Severe malaria is defined by the demonstration of asexual forms of the malaria parasites in the blood in a patient with a potentially fatal manifestation or complication of malaria in whom other diagnoses have been excluded.
Even though the complications have been considered to be almost unique to P. falciparum infection, in recent years, many cases of severe malaria, including deaths, have been reported in P. vivax and P. knowlesi malaria. The case fatality of P. falciparum malaria is around 1 per cent and this accounts for more than half a million deaths per year all over the world; 80% of these deaths are caused by cerebral malaria. The incidence of complications and deaths due to the other two types is much lower.
The criteria for severe malaria, as established by the World Health Organization (WHO) are shown in 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.
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.[2,3]
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).
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).
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.
Severe manifestations and complications of malaria
In a patient with 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 malaria.
|Table 1: Indicators of severe falciparum malaria and poor prognosis [1-6]|
|1. Impaired consciousness [See Cerebral malaria]:||Unarousable coma not attributable to any other cause, with a Glasgow Coma Scale score <11 in adults (non localising, incomprehensible) or a Blantyre Coma Scale of <3 in children|
|2. Metabolic Acidosis||A base deficit of >8 meq/l or, if unavailable, a plasma bicarbonate of <15 mM or venous plasma lactate >5mM. Severe acidosis manifests clinically as respiratory distress–rapid, deep and laboured breathing|
|3. Hypoglycemia||Whole blood glucose concentration of less than 2.2 mmol/l (less than 40 mg/dl).|
|4. Severe anemia||A haemoglobin concentration <5 g/dl or a haematocrit of <15% in children <12 years of age (<7 g/dl and <20%, respectively, in adults) together with a parasite count >10 000/µl|
|5. Renal impairment (acute kidney injury)||Serum creatinine >265 µmol/l (> 3.0 mg/dl) or blood urea >20mM|
|6. Jaundice||Plasma or serum bilirubin >50 µM (3 mg/dl) together with a parasite count >100 000/µl|
|7. Pulmonary edema||Radiologically confirmed, or oxygen saturation <92% on room air with a respiratory rate >30/min, often with chest indrawing and crepitations on auscultation|
|8. Significant bleeding||Including recurrent or prolonged bleeding from nose gums or venepuncture sites; haematemesis or melaena|
Compensated shock is defined as capillary refill ≥3 s or temperature gradient on leg (mid to proximal limb), but no hypotension. Decompensated shock is defined as systolic blood pressure <70 mm Hg in children or <80 mm Hg in adults with evidence of impaired perfusion (cool peripheries or prolonged capillary refill)
P. falciparum parasitaemia >10%
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.
Evaluation of the Patient
Malaria is a very simple disease to diagnose and treat; yet it claims more lives than any other infectious disease in the world. It is therefore very essential that every case of malaria be assessed thoroughly.
General: Functional status, prostration, breathlessness, level of consciousness, hydration, toxicity, puffiness of face and lids, etc.
Vital signs: Pulse rate, blood pressure (hypotension), temperature (hyperpyrexia), respiratory rate (tachypnoea, acidotic breathing).
Other signs: Pallor, Jaundice, Cyanosis, Edema, etc.
Abdomen: Liver, spleen, bowel sounds – Tender hepato/ splenomegaly is more common in acute malaria.
Respiratory system: Basal crackles, wheezes; sometimes, associated pneumonia and its bronchial breath sounds.
C.N.S.: Level of sensorium, convulsions, neck stiffness, ocular fundii, any focal deficits.
Hemoglobin: Anemia is common in malaria. Rapid reduction in level of hemoglobin is seen in falciparum malaria and less than 7 g/ dl should be a warning.
Total leukocyte count: It can vary from low to high, and neutrophilic leukocytosis is common in severe malaria with or without associated bacterial infection. Leukopenia is seen in severe malaria with septicemia, and chronic hypersplenism.
Platelet count: Thrombocytopenia is common in P. falciparum and P. vivax malaria, but it does not correlate with the severity of the infection.
How to do a parasite count?
Thick film: The density of malarial parasites can be read against the leukocytes and an approximate parasite count can be calculated.
- Count the number of asexual forms of the parasite ( rings, trophozoites and schizonts) against 100 leukocytes and multiply by 75, this gives an approximate total per micro liter (mm3).
- The average leukocyte count per microscopic field is about ten. Therefore, multiply the average number of parasites per field by 750, this also gives an approximate total per micro liter.
Thin film: Count the number of parasites within 1000 red blood cells and divide this by 10. This gives the percentage of parasitemia.
A parasite count of 100000 or more per mm3 (or 5% and more) is considered as severe infection.
Blood Glucose: Hypoglycemia is a common problem encountered in malaria and may remain undetected because the symptoms and signs of hypoglycemia viz. sweating, tachycardia etc., are even otherwise seen in malaria. It is very important to monitor the blood glucose levels once at least 6 hours in falciparum malaria, particularly if the patient is pregnant or is receiving quinine.
Moderate elevation in blood urea and creatinine are common. Significant increase is suggestive of renal impairment.
Hyperbilirubinemia is common in malaria, particularly due to hemolysis. Some patients with falciparum malaria may have very high levels of conjugated bilirubin due to associated hepatocyte dysfunction.
Serum albumin levels may be reduced, some times markedly.
Serum aminotransferases, 5′ – nucleotidase and lactic dehydrogenase are elevated.
Prothrombin time and partial thromboplastin time are elevated in 20% of patients with cerebral malaria. Some may have features of disseminated intravascular coagulation.
Hyponatremia is common and needs careful management.
Lactic acidosis is seen in severely ill patients, especially in patients with hypoglycemia and renal dysfunction. It can be suspected if there is a wide anion gap.
Urine examination may show albuminuria, microscopic hematuria, hemoglobinuria and red cell casts. With massive intravascular hemolysis, urine may be black in colour.
- Persistence of fever even after 48 hours of initial treatment.
- Continuously worsening headache.
- Persistent vomiting.
- Any complications of P. falciparum malaria– altered sensorium, convulsions, anemia, jaundice, hyperpyrexia, bleeding and clotting disorders, breathlessness, high coloured urine etc.
- Patients who are at higher risk for development of complications of P. falciparum malaria-extremes of age, pregnancy etc.
- Patients who appear sick and prostrated
- Significant dehydration
- WHO. Severe Malaria. WHO. Tropical Medicine and International Health. 2014;19(Suppl. 1):7–131.[See]
- 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
- Jagannath Sarkar et al. Risk factors for malaria deaths in Jalpaiguri district, West Bengal, India: evidence for further action. Malaria Journal 2009;8:133 Available at
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