infectious disease

1. MALARIA
DR. SANA ANUM

2. HISTORY:
• First record of “periodic fevers” from China
in 2700 BC
• Term “malaria” derived from Italian for
“bad air” – mala aria
• Also known as “ague” or “marsh fever”

3. • First effective treatment was the bark of
the cinchona tree (contains quinine)
• Grows in the Peruvian Andes
• Used by the locals to control malaria
• Jesuits introduced it to Europe in 1640s
• Active ingredients (quinine) isolated from
the bark
• Named by French chemist Pierre Pelletier
and Jean Caventou

4. • The blood stage of malaria life cycle was
recognized in 19th
and early 20th
century
• The latent form of the disease (in the liver)
was only recognized in 1980s
• Explained why apparently “cured” people
could have recurrent episodes years later
in the absence of new exposure

5. WHAT IS MALARIA??
• A disease caused by parasites transmitted to
humans from infected female Anopheles
mosquitoes
• The protozoan parasites of the genus
Plasmodium infect the red blood cells (RBCs)
• Symptoms include fever, chills, and flu-like illness
• If left untreated, the development of severe
complications can cause death
• Malaria is preventable and curable

6. ETIOLOGY:
• obligate intracellular blood born parasite.
• Parasites are inoculated into a human host
• By feeding female anopheline mosquitoes
• The species that infect humans worldwide:
– Plasmodium falciparum (15%)
– Plasmodium vivax (80%)
– Plasmodium ovale
– Plasmodium malariae
– Plasmodium knowlesi (<1%)
• life cycle:
• human host (asexual phase), mosquito vector (sexual

7. PLASMODIUM FALCIPARUM:
• Almost entirely confined to tropics and
subtropics
• Accounts for 15% of malaria infection
• Clinically and morphologically different from other
malarias
– Gametocytes are elongate/sausage-shaped
– Schizogony usually does not take place in
peripheral blood of falciparum malaria
– P. falciparum attacks all stages of red blood cells

8. P. VIVAX:
• ‘ Vivax’ = vigorous (Latin)
• Accounts for 80% of malaria infection
• Predominant malaria parasite in the world
– Only malarial parasite whose range
extends into temperate regions
– Seldom causes severe disease

9. P. falciparum
• Cytoadherence
• Cerebral & placental
pathology
• Infects RBCs of all ages
• Gametocytes develop late
• Anemia can be severe
• Deadliest form
Distinguishing Characteristics
• P. Vivax
• No cytoadherence
• Infects reticulocytes
(young RBCs)
• Gametocytes develop
early
• Milder symptoms
• Most prevalent form

10. Plasmodium ovale
• Only been known since 1922
• Widely distributed in tropical Africa,
especially West African coast
• Main distinctive morphologic feature is
ovoid shape of many of infected RBCs
• Other features: – Parasite not as ameboid
as P. vivax – Nuclei in all stages are larger

11. Plasmodium malariae
• Is rarer than P. vivax or P. falciparum
• Occurs primarily in subtropical and
temperate areas where other malaria spp.
are found
• Distinguishing characteristics:
– Asexual cycle lasts 24 hours longer than
other spp.
– Infected cell is not enlarged

12. Plasmodium knowlesi
• Primarily a primate malaria of Southeast
Asia
• Current overall incidence of infection in
humans is low, but is consistently
misdiagnosed, which can be fatal
• Transmitted by Anopheles leucosphyrus
mosquitoes

14. LIFE CYCLE:
Vocabulary
• Trophozoite: the feeding stage of a
protozoan parasite (intracellular)
• Schizogony: the process of asexual
reproduction in which the nucleus
undergoes multiple divisions prior to cell
division

15. • Merozoite: a product of schizogony which
can infect new host cells, where it can
undergo another round of schizogony or
become a gametocyte
• Gametocyte: A cell, derived from a
merozoite, that can undergo development
to a gamete

16. • After they are released into the blood,
each merozoite invades a red blood cell,
where it produces 8-24 daughter cells in
48 hours
• Daughter cells released into the blood and
are ingested by a feeding mosquito

19. TRANSMISSION:
• Common means of transmission:
– Bite of Anopheles mosquito
• Very unusual means of transmission:
– Congenital malaria (from mother to infant)
– Blood transfusion
– Sharing intravenous needles
– In non-endemic areas, can be transmitted
by mosquitoes infected after biting
infected immigrants/travelers

21. EPIDEMIOLOGY:
• most important parasitic cause of mortality and
morbidity around the world (2-3 million deaths)
• tropical and sutropical areas.
• night bitting mosquito.
• standing water and warn climate.
• pre-requisites: anopheles vector, infected and
susceptible hosts.
• mutant gene: chloroquine resistant P.
falciparum( CPRF).
• spread: direct, inf blood transfusion,
contaminated needles.

