Preface

alaria is a major public health problem in India, accounting for

M sizeable morbidity, mortality and economic loss. Apart from
preventive measures, early diagnosis and complete treatment are
the important modalities that have been adopted to contain the dis-
ease. In view of widespread chloroquine resistance in Plasmodium
falciparum infection, and other recent developments, the national
policy has been revised to meet these challenges.
The guidelines for ‘Diagnosis and Treatment of Malaria in India
(2009)’ were developed during the brainstorming meeting organized
by the National Institute of Malaria Research (NIMR) and sponsored
by WHO Country Office in India. The same have now been revised in
light of changed national drug policy in 2010. These guidelines are
the collaborative effort of National Vector Borne Disease Control
Programme, National Institute of Malaria Research and experts from
different parts of the country. The aim of this endeavour is to guide
the medical professionals on the current methods of diagnosis and
treatment based on the national drug policy. This manual deals with
the treatment of uncomplicated malaria and specific antimalarials
for severe disease. The general management should be carried out
according to the clinical condition of the patient and judgement of
the treating physician. The warning signs of severe malaria have
been listed so as to recognize the condition and give the initial treat-
ment correctly before referring them to a higher facility.
It is hoped that these guidelines will be useful for health care
personnel involved in the treatment of malaria.

Director, NIMR
Director, NVBDCP
© National Institute of Malaria Research, New Delhi

First Edition April 2009

Second Edition June 2011

No part of this document can be reproduced in any form

or by any means without the prior permission of the
Director, National Institute of Malaria Research, Sector 8,
Dwarka, New Delhi.

Printed at M/s. Royal Offset Printers, A-89/1, Naraina Industrial Area

Phase-1, New Delhi-110 028
 Contents

1. Introduction 1

2. Clinical features 1

3. Diagnosis 2

4. Treatment of uncomplicated malaria 3

5. Treatment failure/Drug resistance 5

6. Treatment of severe malaria 8

7. Chemoprophylaxis 11

8. Recommended reading 12

9. Contributors 13

10. Annexure 1 15
 Guidelines for diagnosis and treatment of malaria

1. Introduction
Malaria is one of the major public health problems of the
country. Around 1.5 million confirmed cases are reported annually
by the National Vector Borne Disease Control Programme (NVBDCP),
of which about 50% are due to Plasmodium falciparum. Malaria is
curable if effective treatment is started early. Delay in treatment may
lead to serious consequences including death. Prompt and effective
treatment is also important for controlling the transmission of malaria.
In the past, chloroquine was effective for treating nearly all
cases of malaria. In recent studies, chloroquine-resistant P. falciparum
malaria has been observed with increasing frequency across the
country. The continued treatment of such cases with chloroquine is
probably one of the factors responsible for increased proportion of
P. falciparum relative to P. vivax.
A revised National Drug Policy on Malaria has been adopted
by the Ministry of Health and Family Welfare, Govt. of India in 2010
and these guidelines have been prepared for healthcare personnel
including clinicians involved in the treatment of malaria.

2. Clinical features
Fever is the cardinal symptom of malaria. It can be intermittent
with or without periodicity or continuous. Many cases have chills
and rigors. The fever is often accompanied by headache, myalgia,
arthralgia, anorexia, nausea and vomiting. The symptoms of malaria
can be non-specific and mimic other diseases like viral infections,
enteric fever etc.
Malaria should be suspected in patients residing in endemic
areas and presenting with above symptoms. It should also be
suspected in those patients who have recently visited an endemic
area. Although malaria is known to mimic the signs and symptoms
of many common infectious diseases, the other causes should also
be suspected and investigated in the presence of following
manifestations:

1
 Guidelines for diagnosis and treatment of malaria

• Running nose, cough and other signs of respiratory

infection
• Diarrhoea/dysentery
• Burning micturition and/or lower abdominal pain
• Skin rash/infections
• Abscess
• Painful swelling of joints
• Ear discharge
• Lymphadenopathy
All clinically suspected malaria cases should be investigated
immediately by microscopy and/or Rapid Diagnostic Test (RDT).
3. Diagnosis
3.1 Microscopy
Microscopy of stained thick and thin blood smears remains
the gold standard for confirmation of diagnosis of malaria. The
advantages of microscopy are:
• The sensitivity is high. It is possible to detect malaria para-
sites at low densities. It also helps to quantify the parasite
load.
• It is possible to distinguish the various species of malaria
parasite and their different stages.

