|
Most of the 1-3 million who die each year from malaria are
children, mainly in Africa, which is hyperendemic for malaria. In older children, malaria
has a similar course as in adults. However, in children below the age of 5 years,
particularly infants, the disease tends to be atypical and more severe.
In the first two months of life, children may not
contract malaria or the manifestations may be mild with low-grade parasitemia, due to the
passive immunity offered by the maternal antibodies.
In endemic and hyperendemic areas, the
parasite rate increases with age from 0 to 10% during first three months of life to 80 to
90% by one year of age and the rate persists at a high level during early childhood. The
mortality rate is highest during the first two years of life. By school age, a
considerable degree of immunity would have developed and asymptomatic parasitemia can be
as high as 75% in primary school children. In Africa, on an average about 1 in 20 children
die from malaria, and in worst affected areas, even 1 in 5 or 6 die from malaria and its
related diseases (e.g., anemia).
In areas of low endemicity, where the
immunity is low, severe infection occurs in all age groups including adults. The morbidity
and mortality due to malaria in children tends to be very high in these areas.
Malnutrition does not increase
susceptibility to severe falciparum malaria. In fact, it has been observed that
well-nourished children are more likely to develop severe disease than those with
malnutrition. However, when severe malaria does occur, malnourished children have a higher
morbidity and mortality.
Hemoglobin types in the newborn and
the susceptibility to malaria: It has been observed that congenital malaria and
malarial parasitemia in newborns are very rare, in spite of significant maternal
parasitemia and sequestration of the parasites in the placenta. The reasons for this are
not fully understood. Passive immunity due to maternal antibodies, retarded growth of the
parasites in erythrocytes containing Hemoglobin F and resistance for parasite growth in
old red cells with HbF may be the causes.
Children with heterozygous sickle cell
trait have lower parasite rates and less fatal infections compared to normal children
(however, homozygous sickle cell disease does not protect against fatal infection).
Thalassemias may also confer some protection, may be due to higher levels of HbF. Glucose 6-phosphate dehydrogenase deficiency has been found to have a
protective effect against malaria in some studies.
Severe falciparum
malaria in children
Severe falciparum malaria is the
commonest cause of death in infants and children in areas endemic and hyperendemic for
malaria. Inadequate immunity results in rapid increase in the parasite count and
development of complications. Delay in diagnosis and treatment also contributes to the
mortality.
Clinical features of severe disease
should be given utmost priority. History of travel to malarious area, history of previous
antimalarial therapy, history of vomiting, diarrhoea, fluid intake, urine output,
convulsions etc. should be obtained from parents. Physical examination should include
assessment of hydration and of complications of falciparum malaria. Rectal temperature
should be measured in infants and small children. All children should be weighed on
admission.
Thick and thin films for malaria,
haematocrit and hemoglobin, blood glucose (by finger prick) should be done in all cases.
If the report is likely to be delayed, presumptive antimalarial treatment should be
started. Parasite count should be done in all positive cases of falciparum malaria and a
parasite count of >2% indicates impending problems and >5% should be considered as
severe infection. All cases with severe falciparum malaria should be managed as medical
emergency.
Cerebral malaria:
CNS manifestations are common in
children and they can be due to the following causes:
- Severe infection and cerebral malaria.
- Severe infection and hypoglycemia.
- Hypoglycemia induced by quinine.
- Severe anemia.
- High grade fever.
- Drug induced behavioural changes.
Therefore CNS dysfunction may not
always indicate cerebral malaria and it is very important to differentiate between the
various causes.
Clinical features of cerebral malaria:
The earliest symptoms of cerebral
malaria in children include high-grade fever (37.5-410C) and failure to eat and
drink. Vomiting and cough are common.
Febrile convulsions are common in
children aged 6 months to five years and it may be difficult to differentiate from
cerebral malaria. If coma persists more than 30 minutes after a convulsion in a child with
falciparum malaria, then cerebral malaria should be suspected. Convulsions can continue
after the onset of coma and they are associated with higher morbidity and sequelae.
Some children may have noisy and laboured
breathing. Deep breathing due to acidosis may be seen in some. Cold, clammy skin with a
core-to-skin temperature difference of >100C may be seen. Some children may
have associated shock, with the systolic pressure below 50 mm Hg. Some children may
present with extreme opisthotonus ('bent-like-a-bow') posture, mimicking either tetanus or
meningitis.
