RCSI Royal College of Surgeons in Ireland Coliste Roga na Minle in irinn

Clinical Malaria
Class
Course
Code
Title
Lecturer
Date

IC2
Tropical Medicine
TM
Professor
Samuel McConkey
2015

Aims

Recognise clinical signs of malaria

Recognise signs of severe malaria
Malaria in pregnancy
Where do you get it?
How to diagnose malaria
Treatment of malaria- supportive care
How to treat severe P. falciparum
How to treat P. vivax, ovale, malariae
Treatment in pregnancy

Muscular low backache

Fatigue
Body-ache, myalgia, arthralgia
Headache
Fever
Sweats
Lethargy

Clinical features of uncomplicated

malaria
Minimum incubation period of 7 days
Fever continuous or remittent
Flu-like symptoms
Headache
Myalgia and arthralgia
Back ache

Tinge of jaundice
Children stop playing, stop eating and lie
around

Severe malaria
Cerebral malaria
Anaemia
Metabolic acidosis

Complications of malaria

Hypoglycaemia
Haemoglobinuria
Renal failure
Juandice
Thrombocytopenia
Disseminated intravascular coagulopathy
Pulmonary oedema / Adult Respiratory Distress
Syndrome

Cerebral malaria
Signs of CNS dysfunction
Seizures
Focal neurological signs
Meningeal signs
Decorticate rigidity abnormal flexion
Decerebrate rigidity abnormal extension

Mechanisms of anaemia
Lysis of parasitised erythrocytes
Lysis of non-parasitised erythrocytes
(immune mediated)

Sequestration of parasitised erythrocytes

Sequestration of iron
Dyserythropoesis
Erythrophagocytosis

Metabolic acidosis,
widened anion gap
Hyperventilation
Deep signing respiration (Kussmaul breathing)

Negative inotropism
Impaired level of consciousness, stupor, coma
Vomiting, abdominal pain
K+ shift extracellularly

Treat with hydration, IV fluids and Oxygen

Contact activated lancet

Hand-held glucose meter

Hypoglycaemia
Classic symptoms: anxiety, sweeting,
dilation of the pupils, breathlessness,
laboured breathing, oliguria,
tachycardia, feeling of cold.
Deteriorating consciousness
Generalised convulsions
Extensor posturing
Shock and coma

Renal failure
Oliguria and later anuria
Monitoring:
- Hourly urinary-output
- Creatinine
Treatment:
- Hydration
- Transfusion

Thrombocytopenia
Disseminated intravascular
coagulation

Pathogenesis of thrombocytosis in
malaria
Sequestration and destruction of platelets
Excessive removal of platelets
Platelet consumption as part of DIC

Pulmonary oedema
Adult respiratory distress
syndrome

Severe Malaria in Adults and children

Differential features
Symptoms and signs

Adults

Children

Cough

Rare

Frequent

Convulsions

Common

Very common

Antecendent history

5-7 days

1-2 days

Resolution of coma

2.4 days

1-2 days

Neurological sequelae

<5%

10%

Icterus

Common

Rare

Opening CSF pressure

Usually normal

Usually raised

Pretreatment hypoglycaemia

Rare

Common

Pulmonary Oedema

Not uncommon 10% Rare

Renal Failure

Common

Rare

DIC

10%

Rare

Malaria in pregnancy
non-immunes
Severe complications: hypoglycaemia,
pulmonary oedema
Higher mortality 2-10 fold
Abortion, still birth, premature delivery
Low birth weight infants

Malaria in pregnancy
partially immunes

Primi and secundi gravidae

Abortion, still birth and premature labour
Low birth weight infants
Increase in parasite rates and densities
Placental parasitaemia
Haemolytic anaemia

Density of parasitaemia
Log median parasite count of 38 women
before conception
140 /mm3
Log median parasite count of 38 women
during first pregnancy
1775 /mm3
Log median parasite count of 175 nonpregnant women
185 /mm3

Malaria in pregnancy
Severe haemolytic anaemia in the 2nd
trimester in primipara
No deletiorious effects of quinine infusion on
uterine or foetal function

Fried & Duffy 1996 Science 272, 1502-4

The placenta selects for a parasite subpopulation that binds chondroitin sulphate A.
This parasite sub-population preferentially
sequesters and multiplies int he placenta.

