Malaria and Severe Malaria

1. Severe Malaria.
By
Nirav Hitesh Kumar Valand

2. Introduction
• Malaria is a protozoal disease caused by the Genus
Plasmodium and transmitted by an infected Anopheles
mosquito.
• Four species of the genus Plasmodium cause nearly all
malarial infections in humans i.e. P. falciparum, P. vivax, P.
ovale, and P. malariae.
• Almost all deaths are caused by falciparum malaria.

3. Epidemiology
• In 2017, there were 219 million cases of Malaria worldwide,
with ~435,000 deaths.
• Uganda has the third highest number of P. falciparum
infections in sub-Saharan Africa, and some of the highest
reported malaria transmission rates in the world.

4. Epidemiology
• Accounting for 34 percent of outpatient visits and 37 percent
of hospital admissions, malaria places a heavy burden on the
health system
• Child deaths from malaria have fallen by 40 per cent since
2000, but children under 5 still represent 78 per cent of global
malaria deaths – or 456,000 per year.

6. Pathophysiology
• Four important pathologic processes have been identified in
patients with malaria: fever, anemia, immunopathologic events,
and tissue anoxia.
• Fever occurs when erythrocytes rupture and release merozoites
into the circulation.
• Anemia is caused by hemolysis, sequestration of erythrocytes in
the spleen and other organs, and bone marrow suppression.

7. Cont..
• Immunopathological events are due to excessive production of
proinflammatory cytokines, responsible for tissue anoxia,
formation of immune complexes and immune suppression.
• Cytoadherence of infected erythrocytes to vascular endothelium
leading to obstruction of blood flow and capillary damage, with
resultant vascular leakage of blood, protein, and fluid and tissue
anoxia

8. Cont..
• In addition, hypoglycemia and lactic acidemia are caused by
anaerobic metabolism of glucose.
• The cumulative effects of these pathologic processes may lead to
cerebral, cardiac, pulmonary, intestinal, renal, and hepatic failure.

9. Clinical Features
• Febrile paroxysms x-tised by high fever, sweats, and
headache, as well as myalgia, back pain, abdominal pain,
nausea, vomiting, diarrhea, pallor, and jaundice.
• Distinctive physical signs may include splenomegaly
(common), hepatomegaly, and pallor as a consequence of
anemia.

10. Severe Malaria.
• Main features for severe malaria includes;
ØImpaired consciousness including unarousable coma.
ØGeneralized multiple convulsions; more than 2 in 24 hours.
ØGeneralized weakness (Prostration) or lethargy.
ØDeep labored breathing and respiratory distress.
ØPulmonary edema (Radiological)
ØAbnormal bleeding

11. Cont….
ØSevere pallor.
ØClinical jaundice
ØCirculatory collapse with systolic BP<50mmHg.
ØHemoglobinuria
ØLab findings of;
ØHypoglycemia <4.5g/dl / <2.5 mmol/l
ØHyperparasitemia i.e. >100,000 parasites/µl
ØSevere anemia i.e. Hb <5g/dl
ØHigh blood lactate and serum creatinine

12. Complications of Severe Malaria.
qCerebral malaria
• Is an unarousable coma for >30 min after a generalized
convulsion in a child with P. falciparum parasitemia.
• There is an absence of other reasons for coma.
• Has a fatality rate of 15-20%
• LP shows an increased CSF pressure and proteins.
qRenal failure - Urine output < 12 ml/kg in 24 hours and plasma
creatinine > 3.0 mg/dl, with parasitemia.
qHyperpyrexia; Temp. >39˚c.

13. Cont..
qShock.
qSeizures – 2 or more in 24 hours.
qCirculatory collapse (Algid Malaria)
qSevere anemia – Severe palmar pallor, fast PR, DIB, confusion
and restlessness.
qHypoglycemia – particularly common in children <3 years, and
mimics cerebral malaria.
qRespiratory distress – due to lactic acidosis, there’s deep labored
breathing.

14. Cont…
qHyperreactive malaria syndrome (Tropical splenomegaly
syndrome).
• Chronic complication
• Xtised by hepatomegaly, splenomegaly, anemia and elevated
IgM.
• Impaired immune response to P.falciparum.
• Px – Chronic abd. Swelling, pain, leg swelling, weight loss.