Neurological signs include features of
symmetrical upper motor neuron and brain stem disturbances including disconjugate gaze,
decerebrate and decorticate postures. In children with profound coma, corneal reflex and
'Doll's eye' movements may be absent. Retinal haemorrhages and exudates are rarer than in
adults.
In all comatose children, CSF
examination must be done to rule out other diseases. CSF examination in cerebral
malaria is usually normal; however in some, increase in pressure, protein level and
cell-count (mostly lymphocytes, 50cells/ml) may be seen.
Leukocytosis may be present in severe
disease and may not necessarily indicate bacterial infection.
Treatment: The management of
cerebral malaria in children is same as in adults.
A single intramuscular injection of
phenobarbitone sodium, 10-15mg/kg of body weight can be given prophylactically to prevent
convulsions in all cases of severe falciparum malaria. When convulsions do occur, they can
be controlled immediately with diazepam or paraldehyde.
Bronchopneumonia is a common complication
in children with cerebral malaria. Comatose children should be nursed in either lateral or
semi-prone position and turned frequently to prevent aspiration as well as bedsores.
With effective antimalarial chemotherapy,
children generally regain consciousness in 2-3 days; however, sometimes the coma may last
as long as one week despite the reduction in fever and parasitemia. Prolonged coma may
necessitate nasogastric feeding. About 10% of children who survive may have neurological
sequelae in the form of hemiparesis, cerebellar ataxia, cortical blindness, hypotonia,
spasticity or aphasia.
Severe anemia: Anemia is the
commonest complication of malaria in children. The rate of development and degree of
anemia depend on the severity and duration of parasitemia. In some children, repeated
untreated episodes of malaria can result in normocytic anemia. In these cases, bone marrow
shows changes of dyserythropoeisis and peripheral blood shows low-grade parasitemia,
sometimes with pigmented monocytes. In patients with high parasitemia, anemia may develop
rapidly due to hemolysis of the parasitized red cells and this may worsen even after
completion of antimalarial therapy. It can present with serious problems in children with
pre-existing anaemia.
Children with severe anemia may present
with symptoms and signs of cardiac failure- dyspnoea, tachycardia, gallop rhythm, basal
crackles, hepatomegaly, raised jugular pressure etc. Severe anemia can also cause
confusion, restlessness, retinal haemorrhages and even coma.
Treatment: Furoscemide, 1-2 mg/kg
up to a maximum of 20 mg can be given in children with signs of cardiac failure. Children
with a hematocrit of less than 15% (Hemoglobin less than 5g%) should be given blood
transfusion. 10ml/kg of packed cells or 20 ml/kg of whole blood can be given by slow
transfusion. Whenever possible, parents should be encouraged to donate blood to minimize
the risk of other blood borne infections. Hemoglobin concentration should ideally be
maintained above 7g/dL (hematocrit above 20%).
Renal failure: Renal failure is
uncommon in children. A slight increase in urea and creatinine may sometimes occur due to
dehydration and it returns to normal with rehydration.
Treatment: In older children with
renal dysfunction, the management consists of careful assessment and monitoring, initial
conservative management and if needed, dialysis.
Commonest cause of oliguria in children
with malaria is dehydration. Such patients have signs of dehydration, lower blood
pressure, high urine specific gravity with low urinary sodium, and normal urine
microscopy. Such patients should be carefully rehydrated. If the urine output fails to
improve to about 4ml/kg in the first eight hours despite adequate rehydration, then
furoscemide can be given, starting at 2mg/kg, then doubled at hourly intervals to a
maximum of 8mg/kg. If this fails to improve the urine output, injection dopamine can be
infused at 2-5mg/kg/min through a central venous catheter or a free flowing peripheral
vein. If the child fails to produce more than 4 ml urine/kg body weight at the end of 16
hours, then further fluid load should be withheld. If the conservative measures fail,
dialysis should be considered.
Bleeding disorders: Bleeding
tendencies with prolonged clotting time, thrombocytopenia and decreased coagulation
factors may occur in falciparum malaria. Spontaneous bleeding from various sites,
including the upper GI tract may occur.
