DIAGNOSIS AND TREATMENT OF MALARIA

DR.KRITHIGA S.

Based on Guidelines for Diagnosis and Treatment of Malaria in India 2011 - GOI

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FRAME WORK

• Introduction

• Diagnosis

• Aims of treatment guidelines

• Treatment of uncomplicated malaria

• Drug resistance

• Complications and management of severe malaria

• Treatment for complicated malaria

• Chemoprophylaxis

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Introduction

• MALARIA - major public health problem – 1.5 million

confirmed cases (India ,2010)

• WHO recommends all malaria endemic countries should

evolve their own national anti- malaria drug policy

• It is a set of recommendations and regulations regarding the

availability and rational use of antimalarial drugs in a country.

• It should be the part of the national essential drug policy & the

national malaria control policy (overall national health policy).

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Indroduction

• India’s first national anti - malaria drug policy was drafted in 1982.

This reviewed periodically based on sensitivity studies and current

National Drug Policy on Malaria has been revised in 2011 & adopted

by MOHFW.

• The main purpose provide a framework for the safe and effective

treatment of uncomplicated & severe malaria as well as prevention of

malaria in travellers and vulnerable groups.

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Diagnosis

• Microscopy

• Rapid diagnostic test

• Other tests

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Microscopy :

• Peripheral blood smears – Gold standard

• Thick and thin smears

Advantages

• Sensitivity is high

• Detects parasites even at low densities

• Quantify the load

• Distinguish between various species and different stages

• Requires skills to identify.

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Rapid Diagnostic Test

• Dipstick test

• Immunochromatographic test for detection of malarial

antigens(monoclonal /polyclonal antibodies)

• Detetction of antigens -HRP2, Aldolase, pf LDH

•Faster, Needs only little training

• Has good sensitivity

•Expensive and temperature sensitive

•The antigen may persist upto 2 weeks

after parasite clearance

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Other tests

• QBC

• Serological test

• Parasight F,Optimal assay

• PCR

• Sternal or liver puncture

• Radioimmuno assays, Immuno fluorescence

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Effective treatment policy

All malaria control activities in India come under National vector borne

disease control programme

Aims :

• Complete cure

• Interruption of transmission

• Reduce the progression of uncomplicated malaria to severe disease &

prevent mortality

• Minimizing risk of spread of drug resistant parasites

• Prevention of relapse

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TREATMENT OF UNCOMPLICATED MALARIA

General recommendations

• Avoid starting treatment on an empty stomach. The first dose - under observation.

• Dose repeated if vomiting < 30 minutes.

• Report back, if there is no improvement after 48 hours or if the situation deteriorates.

Treatment of P. vivax malaria

• Confirmed Cases - Chloroquine in full therapeutic dose of 25 mg/kg divided over

three days.

• To prevent relapse (Hypnozoites )-Primaquine 0.25 mg/kg bw daily for 14 days

under supervision

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Treatment of P. falciparum malaria

• Artemisinin Combination Therapy (ACT) should be given to all

confirmed P. falciparum cases found positive by microscopy or RDT.

• ACT --an artemisinin derivative + with a long acting antimalarial

(amodiaquine, lumefantrine, mefloquine or sulfadoxine-pyrimethamine).

• On day 2 ,single dose primaquine (0.75 mg/kg body weight).

• The ACT recommended in the National Programme of India is artesunate (4

mg/kg body weight) daily for 3days and sulfadoxine (25 mg/kg body

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

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• Presently, fixed dose combinations of artemether + lumefantrine, artesunate +

amodiaquine and blisterpack of artesunate + mefloquine are registered for

marketing in India and are available for use.

These rapidly acting drugs, if used alone, can lead to development of drug resistance.

Treatment of Malaria in pregnancy

• ACT : second and third trimesters

• Quinine : in the first trimester

• P. vivax malaria can be treated with chloroquine

Oral artemisinin monotherapy is banned

in India

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Treatment of mixed infections

• Mixed infections should be treated as falciparum malaria.

