythrocytic cycle). The merozoites develop into ring-stage trophozoites. Some then mature into schizonts. The schizonts rupture, releasing merozoites. Some trophozoites differentiate into gametocytes. During a blood meal, an Anopheles mosquito ingests the male (microgametocytes) and female (macrogametocytes), gametocytes beginning the sporogonic cycle. In the mosquito's stomach, the microgametes penetrate the macrogametes, producing zygotes. The zygotes become motile and elongated, developing into ookinetes. The ookinetes invade the midgut wall of the mosquito where they develop into oocysts. The oocysts grow, rupture, and release sporozoites, which travel to the mosquito's salivary glands. Inoculation of the sporozoites into a new human host perpetuates the malaria life cycle. 10
  11. 11. • During merozoite maturation in RBC, host’s Hb is digested and transported to parasites food vacuole and provides amino acids • Free haem which may be toxic to parasite is polymerised to haemozoin by parasitic haem polymerase • RBCs infected with merozoite, ruptures and releases thousands of merozoites along with pyrogens, TNF- α and polymerised haem to show symptoms of Malaria 11
  12. 12. • P. vivax causes BENIGN TERTIAN MALARIA – Benign as it is rarely fatal – Tertian as fever is on every 3rd day (48 h) – Relapse may occur because dormant hypnozoites reside in liver • P. ovale infection has periodicity and relapse similar to P. vivax but is milder and can be cured • P. malariae causes QUARTAN MALARIA – It has 72 h cycles – No exo-erythrocytic stage but relapse may occur • P. falciparum causes MALIGNANT TERTIAN MALARIA – Malignant as it is severe form of malaria – Tertian as fever occurs every after 3rd day – Infected RBCs forms clusters called ROSETTES. Such rosettes may block capillaries of vital organs causing renal failure and encephalopathy (Cerebral Malaria) 12
  13. 13. 13
  14. 14. Clinical presentation • Early symptoms – – – – – – – Headache Malaise Fatigue Nausea Muscular pains Slight diarrhea Slight fever, usually not intermittent • Could mistake for influenza or gastrointestinal infection
  15. 15. Clinical presentation • Acute febrile illness, may have periodic febrile paroxysms every 48 – 72 hours with • Afebrile asymptomatic intervals • Tendency to recrudesce or relapse over months to years • Anemia, thrombocytopenia, jaundice, hepatosplenomegaly, respiratory distress syndrome, renal dysfunction, hypoglycemia, mental status changes, tropical splenomegaly syndrome
  16. 16. Drugs used to treat Malaria-First group 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 4-aminoquinolones: Eg. Chloroquine, Amodiaquine Chincona alkaloids: Quinine Quinoline methanol: Mefloquine Acridine: Mepacrine, Quinacrine 8-aminoquinolines: Primaquine, Bulaquine Biguanides: Porguanil Diaminopyrimidines: Pyrimethamine Artemisinin derivative: Artesunate,Artemether, Arteether Phenanthrene methanol: Halofantrine, Lumefantrine Naphthoquinone: Atovaquone Antibiotics: TTC, Doxycycline, Clindamycin Sulfonamides and Sulfones: Sulfadoxine and Dapsone 16
  17. 17. CLOROQUINE • • • • • • • Available as Chloroquine Phosphate p.o./i.m./slow i.v. infusion very high volume of distribution Metabolised in liver Excreted in urine (70% unionized and 30% metabolized) T1/2 is 3-4 days Terminal T1/2 is 1-2 months MOA • Chloroquine accumulates in parasitized erythrocytes • Diffuse into parasite lysosomes • Inhibit peptide formation and reduces supply of amino acid which is necessary for parasite viability • Also inhibit parasite haem polymerase and thus protects host’s haem to get converted into haemozoin. • At high concentration it also inhibit RNA and DNA 17 synthesis

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