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Severe falciparum malaria is defined by the demonstration of asexual forms of P.
falciparum in a patient with a potentially fatal manifestation or complication of
malaria in whom other diagnoses have been excluded.
Even though the complications are almost unique to P.
falciparum infection, that DOES NOT mean that all cases of P. falciparum
malaria invariably develop complications. The case fatality of P. falciparum malaria is
around 1 per cent and this accounts form 1 to 3 million deaths per year all over the
world. 80% of these deaths are caused by cerebral malaria.
In
1990, the World Health Organization (WHO) established criteria for
severe malaria and these were revised in the year 2000 to include
other clinical manifestations and laboratory values that portend a
poor prognosis based on clinical experience in semi-immune patients
(Table 1). The major complications of severe malaria include
cerebral malaria, pulmonary edema, acute renal failure, severe
anemia, and/or bleeding. Acidosis and hypoglycemia are the most
common metabolic complications. Any of these complications can
develop rapidly and progress to death within hours or days.[1]
The presentation of severe malaria varies with age and geographical distribution.
In areas of high malaria transmission, severe malaria mainly affects children
under five years of age. The mortality rate is higher in adults than in
children but African children develop neuro-cognitive sequelae following severe
malaria more frequently.
In children, the complications include metabolic acidosis (often caused by hypovolaemia), hypoglycaemia, hyperlacticacidaemia, severe anaemia,
seizures and raised intracranial pressure and concomitant bacterial infections
occur more frequently. In adults, renal failure and pulmonary oedema are more common causes of death.[2]
In many patients, several of these complications exist
together or evolve in rapid succession within a few hours. In
clinical practice, patients must be assessed for any of these
signs or symptoms that suggest an increased risk for developing
complications and must be treated immediately. In
various studies risk factors for severe malaria and death
include age greater than 65 years, female sex (especially
when associated with pregnancy), nonimmune status, coexisting
medical conditions, no antimalarial prophylaxis, delay
in treatment, and severity of the illness at admission (coma,
acute renal failure, shock, pulmonary edema, coagulation disorders). In tropical countries with a high transmission
of malaria (hyperendemic areas), severe malaria is predominantly
a disease of young children (1 month to 5 years of age).[1]
Predisposing
factors for complications and death from P. falciparum malaria:
In
various studies, risk factors for severe malaria and death
include age greater than 65 years, female sex (especially
when associated with pregnancy), nonimmune status, coexisting
medical conditions, no antimalarial prophylaxis, delay
in treatment, and severity of the illness at admission (coma,
acute renal failure, shock, pulmonary edema, coagulation disorders). In tropical countries with a high transmission
of malaria (hyperendemic areas), severe malaria is predominantly
a disease of young children (1 month to 5 years of age).[1]
Lab.
abnormalities:
Thrombocytopenia is the most common laboratory abnormality
(60% of cases), followed by hyperbilirubinemia (40%), anemia
(30%), and elevated hepatic aminotransferase levels (25%). The leukocyte count is usually normal or low, but neutrophilia
with a marked increase in band forms (left shift) is
present in the majority of cases. The erythrocyte sedimentation
rate, C-reactive protein, and procalcitonin are almost invariably
elevated. The severity of malaria corresponds to the degree of
the laboratory abnormalities. In one study of travelers who
returned from the tropics, thrombocytopenia and hyperbilirubinemia
had a positive predictive value of 95% for malaria.[1]
Severe
manifestations and complications of P. falciparum malaria
In a patient with falciparum malaria in
whom other diseases have been excluded, the presence of one or more of the following
manifestations is sufficient for a diagnosis of severe falciparum malaria.
Table 1:
Indicators of severe malaria and poor prognosis [1,3-5]
|
Manifestation |
Features |
|
Initial World Health
Organization criteria from 1990 [3] |
| 1. Cerebral malaria: |
Unarousable coma not
attributable to any other cause, with a Glasgow Coma Scale score
≤9;
Coma should persist for at least 30 min after a generalized
convulsion |
| 2. Severe anemia |
Hematocrit <15% or
hemoglobin < 50 g/l in the presence of parasite count >10000/µl |
| 3. Renal failure |
Urine output <400 ml/24 hours in adults (<12 ml/kg/24 hours in children) and a serum creatinine
>265 µmol/l (> 3.0 mg/dl) despite adequate volume repletion |
|
4. Metabolic (Lactic) Acidosis/acidosis |
Metabolic
acidosis is defined by an arterial blood pH of <7.35 with a plasma bicarbonate
concentration of <22 mmol/L; hyperlactatemia is defined as a plasma lactate
concentration of 2-5 mmol/L and lactic acidosis is characterized by a pH <7.25 and a
plasma lactate >5 mmol/L. |
|
5. Pulmonary edema or acute respiratory distress syndrome (ARDS) |
Breathlessness,
bilateral crackles, and other features of pulmonary oedema. The acute lung injury score is calculated on the basis of radiographic densities, severity of
hypoxemia, and positive end-expiratory pressure |
|
6.