• However, antirelapse treatment with primaquine can be given for 14

days, if indicated.

• Clinical malaria (clinical criteria without laboratory confirmation) is

treated with chloroquine in full therapeutic dose of 25 mg/kg body

weight over three days.

If a slide result is obtained later, the treatment should be completed according

to species.

•Suspected cases of malaria ,negative on diagnostic tests should be treated with

full therapeutic dose of choloroquine22-12-2014 13

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DRUG SCHEDULE UNDER NVDCP

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Drug Resistance: Malaria

Major public health problem ,hinders the control of malaria

• In India resistance of falciparum to chloroquine, the first reported in the year 1973

(Diphu of Karbi-Anglong district in Assam state. )

• NVDCP monitors the response of antimalarial drug in Pf malaria parasite in the

through 13 monitoring teams located in 11 Regional Office for Health & Family

Welfares

Objectives:

• To assess the therapeutic response of P.falciparum to currently used anti-malarials

• To establish and generate information on sensitivity of local strains for formulation

of National Drug Policy and recommend needful changes in the control

.

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Tools for monitoring

• From 2002-03 onward, new WHO protocol on "Therapeutic efficacy of anti-malarial

drugs in uncomplicated P.falciparum malaria" is being followed to assess the

efficacy of antimalarial drugs.

• The classification of response according to new protocol is interpreted into three

categories as per the WHO criteria i.e Adequate Clinical and Parasitological

Response (ACPR), Early and Late Treatment Failure (LTF).

• Adequate response : if no fever or parasitaemia till Day 28.

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Early treatment failure (ETF):

Development of danger signs or

• severe malaria on Day 1, 2 or 3, in the presence of parasitaemia;

• PARASETIMIA on Day 2 > on Day 0, irrespective of axillary temperature;

• Day 3 with axillary temperature>37.5°C;

• Day 3, >25% of count on Day 0.

Late clinical failure (LCF):

Development of danger signs or

• Severe malaria in the presence of parasitaemia on any day between Day 4 and

Day 28 (Day 42)

• Presence of parasitaemia on any day between Day 4 and Day 28 (Day 42) with

axillary temperature >37.5°C

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Late parasitological failure (LPF):

• Presence of parasitaemia on any day between Day 7 and Day 28 with axillary

temperature <37.5°C in patients who did not previously meet any of the criteria of

early treatment failure or late clinical failure.

Alternative treatment -Alternative ACT or quinine with Doxycycline.

• To combat the drug resistant in malaria, the National Drug Policy on Malaria

recommends the use of combination therapy in chloroquine resistant areas,

surrounding cluster of Blocks and 117 high endemic districts

• Criteria for change of drug policy

Drug policy is changed for the area/Block PHC reporting 10% or more total

treatment failure (ETF+LTF) to the currently used antimalarials in a sample of

minimum 30 P.falciparum test cases. 22-12-2014 21

SEVERE MALARIA

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Severe manifestations General

•Jaundice (Serum Bilirubin >3 mg/dl)

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

• Hyperparasitaemia (>5% parasitized RBCs)

CNS•Impaired consciousness/coma

•Repeated generalized convulsions

Metabolic :•Hypoglycaemia (Plasma Glucose <40 mg/dl)

• Metabolic acidosis

Circulatory •Severe anaemia (Hb <5 g/dl)

•Pulmonary oedema/acute respiratory distress syndrome

• Circulatory collapse/shock (Systolic BP <80 mm Hg)

•Abnormal bleeding and DIC

Renal :Renal failure (Serum Creatinine >3 mg/dl), Haemoglobinuria22-12-2014 23

Management of Complicated malaria

Requirements for management of complications

Health facilities should be equipped :