22. • congenital malaria: in young infants born to
infected mothers who carried infection during
pregnancy.

24. • 63 outbreaks in US 1957-2003
• 41% of world live in endemic areas
• 700,000 – 2.7 million die/year
(75% African children)
Increasing P. falciparum resistance to chloroquine and now other newer agents
South Asia, Sub-Saharan Africa, Tropical South America, Oceania
Check current recommendations
www.cdc.gov
www.who.int

25. • The key monitoring indicators (indices) of the program
assessment are.
• Annual Parasite Incidences (API).
• Blood Examination Rate (BER) related to the diagnosis
coverage of population.
• Test Positivity rate (TPR) related to true case rate
amongst samples.
• Proportion of P. falciparum indicating epidemiological
prevalence of lethal form.
• The following graph shows trend of the above mentioned
indicators from (2007-2013).

26. • Endemic disease
• Usually does not occur at altitudes – 1500
m
• World wide ease of travel
• Most important parasitic disease of
humans
• Transmitted in over 100 countries
• Affecting more than 3 billion people world
wide

27. WHO IS AT RISK:
• Approx. half of world population at risk for malaria
in 2012
• 104 countries and territories endemic for malaria in
2012
• Estimated 219 million cases annually
• 660,000 deaths from malaria each year
• 80% of malaria deaths occur in just 14 countries
and 80% of cases occur in 17 countries
• Last decade: estimated 1.1 million malaria deaths
averted
• • Strategy: T-3: test, treat, track

28. • Children under 5 years and non- breastfeeding infants
• Pregnant women
– 3-fold increase in severe disease and mortality
– Increased risk of miscarriage, stillbirth
– May have markedly reduced parasitemia (placental sequestration)
• Malnourished
• HIV-infected individuals
Level of prior exposure to malaria predicts severity of disease
• In areas of low to medium transmission
– All ages have risk
• In areas of high transmission
– Children have highest risk (<5 y/o)
– Persons from low transmission areas at risk.
During times of population movement (i.e., refugees or internally
displaced persons (IDPs)
– Those from low endemicity areas
• No pre-existing immunity and more severe disease at all ages

29. PROTECTIVE FACTORS:
• Biological characteristics and behavior
traits can influence risk of developing
malaria
• Newborns are protected by maternal
antibodies
– Antibodies decrease with time, explaining
the vulnerability in children who have
stopped breastfeeding

30. • Two protective genetic traits: sickle cell
trait and absence of Duffy blood
group(p.vivax)
– Both common in Sub-Saharan Africa
• OTHERS:
• thalassemia
• G6PD deficiency
• pyruvate kinase deficiency

32. Manifestations of the Malaria Burden
Infected
Mosquito
Infected
Human
Chronic
effects
Anemia
Neurologic
Cognitive
Developmental
Impaired
growth and
development
Malnutrition
Acute
febrile
illness
Severe illness
Anemia
Hypoglycemia
Cerebral malaria
Death
Respiratory
distress
Pregnancy
Fetus
Maternal
Acute illness
Anemia
Low birth weight
Abortion, stillbirth
Infant and fetal
mortality
Long-term
sequelae
Hypovolemia
Long-term
sequelaeBreman, Alilio, Mills, 2004, Am J Trop Med Hyg

33. Countries With
Widespread Transmission, 2006
Breman and Holloway, 2007, Am J Trop Med Hyg
Population
(millions)
Cases
Confirmed
Cases
Estimated
Afghanistan 31.6 83,000 1,500,000
Djibouti 0.6 2,000 60,000
Pakistan 164.7 24,000 1,600,000
Somalia 8.8 16,000 1,300,000
Surveys of P. falciparum, Eastern Mediterranean
Regional Office (EMRO), 1985-2007

