This document defines severe malaria and describes its symptoms, risk factors, diagnosis, and treatment. Severe malaria is characterized by high parasite levels in the blood and/or organ dysfunction. Diagnosis involves microscopic examination of blood smears, rapid diagnostic tests, or molecular tests. Treatment consists of supportive care and intravenous antimalarial drugs like artesunate or quinine. Complications are treated based on affected organ systems and may involve oxygen supplementation, anticonvulsants, or blood transfusions.

1. MALARIA

2. DEF:
Severe malaria: acute malaria with high levels of
parasitemia( > 5%) and/or major signs of organ
dysfunction.
 Altered consciousness with or without convulsions
 Deep breathing, respiratory distress
 Metabolic acidosis
 Circulatory collapse
 Pulmonary edema or ARDS
 Renal failure, hemoglobinuria
 Clinical jaundice
 DIC
 Severe anemia
 Hypoglycemia

3.  Clinical manifestations vary with age and geography
 In endemic areas: children, pregnant females &
travelers are at more risk
 Older children & adults develop partial immunity to
febrile malarial episodes after repeated infections & are
low risk for severe malaria
 Seizures & severe anemia are common in children
 Hyperparasitemia, acute renal failure, jaundice are
common in adults
 Cerebral malaria, shock, acidosis, respiratory arrest can
occur at any age

4. DIAGNOSIS:
Available malaria diagnostic tools include:
 Clinical/presumptive diagnosis
 Microscopy
Rapid diagnostic tests(detecting antigen or
antibody)
Molecular techniques(detecting parasite genetic
material)

5. Clinical / Presumptive diagnosis :
Typical clinical features includes fever, malaise,
myalgia, arthralgia & headache.
 Histroy, physical exam, routine lab values are
useful in determining whether malaria should be
considered in differential diagnosis of pt’s illness.
 There are no pathognomic clinical features for
diagnosing malaria. Accurate diagnosis include
detection malaria parasites
 There are no routine lab test results specific to
malaria .
 Anemia is usually mild to moderate.(severe in P.
falciparum)

6.  Clinical findings most predictive of malaria
include fever without localizing symptoms,
enlarged spleen, platelet count < 150* 10(9)/l
serum bilirubin >1.3mg/dl
 Even in endemic areas clinical diagnosis is
incorrect
 If parasite based diagnosis is not available &
there is suspicion of P.falciparum infection, it is
reasonable to begin antimalarial therapy to
prevent progression to severe disease
 Presumptive diagnosis depends on relevant
malaria exposure, clinical manifestations like
fever & suggestive lab findings in absence of
clear alternative diagnosis.

7. Parasite Based diagnosis:
 Tools for parasite based diagnosis include:
i) Microscopy:
detection of parasite in Giemsa stained blood smear by
light microscopy is gold standard
 It allows identification of Plasmodium sps. &
quantification of parasitemia. Also enables detection of
hematological abnormalities & other infectious diseases
like filariasis, trypanosomiasis etc.
 Microscopy cannot reliably detect very low parasitemia (<
5-10%)
 Once diagnosis is established treatment is started &
serial smears should be examined to monitor
parasitological response & ensure resolution of response

8. Parasite density monitoring:
 Standard approach to estimating parasite density
in thick blood smear involves counting asexual
parasite forms & wbc in each microscopy field
until 200 wbc’shave been counted.
 Parasite density = {wbc count(cells/microL) / No.
of wbc’s counted } * No. of parasites counted.
 Parasitemia should be monitored during treatment
to ensure adequate response
CDC recommends daily repeat smears until
negative or until treatment day 7.

9. ii) Rapid diagnostic tests: these are
becoming increasingly important diagnostic tools
due to their accuracy, ease of use & quick results.
 Provide qualitative results but not quantitative
information regarding parasite density
 Less useful for diagnosing acute infection.
 a) antigen detection: based on
immunochromatographic lateral flow technique.
 They detect one of the following antigens:
histidine-rich protein 2, Plasmodium lactate
dehydrogenase & aldolase

10. Molecular tests :
 Their use has been limited to reference lab & is
primarily for research & epidemiological purpose
PCR can be used for confirmation of species &
identification of drug resistant mutations for
malaria cases.
 Loop mediated isothermal amplification for
detection of malarial parasite DNA is being
developed to facilitate use of molecular
technology in endemic area