Hypoglycemia |
Whole blood
glucose concentration of less than 2.2 mmol/l (less than 40 mg/dl). |
|
7. Hypotension and shock (algid
malaria) |
Systolic
blood pressure <50 mmHg in children 1-5 years or <70 mm Hg in
patients ≥5 years; cold and clammy skin or a core-skin
temperature difference >100C |
|
8.
Abnormal bleeding and/or disseminated
intavascular coagulation |
Spontaneous bleeding from the gums, nose, gastrointestinal tract, retinal haemorrhages
and/or laboratory evidence of disseminated intravascular coagulation. |
|
9.
Repeated generalised convulsions |
≥3
generalized seizures within 24 hours |
|
10.
Haemoglobinuria |
Macroscopic
black, brown or red urine; not associated with effects of oxidant drugs or enzyme defects
(like G6PD deficiency) |
|
Added World Health
Organization criteria from 2000 [4] |
|
11. Impaired consciousness |
Various
levels of impairment may indicate severe infection although not falling into the
definition of cerebral malaria. These patients are generally arousable |
|
12. Prostration |
Extreme weakness, needs support |
|
13. Hyperparasitemia |
5% parasitized erythrocytes or > 250 000 parasites/µl (in nonimmune individuals) |
| 14.
Hyperpyrexia |
Core body
temperature above 400C |
| 15. Jaundice (Hyperbilirubinemia) |
Serum
bilirubin of more than 43m mol/l (2.5 mg/dl). |
|
Other |
| 16.
Fluid and electrolyte disturbances [5] |
Dehydration, postural hypotension, clinical evidence of hypovolemia |
| 17.
Vomiting of oral drugs |
Patients
with persistent vomiting may have to be admitted for parenteral therapy. |
|
18. Complicating or associated infections |
Aspiration
bronchopneumonia, septicemia, urinary tract infection etc. |
| 19.
Other indicators of poor prognosis [5] |
Leukocyte
count >12,000/cumm; high CSF lactate (>6 mmol/l)and low CSF glucose;
more than 3-fold elevation of
serum enzymes (aminotransferases); increased plasma 5'-nucleotidase; low antithrombin III
levels; peripheral schizontemia; papilloedema/retinal oedema |
|
20.
Malarial Retinopathy |
A large,
prospective autopsy study of children dying with cerebral malaria in
Malawi found malarial retinopathy to be a better indicator of
malarial coma. Similar retinopathy in an adult has also been
reported. |
Differential Diagnosis: The differential diagnosis of fever in a severely ill patient is
broad. Coma and fever may result from meningoencephalitis or malaria. Cerebral
malaria is not associated with signs of meningeal irritation (neck stiffness,
photophobia, Kernig sign) but the patient may be opisthotonic. As untreated
bacterial meningitis is almost invariably fatal, a diagnostic lumbar
puncture should be performed to exclude this condition. There is also considerable
clinical overlap between septicaemia, pneumonia and severe malaria – and these
conditions may coexist. In malaria endemic areas particularly, where
parasitaemia is common in the young age group, it is often impossible to rule
out septicaemia in a shocked or severely ill obtunded child. Where possible,
blood should always be taken on admission for culture, and if there is any doubt,
empirical antibiotic treatment should be started immediately along with antimalarial
treatment.[6]
References:
- Andrej Trampuz,
Matjaz Jereb, Igor Muzlovic, Rajesh M Prabhu. Clinical review:
Severe malaria. Critical Care 2003;7:315-323 Available at
http://ccforum.com/content/7/4/315
Njuguna PW, Newton CR. Management of severe falciparum malaria.
J Postgrad Med [serial online] 2004;50:45-50. Available at
http://www.jpgmonline.com/text.asp?2004/50/1/45/6653
- World Health Organization: Severe and complicated malaria.
Trans R Soc Trop Med Hyg 1990;84(suppl 2):S1-S65.
- World Health Organization: Severe falciparum malaria.
Trans R Soc Trop Med Hyg 2000;94(suppl 1):S1-S90.
- Management of Severe Malaria: A practical handbook. Second edition. World Health Organization. Geneva, 2000. Available at
http://apps.who.int/malaria/docs/hbsm.pdf
- Guidelines for the treatment of malaria. World Health Organization.
Geneva, 2006. pp 41-61. Available at
http://apps.who.int/malaria/docs/TreatmentGuidelines2006.pdf
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