34. PATHOGENESIS:
• Hypoglycemia & lactic acidosis
• Hemolysis & anemia
• TNF-alpha increases anemia
• Splenic sequestration = thrombocytopenia
• Hepatosplenomegaly

35. • P.F. invades RBC at all ages - 106
2500/mcl
· P. Mal: only old RBC – 10,000/mcl
• P. ovale and P. vivax invade young RBC’s.
· Microvascular patholody: secondary Ischemia
Adherence of
• non-deformable parasitezed RBC to endothelium
· Renal failure: hemalysis, Ischemia secondary
microvascular pathology
· Deep Coma: hypoglycemia, microvascular adherent
parasitized RBC
· Pulmonary edema; 2 o: Capillary leak Synd (without

36. Major Manifestations of Malaria
Anemia:

37. INNATE RESISTANCE
• Natural capacity of host to resist infection from malaria.
( which is due to differences in surface receptors ,
intraerythrocytic factors or yet unknown causes. )
• In Endemic zones – repeated infection – development of
resistance.
• Some individuals – vulnerable to infection with one
species – due to difference in genetic constitution of
species.
• Differences in cell membrane – decides
attachment/penetration of merozoites to receptors/cells.
• Sickle cell trait & G-6-PD deficiency – IMMUNE

38. clinical features:
1)1)MajorMajor
• Recurring fevers
• Chills (Assoc. RBC lysis – mature
zchisonts)
• 2) 2) Periodicity S/OPeriodicity S/O
• 48 hours: P. Vivax & Ovale
• 72 hours: P. Malaria
• Non-regular/hectic in P.F. especially in
non- immune
• Patients (who are at highest risk of
complications and death)

39. Severe P.F. (Severe P.F. (>> 10 parasite/ mcl): AC Complications10 parasite/ mcl): AC Complications
– · Renal failure
– · Coma 2 o: hypoglc; TNF, or microvascular
pathology
– · Pul. Edema
– · Thombrocytopenia
– · G. Enteritis – especially diarrhea
– · Ch. P. Falcuparum infection
– Splenomegaly – typically resolves after treatment with
anti-malarial meds. 6-12 mon.
– · P. Malariae assoc. Immune compl. N. Synd.
– · P. Vivax – late splenic rupture with trauma 1-3 mon.
after

40. MALARIA FEVER PAROXYSMSMALARIA FEVER PAROXYSMS
Rigors, headacheRigors, headache
associated with pale cold skinassociated with pale cold skin
(1-2 hours)(1-2 hours)
Delirium, Tachypnoea,Delirium, Tachypnoea,
Hot SkinHot Skin
(Several hours)(Several hours)
FeverFever
Marked sweating and fatigueMarked sweating and fatigue

41. • Patient often symptoms free between
paroxysms

42. • 7 to 30 days after an infective bite,
symptoms appear
• The blood stage parasites are what cause
the symptoms of malaria
• Infected patients are categorized as having
either: – Uncomplicated malaria – Severe
malaria

43. Uncomplicated Malaria
• Initial symptoms non-specific
• Headache
• Muscle aches
• Nausea, vomiting
• Then malarial paroxysms begin
• Shaking chill (10-15 min)
• High fever (typically 10 h; up to 36 h)
• Cycle repeats every 36-72 hours (species
specific)
• Primary attack lasts 2-24 weeks (spp. specific)

44. Signs
• Fever
• Splenomegaly
• Hepatomegaly
• Anemia

45. Symptoms Severe Malaria
• Clinical Manifestation:
• Prostration
• Impaired consciousness
• Respiratory distress
• Multiple convulsions
• Abnormal bleeding
• Jaundice
• Pulmonary edema
• Circulatory collapse

46. • Is nearly always due to P. falciparum
infection • Complications can include: –
Cerebral malaria (neurologic
abnormalities), severe anemia due to
hemolysis, pulminary edema/acute
respiratory distress syndrome,
abnormalities in blood coagulation and
thrombocytopenia, cardiovascular
collapse, shock • Most often occurs in
persons with absent or decreased malaria
immunity

47. • Infected individuals can also be
aysmptomatic • Anti-malarial drugs taken
for prophylaxis can delay the onset of
symptoms by weeks or months • In P.
vivax and P. ovale infections, patients
having recovered from the first illness may
suffer additional, “relapse” attacks, after
months or years without symptoms • This
is due to the reactivation of their dormant
liver stage (hypnozoites)

48. • black water fever:
• shock may also develop in severe
malaria(algid malaria) sometimes from
supervening bacterial infection.

