Malaria

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Malaria is an acute febrile illness caused by infection with Plasmodium parasites and is transmitted from person to person by an infected female anopheles mosquito.

Cause

  • There are five Plasmodium species of malaria parasites which infect humans namely: falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi.
  • P. falciparum is the most virulent and also the most common malaria parasite in Uganda.
Clinical Features of Malaria
  • It may be asymptomatic, mild illness (uncomplicated malaria) or severe illness (severe malaria)
  • Intermittent fever is the most characteristic symptom of malaria. Three classical stages can be distinguished in a typical attack of malaria:
    • The cold stage: the patient feels cold and shivers
    • The hot stage: the patient feels hot
    • The sweating stage: associated with sweating and relief of symptoms
  • A complete physical examination has to be performed in any patient presenting with fever or history of fever
  • When people are frequently exposed to malaria, they develop partial immunity. In such people, the classical stages of a malaria attack above may not be observed
  • Also, in people who have had partial treatment with antimalarial medicines, these classical stages may not be pronounced

Uncomplicated Malaria

Common symptoms/signs of uncomplicated malaria:

  • Fever: above 37.5°C (taken from the axilla ) or history of fever
  • Loss of appetite, mild vomiting, diarrhoea
  • Weakness, headache, joint and muscle pain
  • Mild anaemia (mild pallor of palms and mucous membranes); occurs commonly in children
  • Mild dehydration (dry mouth, coated tongue, and sunken eyes). In adults, sunken eyes are usually a sign of severe dehydration
  • Enlarged spleen (in acute malaria it may be minimally enlarged, soft and mildly tender)

Complicated/Severe Malaria

It is an immediate threat to life and is therefore a medical emergency. Malaria is regarded as severe if there are asexual forms of P. falciparum in blood plus one or more of the following complications in the table below.

Classical definition of severe malaria

COMPLICATION

CRITERION FOR DIAGNOSIS

Defining manifestations

Cerebral malaria

Deep coma (unable to localise a painful stimulus), Normal CSF, parasitaemia

Severe anaemia

Hb <5g/dl with parasitaemia

(<7 g/dl in pregnancy)

Respiratory distress

Tachypnoea, nasal flaring and intercostal recession in a patient with parasitaemia

Hypoglycaemia

Blood glucose <40 mg/dl

(2.2 mmol/L) with parasitaemia

COMPLICATION

CRITERION FOR DIAGNOSIS

Circulatory collapse

Clinical shock (systolic pressure <50 mmHg for children and <80mmHg for adults, with cold peripheries, clammy skin) with parasitaemia

Renal failure

Urine output < 12 ml/kg in 24 hours and plasma creatinine > 3.0 mg/dl, with parasitaemia

Spontaneous bleeding

Parasitaemia with unexplained spontaneous bleeding (haematemesis, melaena, or prolonged bleeding from nose, gum or venipuncture site

Repeated convulsions

2 or more convulsions in 24 hours, with parasitaemia

Acidosis

Deep (acidotic) breathing and plasma bicarbonate <15 mmol/L, with parasitaemia

Haemoglobinuria

Parasitaemia, haemoglobin in urine (dark coloured urine but no RBC’s)

Pulmonary Oedema

Deep breathing, fast breathing, laboured breathing (nasal flaring, intercostal recession and chest in- drawing), Cheyne stokes breathing

Supporting manifestations (some other signs in addition to above complications)

Impaired consciousness

Parasitaemia with depressed level of consciousness but can localize a painful stimulus, or change of behavior, confusion, drowsiness

COMPLICATION

CRITERION FOR DIAGNOSIS

Jaundice

Parasitaemia with unexplained jaundice

Prostration

Unable to sit, in a child normally able to do so or unable to drink in one too young to sit

Severe vomiting

Vomiting everything, not able to drink or breastfeed

Severe dehydration

Sunken eyes, coated tongue, lethargy, inability to drink

Hyperpyrexia

Temperature >39.5°C, with parasitaemia

Hyper- parasitaemia

Parasite count > 250,000 /µl, > 10%

Threatening abortion

Uterine contractions and vaginal bleeding

Differential diagnosis

  • Respiratory tract infection
  • Urinary tract infection
  • Meningitis, otitis media, tonsillitis
  • Abscess, skin sepsis
  • Measles or other infections with rashes (before rash comes)

Investigations for Malaria

Note: All suspected malaria patients MUST be tested by blood slide or RDT before they are treated. NOT all fevers are malaria.