3.2 Rapid Diagnostic Test

Rapid Diagnostic Tests are based on the detection of
circulating parasite antigens. Several types of RDTs are available
(http://www.wpro.who.int/sites/rdt). Some of them can only detect
P. falciparum, while others can detect other parasite species also.
The latter kits are expensive and temperature sensitive. Presently,
NVBDCP supplies RDT kits for detection of P. falciparum at locations
where microscopy results are not obtainable within
24 hours of sample collection.
RDTs are produced by different companies, so there may be
differences in the contents and in the manner in which the test is

2
 Guidelines for diagnosis and treatment of malaria

done. The user’s manual should always be read properly and

instructions followed meticulously. The results should be read at the
specified time. It is the responsibility of the health care personnel
doing a rapid test for malaria to ensure that the kit is within its expiry
date and has been transported and stored under recommended
conditions. Failure to observe these criteria can lead to false/negative
results. It should be noted that Pf HRP-2 based kits may show
positive result up to three weeks after successful treatment.

Early diagnosis and treatment of cases of malaria

aims at:
• Complete cure

• Prevention of progression of uncomplicated malaria to severe

disease

• Prevention of deaths

• Interruption of transmission
• Minimizing risk of selection and spread of drug resistant
parasites

4. Treatment of uncomplicated malaria

All fever cases diagnosed as malaria by RDT or microscopy
should promptly be given effective treatment.
4.1 Treatment of P. vivax malaria
Confirmed P. vivax cases should be treated with chloroquine
in full therapeutic dose of 25 mg/kg divided over three days. In some
patients, P. vivax may cause relapse (A form of P. vivax or P. ovale
parasites called as hypnozoites remain dormant in the liver cells.
These hypnozoites can later cause a relapse). For its prevention,
primaquine should be given at a dose of 0.25 mg/kg body weight
daily for 14 days under supervision. Primaquine is contraindicated in
known G6PD deficient patients, infants and pregnant women. Caution
should be exercised before administering primaquine in areas known

3
 Guidelines for diagnosis and treatment of malaria

to have high prevalence of G6PD deficiency, therefore, it should be

tested if facilities are available. Primaquine can lead to hemolysis in
G6PD deficiency. Patient should be advised to stop primaquine
immediately if he/she develops symptoms like dark coloured urine,
yellow conjunctiva, bluish discolouration of lips, abdominal pain,
nausea, vomiting etc. and should report to the doctor immediately.
4.2 Treatment of P. falciparum malaria
Artemisinin Combination Therapy (ACT) should be given to all
confirmed P. falciparum cases found positive by microscopy or RDT.
This is to be accompanied by single dose primaquine (0.75 mg/kg
body weight) on Day 2.
ACT consists of an artemisinin derivative combined with a long
acting antimalarial (amodiaquine, lumefantrine, mefloquine or
sulfadoxine-pyrimethamine). The ACT recommended in the National
Programme of India is artesunate (4 mg/kg body weight) daily for 3
days and sulfadoxine (25 mg/kg body weight) -pyrimethamine (1.25
mg/kg body weight) on Day 0. Presently, fixed dose combinations
of artemether+ lumefantrine, artesunate + amodiaquine and blister
pack of artesunate + mefloquine are registered for marketing in
India and are available for use. Other ACTs which will be
registered and authorized for marketing in India may also be used as
alternatives.
4.3 Treatment of malaria in pregnancy
ACT should be given for treatment of P. falciparum malaria in
second and third trimesters of pregnancy, while quinine is
recommended in the first trimester. P. vivax malaria can be treated
with chloroquine.

Oral artemisinin monotherapy is banned in India

Artemisinin derivatives must never be administered as
monotherapy for uncomplicated malaria. These rapidly acting
drugs, if used alone, can lead to development of drug resistance.

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 Guidelines for diagnosis and treatment of malaria

4.4 Treatment of mixed infections

Mixed infections with P. falciparum should be treated as
falciparum malaria. However, antirelapse treatment with primaquine
can be given for 14 days, if indicated.
4.5 Treatment based on clinical criteria without
laboratory confirmation
All efforts should be made to diagnose malaria either by
microscopy or RDT. However, special circumstances should be
addressed as mentioned below:
• If RDT for only P. falciparum is used, negative cases show-
ing signs and symptoms of malaria without any other obvi-
ous cause for fever should be considered as ‘clinical ma-
laria’ and 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 accord-
ing to species.
• Suspected malaria cases not confirmed by RDT or micros-
copy should be treated with chloroquine in full therapeutic
dose.
4.6 General recommendations for the management
of uncomplicated malaria
• Avoid starting treatment on an empty stomach. The first
dose should be given under observation.
• Dose should be repeated if vomiting occurs within 30 min-
utes.
• The patient should be asked to report back, if there is no
improvement after 48 hours or if the situation deteriorates.
• The patient should also be examined for concomitant ill-
nesses.
The algorithm for diagnosis and treatment is shown in Chart 1.
5. Treatment failure/Drug resistance
After treatment patient is considered cured if he/she does not
have fever or parasitaemia till Day 28. Some patients may not respond

