This is for learning purposes and not meant to replace any informed medical knowledge.

1. MALARIA
HALIMA IBRAHIM MEDICINE IV
SETH KAMIRE MEDICINE IV
MOI UNIVERSITY, SCHOOL OF MEDICINE

2. MALARIA
 Malaria is a mosquito –borne infectious disease affecting
humans and other animals caused by Plasmodium
species.
 Name is derived from Italian Mal’ aria or bad air
 Malaria continues to be most important cause of fever
and morbidity in the Tropical world
 Malaria has been eradicated from Europe, Most of North
America, USA South America Korea and Japan,

3. EPIDEMIOLOGY
 Kenya has 4 main malaria epidemiological zones,
 Highland epidemic prone areas-western highlands
 Endemic areas (lake and coast),
 Semiarid seasonal malaria transmission areas ,during the rainfall
seasons-northern and south eastern parts of Kenya
 Low risk malaria areas -central highlands of Kenya

4. Mapping Malaria in Kenya

5.  WHO estimates that 3.2 billion people are at risk of malaria worldwide
 In Kenya ,malaria remains a major cause of morbidity and mortality
with more than 70% of the population being at risk of disease (MOH
2014)
 Children under 5 and pregnant women are the most vulnerable to
infection

6. World Malaria Distribution

7. ETIOLOGY
 Malaria is caused by plasmodium species ,which are protozoal blood
parasites
 The following four species can infect humans
▪ P vivax- Central and South America, North Africa, Middle East, Indian
subcontinent; rare in Sub-Saharan Africa.
▪ P falciparum (most dangerous)- Africa, Haiti, Papua New Guinea
▪ P ovale- West Africa
▪ P malariae- mostly in Africa
▪ 5th species, Plasmodium knowlesi, causes malaria in macaques
(monkeys) but can also infect humans.

8.  Malaria is widespread in tropical and subtropical regions,
including parts of the Americas, Asia, and Africa.
 Falciparum accounts for 90% of deaths due to malaria and
vivax is the most widely spread species because it exists in
both temperate and tropical climates (Encarta).
 Transmission mainly by a bite from infected female
anopheles mosquito. Others through blood transfusion,
organ transplant, contaminated needles and congenital
(rare).

9. Risk Groups
Prematurity or low birth weight
Young children in stable transmission areas who have not yet
developed protective immunity against the most severe
forms of the disease;
Pregnant women in stable transmission areas as malaria
causes high rates of miscarriage and can lead to maternal
death;
People with HIV/AIDS;
International travellers from non-endemic areas
Immigrants from endemic areas and their children

10. Behavioral Risk Factors
 Poor rural populations in malaria-endemic areas often cannot afford the housing and
bed nets that would protect them from exposure to mosquitoes.
 Often, cultural beliefs result in use of traditional, ineffective methods of treatment.
 Travelers from non-endemic areas may choose not to use insect repellent or medicines
to prevent malaria. Reasons may include cost, inconvenience, or a lack of knowledge.
 Human activities can create breeding sites for larvae (standing water in irrigation
ditches, burrow pits)
 Agricultural work like harvesting may force increased nighttime exposure to mosquito
bites
 Raising domestic animals near the household may provide alternate sources of blood
meals for Anopheles mosquitoes and thus decrease human exposure
 War, migrations and tourism may expose non-immune individuals to an environment
with high malaria transmission.

11. Protective Factors
 Sickle cell trait- heterozygotes for the abnormal HbS gene
 Hereditary elliptocytosis
 Others: Hemoglobin C, the thalassemias and G6PD deficiency
 Negative Duffy antigen blood group & Hemoglobin E are
protective against P. vivax
 Acquired immunity after repeated attacks- partially protective
 Newborns in the 1st few months of life presumably by maternal
antibodies transferred to them through the placenta.
 ITNs

12. Protective Factors Cont’
1)Sickle cell trait; Sickle trait RBCs infected with P. falciparum deform, presumably bcoz the
parasite reduces the oxygen tension within the RBCs to very low levels as it carries out its
metabolism. Deformation of sickle trait RBCs marks these cells as abnormal & targets them for
destruction by phagocytes.
2) G6PDH deficiency; Glucose-6-phosphate dehydrogenase prevents oxidation of the heme
group. In its absence/deficiency, hemichromes & other species that generate reactive oxygen
species accumulate in RBCs (Janney, et al., 1986). Malaria parasites are easily damaged by these
reactive oxygen species (Friedman, 1979).
(1 & 2 protect against severe disease)

