Complicated malaria refers to any clinical presentation requiring parenteral treatment, including severe malaria which meets strict WHO criteria. Of falciparum malaria cases, around 10% are severe, with a mortality of 10% without treatment but up to 50% for those meeting the severe criteria. Pathophysiology of severe manifestations includes sequestration of infected red blood cells in organs, hypoglycemia, acidosis, anemia, acute renal failure, and shock. Diagnosis involves blood smears to identify Plasmodium species and quantify parasitemia level.

1. MANAGEMENT OF
COMPLICATED
MALARIA
Dr. Freda Dodd-Glover (MB ChB; BSc Med
Sci)

2. Management of Complicated Malaria
FORMAT
INTRODUCTION

AETIOLOGY/EPIDEMIOLOGY

DIFFERENTIAL DIAGNOSES

PATHOPHYSIOLOGY

MANAGEMENT

CONCLUSION

BIBLIOGRAPHY


3. Management of Complicated
Malaria
 INTRODUCTION  Complicated malaria
 Increasing Rates of malaria infection-
refers to any clinical
presentation requiring
WHY?
parenteral treatment.
 POOR CONTROL- drug-resistant
strains of parasites (e.g. chloroquine
 Severe malaria refers
to those patients whose
resistance) presentation meets the strict
 Increasing international WHO case definition of
severe disease as indicated
travel/Immunity
in Table 1
 Delays in diagnosis or treatment.

4. Table 1: WHO case definition of Severe Falciparum
Malaria
Cerebral malaria Unrousable coma (GCS < 11/15), with peripheral P.
falciparum parasitaemia after exclusion of other causes of
encephalopathy
Severe anaemia Normocytic anaemia with haemoglobin <5 g dl−1
(haematocrit<15%) in presence of parasitaemia >10 000
ml−1
Respiratory distress Pulmonary oedema or acute respiratory distress
syndrome (ARDS) Would now also include rapid laboured
‘acidotic’ breathing sometimes abnormal in rhythm
Renal failure Urine output of less than 400 ml in 24 h (or <12 ml kg−1 in
children) and a serum creatinine >265 mmol l−1 (>3.0 mg
dl−1)
Hypoglycaemia Whole blood glucose <2.2 mmol l−1 (40 mg dl−1)
Circulatory collapse (shock) Systolic blood pressure <70 mmHg or core-skin
temperature difference >10°C
Coagulation failure Spontaneous bleeding and/or laboratory evidence of
disseminated intravascular coagulation
Complicated malaria:
Impaired consciousness of any degree, Prostration, Such patients with complicated malaria should be
Jaundice, Intractable vomiting, Parasitaemia ≥2% in non- managed as severe malaria, i.e. with parenteral
immune individuals (no previous malaria) antimalarials even though they do not necessarily meet
the criteria of severe disease.
Online ISSN 1471-8391 - Print ISSN 0007-1420
***Levels of parasitaemia should be interpreted in the light of immunity Copyright © 2012 Oxford University Press

5. Management of Complicated
Malaria
AETIOLOGY/EPIDEMIOLOGY
 Of the four species of malarial parasites
that commonly cause infection in man, P. Of all cases of falciparum malaria, around
falciparum is responsible for virtually all the 10% can be classified as severe,
severe cases and deaths. among which the mortality is 10% (i.e.
1% of all cases) but may rise to as
 The other species, P. vivax, P. ovale and P. high as 50% (of case definition severe
malariae, cause mainly a febrile illness and cases). Any form of complicated or
only rarely lead to severe disease. severe malaria must therefore be
regarded as a life-threatening medical
 Falciparum malaria remains a major cause emergency.
of morbidity and mortality worldwide. The
annual clinical caseload may well be over
500 million, leading to between 1 and 3
million deaths, mainly among young
children . More than 90% of these deaths
occur in sub-Saharan Africa.

