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Epidemiology

Malaria kills over one million children

Malaria
Presented by Daniel Ansong
Dept of Paediatrics

90 90% of malaria death occurs in sub 3000 death per day Prevalence in Ghana?
Saharan Africa

every year

Cerebral malaria BCS <=2

Site %CM Gabon Ghana Kenya Malawi Gambia % Mortality CM C M NON-CM CM P-value

Severe anaemia: Hb<5g/dl or PCV < 15 15%

% Mortality Site % SA SA SA NON-SA SA P-VALUE

Total

8.7 14.1 14 5.4 5.1 6.2 8.4

20 2 0.5 18.8 18 16.7 16 21.7 21 31.0 31 19.6 19

1.9 3.2 3.0 1.5 7.2 2.7

<0.001 <0.001 <0.001 <0.001 <0.001 <0.001

Gabon Ghana Kenya Malawi Gambia Total

25.5 25.8 15.8 8.9 27.0 19.1

5.1 6.1 3.7 7.1 12.4 5.9

2.9 5.1 3.8 2.1 7.2 3.7

0.03 0.29 0.9 <0.001 0.07 <0.001

Hyperlactemia lactate > 5mmol/l

Site % HL % Mortality HL HL Non-HL HL P-value

Hypoglycaemia: Blood glucose < 2.2 mmol/l

Si t e Gabon Ghana Kenya Malawi Gambia Total % HG 6.6 5.0 3.8 2.1 6.3 6.9 % Mortality HG H G Non-HG HG 11.6 2.9 27.5 4.2 21.3 3.1 15.8 2.3 10.3 5.8 15.9 3.2 P-value <0.001 <0.001 <0.001 <0.001 0.09 <0.001

Gabon Ghana Kenya Malawi Gambia Total

43.3 23.6 13.3 32.4 38.6 27.6

6.2 13.2 11.1 5.4 15.8 8.8

1.5 2.9 2.7 1.2 4.1 2.3

<0.001 <0.001 <0.001 <0.001 <0.001 <0.001

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Diagnosis
Laboratory Clinical

Laboratory Diagnosis
Malaria Diagnostic Procedure
Thin and Thick film using Giemsa Staining Buffy coat preparation of concentrate mps Use of Rapid Immunodiagnostic strip test

Malaria positivity 1-10 parasites per 100 high power fields (HPF) + 11-100 Parasites per 100 HPF 11 ++ ++ 1-10 parasites in every HPF +++ More than 10 parasites per HPF ++++

Presentation
Mild Severe

Pathophysiology of Severe Malaraia

Role of RBC (Sequestration of RBC in deep
vascular beds of vital organs. Role of Cytokines-TNF, Interleukin, Nitrous oxide Role of Lactic Acid Role of Platelets and other cells Role of the Spleen, Liver and other organs

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Anaemia

Striking contrast between the palm of of a Kenyan child with anaemia, and that of his mother. Severe anaemia is of is the leading cause of of death in in children with m a l a ri a .

Hypothesis for severe anaemia

The sludging hypothesis (High proportion The permeability hypothesis Mechanical hypothesis Immunological hypothesis
of parasitized RBC in organs)

Severe malaria
Clinical signs suggestive of severe malaria
Haematological indices Hb <5.0g/dl PCV <15 15 Biochemical indices Blood Lactate level >5 mmol/l Blood Glucose of < 2.2 mmol/l Abnormal liver function Abnormal Renal function

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Severe malaria
Clinical indices Prostration Inability to sit without support Inability to suck Inability to stand and walk without support Respiratory distress Haemoglobinuria Convulsion Blantyre coma score of <2

Outline classification of severe malaria in children Group 1:

Children at immediately increase risk of dying who require parenteral antimalarial drugs and support therapy

Prostrated children Respiratory distress (acidotic breathing)

Group 2: Group 3:

Children with a haemoglobin level <5g/dl or a PCV <15 15% Children with 2 or more convulsions within a 24 hours period Children who require parentral treatment because of persistent vomiting
but who lack any specific clinical or laboratory features or group 1 or 2.

Blantyre coma scale A coma scale for Children

Best motor response

Localized painful stimulus With-drawl limb from pain Non-specific or absent response Appropriate cry Moan or inappropriate cry None Direction (eg follows mothers face) Not directed 2 1 0 2 1 0 1 0

Severe malaria
Clinical indices
Prostration Impaired consciousness Multiple convulsions Circulation collapse Pulmonary oedema Abnormal bleeding Jaundice Haemoglobinuria Severe anaemia

Verbal response

Eye movements

Complication with malaria

Cerebral malaria Malaria with Renal failure Malaria associated impaired vision Malaria associated with ataxic gait Malaria associated with hearing loss Malaria with gram negative sepsis Hyper-reactive malaria syndrome HMS (Tropical splenomegaly syndrome) TSS Burkitts lymphoma

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Complications of malaria

Cerebral malaria Definition: Patients unable to localized a painful stimulus (Blantyre coma scale of <=2 with malaria parasite and no other <= cause of neuropathy.