Pulmonary oedema: Children with
cerebral malaria, severe anemia and high parasitemia may develop acute pulmonary oedema.
It may also be due to fluid overload. Tachypnoea is the earliest sign of impending
pulmonary oedema.
Treatment: Pulmonary oedema is
managed with stringent fluid management, propped up position, oxygen inhalation, diuretics
and venesection and letting of blood. If needed, patient has to be started on mechanical
ventilation with positive end expiratory pressure.
Hypoglycemia: This is also
less common in children compared to the adults. It may be associated with lactic acidosis
in severe falciparum infections. It may present with convulsions, or impairment in the
level of consciousness.
Treatment: Intravenous 50%
dextrose, 1 ml/kg, should be given followed by intravenous infusion of 10% dextrose.
Recurrent hypoglycemia may occur even during administration of 10% dextrose. Further
episodes of drug induced, hyperinsulinemic hypoglycemia can be prevented by administration
of somatostatin analogue octreotide. However, it is very expensive.
Fever: In children, high-grade
fever itself can cause various problems and hence should be managed energetically. Fanning
and tepid sponging should be used regularly. Paracetamol injection can be used in
hyperpyrexia.
Antimalarial drugs: In cases of
severe falciparum malaria, the child should be admitted. Oral antimalarials should be
avoided. Chloroquine or quinine injections should be used, depending on the sensitivity.
Chloroquine can be given by intravenous, intramuscular or subcutaneous injections while
quinine can be given by intravenous or intramuscular injections. All intravenous infusions
should be carefully titrated with infusion pumps.
Dose of antimalarials
for severe malaria in children
Drug |
Dose |
Chloroquine |
Intravenous:
5 mg base/kg diluted with normal saline or 5% dextrose 10 ml/kg, infused over 4 hours.
The dose can be repeated every 12 hours to obtain a total dose of 25 mg base/kg. Rapid
I.V. bolus may cause fatal hypotension.
Subcutaneous: 2.5 mg/kg, followed by another 2.5 mg/kg after one hour; repeated
every 12 hours to attain a dose of 25 mg/kg. |
Quinine |
Intravenous:
24mg salt/kg or 20 mg base/kg in normal saline or 5% dextrose, infused over 4 hours as
a bolus, followed by 12 mg salt/kg or 10 mg base/kg infused every eight hours. (Bolus dose
should be skipped in children who have already received quinine in the previous two days).
Note that the dose is slightly higher in children (24 mg of salt per kg as against 20 mg
of salt per kg in adults).
Intramuscular: 10 mg base/kg every eight hours by deep I.M. injections to the
anterior thigh.
The total duration of treatment is 7-10 days. In children with protracted severe
malaria, the dose of quinine may have to be reduced by one third or one half after the
third day until the clinical condition improves, to avoid cumulative toxicity. |
Arteether |
3mg
/ kg IM for 3 days |
Artemether |
3.2mg
/ kg IM followed by 1.6 mg / kg for 5 days or 9.6 mg/kg max. |
Artesunate |
2.4
mg/kg on the first day (additional 1.2 mg/kg after 4 hours in case of severe falciparum
malaria), followed by 1.2 mg/kg daily until patient is able to swallow or for a maximum of
7 days. |
|
|
Dose
of other antimalarial drugs
Severe Malaria:
Differences between Adults and Children
Clinical manifestation |
Adults |
Children |
| Duration
of illness prior to complications |
5-7 days |
1-2 days |
| Convulsions |
Common |
Very common; can be due to severe infection, hypoglycemia,
febrile seizures, severe anemia etc. |
| Abnormal
brain stem reflexes (oculovestibular, oculocervical) |
Rare |
More common |
| C.S.F.
pressure |
Usually normal |
Variable, often raised |
| Resolution
of coma |
2-4 days |
1-2 days |
| Neurological
sequelae |
<5% |
>10% |
| Cough |
Uncommon |
Common |
| Anemia |
Common |
More common and more severe; may be the presenting feature |
| Jaundice |
Common |
Uncommon |
| Pre-treatment
hypoglycemia |
Uncommon |
Common |
| Pulmonary
oedema |
Common |
Rare |
| Renal
failure |
Common |
Rare |
| Bleeding/clotting
disturbances |
Up to 10% |
Rare |
|
