Guidelines Malaria Di Malaysia

FOREWORD
Malaysia has come a long way in the prevention and control of malaria since the
introduction of the Malaria Eradication Programme in 1960. In 2011, we fnally reached
the signifcant milestone of having less than 1 case per 1,000 population and thereby
entered the elimination phase. The National Malaria Elimination Strategic Plan was
introduced in the same year with the target of malaria free status by 2020.
Since the frst guidelines in malaria management was published in 1993, several new developments have
appeared notably the emergence of Plasmodium knowlesi with its diagnostic challenge in identifcation.
The ever growing problem of chloroquine resistance by Plasmodium falciparum and the introduction of
Artemisinin-based combination therapies (ACTs) require clinicians to enhance their knowledge and skills.
Hence, it is timely that the Ministry of Health produce this new guidelines to update all health care workers
on the latest clinical evidence of malaria management.
The Management Guidelines of Malaria in Malaysia 2013 covers all aspects in the management including
diagnosis, management of severe malaria and malaria chemoprophylaxis. A chapter for the monitoring of
treatment response is included to provide a Standard Operating Procedure (SOP) for the National Surveillance
of Drug Response against Malaria Parasite. This would facilitate clinicians to monitor and report cases with
anti-malaria resistance during the disease follow-up.
It is my sincere hope that all health care personnel will fnd this guideline useful and utilize it optimally to
improve the management of malaria in the country.
Last but not least, I would like to acknowledge the contribution of the technical working group in developing
a consensus policy on malaria case management.
DATUK DR. LOKMAN HAKIM BIN SULAIMAN
Deputy Director General (Public Health)
Ministry of Health
Malaysia
1
Management Guidelines Of Malaria In Malaysia
PREFACE
Malaria is a major public-health problem, with over 40% of the worlds population (more than 3.3 billion
people) are at risk for malaria infection to varying degrees in countries with on-going transmission.
Malaria has been reported in Malaysia even before 1900s. In 1990, there were 50,500 cases in Malaysia. A
decade later, in the year 2000, the number of reported cases has reduced to 12,705 cases. In 2012, there were
4,725 cases which is a 63% reduction compared to 2000. The incidence rate in Malaysia has declined to less
than 1 per 1,000 population since 1998. There has also been a reduction in the number of malaria deaths from
43 in 1990 to 35 in 2000 and to 16 deaths in 2012. The mortality rate due to malaria has been around 0.001 per
1,000 population since 2006. All fgures and rates are inclusive of P. knowlesi.The frst case of Plasmodium
knowlesi has been reported in Malaysia in 1965. Based on 2012, P. knowlesi accounted for 38% (1813) of all
cases which is the highest among all Plasmodium species.
Early diagnosis and prompt treatment are fundamental to malaria control and need to be available wherever
malaria occurs. Correct treatment of malarial disease will shorten its duration and largely prevent the
development of complications and death, especially in high-risk groups such as young children and pregnant
women.
Plasmodium knowlesi followed by Plasmodium falciparum causes the most serious form of disease in Malaysia
1
.
Infections with this parasite can be fatal in the absence of prompt recognition of the disease. Plasmodium vivax
may also cause severe infection. Resistance of parasites to antimalarial agents has led to increasing diffculties
for the provision of adequate disease management.
This guideline on the management of malaria has been revised and updated based on previous national
guidelines (published in year 1993) and the latest WHO guideline (2
nd
edition). It is intended primarily for
healthcare personnel in Malaysia for the management of malaria patients.
Reference:
1. William T et al. Increasing incidence of Plasmodium knowlesi malaria following control of P. falciparum
and P. vivaxc Malaria in Sabah, Malaysia. PLoS Negl Trop Dis. 2013;7(1):e2026
2
TECHNICAL WORKING GROUP COMMITTEE MEMBERS
(Alphabetical order)
Dr. Che Kamaludin B Che Ahmad
Public Health Physician
State Health Department, Kelantan
Datuk Dr. Christopher K. C. Lee
Senior Consultant Infectious Disease Physician
Hospital Sungai Buloh, Selangor
Dr. Christina Rundi
Director of State Health Department, Sabah
Dr. Chua Hock Hin
Consultant Infectious Disease Physician
Hospital Umum Sarawak
Dr. Fong Siew Moy
Consultant Infectious Disease Pediatrician
Hospital Likas, Sabah
Ms. Hazimah Bt Hashim
Pharmarcist
Pharmacy Practice & Development Division,
Ministry of Health
Dr. Ho Bee Kiau
Family Medicine Specialist
Botanik Health Clinic
Klang, Selangor
Dr. Jenarun Jelip
State Health Department, Sabah
Dr. Kamarul Azahar B Mohd Razali
Consultant Infectious Disease Paediatrician
Hospital Kuala Lumpur
Mr. Khairul Azan B Hashim
Medical Microbiology Scientifc Of-
fcer
National Public Health Laboratory
Sungai Buloh, Selangor
Dr. Lee Wai Khew
Luyang Health Clinic
Kota Kinabalu, Sabah
Dr. Mahiran Bt Mustafa
Senior Consultant Infectious Disease
Physician
Hospital Raja Perempuan Zainab II
Kota Bharu, Kelantan
Dr. Ooi Choo Huck
State Health Department, Sarawak
Dr. Rose Nani Bt Mudin
Head of Vector Borne Disease Sector
Disease Control Division
Ministry of Health
Dr. Timothy William
Consultant Infectious Disease
Physician
Queen Elizabeth Hospital
3 4
Management Guidelines Of Malaria In Malaysia Management Guidelines Of Malaria In Malaysia
EXTERNAL REVIEWERS
(Alphabetical order)

Professor Balbir Singh
Director, Malaria Research Centre
Faculty of Medicine & Health Sciences
University Malaysia Sarawak
Kuching, Sarawak
Dr. George G. Matthew
Tamparuli Health Clinic
Tuaran, Sabah
Datuk Dr. Jayaram Menon
Senior Consultant Physician
Queen Elizabeth Hospital
ADVISOR
Dr. Chong Chee Kheong
Director of Disease Control Division
Ministry of Health
SECRETARIAT

Dr. Mohd Hafzi B Abdul Hamid
Public Health Physician (Malaria)
Vector Borne Disease Sector
Ministry of Health
Datuk Dr. Lokman Hakim Sulaiman
Deputy Director General (Public Health)
Ministry of Health
Professor Dr. Nicholas Anstey
Professor and Head of Global Health Division
Senior Principal Research Fellow
Menzies School of Health Research,
Australia
Dr. Zubaidah Abdul Wahab
Senior Consultant Microbiologist
Hospital Sungai Buloh, Selangor
Dr. Wan Ming Keong
Senior Medical Offcer (Malaria)
Ministry of Health
3 4
ACRONYM
ACT : Artemisinin-based Combination Therapy
ASMQ : Artesunate / Mefoquine
BD : Bis Die (Latin for twice a day)
BFMP : Blood Film for Malaria Parasite
CVP : Central Venous Pressure
EBT : Exchange Blood Transfusion
EDTA : Ethylenediaminetetraacetic Acid
FDC : Fixed-dose Combination
GCS : Glasgow Coma Scale
G6PD : Glucose-6-Phosphate Dehydrogenase
GI : Gastrointestinal
HDU : High Dependency Unit
ICU : Intensive Care Unit
LDH : Lactate dehydrogenase
NSPEM : National Strategic Plan for Elimination of Malaria
OD : Omne in Die (Latin for once daily)
RDT : Rapid Diagnostic Test
TNF- : Tumor Necrosis Factor Alpha
5 6
TABLE OF CONTENTS
FOREWORD 1
PREFACE 2
TECHNICAL WORKING GROUP COMMITTEE MEMBERS 3
EXTERNAL REVIEWERS 4
ACRONYM 5
TABLE OF CONTENT 6 - 7
CHAPTER 1 : INTRODUCTION
1.1 Epidemiology of Malaria 8
1.2 Epidemiology of Malaria in 2012 8
1.3 Notifcation of Malaria 9
1.4 National Strategic Plan for Elimination of Malaria (2011-2020) 10
CHAPTER 2 : MALARIA PARASITE
2.1 Life cycle 11
2.2 Pathophysiology 12
2.3 Antimalarial drug resistance 12-13
CHAPTER 3 : CLINICAL FEATURES
3.1 Symptoms of Malaria 14
3.2 Defnition of Uncomplicated Malaria 15
3.3 Defnition of Severe and Complicated Malaria 15-16
CHAPTER 4 : DIAGNOSIS OF MALARIA
4.1 Clinical Diagnosis 17
4.2 Laboratory Diagnosis 17
4.2.1 Tests Available For Laboratory Diagnosis 18-20
4.2.2 Quality Checking 21
CHAPTER 5 : MALARIA TREATMENT
5.1 Treatment of Malaria in Adults 22
5.2 Field Treatment 22
5.3 Presumptive Treatment 22-27
5 6
CHAPTER 6 : MANAGEMENT OF SEVERE AND COMPLICATED MALARIA
6.1 For treatment 28
6.2 Referral to hospitals with specialists 28
6.3 Criteria for admission 38
6.4 Criteria for referral:
High Dependency Unit (HDU) or Intensive Care Unit (ICU) 29
6.5 General Management of Severe Malaria 29
6.6 Management of complications of Malaria 30
6.7 Adjunct Therapy 30
6.7.1 Exchange blood transfusion (EBT) 31
6.7.2 Adjunctive Treatments not recommended 31
6.8 Discharge 31
6.9 Follow up 31
CHAPTER 7 : MANAGEMENT OF MALARIA IN PAEDIATRICS
7.1 Uncomplicated Malaria 33-34
7.2 Complicated / Severe Plasmodium falciparum 35-36
7.3 Congenital Malaria 37
7.4 Mixed Malaria Infections 37
CHAPTER 8 : MALARIA CHEMOPROPHYLAXIS
8.1 Risk of Malaria 38
8.2 Chemoprophylaxis 39
8.2.1 Suppressive prophylaxis 39
8.2.2 Causal prophylaxis 39
8.2.3 Considerations when choosing a drug for malaria prophylaxis 39
CHAPTER 9 : TREATMENT RESPONSE MONITORING 42-47

