Plasmodium and antimalarial drugs

-DR.AKIF A.B
STEP TO PG-MD/MS -DR.AKIF A.B

1) There is no liver stage since parasite directly enters blood
2) Hypnozoites are not found
3) Hence there is no relapse
4) No need for Primaquine

1) Infective form to man = Sporozoites present in salivary glands of
Mosquito
2) Infective form to man in case of
blood transfusion
3) Infective form to mosquito = Gametocytes
- To infect mosquito, Gametocyte must be mature, viable, count >12per cubic mm.
merozoites

P.Vivax P.Falciparu
m
P.Malariae P.Ovale
Relapse(Hypn
ozoites)
seen Not seen Not seen Seen
Recrudescene
ce
Not seen seen seen Not seen
Incubation
period
14days 12days 28days 17days
Erythrocytic
cycle
48hrs 48hrs 72hrs 48hrs

Recrudescence is due to persistence of drug resistant parasite.
In Falciparum : Disease appears after 2-3weeks of completion of treatment
In Malariae ; Disease appears very late almost after 60yrs.
-due to hypnozoites
-May reappear after2-3yrs
-Seen in P.vivax and ovale.

Species Disease Periodicity
P.Vivax Benign tertian 48hrs
P.Falciparum Malignant tertian 48hrs
P.Ovale Ovale tertian 48hrs
P.Malariae Quartian 72hrs
P.Knowlesi Quotidian 24hrs

Plasmodium spcies Type of RBC
P.Vivax Young RBCs
P.Falciparum RBCs of all age
P.Ovale Reticulocytes /Young RBCs
P.Malariae Old RBCs

Sickle cell trait Protective from P.falciparum
Thallasemia trait Protective from P.falciparum
Fetal Hb Protective from P.falciparum
G6PD deficiency Protective from P.falciparum
Ovalocytosis Protective from P.falciparum
Duffy negative RBCs Protective from P.vivax

-It is a parasite of monkey but can also affect humans
-Early trophozoite resembles to P.falciparum
-Late trophozoite resembles to P.malariae
-Quotidian malariae

P.Vivax P.Falciparu
m
P.Malariae P.ovale
Forms seen
in
peripheral
blood smear
Early and late
trophozoites,
gametocytes
and schizonts
Ring forms
(early
trophozoites)
and
gametocytes
Similar to that
of vivax
Ring forms are
known as
Band forms.
Similar to that
of vivax
Gametocye Spherical,
almost
occupies RBC
Banana
shape, larger
than RBC
Similar to that
of vivax
Similar to that
of vivax
RBC size Enlarged Normal Normal enlarged
Stippling Schuffner’s
dots ( small
red dots)
Maurer’s
cleft( large
red spots)
Ziemann’s
dots
James dots

Gameto
cytes

Thin smear = for species identification
Thick smear = for quantification

-pLDH and Aldolase = common to all plasmodium species
-HRP-2 Ag detection = specific for P.falciparum

-Most potent and fastest acting schizonticidal drugs
-But have short duration of action, hence cant be used singly and has to be
combined with slower acting drugs
- Acts by producing free radicals and toxic heme products
-Since they produce free radicals, free radicals have teratogenic effect. Hence C.I
in 1st trimester. Can be given in 2nd and 3rd trimester
-Oral drugs : Artesunate, Artemether, Dihydroartemisnin
-Only i.v drug : Artesunate
ARTEMISNISNIN GROUP DRUGS

-I.V Artesunate is DOC in severe falciparum malaria
-Oral artesunate 200mg for 3 days is preferred in Chloroquine resistant malaria
-Not used for prophylaxis since it has short duration of action
-S/E:
GI side effects: Nausea, vomiting, Diarrehea
ARTEMISNISNIN GROUP DRUGS

-Enters vacuole of plasmodium and binds with haem and produces toxic heme
products which is cidal for plasmodium
-Resistance is due to efflux of drug from vacuole
-DOC for treatment and prophylaxis of malaria except falciparum
-It has high volume of distribution and hence loading dose has to be given.
-Other uses : Giardiasis
Amebiasis,
Infectious mononucleosis,
SLE,
RA
CHLOROQUINE

S/E:
C - Convulsions
H - Hemolysis in G6PD deficient pt.
L - Low blood pressure
O -Ocular : Bull’s eye maculopathy
R - qRs and T wave abnormalities
CHLOROQUINE

•Fast acting schizonticidal drugs
•Used in severe falciparum malaria and chloroquine resistant malaria
•Derived from bark of cinchona plant
QUININE and QUINIDINE

