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1. PAEDIATRIC / ADULT MALARIA
BY: BOATENG DANQUAH COLLINS

2. Overview
• Historical perspective
• Aetiology
• Epideomology
• Pathogenesis
• Clinical manifestation
• Diagnosis
• Types of malaria and its presentation
• Management/Treatment
• Complications
• Prevention

3. Historical Perspective
• Malaria is an ancient infection.
• The Greek physician Hippocrates described malaria in
his writings during the 400 s BC.
• Malaria associated with marshes & swamps by
Etruscans (1st
millennium BC) = “Marsh Fever”
• The name “Mal” & “aria” means “bad air” (Italian).

4. Bad air = Malaria
Frontage of LUTH

5. Bad air = Malaria
Scenery around LUTH Canal

6. Historical Perspective
• The exact cause unknown
until late 19th century.
• Charles Alphonse Laveran
[1880], a French surgeon
identified the malaria
parasite in blood of patient.

7. Historical Perspective
• Sir Ronald Ross [1899], a British
physician, demonstrated human to
human plasmodium transmission
by female Anopheles mosquito.
• 1902 Nobel prize for medicine.
• Also is found in apes, monkeys, rats,
birds and reptiles.

8. Historical Perspective
• The 1st
malaria treatment
(1638).
• “Found” when Spanish Jesuit
priests brought Cinchona tree
bark [the source of quinine]
back to Europe from South
America.

9. Historical Perspective
• In 2002 the Plasmodium falciparum genome
decoded.
• Recently, scientists have also decoded genome
sequence of Anopheles gambiae.
• Scientists hope to use information to design
more effective anti-malaria drugs and vaccines.

10. Aetiology
• Malaria is a disease which can be transmitted to people of all
ages.
• It is caused by parasites of the species Plasmodium
• They are spread from person to person through the bites of
infected mosquitoes.
• Via blood transfusion
• Parasite: Plasmodium Sp. – an intracellular protozoan.
– P. vivax.
– P. falciparum.
– P. ovale.
– P. malariae.
• Host: Man.
• Vector: Anopheles (female).

11. Human Plasmodia
P. Vivax P. Falciparum
The most prevalent The most Virulent

12. Epidemiology
• Malaria is a worldwide disease.
• Probably more cases than any other infection.
• It is the leading communicable disease in the
tropics & sub-tropics.
• An estimated 2 billion (about ⅓ of the world
population) exposed to the risk of infection.

13. Disease burden In The World
• Malaria is the world's most important tropical parasitic disease.
– 300 - 500 million clinical cases / year
– 1.5 - 2.7 million deaths / year
– Occurs in 100 countries
– 2.4 billion persons are at risk
• Most cases and deaths (90 %) occur in sub-Saharan Africa,
– mainly in young children.
– Population living in highly endemic areas 74%
– Children likely to die before 5 years of age 5%
– A drain on the resources of both the government and individuals,
• Direct and indirect costs of malaria = USD2,6 Billion

14. Global Distribution of Malaria

15. Epidemiology
• >10% of all deaths in infants & children under-3s
ascribed to malaria.
• Conservatively, about 1 million African deaths every
year.
• About 60% of our hospital patient attendance.

17. Bad air = Malaria
Same @ Frontage of OAUTHC (WGH)

18. Epidemiology
• Falciparum causes the severe & fatal forms of malaria
– It requires higher temperatures for optimal development.
– It is confined more closely to the tropics.
• Vivax + falciparum = 95% of all malaria infections.
• Vivax malaria is the most widespread variety;
– B’cos it is able to withstand therapy & remain chronic.

19. Disease Burden In Ghana
• Malaria is prevalent throughout Ghana
– over 20 million people at risk.
– Epidemics are common and cause high mortality and morbidity every year.
– Malaria contributed over 45% of the causes of outpatient attendance in
2003.
– Malaria also contributes between 30% to 36% of all causes of admissions
– it is the highest cause of death with a mortality rate of 15% to 30%

20. Epidemiology
• Malaria kills over one million children every year
• 90% of malaria deaths occur in sub-Saharan
Africa
• A child dies of malaria every 30 seconds
• Deaths occur within 48 hours of developing
symptoms
• 3000 deaths per day
• ?Prevalence in ghana unknown

21. Epidemiology
• Malaria during pregnancy in malaria-endemic
settings may account for:
– 5-14% of low birth weight newborns
– 30% of “preventable” low birth weight newborns

23. Why Is the Issue of Malaria During Pregnancy
Important
• Each year, more than 30 million women in Africa
become pregnant in malaria-endemic areas.
• Malaria during pregnancy in malaria-endemic
settings may account for:
– 2-15% of maternal anemia
– 5-14% of low birth weight newborns
– 30% of “preventable” low birth weight newborns
– 3-5% of newborn deaths

24. Effect of Malaria on Pregnancy in
Stable Transmission Areas
Asymptomatic Infection
Altered Placental Integrity
Reduced Nutrient and Oxygen Transport
Placental Sequestration
Low Birth Weight (IUGR)
Risk of Newborn Mortality
Plasmodium falciparum malaria
Anemia
Source: WHO 2002.

