Dr. Lokes

h Garg MD.

{MED

.} Santos

h hopital Yamun

a nagar

Indian Guidelines & Protocols For The

Treatment Of Malaria

Introduction

Major public health problem of India

Around 1.5 million confirmed cases are reported annually (NVBDCP) 50% are due to Plasmodium falciparum.

( most severe form of disease )

Causative agent: intracellular plasmodium protozoa.

Species : P.falciparum , P.malariae , P.ovale , P.vivax. (P.knowlesi -documented in malaysia ,

, indonesia,singapur,phillippines)

Transmission: Female anopheles mosquitoes. ( Also transmitted through blood transfusion ,use of contaminated needles, from pregnant women to fetus)

Female Anopheles Mosquitos transmit Malaria

Malaria Kills more people than AIDS

Malaria kills in one year what AIDS kills in 15 years. For every death due to HIV/AIDS there are about 50 deaths due to malaria. To add to the problem is the increasing drug resistance to the established drug.

Malaria Transmission Cycle

Parasite undergoes sexual reproduction in the mosquito

Some merozoites differentiate into male or female gametocyctes

Erythrocytic Cycle: Merozoites infect red blood cells to form schizonts

Dormant liver stages (hypnozoites) of P. vivax and P. ovale

Exo-erythrocytic (hepatic) Cycle: Sporozoites infect liver cells and develop into schizonts, which release merozoites into the blood

MOSQUITO HUMAN

Sporozoites injected into human host during blood meal

Parasites mature in mosquito midgut and migrate to salivary glands

Exo-erythrocytic (hepatic) cycle

Hypnozoites

Sporozoites

Mosquito Salivary Gland

Malaria Life Cycle

Gametocytes

Oocyst

Erythrocytic Cycle

Zygote

The Malaria Transmission CycleSites of Action for Antimalarial Drugs

SPORONTOCIDES:primaquine pyrimethamineproguanil

MOSQUITO HUMAN

GAMETOCYTOCIDES:primaquine

TISSUE SCHIZONTOCIDES:primaquinepyrimethamineproguaniltetracyclines

BLOOD SCHIZONTOCIDES:chloroquinemefloquinequinine/quinidinetetracyclineshalofantrinesulfadoxinepyrimethamineartemisinins

What are Artemisinins ?

Artemisinin derivatives

Methyl Ether

Hemisuccinate

Ethyl Ether

Arteether Artemether

Artesunate

Dihydroartemisin

Qinghaosu ("ching-how-soo")

What is ACT ?

Artemisinin-based combination therapy

(ACT) is an antimalarial combination

therapy with an artemisinin derivative as

one component of the combination given for

at least 3 days.

Clinical Manifestations are related to cycle of events in relation to RBC

Fever -The cardinal symptom of malaria.

chills and rigors.

Headache

myalgia,

Arthralgia

anorexia

Nausea

vomiting.

Clinical features

Why Early Diagnosis & Treatment

Diagnosis

Microscopy Microscopy of stained thick and thin blood smears - gold standard

The sensitivity is high.

Detect malaria parasites at low densities.

Helps to quantify the parasite load.

Distinguish the various species of malaria parasite and their different stages.

Rapid diagnostic test Based on the detection of circulating parasite antigens RDT - based on the detection of P falciparum histidine -rich

protein-2 (PfHRP-2) ,does not detect the other 3 species.

For Vivax and Falciparum -Dipstick tests based on parasite lactate dehydrogenase are now available.

These tests have high sensitivity and specificity, require no special equipment or training, and produce results rapidly.

However, they remain positive for a week or more after the treatment and cure, and, in this situation, can yield false-positive results.

Primaquine is contraindicated inknown G6PD deficient patients, infants and

pregnant women.

Treatment of P. Vivax Malaria

1. Chloroquine : - Drug of choice 25 mg/kg divided over three days i.e.10 mg/kg (600 mg ) on day 1, 10 mg/kg ( 600 mg ) on day 2 & 5 mg/kg on day 3.

2. Primaquine : 0.25 mg/kg 15 mg/day daily for 14 days.

Treatment of uncomplicated P. falciparum malaria

ACT drug of choice

Artemisinin Combination Therapy (ACT) +

single dose primaquine (0.75 mg/kg or 45 mg ) on Day 2.

The ACT recommended in the National Programme of India is Artesunate (4 mg/kg body weight) daily for 3 days

&Sulfadoxine (25 mg/kg body weight)

- pyrimethamine (1.25 mg/kg body weight) on Day 0.