•Cinchonism : headache + tinnitus +Visual disturbance
•Hypotension : Due to Alpha-1 blocking effect
•Hypoglycemia : Due to insulin release. Hence given with
dextrose
•Black water fever : Inadequate therapy leads to
hypersensitivity
QUININE and QUINIDINE
S/E

•Used in treatment and prophylaxis of vivax
•Used along with artesunate in severe falciparum malaria
•S/E : Neuropsychiatric
MEFLOQUINE

• Dihydrofolate Reductase (DHFR) inhibitor
•Used in combination with sulfadoxine and artesunate k/a Artesunate
combination therapy (ACT).
•ACT is used in chloroquine resistant malaria
PYRIMETHAMINE

•Acts on hypnozoite stage and thus prevents relapse
•Used for terminal prophylaxis i.e given with chloroquine to travelers to an
endemic area
•Used for radical cure of vivax and ovale
PRIMAQUINE

•Hemolysis in G6PD deficiency
•Methemoglobinemia
•Anemia
• Leukocytosis
PRIMAQUINE S/E

•Pregnancy
•Lactation
• Infants
PRIMAQUINE C.I

•Halofentine and Lumefantine
• Atovaquone and proguanil
•Pyronaridine
•Antibiotics :
Doxycycline : Used in short term(<6weeks) prophylaxis of malaria
Tetracycline
Clindamycin
OTHER ANTIMALARIAL DRUGS

Treatment of MALARIA
VIVAX Chloroquine for 3days +
Primaquine for 14days
FALCIPARUM Artemether for 3days +
Lumefantine for 3days +
Primaquine single dose on
Day2
Artemether for 3days +
Sulfadoxine 3d +Pyridoxine
3d + Primaquine single dose
on Day2
MIXED INFECTION Same as falciparum
+
Add primaquine for 14days
SEVERE FALCIPARUM
MALARIA
DOC: Artesunate i.v for 48hrs
followed by oral ACT
In pregnancy : Quinine i.v for
48hrs followed by Quinine +
Doxycycline/clindamycin

PROPHYLAXIS OF MALARIA
Short duration (<6wks) Travel duration >6wks
DOC : Doxycycline DOC: Mefloquine
100mgOD started 2days before
travelling and continued for 4wks
after leaving endemic area
250mg weekly started 2weeks
befor travel and continued for
4wks after leaving endemic area

•Primaquine is C.I and given postpartum
•ACT C.I in 1st trimester
MALARIA IN PREGNANCY
Treatment of vivax,
falciparum and mixed
infection
Severe falciparum
malaria
Prophylaxis
1st trimester : Quinine Quinine i.v for 48hrs
followed by Quinine +
Doxycycline/clindamycin
Mefloquine
2nd and 3rd trimester :
ACT

DOC in severe complicated falciparum malaria:
A Chloroquine
B Quinine
C Artesunate
D Artem ether

Ans. B Quinine
a. Quinine is the drug of choice for cerebral malaria. Artemisnins are used in
severe malaria. Chloroquine resistance makes it useless in this indication.
b. Quinine is given in 5% or 10% Dextrose infusion. It should never be mixed in
saline containing solution otherwise it gets precipitated. The main side effects of
Quinine are vomiting, tinnitus, Hypotension.

Drugs causing G6PD are all of the following EXCEPT
A
Quinine
B
Chloroquine
C
Primaquine
D
Pyrimethamine

Ans. D Pyrimethamine
“Antimalarials such as primaquine increase red blood cell fragility in
individuals with G6PD deficiency, leading to profound hemolytic anemia.”
Both chloroquine and quinine occasionally cause hemolysis in some G6PD
patients.
Under pyrimethamine hemolysis in G6PD has not been mentioned unlike the
other drugs.
List is given below:

Drugs causing hemolysis in G6PD

Digoxin levels are increased by addition of which of the following?
A Phenytoin
B Quinidine
C Furosemide
D Steroids

Ans. B. Quinidine
Quinidine reduces binding of digoxin to tissue proteins as well as its renal and
biliary clearance.
As a result, the plasma concentration is doubled and toxicity can occur.
Dose of digoxin therefore is routinely lowered.