5
 Guidelines for diagnosis and treatment of malaria

Chart 1: Algorithm for diagnosis and treatment of malaria

Where microscopy result is available within 24 hours
Clinically suspected malaria case

Take slide for microscopy

P. vivax P. falciparum Negative

CQ 3 days + ACT 3 days + PQ single dose Needs further
PQ 14 days evaluation*
Where microscopy result is not available within 24 hours

Clinical suspected malaria case

Perform RDT

RDT for Pf, Also RDT for Pf & Pv

prepare blood smear

Positive: Treat according

Pf RDT positive Pf RDT Negative to species
ACT 3 days + Send blood slide to laboratory Negative: Needs further
PQ single dose Give CQ for 3 days, and await evaluation*
on Day 2 microscopy result
Microscopy result
• + ve for Pv - PQ for 14 days under supervision.
• + ve for Pf - ACT 3 days + PQ single dose on Day 2
*Look for other causes of fever; repeat blood slide examination after an appropriate interval

Table 1. Chloroquine for P. vivax

Number of tablets
Age in years Day 1 Day 2 Day 3
(10 mg/Kg) (10 mg/Kg) (5 mg/Kg)
<1 ½ ½ ¼
1–4 1 1 ½
5–8 2 2 1
9 – 14 3 3 1½
15 & above 4 4 2

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 Guidelines for diagnosis and treatment of malaria

Table 2. Primaquine for P. vivax (Daily Dosage for 14 days)

Age in years Daily dosage No. of tablets
(in mg base) (2.5 mg base)
<1 Nil Nil
1–4 2.5 1
5–8 5.0 2
9 – 14 10.0 4
15 & above 15.0 6
Note: Primaquine should be given for 14 days under supervision.
Do not give Primaquine to pregnant women and infants and G6PD deficiency cases.

Table 3. ACT (Artesunate + SP) dosage schedule for

P. falciparum
Age in years* Number of tablets
1st Day 2nd Day 3rd Day
<1 AS ½ ½ ½
SP ½ Nil Nil
1–4 AS 1 1 1
SP 1 Nil Nil
5–8 AS 2 2 2
SP 1½ Nil Nil
9 – 14 AS 3 3 3
SP 2 Nil Nil
15 and above AS 4 4 4
SP 3 Nil Nil
AS – Artesunate 50 mg, SP – Sulfadoxine 500 mg + Pyrimethamine 25 mg; *Recently,
blister packs for different age groups have also been formulated. Details of the same are
given in Annexure 1.

Table 4. Primaquine for P. falciparum (Single dose on Day 2)

Age in years Dosage No. of tablets
(in mg base) (7.5 mg base)
<1 Nil 0
1–4 7.5 1
5–8 15 2
9 – 14 30 4
15 & above 45 6
Note: Do not give Primaquine to pregnant women, infants and G6PD deficiency cases.

7
 Guidelines for diagnosis and treatment of malaria

to treatment which may be due to drug resistance or treatment failure,

specially in falciparum malaria. If patient does not respond and
presents with following, he/she should be given alternative treatment.
Early treatment failure (ETF): Development of danger signs
or severe malaria on Day 1, 2 or 3, in the presence of parasitaemia;
parasitaemia on Day 2 higher than on Day 0, irrespective of axillary
temperature; parasitaemia on Day 3 with axillary temperature
>37.5°C; and parasitaemia on 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) in patients who did not previously meet
any of the criteria of early treatment failure; and presence of
parasitaemia on any day between Day 4 and Day 28 (Day 42) with
axillary temperature >37.5°C in patients who did not previously meet
any of the criteria of early treatment failure.
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.
Such cases of falciparum malaria should be given alternative
ACT or quinine with Doxycycline. Doxycycline is contraindicated in
pregnacy, lactation and in children up to 8 years. Treatment failure
with chloroquine in P. vivax malaria is rare in India.
6. Treatment of severe malaria
6.1 Clinical features
Severe manifestations can develop in P. falciparum infection
over a span of time as short as 12 – 24 hours and may lead to death,
if not treated promptly and adequately. Severe malaria is
characterized by one or more of the following features:
• Impaired consciousness/coma
• Repeated generalized convulsions
• Renal failure (Serum Creatinine >3 mg/dl)
• Jaundice (Serum Bilirubin >3 mg/dl)