Appendix 1 48-49
Appendix 2 50-58
Appendix 3 59
7 8
CHAPTER 1: INTRODUCTION
Although malaria control activities over the last few decades have greatly reduced the incidence of malaria in
Malaysia, it is still a major public health problem in the hinterland and less developed parts of the country and
accounts for a considerable number of cases treated at health clinics and admissions to hospitals. In addition,
frequent and affordable travel especially to malaria endemic countries and infux of workers from endemic
countries in search of work have kept the number of imported malaria cases on the constant high and pose a
real threat of re-introducing malaria into areas which have eliminated the disease.
This book aims to cover various aspects of malaria and its management to assist medical and health personnel
in the management of malaria and its complications. If severe cases of malaria are not managed properly, they
can lead to complications and death. In our effort to achieve malaria elimination in Malaysia by 2020, there
is a need for a standardised up-to-date malaria case management guideline.
1.1 Epidemiology of malaria
Malaria cases in Malaysia have been on the decline from 12,705 cases in 2000 to 4,725 cases in 2012.
The incidence rate declined from 0. 55 per 1,000 population in 2000 to 0.16 per 1,000 populations in
2012. For the past decade (2000 2012), malaria cases has reduced from 3,918 cases to 1,097 cases in
Peninsular Malaysia, from 3,011 cases to 1,571 cases in Sarawak and from 5,776 cases to 2052 cases
in Sabah. (Figure 1.1)
There has also been a reduction in the number of malaria deaths from 35 in 2000 and to 16 deaths in
2012. The Case Fatality Rate of malaria has been around 0.3 to 0.5 per 100,000 population since 2006.
(Figure 1.2)
1.2 Epidemiology of malaria in 2012
In 2012, of the 4,725 reported cases, 61.6% were human malaria infection and a signifcant proportions
(38.4%) were zoonotic. Among human malaria infection, P. vivax accounted for 50.2%, followed by
P. falciparum (30.7%), P. malariae (16.7%) and mixed infection (2.2%).
Of the human malaria, 2051 cases (70.4%) were indigenous cases and a small proportion of 861 cases
(29.6%) were imported.
Of the indigenous malaria 74.0% were reported from Sabah followed by 15.9% from Sarawak and
10.1% from Peninsular Malaysia. Of the zoonotic malaria, 56.9% were reported from Sarawak
followed by 23.3% from Peninsular Malaysia and 19.8% from Sabah.
In Peninsular Malaysia, Selangor, Pahang, Kelantan and Perak reported more than 100 cases throughout
the year 2012. A big proportion (78.2%) of the cases were among male with only 21.8% among female.
About 8.5% of the female patients were pregnant. Children below the age of 5 accounted for 2.5% of
all cases whilst those mostly affected were in the age group of 20 29 years (25%). About 61.9% of
the cases were between the ages of 20 to 49 years.
7 8
Source: Vector Borne Disease Sector, Ministry of Health
Figure 1.2: Malaria Deaths and Case Fatality Rate in Malaysia, 2000-2012
9 10
Figure 1.1: Number and Incidence of Malaria (per 1,000 population) in Malaysia, 2000 2012
Source: Vector Borne Disease Sector, Ministry of Health
Incidence (per 1,000 populaton)
1.3 Notifcation of malaria
Malaria is a notifable disease under the Communicable Diseases Control Act 1988 which mandates
notifcation within 7 days. However, to ensure early investigation and institution of control measures,
all practitioners are to notify malaria cases within 24 hours to the nearest health offce.
1.4 National Strategic Plan for Elimination of Malaria (2011-2020)
In 2011, the Malaria Control Programme was re oriented from control to elimination, and MOH
formulated the National Strategic Plan for the Elimination of Malaria (NSPEM) (2011 2020) with
the objective of eliminating locally acquired human-only malaria by 2020.
Seven strategies outlined in the NSPEM (2011 2020) :
strengthen Malaria Surveillance System
intensify control activities using Integrated Vector Management approach
ensure early detection of cases and prompt treatment
heighten preparedness and early response to outbreak
enhance awareness and knowledge on malaria towards social mobilisation and empowerment
strengthen human resource capacity and
conduct relevant researches.
One of the seven main strategies is early detection of cases and prompt treatment which advocate for the use
of Artemisinin-based Combination Therapy (ACT) as frst line treatment for all species.
9 10
CHAPTER 2: MALARIA PARASITE
2.1 Life cycle
Malaria is caused by infection of red blood cells with protozoan parasites of the genus Plasmodium.
The parasites are inoculated into the human host by a feeding female anopheline mosquito. The four
Plasmodium species that are transmitted from humans-to-humans are P. falciparum, P. vivax, P. ovale
and P. malariae. Increasingly, human infections with the simian malaria parasite, P. knowlesi, have
also been reported from the forested regions of Malaysia and other countries in Southeast Asia.
The basic life cycle of all malaria parasites is the same. It comprises of a sexual phase with multiplica-
tion in the mosquito (sporogony) and an asexual phase with multiplication in the human (schizogony).
(Figure 2.1)
Source: Image adapted from Laboratory Identifcation of Parasites of Public Health Concern of the USA
government of Centers for Disease Control and Prevention (CDC)
4
Figure 2.1: Life cycle of Plasmodium species
11
2.2 Pathophysiology
During a blood meal, an infected female Anopheles mosquito injects thousands of malarial sporozoites,
which rapidly enter hepatocytes. Reproduction by asexual fssion (tissue schizogony) takes place to
form a pre-erythrocytic schizont. This part of the life-cycle produces no symptoms.
After a period of time, thousands of merozoites are released into the blood stream to penetrate
erythrocytes after attaching via receptors. The time period before merozoites enter the blood from
the liver is termed as the pre-patent period; incubation period is about 12 days for P. falciparum and
P. knowlesi, 14 days for P. vivax and P. ovale and 30 days for P. malariae.The clinical symptoms
begin after the rupture of the mature schizont-infected erythrocytes, releasing the merozoites and toxic
products of the parasites metabolism into the blood. Most merozoites undergo blood schizogony
within erythrocytes to form trophozoites, evolving to schizonts, which rupture to release new
merozoites. These then invade new erythrocytes and the erythrocytic cycle (48 hours for P.falciparum,
P.vivax, and P.ovale; P.knowlesi 24 hours, P.malariae 72 hours)continues. The rupture of erythrocytes
releases toxins that induce the release of cytokines from macrophages, resulting in an increase in body
temperature, sometimes resulting in periodicity of fever.
Some merozoites mature within erythrocytes into sexual forms called gametocytes, which reproduce
sexually if they are ingested by a mosquito. (Figure 2.1) If left untreated, the parasite counts in a
malaria patient keep increasing every 24, 48 or 72 hours, depending on the Plasmodium species.
2.3 Antimalarial drug resistance
Resistance to antimalarials has been documented for P. falciparum, P. malariae and P. vivax. In P.
falciparum, resistance has been observed in all currently used antimalarials (amodiaquine, chloroquine,
mefoquine, quinine, and sulfadoxine-pyrimethamine) and, more recently, in artemisinin derivatives
in certain parts of the world. The geographical distributions and rates of spread of antimalarial drug
resistance have varied considerably.
P. vivax has developed resistance rapidly to Fansidar (sulfadoxine-pyrimethamine) in many areas,
while resistance to chloroquine is confned largely to Indonesia, Papua New Guinea, Timor-Leste and
other parts of Oceania. There are also reports on resistance from Brazil and Peru.
Chloroquine resistant falciparum malaria was frst reported in Peninsular Malaysia in 1963.
2
Studies
on chloroquine resistant falciparum malaria in the 1960s to 1970s revealed the range of resistance rate
from 3.9% to 50.7%, most of it being mild R1 type.
A study in Peninsular Malaysia in 1993 documented the overall resistance to chloroquine as 63.3% and
to Sulfadoxine-pyrimethamine as 47.4%. RI, RII and R Ill
1
rates for chloroquine were 9.1%, 42.4%
and 12.1% while for sulfadoxine-pyrimethamine they were 10.5%, 21.1% and 15.8%. Degree and
rates of resistance to chloroquine were signifcantly correlated with pre-treatment parasite density, but
not those to sulfadoxine-pyrimethamine
3.
12
References:
1. Guidelines for Treatment of Malaria (2nd edition, WHO, 2010)
2. Montgomery, R., and Eyles, D. E. 1963. Chloroquine resistant falciparum malaria in Malaya. Trans. Roy.
Soc. Trop. Med & Hyg. 57: 409-16
3. S. Lokman Hakim, S.W.A. Sharifah Roohi, Y. Zurkurnai, A. Noor Rain, S.M. Mansor, K. Palmer, V.
Navaratnam and J.W.Mak. Plasmodium falciparum: Increased proportion of severe resistance (RII and
RIII) to chloroquine and high rates of resistance to sulfadoxine-pyrimethamine in Peninsular Malaysia
after two decades. Transactions of The Royal Society of Tropical Medicine And Hygiene (1996) 90, 294-
297
4. The Plasmodium life cycle. Laboratory Identifcation of Parasites of Public Health Concern of the USA
government of Centers for Disease Control and Prevention (CDC).http://www.dpd.cdc.gov/dpdx/HTML/
ImageLibrary/Malaria_il.htm
RI, Delayed Recrudescence: The asexual parasitemia reduces to < 25% of pre-treatment level in 48 hours, but
reappears between 2-4 weeks. RI, Early Recrudescence: The asexual parasitemia reduces to < 25% of pre-
treatment level in 48 hours, but reappears earlier. RII Resistance: Marked reduction in asexual parasitemia
(decrease >25% but <75%) in 48 hours, without complete clearance in 7 days. RIII Resistance: Minimal
reduction in asexual parasitemia, (decrease <25%) or an increase in parasitemia after 48 hours.
13 14
CHAPTER 3: CLINICAL FEATURES
The incubation period of malaria is variable (refer chapter2.2); the average being 1014 days, but may be as
short as 7 days or, in exceptional cases, up to 20 years as in P.malariae infection.
4
Symptoms occur within
6 weeks of the traveler leaving an endemic area in more than 90% of P. falciparum infections, and within 1
year in P. vivax infection. For P. knowlesi, symptoms occur 9-12 days after a person has visited or worked in
a forested or forest-tinge area. There may be a relatively short prodromal period of tiredness and aches.
3.1 Symptoms of malaria
The early symptoms of malaria are non-specifc and similar to the symptoms of a minor systemic
viral illness e.g. headache, lassitude, fatigue, abdominal discomfort, muscle and joint aches, usually
followed by fever, chills, perspiration, anorexia, vomiting and worsening malaise. The most common
presentation of malaria is high fever. The classical paroxysm begins abruptly with an initial cold
stage, with dramatic rigors during which the patient shakes visibly. This leads to a hot stage in
which the patient has a temperature of more than 40C, may be restless and excitable and may vomit
or convulse, and fnally asweating stage, when the fever abates and the patient may fall asleep.
This paroxysm may last 610 hours, and is followed by a prolonged asymptomatic period followed
by further rigors in untreated patients. The classic paroxysm is, however, increasingly uncommon in
clinical practice.
At early stage of malaria infection, without evidence of vital organ dysfunction, if prompt and effective
treatment is given, the patient can experience full rapid recovery. If ineffective medicines are given
or if treatment is delayed, especially in P.knowlesi and P. falciparum malaria, the parasite burden
continues to increase every 24 or 48 hours, severe malaria and even death may ensue. This progression
may occur within a few hours.
In high-transmission areas, such as in many sub-Saharan Africa, the majority of infections are
asymptomatic and infections are acquired repeatedly throughout life. In such areas, symptomatic and
sometimes fatal malaria occurs in the frst few years of life, but, thereafter, it is increasingly likely to
be asymptomatic. This refects a state of imperfect immunity, where the infection is controlled, usually
at levels below those causing symptoms. The rate at which imperfect immunity is acquired depends on
the intensity of transmission.1
The nature of malarial clinical disease depends greatly on the background level of the acquired protective
immunity and intensity of malaria transmission in the area of residence. Non-immune travelers to a
malaria endemic area are at a higher risk of acquiring malaria, unless protective measures are taken.
Immunity is, however, modifed in pregnancy, and it is often gradually lost, at least partially, when
individuals move out of the endemic areas for long durations (usually many years).
13 14
3.2 Defnition of Uncomplicated Malaria
Uncomplicated malaria is defned as symptomatic malaria without signs of severity or evidence
(clinical or laboratory) of vital organ dysfunction. The signs and symptoms of uncomplicated malaria
are non-specifc.
3.3 Defnition of Severe and Complicated Malaria
Severe malaria usually manifests with one or more of the following: coma (cerebral malaria), metabolic
acidosis, severe anaemia, hypoglycaemia, acute renal failure or acute pulmonary oedema. By this
stage of the disease, the case fatality in people receiving treatment is typically 1020%. However, if
left untreated, severe malaria is fatal in the majority of cases. Long-term cognitive impairment is also
common in children with cerebral malaria.
In a patient with malaria infection and no other obvious cause of symptoms, the presence of one or
more of the following clinical or laboratory fndings classifes the patient as suffering from severe
malaria.
Table 3.1: Clinical Features, Laboratory Findings and Complicationsof Severe & Complicated
Malaria
1, 4
Clinical
features
Impaired consciousness or unrousable coma
Prostration
(generalized weakness so that the patient is unable to walk or sit up without
assistance)
Failure to feed/ not tolerating orally
Convulsion
Deep breathing, respiratory distress (acidotic breathing)
Circulatory collapse or shock, systolic blood pressure < 90 mm Hg
(**please refer to physician for local fgure) in adults and < 50 mm Hg in children
Clinical jaundice and evidence of other vital organ dysfunction
Haemoglobinuria
Abnormal spontaneous bleeding
Pulmonary oedema (radiological)
Laboratory
fndings
Hypoglycaemia (blood glucose < 3.0 mmol/l)
Metabolic acidosis (plasma bicarbonate < 18 mmol/l)
Severe normocytic anaemia (Hb < 8 g/dl, packed cell volume < 24%)
Haemoglobinuria
Hyperparasitaemia
(> 20,000/l for P. knowlesi or > 100,000/ l for other Plasmodium species)
Hyperlactataemia
Renal impairment
Complications Cerebral malaria
Anaemia
Respiratory distress / Acute Respiratory Distress Syndrome (ARDS)
Renal failure
Hypoglycaemia
Circulatory collapse (shock)
Coagulopathy
15 16
References:
1. World Health Organization. Guidelines for the treatment of malaria Second edition 2010.
2. World Health Organization. Severe falciparum malaria. Transactions of the Royal Society of Tropical
Medicine and Hygiene, 2000:94(Suppl. 1):190
3. Management of severe malaria: a practical handbook, 2nd ed. Geneva, World Health Organization,
2000.
4. Geoffrey P. Malaria. Protozoal tropical infections 2005; Medicine 33:8:39-43.
5. Rajahram GS et al, Deaths due to Plasmodium knowlesi malaria in Sabah, Malaysia: association with
reporting as Plasmodium malariae and delayed parenteral artesunate Malaria J: 2012:11(1):284
6. Singh, B., and C. Daneshvar. Plasmodium knowlesi malaria in Malaysia. Med J Malaysia. 2010, 65(3):
223-30.
15 16
CHAPTER 4: DIAGNOSIS OF MALARIA
4.1 Clinical Diagnosis
The particular clinical diagnostic criteria vary from area to area according to the intensity of transmission,
the species of malaria parasite and other prevailing causes of fever
3
. Malaria must be excluded in all
febrile patients living in, or returning from, an endemic country, regardless of whether they have been
taking antimalarial drugs. All immigrants from malaria endemic countries with fever should be given
special attention to rule out malaria. Consideration of the possibility of malaria is an important step
in diagnosis, particularly outside endemic areas, and a travel history should be a routine part of any
clinical consultation in febrile patients.
In all settings, clinical suspicion of malaria should be confrmed with a parasitological diagnosis.
However, in settings where parasitological diagnosis is not possible, the decision to provide antimalarial
treatment must be based on the prior probability of the illness being malaria. Malaria should be
suspected in the presence of thrombocytopenia, relative lymphopenia, atypical lymphocytes, and an
elevated lactate dehydrogenase (LDH) level. (Box 3.1) Other possible causes of fever and need for
alternative treatment must always be carefully considered.
4.2 Laboratory Diagnosis
Prompt and accurate diagnosis of malaria is part of effective disease management. The diagnosis of
malaria is based on clinical suspicion and on the detection of parasites in the blood (parasitological
or confrmatory diagnosis). Once Plasmodium is detected, the BFMP test should be done daily during
hospital stay, weekly tests x 4 during follow-up for all species and additional monthly tests x 11 during
follow-up for P.vivax.
4.2.1 Tests Available For Laboratory Diagnosis
Several tests are available for laboratory diagnosis of malaria such as Blood Film for Malaria
Parasite (BFMP), Polymerase Chain Reaction (PCR) and Rapid Diagnostic Test (RDT) and
these will be further elaborated here.
Investigations Notes
Blood Film for Malaria
Parasite (BFMP)
To be done immediately. There is no need to wait for a peak of fever
before examining thick and thin blood flms. If the initial flm is negative,
repeat another 2 samples or more especially at peak of fever if symptoms
persist.
Full Blood Count (FBC) In falciparum malaria, the WBC count is generally normal, with relative
lymphopenia. Neutrophilia suggests secondary bacterial infection or
severe disease. Thrombocytopenia is present in more than 90% of non-
immune patients.
Blood Urea & Serum
Electrolytes (BUSE)
Sodium, calcium and albumin are low; these usually resolve spontaneously
with treatment.
CRP level C-reactive protein (CRP) is raised.
Liver profle Bilirubin is often raised; in the context of normal liver function, this is
related to haemolysis. Although malaria may cause mild elevations of
liver enzymes, jaundice in the presence of liver enzyme abnormalities may
suggest that other diagnoses (e.g. viral hepatitis) should be considered.
Blood glucose Blood glucose can be low in severe cases (with high parasitaemia) and
during quinine treatment in adults.
Table 4.1: Investigating suspected malaria
8
17 18
Table 4.2: Advantages and limitations of microscopy
i. Specimen
For specimen collection, the thick and thin flm should be prepared in one slide and sent in a slide
box to the laboratory. Stained the thick (unfxed) and thin flm (fxed with methanol) with 10%
Giemsa stain in buffered solution with pH7.2 for 10 minutes. Blood taken in EDTA tubes, the
anti-coagulant should have flms made within 2 hours or as soon as possible to minimize morpho-
logical changes in the parasites.If BFMP slides are of poor quality, the medical offcer should be
informed immediately to send both the slide and blood sample in an EDTA tube to the laboratory.
This would help to reduce delay in getting the microscopy results.
ii. Reporting Format
Quantitative malaria microscopy is more accurate to calculate the number of parasites per mi-
cro liter of blood. This method is recommended as it can assist the doctor to assess the disease
severity, monitor response to treatment and the patients progress. The quantitative result should
report different stages of parasite and therefore, the laboratory technician has to calculate both the
asexual (trophozoites,schizonts) and sexual (gametocytes) stages of theparasite. (Box 4.1 and Box
4.2)
Microscopy results recorded as P. malariae should be reported as P. knowlesi / P. malariae to
guide case management. These fndings should be confrmed with PCR.
iii. Laboratory Turnaround Time
Hospital & health clinic with laboratory techinician: Within 1 hour after BFMP slides have reached
the laboratory.
Health Care Clinics: Within the same day as taken.
*Sample sent in EDTA tube may take a longer time to process
Advantages Limitation
High sensitivity. It is possible to detect malarial
parasites at low densities.
Can quantify the parasite load.
Possible to distinguish the various species of
malaria parasite and their different stages.
Need adequately trained laboratory
technician.
17 18
a. Blood Film for Malaria Parasite (BFMP)
Microscopic examination of both thick and thin flm remains the gold standard for
confrmation of malaria. The thick flm is more sensitive for detecting malaria parasites as
the blood is more concentrated which allow for a greater volume of blood to be examined.
On the other hand, the thin flm helps in parasite species identifcation.(Table 3.1)
Box 4.1: Method of calculation
Box 4.2: Example of Calculation and Reporting