  • RDT or thick blood slide for diagnosis of malaria
  • Random blood sugar and Hb level if clinically indicated
  • Lumbar puncture: in case of convulsion/coma and negative malaria tests
  • Thin film for parasite identification

Note on RDTs

  • RDTs (Rapid Diagnostic tests) detect malaria antigen (not whole parasites like the blood slide) and remain positive for 2-3 weeks after effective treatment
  • RDT do not become negative if the patient has already taken antimalarials
  • RDTs are reliable, quick and easily accessible tools for malaria

A blood slide for microscopy is specifically recommended over RDT in the following situations:

  • Patients who have taken antimalarial treatment for 2 days and symptoms persist
  • Patients who completed treatment but come back within 2 weeks
  • RDT negative patients without any other evident cause of fever 

Management of Malaria

NATIONAL MALARIA TREATMENT POLICY 

Uncomplicated Malaria

All patients: including children <4 months of age and pregnant women in 2nd and 3rd trimesters

First line medicine

  • Artemether/Lumefantrine

First line alternative

  • Artesunate/Amodiaquine

Second line medicine

  • Dihydroartemisin/ Piperaquine
  • If not available: quinine tablets

Pregnant women 1st trimester
  • ACT currently used. 

Severe Malaria

All age groups or patient categories

First line

  • IV Artesunate

First line alternative

  • IV Quinine
  • Or Artemether injection

Pre-referral treatment

  • Rectal artesunate for children 6 years and below only. IM Artesunate, IM artemether or quinine where the parental medicine is available

Intermittent preventive treatment in pregnancy
  • Sulfadoxine/Pyrimethamine (SP) for IPT. Start at 13 weeks and give monthly till delivery

Treatment of uncomplicated malaria

The following tables contain dosages for medicines used in treatment of uncomplicated malaria.

Dosage of artemether/lumefantrine 20/120 mg

WEIGHT (KG)

DAY 1

DAY 2

DAY 3

<14

1 tablet at 0 hours

then 1 tablet at 8 hours

1 tab twice daily

1 tab twice daily

15–24

2 tablets at 0 hours,

then, 2 tablets at 8 hours

2 tab twice daily

2 tab twice daily

25–34

3 tablets at 0 hours then 3 tablets at 8hours

3 tab twice daily

3 tab twice daily

>35

4 tablets at 0 hours

then 4 tablets at 8 hours

4 tab twice daily

4 tab twice daily

Note: Give day 2 and day 3 doses every 12 hours

 

Dosage of artesunate (AS) tablets 50 mg once a day

AGE

DAY 1

DAY 2

DAY 3

0–11

months

25 mg (½ tab)

25 mg (½ tab)

25 mg (½ tab)

1–6 years

50 mg

(1 tab)

50 mg

(1 tab)

50 mg

(1 tab)

7–13 years

100 mg

(2 tabs)

100 mg

(2 tabs)

100 mg

(2 tabs)

>13 years

200 mg

(4 tabs)

200 mg

(4 tabs)

200 mg

(4 tabs)

Note: Do not use artesunate alone, give with amodiaquine tabs

 

Dosage of amodiaquine (AQ) 153 mg tablets

AGE

DAY 1

DAY 2

DAY 3

0–11

months

76 mg (1/2 tab)

76 mg (1/2 tab)

76 mg (1/2 tab)

1–6 years

153 mg (1 tab)

153 mg (1 tab)

153 mg (1tab)

7–13 years

306 mg (2 tabs)

306 mg (2 tabs)