13. Protective Factors Cont’
3) Duffy null phenotype – Duffy antigen is the receptor by which P. vivax merozoites enter
RBCs. People who lack the Duffy antigen (FY*O allele) are resistant to P. vivax. The
Duffy null phenotype is most common in people whose ancestors derive from regions in
Africa where vivax malaria is endemic(suB-saharan,north africa)
4) Thalassemias; imbalance in globin chain production characteristic of thalassemia
produces membrane oxidation by hemichromes & other molecules that generate reactive
oxygen species that injure & kill malaria parasites . Thalassemic erythrocytes adhere to
parasitized RBCs much less readily than their normal counterparts. This alteration lessens
the chance of developing cerebral malaria.

14. Environmental Factors
Factors that provide favorable breeding grounds for mosquitoes
▪ Stagnant water pools
▪ Bushy surroundings
▪ Cluttered compounds
▪ Dark areas in the house

15. Transmission
Transmission mainly by a bite from infected female anopheles mosquito. Others
through blood transfusion, organ transplant, contaminated needles and
congenital (rare).
Transmission of Malaria do not occur in <160c and >330c and > 2000 m altitude.
Man – Intermediate host.
Mosquito – Definitive host
– Sporozoites are infective forms
Sporozoites are present in the salivary gland of female anopheles mosquito
After bite of infected mosquito, sporozoites are introduced into blood
circulation.

16. Incubation Period
Which includes Exo eythrocytic cycle time and 1 or 2
erythocytic cycles and varies according to species:
 P. vivax and P. falciparum 10 – 15 days (can vary from weeks
to months)
 P. malariae infection can start after 28 days.
 P. ovale 8 – 24 days

17. Human Cycle
1 Pre erythrocytic
schizogony
2 Erythrocytic Schizogony
3 Gametogony
4 Exoerythrocytic
schizogony

18. Human Life Cycle
 The bite of an infected mosquitoes. Introduces asexual forms of the
parasites called sporozoites into the blood stream
 Sporozoites enter the hepatocytes and transform to schizontes which are
also asexual forms
 Schizonts undergo a process of maturation and multiplication known as
preerythrocytic or hepatoschizogony.
 In p.vivax and p ovale infection sporozoites convert to dormant forms
called hypnozoites which can cause disease after months or years
 Pre erythrocytic schizogony takes 6-16 days and results in the host cell
bursting and releasing thousands of merozoites into the blood

19. Human Life Cycle
 Merozoites enter the erythrocytes and initiate another asexual
reproductive cycle known as erythrocytic shizogony.
 The parasites successfully passes through the stages of trophozoite and
schizont ultimately giving rise to several merozoites.
 Upon maturation merozoites the erythrocytes ruptures releasing the
merozoites and multiple antigenic and pyrogenic substance into the
bloodstream.
 The merozoites again infect a new erythrocytes .
 After few cycles of this erythrocytic schizogony ,some merozoites
differentiate into the sexual forms ;the male and female gametocytes

20. Mosquito Cycle
 A mosquito takes a blood
meal, from a patient with
gametocymia acquires
these sexual forms and
plays host to the sexual
stage of the plasmodial
life cycle.
 Cycle repeats every 48
hours in P.falciparum,
P.ovale, P.vivax
 Cycle repeats every 72
hours in P.malariae

21. A Complex Life Cycle

22. Life Cycle of Plasmodium

24.  Malaria parasite induce release of cytokines i.e TNF-alpha, gamma IFN
which in turn induce release of a cascade of other pro-inflammatory
cytokines e.g IL-8, IL-12, IL-18
 Cytokines are responsible for many symptoms and signs of infection,
particularly fever and malaise.
 Plasma inflammatory cytokine conc. Are inc in both acute P.vivax and
P. falciparum malaria.
 In vivax malaria, a pulse release of TNF occurs at time of shizont rupture
and is followed by xteristic symptoms and signs of ‘paroxysm’ i.e
shivering, cool extremities, headache, chills, spike of fever.
PATHOGENESIS
1. Toxicity & Role of Cytokines

25.  Cytokines are involved in suppression of erythropoiesis(TNF-α), and
inhibition of gluconeogenesis, and fever
 Cytokines may also be important mediators of parasite killing by
activating leukocytes to release toxic oxygen species and NO, and by
generating parasiticidal lipid peroxidase
 So, whereas high conc of cytokines may be harmful, lower levels
promote parasite clearance.