Treatment of uncomplicated P. falciparum malaria

Other ACT can also be used -

Artemether + LumefantrineArtesunate + Amodiaquine

Oral artemisinin monotherapy is banned in IndiaArtemisinin derivatives must never be administered as

monotherapy for uncomplicated malaria. These rapidly actingdrugs, if used alone, can lead to development of drug resistance.

Why Artemisinins ?

Short half-life; hence good for combination Rapid substantial reduction of the parasite biomass Rapid resolution of clinical symptoms Effective action against multi-drug resistant P.

falciparum Reduction of gametocyte carriage No documented parasite resistance yet Few reported adverse effects.

Treatment of malaria in pregnancy

Uncomplicated Pf. - Quinine - Drug for choice in first trimester. - ACT is recommended in 2nd & 3rd trimester

P. vivax malariaCQ drug choice in all trimester

Treatment of mixed infections

Treated as falciparum malaria with ACT.

Antirelapse treatment with primaquine can be given for 14 days

Severe falciparum malaria

Clinical features Impaired consciousness/coma Repeated generalized convulsions

Renal failure (Serum Creatinine >3 mg/dl)

Jaundice (Serum Bilirubin >3 mg/dl)

Severe anaemia (Hb <5 g/dl)

Pulmonary oedema/acute respiratory distress syndrome

Hypoglycaemia (Plasma Glucose <40 mg/dl)

Metabolic acidosis

Circulatory collapse/shock (Systolic BP <80 mm Hg, <50 mm Hg in children)

Abnormal bleeding and Disseminated intravascular coagulation (DIC)

Haemoglobinuria

Hyperpyrexia (Temperature >106o F or >42o C)

Hyperparasitaemia (>5% parasitized RBCs )

Clinical features

Treatment of severe malaria ( falciparum )

Severe malaria is an emergency and treatment should be givenpromptly. Parenteral artemisinin derivatives or quinine shouldbe used irrespective of chloroquine sensitivity.

Artesunate: 2.4 mg/kg body weight i.v. or i.m. given onadmission (time=0), then at 12 hours and 24 hours, thenonce a day (Till patient takes orally or for 7 days). Then full

course of ACT for 3 days Other drugs used are arteether , artemether, quinine ( along with

doxycycline/clindamycin)

Artemether : 3.2 mg/kg body weight i.m. given on admission then 1.6 mg/kg body weight per day.

α−β Arteether: 150 mg daily i.m. for 3 days in adults only

(not recommended for children).

Quinine Quinine: 20 mg quinine salt/kg body weight on admission (i.v. infusion in 5% dextrose/dextrose saline over a period of 4 hours) Maintenance dose of 10 mg/kg body weight 8 hourly Infusion rate should not exceed 5 mg/kg body weight per hour. Loading dose of 20 mg/kg body weight should not be given, if the

patient has already received quinine.. NEVER GIVE BOLUS INJECTION OF QUININE. If parenteral quinine therapy needs to be continued beyond 48 hours, dose should be reduced to 7 mg/kg body weight 8 hourly.

Patients receiving parenteral quinine should be treated with

oral quinine 10 mg/kg body weight three times a day 4 days, along with doxycycline 3 mg/ kg body weight per day for 7 days.

(Doxycycline is contraindicated in pregnant women and children under 8 years of age; instead,

clindamycin 10 mg/kg body weight 12 hourly for 7 days should be used).

Treatment of severe Pf. malaria in pregnancy

First trimester of pregnancy parenteral quinine is the drug of choice.

- If quinine is not available Artemisinin derivatives may be given to save the life of mother

In second and third trimester.- Parenteral artemisinin derivatives are preferred.

Short-term chemoprophylaxis (less than 6 weeks)

Doxycycline:

100 mg daily in adults and 1.5 mg/kg body weight for children more than 8 years old.

Should be started 2 days before travel and continued for 4 weeks after leaving the malarious area.

Long-term chemoprophylaxis(more than 6 weeks)

Mefloquine:

5 mg/kg body weight (up to 250 mg) weekly and should be administered two weeks before, during and four weeks after leaving the area.

Transfusion related malaria

Blood transfusion, IVDU , Organ transplantation

I.P. - short ( no preerythrocytic stage )

C/F & management - same as for naturally acquired infection

Primaquin is unnecessary ( no preerythrocytic stage so relapses do not occur.