b. Polymerase Chain Reaction (PCR)
PCR for confrmation and species determination is indicated in certain situation such
as:
With clinical symptoms of malaria but no malaria parasite seen in BFMP
Mortality cases
Cases having microscopic appearance of P.malariae
10,11
PCR test is available at the National Public Health Laboratory (MKAK) at Sungai
Buloh.
When the thick flm is examined and if P. falciparum parasites are found, they will be counted in the
following way:
Asexual will be calculated against 200 White Blood Cells but in VERY HEAVY infections the
number may be 50 WBCs. The higher the number of WBCs counted the more accurate the fnal
calculation.
Sexual will be counted against WBCs as above.
Please note : A number of assumptions are made here which the doctor should be aware of :
The number of WBCs per micro-liter of blood is 8,000.
The number of red blood cells per micro-liter of blood is 5,000,000.
That one parasite occupies one red blood cell.
Formula for calculation:
No. of parasites X 8,000 = Parasites per l blood
No. of WBCs
Thick flm examined as P. falciparum
No. of Asexual : 100
No of Gametocytes : 10
No of WBC counted : 200
Asexual density : 100 x 8,000 = 100 x 40
200
= 4,000 parasites per l blood
Sexual density : 10 x 8,000 = 10 x 40
200
= 400 parasites per l blood
a Report : = Pf Asexual / sexual
= Pf 4,000 / 400 per l blood
19 20
i. Specimen
Whole blood in EDTA or dried blood spot on flter paper are the preferable specimens
for PCR analysis. Whole blood via venipuncture in EDTA should be kept in a clean
biohazard plastic bag and transported in a cold chain (4C) within 3-4 hoursor minus
20C if a longer period is needed for transportation. For dried blood spot prepared on
flter papers (Whattman Grade 1), blot approximately 125 l of blood (about 20 cent
size in diameter) on the flter paper and leave to air dry. Label with appropriate ID, i.e.
date of sample collection and initials of technician responsible. Dried blood spot should
be transported to the laboratory at room temperature in a separate biohazard zip lock
plastic bag (if specimens are obtained from more than one patient) within 48 hours.
(Note: A thick and thin flm needs to be sent together with whole blood/dried blood
spotspecimen for microscopy diagnosis.)
ii. Laboratory Turnaround Time
Nested PCR : 7 working days
qPCR (real time) : 3 working days
c. Rapid Diagnostic Test (RDT)
Rapid Diagnostic Tests are based on the detection of circulating parasite antigens. Rapid
antigen detection tests (immunochromatographic tests) cannot replace microscopy
but can be supplementary when malaria diagnosis is beingperformed by relatively
inexperienced staff (e.g., in low prevalence areas and outside normal working hours).
Result of RDTs should be always interpreted together with the results of microscopy,
read by an experienced laboratory technician.
In theory malaria RDTs should have high sensitivity (>95%) and should be highly
stable in all situations. Histidine-rich protein-2 is a water-soluble protein produced by
trophozoites and young (but not mature) gametocytes of P. falciparum. The RDTs that
use HRP2 detect P. falciparum only. These tests should be used only for diagnosis of
acute malaria infections, and not for follow-up, as they may remain positive for several
weeks even after successful treatment.Plasmodium lactase dehydrogenase (pLDH) and
the pan-specifc aldolase are produced by both asexual and sexual stages (gametocytes)
of malaria parasites.There is considerable variability in performance of the pLDH and
aldolase-based tests for the non-falciparum species.
9
Because none of the aldolase-
based tests are suffciently sensitive for the non-falciparum species (including P.vivax
and P.knowlesi), the use of pLDH-based RDTs with high sensitivity is recommended.
No commercially available RDTshave been suffciently sensitive overall for P.knowlesi,
thus a negative pLDH-RDT or aldolase-based RDT does not exclude the diagnosis
of knowlesi malaria. Several types of RDTs are available and information on this is
available at the WHO website (http://www.wpro.who.int/sites/rdt).
19 20
References:
1. Marsh K et al. Clinical algorithm for malaria in Africa. Lancet, 1996, 347:13271329.
2. Redd SC et al. Clinical algorithm for treatment of Plasmodium falciparum in children. Lancet, 347:223
227.
3. WHO Expert Committee on Malaria. Twentieth report. Geneva, World Health Organization, 2000 (WHO
Technical Report Series, No. 892).
4. Nwanyanwu OC et al. Malaria and human immunodefciency virus infection among male employees of
a sugar estate in Malawi. Transactions of the Royal Society of Tropical Medicine and Hygiene, 1997,
91:567569.
5. WHO Expert Committee on Malaria. Twentieth report. Geneva, World Health Organization, 2000 in
WHO Technical Report Series, No. 892.
6. Ng OT, Ooi EE, Lee CC, Lee PJ, Ng LC, Wong PS, et al. Naturallyacquired Plasmodium knowlesi
infection, Singapore. EmergInfect Dis 2008;14:814e6.
7. World Health Organization. Guidelines for the treatment of malaria Second edition 2010.
8. Geoffrey P. Malaria. Protozoal tropical infections 2005; Medicine 33:8:39-43
9. Barber et al, Evaluation of the sensitivity of a pLDH-based and an aldolase-based Rapid Diagnostic Test
for the diagnosis of uncomplicated and severe malaria caused by PCR-confrmed Plasmodium knowlesi,
P.falciparum and P. vivax. J Clin Micro 2013;4:1118-1123
10. Informal Consultation on the Public Health Importance of Plasmodium knowlesi. Kuching, Sarawak,
Malaysia 22 to 24 February 2011, World Health Organization.
11. Barber et al. Limitations of microscopy to differentiate Plasmodium species in a region co-endemic for
Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi. Malar J.2013, 812:8
12. Singh, B., and C. Daneshvar. Human infections and detections of Plasmodium knowlesi. Clin. Microbiol.
Rev. 2013, 26(2):165.
13. Barber et al. A prospective comparative study of knowlesi in Spain by Real Time PCR in a traveler from
Southeast Asia. Clin Infect Dis, 2013; 56(3):383-97.
4.2.2 Quality Checking
Quality checking aims at detecting defcienciesin staff competency, reagent, equipment or
infrastructure and work practices which require urgent rectifcation. The processes involved
are shown in Table 4.3.
Table 4.3: Quality Checking Processes
Responsible bodies Actions
Field sampling/Health
Care Clinic /Hospitals
Sending 100% of microscopy-positive slides and 10% of negative slides
to State Vector Laboratory.
State Vector Laboratory/
Kota Kinabalu Public
Health Laboratory
Re-checking 100% of positive slides and 10% of negative slides for
quality control.
Results reported back to the respective laboratory optimally within one
month.
After this all the slides have to be sent to Public Health Lab for quality
control checking.
All positive slides for P. malariae and P. knowlesi to be sent to MKAK
for PCR.
Parasitology &
Mycology Unit,
National Public Health
Laboratory (MKAK)
Rechecking 10% from positive slides and 2% from negative slides,
which are sent from State Vector Laboratory for quality control.
Results reported back to the respective laboratory optimally within 5
weeks upon receipt of slides.
21 22
CHAPTER 5: MALARIA TREATMENT
The aims of malaria treatment are to alleviate symptoms and to prevent relapses and spread of the disease. WHO
recommends the use of Artemisinin Combination Therapy (ACT) as the standard treatment for malaria and
discourages the prescription of monotherapy or sub-standard ACT as this will promote resistant plasmodium.
5.1 Treatment of Malaria in Adults
The treatment regimen is as shown in Table 5.1. Treatment of malaria has to be modifed in pregnancy
due to contraindication for use of certain antimalarials. (Table 5.2)
5.2 Field Treatment
Field treatment for malaria is not advisable as a routine mode of treatment. However, it is still practiced
in certain remote areas in Sarawak and probably Sabah due to unforeseen logistic situation. However, this
is limited to interior areas where it is only reachable by fying doctor services, the patient with clinically
uncomplicated malaria. The treatment should follow treatment guidelines accordingly. However, all
malaria cases must be encouraged to be hospitalized.
*As testing for G6PD defciency is not readily available at feld level, patient need to be educated on
signs and symptoms of hemolysis i.e. dark colour urine. Patient needs to be advised to stop primaquine
immediately if such signs and symptoms are present.
History of previous anti malarial exposure especially to primaquine can be elicited. If there is no history of
adverse reaction to primaquine, then it may be reasonable to assume that there is no G6PD defciency.
5.3 Presumptive Treatment
Presumptive treatment is given for those patients whom a blood flm was taken but the results would not
be available at that moment due to logistic reason, like those in very remote areas and risks of defaulting
follow-up. This is only done under extreme circumstances. This mode of treatment is given to those in
endemic areas with classical symptoms of malaria i.e. fever for more than 3 days with chills and rigors.
The treatment should be based on the predominant species in that area. (Refer table 5.2) Sulphadoxine/
Pyrimethamine (SP or Fansidar) should not be used for feld treatment or presumptive treatment for
malaria due to high level of resistance.
4
21 22
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References:
1. WHO guidelines for the treatment of malaria, Second Edition 2010
2. WHO A Practical Handbook: Management of Severe Malaria Third Edition 2012
3. McGready et al, Lancet ID, 2012
4. Abdullah NR et al. High prevalence of mutation in the Plamodisum falciparum dhfr and dhps genes in
feld isolates from Sabah, Northern Borneo. Malar J. 2013. 12;12(1):198.
27 28
CHAPTER 6: MANAGEMENT OF SEVERE AND COMPLICATED MALARIA
Severe malaria is caused by the presence of a high density of asexual forms of Plasmodium in the patients
body. Such a patient needs urgent management at secondary or tertiary hospitals. However, in areas of high
malarial endemicity or in outbreak situation, clinical suspicion alone should prompt a therapeutic trial with an
appropriate antimalarial drug even if blood smears are negative.
6.1 For treatment
All malaria patients should be admitted. In exceptional cases where this is not possible, uncomplicated
malaria can be managed at out-patient clinics with close monitoring.
However, for patients with the following features, admission is mandatory:
a. patients with manifestations of severe/ complicated malaria (refer Chapter 3)
b. patients who cannot tolerate orally
c. patients with high parasitaemia (>100 000/l) [> 20,000/l for P.knowlesi]
5
d. patients with G6PD defciency
e. all pregnant mothers with acute malaria
f. patients with severe malnutrition
g. children
6.2 Referral to hospitals with specialists
These patients should be referred to hospitals with specialists for further management:
a. all patients with severe and complicated malaria
b. immuno-compromised patients with signifcant co-morbidities e.g. hepatic or renal dysfunction
c. pregnant mothers
Box 6.1: Steps to referral
When referring patients, ensure
referral letter and BFMP slides are sent along
antimalaria treatment is commenced prior to transfer
If referral is not possible
If admission is not possible either to district hospitals or hospitals without specialists,
these patients must be discussed with the Physicians/Infectious Disease Specialists
regarding the plan of management
6.3 Criteria for admission
All patients diagnosed as malaria or suspected malaria should be admitted. In situations where this is
not possible, they should be treated and followed-up daily by a doctor or assistant medical offcer (in
area where there is no doctor).
27 28
6.4 Criteria for referral to the High Dependency Unit (HDU) or Intensive Care Unit (ICU)
If a patient has any of the features of severe malaria, the patient should be referred to a hospital with
a HDU or ICU.
All patients with complicated malaria should be referred to the Physician on call.
An early referral to intensivist should be made for further evaluation and management.
If the patient cannot be transferred, then the patient should be monitored closely in the district
hospital in close consultation with the physician.
6.5 General Management for Severe Malaria
1. Take a complete History and physical examination.
a. Examine the Glasgow Coma Scale (GCS), presence of neck stiffness, Blood pressure, Pulse rate,
Respiratory rate. Examine the fundi as well.
2. Send the following investigations:
a. Blood for Culture and Sensitivity.
b. Full Blood Count.
c. Prothrombin Time (PT), Partial Thromboplastin Time (PTT).
d. Serum Urea and Electrolytes, Creatinine.
e. Blood glucose.
f. Liver Function Test.
g. Chest X-ray.
h. Arterial Blood gas.
i. Serum Lactate (if available)
3. Admit the patient to the ICU or the High Dependency Unit
4. The patient should be referred to the Physician or the Intensivist.
5. Give IV Artesunate (2.4 mg/kg) stat. If this is not possible, give it IM. Administer IV Quinine if IV
Artesunate is not available (and IM, if no IV access). For complete dosing, please look at the section
on antimalarial treatment.
6. Administer the intravenous antimalarial for at least 24 hours before switching to an oral formulation
if the patient improves and can tolerate orally.
7. Close observation of the vital signs, GCS, by the nurses and doctor is of vital importance
8. Pulmonary oedema is a grave complication of severe knowlesi and falciparum.
It has a high mortality (over 80%in falciparum malaria); the prognosis is better in vivax malaria.
Pulmonary oedema may develop several days after chemotherapy has been started, at a time when
the patients general condition is improving and the peripheral parasitaemia is falling.
a. Close input output monitoring is very important as the patient can develop pulmonary oedema
easily if too much fuids are given. Give fuids just enough to maintain the circulation and correct
dehydration.
b. Children with severe malaria who are unable to retain oral fuids should be managed with half
normal saline (0.45%) with 5% dextrose with maintenance fuids (3-4ml/kg/hour), and adults at
1-2ml/kg body weight per hour, until the patient is able to take and retain oral fuids.
c. Rapid fuid boluses are contraindicated in severe malaria resuscitation. Dehydration should be
managed cautiously and ideally guided by urine output (with a urine output goal of > 1ml/kg body
weight per hour), unless the patient has anuric renal failure or pulmonary oedema, for which fuid
management should be tailored to the needs of the patient and reassessed frequently.
29 30
Manifestations/
Complications
Immediate Management
Coma
(cerebral malaria)
Maintain airways and for ventilator support if necessary; exclude other treatable
causes of coma (e.g. hypoglycaemia, bacterial meningitis); avoid harmful
ancillary treatment, such as corticosteroids, heparin and adrenaline.
Convulsions
Maintain airways; treat promptly with intravenous or rectal diazepam and/ or other
anticonvulsants. Check blood glucose, blood urea and serum electrolytes.
Prophylactic anticonvulsants are not recommended.
Hypoglycaemia Correct hypoglycaemia and maintain with glucose containing infusion
Acute renal failure
Exclude pre-renal causes, check fuid balance and urinary sodium in established
renal failure initiate haemofltration or haemodialysis, or peritoneal dialysis.
Severe Anaemia Blood transfusion where indicated.
Acute pulmonary
oedema
Prop patient up at an angle of 45, give oxygen and other respiratory support as
indicated. Adjust fuid therapy appropriately. Diuretics if necessary.
Shock
Assess hydration status. Give appropriate fuid therapy Achieve CVP
measurement 8-12cm H
2O
. Suspect septicaemia (bacterial in origin) in
unexplained clinical deterioration. Take blood for cultures; give parenteral
broad-spectrum antimicrobials and change it according to culture results.
6.7 Adjunct therapy
In an attempt to reduce the unacceptably high mortality of severe malaria, besides appropriate and
effective antimalarial drugs, various adjunctive treatments for the complications of malaria have
been evaluated in clinical trials. Adjunctive therapy is defned as any additional therapy that modifes
physiologic processes caused by malaria. These therapies may act directly on specifc biologic pathways
altered by malaria or more generally on end-stage factors produced in malaria by a number of different
specifc processes.
9. If the patients GCS is reduced, look for other causes such as meningitis. A lumbar puncture may
then be indicated and antibiotics instituted.
10. There is considerable clinical overlap between septicaemia, pneumonia and severe malaria, and
these conditions may coexist .If secondary infections are suspected, then start the patient on a
broad spectrum IV antibiotic such as Ceftriaxone 2g OD ( after a septic workout is done).
11. Monitor for clinical and parasitological therapeutic response.
12. High fever can be managed by tepid sponging and Paracetamol.
6.6 Management of complications of malaria
Malaria may become a medical emergency without prompt and appropriate treatment. Complications
can rapidly set in which may cause death. Most cases of severe malaria are caused by P. falciparum
infection. Rarely, P. vivax or P. ovale produce serious complications and even death. In Malaysia, P.
knowlesi has caused severe malaria and serious complication as a result of hyperparasitaemia.
Table 6.1: Immediate clinical management of severe manifestations and complications of malaria
29 30
6.7.1 Exchange blood transfusion (EBT)
There is no consensus on the indications, benefts and risk involved on EBT in severe malaria
as no randomized clinical trial has ever been conducted on EBT. The procedure requires
expertise and intense monitoring, which limits its suitability in resource-limited settings.
The rationale for EBT has been variously proposed as:
Removing infected red blood cells from the circulation and, therefore, lowering the
parasite burden
Reducing rapidly both the antigen load and the burden of parasite-derived toxins and
toxic mediators
Replacing the rigid unparasitized and parasitized red cells by more deformable cells and,
therefore, reducing microcirculatory obstruction.