25. Effect of Malaria on Pregnancy in
Unstable Transmission Areas
Acquired Immunity – Low
Clinical Illness
Severe Disease
Risk to Mother Risk to Fetus
Source: WHO 2002.

26. Pathogenesis
• The 4 important pathologic processes:
1. Fever,
• It occurs when the infected rbcs rupture and release pyrogens and
merozoites
2. Anaemia,
3. Immunopathologic events &
4. Tissue anoxia.

27. Pathogenesis: Anaemia
• Caused by:
1. Haemolysis:
• Haemolysis is more severe in a child with Fe2+
def anaemia.
2. RBC Sequestration in the organs particularly, spleen
3. Suppression of bone marrow RBC production.
4. Bleeding (DIC in P. falciparum).

28. Pathogenesis: Cytoadherence
• Infected RBCs cytoadherence to vascular
endothelium occurs [P. falciparum malaria]***.
• Lead to:
– Obstruction of the blood flow,
– Capillary & vascular damage,
– Vascular leakage of proteins & fluid, and oedema and
tissue anoxia:
• In the brain (pathogenesis of cerebral malaria),
• In the heart, lungs, intestines & kidneys.

29. Pathogenesis: Immunopathology
• Immunopathologic events include:
– Polyclonal activation resulting in both:
• Hypergammaglobulinaemia (e.g. in Tropical splenomegaly
syndrome or Hyper-immune malaria syndrome) &
• Formation of immune complexes.
– There is also immunosuppresion &
– Release of cytokines e.g. TNF = responsible for many of

30. Immunity
• Newborn/ young infants seldom have malaria.
• Malaria in them is rarely severe:
1. Maternal anti-malarial antibodies trans-placentally.
2. Maternal anti-malarial antibodies via breast milk.
3. Persistent Hb F (till age 6/ 12) makes RBCs relatively
resistant to (P. falciparum) parasitisation.

31. Immunity
4. Breast milk is relatively poor in para-aminobenzoic
acid (PABA).
– Lots of PABA needed for the growth of plasmodium.
5. Maternal anti-malarial therapy.
– About 10% of dose gets to baby via the breast milk.
6. Maternal vector-avoidance behaviour.
– Minimises baby’s exposure to mosquito bites.

32. Immunity
• Others protective means include:
1. Haemoglobin F,
2. Trait of sickle erythrocyte (carrier state),
3. Duffy-blood-group-antigen lacking RBCs resistant to P. vivax.

33. Immunity
• Children between 6/ 12 - 5 years have little specific
immunity to malaria species thus they suffer yearly
attacks that can even be fatal.
• With acquired immunity, severe symptoms of
malaria become less common.
• This may not happen until about 11 years.

34. Clinical manifestation
• Febrile paroxyms occur after incubation
peroid.
• P.fal=9-14 days
• Vivax=12-17
• Ovale =16-18
• Malariae=18-30

35. Clinical signs
• Infants signs and symptoms may be non
specific
• Fever
• Rigors chills
• Abdominal pain
• Joint pains
• Others
• Malaria can mimic a lot of other conditions

36. CLINICAL MANIFESTATION
• P. falciparum is the most severe form.
– Fatality in the P. falciparum can be as high as 30% if not
urgently addressed.
– Associated with more intense parasitaemia that can be
up to 60% of RBC (both mature & immature RBC).
• P. vivax and P. ovale primarily infect immature RBC
while P. malariae infect only mature RBC.
– These malaria infections are usually mild.

37. Diagnosis
• Clinical
• laboratory

38. LABORATORY DIAGNOSIS
Peripheral Blood Smear
(The Gold Standard)

39. DIAGNOSIS
• Giemsa-stained smears of peripheral blood.
• Both thick & thin smears should be examined.
– Thick film: Identifies degree of parasitisation.
– Thin film: Identify the Plasmodium species.
• P. falciparum smears best obtained after a febrile paroxysm.
• A single negative blood smear does not exclude malaria.
• Repeat smears may be required.