11. TREATMENT:
 Supportive measures: oxygen, ventilatory
support, cardiac monitoring, pulse oximetry
 Unconscious pts require lumbar puncture to rule
out concomitant bacterial meningitis
 Repeat clinical assessment should be
preformed every 2-4 hrs & lab investigations
every 6 hrs to detect & treat complications
 If coma score decreases, investigatons should
focus on possibility of seizures, hypoglycemia or
worsening anemia
 Predictors for fatality include acidosis, impaired
consciousness, elevated blood urea nitrogen
etc

12. ANTI MALARIAL THERAPY
Two classes of drugs are available for parenteral
therapy:
 Cinchona alkaloids: Quinine & Quinidine
 Artemisinin derivatives: Artesunate, Artemether,
Artemotil.
 I.V Artesunate is preferable treatment in adults &
childern with severe falciparum malaria. If not
available then I.V quinine is the drug of choice

13. Artemisinins
 These clear parasitemia more rapidly then
quinine.
 They are active against gametocytes
 Artesunate is preferred for treatment of severe
malaria
 Has lower mortality rate ,better tolerated then
quinine & acts rapidly
 Eligible pts for parenteral artesunate thrapy
include those with parasitemia >5%, with signs of
severe malaria, or intolerance to oral medications

14. Dosage :
 Standard dosing regimen for I.V artesunate
consists of 5 doses :
 2.4mg/kg as 1st dose followed by 2.4mg/kg at 12
& 24hrs followed by 2.4mg/kg od.
 Total dose can be administered in three doses as
4mg/kg at 0, 24 & 48hrs
 Dosing need not be adjusted for hepatic or renal
failure
 Adverse effects: nausea, vomiting, anorexia&
dizziness. Delayed onset anemia may occur in pts
with severe malaria after completion of artesunate
therapy & transfusion may be required

15. Quinine / Quinidine
 I.V.quinine remains treatment of choice In places
where I.V artesunate is not readily available.
 I.V.quinine dihydrochloride loading dose :
20mg/kg(in 5% dextrose) over 4 hrs followed by
20-30mg/kg in 2-3 equal administrations of
10mg/kg(over 2 hrs at 8 or 12 hrs)
 I.V.quinine gluconate loading dose 10m/kg in NS
over 1 hr followed by 0.02mg/kg /min continuous
infusion.
 I.M injections: 2 injections of 10mg/kg(dilute to 60-
100mg/ml)should be administered 4 hrs apart.
Anterior thigh is preferred.

16.  Quinine & Quinidine acts on pancreatic
secretagogues leading to hyperinsulinemic
hypoglycemia
 Other adverse effects include tinnitus, reversible
hearing loss, nausea, vomiting, dizziness &visual
disturbance.
 Quinidine causes QT prolongation & should be
administered with ECG monitoring.
 These can be combined with doxycyclin,
tetracyclin or clindamycin

17. Pre-referral Treatment:
 In rural endemic areas, where immediate I.V.
therapy is not available, pts should be treated
with pre referral dose of I.M quinine or an
artesunate or intrarectal administration of
artesunate.
 Single artesunate recal suppository dose for pts >
6yrs- 400mg
 If referral is impossible, I.M or rectal treatment
should be continued until pts can tolerate oral
medication

18. Completing therapy:
Total duration of therapy for severe malaria:
 Quinine / Quinidine : 7 days
 artimisinin-based therapy : 3 days
 Oral therapy is started after acute stage of
therapy is treated with parenteral therapy & when
pt can swallow.
 For uncomplicated malaria, full course of
treatment with atovaquone-proguanil or
mefloquine may be administered
 Mefloquine is avoided in pts presenting with
altered consciousness

19. Respiratory status:
 Presence of hypoxia or rales should raise suspicion of
concomitant LRTI
 Pulmonary edema may develop in pts with renal
failure
 ARDS may also complicate severe malaria
 Management ranges from supplementary oxygen to
mechanical ventilation with positive end expiratory
pressure
 Deep breathing-indicates metabolic acidosis & has
poor prognosis

20. Neurologic status:
 Standard clinical case of cerebral malaria includes:
 Blantyre coma score </= 2
 P.falciparum parasitemia
 No other identifiable cause of coma
 Histologic hallmark of cerebral malaria is cerebral
sequestration of parasitized erythrocytes

21. Malarial retinopathy:
 Pathognomic of cerebral malaria
 Features: White centered hemorrhages, vessel
changes & whitening in areas of retina.
 Optic fundi should be evaluated following instillation
of mydriatics.
 Measurement of plasma pHRP2 concentration may
be useful marker for presence of retinopathy

22. Lumbar puncture:
 Pts with altered sensorium should undergo lumbar
puncture to exclude concomitant bacterial meningitis
 In pts with cerebral malaria:
 pressure is about 16cm of CSF.
 elevated total protein level & cell count
Seizure management:
 May be generalized or focal with subtle clinical signs.
Cause should be evaluated besides cerebral malaria(
hypoglycemia, fever).