6.7.2 Adjunctive Treatments not recommended
Other supportive strategies and interventions have been used in severe malaria patients in an
effort to further reduce the mortality, but very few are supported by evidence of beneft and
this includes the use of these listed drugs.
1-3
Modulate the immune response to P. falciparum (dexamethasone, intravenous
immunoglobulin, monoclonal antibodies to TNF-, pentoxifylline and curdlan sulfate)*
Reduce iron burden (iron chelation with desferrioxamine or deferipone)
Reduce oxidative stress (N-acetylcysteine [NAC])
Counteract the prothrombotic state and prevents the formation of rosettes of infected red
blood cells (RBCs) (heparin and aspirin).
Reduce parasitemia (EBT).
Expand volume and potentially decrease acidosis (albumin)**
Decrease intracranial pressure and cerebral edema (mannitol and dexamethasone)
Prevent seizure activity (prophylactic phenobarbital).
Note
* Use of high dose steroid was associated with bleeding and seizures, and prolonged coma resolution
time when compared with placebos.
** Albumin is the only adjunctive therapy to date associated with reduced mortality in children
with severe malaria from a single, small study. A multicenter randomized clinical trial comparing
volume expansion with albumin or saline to treatment with maintenance fuids in febrile children
with impaired perfusion is currently being conducted.
4
6.8 Discharge
All patients diagnosed with malaria must be admitted for the duration of treatment to ensure
completion. In high transmission settings, it is important to keep the patients warded until they are
cleared of gametocytes which play a crucial role in the spread of malaria and thus of public health
concern.Otherwise, the patients can be discharged once they are clinically well with two negative BFMP
slides within 48 hours.
6.9 Follow-up
Patients should be followed up weekly for a month. Thereafter, follow up for those infected with P.
vivax infection should be followed up monthly for one year. However, if antimalarial drug resistance is
suspected, follow-up should be extended; for example, in the case of suspected P. falciparum resistance,
beyond one month. Such cases should be notifed to the state and ministerial level for further action.
31 32
References:
1. WHO Guidelines for the treatment of malaria 2nd edition 2011
2. G Watt, K Jongsakul and R Ruangvirayuth. A pilot study of N Acetylcystein as adjunctive therapy for
severe malaria. Q J Med 2002 95: 285-290
3. John C. C., Kutamba E., Mugarura K., Opoka R. O..Adjunctive therapy for cerebral malaria and other
severe forms of Plasmodium falciparum malaria.Expert review of antiinfective therapy.2010,8(9):997-
1008
4. Maitland K, Nadel S, Pollard AJ, Williams TN, Newton CR, Levin M. Management of severe malaria in
children: proposed guidelines for the United Kingdom. Br Med J. 2005; 331(7512):337343.
5. Barber BEet al, A prospective comparative study of knowlesi, falciparum, and vivax malaria in Sabah,
Malaysia: high proportion with severe disease from Plasmodium knowlesi and Plasmodium vivax but no
mortality with early referral and artesunate therapy. Clin. Infect Dis. 2013; 56(3):383-97.
6. Management of Severe Malaria: A Practical Handbook. WHO Third Edition 2012
7. William T et al. Severe Plasmodium knowlesi malaria in a tertiary care hospital, Sabah, Malaysia. Emerg
Infect Dis. 2011,17(7):1248-55
8. Barber BE et al, A prospective comparative study of knowlesi, falciparum, and vivax malaria in Sabah,
Malaysia: high proportion with severe disease from Plasmodium knowlesi and Plasmodium vivax but no
mortality with early referral and artesunate therapy. Clin. Infect Dis. 2013; 56(3):383-97
31 32
FIRST LINE TREATMENT
PREFERRED TREATMENT ALTERNATIVE TREATMENT
Artesunate / mefoquine FDC (ASMQ) Artemether / lumefantrine (Riamet)
CHAPTER 7: MANAGEMENT OF MALARIA IN PAEDIATRICS
The treatment regimen for pediatric patients is the same as for adults except that the drug dose is adjusted
according to the weight of the patient. In addition, drug such as doxycyline is contra-indicated in children
less than eight years old. Primaquine should be given to pediatric patients only after they have been screened
for G6PD defciency.
7.1 Uncomplicated malaria
Symptomatic infection with malaria parasitaemia without signs of severity or evidence (clinical or
laboratory) of vital organ dysfunction.
Table 7.1: Treatment for Uncomplicated Plasmodium falciparum malaria
Weight (kg) Age Dose
5-8 6-11 months 1 ASMQ FDC 25/55mg
once daily for 3 days
9-17 1-6 years 2 ASMQ FDC 25/55mg
18-29 7-12 years 1 ASMQ FDC
100/220mg
>30 >13 years 2 ASMQ FDC
100/220mg
Weight (kg) Dose
5-14 DI: 1 tab stat then 1 tab again
after 8 hours
D2-3: 1 tab BD
15-24 D1: 2 tabs stat then 2 tabs again
after 8 hours
D2-3: 2 tablets BD
25-35 D1: 3 tabs stat then 3 tabs again
after 8 hours
D2-3: 3 tablets BD
>35 D1: 4 tabs stat then again 4 tabs
after 8 hours
D2-3: 4 tabs BD
33 34
Add a single 0.75 mg base/kg primaquine dose should be given to all patients with confrmed P. falciparum
malaria on the frst day of treatment in addition to an ACT. Check G6PD before giving primaquine.
Avoid ASMQ in children with epilepsy as well.
Riamet should be administered with high fat diet preferable to be taken with milk to enhance absorption
Both ASMQ FDC and Riamet are Artemisinin-based Combination Treatment (ACT).
SECOND-LINE TREATMENT FOR TREATMENT FAILURE
An alternative ACT ( if Riamet were used in the frst regimen, use ASMQ for treatment failure
and vice-versa)
OR
(oral) Artesunate 4mg/kg OD plus clindamycin 10mg/kg bd for a total of 7 days
OR
Quinine 10mgsalt/kg 8 hourly plus clindamycin 10mg/kg bd for a total of 7 days.
Add primaquine 0.75mg base/kg single dose OD if gametocyte is present at any time during treatment.
Check G6PD before giving primaquine.
Table 7.2: Treatment for Plasmodium vivax, knowlesi or malariae
Treatment for Plasmodium vivax Treatment for Plasmodium knowlesi or malariae
Total chloroquine 25mg base/kg divided over 3 days
D1:10 mg base/kg stat then 5 mg base/kg 6 hours
later
D2: 5 mg base/kg OD
D3: 5 mg base/kg OD
AND
Primaquine* 0. 5 mgbase/kg daily for 14 days
Total chloroquine 25mg base/kg divided over 3 days
D1: 10 mg base/kg stat then 5 mg base/kg 6 hours
later
D2: 5 mg base/kg OD
D3: 5 mg base/kg OD
NOTE: *Chloroquine should be prescribed as mg base in the drug chart.
P. malariae and P. knowlesi do not form hypnozoites, hence do not require radical cure with primaquine
33 34
Treatment of chloroquine-resistant P. vivax, knowlesi or malariae
ACT (Riamet or ASMQ) should be used for relapse or chloroquine resistant P.vivax. For radical cure in P.
vivax, ACT must be combined with supervised 14-day primaquine therapy.
Quinine 10mg salt/kg three times a day for 7 days is also effective for chloroquine resistant P. vivax and this
must be combined with primaquine for antihypnozoite activity.
Mefoquine 15mg/kg single dose combined with primaquine have been found to be effective.
Primaquine may cause life-threatening haemolysis in individuals with G6PD defciency. G6PD testing is
required before administration of primaquine. For those found to have mild to moderate G6PD defciency,
an intermittent primaquine regimen of 0.75mg base/kg weekly for 8 weeks can be given under medical
supervision. In severe G6PD defciency primaquine is contraindicated and should not be used.
Severe and complicated P. vivax, knowlesi or malariae should be managed as for severe falciparum malaria
(see below).
7.2 Complicated/severe Plasmodium falciparum
All Plasmodium species can potentially cause severe malaria, the commonest being P. falciparum.
Young children especially those aged below 5 years old are more prone to develop severe or complicated
malaria.
Clinical features Laboratory fndings:
impaired consciousness or unarousable coma
prostration
failure to feed
multiple convulsions
(more than two episodes in 24 h)
deep breathing, respiratory distress
(acidotic breathing)
circulatory collapse or shock
clinical jaundice plus evidence of other vital
organ dysfunction
haemoglobinuria
abnormal spontaneous bleeding
pulmonary oedema (radiological)
hypoglycaemia
(blood glucose < 2.2 mmol/l or < 40 mg/dl)
metabolic acidosis
(plasma bicarbonate < 15 mmol/l)
severe anaemia
(Hb < 5 g/dl, packed cell volume < 15%)
haemoglobinuria
hyperparasitaemia (> 2%/100,000/l in
low intensity transmission areas or > 5% or
250,000/l in areas of high stable malaria
transmission intensity)
hyperlactataemia (lactate > 5mmol/l)
renal impairment
35 36
Table 7.3: Treatment for Complicated Plasmodium falciparum
FIRST LINE TREATMENT
D1: IV artesunate 2.4 mg/kg on admission, then repeat again at 12h
D2-7: IV artesunate 2.4 mg/kg OD or switch to oral ACT
Parenteral artesunate should be given for a minimum of 24h or until patient is able to take orally and
thereafter to complete treatment with a complete course of oral ACT (ASMQor Riamet). Avoid using ASMQ
(Artesunate + mefoquine) if patient presented initially with impaired consciousness as increased incidence of
neuropsychiatric complications associated with mefoquine following cerebral malaria have been reported.
IM artesunate (same dose as IV) can be used in patients with diffcult intravenous access.
Children with severe malaria should be started should be started on broad-spectrum antibiotic treatment
immediately at the same time as antimalarial treatment.
SECOND LINE TREATMENT
D1 : IV Quinine loading 7mg salt/kg over 1 hour followed by infusion quinine 10mg salt/kg over 4 hours
then 10mg/kg 8hourly
OR
Loading 20mg salt/kg over 4 hours then IV 10mg salt/kg 8 hourly
(Dilute quinine in 250ml of D5% over 4 hours)
D2-7 : IV Quinine 10mg/kg 8 hourly
AND
Doxycycline (>8yrs) (3.5 mg/kg OD) OR Clindamycin (<8yrs) (10 mg/kg/dose bd) given for 7 days
Quinine infusion rate should not exceed 5 mg salt/kg body weight per hour
Change to oral Quinine if able to tolerate orally. (Max Quinine per dose = 600mg.) Reduce IV quinine dose
by one third of total dose if unable to change to Oral quinine after 48 hours or in cases with renal failure or
liver impairment.
35 36
7.3 Congenital malaria
Congenital malaria is uncommon. It can be acquired by transmission of parasites from mother to child
during pregnancy or perinataly during labour. Incidence varying from 0.3 to 33% has been reported
from both endemic and non-endemic countries. Congenital malaria from P. vivax is more commonly
reported in Asia whereas infection from P. falciparum is mainly described in African countries. Most
babies present with symptoms between 10 and 30 days of age (range: 14hr to several months of age). The
clinical features of neonatal malaria include anaemia (77%), fever (745), liver and spleen enlargement
(68%), poor feeding/lethargy/irritability, jaundice and severe thrombocytopaenia. Congenital malaria
may mimic neonatal sepsis and should be considered in the differential diagnosis of neonatal sepsis.
All newborn babies of mother with malaria should been screened for congenital malaria.
Treatment for P vivax infection: chloroquine, total dose of 25mg base/kg orally divided over 3 days
D1: 10 mg base/kg stat then 5 mg base/kg 6 hours later
D2: 5 mg base/kg OD
D3: 5 mg base/kg OD
Primaquine is not required for treatment as the tissue/ exo-erythrocytic phase is absent in congenital
malaria.
Treatment for P.falciparum infection: quinine 10mg/kg q8 hourly for 1 week.
7.4 Mixed Malaria infections
Mixed malaria infections are not uncommon. ACTs are effective against all malaria species and are
the treatment of choice. Treatment with primaquine should be given to patients with confrmed P.vivax
infection.
References:
1. Dondorp A, et al. Artesunate versus quinine in the treatment of severe falciparum malaria in
African children (AQUAMAT): on open-label, randomized trial; Lancet 2010 Nov 13:376(9753):
1647-1657
2. WHO Malaria treatment Guidelines 2010
3. UK Malaria guidelines 2007, Metha PN 2004
4. Neena V. et al. Congenital malaria with atypical presentation: a case report from low transmission
area in India. Malaria Journal 2007, 6:43
5. Del Punta et al. Congential Plasmodium vivax malaria mimicking neonatal sepsis: a case report.
Malaria Journal 2010, 9:63
6. Red Book 2009
37 38
CHAPTER 8: MALARIA CHEMOPROPHYLAXIS
Malaria prevention consists of a combination of mosquito avoidance measures and chemoprophylaxis.
The mosquito avoidance measures include insect repellant, wearing long sleeves, long pants, sleeping in a
mosquito-free setting or using an insecticide-treated bednet. The use of diethyltoluamide (DEET) 20-50%
in lotions, spray or roll-on formulation is safe and effective when applied to the skin of adults and children.
Although diethyltoluamide may be used in children > 2 months, it should be used with caution. Because of
their increased surface-area-to-body-mass ratio, children may be at increased risk for toxicity due to greater
skin absorption. Low-concentration products should be used and applied sparingly. No antimalarial drug is
100% protective and must be combined with the use of personal protective measures
8.1 Risk of malaria
The risk of acquiring malaria differs substantially from region to region and from traveler to traveler,
even within a single country as it depends on several factors such as transmission intensity, duration
of stay in the endemic area and the effcacy of preventive measures. Often, the risk to the indigenous
population is used as a guideline for the risk to the traveler. Travelers with the highest estimated
relative risk for infection are those going to West Africa and Oceania. Travelers going to other parts of
Africa, South Asia, and South America have a moderate estimated relative risk for infection. Travelers
with lower estimated relative risk are those going to Central America and other parts of Asia. (1) All
travelers should seek medical attention in the event of fever during or after return from travel to areas
with malaria.
Risk groups include:
a. Travelers or visitors to endemic areas
b. Army personnel
c. Loggers/rubber tappers
d. Workers in endemic areas e.g. dam construction, plantation
Caution:
Patient with severe splenic dysfunction or pregnant women should avoid traveling to endemic areas.
37 38
8.2 Chemoprophylaxis
There are two types of chemoprophylaxis: suppressive and causal prophylaxis.
8.2.1 Suppressive prophylaxis
Chloroquine, proguanil, mefoquine, and doxycycline are suppressive prophylactics. This means
that they are only effective at killing the malaria parasite once it has entered the erythrocytic
stage (blood stage) of its life cycle, and therefore have no effect until the liver stage is complete.
That is why these prophylactics must continue to be taken for four weeks after leaving the area
of risk.
8.2.2 Causal prophylaxis
Causal prophylactics target not only the blood stages of malaria, but the initial liver stage as
well. This means that the user can stop taking the drug seven days after leaving the area of risk.
Atovaquone/Proguanil (Malarone) and primaquine are the only causal prophylactics in current
use.
8.2.3 Considerations when choosing a drug for malaria prophylaxis
a. Check risk of exposure to malaria and the recommended drugs listed in country-specifc
tables as in Appendix 1 or updated version on-line in the internet.
b. For all medicines, consider the possibility of drug-drug interactions with other medicines
that the person might be taking as well.
c. When deciding which drug to use, consider length of trip, previous adverse reactions and
current medical history.
d. Start chemoprophylaxis earlier if there are particular concerns about tolerance to the
medications. For example, mefoquine can be started 34 weeks in advance to allow potential
adverse events (AE) to occur before travel.
e. The use of the same or related drugs that have been taken for prophylaxis is not recommended
to treat malaria.
39 40
DRUG ADVANTAGES DISADVANTAGES
Doxycycline*
Dose: 100mg daily
Start: 1-2 days before departure
Stop: 4 weeks after travel
Maximum duration: 2 years
Pediatric Dosage
1.5mg base/kg once daily
(max. 100 mg)
<25kg or <8 yr: Do Not Use
25-35kg or 8-10 yr: 50mg
36-50kg or 11-13 yr: 75mg
>50kg or >14 yr: 100mg
Some people prefer to take a
daily medicine
Good for short trip and last-
minute travelers because the
drug is started 1-2 days before
traveling
Tends to be the least expensive
Doxycycline also can prevent
some additional infections
(e.g., Rickettsiae and lep-
tospirosis) and so it may be
preferred by people planning to
do lots of hiking, camping, and
swimming in fresh water
Contraindicated in pregnancy
and children <8 years old
Photosensitivity need to avoid
considerable sun exposure
Gastrointestinal (GIT) upset
Vaginal candidiasis
Atovaquone/Proguanil
(Malarone) 100/250mg*
Dose: 1 tablet daily
Start: 1-2 days before departure
Stop: 7 days after travel
Pediatric Dosage
Pediatric tablet of 62.5 mg
atovaquone and 25 mg proguanil:
5-8 kg: 1/2 tablet daily
>8-10 kg: 3/4 tablet daily
>10-20 kg: 1 tablet daily
>20-30 kg: 2 tablets daily
>30-40 kg: 3 tablets daily
>40 kg: 1 adult tablet daily
Good for last-minute travelers
Good choice for shorter trips
Very well-tolerated medicine
side effects uncommon
Contraindicated in pregnancy
or breastfeeding and patient
with severe renal impairment
Expensive
39 40
Table 8.1: Advantages and Disadvantages of Chemoprophylaxis
DRUG ADVANTAGES DISADVANTAGES
Mefoquine(Lariam)**
Dose: 250mg weekly
Start: 2 weeks before departure
Stop: 4 weeks after travel
Maximum duration: 1 year
Pediatric Dosage
<15 kg: 5mg of salt/kg;
15-19 kg: 1/4 tab/week;
20-30 kg: 1/2 tab/week;
31-45 kg: 3/4 tab/week;
>45 kg: 1 tab/week
Good choice for long trips
because it is taken only weekly
Can be used in second and
third trimester of pregnancy
and in frst trimester if there is
no other option
Cannot be used in areas with
mefoquine resistance
Cannot be used in patients with
certain psychiatric conditions,
patients with epilepsy or car-
diac conduction abnormalities
Not a good choice for last-
minute travelers and for trips of
short duration
* Preferred choice for Malaysia
** Alternative
References:
1. British National Formulary Edition 61 March 2011
2. The World Health Organization provides country-specifc advice on malaria prevention.
3. 2007 guidelines are available from the UK Health Protection Agency website

