1. Malaria is a life-threatening tropical disease caused by Plasmodium parasites transmitted via mosquito bites. 2. Malaysia has seen a large reduction in malaria cases from the 1980s but remains at risk due to its equatorial climate. 3. Malaria symptoms vary from mild to severe and can include fever, chills, headaches and more, with severe cases potentially involving coma, respiratory distress or kidney failure if left untreated.

1. Malaria
By
Ebson Anak Ngumbang

2. Introduction
• Malaria is a tropic life threatening disease.
• A disease caused by members of the protozoan
genus Plasmodium, a widespread group of sporozoans
that pasitize the human liver and red blood cells.
• Humans are infected with Plasmodium protozoa when bitten
by an infective female Anopheles mosquito vector.
• Symptoms may appear within weeks to months or even years.
• There are 4 species:
– plasmodium falciparum
– plasmodium vivax
– plasmodium ovale
– plasmodium malariae

3. Malaria in Malaysia
• Malaysia is situated in the hot, humid
equatorial region and thereforeis receptive
and vulnerable for the transmission of
malaria.
• The number of cases has shown a tremendous
reduction from 181,495 cases at the start of
the Eradication Programme in 1967 Tto
44,226 cases at the end of the Eradication
Programme in 1980.

4. Distribution of malaria cases in
Malaysia
Source: WHO, 2011

5. Malaria Trend in Malaysia
1995-2010

7. Malaria Transmission Cycle
Exo-erythrocytic (hepatic) Cycle:
Sporozoites injected Sporozoites infect liver cells and
into human host during develop into schizonts, which release
blood meal merozoites into the blood
Parasites
mature in
mosquito
midgut and Dormant liver stages
MOSQUITO HUMAN
migrate to (hypnozoites) of P.
salivary vivax and P. ovale
glands
Erythrocytic Cycle:
Merozoites infect red
Parasite undergoes Some merozoites
blood cells to form
sexual reproduction in differentiate into male or
schizonts
the mosquito female gametocyctes

9. Who is at risk?
• young children
• pregnant women
• people with HIV/AIDS
• international travelers from non-endemic
areas
• immigrants from endemic areas and their
children

10. Clinical features and classification of
malaria
uncomplicated malaria severe malaria
in special groups (young children, pregnant women, HIV
/AIDS)
in travellers (from non-malaria endemic regions)
in epidemics and complex emergency situations

11. UNCOMPLICATED MALARIA (all species)
– Uncomplicated malaria definition:
Fever and any of the following:
• Headache,
• Body and joint pains
• Feeling cold and sometimes shivering
• Loss of appetite and sometimes abdominal pains
• Diarrhoea, nausea and vomiting.
• Hepatospleenomegaly

12. SEVERE COMPLICATED MALARIA
Confusion, or drowsiness with extreme weakness (prostration).
In addition, the following may develop:
Alteration in the level of consciousness (ranging from drowsiness to deep coma)
Cerebral malaria (unrousable coma not attributable to any other cause in a
patient with falciparum malaria)
Respiratory distress (acidotic breathing)
Multiple generalized convulsions (2 or more episodes within a 24 hour period)
Shock (circulatory collapse, septicaemia)
Pulmonary oedema
Abnormal bleeding (Disseminated Intravascular coagulopathy)
Jaundice
Haemoglobinuria (black water fever)
Acute renal failure - presenting as oliguria or anuria
Severe anaemia (Haemoglobin < 5g/dl or Haematocrit < 15%)
High fever
Hypoglycaemia (blood glucose level < 2.2.mmol/l)
defined as the detection of P. falciparum in the peripheral blood

13. Malaria Diagnosis
• All clinically suspected malaria cases require
laboratory examination and confirmation.
• Only in case where laboratory confirmation is
not possible start treatment immediately.
• Parasitological confirmation is done by thin-
thick blood smear microscopy examination or
by dipstick (Rapid Diagnostic Test [RDT]).
Guidelines for the Treatment of Malaria

14. Differential diagnosis for
uncomplicated malaria
Consider other illnesses, such as:
• Upper respiratory tract infection
(Pharyngitis, tonsillitis, ear infection),
pneumonia , measles, dengue, influenza,
typhoid fever.
Remember that the patient may be suffering
from more than one illness.

