Malaria

Severe malaria
Severe malaria, which is due to Plasmodium falciparum, is serious enough to
be an immediate threat to life. The illness starts with fever and often vomiting.
Children can deteriorate rapidly over 1–2 days, going into coma (cerebral
malaria) or shock, or manifesting convulsions, severe anaemia and acidosis.
Diagnosis
History. This will indicate a change of behaviour, confusion, drowsiness, and
generalized weakness.
Examination. The main features are:
■ fever
■ lethargic or unconscious
■ generalized convulsions
■ acidosis (presenting with deep, laboured breathing)
■ generalized weakness (prostration), so that the child can no longer walk or
sit up without assistance
■ jaundice
■ respiratory distress, pulmonary oedema
■ shock
■ bleeding tendency
■ severe pallor.
Laboratory investigations. Children with the following findings have severe
malaria:
• severe anaemia (haematocrit <15%; haemoglobin <5 g/dl)
• hypoglycaemia (blood glucose <2.5 mmol/litre or <45 mg/dl).
In children with altered consciousness and/or convulsions, check:
• blood glucose.
In addition, in all children suspected of severe malaria, check:
• thick blood smears (and thin blood smear if species identification required)
• haematocrit.
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In suspected cerebral malaria (i.e. children with unrousable coma for no obvious
cause), perform a lumbar puncture to exclude bacterial meningitis—if there
are no contra-indications to lumbar puncture (see page 316). If bacterial
meningitis cannot be excluded, give treatment for this also (see page 150).
If severe malaria is suspected on clinical findings and the blood smear is
negative, repeat the blood smear.
Treatment
Emergency measures—to be taken within the first hour:
➤Check for hypoglycaemia and correct, if present (see below, page 143).
➤Treat convulsions with rectal diazepam or paraldehyde (see Chart 9, page
14) or with IM paraldehyde (see Appendix 2, page 342)
➤Restore the circulating blood volume (see fluid balance disturbances, page
141 below)
➤If the child is unconscious, minimize the risk of aspiration pneumonia by
inserting a nasogastric tube and removing the gastric contents by suction.
➤Treat severe anaemia (see below, page 142)
➤Start treatment with an effective antimalarial (see below).
Antimalarial treatment
➤If blood smear confirmation of malaria is likely to take more than one hour,
start antimalarial treatment before the diagnosis is confirmed.
• Quinine is the drug of choice in all African countries and most other countries,
except in parts of south-east Asia and the Amazon basin. Give it preferably
IV in normal saline or 5% glucose; if this is not possible, give it IM. Replace
with oral administration as soon as possible.
➤IV quinine. Give a loading dose of quinine (20 mg/kg of quinine dihydrochloride
salt) in 10 ml/kg of IV fluid over a period of 4 hours. Some 8 hours
after the start of the loading dose, give 10 mg/kg quinine salt in IV fluid over
2 hours, and repeat every 8 hours until the child is able to take oral treatment.
Then, give oral quinine doses to complete 7 days of treatment or give one
dose of sulfadoxine-pyrimethamine (SP) where there is no SP resistance. If
there is resistance to SP, give a full therapeutic dose of artemisinin-based
combination therapy. It is essential that the loading dose of quinine is given
only if there is close nursing supervision of the infusion and control of the
infusion rate. If this is not possible, it is safer to give IM quinine.
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➤IM quinine. If IV infusion is not possible, quinine dihydrochloride can be
given in the same dosages by IM injection. Give 10 mg of quinine salt per
kg IM and repeat after 4 hours. Then, give every 8 hours until the malaria is
no longer severe. The parenteral solution should be diluted before use
because it is better absorbed and less painful.
➤IM artemether. Give 3.2 mg/kg IM on the first day, followed by 1.6 mg/kg
IM daily for a minimum of 3 days until the child can take oral treatment. Use
a 1 ml tuberculin syringe to give the small injection volume.
➤IV artesunate. Give 2.4 mg/kg IV or IM on admission, followed by 1.2 mg/
kg IV or IM after 12 hours, then daily for a minimum of 3 days until the child
can take oral treatment of another effective antimalarial.
Complete treatment in severe malaria following parenteral artesunate or
artemether administration by giving a full course of artemisinin-based
combination therapy or oral quinine to complete 7 days of treatment. If available
and affordable, quinine should be combined with clindamycin.