• Parenteral antimalarials, antipyretics,

antibiotics,anticonvulsants

• Intravenous infusion facilities

• Special nursing for patients in coma

• Blood transfusion

• Well-equipped laboratory

• Oxygen22-12-2014 24

Management of other signs and complications

Hyper pyrexia (rectal temp >39 c) •Tepid sponging

•Cool environment

•Para 5mg/kg/bw

Dehydration •IV fluids

•Monitor I/O

Acute renal failure(with

anuria/oliguria/blackwaterfever)

•IV fluids

•Furosemide IV or IM

•Dialysis

•Watch on urea/creatinine/k levels

•Alkanize the urine

Hyperkalemia •>7mmol

•Ca charged resins 15-30gms TDS

•If >60mol NaHco3 infusion with insulin

Hypokalemia •10 cc KCl in 24 hrs22-12-2014 25

Pulmonary edema •Prop up 45 ,oxygen

•Fluid balance and diuretics

GIT symptoms •IV fluids, chlorpromazine IV or IM

Shock •IV plasma expanders

•Corticosteriods

•Dopamine

Anemia(PCV <20, HB <7), bleeding •Whole blood /Packed cell transfusion

•Vit K (bleeding)

Convulsions •Diazepam (0.2 mg/kg/Bw)IM or IV 8hrly

•Phenytoin sodium 5 mg/kg/bw

•Phenobarbitone 5-10 mg/kg/Bw

Hypoglycemia •IV glucose 50% followed by 5-10% glucose

•Monitor blood sugar levels

Hyperparasaitemia •Exchange transfusion22-12-2014 26

Severe malaria :

cases negative on microscopy

– asexual parasites in patients with severe infections

– due to sequestration and partial treatment.

• Confirm by RDT or repeat microscopy

• If clinical presentation indicates severe malaria and there is

no alternative explanation these patients, treated accordingly.

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Specific antimalarial treatment of severe malaria

• Parenteral artemisinin derivatives or quinine should be used irrespective of

chloroquine sensitivity.

DRUG DOSE

• Artesunate: 2.4 mg/kg body weight i.v. or i.m. given on admission (time=0),

then at 12 hours and 24 hours, then once a day (Care should be

taken to dilute artesunate powder in 5% Sodium bi-carbonate

provided in the pack).

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

body weight per day

• Arteether: 150 mg daily i.m. for 3 days in adults only(not recommended

for children)

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Quinine:

20 mg quinine salt/kg body weight on admission

• (i.v. infusion in 5% dextrose/dextrose saline over a period of 4 hrs)

followed by maintenance dose of 10 mg/kg bodyweight 8 hrly;

• infusion rate should not exceed 5mg/kg body weight per hr

• 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

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Once the patient can take oral therapy, further follow-up treatment should be as

below:

• Patients on parenteral quinine should be treated

• oral quinine 10 mg/kg body weight TDS to complete a course of 7 days,

• Along with doxycycline 3 mg/ kg body weight per day for 7 days. (If

contraindicated, Clindamycin 12 hourly for 7 days should be used).

• Patients receiving artemisinin derivatives should get full course of oral

ACT. However, ACT containing mefloquine should be avoided in cerebral

malaria due to neuropsychiatric complications.

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• IV prefered over IM , should be given for min of 24 hours once

started.

•

Severe malaria due to P. Vivax

• Rare in India

• Treated like severe P. falciparum malaria

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First trimester Parenteral quinine (DOC)Artemisinin derivatives

In Second and Third trimester Parenteral Artemisinin

•

• ChemoprophylaxisRecommended for travellers, migrant

labourers and military personnels

• Use of personal protection measures

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Chemoprophylaxis

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Less than 6 weeks

• Doxycycline: 100 mg daily in

adults and 1.5 mg/kg body

weight for children > 8 years

• started 2 days before travel

and continued for 4 weeks

after leaving the malarious

area

Greater than 6 weeks

• Melfoquine 250mg weekly

2 weeks before,during and 4

weeks after exposure

• It is contraindicated in people

with h/o convulsions,neuropsy

problems and cardiac

conditions.