26. 2. Sequestration & Cytoadherence
 RBCs adhere to the capillary and post capillary venular endothelium in the deep
microvasculature.
 Mediated by the electron-dense protuberances on the surface of the infected
erythrocyte.
 These 'knobs' are expressed during the trophozoite and schizont stages and are
formed as a result of parasite proteins exported to the erythrocyte membrane (
restricted to P. falciparum)
 PfEMP-1 ( P. falciparum erythrocyte membrane adhesive protein) is the
cytoadherence ligand that mediates attachment to receptors on venular and
capillary endothelium.
 It can block /impair blood flow due to it’s large numbers. This further interferes
with the microcirculation and metabolism and allows parasite development
away from the principal host defense, splenic processing and filtration

27.  Cytoadherence leads to sequestration of the parasites in various organs such
as the heart, lung, brain, liver, kidney, intestines, adipose tissue, subcutaneous
tissues, and placenta
 Mediated by pfEMP-1, sequestrin, ICAM-1 (brain), chondroitin sulfate B
(placenta), and CD36 (other organs)
 Interfere with microcirculatory flow and metabolism. Blocks blood flow,
limits the local oxygen supply, hampers mitochondrial ATP synthesis, the
avoidance of the spleen and the subsequent elimination of infected
erythrocytes.

28.  Several sticky proteins present on the surface of vascular endothelium have
been shown to bind parasitized red cells, most important being CD36
 CD36 is constitutionally expressed on vascular endothelium & monocytes and
but not on surface of cerebral vessels
 CD36 is expressed platelets, & platelets may form a bridge btwn infected
erythrocytes and vascular endothelium
 The intercellular adhesion molecule (ICAM) appears to be the major
cytoadherence receptor in the brain
 Other endothelial proteins VCAM, PECAM, E-selectin and alpha/beta integrin,
have been shown to bind in some circumstances
3. Vascular Endothelial Ligands

29.  Erythrocytes containing mature parasites also adhere to uninfected erythrocytes;
leading to formation of ‘rosettes’
 Parasite species that don’t sequester do form rosettes e.g P. vivax, whereas all fresh
isolates of P. falciparum cytoadhere, not all rosette
 Unlike cytoadherence, resetting is inhibited by certain heparin subfractions & calcium
chelators
 Rosetting is mediated by attachement of specific domains of PfEMP1 to the
complement receptor CR1, heparin sulphate, blood group Ag A, and probably other
red cell surface molecules
 Attachement is facilitated by serum components
 Rosetting may encourage cytoadherence by reducing flow, which would enhance
anaerobic glycolysis, reduce pH , and facilitate adherence of infected erythrocytes to
venular endothelium
4. Rosetting & Aggregation

30.  Trophozoites feed on hemoglobin forming a food vacuole .The amino acids
are utilized for protein synthesis and heme detoxified by heme polymerase
and sequestered as hemozoin .This reduces the concentration of Hb in blood
(low MCHC).
 The parasite gets energy from anaerobic glycolysis of glucose using
plasmodium LDH. The glucose is metabolized to lactate. This results in
hypoglycemia and lactic acidosis.
5. Parasite nutrition

31. a) Results from:
 Hemin-induced oxidative damage of the red cell membrane
 Alterations in the phospholipid bilayer and attached spectrin network by the
proteins transported to the red cell membrane
 Thermally driven membrane fluctuations due to fever
 Inhibition of the Na+/K+ pump on the red cell membrane, possibly by nitric
oxide (NO)
b) Reduced RBC deformability leads to increased splenic clearance and
loss of red cells, causing anemia. Hemolysis, suppression of erythropoiesis by
cytokines, and hemozoin-induced apoptosis in developing erythroid cells also
contribute to the development of anemia in severe malaria.
6. RBC Membrane Rigidity & Deformability

32. PATHOPHYSIOLOGY
Result from:
 Destruction of erythrocyte, both infected and
uninfected
 The consequent liberation of parasite and erythrocytic
material into circulation
 Host reaction to these events

33. PATHOPHYSIOLOGY Cont’
 Four important pathologic factors have been identified in patients with
malaria
1. Fever
2. Anaemia
3. Immunopathologic events
4. Tissue anoxia

34. 1. Fever
 Occurs when erythrocytes rupture and release merozoites into the
circulation

35. 2. Anaemia
 Anemia is caused by hemolysis, sequestration of erythrocytes in the
spleen and other organs, and bone marrow suppression.

