Background
Methods
Patients
Data collection
Definitions and criteria
Data handling and statistical analysis
Results
Patient characteristics
Characteristics | Value |
---|---|
Median age (range), y
| |
Adult (n = 65) | 46.9 (18.4 - 83.6) |
Child (n = 3) | 4.8 (2.8 - 5.2) |
Men, n (%)
| 47 (69) |
Continent of birth, n (%)
| |
Europe | 34 (50) |
Africa | 27 (40) |
Other | 7 (10) |
Immunity status*, n (%)
| |
Non-immune | 39 (57) |
Partially immune | 29 (43) |
Semi immune | 0 (0) |
Chemoprophylaxis, n (%)
| |
Adequate | 1 (2) |
Inadequate | 58 (85) |
Absent | 49 (72) |
Inappropriate | 9 (13) |
Unknown | 9 (13) |
Indication for artesunate, n (%)
| |
Severe malaria§ (> 1 of the following criteria) | 51 (75) |
Impaired consciousness | 18 (26) |
Multiple convulsions (> 2 episodes/24 h) | 0 (0) |
Respiratory distress or pulmonary edema | 4 (6) |
Shock (systolic blood pressure < 70 mm Hg) | 6 (9) |
Haemoglobinuria | 2 (3) |
Abnormal bleeding | 1 (2) |
Hypoglycaemia (glucose < 2.2. mmol/L) | 1 (2) |
Acidaemia (pH < 7.25) | 3 (4) |
Acidosis (plasma bicarbonate < 15 mmol/L) | 4 (6) |
Anaemia (Hb < 3.1 mmol/l or haematocrit < 15%) | 0 (0) |
Hyperparasitaemia (> 5%) | 33 (49) |
Hyperlactataemia (lactate > 5 mmol/L) | 8 (12) |
Renal impairment (creatinine > 265 μmol/L) | 7 (11) |
Jaundice (bilirubin > 50 μmol/L) | 24 (35) |
Non severe malaria on admission
| 17 (25) |
Clinical deterioration to severe malaria | 4 (6) |
Parasitaemia between 2-5% | 4 (6) |
Unable to take oral medication† | 5 (7) |
Other‡ | 4 (6) |
Characteristic | Number of patients (%) | Value |
---|---|---|
Mean weight (SD), kg | 53 (78) | 73.2 (20) |
Mean temperature (SD), °C | 60 (88) | 38.6 (1.3) |
Mean respiratory rate (SD), breaths/min | 16 (24) | 25 (8) |
Mean heart rate (SD), beats/min | 64 (94) | 106 (18) |
Mean systolic blood pressure (SD), mm Hg | 63 (93) | 115 (19) |
Mean diastolic blood pressure (SD), mm Hg | 63 (93) | 66 (13) |
Median parasitaemia (range),% parasitized erythrocytes | 68 (100) | 5.0 (0.05-37.4) |
Median haemoglobin (range), mmol/L | 68 (100) | 8.0 (3-10.2) |
Median haematocrit (range),% | 66 (97) | 38 (18-50) |
Mean erythrocytes (SD), × 1012 cells/L | 51 (75) | 4.2 (1.2) |
Median leukocyte count (range), × 109cells/L | 68 (100) | 5.2 (2.5-13.2) |
Median serum urea (range), mmol/L | 66 (97) | 10 (2-94) |
Median serum creatinine (range), μmol/L | 68 (100) | 92 (3-1081) |
Median total bilirubin (range), μmol/L | 60 (88) | 42 (0-299) |
Median sodium (range), mmol/L | 68 (100) | 134 (121-146) |
Median potassium (range), mmol/L | 65 (96) | 3.8 (2.7-41.0) |
Median glucose (range), mmol/L | 61 (90) | 6.4(2.0-18.4) |
Median pH (range) | 35 (51) | 7.45 (6.71-7.57) |
Median base excess (range), mmol/L | 40 (59) | 0.8 (-18.0-28.6) |
Mean HCO3- (SD), mmol/L | 44 (65) | 21.3 (4.9) |
Median plasma lactate (range), mmol/L | 35 (51) | 2.8 (9.0-34.0) |
Treatment
Variable | Number of patients (ntotal = 68) |
---|---|
Initial treatment, n (%)
| |
Artesunate | 43 (63) |
monotherapy | 39 (57) |
+ clindamycin | 2 (3) |
+ doxycycline | 2 (3) |
Quinine | 19 (28) |
AP | 2 (3) |
AL | 2 (3) |
SP + doxycycline | 1 (2) |
Unknown oral anti-malarial | 1 (2) |
Artesunate
| |
Median number of doses (range) | 3 (1-7) |
Median cumulative dose (range), mg | 600 (120-1320) |
Median cumulative dose/bodyweight (range), mg/kg | 7.5 (2.3-18.1) |
Oral anti-malarial drug after artesunate, n (%)
| |
AP | 41 (60) |
AL | 20 (29) |
Doxycycline | 2 (3) |
Doxycycline + Quinine | 1 (2) |
Clindamycin + Quinine | 1 (2) |
AP + mefloquine | 1 (2) |
Primaquine | 1 (2) |
Mefloquine | 1 (2) |
Supportive care, n (%)
| |
Erythrocytapheresis | 4 (6) |
Exchange transfusion | 13 (19) |
Blood transfusion | 9 (13) |
Platelets transfusion | 1 (2) |
Mechanical ventilation | 6 (9) |
Haemodialysis | 5 (7) |
Efficacy
Endpoint | Number of patients (n = 68) |
---|---|
Mortality, n (%) | |