306 mg (2 tabs)

>13 years

612 mg (4 tabs)

612 mg (4 tabs)

612 mg (4 tabs)

Note: Do not use amodiaquine alone, use with artesunate tabs

 

Dosage of dihydroartemisinin (DHA)/Piperaquine tablets (PPQ) (40/320 mg) tablets

WEIGHT (KG)

AGE

DAY 1

DAY 2

DAY 3

<5–9.9

<6 month– 1 year

0.5

0.5

0.5

10–20

2–7 years

1

1

1

20-40

8-13 years

2

2

2

40-60

 

3

3

3

60-80

 

4

4

4

>80

 

5

5

5

Dosage for Pyronaridine Tetraphosphate / Artesunate

Dosage of quinine tablets (1 quinine tab=300 mg salt)

WEIGHT (KG)

AGE

DOSE (TO BE GIVEN EVERY 8 HOURS FOR 7 DAYS)

<5–10

3 months–1 year

75 mg ( tab)

10–18

1–5 years

150 mg (½ tab)

18–24

5–7 years

225 mg ( tab)

24–30

7–10 years

300 mg (1 tab)

30–40

10–13 years

375 mg (1 tab)

40–50

13–15 years

450 mg (1½ tab)

> 50

> 15 years

600 (2 tabs)

Management of severe malaria

  • Manage complications as recommended in the section below
  • Manage fluids very carefully. Adults with severe malaria are very vunerable to fluid overload, while children are more likely to be dehydrated
  • Monitor vitals signs carefully including urine output
    • Intravenous artesunate is the medicine of choice
    • At a health unit without admission and IV drug administration facilities, give a pre-referral dose of rectal artesunate ( see dosing tables below) as soon as possible and refer for further management
    • At a health unit with admission and IV drug administration facilities, treat with IV artesunate as in the table below
  • If IV route is not possible, use IM route
  • If artesunate not available, use IM artemether (into the thigh, never in the buttock) or IV quinine

Dosage of rectal artesunate

WEIGHT (KG)

AGE

ARTESUNATE DOSE (MG)

REGIMEN (SINGLE DOSE)

5kg to<14

4 months to

<3years

100mg

1 supp (100 mg)

14-19

3 years to less than 6 years

100 mg

2 supp of 100mg

Note

In the event that an artesunate suppository is expelled from the rectum within 30 minutes of insertion, insert a repeat dose.

Hold the buttocks (especially in young children) together for 10 minutes to ensure retention of rectal dose

 

Dosage of intravenous artesunate for severe malaria

Artesunate IV

DOSE

TIME

QUANTITY

First dose: on admission Loading dose

At 0 hours

Child less than 20 kg: 3 mg/kg Adults and child

>20kg: 2.4 mg/kg

Second dose

At 12 hours

Third dose

At 24 hours

Then once a day until patient is able to tolerate oral medication, then give a full course of oral ACT.* currently all severe malaria cases to be discharged on DP. Then reviewed every month for 3 months and given monthly DP for post severe malaria chemoprevention.

Preparation of IV or IM artesunate

  • IV artesunate is usually dispensed in powder vial of 30mg, 60 mg, 120mg, pre-packed with sodium bicarbonate solution 1 ml
  • Calculate the dose in mg according to the weight and the number of vials needed
  • Reconstitute each vial separately, and use within 1 hour
  • Reconstitution: inject all the content of the bicarbonate ampoule (1 ml) in the artesunate vial. Shake gently till solution become clear (discard if not clear after 2 minutes)

IV use

  • Dilution: dilute solution by adding 5 ml of sodium chloride 0.9% (normal saline) or Dextrose 5%, obtaining a concentration of 10 mg/ml
  • Calculate the required volume and withdraw
  • Give by IV injection slowly over 5 minutes

IM use

  • Dilution: dilute solution by adding 2 ml of sodium chloride 0.9%, obtaining a concentration of 20 mg/ml
    • Inject into the upper outer anterior thigh, NEVER in the buttock

DO NOT USE WATER FOR INJECTION FOR DILUTION

Dosage of IM artemether

Artemether

DOSE

TIME

QUANTITY

First dose: on admission Loading dose

At 0 hours

3.2 mg/kg

Second dose

At 24 hours

1.6 mg/kg

Third dose

At 48 hours

1.6 mg/kg

Then once a day until patient is able to tolerate oral medication, then give a full course of oral ACT. If after 48hours (day 3) the patient is still un stable and parasites density is still almost the same as at day 0, switch to IV quinine for 3 to 4 doses then discharge on ACT (DP).