49. DIAGNOSIS:
There are two ways to diagnose malaria in
humans:
– Clinical diagnosis – based on clinical criteria
(signs and symptoms)
– Very low specificity; unreliable; inaccurate
– Parasitological diagnosis
– based on detection of parasites in the blood
– Requires skill; time-consuming; laborious

50. CLINCAL DX:
• Since signs and symptoms of malaria are
nonspecific, it’s clinically diagnosed mostly
on the basis of fever or history of fever
• Where malaria risk is low:
– Diagnosis based on exposure to malaria
and history of fever in previous 3 days
• Where malaria risk is high:
– Diagnosis based on history of fever in
previous 24h and/or presence of anemia

51. Parasitological Diagnosis
• Two methods of parasitological diagnosis
• Light microscopy (blood smears)
• – Rapid diagnostic tests

54. • Giemsa-stained blood smears
– Thick: best used as screening procedure
– Count 200 White Blood Cells (WBCs)
– Parasitaemia = no. of parasites*8000/no.
of WBCs
– Thin: best for specific diagnosis
– Infected RBCs/100 RBCs

55. • Blood smears allow identification of the
infecting species – Important because
treatment varies depending on
Plasmodium species

57. Plasmodium falciparum: Blood Stage Parasites
Thin Blood Smears
 1: Normal red cell
 2-18: Trophozoites
 ( 2-10: ring-stage
trophozoites)
 19-26: Schizonts ( 26 is a
ruptured schizont)
 27, 28: Mature
macrogametocytes
(female)
 29, 30: Mature
microgametocytes
 (male)

58. Plasmodium vivax: Blood Stage Parasites
Thin Blood Smears
 1: Normal red cell
 2-6: Young trophozoites
 (ring stage
parasites)
 7-18: Trophozoites
 19-27: Schizonts
 28,29:
Macrogametocytes
 (female)
 30: Microgametocyte
 (male)

59. Plasmodium ovale: Blood Stage Parasites
Thin Blood Smears
 1: Normal red cell
 2-5: Young trophozoites
 6-15: Trophozoites
 16-23: Schizonts
 24: Macrogametocytes
 (female)
 25: Microgametocyte
 (male)

60. Plasmodium malariae: Blood Stage Parasites
Thin Blood Smears
 1: Normal red cell
 2-5: Young
trophozoites
 (rings)
 6-13: Trophozoites
 14-22: Schizonts
 23: Developing
 gametocyte
 24: Macrogametocyte
 (female)
 25: Microgametocyte
 (male)

62. Risk factors for poor prognosis in
cerebral malaria
o Creatinine
o Bilirubin
o Lactates

63. MALARIA COMPLICATIONS
Majority of complications (apart from anemia)
associated with P. falciparum
* Anemia: presents in most severe infections and
parallels
parasitaemia
•
Hemolysis of infected RBC
•
Delayed retics. release from BM
•
Immune – mediated hemolysis of non-
infected RBC

64. Non-immune: (primary infection)
•
Haemoglobinuria
•
Black water fever
• Exaggerated haemolytic response to quinine –
sensitized RBC
• Mild unconjugated jaundice common, and
parallels hemolysis. Hepatocellular dysfunction
may contribute to jaundice.

65. Tissue hypoxia related complications
Hypoxia results from altered microcirculation +
anemia.
Maturation of erythyrocyte schizonts in P.
falciparum takes place in tissue
capillaries and venules.
P. falciparum parasitized RBC sequestered in
micro circulation because:
Altered deformability of parasitized RBC
Adhesion involving parasite – derived proteins
within RBC and glycoproteins on vascular
endothelium.