8
 Guidelines for diagnosis and treatment of malaria

• 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 coagu-
lation (DIC)
• Haemoglobinuria
• Hyperpyrexia (Temperature >106o F or >42o C)
• Hyperparasitaemia (>5% parasitized RBCs )
Foetal and maternal complications are more common in
pregnancy with severe malaria; therefore, they need prompt attention.

6.2 Diagnosis of severe malaria cases negative on

microscopy
Microscopic evidence may be negative for asexual parasites
in patients with severe infections due to sequestration and partial
treatment. Efforts should be made to confirm these cases by RDT or
repeat microscopy. However, if clinical presentation indicates severe
malaria and there is no alternative explanation these patients should
be treated accordingly.

6.3 Requirements for management of complications

For management of severe malaria, health facilities should be
equipped with the following:
• Parenteral antimalarials, antipyretics, antibiotics,
anticonvulsants
• Intravenous infusion facilities
• Special nursing for patients in coma
• Blood transfusion
• Well-equipped laboratory
• Oxygen

9
 Guidelines for diagnosis and treatment of malaria

If these items are not available, the patient must be referred

without delay to a facility, where they are available.

6.4 Specific antimalarial treatment of severe malaria

Severe malaria is an emergency and treatment should be given
promptly. Parenteral artemisinin derivatives or quinine should
be used irrespective of chloroquine sensitivity.
• 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).
• Quinine: 20 mg quinine salt/kg body weight on admission
(i.v. infusion in 5% dextrose/dextrose saline over a period of
4 hours) followed by 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.
• 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).

Note:
• Once the patient can take oral therapy, further follow-up
treatment should be as below:
• Patients receiving parenteral quinine should be treated with
oral quinine 10 mg/kg body weight three times a day to
complete a course of 7 days, along with doxycycline 3 mg/
kg body weight per day for 7 days. (Doxycycline is contrain-
dicated in pregnant women and children under 8 years of

10
 Guidelines for diagnosis and treatment of malaria

age; instead, clindamycin 10 mg/kg body weight 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.
• Intravenous preparations should be preferred over
intramuscular preparations. Parenteral treatment
should be given for minimum of 24 hours once started.
• In first trimester of pregnancy, parenteral quinine is
the drug of choice. However, if quinine is not available,
artemisinin derivatives may be given to save the life of mother.
In second and third trimester, parenteral artemisinin deriva-
tives are preferred.
6.5 Severe malaria due to P. vivax
In recent years, increased attention has been drawn to severe
malaria caused by P. vivax. Some cases have been reported in India,
and there is reason to fear that this problem may become more
common in the coming years. Severe malaria caused by
P. vivax should be treated like severe P. falciparum malaria.
7. Chemoprophylaxis
Chemoprophylaxis is recommended for travellers, migrant
labourers and military personnel exposed to malaria in highly endemic
areas. Use of personal protection measures like insecticide-treated
bednets should be encouraged for pregnant women and other
vulnerable populations.
7.1 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. The drug should be started
2 days before travel and continued for 4 weeks after leaving the
malarious area.
Note: Doxycycline is contraindicated in pregnant and lactating women
and children less than 8 years.

11
 Guidelines for diagnosis and treatment of malaria

7.2 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.
Note: Mefloquine is contraindicated in cases with history of convulsions,
neuropsychiatric problems and cardiac conditions.