36. 3. Tissue Anoxia
 Cytoadherence of infected erythrocytes to vascular endothelium
occurs in P. falciparum malaria and may lead to obstruction of blood
flow and capillary damage, with resultant vascular leakage of blood,
protein, and fluid and tissue anoxia
 The cumulative effects of these pathologic processes may lead to
cerebral, cardiac, pulmonary, intestinal, renal and hepatic failure.

37. 4. Immunopathologic Events
 Immunopathologic events that have been documented in patients with
malaria include excessive production of proinflammatory cytokines, such
as tumor necrosis factor, that may be responsible for most of the
pathology of the disease, including
1. Tissue anoxia;
2. Polyclonal activation resulting in both hypergammaglobulinemia and
the formation of immune complexes; and immunosuppression

38. CLINICAL PRESENTATION

39. CLINICAL PRESENTATION
 Malaria can mimic any febrile illness and should be suspected in any febrile child who
has recently been in malarious area
 Older children may manifest the classic periodicity of fever with chills and shivering,
sweating.
 After the mosquito bite children are asymptomatic while the parasite complete the
liver cycle and 1 erythrocytic cycle which takes 8-18 days depending on the species.
 Children then become restless, drowsy ,apathetic and anorexic
 Older children may report body aching ,headache and nausea.

40. CLINICAL PRESENTATION
 Fever is usually continuous and may be very high(40 c) from the first day
 Many children have only flu like respiratory symptoms with mild cough and cold,
 Vomiting, mild diarrhea with dark green mucoid stools
 Occasionally profuse diarrhea with dehydration and circulatory failure
 Seizures can be before or with fevers
 Babies that got infected through transplacental transmission have fever ,are irritable,
refuse feeds, often develop anemia ,jaundice and hepatosplenomegaly

41. Physical examination
 Temperature of 40 and higher are often observed
 Liver may be slightly tender with hepatomegaly
 Dehydration
 Splenomegaly takes many days, in children from an endemic area ,severe
splenomegaly sometimes occurs
 Pallor in prolonged malaria
 Mild jaundice ,with heavy parasitemia and large scale destruction of
erythrocytes.

42. Paroxysmal
 Malaria tertiana: 48h between
fevers (P. vivax and ovale)
 Malaria quartana: 72h
between fevers (P. malariae)
 Malaria tropica: irregular high
fever (P. falciparum

43. Differential diagnosis
 Viral infections such as influenza ,
 hepatitis
 Pneumonia
 Menengitis, encephalitis
 Endocarditis
 Gastroenteritis
 Pyelonephritis
 Tuberculosis
 Typhoid fever
 Yellow fever

44. INVESTIGATIONS
DIAGNOSTIC
1.Microscopy:
– Thin and thick blood smears for malaria parasites.
– Thick films: Parasite detection , quantification and monitoring treatment.
– Thin films: Species Identification.
– Sensitivity: 86-96%.
Plus system:
+ represents 1-10/100 thick blood films
++ represents 11-100/100 thick blood films
+++ represents 1-10 per single thick blood film
++++ > 10 parasites per single thick blood film

45. Microscopy – Gold standard
Thin and thick slides
➢ 86-98% Sensitive for high
parasitemia(> 320/uL);
➢ Thick- for parasite detection &
quantification of palsmodium
density. Treatment monitoring
➢ Thin- for species identification
(qualitative).
➢ 1 -ve smear doesn’t R/o malaria. @ least
3 smears should be taken

47. INVESTIGATION CONT’D
2.QBC - Quantitative Buffy Coat
3.PCR – Polymerase chain reaction
4.RDT – Rapid Diagnostic Test
 Immunochromatographic
 Detect parasite antigen Eg pLDH, HRP
5.Clinical chemistry –LFTs, U/E/C,RBS
6.Complete blood count.
7. CSF analysis-gross appearance,glucose,protein,m/c/s

48. COMPLICATIONS
 The World Health Organization has identified 10 complications of
P.falciparum malaria that define severe malaria
 The most common complications in children are
1. severe anemia,
2. impaired consciousness (including cerebral malaria),
3. respiratory distress (a result of metabolic acidosis),
4. multiple seizures,
5. prostration
6. jaundice.

