Plasmodium and antimalarial drugs

MALARIA-DR.AKIF A.B

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

When Transmitted by blood transfusion

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


INFECTIVE FORMS1) 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.Falciparum

P.Malariae P.Ovale

Relapse(Hypnozoites)

seen Not seen Not seen Seen

Recrudescenece

Not seen seen seen Not seen

Incubation period

14days 12days 28days 17days

Erythrocytic cycle

48hrs 48hrs 72hrs 48hrs


RECRUDESCENCE

RELAPSE

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


Larvae


NATURE OF RBCsPlasmodium spcies Type of RBC

P.Vivax Young RBCs

P.Falciparum RBCs of all age

P.Ovale Reticulocytes /Young RBCs

P.Malariae Old RBCs


PROTECTIVE FROM MALARIA

Sickle cell trait Protective from P.falciparumThallasemia 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


Plasmodium knowlesi-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.Falciparum

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.


Gametocye Spherical, almost occupies RBC

Banana shape, larger than RBC



RBC size Enlarged Normal Normal enlargedStippling Schuffner’s

dots ( small red dots)

Maurer’s cleft( large red spots)

Ziemann’s dots

James dots


Maurer’s Cleft


P.falciparum

Gametocytes


Blood Smear Examination

Thin smear = for species identification

Thick smear = for quantification


ANTIGEN DETECTIONTESTS

-pLDH and Aldolase = common to all plasmodium species

-HRP-2 Ag detection = specific for P.falciparum


ANTI MALARIAL DRUGS

-DR.AKIF A.B


-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 QUINIDINES/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 MALARIAVIVAX 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 MALARIAShort duration (<6wks) Travel duration >6wksDOC : 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 PREGNANCYTreatment 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


PRACTICE QUESTIONS


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 AQuinineBChloroquine CPrimaquineDPyrimethamine


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 gametocytesd. 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 agesP. Vivax infects RBC’s < 14 dP. Malariae infects old RBC’sP. 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.


Plasmodium and antimalarial drugs

Health & Medicine

Transcript of Plasmodium and antimalarial drugs