Malaria

Introduction

Malaria is an infectious protozoan disease transmitted by the female Anopheles mosquito.
It is a major public and private health problem and indeed a cause and consequence of national underdevelopment.
Five species of the parasite cause the disease in humans:

  1. Plasmodium falciparum,
  2. P. malariae,
  3. P. vivax,
  4. P. ovale and
  5. P.knowlesi

Plasmodium falciparum is a unicellular protozoan parasite of humans, and the deadliest species of Plasmodium that causes malaria in humans.

Mode of Transmission

Principal mode of spread: bites from infected female Anopheles mosquito Peak feeding times are usually dusk and dawn, but also throughout the night
Other uncommon modes are:

  • Blood transfusion
  • Mother-to-child transmission

Classification based on clinical course of P. falciparum

  • Asymptomatic parasitaemia
  • Acute Uncomplicated malaria
  • Severe malaria

Asymptomatic parasitaemia:

Older children and adults living in high malaria endemicity

  • Have acquired natural immunity to clinical disease
  • Have malaria parasites in the peripheral blood but no symptoms

Acute Uncomplicated malaria:

This presents with clinical features, usually non specific:

  • Fever
  • Chills
  • Headache
  • Malaise
  • Aches and body pain
  • Weakness
  • Tiredness
  • Pallor
  • Anorexia
  • Vomiting
  • Bitterness in the mouth
  • Excessive sweating
  • Hepatosplenomegaly
  • Jaundice

Severe (Complicated) malaria:

Malaria is severe when there is:

  • Repeated vomiting
  • Prostration
  • Impaired consciousness
  • Severe anaemia (Haemoglobin<5g/dl)
  • Circulatory collapse (Algid malaria)
  • Hypoglycaemia (whole blood glucose <2.2mol/L)
  • Pulmonary oedema
  • Abnormal bleeding/DIC
  • Jaundice (Serum bilirubin >3g/dl)
  • Haemoglobinuria (Black water fever)
  • Febrile seizures
  • Acute renal failure
  • Hyperparasitaemia (>5% of RBCs are parasitized)
  • Hyperpyrexia (Temp> 40°C)
  • Lactic acidosis

Other early complications include:

  • Pneumonia
  • Septicaemia
  • Preterm contractions/preterm labour
  • Abortions
  • Low birth weight
  • Intrauterine deaths
  • Congenital malaria

Late complications:

  • Hyperreactive malaria splenomegaly
  • Quartan malaria nephropathy
  • Possibly, Burkitt’s lymphoma
  • Cerebral malaria

A severe form of malaria

  • Occurs usually in children and in non immune adults
  • Manifests with diffuse and symmetric encephalopathy; focal neurologic signs are unusual
  • Requires prompt and
    effective therapy to avoid fatality

Diagnosis of malaria

  • Clinical diagnosis alone is presumptive, it gives room for over-diagnosis
  • Confirmatory diagnosis is based on the detection of parasites in the blood
  • Parasitological confirmation is recommended in all suspected cases of malaria
  • Light microscopy remains the gold standard
  • Microscopic diagnosis should not delay appropriate treatment if there is a clinical suspicion of severe malaria
  • Rapid Diagnostic Test is used in Primary Health Care levels

Differential diagnoses

  • Meningitis
  • Typhoid fever
  • Encephalitis
  • Septicaemia
  • Other causes of fever

Investigations

  • Blood smear for malaria parasites
  • Packed cell volume; haemoglobin concentration
  • White cell count with differentials
  • Blood sugar
  • Urinalysis
  • Electrolytes and Urea; Creatinine
  • Stool microscopy for ova; occult blood
  • Chest radiograph
  • Cerebrospinal fluid biochemistry; microscopy, culture and sensitivity

Treatment objectives

  • Eradicate parasitaemia
  • Prevent progression to severe malaria
  • Attend to the immediate threats of life
  • Prevent transmission of gametocytes
  • Provide personal protection against malaria
  • Provide chemoprophylaxis in susceptible groups

Drug treatment

Uncomplicated malaria

  • Artemisinin-based Combination Therapy (ACTs) are the current recommended treatments for uncomplicatedbmalaria globally
  • Artemether-Lumefantrine (AL) is the medicine of choice while Artesunate Amodiaquine(AA) is the alternative

Dosage Regimen for Artemether-Lumefantrine:

WeightNo of tablets/dose

(20/120)mg tab
No of tablets/dose

(40/240)mg tab
No of tablets/dose

(80/480)mg tab
5 - < 15kg1 tabs twice dlyx3daysΝΑΝΑ
15 - < 25kg2 tabs twice dlyx3days1tab twice dlyx3daysΝΑ
25 - < 35 kg3 tabs twice dlyx3daysΝΑΝΑ
> 35kg4 tabs twice dlyx3days2tabs twice dlyx3ady1tab twice dly x3ays