49. WHO CLASSIFICATION OF SEVERE
MALARIA
Common and associated with
higher mortality
 Altered level of consciousness
 Convulsions
 Respiratory distress
 Severe anemia(<5g/dl)
 Hypoglycemia(blood glucose of
<2.5mmol/l or <48mg/dl)
 Prostration(inability to sit up or feed in
young infants
Uncommon
 Hyperparasitemia
 Renal impairment
 Abnormal bleeding
 Circulatory collapse
 Pulmonary oedema
 Jaundice
 Haemoglobinuria
 acidosis

50. Severe Malaria Anemia (<5g/dl)
 ls the most common severe complication of malaria in children and is the
leading cause of anemia leading to hospital admission in African children.
 Anemia is associated with hemolysis, but removal of infected erythrocytes by
the spleen and impairment of erythropoiesis likely play a greater role than
hemolysis in the pathogenesis of severe malarial anemia.
 With appropriate and timely treatment, severe malarial anemia usually has a
relatively low mortality This is indicated by severe palmar pallor, often with a
fast pulse rate, difficult breathing, confusion or restlessness.
 Signs of heart failure such as gallop rhythm, enlarged liver and, rarely,
pulmonary edema (fast breathing, fine basal crackles on auscultation) may
be present
 Rx transfuse 10mls/kg of PRBC in 2-4hrs OR 20MLS/kg of whole blood over 4hrs
urgently.

51. Severe Anemia Cont’
 Begin treatment with iron and folate imm. after completion of antimalarial treatment
or on discharge (omit iron for any child with S. malnutrition until recovery).
❖ Give a daily iron–folate tablet or iron syrup for 14 days; Ask the parent to return with
the child in 14 days.
❖ Treat for 3 months, as it takes 2–4 weeks to correct anaemia and 1–3 months to build
up iron stores.
❖ If the child is > 1 year and has not received mebendazole in the previous 6 months,
give one dose of mebendazole (500 mg) for possible hookworm or whipworm
infestation

52. Cerebral Malaria
 Is defined as the presence of coma in a child with P. falciparum parasitemia
and an absence of other reasons for coma.
 Children with altered mental status who are not in coma fall into the larger
category of impaired consciousness
 Cerebral malaria has a fatality rate of 15-20% and is associated with long-term
cognitive impairment in children.
 Physical findings: fever, seizures, muscular twitching, rhythmic mvt of the head
or extremities, contracted or unequal pupils, retinal hemorrhages, hemiplegia,
absent or exaggerated deep tendon reflexes, and +ve Babinski sign
 LP reveals increased pressure and CSF protein with no pleocytosis and normal
glucose and protein concentrations.

53. Hypoglycaemia
 Hypoglycemia (RBS <2.5 mmol/litre or <45 mg/dl) is particularly common
in children <3 years old, in children with convulsions or
hyperparasitaemia, and in comatose patients.
 Occurs as a result of anaerobic metabolism of glucose
 It is easily overlooked because clinical signs may mimic cerebral
malaria.
 Give boluses of 5 ml/kg of 10% dextrose IV rapidly or give sublingual
sugar solution. Ensure maintenance fluid has at least D5W or is fed.
Recheck RBS after 30 min, and repeat the dextrose (5 ml/kg) if the level
is still low.

54. Metabolic Acidosis
 This presents with deep breathing while the chest is clear—sometimes
accompanied by lower chest wall indrawing.
 Lactic acidosis due to anaerobic metabolism of glucose.
 It is caused by systemic metabolic acidosis (frequently lactic acidosis)
and may develop in a fully conscious child, but more often in children
with cerebral malaria or severe anaemia.
 Leads to respiratory distress ,making it a poor prognostic factor
 Rx is by high frequency mechanical ventilation to reduce lung injury.
Indications: Arterial blood pH <7.2, PCO2 ≥60mmHg, PO2 ≤50mmHg &
persistent apnea.

55. Convulsions
 Give anticonvulsant treatment with rectal diazepam or slow IV injection. Slow IV diazepam
0.3mg/kg, or paraldehyde 0.1 ml/kg will usually control convulsions OR diazepam PR 0.5mg/kg.
 If there are repeated convulsions, give IM Phenobarbitone 15mg/kg loading dose then
2.5mg/kg/day for 48hrs OR IV Phenytoin: 15mg/kg loading (iv over 20-30 mins), then
maintenance at 5mg/kg/day

56. Acute Renal Failure
 Renal tubular necrosis
➢RBC sequestration interferes with microcirculation
➢Cellular injury upon microvascular obstruction
 Mild in young children, worse in older
 In survivors, urine flow resumes in a median of 4 days, and serum
creatinine levels return to normal in a mean of 17 days