66. Cerebral malaria
 Most severe common complication
Renal Failure
 Most severe common complication
 ATN
 Dehydration
 Hypotension
 Hypervescosity
Pulmonary Edema
 ARDS – may complicate acute phase of severe
malaise. Fluid overload may
contribute.

67. Hypoglycemia
 Glucose consumption
 Lactic acidosis
 Quinine/quinidine --- insulin secretion
Bleeding
 Thrombocytopenia
 Consumption coagulopathy
Shock: Endotoxemia
Diarrhea
Hyponatremia (? SIADH)

68. »LATE COMPLICATIONLATE COMPLICATION
–
– Tropical splenomegaly in P. Falciparum
endemic areas.
– N. syndrome with P. malariae.
– Burkett’s lymphoma (PF - EBV)

69. Poor prognostic signs:
severe falciparum malaria
age:3yrs
pregnancy,
respiratory distress
,fits,
coma,
absent corneal reflex,
papilloedema,pulmonary edema,
HCO3-<15mmol/l,
plasma or CSF lactate>5mmol/l,
glucose<2.2mmol/l,
hyperparasytemia(>5%RBCs or 250,000/ul,
Hb <5gm/dl,
DIC,
renal failure.

70. TREATMENT:
• Should commence as soon as possible •
The treatment depends on:
• – species of infecting parasite
• – area where the infection was acquired
and its drug- resistance status
• – clinical status of the patient
• – any accompanying illness or condition,
pregnancy, and drug allergies

71. • Treatment should be based on laboratory-
confirmed diagnosis where possible •
Different kinds of treatment:
– Suppressive therapy (chemoprophylaxis)
– Clinical cure
– Radical cure
Notes: •Suppressive therapy: attempts to destroy parasites as they enter
bloodstream with small doses of drugs effective against erythrocytic stages
•Clinical cure: larger doses of drugs to eliminate large numbers of erythrocytic
parasites present in a clinical attack
•Radical cure: implies elimination of not only bloodstream infection but also
the tissues stages in liver as well;
patient may still be infectious after this because of gametocytes
remaining in circulation blood or hypnozoites in liver that
aren’t killed by drug

72. • Determination of infecting species
important because:
– P. falciparum can cause rapidly
progressive severe illness or death while
other species rarely cause severe illness
– P. vivax and P. ovale require treatment for
hypnozoite forms that remain dormant in
liver
– P. falciparum and P. vivax have different
drug resistance patterns in different
regions

73. • Most drugs used in treatment are active in the
blood stage:
• – Chloroquine, sulfadoxine- pyrimethamine
(Fansidar),
• mefloquine (Lariam),
• atovaquone-proguanil (Malarone),
• quinine, doxycycline, artemesin derivatives –
Primaquine is active against the dormant liver
stages
• WHO recommends artemesin- based
combination therapy (ACT)

74. • If treatment must be initiated before the
species is known treat as P .falciparum
• P falciparum should be presumed to be
chloroquine resistant, except in a few areas of
Central America and the Middle East
• Primaquine should be given if Plasmodium
vivax or Plasmodium ovale is likely

75. RESISTANCE PATTERNSRESISTANCE PATTERNS
 Chloroquine-resistant P falciparum:
Eastern Hemisphere: All of sub-Saharan Africa, Saudi Arabia,
Yemen, Iran, Pakistan, Afghanistan, China, Nepal, and all of
Southeast Asia
• Western Hemisphere: Panama, Haiti, Brazil, Peru, Bolivia,
Colombia, Venezuela, Ecuador, French Guiana, Guyana, and
Suriname
• -Chloroquine-sensitive P falciparum:
Eastern Hemisphere: Turkey, Iraq, Syria, Georgia, Azerbaijan,
Tajikistan, Turkmenistan, and Kyrgyzstan
Western Hemisphere: Argentina, Paraguay, Mexico, Guatemala, Costa
Rica, Honduras, Nicaragua, El Salvador, and Dominican Republic
• -Mefloquine-resistant P falciparum:
Southeast Asia: Regions of Vietnam, Laos, Thailand, Burma, and
Cambodia
• -Chloroquine-resistant P vivax:

76. • Blood Schizonticides
– may be used for
suppression or
treatment of an acute
attack of malaria
– Most have no effect
on either the pre-
(exo)erythrocytic
stages of the
parasites or
gametocytes
• Quinine (Quinidine)
• Chloroquine (Aralen,
Nivaquine)
• Hydroxychloroquine
(Plaquenil)
• Amodiaquine (Camoquin)
• Pyrimethamine (Daraprim)
• Mefloquine (Lariam)
• Tetraycycline
• Doxycycline
• Halofantrine
• Proguanil (Paludrine)
• Artemisinine (Qinghaosu)

77. • Tissue Schizonticides
• – Act as causal prophylactics by
destroying developmental stages of
parasite in the liver
• – Only primaquine is effective against
tissue stages

78. • Gametocyticides
– Chloroquine and
amodiaquine are
effective against
gametocytes of P.
vivax, P. ovale, and
P. malariae but not
mature gametocytes
of P. falciparum
– Primaquine works
against all four spp.
• • Chloroquine
• • Amodiaquine
• • Primaquine

79. Drug Resistance
• Drug resistance has been confirmed in P.
falciparum and P. vivax
• P. falciparum is usually completely
resistant to chloroquine
• Resistance in P. falciparum has been
documented with nearly all other drugs,
though this is less widespread
• P. vivax resistant to chloroquine in SE
Asia, India, and S. America

80. • Uncomplicated P falciparum infection :
• Artemether-Iumefantrine or,
• Atovaquone-proguanil or,
• Quinine or,
• Mefloquine.
• Uncomplicated Plasmodium malariae,
Plasmodium knowlesi, or chloroquine-
sensitive P falciparum infection:
• Chloroquine phosphate or,
• Hydroxychloroquine.
• Uncomplicated P vivax or P ovale
infection, expected to be chloroquine-
susceptible:
• Chloroquine phosphate or,

81. • Uncomplicated P vivax infection,
expected to be chloroquine-resistant:
• Quinine or,
• Atovaquone-proguanil or,
• Mefloquine or,
• Amodiaquine.

82. COMPLICATEDCOMPLICATED MALARIA
• Quinidine gluconate 10 mg/kg loading dose over
1-2h, then 1.2 mg/kg/h for at least 24h
• Once parasitemia is < 1% and patient can take
oral medication, switch to quinine 650 mg PO
TID to complete 3-d course (7-d course if
malaria was acquired in southern Asia)
• In addition, give doxycycline 100 mg IV or PO
BID for 7d.
• for pregnant women, instead of doxycycline, give
clindamycin 20 mg base/kg/day PO divided TID
for 7d

83. Other Measures in TreatingOther Measures in Treating
Severe MalariaSevere Malaria
– 1)1) Antibodies against TNF - α they
decrease fever
but no effect on mortality & morbidity
– reason Effects of other cytokines as IL –
1, TNF- β
• 2)2) Steroids
• - Harmful by controlled trials
• - Dexamethasone longer duration of coma + worse
outcomes than patient receiving quinine
alone (NEWJ 1982, Warrel et al)
• 3) Reducing mosquito – human contact
• 4) Malaria vaccine

84. Additional Supportive MeasuresAdditional Supportive Measures
· Blood Tx / Exchange Tx
· Hypoglycemia treatment and prophylaxis
especially in
pregnant women.
· Avoidance of IVF overload
· Dialysis
· Heparin for consumption coagulation
· Pregnant woman should receive
prophylaxis
· Non-immune travellers

85. Monitoring drug resistance
• THERAPEUTIC EFFICACY SURVEILLANCE or
TES
– Standardized protocols developed by WHO wherein
response is classified using clinical and parasitological
criteria
– Gold standard for treatment guidelines
– Limited by host immunity, prior treatment with
antimalarials, and drug pharmacokinetics/dynamics.
• IN VITRO TESTS
– Parasites are allowed to mature in microplates pre-
dosed with differing dilutions of antimalarial drug
– These tests provide baseline data and trends; forecast;
precede in vivo resistance
– HRP2 or pLDH, enzymes produced by the parasite can
also be measured

86. • MOLECULAR MARKERS of drug resistance
– P. falciparum – Chloroquine (pfcrt76), sulfadoxine
(dhfr51, dhfr59, dhfr108), and pyrimethamine (dhps436,
dhps437, and dhps540),
– Provide baseline data and trends
– Correlation between mutations and in vivo/in vitro data

