Malaria

Question 1

What are the major species causing Malarial illness?

Answer 1

Malaria

Cause
* Caused by Plasmodium
* P. vivax → milder, m/c outside Africa
* P. falciparum
* P. ovale
* P. malariae

Question 2

What are the risk factors for severe malaria?

Answer 2

Risk factors
1)=>Pregnancy
* ↑ mortality in mother and baby

2)=>Age
* <5 years in high transmission areas
* Any age in low transmission areas

3)=> Immunosuppression
* e.g. HIV
* Non-immune travellers to endemic areas

Question 3

Clinical features of severe malaria

Answer 3

• Severe prostration
• Shock
  
  • Compensated (CRT >3 sec but no hypotension)
  • Decompensated
• ↓ GCS (<11), encephalopathy
  
  • Multiple seizures
• Acidotic breathing
• Clinical jaundice
• Haemoglobinuria
• Spontaneous bleeding
• Radiological pulmonary oedema

Question 4

Poor prognostic signs of Malaria

Answer 4

Poor Prognostic Indicators
* Age <3 years
* Cerebral malaria
* Shock, MOF
*↑ Lactataemia
* ↓ Glycaemia
* Renal failure
* Severe anaemia
* Hyperparasitaemia
* CSF ↑ lactate / ↓ glucose

Question 5

Laboratory findings in severe Malaria

Answer 5

Labs in severe malaria
* Metabolic acidosis
* ↑ Lactate
* Hypoglycaemia
* Renal impairment
* Severe normocytic anaemia
* Hyperparasitaemia (>10%)
* Haemoglobinuria

=>Jaundice common, but hepatic failure uncommon

=>Acidosis and hyperlactatemia Multifactorial:
* Tissue hypoxia
* Liver dysfunction
* Abnormal renal bicarb clearance

Question 6

Differential Diagnosis

Answer 6

• Meningitis
• Haemorrhagic fevers
• Leptospirosis
• Febrile convulsions

Question 7

Define Cerebral malaria

Answer 7

=>Term used for altered conscious state associated with Falciparum malaria & Not attributable to other conditions, e.g.:
* Hypoglycaemia
* Seizures
* Sedative
* Non malarial causes

Question 8

What is the pathophysiology of cerebral malaria?

Answer 8

5 Hypotheses
1). Cytoadherence
* Parasite-infested RBCs have a tendency to adhere to: Other non-infected RBCs &
Endothelium
* Leads to embedding in deep vascular beds–>Sequestration of parasitized RBCs-> clogging of cerebral capillaries
* Also results in escape from splenic clearance

2). Impaired cerebral perfusion and hypoxia–>
Sequestration, reduced erythrocyte deformability–> reduced microvascular flow–> hypoxia and metabolic stress rather than widespread tissue necrosis.

3). Cytokine-mediated synaptic dysfunction

4). Endothelial injury ->Neuronal injury from malarial toxins

5). Secondary insults–> Seizures, fever, hypoglycaemia, and intracranial HTN increase risk of neuronal injury

Question 9

Describe the clinical features of cerebral malaria

Answer 9

Clinical Features
* Fever
* Headache, body ache
* Delirium
* Visual symptoms
* Intracranial hypertension
* Seizures
* Coma
* Abnormal tone & posturing
* Hypoglycaemia
* Acidosis

Question 10

Diagnostic testing

Answer 10

• Thick and thin films
• Rapid diagnostic tests(RDT)
• PCR testing

Question 11

Tt for Uncomplicated Plasmodium falciparum malaria

Answer 11

=>Combination therapy with ≥2 antimalarial drugs with independent modes of action recommended.

=>Recommended regimens
1). Artesunate + amodiaquine
* Artesunate 4 mg/kg
* Amodiaquine 10 mg/kg
* OD for 3 days

2)Artesunate + sulfadoxine–pyrimethamine
* Artesunate 4 mg/kg daily × 3 days
* Sulfadoxine–pyrimethamine–>One dose on day 1.

3). Artesunate + mefloquine
* Once a day for 3 days

=>If 1st-trimester pregnancy,
Quinine + clindamycin should be used

=>2nd & 3rd trimester → Artesunate-based combination therapy

=>Second line-> Quinine + Tetracycline

Question 11

Thick & thin films

Answer 11

=>Thick films- detection of parasite
* Larger amount of blood examined
* Used for detection of parasite

=>Thin films->detection of morphology & density
* Used for detection of morphology
* Used to assess parasite density (count)

Question 11

RDTs
&
PCR testing
Pros and Cons

Answer 11

1). Histidine-rich protein (specific for Plasmodium falciparum)->
* Good sensitivity & specificity

2). Parasite lactate dehydrogenase (LDH)

3). Aldolase

=>Limitations:
* Sensitivity ↓ as parasitic load ↓
* Cannot detect parasite load
* Less sensitive for vivax

=>PCR tests
* Rapid
* Expensive

Question 12

Role of Exchange Transfusion in Malaria

Answer 12

Exchange transfusion
* Considered in severe malaria with:
* Parasite count >10%
* Children with sickle cell anaemia
* Persistent acidosis / MOF unresponsive to first-line therapy
* Helps by removing parasitised RBCs and circulating toxins
* No strong evidence in favour

Question 12

Tt regimen for Complicated Falciparum Malaria

Answer 12

Complicated / Severe Plasmodium falciparum malaria

First-line
* Artesunate–>2.4 mg/kg IV
@ 0 hrs, 12 hrs, and 24 hrs
* Then once daily
* If parenteral artesunate not available–> Artemether
* Less preferably quinine

=>Parenteral antimalarials for initial 24 hrs, irrespective of whether patient can tolerate oral therapy, then oral therapy as per guidelines

Single agent IV for first 24 hrs foll. by combination therapy

Question 13

Clinical points of note

Answer 13

=>Shock may be due to splenic rupture or GI bleed

=>Low threshold for dialysis

=>Quinine->Kills mature forms, not premature
* Will leave immature forms

=>Artesunate kills young and mature forms

**=>EvidenceCochrane review–>IV Artesunate reduces risk of death in both children and adults when Compared to Quinine
**