4. Centers for Disease Control and Prevention website. Available at http://www.cdc.gov.
Accessed in Jan 2012.
41
CHAPTER 9: TREATMENT RESPONSE MONITORING
DRS_Annex 1
National Surveillance of Drug Response Against
Malaria Parasite (P.falciparum, P.knowlesi and P.malariae)
Note: This form is to be completed for all cases of P. falciparum, P.knowlesi and P.malariae seen and treated
with the frst line drugs at the all hospitals/clinics.
INFORMANT
1. Hospital
Name of Reporting Offcer Designation of Reporting Offcer
Medical Offcer
Coordinator
2. PATIENTS DEMOGRAPHIC DATA
Patients Initial Patients ID (Reg. No/NRIC)
Age (Years) Ethnic
Gender () Body
weight
(kg
Female
Male
3. DRUG/MEDICATION HISTORY
Day of treatment
Actual number of tablet given to and taken by the patient
AL ASMQ Others (Specify):
Adult dose Paeds dose
D0
D1
D2
4. PARASITE RESPONSE
Type of parasite () P.falciparum P.knowlesi P.malariae
Follow-up slide post treatment Parasite density (per uL blood)
Day Date Due* Actual Date** Asexual Sexual (gametocyte)
D0
D3
D7
D14
D21
D28
D42
5. CASE INVESTIGATION
Was this patient treated
before for malaria ()?
No
Yes What type of medication?(If known)
When was medication taken?
(eg: 1 week/month prior to current
treatment)
Probable Source of Infec-
tion in This Case ()
Local
Imported From where?
6. VERIFICATION AND VALIDATION (Epid.Offcer/MOH)
Signature
AL=Artemether-Lumefantrine (Riamet) ASMQ = Artesunate-Mefoquine D0 = Day of starting the treatment
* Enter the date due for the subsequent post-treatment follow-up (D3, D7, D14, D21, D28, D42)
**Enter the actual date of slide collection during follow-up
Name
42
DRS_Annex 2
STANDARD OPERATING PROCEDURE
NATIONAL SURVEILLANCE OF DRUG RESPONSE AGAINST MALARIA PARASITE,
MINISTRY OF HEALTH MALAYSIA
1. Organisation and Standard Operating Procedure (refer DRS_Annex 3)
1.1 Medical Offcer of Health (MOH) at the District Health Offce is responsible to coordinate and
monitor surveillance activity.
1.2 Appoint a dedicated staff to act as coordinator (e.g: PPKP).
1.3 Identify all Medical Offcers who manage malaria cases (from medical & paediatric wards) at all
hospitals in the district.
1.4 Brief the medical offcers, Sisters and senior Laboratory Technologist on the surveillance mechanism
while patient admitted in the ward and provide the coordinators contact phone number. The
coordinator will continue the surveillance process after patient being discharged from the ward.
1.5 Coordinator to provide and distribute the Surveillance Form (DRS_Annex 1) to MOs/Sisters of the
relevant wards
1.6 MOH to instruct the MOs to carry out the surveillance activities.
1.7 MOs complete the Surveillance Form, inform coordinator via phone and return the form to the
coordinator once patient is discharge. The coordinator will continue the follow-up procedure and
complete the form.
1.8 Coordinator compiles all Surveillance Form and key in data into e-Vekpro completely.
1.9 Coordinator checks the total number of P. falciparum, P.knowlesi and P.malariae malaria cases
admitted for the month and prepares Reporting Format (DRS_Annex 4) for the MOH to verify and
validate.
1.10 Send the Reporting Format (Drs_Annex 4) to State Health Offce.
1.11 State KPP will compile reports from all districts, prepares Reporting Format (Drs_Annex 5) and
submit to Vector Bourne Disease Section, on a monthly basis to :-
National Anti-Malarial Surveillance,
C/o Malaria Unit,
Vector Bourne Diseases Section,
Disease Control Division, Block E10, Parcel E,
Ministry of Health Malaysia, Precint 1,
62590, Putrajaya.
1.12 Vector Borne Disease Section will compile reports from all states and prepare monthly report.
2. Patient enrolment
2.1 Inclusion criteria :
2.1.1 Admit patient
2.1.2 Confrmed laboratory diagnosis of the presence of mono-infection asexual stages of Ability
P.falciparum, P.knowlesi or P.malariae.
2.1.3 Ability to swallow oral medication.
2.1.4 Non-severe and uncomplicated malaria cases treated with frst-line treatment regime (refer
Guidelines for Management of Malaria 2013).
2.2 Attach the Surveillance Form (DRS_Annex 1) to the patient Case Note and enter the information
accordingly.
2.3 From the history, acquire the information on previous history of malaria treatment and probable
source of infection. Enter the information in Section 5 of the Surveillance Form accordingly.
3. Treatment regime and medication history
3.1 Calculate the artemther-lumefantrine (AL-Riamet) and artesunate-mefoquine (ASMQ-FDC) dosage
based on the body weight according to the following regime:-
Treatment regime : 3 days treatment schedule (D0, D1 and D2).