57. Black Water Fever
 Large amounts of hemoglobin & malarial pigments may be present in
the urine 2o to massive intravascular hemolysis, producing dark urine
 It is a manifestation of infection with P. falciparum occurring in persons
who have been previously infected and have had been inadequate
dose of quinine
 It is characterized by intravascular hemolysis fever, and
Haemoglobunuria
 Cardiovascular collapse and shock
 Abnormalities in blood coagulation and thrombocytopenia (decrease in
blood platelets)

58. Jaundice
 Mild jaundice due to hemolysis in malaria is common.
 Severe jaundice due to
➢ hemolysis
➢ hepatocyte injury(sequestration in hepatic microvasculature), and
➢ cholestasis may occur in the setting of P. falciparum infection
 Hepatic dysfunction contributes to hypoglycemia, lactic acidosis, and
impaired drug metabolism.

59. Pulmonary Edema
 Sequestration of parasitized RBCs in the lung
 increased leakage from the pulmonary vasculature resulting from
cytokine release.
 IV Fluid overload at Rx may also be a culprit.

60.  Maintenance IVF-IF patient not able to take orally.
 DO NOT GIVE bolus IVF unless the patient has signs of circulatory
collapse resulting from diarrhea.
Maintenance IVF

61. Other Supportive Rx
 Respiratory distress-oxygen as required can be used.
 Febrile children-paracetamol 10-15mg/kg/dose 8hourly.
 Coma- Check ABC, maintain airway, place patient on his side, exclude other causes of coma
like hypoglycemia, bacterial meningitis. Skin care & bladder care, chest physiotherapy,
nutritional support. Do not use steroids, intubate if necessary. Proper nursing care to avoid
aspiration & pressure sores.

62. Long-term complications
HYPEREACTIVE MALARIAL SPLENOMEGALY
 Hypergammaglobulinaemia, normocytic normochromic anemia, splenomegaly.
 Patients exhibit abnormal immunologic reaction to repeated infection-massive
splenomegaly, hepatomegally, elevated IgM, hepatic sinusoidal lymphocytosis and
peripheral B cell lymphocytosis.
 There is uninhibited B cell production of IgM & formation of cryoglobulins.
 Results in Reticuloendothelial hyperplasia and splenomegaly.
 Diagnosed by biopsy of liver.
 Chemoprophylaxis- proguanil.

63. Long-term complications Cont’
 BURKITTS LYMPHOMA AND EBV
-Malaria related immunosuppression provokes infection with lymphoma causing viruses.
-Prevalence of this childhood tumor high in malarious areas
➢ Neurologic complications-Some 10% of children who survive cerebral malaria will
have neurological sequelae, which will persist into the convalescent period.

64. TREATMENT
Uncomplicated malaria
Supportive Rx
 Fever :hyperpyrexia (T>39.5°C)-paracetamol or Ibuprofen +
mechanical methods.
 Adequate fluids and nutrition.
Definitive Rx.
-First line is artemisinin combination therapy as outpatient.

65. ACT
Artemisinin-based Combination Therapy;
 Artemether plus lumefantrine,
 Artesunate plus amodiaquine,
 Artesunate plus mefloquine,
 Artesunate plus sulfadoxine-pyrimethamine (Fansidar)
 Dihydroartemisinin plus piperaquine

66. Uncomplicated Malaria
1st line
Artemether (20mg) + Lumefantrine (120mg) (artemisinin)
Dosing
 <5kg ………………….……….…1/2 tablet
 5 – 14 kg (5mnth - 3yrs)………1 tablet
 15 – 24 kg (3 - 7 yrs)…………..2 tablets
 25 – 34 kg (8 - 11 yrs)……...….3 tablets
 >34kg ( >12yrs)…………………4tablets
Stat, +8hrs, BD on Day 2 and Day 3
Give with food. Fatty foods increase absorption.