6. Management of Complicated
Malaria
DIFFERENTIAL
acute coma renal failure
DIAGNOSES •viral encephalitis (herpes •Glomerulonephritis
 typhoid simplex, HIV, mumps, etc) •hypertension.
 respiratory and urinary tract •bacterial meningoencephalitis •herbal medicines
infections. (pyogenic and rarely •Snakebite
tuberculous)
 viral illnesses (such as •fungal and protozoal jaundice and
influenza, dengue fever etc) meningoencephalitis (African hepatomegaly
trypanosomiasis), •viral hepatitis
• cerebral typhoid, •alcohol
• brain abscess •drug-induced
•heat stroke diseases
cerebrovascular events •biliary disease
•hypertensive encephalopathy •yellow fever

7. Management of Complicated
Malaria
PATHOPHYSIOLOGY
 Altered consciousness or coma.
It is believed that coma or alteration of the level of consciousness is caused by
sequestration of infected RBCs in the brain.
 • Hypoglycaemia
This is as a result of impaired production or release of glucose in the liver and
increased utilization in the tissues. Hypoglycaemia may also result from reduced
intake or use of drugs such as quinine.

8. Management of Complicated
Malaria
 Convulsions
- sequestration of infected RBCs in the brain
- severe accompanying metabolic disorders e.g. Hyponatraemia.
 • Raised intracranial pressure
The cause of this is not exactly known but has been noted present from time to time
during the illness and may be due to increased mass of red blood cells sequestered
in the brain, or because of dilatation of vessels in the brain in response to locally
generated cytokines. Raised intracranial pressure is not the primary cause of coma
or death in a majority of cases.
 • Anaemia
This is partly due to the destruction of red cells that contain parasites. Several other
mechanisms may accelerate the development of anaemia. These include destruction
of non-parasitised red blood cells, bone marrow suppression, intravascular
haemolysis, abnormal bleeding and renal failure

9. Management of Complicated
Malaria
 Acidosis
Probably due to a relative shortage of oxygen in tissues occupied by
sequestered parasites. This shortage of oxygen is made worse by
hypovolaemia and/or severe anaemia as both of these conditions may
impair the supply of oxygen to tissues. This lack of oxygen in tissues forces
the tissues to get their energy by other biochemical pathways not
dependent on oxygen. The result of this is the release of lactic acid, leading
to metabolic acidosis. There is evidence that drugs containing salicylates
e.g. Aspirin often given to lower fever may exacerbate this metabolic
acidosis.
• Acute renal failure
 Acute tubular necrosis is a common complication in adults, but it is rarely
seen in children. It is fully reversible if the patient is kept alive e.g. by
peritoneal dialysis, for a period ranging from a few days to 3 weeks. Renal

10. Management of Complicated
Malaria
 • Pulmonary oedema and Adult respiratory distress syndrome (ARDS)
-Pulmonary oedema (non-cardiogenic) may result from excessive fluid
replacement by intravenous (iv) fluids especially if there is renal failure.
- Adult respiratory distress syndrome (ARDS) appears to be due to a direct
effect of parasites sequestered in the lungs, possibly through release of
cytokines. Both of these complications are usually found in children in
endemic areas.
 • Haemoglobinuria
- rapid breakdown of red blood cells in the circulation (massive
intravascular haemolysis).

11.  Jaundice
Jaundice is more common in adults than children and is due to
haemolysis and partly to liver dysfunction.
 • Shock
-Inadequate cardiac output and poor tissue perfusion. In some patients
it may occur concurrently with bacteraemia.
 • Platelets
In P. falciparum malaria, the platelet count is typically low.
Nevertheless, spontaneous bleeding is rare in both children and adults.
When it develops it results from disseminated intravascular
coagulopathy (DIC).

12. Management of Complicated
Malaria
INVESTIGATIONS
 Blood - THICK/THIN films/Rapid Antigen Test - P. falciparum malaria with possibly
hyperparasitaemia.
Thin films, which are a monolayer of red cells dried and fixed with methanol,
can provide valuable clinical information:
a- The intensity of infection or parasitaemia (usually measured as the percentage
of red cells infected). Parasitaemia does not always correlate with disease severity,
higher parasitaemias = special consideration for parenteral Rx.
+ = 1–10 per 100 thick fields.
++ = 11-100 per 100 thick fields.
+++ = 1–10 per thick field.
++++ = >10 per thick field.

