2. Malaria is a mosquito-borne infectious
disease of humans and other animals caused
by protists (a type of microorganism) of the
genus Plasmodium. It begins with a bite from
an infected female mosquito (Anopheles
Mosquito), which introduces the protists via
its saliva into the circulatory system.
3. Five species of Plasmodium can infect and be
transmitted by humans. The vast majority of
deaths are caused by P. falciparum
while P. vivax , P. ovale and P. malariae cause
a generally milder form of malaria that is
rarely fatal.
6. The pathological changes in malaria are
related to the development of asexual
parasites in the blood.
The release of malaria antigens, pigment and
toxins gives rise to a cascade of pathological
events.
7. Cytokines,
Tumour necrosis factor (TN fd),
The effects of other circulating “endogenous
pyrogens” such as interlukin-1 (IL-1) and IL-
6. TNF
8. 1. Individual organs
2. Central nervous system
3. Anaemia
4. Bone marrow
5. The spleen
6. The kidneys
9. 1. Adrenals
2. The lungs
3. The cardiovascular system
4. Gastro-intestinal tract
5. Placenta
10. Cerebral malaria and coma.
Hyperpyrexia.
Haemolytic Anaemia.
Non cardiogenic pulmonary oedema (ARDS )
Acute tubular necrosis and renal failure
Acute Hepatomegaly and centrilobular
necrosis
Hypoglycaemia
An adrenal insufficiency like syndrome
Cardiac dysrhythmias
Lactic acidosis.
11.
12. a. Primaquine
b. Artemisinin
c. Quinine
d. Chloroquine
e. Pyrimethamine
f. Proguanil
g. Sulfonamides
h. Mefloquine
i. Atovaquone
j. Doxycycline
k. Clindamycin
13.
14. Primaquine is a highly active 8-
aminoquinolone that is used in treating all
types of malaria infection. It is most
effective against gametocytes but also acts
on hypnozoites, blood schizonticytes and the
dormant plasmodia in P. vivax and P. ovale.
15. Metabolites of primaquine are believed to
act as oxidants that are responsible for the
schizonticidal action as well as for the
hemolysis and methemoglobinemia
encountered as toxicities.
16.
17. Drug-induced hemolytic anemia in patients
with genetically low levels of glucose-6-
phosphate dehydrogenase
Ethemoglobinemia
Granulocytopenia
Agranulocytosis
Primaquine is contraindicated during
pregnancy. All plasmodium species may
develop resistance to primaquine.
18. Artemisinin (or one of its derivatives) is
available for the treatment of
severe, multidrug-resistant P. Falciparum
malaria.
Artemisinin is extracted from a herb,qing
hao
Also called sweet wormwood or annual
wormwood.
19. Extensive structure-activity studies have
confirmed the requirement for an
endoperoxide moiety for antimalarial activity
these compounds act rapidly against the
asexual erythrocytic stages of P. Vivax and P.
Falciparum.
20. Artemisinin action involves two steps
First, heme iron within the parasite catalyzes
cleavage of the endoperoxide bridge. This is
followed by rearrangement to produce a
carbon-centered radical that alkylates and
damages macromolecules in the
parasite, likely including the ortholog of
sarco/endoplasmic reticulum ca2+-atpase
21.
22. Chloroquine [klor-oh-kwin] is a synthetic 4-
aminoquinoline that has been the mainstay
of antimalarial therapy, and it is the drug of
choice in the treatment of erythrocytic P.
Falciparum malaria, except in resistant
strains. Chloroquine is less effective against
P. Vivax malaria. It is highly specific for the
asexual form of plasmodia.
23. Asexual malaria parasites flourish in host erythrocytes by
digesting hemoglobin in their acidic food vacuoles,
it generates free radicals and heme (ferriprotoporphyrin IX) as
highly reactive by-products. Perhaps aided by histidine-rich
proteins and lipids,
heme is sequestered as an insoluble unreactive malarial pigment
termed hemozoin.
Chloroquine concentrates in the food vacuoles of susceptible
plasmodia, where it binds to heme as it is released during
hemoglobin degradation and disrupts heme sequestration.
Failure to inactivate heme or even enhanced toxicity of drug-
heme complexes is thought to kill the parasites via oxidative
damage to membranes, digestive proteases, and possibly other
critical biomolecules. Other quinolines such as
quinine, amodiaquine, and mefloquine, as well as other
aminoalcohol analogs (lumefantrine, halofantrine) may act by a
similar mechanism, although differences in their actions have
been proposed
24.
25.
26. At higher doses, many more toxic effects
occur, such as gastrointestinal
upset, pruritus, headaches, and blurring of vision
An ophthalmologic examination should be
routinely performed.
Discoloration of the nail beds and mucous
membranes may be seen on chronic
administration.
Chloroquine should be used cautiously in
patients with hepatic dysfunction or severe
gastrointestinal problems or in patients with
neurologic or blood disorders.
Chloroquine can cause electrocardiographic
changes, because it has a quinidine-like effect.
27. Quinine is the chief alkaloid of cinchona
Quinine acts primarily against asexual
erythrocytic forms; it has little effect on
hepatic forms of malarial parasites. The
alkaloid also is gametocidal for P. vivax and
P. malariae but not for P. falciparum.
28. Quinine is more toxic and less effective than
chloroquine against malarial parasites
susceptible to both drugs.
However, quinine, along with its
stereoisomer quinidine, is especially valuable
for the parenteral treatment of severe illness
owing to drug-resistant strains of P.
falciparum, even though these strains have
become more resistant to both agents in
certain parts of Southeast Asia and South
America. Because of its toxicity and short
half-life, quinine generally is not used for
prophylaxis.