Clinical and epidemiological characterization of severe Plasmodium vivax malaria in Gujarat, India

Figures & data

Table 1. Criteria used for the definition of severe malaria.

Clinical features	Description
Impaired consciousness	Including unarousable coma Assessment by Glasgow scale (10 or less) or Blantyre scale (3 or less) Normal cerebrospinal fluid
Prostration	Generalized weakness so that the patient is unable to sit, stand, or walk without assistance
Multiple convulsions	Jerky limb movements and staring eyes; more than two episodes within 24 hours
Deep breathing and respiratory distress	Acidotic breathing, arterial pH <7.35
Acute pulmonary oedema and acute respiratory distress syndrome	Tachypnea, dyspnea, and bilateral basal rales
Circulatory collapse or shock	Systolic blood pressure <80 mm Hg in adults, and <50 mm Hg in children
Acute kidney injury	Urine output <400 ml/24 hours in adults and <0.5 ml/kg in children
Clinical jaundice plus evidence of other vital organ dysfunction	Serum bilirubin > 3 mg/dl
Abnormal bleeding	Spontaneous bleeding at gums, nose, venipuncture sites, gastrointestinal tract, blood tests suggestive of disseminated intravascular coagulation
Laboratory
Hypoglycemia	<2.2 mmol/l or < 40 mg/dl. Anxiety, sweating, palpitation, dilatation of pupils, breathlessness, convulsions, alteration of consciousness
Metabolic acidosis	Plasma bicarbonate < 15 mmol/l
Severe normocytic anemia	Hemoglobin,5 g/dl or packed cell volume < 15% in children, hemoglobin <7 g/dl or packed cell volume <20% in adults
Hemoglobinuria	Urine is positive for hemoglobin
Hyperlactatemia*	Lactate > 5 mmol/l
Renal impairment	Blood urea > 20 mM
Pulmonary oedema	Radiological: bilateral infiltration in the lungs on chest film
Hyperparasitemia	Parasite density > 100,000/µl (~ 2.5% parasitemia), appearance of peripheral schizontemia

*Not measured in our cohort.

Table 2. Demographic, socioeconomic, and epidemiological characteristics of severe malaria patients at the time of admission. Unless otherwise stated, values are expressed in the number of patients; percentages are in brackets. P-values were obtained by Chi-square or Mann–Whitney U tests; NA: not applicable; IQR: interquartile range; Pv: P. vivax; Pf: P. falciparum.

		Pv (n = 30)	Pf (n = 8)	p Value
Female		14 (46.7)	3 (37.5)	0.6431
Age, y, median±IQR		33.5 ± 23.5	28.0 ± 26.0	0.5319
Education status
	Primary school	19 (63.3)	5 (62.5)	0.3412
	Secondary school	6 (20.0)	3 (37.5)
	None	5 (16.7)	0
Occupation
	Daily labour	9 (30.0)	1 (12.5)	0.3004
	Salary service	7 (23.3)	4 (50.0)
	Other	14 (46.7)	3 (37.5)
Annual income
	Above poverty line	20 (66.7)	3 (37.5)	0.1337
	Below poverty line	10 (33.3)	5 (62.5)
House structure
	Brick/concrete/other	16 (53.3)	5 (62.5)	0.6431
	Thatch	14 (46.7)	3 (37.5)
Water source
	Bore well	3 (10.0)	2 (25.0)	0.2648
	Public tank/pump/other	27 (90.0)	6 (75.0)
Malaria history
	Yes	5 (16.7)	1 (12.5)	0.774
	No	25 (83.3)	7 (87.5)
Co-infections
	Yes	6 (20.0)	0	0.1681
	No	24 (80.0)	8 (100.0)
Pregnancy
	Yes	2 (14.3)	0	0.4858
	No	12 (85.7)	3 (100.0)
Weight, kg, median±IQR		60.0 ± 13.3	61.0 ± 17.0	0.9648
Height, cm, median±IQR		160.0 ± 11.8	164.0 ± 18.3	0.4641
Heart rate, beats/minutes, median±IQR		88.0 ± 15.0	84.0 ± 12.0	0.3601
Temperature °C, median±IQR		37.2 ± 0.4	37.2 ± 0.2	0.2798

Figure 1. Flowchart of the study: of the initial 50 patients enrolled in the study, 9 were negative using PCR. Two did not match the WHO criteria for severe malaria, and of the 39 severe malaria cases, 30 were infected with P. vivax (Pv), 8 with P. falciparum (Pf), and one with both parasite species.