Dosage Regimen for for Artesunate Amodiaquine

Weight/AgeTablet strengthDosage Regimen
4.5kg - <9kg
(2mnths-11mnths)
25mg/67.5mg1 tablet once dly x3days
9kg - <18kg
(l yr--5yrs)
50mg/135mg1 tablet once dly x3days
18kg-- <36kg
(6yrs--- 13yrs)
100mg/270mg1 tablet once dly x3days
36kg and above
14 years and above
100mg/270mg2 tablets once dlyx3days

Other ACTs available for the treatment of uncomplicated malaria:

  • Artesunate-Mefloquine
  • Dihydroartemisinin- Piperaquine
  • Artemisinin-Piperaquine

Children <5kg with uncomplicated malaria with an ACT at the same mg/kg between target dose as for children weighing 5kg.
It is vital to prevent severe dise therefore as soon as a presumptive diagnosis of malarial is made:

  • Insert artesunate suppository per rectum as a single dose
  • Re-insert if expelled; in young children the buttocks may need to be held or taped together for 10 minutes to ensure retention of the rectal dose, in adults one or more artesunate suppositories should be inserted however dose should be given once and followed as soon as possible by definitive therapy

Severe malaria

  • Parenteral Artesunate is the drug of choice, and treatment should be started without delay
  • If not available other effective parenteral antimalarial should be commenced

Adults and Children >20kg:

  • Artesunate 2.4mg/kg (BW) IV or IM given on admission (time 0), then 12hrs and 24hrs, then once a day.
  • There is no upper limit to the total dose of artesunate

Children <20kg:

  • Artesunate 3mg/kg (BW) IV or IM given on admission(time 0), then 12hrs and 24hrs, then once a day.

Parenteral artemether or quinine is an
alternative if parenteral artesunate is not available

  • Artemether 3.2mg/kg (BW) IM given on admission then 1.6 mg/kg (BW) per day; or
  • Quinine 20mg salt/kg (BW) on admission (IV infusion or divided IM injections), then 10mg/kg (BW) every 8 hrs; infusion rate should not exceed 5mg/kg (BW) per hr.

Note: Give parenteral antimalarials in the treatment of severe malaria for a minimum or 24hrs once started (irrespective of the patients ability to tolerate oral medications early) and
thereafter complete treatment by giving a complete course of the recommended ACT.
In all cases, patient’s progress should be monitored and management changed as deemed necessary

Supportive measures

  • Paracetamol (oral/rectal) for symptomatic relief
  • If temperature is >38.5°C, wipe with wet towel, and fan to lower the temperature

Pulmonary oedema

  • Nurse in cardiac position
  • Give oxygen
  • Furosemide 2-4 mg/kg intravenously
  • Exclude anaemia as the cause of heart of the failure

Renal failure

  • Give fluids if patient is dehydrated: 20 ml/kg of chloride injection 0.9%, and challenge with furosemide 1-2mg/kg
  • Catheterize to monitor urinary output
  • If no urine within the next 24 hours, refer for peritoneal or haemodialysis

Profuse bleeding

  • Transfuse with screened fresh whole blood
  • Give pre-referral treatment and refer urgently

Meningitis

  • If meningitis is suspected, and cannot be excluded immediately by lumbar puncture, give appropriate antibiotics

Other severe diseases should be treated accordingly

Treatments not recommended

  • Corticosteroids and other anti-inflammatory agents; agents used for cerebral oedema e.g. urea, adrenaline, heparin
    • Have no role in the treatment of severe malaria

Notable adverse drug reactions, caution and
contraindication

  • Mefloquine should be avoided if the patient had cerebral malaria because of the increased risk of seizure, encephalopathy and psychosis

Prevention

  • Personal protection
  • Reduce the frequency of mosquito bites by avoiding exposure to mosquitoes at their peak feeding times
  • Use insect repellants
  • Put on suitable clothing
  • Use insecticide-impregnated bed nets (ITN)
  • Chemoprohylaxis
    • Indicated for:
      • Children born to non-immune mothers in endemic areas
      • Pregnant women (see section on antenatal care)
      • Travellers to endemic areas
      • People with sickle cell anaemia should have regular chemoprophylaxis (see Sickle Cell Disease)

Recommended antimalarial prophylaxis

  • Mefloquine
  • Atovaquone-Proguanil

Mefloquine:

  • 5 mg base/kg weekly, giving an adult dose of 250 mg base weekly
  • If tablets are available, an appropriate
    fraction can be given to child aged 8- 13 years
  • Contraindicated in children <8 years and in pregnant women
  • Commence 2-3 weeks prior to arrival,bweekly in country and thereafter for 2-3 weeks after departure

Atovaquone-Proguanil

  • Fixed dose combination, administered daily.
  • Commence 1-2 days prior to arrival, then continue throughout stay, and for 7days after departure

Atovaquone-Proguanil Dosage Regimen

Weight (kg)Total daily doseDosage Regimen
11-206.25mg/25mg1 Paediatric Tablet dly
21-3012.5mg/50mg2 Paediatric Tablet dly as a single dose
31-40187.5mg/75mg3 Paediatric Tablet dly as a single dose
>40kg250mg/100mg1 Tablet( adult strength) as a single dose

Chemoprophylaxis is not recommended for individuals living with areas of intense transmission