43 44
3.2 Ascertain the strength of the drug component for each tablet and determine the number of tablet
required for each drug.
3.3 Instruct the nurse to supervise the taking of the medication. If the patient vomits within hour of
consumption, repeat the dose and indicates that in the appropriate drug column of Section 3 with the
initial rpt.
3.4 Record the actual number of tablet given to and taken by the patient in Section 3. Record also other
concomitants treatment (e.g. paracetamol, antibiotics, etc).
(NOTE: D0 is the frst day of treatment)
4. Parasite response and monitoring
4.1 Original slide that confrm the diagnosis (D0) must be kept for future reference.
4.2 Clinically monitor the case according to the standard management as per guidelines protocol.
4.3 Repeat BFMP one day after the last dose of AL/ASMQ (D3). Enter the result in Section 4 of the
Surveillance Form. (You may repeat BFMP on D1 and D2 if clinically justifed e.g. no evidence of
clinical improvement or clinically getting worse).
4.4 If the result on D3 is negative, repeat BFMP on D5, D6 and D7. If continue to be negative, dis
charge the patient. Enter the result of D7 in the Surveillance Form. MOs inform the coordinator
and return the form to the coordinator.
4.5 Coordinator arrange for the patient to be followed-up on D14 at patients house. Inform the patient
of the appointed date for the BFMP taking.
4.6 If BFMP negative, enter the result in the Surveillance Form and inform the patient for D21, D28
and D42 visit for similar follow-up. Stress the importance of complete monitoring to ensure com
pliance.
4.7 If BFMP continues to be negative until D42 or if patient failed to return after 42 days of initiation
of treatment, conclude the surveillance.
4.8 If :-
4.8.1 BFMP is positive during any of the follow-up (D3, D5-D7, D14, D21, D28, D42), or
BFMP is repeated and the asexual density is not less than 25% and 50% on D1 and D2
respectively compared to D0 density, or
4.8.2 Patient shows clinical deterioration, concludes the surveillance. If surveillance is conclud
ed because of clinical deterioration, indicate such reason (e.g. Treatment failure on D2) in
Section 4 (just write anywhere).
4.8.3 If conclusion of treatment failure is made on D14, D21, D28 and D42; send both of D0 and
the current positive slides to IMR for genotyping. Preferably, send spotted blood sample on
flter paper.
5. Submission of surveillance format
5.1 Once the surveillance is concluded, the coordinator check all the information entered into the
Surveillance Form and key in data into e-Vekpro completely. Prepare the report with verifcation
and validation by the MOH.
5.2 Send the report Form to the national coordinator, close the case for surveillance.
Drug artemether-lumefantrine (AL-Riamet) artesunate-mefoquine (ASMQ-FDC)
Dose per day 2 doses (BD) 1 dose (OD)
Total dose 2 X 3 days = total 6 doses 1 X 3 days = total 3 doses
Dosage
calculation
5 - < 15 kg : 1 tablet per dose
15 - < 25 kg : 2 tablets per dose
25 - < 35 kg : 3 tablets per dose
35 kg : 4 tablets per dose
< 10 kg : 1 tablet AS 25mg OD X 3 days,
MQ 125mg single dose
10 -20 kg : 2 tablets ASMQ 25/55mg per dose
20 -40 kg : 1 tablet ASMQ 100/220mg per dose
40kg : 2 tablets ASMQ 100/220mg per dose
43 44
DRS_Annex 3
Standard Operating Procedure Flow Chart :
District Health Offce Medical Offcer of Health (MOH)
at the District Health Offce is responsible to coordinate and
monitor surveillance activity.
District Health Offce MOH Appoint a dedicated staff to
act as coordinator (eg: PPKP).
District Health Offce MOH and coordinator identify
Medical Offcer (MO)who incharge and manage malaria
cases in district hospital.
District Hospital MOH/coordinator brief MOs, Sisters
and senior Laboratory Technologist on the surveillance
mechanism.
District Hospital Coordinator provides the Surveillance
Form (DRS_Annex 1)and distribute to the MOs/Sisters of
the relevant wards
District Hospital MOs complete the Surveillance Form,
inform coordinator via phone and return the form to the
coordinator once patient is discharge.
District Health Offce
i. Coordinator prepares Reporting Format (DRS_Annex 4).
ii. MOH verify and validate the report.
National VBDS Compile and prepare monthly report.
Prosedure end.

