Malaria

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Introduction

  • An infectious protozoan disease transmitted by the female Anopheles mosquito
  • 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:
    • Plasmodium falciparum, P. malariae, P. vivax, P. ovale and P. knowlesi
    • P. falciparum accounts for 98% of all cases of malaria in Nigeria and is responsible for the severe form of the disease
  • 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:

Present 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
  • Pallor
  • Hepatosplenomegaly
  • Jaundice

Severe (Complicated) malaria:

Is a medical emergency requiring prompt attention

Indications for severity could be clinical or laboratory

Clinical:

  • Prostration
  • Impaired consciousness or unrousable coma
  • Failure to feed
  • Respiratory distress
  • Multiple convulsions - more than 2 episodes in 24 hours
  • Circulatory collapse (Algid malaria)
  • Pulmonary oedema (radiological)
  • Abnormal bleeding/DIC
  • Jaundice

 Laboratory:

  • Severe anaemia
  • Hypoglycemia (blood glucose < 2 mmol/L)
  • Acidosis (HCO < 15 mmol/L)
  • Haemoglobinur3ia (black water fever)
  • Renal impairment (creatinine > 265 μmol/L)
  • Hyperlactataemia (> 5 mmol/L)
  • Hyperparasitaemia (> 5% or 250,000/ μL)

Indicators of poor prognosis in severe malaria:

Clinical:

  • Marked agitation
  • Hyperventilation (respiratory distress)
  • Hypothermia (<36.50C)
  • Deep coma
  • Repeated convulsions
  • Bleeding
  • Anuria
  • Haemodynamic shock

Laboratory:

  • Hyperparasitemia (> 100,000 /μgL; about 2% of cells infected)
  • Blood film showing >20% of parasite to be 'late stage'
  • Blood film showing > 5% of neutrophils with visible pigments
  • Hypoglycemia (<2.2 mmol/L)
  • Hyperlactatemia (> 5 mmol/L)
  • Acidosis (arterial PH > 3, serum HCO > 15 mmol/L)
  • Elevated serum creatinine (> 265 μmol/L3)
  • Elevated total bilirubin (> 50 μmol/L)
  • Leukocytosis (>12,000 /μL)
  • Severe anaemia (PCV >15%)
  • Coagulopathy
  • Decreased platelet count (< 50,000 /μL)
  • Prolonged prothrombin time
  • Decreased fibrinogen

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
  • Malaria with coma persisting for > 30 min after a seizure is considered to be cerebral 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, 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

  • Typhoid fever
  • Meningitis
  • 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 goals

  • 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

All patients suspected of malaria should have prompt parasitological confirmation by microscopy or RDTs before treatment.

Uncomplicated malaria

  • Artemisinin-based Combination Therapy (ACTs) are the current recommended treatments for uncomplicated malaria globally.
  • ACTs are the recommended treatment of uncomplicated malaria in all trimesters of pregnancy
  • Artemether-Lumefantrine (AL) is the medicine of choice while Artesunate-Amodiaquine (AA), Dihydroartemisinin Piperaquine and Artesunate-Pyronaridine are alternatives

 

Dosage Regimen for AL:

Weight

No of tablets/dose

(20/120)mg tab

No of tablets/dose

(40/240)mg tab

No of tablets/dose

(80/480)mg tab

5 -- <15kg

1 tab twice dly x 3days

   NA  NA

15 -- <25kg

2 tabs twice dly x 3days

1tab twice dly x 3days

 NA

25 -- <35kg

3 tabs twice dly x 3days

 NA

 NA

     > 35kg

4 tabs twice dly x 3days

2tabs twice dly x 3day

1tab twice dly x3ays

Dosage Regimen for AA:

Weight/Age

Tablet strength

Dosage Regimen

4.5kg-- <9kg

(2mnths--- 11mnths)

  25mg/67.5mg

1 tablet once dly x 3 days

9kg-- <18kg

(1yr-- 5yrs)

50mg/135mg

1 tablet once dly x3 days

18kg-- <36kg

( 6yrs--- 13yrs)

100mg/270mg

1 tablet once dly x 3days

36kg and above

14 years and above

100mg/270mg

2 tablets once dly x3 days

Other ACTs available for the treatment of uncomplicated malaria:

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

Pre-referral treatment of severe malaria

To mitigate poor outcome, pre-referral treatment should be offered in cases of severe disease.

  • As soon as a presumptive diagnosis of severe malaria is made, recommended pre-referral treatment options include any of these; rectal Artesunate, Artesunate IM, Artemether IM or Quinine IM, in the order of preference.
  • Dosing regimen
    • IM Artesunate: 3 mg/kg (children <6 years or < 20 kg); 4 mg/kg (older children and adults)
    • Rectal Artesunate: 10 mg/kg body-weight single
    • IM Artemether: 2 mg/kg
    • IM Quinine: 10 mg/kg

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 > 20 kg:Artesunate 4 mg/kg (BW) IV or IM given on admission (time 0), then 12 hours and 24 hours, then once a day. There is no upper limit to the total dose of artesunate.
  • Children ≤20 kg:
  • Artesunate 3 mg/kg (BW) IV or IM given on admission (time 0), then 12 hours and 24 hours, then once a day
  • Parenteral artemether or quinine is an alternative if parenteral artesunate is not available
  • Artemether 3.2 mg/kg (BW) IM given on admission then 1.6 mg/kg (BW) per day; or
  • Quinine 20 mg salt/kg (BW) on admission (IV infusion or divided IM injections), then 10 mg/kg (BW) every 8 hours; infusion rate should not exceed 5 mg/kg (BW) per hr.

Note: Give parenteral antimalarials in the treatment of severe malaria for a minimum of 24 hours once started (irrespective of the patient's ability to tolerate oral medications earlier) and thereafter complete treatment by giving a complete course of the recommended ACT.

Follow-up treatment

  • After the initial 24 hours parenteral treatment, and once the patient can tolerate oral therapy, complete treatment with a full course of ACT (Arthemeter + Lumefantrine, OR Artesunate + Amodiaquine, OR Dihydroartemisinin + Piperaquine OR Pyronaridine + Artesunate) for 3- days irrespective of the number of days for which patient was on parenteral artesunate prior to the commencement of oral administration.

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 heart 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

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

  • High dose Corticosteroids and other anti-inflammatory agents
  • Agents used for cerebral oedema e.g. Urea
  • Adrenaline
  • Heparin

Notable adverse drug reactions, contraindications and caution

  • 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 Diseases)

Recommended antimalarial prophylaxis in Nigeria:

The recommended chemoprophylaxis for non-immune visitors should be available in the visitor's country of origin. Mefloquine, and Atovaquone-Proguanil are recommended for use in Nigeria.

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, weekly 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 7 days after departure

Atovaquone-Proguanil Dosage Regimen:

Weight(kg)

Total daily dose

Dosage Regimen

11-20kg

62.5mg/25mg

1 Paediatric Tablet dly

21-30kg

12.5mg/50mg

2 Paediatric Tablet dly as a single dose

31-40kg

187.5mg/75mg

3 Paediatric Tablet dly as a single dose

>40kg

250mg/100mg

1 Tablet( adult strength) as a single dose

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