Supportive care
➤Examine all children with convulsions for hyperpyrexia and hypoglycaemia.
Treat hypoglycaemia (see below, page 143). If a temperature of ≥39 °C
(≥102.2 °F) is causing the child distress or discomfort, give paracetamol.
➤If meningitis is a possible diagnosis and cannot be excluded by a lumbar
puncture (see above), give parenteral antibiotics immediately (see page 150).
• Avoid useless or harmful ancillary drugs like corticosteroids and other antiinflammatory
drugs, urea, invert glucose, low-molecular dextran, heparin,
adrenaline (epinephrine), prostacyclin and cyclosporin.
In an unconscious child:
➤Maintain a clear airway.
➤Nurse the child on the side to avoid aspiration of fluids.
➤Turn the patient every 2 hours.
• Do not allow the child to lie in a wet bed.
• Pay attention to pressure points.
Take the following precautions in the delivery of fluids:
• Check for dehydration (see page 111) and treat appropriately.
• During rehydration, examine frequently for signs of fluid overload. The most
reliable sign is an enlarged liver. Additional signs are gallop rhythm, fine
crackles at lung bases and/or fullness of neck veins when upright. Eyelid
oedema is a useful sign in infants.
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• If, after careful rehydration, the urine output over 24 hours is less than
4 ml/kg body weight, give IV furosemide, initially at 2 mg/kg body weight.
If there is no response, double the dose at hourly intervals to a maximum of
8 mg/kg body weight (given over 15 minutes).
• In children with no dehydration, ensure that they receive their daily fluid
requirements but take care not to exceed the recommended limits (see
section 10.2, page 273). Be particularly careful in monitoring IV fluids.
Complications
Coma (cerebral malaria)
• Assess the level of consciousness according to the AVPU or another locally
used coma scale for children (see page 17).
• Give meticulous nursing care and pay careful attention to the airway, eyes,
mucosae, skin and fluid requirements.
• Exclude other treatable causes of coma (e.g. hypoglycaemia, bacterial
meningitis). Perform a lumbar puncture if there are no signs of raised
intracranial pressure (see above). If you cannot do a lumbar puncture and
cannot exclude meningitis, give antibiotics as for bacterial meningitis.
➤Convulsions are common before and after the onset of coma. When
convulsions are present, give anticonvulsant treatment with rectal diazepam
or paraldehyde (see Chart 9, page 14) or IM paraldehyde (see Appendix 2,
page 342). Correct any possible contributing cause such as hypoglycaemia
or very high fever. If there are repeated convulsions, give phenobarbital
(see page 343).
Some children may have a cold, clammy skin. Some of them may be in shock
(cold extremities, weak pulse, capillary refill longer than 3 seconds). These
features are not usually due to malaria alone. Suspect an additional bacteraemia
and give both an antimalarial and antibiotic treatment, as for septicaemia (see
section 6.5, page 158).
Severe anaemia
This is indicated by severe palmar pallor, often with a fast pulse rate, difficult
breathing, confusion or restlessness. Signs of heart failure such as gallop
rhythm, enlarged liver and, rarely, pulmonary oedema (fast breathing, fine basal
crackles on auscultation) may be present.
➤Give a blood transfusion as soon as possible (see page 277) to:
— all children with a haematocrit of ≤12% or Hb of ≤4 g/dl
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— less severely anaemic children (haematocrit >12–15%; Hb 4–5 g/dl)
with any of the following:
— clinically detectable dehydration
— shock
— impaired consciousness
— deep and laboured breathing
— heart failure
— very high parasitaemia (>10% of red cells parasitized).
➤Give packed cells (10 ml/kg body weight), if available, over 3–4 hours in
preference to whole blood. If not available, give fresh whole blood (20 ml/
kg body weight) over 3–4 hours.
• A diuretic is not usually indicated because many of these children have a
low blood volume (hypovolaemia).
• Check the respiratory rate and pulse rate every 15 minutes. If one of them
rises, transfuse more slowly. If there is any evidence of fluid overload due
to the blood transfusion, give IV furosemide (1–2 mg/kg body weight) up to
a maximum total of 20 mg.
• After the transfusion, if the Hb remains low, repeat the transfusion.
• In severely malnourished children, fluid overload is a common and serious
complication. Give whole blood (10 ml/kg body weight rather than 20 ml/
kg) once only and do not repeat the transfusion.