15. Differential diagnosis for severe malaria
Consider other illness, such as:
measles, meningitis, tonsilitis,, dengue, otitis
media (ear infection), influenza, pneumonia,
typhoid fever, tuberculosis, hypoglycemia.

16. THE PHARMACOLOGY OF ANTIMALARIALS
Class Definition Class Definition Examples Class Definition Examples
Examples
Blood Act on (erythrocytic) stage of the Quinine, artemisinins,
schizonticidal parasite thereby terminating amodiaquine, chloroquine,
drugs clinical illness lumefantrine, tetracyclinea ,
atovaquone, sulphadoxine,
clindamycina , proguanila
Tissue Act on primary tissue forms of Primaquine, pyrimethamine,
schizonticidal plasmodia which initiate the proguanil, tetracycline
drugs erythrocytic stage. They block
further
development of the
infection
Gametocytocidal Destroy sexual forms of the Primaquine, artemisinins,
drugs parasite thereby preventing quinineb
transmission of infection to
mosquitoes
a
Slow acting, cannot be used alone to avert clinical symptoms
b
Weakly gametocytocidal

17. THE PHARMACOLOGY OF ANTIMALARIALS
(cont.)
Class Definition Class Definition Examples Class Definition
Examples Examples
Hypnozoitocidal drugs These act on persistent Primaquine,
liver stages of P.ovale tafenoquine
and P.vivax which cause
recurrent illness
Sporozontocidal drugs These act by affecting Primaquine, proguanil,
further development of chlorguanil
gametocytes into oocytes
within the mosquito thus
abating transmission

19. 1. Treatment of severe falciparum malaria
Preferred regime Alternative regime
IV Artesunate (60mg): 2.4mg/kg on IV Quinine loading 7mg salt /kg over 1hr
admission, followed by 2.4mg/kg at 12h & followed by infusion quinine 10mg salt/kg over
24h, then once daily for 7 days. 4 hrs, then 10mg salt/kg Q8H or IV Quinine
20mg/kg over 4 hrs, then 10mg/kg Q8H.
Once the patient can tolerate oral therapy, Plus
treatment should be switched to a complete Adult & child >8yrs old: Doxycycline (3.5mg/
dosage of Riamet (artemether/lumefantrine) kg once daily)
for 3 day. or
Pregnant women & child < 8yrs old:
Clindamycin (10mg/kg twice daily). Both drug
can be given for 7 days.
Reconstitute with 5% Sodium Bicarbonate & Dilute injection quinine in 250ml od D5%
shake 2-3min until clear solution obtained. and infused over 4hrs.
Then add 5ml of D5% or 0.9%NaCl to create
total volume of 6ml. Infusion rate should not exceed 5 mg salt/kg
Slow IV injection with rate of 3-4ml/min or per hour.
IM injection to the anterior thigh.
The solution should be prepared freshly for
each administration & should not be stored.

20. 2. Treatment of uncomplicated p.falciparum

21. Children under 5 kg or below 4 months should not be given Riamet
instead treat with the following regimen (see table).
Dosage and administration Plasmodium falciparum for young
infant
Weight
Age Group Artesunate or *Quinine
group
Oral
** IM first dose Quinine 10
***Oral
Artesunate 1.2 mg/kgTDS
0-4 Artesunate
<5 kg mg/kg or IM for 4 days
months 2mg/kg/day
Arthemeter 1.6 then 15-20
day 2 to day 7
mg/kg) mg/kg TDS
for 4 days
Source: Malaria in Children, Department of tropical Pediatrics, Faculty of Tropical Medicine,
Mahidol University.
referably Artesunate/Artemether IM on day 1 if available
When Artesunate/Artemether IM is unavailable, give oral Artesunate from day 1 to day 7
eat the young infant with Quinine when oral Artesunate is not available

22. 3. Treatment of malaria caused by
p.knowlesi & mixed infection (p. falciparum
+ p. vivax)
• Treat as p. falciparum

23. Important notes
Riamet tablets should be taken with or after food.
Patient with acute malaria re frequently averse to food, the dose may be
taken with fluid and encourage patient to resume normal eating as soon as
food can be tolerated.
Watch all patients swallowing the first dose of Riamet® and observe for 1
hour after the intake. In the event of vomiting within one hour of
administration, a repeat dose should be taken.
For small children Riamet® can be crushed, diluted in water and then put
either directly into the mouth using a syringe or given with a spoon.
Riamet may cause fatigue and dizziness. Warn patient not to drive or use
machines.
Instruct patient to report signs/symptoms of QT interval prolongation.