Daily monitoring

Collect form : On the
same day of patient
discharge

On the same day of
patient discharge

First week of the
following month

Before the 10
th
of the
following month

Before the 15
th
of the
following month
District Health Offce Coordinator incharge:
i. Collect form (DRS_Annex 1) from MOs
ii. Continue follow-up patient until D42 treatment
iii.Key in data in Vekpro online system completely
District Health Offce
i. Coordinator prepares Reporting Format (DRS_Annex 4).
ii. MOH verify and validate the report.
State Health Offce State KPP compile and verify/vali-
date report. Send the Reporting Format (DRS_Annex 5) to
Vector Borne Disease Section.
1.1
1.2
1.3
1.4
1.5
1.6
1.7
1.8
1.9
1.10
1.11
1.12
District Hospital MOs begin and carry out the
surveillance activities.
6
6
6
6
6
6
6
6
6
6
6
6
6
Prosedure Start.
45 46
DRS_Annex 4
REPORTING FORMAT (District)
Month Year
District Type of Parasite : Pf Pk Pm
No. Hospital No. of patient
admitted for
the month
No. of patient
enrolled for
anti-malaria
surveillance
for the month
No. of
surveillance
concluded in
the month
No. of
surveillance
form
submitted for
the month
No. of
resistance
cases
Total