87. • Chloroquine
• (10 mg of base/kg stat followed by 5 mg/kg at 12, 24, and 36
h or by 10 mg/kg at 24 h and 5 mg/kg at 48 h)
• or
• Amodiaquine
• (10–12 mg of base/kg qd for 3 days)

88. Radical Rx:
• Vivax or Ovale
• Primaquine
• (0.5 mg of base/kg qd) should be given
for 14 days to prevent relapse.
• In mild G6PD deficiency, 0.75 mg of
base/kg should be given once weekly for
6–8 weeks.
• Not be given in severe G6PD deficiency

89. Table 1 : Dosage and administration Coartem
(Artemether 20
mg/Lumefantrine 120 mg) for uncomplicated
malaria falciparum
Age group Weight group
Blister
color
(Day 1) (Day 2) (Day 3)
4 months
to 5yrs
5 to 14 kg Yellow
1 tb , 1 tb , 1 tb ,
1 tb  1 tb  1 tb 
6 to 11y 15 to 24 kg Blue
2 tb , 2 tb , 2 tb ,
2 tb  2 tb  2 tb 
12 to 14y 25 to 34 kg Orange
3 tb , 3 tb , 3 tb ,
3 tb  3 tb  3 tb 
> 14y > 34 Green
4 tb , 4 tb , 4 tb ,
4 tb  4 tb  4 tb 
Source: Guideline for the treatment of malaria, WHO; 2006

90. Table 2. Dosage and administration
Plasmodium
falciparum for young infant
Age Group
Weight
group
Artesunate or *Quinine
0 - 4
months
<5 kg
** IM first dose
Artesunate 1.2
mg/kg or IM
Arthemeter 1.6
mg/kg)
***Oral
Artesunate
2mg/kg/day
day 2 to day 7
Oral
Quinine 10
mg/TID for
4 days
then 15-20
mg/kg TID
for 4 days
Source: Malaria in Children, Department of tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University.
** Preferably Artesunate/Artemether IM on day 1 if available
*** When Artesunate/Artemether IM is unavailable, give oral Artesunate from day 1 to day 7
* Treat the young infant with Quinine when oral Artesunate is not available

91. Table 4a. Dosage and administration of Chloroquine
and Primaquine for malaria vivax.
Age Group
* Weight
group (Kg)
CHLOROQUINE
(150 mg base) 10 mg/kg on the
first two days.
5 mg/kg on day 3
PRIMAQUINE
(15 mg base)
0.5 mg/kg bw
Give for 3 days
Start concurrently with CQ
and give daily for 14 days
Day 1 Day 2 Day 3
4 months up to
12 months
4 - <10 ½ ½ ¼ -
13 months up to 5
years
10 - <19 1 1 ½ ¼
6 - 7 years 19 - < 24 1½ 1½ 1 ½
8 - 11 years 24 - <35 2½ 2½ 1 ¾
12 - 14 years 35 - < 50 3 3 2 1½
15 + 50 or more 4 4 2 2

92. Table 4b. Dosage and administration of
Chloroquine for malaria vivax in young infant
Age
Group
Weight
group
Chloroquine
Day 1 Day 2 Day 3
0 - 4
months
<5 kg 10 mg/kg 5 mg/kg 5 mg/kg

93. Falciparum
• Artesunatec (3 days)
• +
• Sulfadoxine/Pyrimethamine as a single dose
• or
• Artesunatec (3 days)
• +
• Amodiaquine (3 days)

94. Multidrug-resistant Falciparum
• Artemether-Lumefantrinec
• (bid for 3 days with food)
• or
• Artesunatec (3 days)
• +
• Mefloquine (3 days )

95. Second-line treatment/treatment of
imported
• Artesunatec (7 days) or Quinine(tid for 7 days)
• plus 1 of the following 3:
• 1. Tetracycline(qid for 7 days)
• 2. Doxycycline(qd for 7 days)
• 3. Clindamycin (bid for 7 days)
• or
• Atovaquone-Proguanil
• (qd for 3 days with food)

