Clinical Malaria

8/17/2019 Clinical Malaria

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Clinical Malaria

Class IC2Course Tropical Medicine

Code TM

Title Professor

Lecturer Samuel McConkey

Date 2015

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn


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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


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Muscular low backacheFatigue

Body-ache, myalgia, arthralgia

Headache

Fever

SweatsLethargy


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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


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Severe malaria• Cerebral malaria

• Anaemia• Metabolic acidosis

• Hypoglycaemia

• Haemoglobinuria

• Renal failure

• Juandice

• Thrombocytopenia

• Disseminated intravascular coagulopathy• Pulmonary oedema / Adult Respiratory Distress

Syndrome

Complications of malaria


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Cerebral malaria

Signs of CNS dysfunction

Seizures

Focal neurological signs

Meningeal signs

Decorticate rigidity – abnormal flexion

Decerebrate rigidity – abnormal extension


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Mechanisms of anaemia

• Lysis of parasitised erythrocytes

• Lysis of non-parasitised erythrocytes

– (immune mediated)

• Sequestration of parasitised erythrocytes

• Sequestration of iron

• Dyserythropoesis• Erythrophagocytosis


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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


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Contact activated lancet

Hand-held glucose meter


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Hypoglycaemia

Classic symptoms: anxiety, sweeting,

dilation of the pupils, breathlessness,

laboured breathing, oliguria,

tachycardia, feeling of cold.

Deteriorating consciousness

Generalised convulsionsExtensor posturing

Shock and coma


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Renal failure

Oliguria and later anuriaMonitoring:

- Hourly urinary-output

- Creatinine

Treatment:

- Hydration

- Transfusion


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Thrombocytopenia

Disseminated intravascular

coagulation


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Pathogenesis of thrombocytosis in

malaria

Sequestration and destruction of platelets

Excessive removal of platelets

Platelet consumption as part of DIC


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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 daysResolution of coma 2.4 days 1-2 days

Neurological sequelae


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Malaria in pregnancy

non-immunes

• Severe complications: hypoglycaemia,

pulmonary oedema

• Higher mortality 2-10 fold

• Abortion, still birth, premature delivery

• Low birth weight infants


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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


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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 non-

pregnant women 185 /mm3


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Severe haemolytic anaemia in the 2nd

trimester in primipara

No deletiorious effects of quinine infusion on

uterine or foetal function


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Fried & Duffy 1996 Science 272, 1502-4

• The placenta selects for a parasite sub-

population that binds chondroitin sulphate A.

• This parasite sub-population preferentially

sequesters and multiplies int he placenta.


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Simplified regimens

Sulfadoxine-pyrimethamine once at booking

(usually in 2

nd

trimester)Repeated once at beginning of 3rd Trimester

Given with tetanus toxoid


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HIV seropositive women

• Increased prevalence of parasitaemia

• Increased density of parasitaemia

• Increased placental parasitaemia• Increased cord-blood parasitaemia


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Natural history of P. falciparum

immunity

Acquired immunity can be lost or altered by

Pregnancy

SteroidsProlonged residence in non-malarious

area

SplenectomyImmunosuppressive drugs


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Where do you get it?


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Transmission of malaria

Female Anopheles spp. – Airport malaria

Blood transfusion

Syringe passage among IVDUCongenital

Organ transplantation: heart kidneys


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Airport malaria 1966 -1999

France 26

Belgium 17

United Kingdom 14Switzerland 9

United States of America 4

Total 89

Aircraft disinfection


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Diagnosis of malaria

1. Clinical

2. Parasitological

3. Immunological

4. Molecular


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Clinical diagnosis

• High index of suspicion

• History of travel

• Great mimic

• Missdiagnosis

– Influenza

– Viral hepatitis

– Meningitis


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Immunological

Detect plasmodial LDH (Optimal),aldolase (ICT),

or histidine-rich protein-2 (ParaScreen)

Some detect P. falciparum,some P. vivax

some pan-specific


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Molecular

• PCR

• DNA hybridisation- DNA probes

General management of a


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General management of a

patient with malariaFrequent 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 countConsider central venous line, arterial line

Pyrexia > 39C remove patient’s clothing, tepid sponge,fan and antipyretic

Consider other infections, cultures, lumbar puncture


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Artemisinin: arthemether:


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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)


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Quinine - adverse effects

• Cinchonism on day 2 or 3

– Buzzing in ears (tinnitus)

– Dizziness

– Nausea, anorexia

– Blurred vision

• Hypoglycaemia

• Optic atrophy is rare


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Combination Therapy (ACT)

• Protects the slow acting drug

• Delays development of resistance


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P. falciparum Severe malaria

Artesunate IV or IV Quinine

And either

Doxycycline or clindamycin

• Switch to oral when tolerated


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P. falciparum non-severe malaria

Artemether + lumefantrine PO (Co-artem)

Proguanil+ atovaquone (Malarone)

Quinine PO and doxycycline or clindamycin

Mefloquine (Lariam)


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Malaria

Plasmodium falciparum

Plasmodium vivax

Plasmodium ovalePlasmodium malariae

Plasmodium knowlesi


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Further reading

Malaria chapter by Nick White, in Manson’s

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


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Genetic factors and severe malaria

Protective

TNF alleles in promotor region

Haptoglobin phenotype

HH131 genotype

More severe

R131 allele

Genetic factors enhancing


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Genetic factors enhancing

immunity

HbS heterozygotesa 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


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Malaria in Ireland 2011

Plasmodium falciparum 43Plasmodium vivax 18

Deaths 1

Malaria in UK 2003

Plasmodium falciparum 1576Plasmodium vivax 322

Deaths 16

Clinical Malaria

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