23.  Benzodiazepines- 1st line agents.
 Diazepam (0.4mg/kg) I.V/per rectum . Lorazepam
(0.1mg/kg) I.V. dose can be repeated once if seizures
do not cease within 5 min of initial dose
 Other options: Phenobarbital (15-20mg/kg slow I.V) or
phenytoin (18mg/kg diluted in 100ml NS infused over
20 min)
 Maintenance doses: phenobarbital(5-15ml/kg/day
orally or slow I.V every 12 hrs) or phenytoin
(10mg/kg/day I.V every 12 hrs)
 Pts with severe malaria should not receive routine
seizure prophylaxis in absence of clinical seizure
activity

24. Anemia :
 Pts with severe anemia may present with or without
altered consciousness
 Hb conc & hematocrit are routinely measured.
 Transfusion should be reserved for pts with poor
prognosis: altered consciousness, high output cardiac
failure, respiratory distress, cool peripheries, high
density parasitemia, hb <4-5g/dl.
 Degree of anemia & level of parasitemia- useful for
predicting need for transfusion & volume to be
transfused.
 10ml/kg of packed cells or 20ml/kg of whole blood are
well tolerated as pts are hypovolemic

25. Exchange transfusion:
 Means to remove infected RBC from circulation &
reduce parasite burden.
 Not regularly used as there is no difference in
outcome.
Coagulopathy:
 DIC is rare in severe malaria
 Thrombocytopenia is common
 Microcirculation in many organs is occluded by fibrin
thrombi

26. Fluids & Nutrition:
Hypoglycemia: common complication of malaria&
marker of severe disease.
 Pathogenesis- parasite glucose consumption &/or
impaired host gluconeogensis
 Administration of quinine/quinidine can cause iatrogenic
hypoglycemia
 Clinical manifestations- seizure& altered consciousness.
Blood glucose conc. Should be assessed
 Administration of initial I.V bolus of dextrose (0.25g/kg).
Blood glucose measurement after 15 min with
administration of repeat bolus until pt is normoglycemic
 Maintainance: with 5% or 10% dextrose

27. Volume management:
 There is thin line b/w under & over hydration
 Reliable markers for intravascular volume depletion:
cool peripheries, delayed capillary refill, low venous
pressure & low urine output.
 Clinical symptoms resolve with transfusion
 When transfusion is not indicated, repeated bolus of
NS or Albumin may de productive
 In cases with renal failure, renal replacement therapy
is beneficial
 Maintenance fluids:5% dextrose

28. Nutrition:
 Substitutes like “ eggnog”(eggs, milk, sugar& oil) or
high calorie drinks may be used in endemic areas
where commercial preparations are not available.
 NG feeding in comatose pts or who are unable to eat
& drink.
 Most pts eat & drink by 5-7 days.
Fever:
 > 38.5oc is common. Reflect host response to
endogenous pyrogens released at time of schizont
rupture.

29.  Paracetamol(acetaminophen- 15mg/kg every 6hrs
orally)reasonable antipyretic agent.
 If fever persists ibuprofen(10mg/kg every 6 hrs orally)
Bacterial infections:
 Severe anemia- risk factor for nontyphoidal
Salmonella septicemia
 Falciparum infection- major risk factor for bacteremia
with multiple organisms.
 Infection should be suspected in pts with severe
anemia& signs of sepsis
 Broad spectrum antibiotic therapy with activity against
gram –ve bacilli should be initiated

30. Pregnancy:
 Pregnant women are more likely to develop severe
P.falciparum malaria particularly in 2nd & 3rd
trimesters
 Fetal death & premature labor are common with
maternal mortality rate upto 50%
 Prompt treatment is required. Artesunate or
Artemether are preferred over quinines in 2nd & 3rd
trimesters as quinines are associated with recurrent
hypoglycemia
 In 1st trimester either Artemisinins or quinines are
acceptible. In this period, hypoglycemia with quinines
is lower & uncertainities regarding safety of
artemisinins is greater.