8. Recommended reading
1. Malaria in India. Guidelines for its control. National Vector
Borne Disease Control Programme. http://www.nvbdcp.gov.in/
malaria-new.html
2. National drug policy on malaria (2010). Ministry of Health and
Family Welfare/Directorate of National Vector Borne Disease
Control Programme, Govt. of India. http://www.nvbdcp.gov.in
3. Rapid diagnostic tests. Website of WHO Regional Office for
the Western Pacific. http://www.wpro.who.int/sites/rdt
4. WHO Guidelines for the Treatment of Malaria, second edition.
Geneva, World Health Organization (2010). http://www.who.int/
malaria/publications/atoz/9789241547925/enindex.html
5. Regional guidelines for the management of severe falciparum
malaria in small hospitals, World Health Organization, Re-
gional Office for South-East Asia (2006). New Delhi, WHO/
SEARO. http://www.searo.who.int/LinkFiles/Tools_&_ Guide-
lines_ Smallhospitals.pdf
6. Regional guidelines for the management of severe falciparum
malaria in large hospitals. World Health Organization, Regional
Office for South-East Asia (2006). New Delhi, WHO/SEARO.
http://www.searo.who.int/LinkFilesTools_&_Guidelines_
LargelHospitals.pdf
7. Drug resistance in malaria. WHO/CDS/CSR/DRS/2001.4
8. Kochar DK, Das A, Kochar SK et al. (2009). Severe Plasmo-
dium vivax malaria: A report on serial cases from Bikaner in
northwestern India. Am J Trop Med Hyg 80 (2): 194–8.

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 Guidelines for diagnosis and treatment of malaria

Contributors

Dr. Anup Anvikar, Scientist D

National Institute of Malaria Research, New Delhi
E-mail: anvikar@rediffmail.com

Mrs. Usha Arora, Senior Research Officer

National Vector Borne Disease Control Programme, Delhi
E-mail: uarora2006@yahoo.co.in

Dr. D. Chattopadhya, Additional Director

National Centre for Disease Control, Delhi
E-mail: dchattopadhya@yahoo.co.in

Dr. Bidyut Das, Professor & Head

Department of Medicine
Medical College, Burla, Sambalpur
E-mail: bidyutdas@hotmail.com

Prof. A.P. Dash, Regional Adviser

WHO-SEARO, New Delhi
E-mail: apdash2@rediffmail.com

Dr. A.C. Dhariwal, Director

National Vector Borne Disease Control Programme, Delhi
E-mail: dr_dhariwal@yahoo.co.in

Dr. G.P.S. Dhillon, Former Director

National Vector Borne Disease Control Programme, Delhi
E-mail: drgpsdhillon@hotmail.com

Dr. V.K. Dua, Scientist G

National Institute of Malaria Research, New Delhi
E-mail: vkdua51@gmail.com

Dr. A. Gunasekar, National Professional Officer

WR India, New Delhi
E-mail: gunasekara@searo.who.int

(contd...)

13
 Guidelines for diagnosis and treatment of malaria

Dr. Dhanpat Kumar Kochar, Former Professor and Head

Cerebral Malaria Research Centre
S.P. Medical College, Bikaner &
Consultant Neurologist and Chief Research Coordinator
Kothari Medical & Research Institute, Bikaner
E-mail: drdkkochar@yahoo.com

Dr. Shiv Lal, Advisor

National Centre for Disease Control, Delhi
E-mail: drlalshiv@gmail.com

Dr. Sanjib Mohanty, Joint Director

Ispat General Hospital, Rourkela
E-mail: sanjibmalaria@rediffmail.com

Dr. S. Pattanayak, Former Director

National Malaria Eradication Programme, Delhi &
Former Regional Adviser, WHO-SEARO, New Delhi
E-mail: sadanand@gmail.com

Dr. G.S. Sonal, Additional Director

National Vector Borne Disease Control Programme, Delhi
E-mail: gssnvbdcp@gmail.com

Dr. Neena Valecha, Director

National Institute of Malaria Research, New Delhi
E-mail: neenavalecha@gmail.com

NIMR/TRS/2011/1
14
 Annexure 1
Drug schedule of ACT for different age groups
as per blister pack

Age group 1st Day 2nd Day 3rd Day

(years) AS SP AS PQ AS

0–1 1 1 1 Nil 1
(25 mg) (250 + 12.5 mg) (25 mg) (25 mg)
1–4 1 1 1 1 1

15
(50 mg) (500 + 25 mg) (50 mg) (7.5 mg base) (50 mg)
5–8 1 1 1 2 1
(100 mg) (750+ 37.5 mg) (100 mg) (7.5 mg base each) (100 mg)
9–14 1 2 1* 4 1*
(150 mg) (500 + 25 mg) (150 mg) (7.5 mg base each) (150 mg)
Guidelines for diagnosis and treatment of malaria

15 & above 1 2 1 6 1
(200 mg) (750 + 37.5 mg each) (200 mg) (7.5 mg base each) (200 mg)
* Previous supply in some places, blister packs for age group 9-14 contains two tablets of artesunate with 100 mg and 50
mg strength.
 NOTES

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