Cerebral malaria Malaria with Renal failure Malaria associated impaired vision Malaria associated with ataxic gait Malaria associated with hearing loss Malaria with gram-negative sepsis Hyper-reactive malaria syndrome HMS (Tropical splenomegaly syndrome) TSS Burkitts lymphoma

Cerebral malaria

A child with cerebral malaria, exhibiting severe opisthotonic (extensor) posturing. Between 10% to 10 to 20 20% of of children with cerebral malaria die, while approximately 7% are left with n e u ro l o g i c a l s e q u e l a e .

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Acute renal failure

Common complication of severe falciparum malaria Almost exclusively in adults an older children Serum creatinine concentration >265 mol/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 Definition of Malaria Acute Renal failure (MARF)

Acute Renal Failure

Two Categories of MARF 1. Acute renal failure with multiple organ failure 1.
(Associated with poor prognosis)

2. Acute infection with renal failure (Good prognosis 2.

provided there is dialyisis available.

Hyper-reactive malaria syndrome (HMS) Hyper-reactive malaria syndrome (HMS)

Diagnostic Criteria for HMS

HMS is a specific disorder characterized by massive

splenomegaly and anaemia.

Common disorder in many malarious areas and affects

up to two perecent 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

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

Major Criteria

Management of Malaria
Objective behind the management of malaria To provide prompt treatment To reduce burden of parasitaemia To identify complications and respond appropriately and
promptly To minimizes the extent of complications To prevent infections
Clinical Malaria

Mild and moderate

Severe and complicated Malaria

Oral medication and monitoring

Parenteral medication

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Treatment of malaria Management of malaria

Chemotherapy for severe malaria

Choice of treatment will depend of the clinical condition

of the patient and some genetic consideration

Treatment of Malaria

Patient with severe falciparum malaria and those who

Chemotherapy Chloroquine Amodiaquine Quinine Sulfadoxine and pyrimethamine (SP) Artesimine derivative Supportive treatment Fluids Anticonvulsants Analgesic Antipyretics Packed Red Cells others

are vomiting will require parentral treatment at least during the initial phase of management.

Prior medication will guide the choice of antimalaria

Treatment of malaria
Quinine

Treatment of Malaria
Side effect of Quinine

Currently the most widely used drug in the management of severe Dose regime 20 20mg/kg body weight as a start dose (Deep
falciparum malaria. intramuscular injection. Followed by maintenance dose of 10 10mg/kg body weight after 12 12hours and subsequently 12 12hours interval till patient can tolerate oral medication Oral quinine is given at 10 10mg/kg body weight (3X daily ) for the additional days. Maximum of 7days is allowed. IV-quinine is recommended but requires strict monitoring IV

Severe life threatening toxicity are rare Cinchonism-When plasma concentration is more than 5mg/L. Characterized by Tinnitus, high tone deafness, nausea, uneasiness, malaise and blurring of vision. Vomiting is likely if core temperatures are high.- Not and indication for stopping treatment

2. 2. 3. 3 . 4. 4.

Hypotension, Myocardial conduction disturbances blindness, deafness, and coma is associated with plasma concentration below 20 20mg/L Hypoglycaemia-Due to hyper-Insulinaemia Thrombocytopenia, coombs-positive haemolytic anaemia, haemolytic uraemic Syndrome

Treatment of malaria C hl o r o q ui ne

Drug Resistance
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 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

Definition: Defined by WHO as the ability of parasite to

Remains an effective treatment for severe malaria in those few

areas where p. falciparum retains full sensitivity

Amodiaquine Amodiaquine may be a useful substitute for chloroquine when oral Amodiaquine is rapidly and extensively converted to a
treatment is required. Parentral formulation is not available pharmacologically active metabolite, des-ethylamodiaquine, following oral administration, ant it seems that this metabolite is responsible for most of the antimalaria activity.

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Prevention Vector control

Residual Indoor Spraying Outdoor spraying Use of ITBNs Indoor spraying

Chemo-prophylaxis
Chloroquine Progaunil Mefloquine
Vaccine

Thank you

Assignment
Write briefly on malaria preventive
initiatives in sub-Saharan Africa (Maximum of 2 pages)