15. • Diagnostic criteria
ØMajor criteria include the following:
§Gross splenomegaly 10 cm or more below the costal margin in
adults for which no other cause can be found
§Elevated serum IgM level 2 standard deviations or more above
the local mean
§Clinical and immunologic responses to antimalarial therapy
§Regression of splenomegaly by 40% by 6 months after start of
therapy
§High antibody levels of Plasmodium species (≥1:800)

16. ØMinor criteria include the following:
• Hepatic sinusoidal lymphocytosis
• Normal cellular and humoral responses to antigenic challenge,
including a normal phytohemagglutination response
• Hypersplenism
• Lymphocytic proliferation
• Familial occurrence
Cont..

17. Investigations
• RDT or thick blood slide for diagnosis of malaria
• Random blood sugar and Hb level if clinically indicated
• LP in cases of coma and convulsions.

18. Management.
• First line treatment for severe malaria is IV artesunate.
• Dosage is 3mg/kg for children <20kg and 2.4mg/kg for
children >20kg.
ØFirst dose – on admission
ØSecond dose – at 12 hours.
ØThird dose – at 24 hours.
• Then once a day until patient is able to tolerate oral
medication, then give a full course of oral ACT.

19. Cont..
• Quinine
• Give a loading dose of quinine dihydrochloride salt at 20
mg/kg by infusion in 10 ml/kg of IV fl uid over 2–4 h.
• Then, 8 h after the start of the loading dose, give 10 mg/kg
quinine salt in IV fl uid over 2 h, and repeat every 8 h until
the child can take oral medication.
• The infusion rate should not exceed a total of 5 mg/kg per h
of quinine dihydrochloride salt.

20. Cont..
• Artemether.
• Given by IM
• First dose is at admission i.e. 3.2mg/kg
• Second dose after 24hrs i.e. 1.6mg/kg
• Third dose after 48 hours i.e. 1.6 mg/kg
• Then once a day until patient is able to tolerate oral
medication, then give a full course of oral ACT

22. ØConcomitant use of antibx.
ØSepticemia and severe malaria are associated
ØThere is substantial diagnostic overlap, particularly in
children in areas of moderate and high transmission.
ØBroad- spectrum antibiotic treatment should be given with
antimalarial drugs to all children with suspected severe
malaria until a bacterial infection is excluded

23. Management of complications.
• Cerebral malaria.
ØExclude other causes of coma e.g. hypoglycemia, bacterial
meningitis.
ØPerform LP if there are no CIs to R/o bacterial meningitis.
ØMonitor vital signs

24. Cont..
• Seizures
ØGive IV diazepam 0.2kg/mg slowly (Max 10mg) or rectal
diazepam 0.5mg/kg.
ØIf convulsions still persist:
ØGive phenobarbital 10-15 mg/kg loading dose then2.5 mg/kg
once or twice daily if still necessary or phenytoin 15 mg/kg
loading dose.
ØCheck blood glucose to R/o hypoglycemia.

25. Cont..
• Hypoglycemia.
• Give 5mg/kg of dextrose 10% by a slow bolus over 5-7 min.
• Recheck the blood glucose after 30 min, and repeat the
dextrose (5 ml/kg) if the level is low.
• Once the child can take food orally, stop IV treatment and
feed the child by nasogastric tube.
• Breastfeed every 3 h, if possible, or give milk feeds of 15 ml/
kg if the child can swallow

26. • Severe anemia.
• Give 10 ml/kg packed cells or 20 ml/kg whole blood over 3–
4 h.
• Check the respiratory rate and pulse rate every 15 min. If one
of them rises, transfuse more slowly.
• Repeat if the Hb remains low.
• In severely malnourished children, fluid overload is common.
Give whole blood (10 ml/kg rather than 20 ml/kg) once only

27. • Shock
• Correct hypovolaemia as appropriate, Give sodium chloride
0.9% by fast IV infusion bolus 20 ml/kg in 15 min and
monitor fluid balance charts.
• Take blood for culture and give parenteral broad spectrum
antibx.

28. • Renal failure
• Careful fluid challenge with 20 ml/kg of normal saline,
followed by furosemide 1 mg/kg (max 5 mg/kg)
• If no response noted; restrict fluid intake;
• dialysis indicated in presence of refractory hyperkalemia or
metabolic acidosis, fluid overload and rapid rise of serum
creatinine.

29. • Respiratory acidosis.
• Give Oxygen.
• Correct reversible causes of acidosis, especially dehydration
and severe anemia.
• Hyperpyrexia.
• Give paracetamol 1 g every 6 hours 10 mg/kg
• tepid sponging
• fanning