Table 1.
Clinical and laboratory features of severe malaria and their prognostic value.
| Clinical feature | Definition | Frequency (± to +++) |
Prognostic Value (± to +++) |
Range of effect size [95% CI]) |
|---|---|---|---|---|
| Impaired Consciousness | Glasgow Coma Score < 11 or Blantyre score < 3 in children who are too young to speak | +++ | +++ | Marsh et al., [10] RR 2.00 [0.90–4.10] Leopold el al., [73] RR 4.38 [3.75–5.12] (“coma”) Jallow et al., [29] RR 4.50 [3.60–5.60] Marsh et al., [10] RR 12.6 [7.20–22.0] (“coma”, defined as when patients are unable to locate painful stimuli) Evans et al., [71] RR 13.5 [CI not stated] |
| Respiratory Distress | Rapid, deep and labored breathing or oxygen saturations < 92% | +++ | +++ | Waller et al., [69] RR 2.70 [1.20–5.80] (abnormal chest signs) Jallow et al., [29] RR 3.40 [2.80–4.20] Evans et al., [71] RR 3.91 [2.83–5.41] Maitland et al., [68] OR 5.10 [2.90–9.00] Gérardin et al., [234] OR 7.44 [2.82–21.7] Marsh et al., [10] RR 9.40 [5.50–16.2] Njuguna et al., [23] OR 9.41 [7.69–11.5] Waller et al., [69] RR 11.4 [4.00–33.0] (pulmonary complications) |
| Multiple Convulsions | 2 or more seizures within 24 hours | +++ | + | Jallow et al., [29] RR 2.0 [1.50–2.50] Njuguna et al., [23] OR 2.21 [1.67 to 2.92] Marsh et al., [10] RR 2.90 [1.70–4.90] Gérardin et al., [234] OR 3.01 [1.14–7.58] |
| Prostration | Inability to sit unassisted or feed (in babies) due to extreme weakness | +++ | + | Njuguna et al., [23] OR 1.05 (0.71 to 1.56) Marsh et al., [10] RR 1.80 [0.90–3.60] Waller et al., [69] RR 2.40 [1.10–5.00] Evans et al., [71] RR 3.15 [1.67–5.95] Jallow et al., [29] RR 3.70 [1.50–9.00] |
| Shock | Compensated: capillary refill time > 3s or temperature gradient from mid to proximal limb Decompensated: systolic blood pressure < 70mmHg |
+ | +++ | Evans et al., [71] RR 2.26 [1.63–3.13] Jallow et al., [29] RR 2.80 [1.00–8.30] Maitland et al., [68] OR 2.80 [1.50–5.20] Njuguna et al., [23] OR 4.76 [3.40 to 6.66] |
| Pulmonary Edema | Radiologically confirmed or oxygen saturation <92% in air with respiratory rate >30/min, may be associated with clinical wheeze/crepitations | ± | +++ | Gérardin et al., [234] OR 0 [0.00–54.43] Leopold el al., [73] 4.54 (95% CI 3.07–6.71) |
| Significant Bleeding | Including recurrent or prolonged bleeding from nose, gums or venepuncture sites; blood in vomit or stool | ± | +++ | NA |
| Jaundice | Plasma or serum bilirubin >50 µM with a parasite count >10,000/µl | + | ++ | Jallow et al., [29] RR 1.60 [1.20–2.10] Njuguna et al., [23] OR 2.43 [1.49 to 3.98] Gérardin et al., [234] OR 2.69 [0.99–6.88] Marsh et al., [10] RR 4.60 [2.20–9.40] |
| Severe Malaria Anemia | Hemoglobin < 5g/dL or hematocrit < 15% | +++ | + | Evans et al., [71] RR 0.37 [0.28–0.50] Jallow et al., [29] RR 0.50 [0.40–0.70] Marsh et al., [10] RR 1.40 [0.80–2.50] Gérardin et al., [234] OR 1.45 [0.40–4.27] Maitland et al., [68] OR 1.70 [1.00–3.10] Obonyo et al., [235] RR 2.04 [1.32–3.16] Njuguna et al., [23] OR 2.24 [1.94–2.60] Waller et al., [69] RR 3.40 [1.60–7.10] |
| Hypoglycemia | Blood or plasma glucose < 2.2mM | +++ | +++ | Jallow et al., [29] RR 1.80 [1.40–2.30] Gérardin et al., [234] OR 2.97 [0.89–8.64] Maitland et al., [68] OR 3.40 [1.70–6.70] Evans et al., [71] RR 4.25 [3.09–5.83] Marsh et al., [10] RR 5.40 [2.90–10.2] Waller et al., [69] RR 7.10 [3.60–13.8] Njuguna et al., [23] OR 8.81 [6.98 to 11.1] |
| Metabolic Acidosis | Base deficit of >8 mEq/L or plasma bicarbonate of <15 mM. | +++ | +++ | Marsh et al., [10] RR 2.10 [0.60–7.00] Maitland et al., [68] OR 2.30 [1.20–4.40] Jallow et al., [29] RR 5.60 [2.40–12.9] Gérardin et al., [234] OR 5.94 [2.28–15.1] Njuguna et al., [23] OR 7.07 [5.77–8.67] |
| Hyperlactataemia | Plasma or whole blood lactate > 5mM | +++ | +++ | Jallow et al., [29] RR 1.30 [0.80–2.20] Evans et al., [71] RR 1.37 [0.74–2.54] (lactate 5.0–6.9 mmol/L) Evans et al., [71] RR 2.60 [1.40–4.81] (lactate 7.0–8.9 mmol/L) Evans et al., [71] RR 6.28 [3.74–10.6] (lactate ≥ 9 mmol/L) |
| Renal Impairment | Plasma or serum creatinine >265µM (3 mg/dl) or blood urea >20 mM | + | ++ | Maitland et al., [68] OR 3.00 [1.70–5.40] (creatinine >80 μmol/L) Jallow et al., [29] RR 5.10 [3.20–8.00] Njuguna et al., [23] OR 6.09 [4.43–8.37] (kidney injury) Gérardin et al., [234] OR 11.3 [1.40–87.4] |
| Hyperparasitaemia | P. falciparum parasitemia >10% in peripheral blood | ++ | ± | Gérardin et al., [234] OR 0.79 [0.14–2.83] (parasitemia≥4%) Njuguna et al., [23] OR 1.19 [1.02–1.38] Evans et al., [71] RR 1.37 [0.90–2.08] Marsh et al., [10] RR 1.40 [0.60–3.00] Jallow et al., [29] RR 1.60 [1.10–2.30] Waller et al., [69] children with hyperparasitaemia (parasite count ≥ 500, 000/µL) were 2.20 [1.10–4.40] times more likely to die. |
| Thrombocytopenia | Platelet levels < 20,000/µL | NA | NA | Gérardin et al., [234] OR 6.13 [1.70–32.8] (platelet count < 100,000/mm3) Lampah et al., [236] OR 11.3 [9.49–13.4] (platelet count < 50,000 g/dL) |
Legend
The definition, frequency, and prognostic value of clinical and laboratory features of SM in children under 12 y of age are indicated semi-quantitatively from equivocal (±) to high (+++), based on “Severe Malaria” Review published by the World Health Organization in Tropical Medicine and International Health 2014 SM [17]. Effect sizes and confidence intervals are shown for studies that analyzed the association of any severity feature with death without adjustment for the presence of other severity features and quantified the effect size. Studies where this was unclear have been excluded from the table. Abbreviations: Confidence Interval (CI); Odds Ratio (OR); Relative Risk (RR)