1) Man is intermediate host for: (DNB June 2011)
A Brugia malayi
B W. Bancrofti
C Plasmodium
D Echinococcus

Ans. C & D
Humans act as intermediate host for
Plasmodium,
Toxoplasma,
Babesia and
Echinococcus,
T. Solium.
Intermediate host for W. Bancrofti and Brugia malayi is mosquito

2) In malaria, infective stage injected into human subjects by the mosquito is:
A Sporozoite
B Merozoite
C Cryptozoite
D Gametocyte

Ans. A Sporozoite
Man: intermediate host
a. Female anopheles mosquito: definitive host
b. In malaria infective stage for humans is sporozoites.
c. Human cycle (Schizogony/ asexual cycle):
female anopheline mosquito bites→ sporozoites injected→ general
circulation→ invade hepatocytes→ preerythrocytic schizogony→
merozoites→ invade rbcs→ erythrocytic schizogony→ some merozoites
develop into gametocytes
d. Mosquito cycle (Sporogony/ sexual cycle): female anopheline mosquito
bites→ picks macrogametocyte & microgametocyte→ exflagellation of
microgametocyte→ penetrates one macrogamete→ zygote→ ookinete→
penetrates the epithelial lining & muscular wall & lies below the outer limiting
membrane of the stomach→ oocyst→ sporocyst containing sporozoites→
rupture, sporozoites liberated in the body cavity→ reach salivary gland

3. Duration of pre-erythrocytic schizogony in Plasmodium falciparum
is: (AIIMS Nov 2011)
A 2 days
B 5 days
C 9 days
D 13 days

Ans. B 5 days
Duration of Pre-erythrocytic (exo-erythrocytic) schizogony:
P. Falciparum-5.5 days,
P. Vivax-8 days,
P. Ovale- 9 days,
P. Malariae- 15days.

4. What is the site of pre-erythrocytic cycle of malaria?
A Anopheles
B Paranchymal cells of liver
C Kupfer cells of liver
D Spleen

Ans. B Parenchymal cells of liver.
Pre-erythrocytic stage occurs in the hepatocytes

5. Blackwater fever results from: (DNB Dec 2011)
A Intravascular haemolysis
B Nephrotic syndrome
C Alkaptonuria
D Paroxysmal nocturnal hemoglobinuria

Ans. A Intravascular haemolysis
a. Black water fever is because of intravascular hemolysis.
b. It is caused by rapid and massive destruction of red blood cells with the
production of hemoglobinemia, hemoglobinuria, intense jaundice, anuria,
and finally death
c. In the majority of cases. The most probable explanation for blackwater
fever is an autoimmune reaction apparently caused by the interaction of the
malaria and quinine

6. In falciparum malaria, all the following states are seen except:.
A Ring stage
B Gametocyte
C Schizont
D Sporozoite

Ans. C Schizont
a. Erythrocytic schizogony occurs in the capillaries of internal organs and only
the early ring forms and the gametocytes are seen in the peripheral smear.
b. Late trophozoite and schizont are not seen in peripheral blood in falciparum
malaria.

7. Banana shaped gametocytes in peripheral smear are seen
in infection with: (AIIMS May 2011)
A Plasmodium vivax
B Plasmodium malaria
C Plasmodium falciparum
D Plasmodium ovale

Ans. C Plasmodium falciparum
Banana shaped or crescent shaped gametocytes
are seen in P. Falciparum.

8. All are seen in Plasmodium falciparum infection except:
A Hemoglobinuria
B Cerebral malaria
C Relapses
D Malignant malaria

Ans. C Relapses
Relapses are due to hypnozoites in liver. These are seen in case of P.vivax and
P.ovale. P. Falciparum is not associated with relapses.

9. Microscopic examination of a thin blood smear from a patient suspected
of having malaria reveals numerous normal size erythrocytes without
stippling but with ring stages, many with multiple ring stages and applique
forms. Several erythrocytes show developing trophozoites that are spread
across the erythrocytes in a band fashion. Which of the following is the
most likely cause of infection? (AIPG 2011)
A Plasmodium vivax
B Plasmodium malariae
D A mixed infection with two plasmodium species

Ans. D A mixed infection with two plasmodium species
a. Multiple ring stages and applique forms are indicative of P. Falciparum;
several erythrocytes show developing trophozoites that are spread across
the erythrocytes in a band fashion that is indicative of P. Malariae infection.
b. Normal size erythrocytes without stippling (Schuffner dots) would exclude P.
Vivax and P. Ovale.

10. A patient in the city of Pune was diagnosed with malaria acquired
through a blood transfusion. A discussion of this case by physicians
included the following statements. Which statement is correct?
A The infected blood contained sporozoites.
B The patient should be treated with chloroquine and primaquine.
C The patient should be treated to eradicate the stages responsible for
symptoms.
D The blood donor had chloroquine-resistant malaria.