Prepared by:
_______________________
(Coordinator)
Verifed and validated by:
_______________________
(District health offcer)
45 46
DRS_Annex 5
REPORTING FORMAT (State)
Month Year
District Type of Parasite: Pf Pk Pm
No. Hospital No. of patient
admitted for
the month
No. of patient
enrolled for
anti-malaria
surveillance
for the month
No. of
surveillance
concluded in
the month
No. of
surveillance
form
submitted for
the month
No. of
resistance
cases
Total

Prepared by:
_______________________
Verifed and validated by:
_______________________
(State KPP-Vector)
47 48
Appendix 1
MALARIA PROPHYLAXIS RECOMMENDATIONS
Country Estimated
Relative Risk
Drug
Resistance
Recommended
Chemoprophylaxis
Remarks
Afghanistan High Chloroquine Doxycline/ mefoquine/
proguanil
Argentina Low None Primaquine / doxycycline P. vivax 100%
Bangladesh Moderate Chloroquine Proguanil, doxycycline, or
mefoquine
P. falciparum 77%
P. vivax 23%
Botswana Very Low Chloroquine Atovaquone/ proguanil,
doxycycline, or mefoquine
Brazil Low Chloroquine Atovaquone/ proguanil,
Burma Moderate Chloroquine Atovaquone/ proguanil,
P. falciparum 86%
P. vivax 12%
P. malariae 2%
Cambodia Moderate Chloroquine Atovaquone/ proguanil,
P. falciparum 86%
P. vivax 12%
P. malariae 2%
Cameroon High Chloroquine Atovaquone/ proguanil,
Central
African
Republic
High Chloroquine Atovaquone/ proguanil,
P. falciparum 85%
P. malariae,
P. ovale, and P. vivax
15%
China Low Chloroquine
Mefoquine
Atovaquone/ proguanil,
Along China-Burma
border, Hainan ,Anhui,
Guizhou, Henan, and
Hubei provinces
Congo High Chloroquine Atovaquone/ proguanil,
Ethiopia Moderate Chloroquine Atovaquone/ proguanil,
Gambia High Chloroquine Atovaquone/ proguanil,
Haiti Moderate Chloroquine Atovaquone/ proguanil,
P. falciparum 100%
Kenya Moderate Chloroquine Atovaquone/ proguanil,
P. falciparum 85%
P. vivax 5-10%
P. ovale up to 5%
47 48
Country Estimated
Relative Risk
Drug
Resistance
Recommended
Chemoprophylaxis
Remarks
Laos Very Low Chloroquine Atovaquone/ proguanil,
doxycycline, or
mefoquine
P. falciparum 95%
P. vivax 4%
P. malariae and P. ovale 1%
Liberia High Chloroquine Atovaquone/ proguanil,
doxycycline, or
mefoquine
Madagascar Moderate Chloroquine Atovaquone/ proguanil,
doxycycline, or
mefoquine
Malaysia**
Present in
rural areas
of Sabah,
Sarawak and
Peninsular
Malaysia.
Low Chloroquine Atovaquone/ proguanil,
doxycycline, mefoquine
P. knowlesi (commonest) 38%
P. vivax 31% P. falciparum 19%
P. malariae 10%
Mixed 2%
Mexico Low None Chloroquine, primaquine
or doxycycline
P. vivax 100%
Namibia Moderate Chloroquine Atovaquone/ proguanil,
doxycycline, or
mefoquine
P. falciparum 90%
P. malariae, P. ovale, and P.
vivax 10%
Nigeria High Chloroquine Atovaquone/ proguanil,
doxycycline, or
mefoquin
P. falciparum 85%
P. ovale 5-10%
P. vivax rare
Pakistan Moderate Chloroquine Atovaquone/ proguanil,
doxycycline, or
mefoquin
P. falciparum 70%
P. vivax 30%
Source: Adapted from CDC Yellow Book 2010, available at http://wwwnc.cdc.gov)
49

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References:
1. World Health Organization. Guidelines for the Treatment of Malaria. Second edition. 2010. Geneva:
WHO Press.
2. Lalloo DG, Shingadia D, Pasvol G, et al. UK malaria treatment guidelines. Journal of Infection
2007;54:111-121.
3. Centers for Disease Control and Prevention. Treatment of Malaria (Guidelines for Clinicians). April
2011. http://www.cdc.gov/malaria/resources/pdf/clinicalguidance.pdf
4. Department of Health, Republic of South Africa. Guidelines for the Treatment of Malaria in South Africa.
2008.
5. Centre for Disease Control, Department of Health, Northern Territory. Malaria Guidelines for Health
Professionals in the Northern Territory. September 2012. http://www.health.nt.gov.au/library/scripts/
objectifyMedia.aspx?fle=pdf/10/94.pdf&
6. Ministry of Health Malaysia. National Antibiotic Guideline 2008.
7. Ministry of Health Drug Formulary 2009.
8. Rosenthal PJ. Artesunate for the treatment of severe Falciparum malaria. N Engl J Med April 24,
2008;358:1829-1836.
9. Baird JK and Hoffman SL. Primaquine therapy for malaria. CID 2004:39.

10. Franois N, McGready R, Mutabingwa T. Case management of malaria in pregnancy. Lancet Infect Dis
2007;7:11825.
11. McGready R, Cho T, Samuel, et al. Randomized comparison of quinine-clindamycin versus artesunate in
the treatment of falciparum malaria in pregnancy. Trans R Soc Trop Med Hyg 2001;95:65156.
12. McGready R, Brockman A, Cho T, et al. Randomized comparison of mefoquine-artesunate versus
quinine in the treatment of multidrug-resistant falciparum malaria in pregnancy. Trans R Soc Trop Med
Hyg 2000;94:68993.
13. Deen JL, von Seidlein L, Pinder M, Walraven GE, Greenwood BM. The safety of the combination artesunate
and pyrimethamine sulfadoxine given during pregnancy. Trans R Soc Trop Med Hyg 2001;95:42428.
14. McGready R, Cho T, Keo NK, et al. Artemisinin antimalarials in pregnancy: a prospective treatment
study of 539 episodes of multidrug-resistant Plasmodium falciparum. Clin Infect Dis 2001;33:200916.
15. McGready R, Khan Keo N, Villegas L, White NJ, Looareesuwan S, Nosten F. Artesunate-atovaquone-
proguanil rescue treatment of multidrug-resistant Plasmodium falciparum malaria in pregnancy: a
preliminary report. Trans R Soc Trop Med Hyg 2003; 97: 13.
16. Adam I, Elwasila E, Mohammed Ali DA, Elansari E, Elbashir MI. Artemether in the treatment of
falciparum malaria during pregnancy in eastern Sudan. Trans R Soc Trop Med Hyg 2004;98:50913.
17. Dondorp A, Nosten F, Stepniewska K, Day N, White N. South East Asian Quinine Artesunate Malaria
Trial (SEAQUAMAT) group. Artesunate versus quinine for treatment of severe falciparum malaria: a
randomised trial. Lancet 2005;366 71725.
57 58
18. Adam I, Ali DM, Abdalla MA. Artesunate plus sulfadoxinepyrimethamine in the treatment of
uncomplicated Plasmodium falciparum malaria during pregnancy in eastern Sudan. Trans R Soc Trop
Med Hyg 2006;100:63235.
19. Sowunmi A, Oduola AM, Ogundahunsi OA, Fehintola FA, Ilesanmi OA, Akinyinka OO. Randomised trial
of artemether versus artemether mefoquine for the treatment of chloroquine/sulfadoxine-pyrimethamine-
resistant falciparum malaria during pregnancy. J Obstet Gynaecol 1998;18:32227.
20. Package Insert: Riamet (Artemether 20mg + Lumefantrine 120mg), October 2002.
21. Package Insert: Lariam (Mefoquine hydrochloride), September 2010.
22. Package Insert: Malakin Injection (Quinine Dihydrochloride), October 2010.
23. Package Insert: Quinine Tablet, March 2009.
24. Package Insert: Primaquine Tablet.
25. Package Insert: Fansidar (Sulfadoxine and Pyrimethamine), 2nd July 2010.
26. Package Insert: Artesun (Artesunic acid).
27. Package Insert: ASMQ FDC (Artesunate and Mefoquine hydrochloride) Tablet 100/220 mg, February
2012.
28. CDC- Treatment of Malaria (Guidelines for Clinicians), April 2011.
29. Pindaan Senarai Ubat-ubatan Kementerian Kesihatan Malaysia, 9th August 2012.
30. Pindaan Senarai Ubat-ubatan Kementerian Kesihatan Malaysia, April 2013.
31. Lacy, C., Armstrong, L.L. Goldman, M.P et al. 2011. Drug Information Handbook. 20
th
Edition. Ohio:
Lexi-Comp Inc.
32. BMJ Group and the Royal Pharmaceutical Society of Great Britain. British National Formulary. March
2011. London: Pharmaceutical Press.
33. MIMS USA (2013). Artesunate (viewed 10th June 2013). http://www.mims.com/USA/drug/info/
artesunate/
57 58
Appendix 3
SELECTED FURTHER READING
This guidelines and manuals from which the recommendations in this manual were derived are:
1. Guidelines for the treatment of malaria, 2
nd
Ed. Geneva, World Health organization, 2010. http://www.
who.int/malaria/publications/atoz/9789241547925/en/index.html.
2. WHO pocket book of hospital care for children: guidelines for the management of common illnesses
with limited resources. Geneva, World Health organization, 2005.
3. Universal access to malaria diagnostic testing: an operational manual. Geneva, World Health organiza-
tion, 2011. http://whqlibdoc.who.int/publications/2011/9789241502092_eng.pdf.
4. Recommendations for the management of common childhood conditions: Evidence for technical update
of pocket book recommendations. Geneva, World Health organization, 2012. http://www.who.int/mater-
nal_child_adolescent/documents/management_childhood_conditions/en/index.html.
5. Informal Consultation on the Public Health Importance of Plasmodium knowlesi. Kuching, Sarawak,
Malaysia, 22 to 24 February 2011, World Health Organization.
59
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