24. 4. Treatment of of malaria caused by p.vivax, p.
ovale or p. malariae.
CHLOROQUINE
PRIMAQUINE
(150 mg base/tab) 25 mg base/kg
(7.5 mg base/tab)
divided over 3 days
Day 1 Day 2 Day 3 Start concurrently with CHLOROQUINE 0.5
mg base/kg Q24H for 2 weeks
Take with food
10mg
Check G6PD status before start primaquine
base/kg
5mg In mild-to-moderate G6PD deficiency,
stat, 5mg base/
base/kg primaquine 0.75 mg base/kg body weight
then kg Q24H
Q24H given once a week for 8 weeks.
5mg
In severe G6PD deficiency, primaquine is
base/kg
contraindicated and should not be used.
1 tab of chloroquine phosphate 250mg equivalent to 150mg base. Calculation of dose for
chloroquine is based on BASE, not SALT form. 1 tab of primaquine phosphate contains
7.5mg base.

25. Treatment in specific population & situations
Specific Preferred regime Alternative regime
populations
Pregnancy Quinine plus clindamycin to be given for Artesunate plus Clindamycin for
7 day 7 days is indicated if first line
treatment fails
Lactating Should receive standard antimalarial treatment (including ACTs) except
women for dapsone, primaquine and tetracyclines, which should be withheld
during lactation
Hepatic Chloroquine: 30-50% is modified by liver, appropriate dosage adjustment
impairment is needed, monitor closely.
Quinine : Mild to moderate hepatic impairment-no dosage adjustment,
monitor closely.
Artemisinins : No dosage adjustment
Renal Chloroquine : ClCr<10ml/min-50% of normal dose.
Impairment Hemodialysis, peritoneal dialysis: 50% of normal dose.
Continuous Renal Replacement Therapy(CRRT) :100% of normal dose.
Quinine : .ClCr 10-50ml/min : Administer Q8-12H, CLCr<10ml/min :
administer Q24H,Severe chronic renal failure not on dialysis : initial dose:
600mg followed by 300mg Q12H, Hemo- or peritoneal dialysis: administer
Q24H ,Continuous arteriovenous or hemodialysis: Administer Q8-12H.
Artemisinin : no dosage adjustment.

26. Treatment of complications of malaria
• Severe & complicated falciparum or knowlesi
malaria is a medical emergency that requires
intervention and intensive care as rapidly as
possible.
• Fluid, electolyte glucose & acid-base balance
must be monitored.Intake & output should be
carefully recorded.

27. Immediate clinical management of severe manifestations and
complications of P. falciparum malaria
Definitive clinical features Immediate management/treatment
Come (Cerebral malaria) Monitor & record level of consciousness using Glaslow coma
scale, temperature, respiratory, and depth, BP and vital signs.
Hyperpyrexia (rectal body Treated by sponging, fanning &with an antipyretic drug.
temperature >40°C) Rectal paracetamol is preferred over more nephrotoxic drugs
(e.g. NSAIDs)
Convulsions A slow IV injection of diazepam(0.15mg/kg, maximum 20mg
for adults).
Hypoglycaemia (glucose Correct with 50% dextrose (as infusion fluids). Check blood
conc. <2.8mmol/L) glucose Q4-6H in the first 48hrs.
Severe anaemia (hb < Transfuse with packed cells. Monitor carefully to avoid fluid
7g/dl) overload. Give small IV dose of frusemide, 20mg, as necessary
during blood transfusion to avoid circulatory overload.
Acute pulmonary oedema Prop patient upright (45°), give oxygen, give IV diuretic (but
most patient response poorly to diuretics), stop intravenous
fluids. Early mechanical ventilation should be considered.