40. Thick Blood Film & Thin Blood Film
(density) (Species)

41. Degree of Parasitaemia
The “plus system”
– Less precise.
• + = 1–10/ 100 thick fields.
• ++ = 11–100/ 100 thick fields.
• +++ = 1–10/ thick field.
• ++++ = >10/ thick field.

42. Other Diagnostic tests
1. Anti-malarial Antibodies:
– Finger prick test,
– Radio-immuno assay,
– Immunofluorescence,
– Enzyme immuno assay
2. Quantitative Buffy Coat (QBC)
Test,
3. Polymerase Chain Reaction
(PCR),
4. Intra-leucocytic malaria
pigment,
5. Flowcytometry,
6. Mass spectrometry,
• These are not
generally available in
the area where
malaria is endemic.

43. Other Investigations
1. Haemoglobin/ PCV,
2. Urine analysis
3. Blood glucose,
4. Total blood cell and differential count,
5. Serum bilirubin,
6. Serum creatinine, BUN, AST, ALT,
7. Prothrombin time & Clotting profile,
8. Blood culture (1/3 positive).

44. DIFFERENTIAL DIAGNOSIS
• This is very broad; in fact any “fever” in the tropics is
assumed to be malaria until proven otherwise.
– Viral ailments:
• Influenza, hepatitis & even common cold.
– Typhoid fever,
– Yellow fever,
– Tuberculosis,
– Pneumonia,
– Meningitis,
– Septicaemia.

45. TYPES OF MALARIA AND CLINICAL
PRESENTATION
• UNCOMPLICATED OR MILD
• COMPLICATED OR SEVERE
• CEREBRAL MALARIA

46. Definition
• Uncomplicated: Fever in the presence of asexual
parasitaemia in peripheral blood
• Other possible signs , isolated or associated
Chills , abundant sweating
Muscular or articular pains
Diarrhoea, nausea, vomiting, abdominal pains
Irritability, lethargy, refuse to eat
NB: Presentation can vary according to age of the
child

47. Severe malaria-1
• Severe/complicated: malaria with any life threatening complication
• Clinical indices
Prostration Hypoglycaemia
Impaired consciousness Acute renal failure
Multiple convulsions Hyperpyrexia
Circulatory collapse
Pulmonary oedema
Abnormal bleeding
Jaundice
Haemoglobinuria
Severe anaemia

48. Severe malaria-2
Clinical indices
Prostration
Inability to sit without support
Inability to suck/eat
Inability to stand and walk without
support
 Respiratory distress
Blantyre coma score <4

49. Severe malaria -3
• Laboratory findings suggestive of severe malaria
Hyperparasitaemia
Asexual parasites counts exceeds 250,000/cu,mls
Haematological indices
Hb <5.0g/dl
PCV <15%
Biochemical indices
Blood Lactate level >5 mmol/l
Blood Glucose of < 2.2 mmol/l
Abnormal liver function
Abnormal Renal function

50. SEVERE ANAEMIA IN MALARIA
• This occurs as a result of:
Destruction of infected red blood cells by the
spleen
TNF mediated depression of erythropoiesis
Immune mediated haemolysis
Depletion of folate stores
Treatment: Blood transfusion

51. Clinical Recognition - 1

52. CONVULSION IN MALARIA
• This may result from:
 High temperature
 Hypoglycaemia
 Hypoxaemia from severe anaemia
 Fluid and electrolyte imbalance
 Brain oedema.
Treatment: Anticonvulsants- Diazepam,
Phenobarbitone + correction of any of above if
present.

53. HYPOGLYCAEMIA IN MALARIA
• It occurs as a result of:
Decreased intake
Increased glucose utilization
Impaired gluconeogenesis
Antimalarial mediated
Hyperinsulinaemia induced by malaria
Treatment: 5ml/kg IV bolus of 10% dextrose
5ml/kg/hr for maintenance; oral/gastric feeding

54. LACTIC ACIDOSIS IN MALARIA
Elevated levels of lactic acid results from:
• Tissue glycolysis particularly in skeletal muscles
• Severe anaemia from haemolysis
• Increase metabolic activity
• Dehydration
• Heart failure
Treatment : Correction of above factors

55. BREATHING DIFFICULTIES IN MALARIA
• This may may due to any of the following:
 Heart failure resulting from severe anaemia
 Acute respiratory distress syndrome which occurs as
result of malaria parasites in the lungs
 Acidosis,which causes deep and rapid breathing
 Aspiration

62. CEREBRAL MALARIA
Definition: Patient with unarousable coma
(Blantyre coma score of ≤2) and has evidence
of Falciparum malaria parasite and no other
cause of encephalopathy.