Dosage of quinine IV

  • 10 mg/kg in dextrose 5% every 8 hours till patient is able to tolerate oral medication 
  • Then complete with a full dose of ACT (3 days) or quinine tablets to complete 7 days

Management of Complications of Severe Malaria

COMPLICATION

TREATMENT

Hyperpyrexia
  • Give paracetamol 1 g every 6 hours
  • Child: 10 mg/kg + tepid sponging + fanning

Convulsions
  • Give diazepam 0.2 mg/kg (max 10 mg) slow IV or (in adults) IM or 0.5 mg/kg rectally

If convulsions still persist:

  • Give phenobarbital 200 mg IM/IV
    • Child: 10-15 mg/kg loading dose then
    • 2.5 mg/kg once or twice daily if still necessary
    • Or phenytoin 15 mg/kg loading dose

Hypoglycaemia
  • Adult: dextrose 25% 2 ml/kg by slow IV bolus over 3-5 min (to prepare, take dextrose 50% 1 ml/kg and dilute with an equal volume of water for injections)
  • Child: dextrose 10% 5 ml/kg by slow IV bolus over 5-7 min (to prepare, take 1 ml/kg of dextrose 50% and dilute with 4 ml/kg water for injection)
  • DO NOT GIVE UNDILUTED 50% dextrose
  • Monitor blood glucose frequently
  • Ensure patient is feeding

Acidosis
  • Correct fluid & electrolyte balance
  • If there is severe acidosis without sodium depletion:
    • Give sodium bicarbonate 8.4% infusion 50 ml IV
    • Monitor plasma pH

Severe anaemia
  • Do blood grouping and cross- matching
  • Transfuse patient with packed cells 10-15 ml/kg or whole blood 20 ml/ kg especially if the anaemia is also causing heart failure
  • Repeat Hb before discharge and preferably 28 days after discharge

Pulmonary Oedema
  • Regulate the IV infusion (do not overload with IV fluids)
  • Prop up the patient
  • Give oxygen
  • Give furosemide 1-2 mg/kg

Acute Renal Failure
  • Urine output: <17 ml/hour for adult or <0.3 ml/kg/hour for a child
  • Check to ensure that the cause of oliguria is not dehydration or shock
  • If due to acute renal failure: Give a challenge dose of furosemide 40 mg IM or slow IV (child: 1 mg/kg)

If this fails:

  • Refer for peritoneal dialysis or haemodialysis

Shock
  • If systolic BP <80 mmHg (adult) or <50 mmHg (child) or if peripheral pulse absent and capillary refill is slow (>2 seconds)
    • Raise the foot of the bed
    • Give sodium chloride 0.9% by fast IV infusion bolus 20 ml/kg in 15 min
    • Review fluid balance and urinary outputs
    • Look for evidence of haemorrhage or septicaemia and treat accordingly

Haemoglobinuria (intravascular haemolysis)
  • Rehydrate the patient
  • Assess for anaemia and transfuse if necessary

Dehydration
  • Rehydrate using ORS or IV RL or NS
  • Over-enthusiasitc IV infusion may harm the patient and lead to fluid overload and pulmonary oedema

Bleeding
  • Transfuse patient with whole fresh blood to provide lacking clotting factors

Coma
  • Check and treat for hypoglycaemia: if not responding within 20 min, consider another cause
  • Provide intensive nursing care with:
    • IV drip (for rehydration and IV medication)
    • NGT (for feeding and oral medication)
    • Urethral catheter (to monitor urine output)
    • Turning of patient frequently to avoid bed sores

Criteria for referral to regional/tertiary hospital

  • Persistent renal failure needing dialysis
  • Any complication that cannot be managed locally

Management of RDT/Blood Smear Negative Patients

Patients who have a negative malaria test (most likely, if RDT is used) do not have malaria so other causes of fever have to be investigated for appropriate treatment.