13. Management of Complicated
Malaria
RDT :
-pfHRp2 pfHRP2 – 2 lines
-PMA pfHRP2/PMA- 3
-pLDH lines
pLDH – 3 lines

14. Management of Complicated
Malaria
b- Parasite maturity The presence of more mature ring forms, trophozoites
containing pigment or schizonts in the peripheral blood film is associated with a
worse prognosis than in those patients with only small immature ring forms .
c- Neutrophils containing malarial pigment (hemozoin) The presence of malarial
pigment in peripheral blood polymorphs reflects prolonged infection and a large
sequestered parasite burden. The finding of ≥5% of polymorphs containing hemozoin
is associated with a poorer prognosis .
d- Monitoring the effect of treatment Peripheral blood films should be carefully
examined at least once daily in complicated and severe malaria. An initial increase in
parasitaemia is not uncommon during the first 18–24 h of treatment and
paradoxically, may be of favourable prognostic significance.

15. Management of Complicated
Malaria
 Blood - Hypoglycaemia - RBS
Acidosis i.e metabolic acidosis- Blood gases
Hyperlacticaemia
Severe normocytic anaemia packed cell volume < 15%, Hb < 5 gldl). - FBC
Renal impairment, as indicated by abnormal creatinine and urea levels. – BUE &
Cr
 Urine - Haemoglobinuria (BLACK WATER FEVER – ?quinine,artemisinin, ?
Haemoglobinopathies-G6PD
 LP- CSF to exclude meningitis/ meningoencephalitis

16. Management of Complicated
Malaria
 TREATMENT
SUPPORTIVE THERAPY
 HYDRATION MONITORING
 GLYCAEMIC CONTROL
 PARENTERAL MEDICATION- Cinchona alkaloids (eg. quinine) +/-
clindamycin/doxycycline/tetracycline
(recrudecense prevention)
 Artemisinin derivatives
 *** EXCHANGE Transfusion
 CARE OF THE UNCONSCIOUS

17. Management of Complicated
Malaria
 HYDRATION MONITORING:
 Input-output chart
 Electrolytes : Na, K, Ca, Mg, Phosphate

18. Management of Complicated
Malaria
 GLYCAEMIC CONTROL:
 FBS/RBS monitoring – regularly esp. in the unconscious. Quinine
 IV Dextrose infusion
NB: Irreversible neuroglycopenia

19. Management of Complicated
Malaria
 Cinchona Alkaloids : Quinine/quinidine
 Ideally ICU/HDU supervision
 Narrow therapeutic index : Cardiac arrhythmias
Hypotension
Hypoglycaemia
Prolongation of QTc Interval on ECG
Loading dose: 20mg/kg over 4 hrs
Maintenance dose: 10 mg/kg over 4 hrs 8 hrly till parasitaemia< 1%

20. Management of Complicated
Malaria
 ARTEMISININ DERIVATIVES: Artesunate (water soluble - iv)
Arthemeter (fat soluble – im)
- more rapid parasite clearance (active on the immature parasite forms)
- safer and simpler to administer.
- reduce mortality in adults by over a third (35%) in complicated and severe
malaria when compared to intravenous quinine (15% as opposed to 22%) (P =
0.0002).
- fewer episodes of hypoglycaemia than quinine.
- Reassuringly, the effects of artesunate were greatest in patients with
hyperparasitaemia.
- Artesunate has a limited shelf life.
- The dose is 2.4 mg kg−1 IV, followed by the same dose at 12 and 24 h, then
once daily until the patient is able to take artesunate (2 mg kg−1 per day) per os

21. Management of Complicated
Malaria
 CARE OF THE UNCONSCIOUS:
 Frequent turning in bed
 NG feeding
 Eye and oral care
 Toileting needs
 Seizure chart

22. Management of Complicated
Malaria
 CONCLUSION:
 Falciparum malaria is potentially life-threatening.
 Blood film microscopy is the gold-standard for diagnosis of malaria.
 Parenteral treatment is required in severe / complicated malaria.
 Artemisinin derivatives are safer and more effective than the cinchona
alkaloids.
 Prompt and adequate treatment are essential to survival.

23. Management of Complicated Malaria -
References
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 Castelli F, Carosi G. Diagnosis of malaria infection In Castelli F, Carosi G ed Handbook of malaria infection in the tropics.
Organissazione per la cooperazione sanitaria internazionale 1997 pp 114
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2005;434:214–17.
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 ter Kuile F, White NJ, Holloway P et al. Plasmodium falciparum: in vitro studies of the pharmacodynamic properties of drugs used for the
treatment of severe malaria. Exp Parasitol 1993;76:85–95.
 Dondorp A, Nosten F, Stepniewska K et al. Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial. Lancet