Table 3. Summary of clinical signs and symptoms of enrolled severe malaria patients. Values are expressed in the number of patients and percentages are in brackets. P-values were obtained by Chi-square test; NA: not applicable; Pv: P. vivax; Pf: P. falciparum.

	Pv	Pf	p Value
Headache	29 (96.7)	8 (100.0)	0.6007
Chills	30 (100.0)	8 (100.0)	NA
Aches or pains	16 (53.3)	3 (37.5)	0.4261
Fatigue	5 (16.7)	3 (37.5)	0.1991
Vomiting	23 (76.7)	7 (87.5)	0.5043
Lack of appetite	9 (30.0)	2 (25.0)	0.7817
Cough	9 (30.0)	4 (50.0)	0.2894
Dizziness	5 (16.7)	1 (12.5)	0.774
Sweating	1 (3.3)	2 (25.0)	0.0435
Abdominal pain	22 (73.3)	6 (75.0)	0.9242
Diarrhoea	3 (10.0)	1 (12.5)	0.8378
Lower back pain	4 (13.3)	1 (12.5)	0.9506
Eye pain	0 (0)	0 (0)	NA
Paleness	0 (0)	0 (0)	NA
Chest pain	2 (6.7)	0 (0)	0.4531
Rash	0 (0)	0 (0)	NA
Ear pain	0 (0)	0 (0)	NA
Splenomegaly	0 (0)	0 (0)	NA

Table 4. Hematological and biochemical laboratory findings of severe malaria patients. Values are expressed in median ± interquartile range; patient numbers are in brackets. P-values were obtained by Mann–Whitney U tests; NA: not applicable; Pv: P. vivax; Pf: P. falciparum.

	Pv	Pf	p Value
Hemoglobin levels (g/dL)	10.7 ± 3.8 (27)	8.1 ± 5.6 (8)	0.0568
Hematocrit (%)	33.9 ± 12.7 (27)	24.5 ± 19.5 (8)	0.0147
Platelet counts (x10^9/L)	67.0 ± 72.8 (24)	42.0 ± 72.0 (7)	0.1492
Serum bilirubin (mg/dL)	2.7 ± 2.9 (22)	2.0 ± 1.7 (3)	0.3483
Serum creatinine (mg/dL)	0.8 ± 0.4 (22)	0.9 ± 9.4 (3)	0.1304
Blood urea (mg/dL)	25.2 ± 18.5 (22)	51.2 ± 87.9 (3)	0.107
ALT levels (U/L)	24.1 ± 64.6 (21)	72.0 ± 67.8 (3)	0.6196
Blood glucose (mg/dL)	127.0 ± 42.5 (5)	126.0 ± 74.8 (5)	0.9444
Sodium levels (mmol/L)	134.5 ± 10.7 (16)	130.3 ± 6.5 (2)	0.268

Table 5. Summary of symptoms of the severity of patients enrolled in the study according to WHO criteria of severe malaria. Values are expressed in the number of patients and percentages are in brackets. P-values were obtained by the chi-square test; NA: not applicable; Pv: P. vivax; Pf: P. falciparum.

Symptoms	Pv	Pf	p Value
Impaired consciousness	0 (0)	1 (12.5)	0.0497
Prostration	27 (90)	8 (100)	0.3514
Multiple convulsions	21 (70)	7 (87.5)	0.3179
Deep breath and respiratory distress	0 (0)	2 (25)	0.0049
Acute respiratory distress syndrome	0 (0)	0 (0)	NA
Shock	1 (3.3)	0 (0)	0.6007
Clinical jaundice	10 (33.3)	0 (0)	0.0571
Abnormal bleeding	1 (3.3)	0 (0)	0.6007
Hypoglycemia	0 (0)	0 (0)	NA
Metabolic acidosis	1 (3.3)	0 (0)	0.6007
Severe anemia	1 (3.3)	2 (25)	0.0435
Hemoglobinurea	1 (3.3)	0 (0)	0.6007
Hyperlactatemia	0 (0)	0 (0)	NA
Renal impairment	12 (40)	3 (37.5)	0.8977
Pulmonary edema	0 (0)	0 (0)	NA
Hyperparasitemia	0 (0)	0 (0)	NA