96. Follow-up of uncomplicated
malaria:
For adult:
• Quinine (10mg salt /kg bw three times a day) + doxycycline
(3.0mg/kg bw once a day) for 7 days. Do not give doxycycline
with milk or iron, which will reduce its absorption.
• If patient is in health facility where microscopy facility is not
available patient should be referred to the facility where
microscope is available. If refer is not possible treatment
should be given Quinine + Doxycycline. Please refer to Table 5 for
details of the prescription.
• Doxycycline should not be given to pregnant or lactating
woman, or child aged up to 8 years.
For pregnant or lactated woman or child less than 8 years:
• Quinine (10mg salt /kg bw three times a day) + clindamycin
(10mg/kg bw twice a day) for 7days. For small children,
(quinine and clindamycin) crush tablets and mix with water and
sugar.

97. • For high transmission areas where
parasitological confirmation is not
available, children <5 yrs of age is
recommended to be treated with anti
malarial drugs when symptomatic
(especially fever).

98. Pre-referral treatment of severe
malaria
• A patient who is non responsive should be quickly
assessed and managed. This includes assessment of
the airway, breathing and circulation. The staff at the
first level health facility should be able to maintain
airway, provide assisted breathing and manage shock
if required.
• Pre-referral treatment for severe malaria the
administration of Artesunate by the rectal route is
recommended for all except pregnant women first
trimester pregnancy. For the complete dosage and
treatment.
• Check blood sugar, if possible!

99. • In case Artesunate suppository is not
available IM quinine injection 20mg/kg bw
should be given. The Quinine injection
dosage should be split and injections
given in the anterior part of the thigh.
• In case Artesunate suppository is not
available, give also Quinine for children
with severe malaria.

100. • Very few areas now have chloroquine-
sensitive P. falciparum
• Tetracycline and Doxycycline should not be
given to pregnant women or to children <8
years of age
• Oral treatment should be substituted as soon as
the patient recovers sufficiently to take fluids
by mouth

101. • WHO now recommends Artemisinin-based
combinations as first-line treatment for
uncomplicated Falciparum

102. • Quinine, Quinidine...Common: Hypoglycemia
• Chloroquine.....Acute: Hypotensive shock
(parenteral), cardiac arrhythmias, neuropsychiatric
reactions
• Chronic: Retinopathy (cumulative dose, >100 g),
skeletal and cardiac myopathy
• Primaquine....Massive hemolysis in subjects with
severe G6PD deficiency

103. • Pregnant women with vivax or ovale malaria
should not be given Primaquine but should
receive suppressive prophylaxis with
Chloroquine (5 mg of base/kg per week) until
delivery, after which radical treatment can be
given.

104. • Summary (1)
• Malaria is a protozoan parasite with 5
species that affect humans
• Malaria transmission involves a mosquito
vector of the Anopheles species
• Children under 5 years old and pregnant
women are most at risk for malaria
• Sub-saharan Africa is the most affected
region in the world, accounting for 90% of
deaths from falciparum malaria.

105. • Symptoms of malaria include fever, but later,
coma and prostration are seen in severe malaria
• Diagnosis is made by microscopy looking at
blood smears, but also with Rapid Diagnostic
Tests (RDTs)
• Treatment is critical in terms of timing, kind of
drug and administration with respect to the
specifics of the patient and the local resistance
patterns.
• Understanding the biology and lifecycle of
malaria lends insight into strategy for diagnosis,
treatment and prevention (see previous module

106. Liver stage: 6 – 14 days
Blood stage: 48 – 72 hrs
Incubation period: 21 days

107. PITFALLS:
• Failure to take full travel hx, including stop-overs
in transit and failure to check if the patient has
already recieved treatment which might make
the blood smear negative.
• Delay in rx while seeking labs.
• Failure to examine enough blood films before
excluding the dx.
• Belief that drug will work, when the parasite is
one step ahead.
• Not having IV qiunine available immediately
(quinidine is an alternative)
• Not observing the falciparum pt. for first few day
• Forgetting that malarianis an imp cause of
coma , deep jaundice , severe anemia and renal
failure in the tropics

108. • Fevers of the South
• “Humanity has but three great enemies,
•
Fever, famine and war: of these by far the
•
greatest, by far the most terrible is fever.”
William Osler,1896