Ans. C The patient should be treated to eradicate the stages
responsible for symptoms.
a. The primary goal should be to treat the patient to eliminate the erythrocytic cycle
that is the cause of symptoms.
b. This would constitute a radical cure because the liver phase only occurs if infection
is initiated by sporozoites. Thus, treating with primaquine (B) is not necessary
because the patient will not harbor hypnozoites.
c. Likewise, (A) is not correct because sporozoites are only acquired from
mosquitoes. Transfusion malaria is caused by schizonts and merozoites present in
the transferred blood.
d. There is no way to know that the malaria is chloroquine resistant until after
treatment with chloroquine (D)

11. Cerebral malaria most commonly attends infection with which of the following?
A Plasmodium vivax
B Plasmodium malariae
D Plasmodium ovale

Ans. C Plasmodium falciparum
a. Cerebral malaria involves the clinical manifestations of Plasmodium
falciparum malaria that induce changes in mental status and coma and is
accompanied by fever.
b. Without treatment, cerebral malaria is fatal in 24-72 hours and the mortality
ratio is between 25-50 percent.
c. The common histopathological finding is the sequestration of parasitized and
nonparasitized red blood cells in cerebral capillaries and venules.

12. A 29-year-old man feels tired and has sore muscles, so he consults a physician,
who examines him, but decides not to admit him to the hospital. The man
subsequently develops a disabling illness complicated by severe anemia, pulmonary
edema, renal failure, and shock. Which of the following organisms is the most likely
pathogen? (AIPG 2012)
A Babesia microti
B Plasmodium falciparum
C Plasmodium malariae
D Plasmodium ovale

Ans. B Plasmodium falciparum
a.This is the history of complicated P. Falciparum infection.
b. The complications associated with P. Falciparum include: pernicious malaria,
black water fever, algid malaria, cerebral malaria, pulmonary edema, ARDS and
metabolic acidosis.

13. Which of the following species of Plasmodium has
special affinity for reticulocytes: (AIIMS Nov 2012)
A P ovale
B P vivax
C P malariae
D P falciparum

Ans. A P ovale
P. Falciparum infects RBC’s of all ages
P. Vivax infects RBC’s < 14 d
P. Malariae infects old RBC’s
P. Ovale selectively infect reticulocytes

14. All of the following are complication of Plasmodium falciparum infection except
A Blackwater fever
B Cerebral malaria
C Recrudescent malaria
D Nephropathy

Ans. D Nephropathy
a. Nephropathy is seen in Plasmodium malariae.
b. Recrudescence result from persistent erythrocytic infection, which re-emerges
within a defined period -usually taken as 28 days following antimalarial
treatment in endemic areas.
c. Relapse occurs due to reactivation of hypnozoites in the liver.
d. Blackwater fever results due to severe intravascular hemolysis.
e. Cerebral malaria occurs due to sequestration, rosetting and cytoadherence in
cerebral capillaries.

15. Which species of malaria causes nephrotic syndrome
A Plasmodium ovale
B Plasmodium falciparum
C Plasmodium vivax
D Plasmodium malariae

D Plasmodium malariae

16. Which one of the following is detected by the
antigen detection test for the diagnosis of P.
Falciparum malaria (AIIMS Nov 2012)
A CSP
B MSA
C HRP1
D HRP2

Ans. D HRP2
Malaria rapid diagnostic tests detect the presence of malarial antigens in the blood
of the patient. Malarial HRP-II, LDH and aldolase are detected. These are immune-
chromatographic tests.

17. Infection with Babesia is most commonly observed in which of the following?
A AIDS patient
B Foresters
C Patients without a spleen
D Transfusion recipients

Ans. C Patients without a spleen
a. Babesia is a tick-borne organism transmitted by I. Scaputaris, the same tick
that transmits Lyrne disease.
b. Babesia is often mistaken for Plasmodia (causative organism of malaria) on a
blood smear. Patients become anemic and develop hepatosplenomegaly, but
patients who are asplenic are at a much greater risk.
c. Transfusion recipients, foresters, and immunosuppressed patients may be at
risk of acquiring disease but not to the same extent as those patients who have
been splenectomized.

18. Maltese cross is associated with (DNB June 2012)
A Candida albicans
B Penicillium marneffii
C Babesia microti
D Cryptococcus

Ans. C Babesia microti
Tetrad forms in RBC’s which represent budding merozoites are called Maltese cross.

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