Hypoglycaemia
Hypoglycaemia (blood glucose: <2.5 mmol/litre or <45 mg/dl) is particularly
common in children under 3 years old, in children with convulsions or
hyperparasitaemia, and in comatose patients. It is easily overlooked because
clinical signs may mimic cerebral malaria.
➤Give 5 ml/kg of 10% glucose (dextrose) solution IV rapidly (see Chart 10,
page 15). Recheck the blood glucose in 30 minutes, and repeat the dextrose
(5 ml/kg) if the level is low (<2.5 mmol/litre or <45 mg/dl).
Prevent further hypoglycaemia in an unconscious child by giving 10% glucose
(dextrose) infusion (add 10 ml of 50% glucose to 90 ml of a 5% glucose
solution, or 10 ml of 50% glucose to 40 ml of sterile water). Do not exceed
maintenance fluid requirements for the child’s weight (see section 10.2, page
273). If the child develops signs of fluid overload, stop the infusion; repeat the
10% glucose (5 ml/kg) at regular intervals.
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Once the child is conscious, stop IV treatment. Feed the child as soon as it is
possible. Breastfeed every 3 hours, if possible, or give milk feeds of 15 ml/kg
if the child can swallow. If not able to feed without risk of aspiration, give
sugar solution by nasogastric tube (see Chapter 1, page 4). Continue to monitor
the blood glucose level, and treat accordingly (as above) if found to be <2.5
mmol/ litre or <45 mg/dl.
Respiratory distress (acidosis)
This presents with deep, laboured breathing while the chest is clear—
sometimes accompanied by lower chest wall indrawing. It is caused by systemic
metabolic acidosis (frequently lactic acidosis) and may develop in a fully
conscious child, but more often in children with cerebral malaria or severe
anaemia.
• Correct reversible causes of acidosis, especially dehydration and severe
anaemia.
— If Hb is ≥5 g/dl, give 20 ml/kg of normal saline or an isotonic glucoseelectrolyte
solution IV over 30 minutes.
— If Hb is <5 g/dl, give whole blood (10 ml/kg) over 30 minutes, and a
further 10 ml/kg over 1–2 hours without diuretics. Check the respiratory
rate and pulse rate every 15 minutes. If either of these shows any rise,
transfuse more slowly to avoid precipitating pulmonary oedema (see
guidelines on blood transfusion in section 10.6, page 277).
Aspiration pneumonia
Treat aspiration pneumonia immediately because it can be fatal.
➤Place the child on his/her side. Give IM or IV chloramphenicol (25 mg/kg
every 8 hours) until the child can take this orally, for a total of 7 days. Give
oxygen if the SaO2 is <90%, or, if you cannot do pulse oximetry, there is
cyanosis, severe lower chest wall indrawing or a respiratory rate of ≥70/
minute.
Monitoring
The child should be checked by nurses at least every 3 hours and by a doctor
at least twice a day. The rate of IV infusion should be checked hourly. Children
with cold extremities, hypoglycaemia on admission, respiratory distress, and/
or deep coma are at highest risk of death. It is particularly important that these
children be kept under very close observation.
• Monitor and report immediately any change in the level of consciousness,
convulsions, or changes in the child’s behaviour.
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• Monitor the temperature, pulse rate, respiratory rate (and, if possible, blood
pressure) every 6 hours, for at least the first 48 hours.
• Monitor the blood glucose level every 3 hours until the child is fully
conscious.
• Check the rate of IV infusion regularly. If available, use a giving chamber
with a volume of 100–150 ml. Be very careful about overinfusion of fluids
from a 500 ml or 1 litre bottle or bag, especially if the child is not supervised
all the time. Partially empty the IV bottle or bag. If the risk of overinfusion
cannot be ruled out, rehydration using a nasogastric tube may be safer.
• Keep a careful record of fluid intake (including IV) and output.
6.2.2 Malaria (non-severe)
Diagnosis
The child has:
• fever (temperature ≥37.5 °C or ≥99.5 °F) or history of fever, and
• a positive blood smear or positive rapid diagnostic test for malaria.
None of the following is present, on examination:
— altered consciousness
— severe anaemia (haematocrit <15% or haemoglobin <5 g/dl)
— hypoglycaemia (blood glucose <2.5 mmol/litre or <45 mg/dl)
— respiratory distress
— jaundice.
Note: If a child in a malarious area has fever, but it is not possible to confirm
with a blood film, treat the child as for malaria.
