TREATMENT OF MALARIA

- Dr.Akif A.B

Chloroquine sensitive malaria

Chloroquine 10mg/kg bw stat dose followed by10mg/kg on 2nd day

f/b5mg/kg bw on 3rd day

orChloroquine 10mg/kg bw

f/b5mg/kg at 6hr,24 hrs & 48hrs

Add Primaquine 0.25-0.5mg/kg bw/ day for 14 days only if G6PD levels are normal

This chloroquine level resides for about 2-3 weeks in blood, thus prevents the firstRelapse of P.vivax which generally occurs at 3wks after onset of primary illness.

So relapses begin after 5-6wks of illness if not treated with Primaquine.

CHLOROQUINES/E:

- It is generally well tolerated in therapeutic doses of malaria

- Large doses used in treatment of Rheumatoid Arthritis are usually associated with higher frequency of side effects

- Pruritis is a common side effect and is more severe in darkly skinned individuals.

- Other rare side effects : 1) elevated liver enzymes2) GI disturbances3) convulsions, retinopathy and arrhythmias

Overdosages can be dangerous and can lead to death within hours.Pt. may progress from feeling dizzy and drowsy with headache and gi upset to sudden visual loss, convulsions, hypokalemia, hypotension and cardiac arrhythmias

The most important side effect of Primaquine is hemolysis in G6PD deficientPatients

Amount of hemolysis depends on dosage, duration of exposure and degree of G6PD Deficiency

Primaquine is rapidly eliminated from the body. So hemolysis will stop once the drug is stopped.

So Pt. being treated with Primaquine should be looked for anemia, red or black urine and should be stopped immediately if present.

A single dose of 0.25mg/kg bw Primaquine as Gametocidal will not lead to hemolysis even in G6PD deficient pt. So it is not necessary to check G6PD status for single dose administration as given in Falciparum malariae.

FALCIPARUM MALARIA

ACT should be given for 3 days.

1) Hypersensitivityreactions

2) GI Diturbances

3) Cough

4) Rash

5) Arthralgia

6) Delayed hemolysis

SEVERE FALCIPARUMMALARIA

SEVERE MALARIA

Impaired consciousness

Prostration

Multiple convulsions

Acidosis

Hypoglycemia

Anemia

Jaundice

Pulmonary edema

Significant bleeding

Shock

ARTESUNATE > ARTEMETHER > QUININE irrespective of whether patient isA infant or pregnant or a lactating female.

Mortality from untreated severe malaria is almost 100%.

With effective treatment mortality reduces to 10-20%

If a pt. presents with severe anemia , there are more chances of survival ascompared to acidosis

Therapeutic objective : is to prevent the patient from dying

Artesunate Dosage : 2.4mg/kg

Studies have shown that artesunate dosage between 1.5-4mg/kg dose is not associated with any toxicity

Artesunate and Post Treatment Hemolysis

- Starts 7days after treatment with Artesunate

- Between 2010 and 2012, there were 6 reports involving a total of 19 Europeantravellers with severe malaria who were treated with artesunate injection

and developed delayed hemolysis. Out of 6 , 1 was adult

Artesunate rapidly kills ring stages parasites

Taken out of RBCs by Spleen

This infected RBCs have a shorter life span

Leads to hemolysis

ARTESUNATE ARTEMETHER QUININE

- Water soluble and can be given Intavenously

- Oily solution- Should be given only I.M

I.V or I.M both are equally effective

Rapidly converts into Dihydroartemisnin, the active form.

Converts slowly Loading dose : 20mg/kg f/b

10mg/kg every 8hrly

Artesunate powder is diluted with 5ml of 5%D and given I.V or I.M

Only I.M / Oral If no improvement in 48hrs, dose reduced to 10mg/kg every 12hrly

2.4mg/kg bw / dose 3.2mg/kg statf/b

1.6mg/kg daily

Shouldn’t be infused rapidly.- Dilute in 5%D and infuse over 4hrs ( not >5mg/kg/hour)

Dose adjustment is not required for Artemisnin derivatives in Liver or Kidney diseases.

FOLLOW ON TREATMENT- 24hrs parenteral f/b complete ACT

- In ACT, Artemisnin + Mefloquine should be avoided in Pt. presenting withunconsciousness or altered consciousness.

- If ACT not available : Artesunate/Quinine + Doxycycline(7d)or

Artesunate/Quinine + Clindamycin(preferred in Pregnancy)

MANAGEMENT OF COMPLICATIONS OF SEVERE FALCIPARUM MALARIA

Coma

Hypoglycemia

Convulsions

Hyperpyrexia

Pulmonary edema

Severe anemia

Acute kidney injury

Coagulopathy

Metabolic acidosis

shock

TREATMENT OFSEVERE FALCIPARUM MALARIA

IN PREGNANCY

- Artesunate > artemether > quinine

- 2nd & 3rd trimester > 1st trimester

- Hypoglycemia and pulmonary edema

- Risk of mortality 50% more in pregnant > non pregnant

- Fetal demise and premature labor

- Teratogenic effects : decreases embryonic erythroblasts, cardiac myopathy delay in limb and tail development

SEVERE VIVAX MALARIA

- Very rare

- Anemia, thrombocytopenia , acute pulmonary edema are common

TREATMENT

Parenteral Artesunate > Artemether > Quinine for 24hrsf/b

ACT or Chloroquine

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.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

Erythrocyticcycle

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.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.

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’sdots ( small red dots)

Maurer’s cleft( large red spots)

Ziemann’sdots

James dots

Gametocytes

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

-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 hemeproducts 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

•Hemolysis in G6PD deficiency

•Methemoglobinemia

•Anemia

• Leukocytosis

PRIMAQUINE S/E

•Pregnancy

•Lactation

• Infants

PRIMAQUINE C.I