67. Uncomplicated Malaria
2nd Line
Dihydroartemisinin - piperaquine
Dosing
 3 – <3yrs…………..……….1 paed tab
 3 - 5 yrs……………….…….2 paed tabs
 6 - 11 yrs……………………1 adult tab
 12-16yrs…………………….2 adult tab
 >16yrs………………………3 adult tab
OD for 3 days

68. Severe Malaria
 Fever plus any of:
❖ AVPU=V,P,U OR
❖ Unable to drink OR
❖ Respiratory distress with acidotic breathing OR
❖ Severe anaemia OR
❖ Hypoglycemia <2.5mmols/l OR
❖ >2 convulsions
 If a high quality blood slide is negative with signs of SEVERE malaria, start
presumptive treatment BUT REPEAT testing and STOP treatment if test is
negative

69. Severe malaria(WHO criteria)
Defining Criteria Finding
cerebral malaria (unarousable coma) Unarousable coma (GCS <11/15) not attributable to any other
cause in a patient with falciparum malaria. Coma should persist at
least 30 mins after a generalized convulsion to make the distinction
from transient post-ictal coma.
severe anemia Normocytic anemia with HCT <15% or Hb <5 g/dL in the presence
of parasitemia >10,000/µL. If microcytic indices seen, need to
consider IDA, thalassemia and hemoglobinopathy.
renal failure urine output <400 mL in 24 h in adults, or ,12 Ml/kg in children,
failing to improve after rehydration, and serum creatinine >265
µmol/L (>3 mg/dL)
Respiratory distress Pulmonary edema or ARDS. Also rapid labored
‘acidotic’ breathing sometimes abnormal in rhythm

70. hypoglycemia whole blood glucose <2.2 mmol/L (<40 mg/dL)
circulatory collapse, shock hypotension (systolic blood pressure <50 mm Hg in
children 1-5 years old; <70 mm Hg in adults) with
cold, clammy skin or a core-skin temp difference
>10°C
spontaneous bleeding. DIC spontaneous bleeding from gums, nose, GI tract or
other sites, with laboratory evidence of DIC
repeated generalized seizures more than 2 observed seizures (>=3) within 24 hours
despite cooling
acidemia or acidosis arterial pH <7.25, plasma bicarbonate <15 mmol/L
malarial hemoglobinuria need to exclude hemoglobinuria due to
antimalarial medications and to G6PD deficiency

71. Complicated Malaria
Impaired consciousness of any degree, Prostration,
Jaundice, Intractable vomiting, Parasitaemia ≥2% in non-
immune individuals (no previous malaria)
Such patients with complicated malaria should be
managed as severe malaria, i.e. with parenteral
antimalarials even though they do not necessarily meet
the criteria of severe disease.

72. Treatment of Severe Malaria
 Parenteral artesunate is the drug of choice for the treatment of severe P.
falciparum malaria. If it is not available, parenteral artemether or quinine
should be used.
1. Artesunate: Give at 3mg/kg/dose for wt ≤ 20Kg and 2.4mg/kg/dose for wt>20kg IV or IM
on admission 0h, then12 h & then 24 h, then OD until the child can take PO but
for a min of 24 h even if the child can tolerate PO earlier or for max of 7 days.
2. Quinine: Give a loading dose of quinine dihydrochloride salt at 20 mg/kg by
infusion in 10 ml/kg of IVF or D10W over 2–4 h. Then after 8 h give 10 mg/kg
quinine salt in IVF over 2 h, and repeat q8h until the child can take PO or for 7
days. The infusion rate should not exceed a total of 5 mg/kg/h of quinine
dihydrochloride salt.
N/B: IV quinine should never be given as a bolus injection but as a 2–4 h infusion
under close nursing supervision.

73. Treatment of Severe Malaria
For IM Quinine
 take 1ml of the 2mls in a 600mg Quinine suphate iv vial and add 5mls water for
injection – this makes a 50mg/ml solution. Do not give more than 3mls per injection site.
Quinine syrup is not recommended since its bioavailability, stability & efficacy in oral
formulations has not been established. ACT syrup are also not recommended since
Artemether is unstable in liquid form unless freshly constituted as in dispersible tablets or
satchets preparations.
3. Artemether: Give artemether at 3.2 mg/kg IM on admission, then 1.6 mg/kg daily until
the child can take oral medication.
Give parenteral antimalarial agent for the treatment of severe malaria for at least 24 h;
thereafter, complete treatment with a full course (3 days) of artemisinin-based combination
therapy typically the 1st line oral anti-malarial, AL OR Quinine tabs for IV Quininie Rx

74. Anti-malarial drug doses & preparation
ARTESUNATE
 Artesunate typically comes as a powder together with a 1ml vial of 5% bicarbonate
that then needs to be further diluted with either normal saline or 5% dextrose - the
amount to use depends on whether the drug is to be given iv or im (see table below)
 DO NOT use water for injection to prepare artesunate for injection
 DO NOT give artesunate if the solution in the syringe is cloudy
 DO NOT give artesunate as a slow iv drip (infusion)
 YOU MUST use artesunate within 1 hour after it is prepared for injection
 Weight ≤ 20Kg at 3mg/kg/dose and >20Kg at 2.4mg/kg/dose of Artesunate