Simplified regimens
Sulfadoxine-pyrimethamine once at booking
(usually in 2nd trimester)
Repeated once at beginning of 3rd Trimester
Given with tetanus toxoid

HIV seropositive women

Increased prevalence of parasitaemia

Increased density of parasitaemia
Increased placental parasitaemia
Increased cord-blood parasitaemia

Natural history of P. falciparum

immunity
Acquired immunity can be lost or altered by
Pregnancy
Steroids
Prolonged residence in non-malarious
area
Splenectomy
Immunosuppressive drugs

Where do you get it?

Transmission of malaria
Female Anopheles spp. Airport malaria
Blood transfusion
Syringe passage among IVDU
Congenital
Organ transplantation: heart kidneys

Airport malaria 1966 -1999

France
26
Belgium
17
United Kingdom
14
Switzerland
9
United States of America 4

Total
Aircraft disinfection

89

Diagnosis of malaria
1.
2.
3.
4.

Clinical
Parasitological
Immunological
Molecular

Clinical diagnosis

High index of suspicion

History of travel
Great mimic
Missdiagnosis
Influenza
Viral hepatitis
Meningitis

Immunological
Detect plasmodial LDH (Optimal),
aldolase (ICT),
or histidine-rich protein-2 (ParaScreen)
Some detect P. falciparum,
some P. vivax
some pan-specific

Molecular
PCR
DNA hybridisation- DNA probes

General management of a
patient with malaria
Frequent assessment of vital signs
-Early Warning Score
Artificial homeostasis, H2O, O2, H+, glucose, Na,
Mg2+, Ca2+, Creatinine, BP, temperature, red
cells
Assess and treat: hydration, hypoglycaemia, hypoxia
Measure and monitor urine output e.g catheter
Daily thin film to measure parasite count
Consider central venous line, arterial line
Pyrexia > 39C remove patients clothing, tepid sponge,
fan and antipyretic
Consider other infections, cultures, lumbar puncture

Artemisinin: arthemether:
artesunate
Most rapid action - 95% clearance within
24 hours - all stages
Cmax 1 h (oral), 5min(IV), 4-9 hours (IM)
metabolised in liver
half life 9 hours- (oral)
20-45 min (IV)

Quinine - adverse effects

Cinchonism on day 2 or 3
Buzzing in ears (tinnitus)
Dizziness
Nausea, anorexia
Blurred vision

Hypoglycaemia
Optic atrophy is rare

Combination Therapy (ACT)

Protects the slow acting drug
Delays development of resistance

P. falciparum Severe malaria

Artesunate IV or IV Quinine
And either
Doxycycline or clindamycin
Switch to oral when tolerated

P. falciparum non-severe malaria

Artemether + lumefantrine PO (Co-artem)
Proguanil+ atovaquone (Malarone)
Quinine PO and doxycycline or clindamycin
Mefloquine (Lariam)

Other non-severe malaria

Chloroquine
Sulfadoxine + Pyrimethamine (Fansidar)
Or as for P. falciparum
Later
Add Primiquine to prevent relapse for
P. ovale, and P. vivax

Malaria
Plasmodium falciparum
Plasmodium vivax
Plasmodium ovale
Plasmodium malariae
Plasmodium knowlesi

Further reading
Malaria chapter by Nick White, in Mansons
Tropical Diseases ed. Cook and Zumla
Effectiveness of antimalarial drugs Kevin
Baird NEJM April 2005 352:1565
Management of severe malaria in children
K. Maitland, A. Pollard, M. Levin. BMJ
August 2005 331:337

Genetic factors and severe malaria

Protective
TNF alleles in promotor region
Haptoglobin phenotype
HH131 genotype
More severe
R131 allele

Genetic factors enhancing

immunity
HbS heterozygotes
a thalassaemia heterozygotes
b thalassaemia heterozygotes
HbC homozygotes (93%) heterozygotes (29%)
G6PD deficiency
HLA BW 53
HLA DRB 1302
Ovalocytosis
?HbE heterozygotes and homozygotes
R131 alleles

Malaria in Ireland 2011

Plasmodium falciparum
Plasmodium vivax
Deaths

43
18
1

Malaria in UK 2003
Plasmodium falciparum 1576
Plasmodium vivax
322
Deaths
16