  • Re-assess patient history, clinical signs and laboratory results. Consider other frequent causes of fever such as:
    • If running nose, sore throat and cough: viral upper respiratory infection
    • If swollen tonsils with exudate on it: tonsilitis
    • If ear pain and discharge: otitis
    • If cough, rapid breathing and difficulty in breathing: pneumonia
    • If urinary symptoms: urinary tract infection
    • If vomiting, diarrhoea and abdominal pain: gastro-enteritis
    • If skin rash: measles or other viral rash
  • If malaria is still suspected, investigate according to the flowchart below
    • If signs/symptoms of severe malaria, RDT and blood slide negative but no other diagnosis is found, consider treating for malaria anyway but repeat RDTs after 24 hours to confirm. Also add a broad spectrum antibiotic. 
    • If RDT and blood slide negative, no signs of other illness and no signs of severe sickness (patient has no danger signs) treat symptomatically with antipyretics, advise patient to return immediately if condition worsens or in 2 days if fever

Possible reasons for false negative tests (test is negative but patient has malaria):

  • Low peripheral parasitaemia
  • Technical error in performing the test or test reagents that are out of date
  • Sequestration of parasites in the internal organs
  • Having already taken antimalarial drugs, inadequate or incomplete dose: this affects only microscopy, while RDT remains positive even if the patient has already taken an antimalarial
  • Using prophylactic treatment for malaria

Malaria Prophylaxis

Not recommended for all those living in a highly endemic area like Uganda. However, it is recommended for certain high-risk groups but is not 100% effective.

 

PATIENT GROUP

PROPHYLAXIS

Pregnancy

In endemic areas, pregnant women carry malaria parasites in their blood or placenta, which is harmful to the health of both mother and foetus
  • Give intermittent preventive treatment (IPT) to ensure the well-being of mother and foetus
  • SP single dose (3 tabs) given at 13 weeks and continued monthly until delivery
  • Ensure doses are taken under supervision by the health provider as directly observed therapy (DOT)
  • Record doses on the patient’s card and treatment register and summarise further in the delivery book and monthly returns
  • Do not give SP in HIV patients on cotrimoxazole

Sickle cell disease

Sulphadoxine- pyrimethamine (SP) - see section 11.1.3

Chloroquine is the alteranative: Adult: 300 mg base weekly, Child: 5 mg (base)/kg weekly

People living with HIV
  • Cotrimoxazole daily as per national guidelines

Non-immune visitors/tourists

Mefloquine

  • Adult: 250 mg once weekly
  • Child: 5 mg/kg once weekly

Malaria Prevention and Control

Give effective treatment and prophylaxis

  • Eliminate parasites from the human population by early diagnosis and effective treatment
  • Protect vulnerable groups with chemoprophylaxis
  • Give IPT to all pregnant women

Reduce human-mosquito contact

  • Use insecticide-treated materials (e.g. bed nets)
  • Destroy adult mosquitoes by indoor residual spraying of dwellings with insecticide or use of knock-down sprays
  • Screen houses
  • Carefully select house sites avoiding mosquito-infested areas
  • Wear clothes which cover the arms and legs and use repellent mosquito coils and creams/sprays on the skin when sitting outdoors at night

Control mosquito breeding sites

  • Eliminate collections of stagnant water where mosquitoes breed, g. in empty cans/ containers, potholes, old car tyres, plastic bags, and footprints by disposal, draining, or covering with soil or sand
  • Destroy mosquito larvae by dosing stagnant water bodies with larvicides or with biological methods (e.g. larvae-eating fish)

Give public health education on the above measures