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Persistent endothelial activation and inflammation after Plasmodium falciparum Infection in Malawian children.

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(10)

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(11)

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2'3#"4%*/0*5*#(,)

;()# $**0*&$.-,# 30&'# &',# *&%+7#we wish to thank Eric Borgstein (Queen Elizabeth

Hospital, Blantyre, Malawi); Grace Matimati, Patricia Phula, Simon Ewing and the

Paediatric Research Ward clinical team (Wellcome Trust Clinical Research

Programme and Blantyre Malaria Project) and the Department of Paediatrics and

Child Health B\%,,.#X"0]$6,&'#L(*50&$">#^"$.&7),>#C$"$30I1#

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(12)

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(16)

Table 1. Clinical characteristics and soluble plasma markers in children with cerebral malaria, uncomplicated malaria, mild febrile illness and healthy controls

Healthy controls (n=36)

Mild febrile illness (n=88)

Uncomplicated malaria (n=84)

Cerebral malaria (n=18) Age - years - mean (95% CI1) 4.6 (3.7-5.7) 3.2 (2.8-3.6)* 4.7 (4.1-5.3) 4.1 (3.3-5.2)

Female sex - number (%) 13 (36) 35 (40) 47 (56) 8 (44)

Clinical parameters on day 0 - mean (95% CI):

Axillary temperature 36.6 (36.5-36.7) 38.4 (38.2-38.5)*** 38.5 (38.4-38.7)*** 39.0 (38.5-39.6)***

Heart rate - beats/ min 109 (104-114) 127 (119-135)*** 130 (124-137)*** 145 (129-163)***

Systolic blood pressure - mmHg 107 (101-113) 114 (110-117)* 113 (110-117)* 97 (92-102)**

Respiratory rate - breaths/ min 28 (26-30) 30 (29-31) 28 (27-29) 46 (42-51)***

Glucose - mmol/ L 5.0 (4.8-5.2) 5.1 (4.9-5.3) 5.7 (5.4-6.0)** 5.6 (4.6-6.9)*

Lactate - mmol/ L 1.8 (1.7-2.0) 1.7 (1.6-1.9) 2.3 (2.1-2.5) 5.2 (3.9-6.9)***

Hemoglobin - g/ L 10.4 (9.9-11.0) 10.7 (10.3-11.1) 9.0 (8.6-9.4)** 6.1 (5.4-7.0)***

Platelets - x109/ L 380 (347-416) 300 (267-338)* 110 (93-131)*** 31 (21-46)***

Parasitemia ± parasites x103ȝO 0 0 20 (9.9-40) 68 (27-171)

HIV2 positive - number (%) 0 (0) 4 (4.8) 3 (3.5) 2 (11.1)

sICAM-1 pg/ mL day 0 198 (160-247) 316 (295-339)*** 464 (295-505)*** 624 (377-1033)***

sICAM-1 pg/ mL day 7 - 258 (235-282) 343 (299-394)*** 478 (364-626)***

sICAM-1 pg/ mL day 28 - 269 (242-299)* 277 (251-304)** 291 (201-421)

sE-selectin pg/ mL day 0 68 (57-82) 122 (105-142)*** 147 (130-160)*** 205 (158-266)***

sE-selectin pg/ mL day 7 - 76 (66-87) 79 (68-91) 109 (77-154)*

sE-selectin pg/ mL day 28 - 79 (68-92) 82 (74-91) 93 (64-135)

Ang-2 pg/ mL day 0 232 (207-261) 382 (339-431)*** 579 (523-641)*** 1536 (1190-1982)***

Ang-2 pg/ mL day 7 - 383 (333-440)*** 442 (389-502)*** 548 (401-749)***

Ang-2 pg/ mL day 28 - 311 (275-350)** 320 (285-359)** 307 (213-443)

sTM pg/ mL day 0 4.7 (4.2-5.2) 4.5 (4.2-4.9) 6.0 (5.4-6.5)* 9.1 (7.5-11.1)***

sTM pg/ mL day 7 - 4.7 (4.3-5.1) 5.0 (4.4-5.6) 5.6 (4.3-7.2)

sTM pg/ mL day 28 - 5.2 (4.8-5.6) 4.6 (4.1-5.3) 4.1 (3.4-5.1)

CRP mg/ mL enrolment 0.41 (0.23-0.74) 26.7 (20-35)*** 75 (61-92)*** 149 (111-199)***

CRP mg/ mL day 7 - 3.0 (2.0-4.4)*** 5.3 (4.2-6.7)*** 16.0 (8.3-32)***

CRP mg/ mL day 28 - 0.62 (0.37-1.0) 0.73 (0.48-1.1) 12.7 (3.1-52)***

F1+2 pg/ mL day 0 176 (140-220) 142 (120-167) 219 (180-268) 376 (245-577)*

F1+2 pg/ mL day 7 - 176 (135-229) 220 (186-260) 500 (279-898)***

F1+2 pg/ mL day 28 - 174 (138-221) 142 (111-182) 180 (105-310)

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224 fully conscious patients aged1-12 with

temperature >38.5 screened for enrollment

91 had positive RDT 94 had negative RDT

185 met all inclusion criteria and gave consent

4 blood sample not collected 2 withdrew

3 blood sample not collected 4 had negative smears

for malaria

88 in non-malarial febrile

illness group at day 0 malaria group at day 0 84 in uncomplicated

30 patients did not attend follow up

2 died 5 had parasitaemia or

fever at follow up 6 blood sample not

collected 33 did not attend follow

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fever at follow up 6 blood sample not

collected

41 patients followed up to 1 month 47 patients followed up to

1 month

Uncomplicated febrile illness Healthy controls

39 well children attending routine surgery

aged 1-12 screened for enrollment

36 met all inclusion criteria and gave consent

36 in healthy controls group day 0

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43 comatose children aged 1-12 with cerebral

malaria screened

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References

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