among severe malaria,% (n = 55) | 2* (3.6) |
Mean parasite clearance times (95% CI), hours† | |
PCT50% | 4.4 (3.9 - 5.2) |
PCT90% | 14.8 (13.0 - 17.2) |
PCT99% | 29.5 (25.9 - 34.4) |
ICU admittance, n (%) | 42 (62) |
Median duration of ICU stay (range), days | 2 (1-35) |
Median duration of hospital stay (range), days | 4.5 (1-76) |
Safety
Complication | Number of patients (%) | Recovery* |
---|---|---|
Haematological, n (%)
| ||
Abnormal bleeding | 1 (2) | Recovered |
Anemia | 32 (47) | |
hemolytic† | 7 (10) | Recovered in all |
severe (Hb< 3.6 mmol/l) | 2 (3) | Recovered in all |
moderately severe (3.7 - 6.1 mmol/l) | 23 (34) | Recovered in 11/11 ‡ |
Thrombocytopenia (< 20 giga/L) | 16 (24) | Recovered in all |
Hemoglobinuria | 1 (2) | Recovered |
Hepatobiliary, n (%)
| ||
Elevated liver enzymes (LDH > 2x URL) | 31 (46) | Recovery in 14/14‡ |
Renal, n (%)
| ||
Acute renal insufficiency | 7 (10) | Recovered in 5/5 ‡ |
Acute tubular necrosis | 1 (2) | Recovered |
Anuria | 1 (2) | Not resolved, still in need of dialysis |
Elevated creatinine levels (> 20% above URL) | 9 (13) | Recovered in 4/4‡ |
Nervous system, n (%)
| ||
Anal sphincter dysfunction | 1 (2) | Recovered |
Aphasia | 1 (2) | Recovered |
Cerebral edema | 1 (2) | Recovered |
Coma | 2 (3) | Recovered |
Convulsion | 3 (4) | Recovered |
Delirium | 2 (3) | Recovered in 1/2 § |
Diplopia | 1 (2) | Restoring but lost to follow up |
Neurological deficit | 1 (2) | Recovered |
Truncal ataxia | 1 (2) | Restoring but lost to follow up |
Cardiovascular, n (%
| ||
Arterial hypertension | 1 (2) | Recovered |
Atrial flutter | 2 (3) | Recovered |
AV Block (1st degree) | 1 (2) | Recovered |
Prolonged QTc interval | 1 (2) | Recovered |
Sinus bradycardia | 1 (2) | Recovered║ |
Supraventricular tachycardia | 1 (2) | Recovered |
Thrombophlebitis | 2 (3) | Recovered |
Respiratory, n (%)
| ||
Exercise induced dyspnea | 1 (2) | Recovered |
Pneumonia | 4 (6) | Recovered |
Respiratory insufficiency | 4 (6) | Recovered |
Other, n (%)
| ||
Deafness | 3 (4) | Recovered in 2/3¶ |
Diarrhoea | 3 (4) | Recovered |
Fever | 1 (2) | Recovered |
Furunculosis | 1 (2) | Recovered |
Hypoglycaemia | 1 (2) | Recovered |
Peri-anal abcess | 1 (2) | Recovered |
Rash | 2 (3) | Recovered |
Reactive arthritis | 1 (2) | Recovered |
Sepsis | 1 (2) | Recovered |
Tropical ulcers | 1 (2) | Recovered |
Patient (gender, age) | Severe malaria criteria | Anti-malarial treatment | PCT (days)* | Hb nadir(days)* | Additional diagnostics | Treatment for haemolysis |
---|---|---|---|---|---|---|
Late onset hemolysis
| ||||||
1 (♂, 53y) | Hyperparasitaemia (34%), impaired consciousness, jaundice | Q AS (2 doses) AP AET | 4 | 4.3 (D20) | Coombs: C3d+ | None |
4 (♀, 50y) | Hyperparasitaemia (19%), impaired consciousness, jaundice, acidosis, hyperlactaemia, renal impairment | AS (4 doses) AP MET | 3 | 4.4 (D30) | Multiple in the context of an unexplained neurological disorder‡; coombs not performed | None |
38 (♀, 50y) | Hyperparasitaemia(11%), jaundice | AS (4 doses) AP | 3 | 2.8 (D13) | Coombs: neg; G6PD deficient (heterozygous); Shigellaflexneri dysentery | Transfusion(4 PC) |
55 (♀, 44y) | Hyperparasitaemia (37%) | Q AS (3 doses) AL | 4 | 3.8 (D15) | Coombs: IgG +, C3d+ | Transfusion(2 × 3 PC) Steroids |
58 (♂, 5y) | Hyperparasitaemia (12%), impaired consciousness, shock | Q AS (doses) AL | 4(FCT 10 d) | 3.8 (D8) | Coombs: neg; hemoculture - | None |
59 (♀, 50y) | Hyperparasitaemia (30%), hemoglobinuria, jaundice | AS (doses) AL | 10 (FCT 17 d) | 4.3 (D13) | Coombs: IgG+, IgM+, hemoculture - G6PD: normal | Transfusion (2 PC) Steroids |
Persistent hemolysis
| ||||||
28 (♂, 71y) | Hyperparasitaemia (20%), impaired consciousness, respiratory distress, acidosis, hypoglycaemia, hyperlactaemia, renal impairment | Q AS (doses) AL AET | 7† | 3.7 (D13) | Coombs: neg | Transfusion (7 times, total of 24 PC) |