Treatment
Treat at home with a first-line antimalarial, as recommended in the national
guidelines. WHO now recommends artemisinin-based combination therapy as
first line treatment (see possible regimens below). Chloroquine and sulfadoxinepyrimethamine
are no longer the first- and second-line antimalarials due to
high level of drug resistance to these medicines in many countries for falciparum
malaria. However, chloroquine is the treatment for non-falciparum malaria
(P. vivax, P. ovale, P. malariae).
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Treat for 3 days with one of the following regimens recommended by
WHO:
➤Artemether/lumefantrine. Combined tablets containing 20 mg of artemether
and 120 mg of lumefantrine:
Combined tablet: child 5–<15 kg: 1 tablet two times a day for 3 days;
child 15–24 kg: 2 tablets two times a day for 3 days
➤Artesunate plus amodiaquine. Separate tablets of 50 mg artesunate and
153 mg base of amodiaquine:
Artesunate: child 3–<10 kg: 1/2 tablet once daily for 3 days;
child 10 kg or over: 1 tablet once daily for 3 days.
Amodiaquine: child 3–<10 kg: 1/2 tablet once daily for 3 days;
child 10 kg or over: 1 tablet once daily for 3 days
➤Artesunate plus sulfadoxine/pyrimethamine. Separate tablets of 50 mg
artesunate and 500 mg sulfadoxine/25 mg pyrimethamine:
Artesunate: child 3–<10 kg: 1/2 tablet once daily for 3 days;
child 10 kg or over: 1 tablet once daily for 3 days.
Sulfadoxine/pyrimethamine: child 3–<10kg: 1/2 tablet once on day 1;
child 10 kg or over: 1 tablet once on day 1
➤Artesunate plus mefloquine. Separate tablets of 50 mg artesunate and
250 mg base of mefloquine:
Artesunate: child 3–<10 kg: 1/2 tablet once daily for 3 days;
child 10 kg or over: 1 tablet once daily for 3 days.
Mefloquine: child 3–<10 kg: 1/2 tablet once on day 2;
child 10 kg or over: 1 tablet once on day 2
➤Amodiaquine plus sulfadoxine/pyrimethamine. Separate tablets of 153 mg
base of amodiaquine and 500 mg sulfadoxine/25 mg pyrimethamine
Amodiaquine: child 3–<10 kg: 1/2 tablet once daily for 3 days;
child 10 kg or over: 1 tablet once daily for 3 days
Sulfadoxine/pyrimethamine: child 3–<10 kg: 1/2 tablet once on day 1;
child 10 kg or over: 1 tablet once on day 1.
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Complications
Anaemia (not severe)
In any child with palmar pallor, determine the haemoglobin or haematocrit
level. Check that severe anaemia is not present. Haemoglobin between
5 g/dl and 9.3 g/dl (equivalent to a haematocrit of between approximately 15%
and 27%) indicates non-severe anaemia. Begin treatment (omit iron in any
child with severe malnutrition).
➤Give home treatment with a daily dose
of iron/folate tablet or iron syrup for
14 days: see page 315). Note: If
the child is taking sulfadoxinepyrimethamine
for malaria, do
not give iron tablets that
contain folate until a followup
visit in 2 weeks. The
folate may interfere with the
action of the antimalarial.
• Ask the parent to return with the
child in 14 days. Treat for 3 months, where
possible (it takes 2–4 weeks to correct the
anaemia and 1–3 months to build up iron stores).
➤If the child is over 1 year and has not had mebendazole in the previous
6 months, give one dose of mebendazole (500 mg) for possible hookworm
or whipworm infestation (see page 340).
➤Advise the mother about good feeding practices.
• Omit iron in any child with severe malnutrition in the acute phase.
Follow-up
Tell the mother to return if the fever persists for two days after starting treatment,
or sooner if the child’s condition gets worse. She should also return if the
fever comes back.
If this happens: check if the child actually took the treatment and repeat a
blood smear. If the treatment was not taken, repeat it. If it was taken but the
blood smear is still positive, treat with a second-line antimalarial. Reassess
the child to exclude the possibility of other causes of fever (see pages 133–
139, and sections 6.3 to 6.10 below).
If the fever persists after two days of treatment with the second-line antimalarial,
ask the mother to return with the child to reassess for other causes of fever.
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Palmar pallor—
sign of anaemia
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