28. Immediate clinical management of severe manifestations and
complications of P. falciparum malaria (cont.)
Definitive clinical features Immediate management/treatment
Acute renal failure (urine Exclude pre-renal causes by assessing hydration status.
output <400ml in 24hrs in Rule out urinary tract obstruction by abdominal examination
adults or 0.5ml/kg/hr, or ultrasound.
failing to improve after Give intravenous normal saline
rehydration & a serum If in established renal failure add haemofiltration or
creatinine of >265μmol/L) haemodialysis, or if unavailable, peritoneal dialysis.
Disseminated Transfuse with packed cell, clotting factors or platelet.
intravascular Usual regime: Cryoprecipitate 10units,platelets 4-8units,
Coagulopathy (DIVC) fresh frozen plasma(10-15ml/kg).
For prolonged PT, give vitamin K, 10mg by slow IV injection.
metabolic acidosis Infuse sodium bicarbonate 8.4% 1mg/kg over 30min and
repeat if needed.
if severe, add haemodialysis.
Shock (hypotension with Suspect septicaemia, take blood for cultures; give parenteral
systolic blood pressure broad-spectrum antimicrobials, correct haemodynamic
<70mmHg) disturbances.

29. Monitoring & follow-up
• Blood smear should be repeated daily
(twice daily in severe infection). Within
48-72 hr after start of treatment, patients
usually become afebrile and improve
clinically except in complicated cases.
• All patients should be investigated with
repeated blood film of malarial parasite
one month upon recovery of malarial
infection, to ensure no recrudescence.

30. Prevention
•Avoid mosquito bites:
Wearing long sleeves, trousers.
Insecticide Treated Bednets
Repellent creams or sprays.

31. Chemoprophylaxis
• Indicated for travellers travel to
endemic areas in Malaysia.
• Mefloquinine 250mg weekly (up to 1
year) or doxycycline 100mg daily (up
to 3 month), to start 1 week before
and continue till 4 weeks after leaving
the area.

32. Dosing schedule for mefloquine
Weight Age No of tablets per
week
< 5 kg < 3 months Not
recommended
5 - 12 kg 3 - 23 months 1/4
13 - 24 kg 2 - 7 yrs 1/2
25 - 35 kg 8 - 10 yrs 3/4
36 and above 11 yrs and above 1

33. Dosing schedule for doxycycline
Weight in kg Age in years No of tablets
< 25 <8 Contraindicated
25 - 35 8 - 10 ½
36 - 50 11 - 13 ¾
50+ 14+ 1

36. Tx failure of uncomplicated
• A failure to clear malarial parasitaemia and/or resolve clinical
symptoms despite the administration of an antimalarial. So
while drug resistance may lead to treatment failure, not all
treatment failures are caused by drug resistance.
• Treatment failure can also be the result of incorrect dosing,
problems of treatment adherence (compliance), poor drug
quality, interactions with other drugs, compromised drug
absorption, or misdiagnosis of the patient. Apart from leading
to inappropriate case management, all these factors may also
accelerate the spread of true drug resistance by exposure of
the parasites to inadequate drug levels.

37. Tx failure for uncomplicated
malaria
• Treatment failures within 14 days of initial treatment should be treated
with a second-line antimalaria.
• the following second-line treatments are recommended,
• in order of preference:
• ■ an alternative ACT known to be effective in the region,
• ■ artesunate plus tetracycline or doxycycline or clindamycin (given for a
total of 7 days),
• ■ quinine plus tetracycline or doxycycline or clindamycin (given for a total
of 7 days).

38. References
• WHO Guidelines for the treatment of malaria -- 2nd edition.(2010)
• Management of severe malaria : a practical handbook. – 2nd ed.(2000)
• MICROMEDEX 2.0
• NATIONAL GUIDELINES FOR THE DIAGNOSIS, TREATMENT AND
PREVENTION OF MALARIA IN KENYA.THIRD EDITION 2010.
• http://www.akademisains.gov.my/download/tropical/Lokman.pdf
• http://www.who.int/malaria/publications/country-profiles/profile_mys_en.pdf