63. Table 1:Blantyre coma scale: Responses to painful stimulus
applied to sternum
Score
Verbal
response
Appropriate cry
Inappropriate
cry/moan
No cry
2
1
0
Motor
response
Localising pain
Withdrawal from pain
only
No response
2
1
0
Eye
movement
Directed
Not directed
1
0

67. Cerebral malaria
– A child with cerebral malaria, exhibiting severe opisthotonic (extensor) posturing.
Between 10% to 20% of children with cerebral malaria die, while approximately
7% are left with neurological sequelae.

68. PATHOPHYSIOLOGY OF CEREBRAL MALARIA
Mechanism of cerebral malaria unclear
Suggested hypotheses:
• ‘Sludging’ Hypothesis
• Permeability Hypothesis
• Mechanical Hypothesis
• Decreased deformability
• Cytoadherence
• Cytokines- TNF

69. Management of Malaria
Reasons why the children die;
• Delay in seeking treatment/delay in starting
treatment
• Inappropriate or ineffective treatment
• Failure to recognize and manage
complications

70. Management of Malaria
Objectives
• To provide prompt treatment
• To reduce burden of parasitaemia
• To identify complications and respond appropriately and
promptly
• To minimize the extent of complications
• To prevent infections

71. Clinical Malaria
Mild
Severe and complicated
Malaria
Oral medication and monitoring
Parenteral medication
Quinine or Artemisinine derivative

72. Management of malaria
Treatment of Malaria
Chemotherapy
•Amodiaquine
•Quinine
•Sulfadoxine and
pyrimethamine (SP)
•Artemisinine derivatives
Supportive treatment
•Fluids
•Anticonvulsants
•Analgesic
•Antipyretics
•Packed Red Cells
•others

73. Treatment of malaria -1
Chemotherapy for severe malaria
• Choice will depend on the clinical condition of the patient and
some general consideration
• Patients with severe falciparum malaria and those who have
repeated vomiting will require parenteral treatment at least
during the initial phase of management.
• Prior medication will guide the choice of antimalarial

74. Treatment of malaria -2
Uncomplicated Malaria
• Amodiaquine: 10mg/kg daily for 3 days
• Amodiaquine-Artesunate
Amodiaquine: 10mg/kg daily for 3 days
Artesunate : 4mg/kg daily for 3 days
• Artemether /Lumefantrine: 120/20mg( 5-14kg)
240/40mg(15-24kg)
etc

75. Treatment of malaria -2
SEVERE:
ARTEMISININE DERIVATIVES
• ARTESUNATE: 2.4mg/kg I.V bolus on admission ,repeat at 12
hours and 24hr for at least 24hr, followed by a full course of ACT.
Above 20kg give 3mg/kg
• Artemether: 3.2mg/kg IM only on admission then 1.6mg/kg for
at least 24hrs, followed by a full course of ACT
• ARTESUNATE: Rectal 5mg/kg bd for 24hours then 5mg/kg daily
for 4days

76. Treatment of malaria -3
Quinine.
• Dose regimen 20mg/kg stat (Deep IM). Followed by
maintenance dose of 10mg/kg body weight 8hourly till
patient can tolerate oral medication
• Oral quinine: 10mg/kg 3x daily for 7 days
• Maximum of 600mg per dose
• IV-quinine is rarely practiced now
• Beware of hypoglycaemia

77. SUPPORTIVE CARE
• MANAGE
Dehydration
Hypoglycaemia
Anaemia
Seizures
Treat co-infection with bacterial pathogens
Optimize nutritional state

78. Drug Resistance
Definition: Defined by WHO as the ability of parasite to
multiply or to survive in the presence of concentrations of a
drug that normally destroy parasites of the same species or
prevent their multiplication.
Levels of Resistance:
• RI-Following treatment, parasitaemia clears but a
recrudescence occurs.
• RII –Following treatment, there is a reduction but not a
clearance of parasitaemia
• RIII-Following treatment there is no reduction of parasitaemia

79. COMPLICATIONS
• Severe anaemia
• Cerebral malaria
• Febrile convulsion
• Metabolic acidosis
• Hypoglycaemia,
• Renal failure
• “Black water fever”
• Pulmonary oedema
• Thrombocytopaenia
• Splenic rupture
• Hyperparasitisation
• Algid malaria
• Nephrotic syndrome is also said to be a long-term
complication of P. malariae infection.

