Differing Causes of Lactic Acidosis and Deep Breathing in Cerebral Malaria and Severe Malarial Anemia May Explain Differences in Acidosis-Related Mortality.
Lactic acidosis (LA) is a marker for mortality in severe malaria, but the mechanisms that lead to LA in the different types of severe malaria and the extent to which LA-associated mortality differs by type of severe malaria are not well described. We assessed the frequency of LA in children admitted to Mulago Hospital, Kampala, Uganda with cerebral malaria (CM, n = 193) or severe malarial anemia (SMA, n = 216). LA was compared to mortality and measures of parasite biomass and sequestration (P. falciparum histidine-rich protein-2 (PfHRP2) concentration, platelet count), and to a measure of systemic tissue oxygen delivery (hemoglobin level). LA was more frequent in children with SMA than CM (SMA, 47.7%, CM, 34.2%, P = 0.006), but mortality was higher in children with CM (13.0%) than SMA (0.5%, P<0.0001). In CM, LA was associated with increased PfHRP2 concentration and decreased platelet count but was not associated with hemoglobin level. In contrast, in SMA, LA was associated with a decreased hemoglobin level, but was not associated with PfHRP2 concentration or platelet count. LA was related to mortality only in CM. In multivariable regression analysis of the effect PfHRP2 and hemoglobin levels on LA and DB, only PfHRP2 level increased risk of LA and DB in CM, while in SMA, elevated hemoglobin strongly decreased risk of LA and DB, and PfHRP2 level modestly increased risk of LA. The study findings suggest that LA in CM is due primarily to parasite sequestration, which currently has no effective adjunctive therapy, while LA in SMA is due primarily to anemia, which is rapidly corrected with blood transfusion. Differing etiologies of LA in CM and SMA may explain why LA is associated with mortality in CM but not SMA.
Columbia University College of Physicians and Surgeons, School of Medicine, New York, New York, United States of America.
Nathan R
NR
Brand
Makerere University, Department of Pediatrics, Kampala, Uganda.
Robert O
RO
Opoka
University of Minnesota, Department of Pediatrics, Minneapolis, Minnesota, United States of America.
Karen E S
KE
Hamre
Indiana University, Department of Pediatrics, Indianapolis, Indiana, United States of America.
Chandy C
http://orcid.org/0000-0002-1634-1411
CC
John
PLoS Pathog. 2006 Sep;2(9):e100
17009869
J Infect Dis. 2009 Dec 15;200(12):1834-41
19911989
Clin Infect Dis. 2011 Sep;53(6):548-54
21865191
Exp Parasitol. 1995 Jun;80(4):624-32
7758543
Lancet. 2010 Nov 13;376(9753):1647-57
21062666
Clin Infect Dis. 2012 Apr;54(8):1080-90
22412067
Trop Med Int Health. 1997 Feb;2(2):165-78
9472302
J Infect Dis. 2008 Jan 1;197(1):72-8
18171288
Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1805-10
11172032
Malar J. 2005 Jan 09;4:1
15638948
J Infect. 2013 Sep;67(3):220-30
23623771
PLoS Med. 2005 Aug;2(8):e204
16104831
QJM. 1997 Sep;90(9):563-9
9349448
N Engl J Med. 1995 May 25;332(21):1399-404
7723795
Am J Trop Med Hyg. 2013 Apr;88(4):747-56
23358640
Ann Trop Med Parasitol. 1996 Aug;90(4):395-402
8944083
Ann Intern Med. 1990 Apr 1;112(7):492-8
2156475
Clin Infect Dis. 2005 Oct 1;41(7):948-57
16142658
J Infect Dis. 2006 Nov 15;194(10):1438-46
17054074
Am J Trop Med Hyg. 2007 Dec;77(6 Suppl):36-47
18165473
Crit Care Med. 2015 Mar;43(3):567-73
25479113
Malar J. 2013 Feb 06;12:55
23388470
QJM. 1997 Apr;90(4):263-70
9307760
Am J Trop Med Hyg. 1996 Nov;55(5):521-4
8940984
MBio. 2015 Sep 22;6(5):e01390-15
26396242
Chest. 2016 Jan;149(1):252-61
26378980
PLoS Med. 2012;9(8):e1001297
22927801
Crit Care. 2015 Sep 07;19:317
26343146
Am J Trop Med Hyg. 1996 Nov;55(5):525-30
8940985
Pharmacol Ther. 1998 Jul;79(1):1-53
9719344
J Infect Dis. 2003 Feb 1;187(3):461-6
12552430
N Engl J Med. 1992 Nov 26;327(22):1564-9
1435883