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Dr. lokesh Garg md., MR. Satish kamboj
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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.
Recommended