80. COMPLICATIONS OF MALARIA
ACUTE:
Cerebral malaria
• Impaired vision
• Ataxic gait
• Hearing loss
Severe malaria
• Gram-negative sepsis
• Renal failure
LONG TERM:
• Hyper-reactive malaria syndrome HMS (Tropical splenomegaly syndrome) TSS
• Burkitts lymphoma

81. Hyper-reactive malaria syndrome (HMS)
• HMS is a specific disorder characterized by massive
splenomegaly and anaemia.
• Common disorder in many malarious areas and affects up to
two precent of the population in West Africa.
• HMS occurs twice as frequently in female as in males and any
person over 10 years can be affected

82. Hyper-reactive malaria syndrome (HMS)
Diagnostic Criteria for HMS
Major Criteria
• Spleen of a least 10 cm
• Long-term residence in malarious area
• Raised serum IgM
• Response to anti-malaria drugs
Minor Criteria
• Liver biopsy showing hepatitic sinusoidal lymphocytosis
• Normal immune response to antigen challenge
• Normal phytohaemagglutination response
• Hypersplenism
• Lymphocyte proliferation
• Familial occurrence

83. Acute renal failure
• Common complication of severe falciparum malaria
• Almost exclusively in adults an older children
Definition of Malaria Acute Renal failure (MARF)
• Serum creatinine concentration >265 µmol/l (3mg/dl) with
24 hour urine output <400ml, in spite of rehydration, in
patients who have asexual forms of p.falciparum in their
peripheral blood film
• Typical presentation of patient with delayed referral and/or
delayed treatment.
• Common in males

84. Acute Renal Failure
Two Categories of MARF
1. Acute renal failure with multiple organ failure (Associated
with poor prognosis)
2. Acute infection with renal failure (Good prognosis provided
there is dialyisis available.

85. Prevention & Control
• Good personal hygiene
• Environmental hygiene
• Good Nutrition and immunity
• Early diagnosis and treatment
– Presumptive treatment of all cases
– Radical treatment
– Ensure compliance
• Personal protection
• Protection against mosquito bites
• Chemoprophylaxis

86. Components of Malaria Control
1. Quality focused antenatal care and health
education of pregnant women
2. Health education of parents
3. Use of insecticide-treated nets (ITNs)
4. Improved case management of malaria

87. Health Education on Malaria: What To Tell
Parents
• Pregnant women (especially primigravida, secundigravida and
HIV-infected women) are at higher risk of malaria
• Malaria:
– Is transmitted through mosquito bites
– Can cause severe anemia and other complications with
adverse consequences for children
– Can be prevented through the use of ITNs
– Can be treated easily if recognized early but complicated
malaria requires specialized treatment

88. Use of Insecticide-Treated Nets (ITNs)
• Shown to result in reduction of
newborns born with LBW or
prematurity
• Reduce transmission by physically
preventing vector mosquitoes from
landing on sleeping persons
• Repel and kill mosquitoes that come in
contact with the net
• Kill other insects like cockroaches, lice,
ticks and bed bugs
• Should be used by pregnant women as
early during pregnancy as possible and
use should be encouraged throughout
pregnancy and in the postpartum
period

89. Personal Protection: Insecticide treated
materials (nets)

90. Reasons for incomplete protection against
malaria
1.Polymorphism & clonal variation in antigens of
plasmodium
2.Parasite-induced immunosuppression
Intracellular parasites
3.Lack of Merozoite Surface proteins on infected
RBCs.

91. Problems in vaccine production
1. Inability to grow the parasite in large quantities
2. Parasites’ ingenious ways of avoiding hosts’ immune response
3. Complexity of conducting clinical & field trials
4. Mutation of the parasites
5. Antigenic variations
6. Multiple antigens, specific to species and stages

92. CURRENT/FUTURE
• Malaria vaccine:
Mozambican trial
RTS,S/AS02A (Mosquirix)
(GSK Biologicals and funded by MVI)
• Artificial artemisinine- Switzerland

93. CONCLUSION
MALARIA
• KILLS A CHILD EVERY 30 SECONDS
• DEATHS OCCUR WITHIN 48 HOURS OF SYMPTOMS
• EARLY RECOGNITION OF COMPLICATIONS AND
PROMPT TREATMENT WITH THE APPROPRIATE
MEDICATION REDUCE THE MORBIDITY AND
MORTALITY.

94. Personal & Environmental hygiene is key!!!

95. THANK YOU
THANK YOU
THANK YOU
THANK YOU