75. Preparing IV/IM Artesunate
IV IM
Artesunate powder (mg) 60 mg 60 mg
Sodium Bicarbonate (mls,5 % ) 1 mL 1 mL
Normal Saline or 5% Dextrose (mls) 5 mL 2 mL
Artesunate concentration (mg/ml) 10 mg/mL 20mg/mL

76. Quinine IV
For IV infusion typically 5% or 10% dextrose is used.
 Use at least 1ml fluid for each 1mg of quinine to be given
 DO NOT infuse quinine at a rate of more than 5mg/kg/hour
❖ Use 5% Dextrose or normal saline for infusion with 1 ml of fluid for each 1mg of quinine.
❖ The 20mg/kg loading dose therefore takes 4 hours or longer
❖ The 10mg/kg maintenance dose therefore takes 2 hours or longer

77. Quinine IM
 Take 1ml of the 2mls in a 600mg Quinine sulphate IV vial and add 5mls water for injection - this
makes a 50mg/ml solution.
 For a loading dose this will mean giving 0.4mls/kg
 For the maintenance dosing this will mean giving 0.2mls/kg
 If you need to give more than 3mls (a child over 8 kg for a loading dose or over 15kg for
maintenance doses then give the dose into two IM sites – do not give more than 3mls per injection
site.
Quinine PO
 For oral Quinine 200 mg Quinine Sulphate = 200mg Quinine Hydrochloride or
 Dihydrochloride but = 300mg Quinine Bisulphate. The table of doses below is ONLY
 correct for a 200mg Quinine Sulphate tablet.

78. Quinine S/E
 Cinchonism- tinnitus, high tone deafness, visual disturbances,
headache, dysphoria, nausea and vomiting and postural hypotension
 Hypoglycemia
 Cardiac arrhythmias

79. Treatment Failure
 Get Hx of compliance, vomiting of meds
 Repeat microscopy- fever and a +ve blood slide after 14 days, assume it is
another attack and repeat 1st line.
 Repeat full 1st line dose in Non compliance
 Consider other causes of illness / co-morbidity
 A child on oral antimalarials who develops signs of severe malaria (Unable to
sit or drink, AVPU=U or P and / or respiratory distress) at any stage should be
changed to IV Artesunate (or Quinine if not available).
 If a child on oral antimalarials has fever and a +ve blood slide after 3 days
(72 hours) then check compliance with therapy and if treatment failure
proceed to 2nd line treatment.

80. PREVENTION
 Effective case management
 Halt malaria transmission- ITN, spraying, repellants, long sleeve clothes
 Vector control - larviciding
 Chemoprophylaxis- mefloquine, proquanile, malarone
 Environmental management- clear bush, drain still waters
 Indoor residual spraying, bed nets treated with long-lasting insecticide
 Access at all public health facilities to effective malaria treatment and
diagnosis, and
 Community health workers trained in dealing with malaria.

81. PREVENTION
The vector mosquitoes that transmit malaria usually feed at night; thus, it is
advisable to diminish exposure between dusk and dawn by:
-Remaining in screened areas whenever possible Using mosquito
netting, ideally treated with permethrin
-Covering exposed skin with clothing Applying insect repellent.
 Chemoprophylaxis is necessary for all visitors to and residents of the
tropics who have not lived there since infancy
• Chemoprophylaxis should be started 1–2 wk before entering the
endemic area (except for doxycycline administration, which can begin
1–2 days before departure) and continue for at least 4 wk after leaving.

82. Chemoprophylaxis
 Non-immune visitors- mefloquine or atovaquone-proguanil or
doxycycline.
 Sickle cell disease patients- proguanil 3.5mg/kg daily
 Patients with hyperimmune malaria splenomegaly- proguanil.

83. References
i. Nelson’s textbook of paediatrics 20th edition.
ii. Medscape
iii. Kenya Malaria treatment guide lines
iv. Kenya Ministry of heakth,malaria control
v. WHO treatment guideline
vi. MTRH CHAP protocol.

84. WORLD MALARIA DAY
(25th April)
SETH KAMIRE- SKAMIRE92@GMAIL.COM
MEDICAL STUDENT