Immediate Transfusion in African Children with Uncomplicated Severe Anemia.


Journal

The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562

Informations de publication

Date de publication:
01 08 2019
Historique:
entrez: 1 8 2019
pubmed: 1 8 2019
medline: 8 8 2019
Statut: ppublish

Résumé

The World Health Organization recommends not performing transfusions in African children hospitalized for uncomplicated severe anemia (hemoglobin level of 4 to 6 g per deciliter and no signs of clinical severity). However, high mortality and readmission rates suggest that less restrictive transfusion strategies might improve outcomes. In this factorial, open-label, randomized, controlled trial, we assigned Ugandan and Malawian children 2 months to 12 years of age with uncomplicated severe anemia to immediate transfusion with 20 ml or 30 ml of whole-blood equivalent per kilogram of body weight, as determined in a second simultaneous randomization, or no immediate transfusion (control group), in which transfusion with 20 ml of whole-blood equivalent per kilogram was triggered by new signs of clinical severity or a drop in hemoglobin to below 4 g per deciliter. The primary outcome was 28-day mortality. Three other randomizations investigated transfusion volume, postdischarge supplementation with micronutrients, and postdischarge prophylaxis with trimethoprim-sulfamethoxazole. A total of 1565 children (median age, 26 months) underwent randomization, with 778 assigned to the immediate-transfusion group and 787 to the control group; 984 children (62.9%) had malaria. The children were followed for 180 days, and 71 (4.5%) were lost to follow-up. During the primary hospitalization, transfusion was performed in all the children in the immediate-transfusion group and in 386 (49.0%) in the control group (median time to transfusion, 1.3 hours vs. 24.9 hours after randomization). The mean (±SD) total blood volume transfused per child was 314±228 ml in the immediate-transfusion group and 142±224 ml in the control group. Death had occurred by 28 days in 7 children (0.9%) in the immediate-transfusion group and in 13 (1.7%) in the control group (hazard ratio, 0.54; 95% confidence interval [CI], 0.22 to 1.36; P = 0.19) and by 180 days in 35 (4.5%) and 47 (6.0%), respectively (hazard ratio, 0.75; 95% CI, 0.48 to 1.15), without evidence of interaction with other randomizations (P>0.20) or evidence of between-group differences in readmissions, serious adverse events, or hemoglobin recovery at 180 days. The mean length of hospital stay was 0.9 days longer in the control group. There was no evidence of differences in clinical outcomes over 6 months between the children who received immediate transfusion and those who did not. The triggered-transfusion strategy in the control group resulted in lower blood use; however, the length of hospital stay was longer, and this strategy required clinical and hemoglobin monitoring. (Funded by the Medical Research Council and Department for International Development; TRACT Current Controlled Trials number, ISRCTN84086586.).

Sections du résumé

BACKGROUND
The World Health Organization recommends not performing transfusions in African children hospitalized for uncomplicated severe anemia (hemoglobin level of 4 to 6 g per deciliter and no signs of clinical severity). However, high mortality and readmission rates suggest that less restrictive transfusion strategies might improve outcomes.
METHODS
In this factorial, open-label, randomized, controlled trial, we assigned Ugandan and Malawian children 2 months to 12 years of age with uncomplicated severe anemia to immediate transfusion with 20 ml or 30 ml of whole-blood equivalent per kilogram of body weight, as determined in a second simultaneous randomization, or no immediate transfusion (control group), in which transfusion with 20 ml of whole-blood equivalent per kilogram was triggered by new signs of clinical severity or a drop in hemoglobin to below 4 g per deciliter. The primary outcome was 28-day mortality. Three other randomizations investigated transfusion volume, postdischarge supplementation with micronutrients, and postdischarge prophylaxis with trimethoprim-sulfamethoxazole.
RESULTS
A total of 1565 children (median age, 26 months) underwent randomization, with 778 assigned to the immediate-transfusion group and 787 to the control group; 984 children (62.9%) had malaria. The children were followed for 180 days, and 71 (4.5%) were lost to follow-up. During the primary hospitalization, transfusion was performed in all the children in the immediate-transfusion group and in 386 (49.0%) in the control group (median time to transfusion, 1.3 hours vs. 24.9 hours after randomization). The mean (±SD) total blood volume transfused per child was 314±228 ml in the immediate-transfusion group and 142±224 ml in the control group. Death had occurred by 28 days in 7 children (0.9%) in the immediate-transfusion group and in 13 (1.7%) in the control group (hazard ratio, 0.54; 95% confidence interval [CI], 0.22 to 1.36; P = 0.19) and by 180 days in 35 (4.5%) and 47 (6.0%), respectively (hazard ratio, 0.75; 95% CI, 0.48 to 1.15), without evidence of interaction with other randomizations (P>0.20) or evidence of between-group differences in readmissions, serious adverse events, or hemoglobin recovery at 180 days. The mean length of hospital stay was 0.9 days longer in the control group.
CONCLUSIONS
There was no evidence of differences in clinical outcomes over 6 months between the children who received immediate transfusion and those who did not. The triggered-transfusion strategy in the control group resulted in lower blood use; however, the length of hospital stay was longer, and this strategy required clinical and hemoglobin monitoring. (Funded by the Medical Research Council and Department for International Development; TRACT Current Controlled Trials number, ISRCTN84086586.).

Identifiants

pubmed: 31365799
doi: 10.1056/NEJMoa1900105
pmc: PMC7611152
mid: EMS127442
doi:

Substances chimiques

Hemoglobins 0

Banques de données

ISRCTN
['ISRCTN84086586']

Types de publication

Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

407-419

Subventions

Organisme : Medical Research Council
ID : MC_UU_12023/17
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_MR/R019258/1
Pays : United Kingdom
Organisme : University Hospital Southampton NHS Foundation Trust
ID : MR/J012483
Pays : International
Organisme : Wellcome Trust
ID : 202800/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12023/26
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/J012483/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U122886353
Pays : United Kingdom

Investigateurs

S Kiguli (S)
R O Opoka (RO)
E Nabawanuka (E)
J Kayaga (J)
C Williams Musika (C)
E Kadama (E)
I Mbwali (I)
L Nuwabaine (L)
R Nakikwaku (R)
J Nsubuga (J)
K Mpande (K)
R Adoo (R)
O Ouma (O)
N K Adia (NK)
P Olupot-Olupot (P)
J Nteziyaremye (J)
C Namanyanja (C)
G Passi (G)
T Sennyondo (T)
R Adong (R)
C B Okalebo (CB)
E Atimango (E)
S Mwamula (S)
J Kapsindet (J)
G Kiluli (G)
R Muhindo (R)
G Masifa (G)
N Thembo (N)
G Odong (G)
C Engoru (C)
F Alaroker (F)
M Nakuya (M)
D Aromut (D)
M Ariima (M)
M Itipe (M)
M G Atim (MG)
M Abeno (M)
B Amede (B)
M Olupot (M)
S Okwi (S)
M G Kulume (MG)
G Among (G)
P Onyas (P)
E D Achipa (ED)
K Maitland (K)
A Mpoya (A)
P Maitha (P)
S Uyoga (S)
T N Williams (TN)
A Macharia (A)
M Mallewa (M)
Y Chimalizeni (Y)
N Kennedy (N)
F Kumwenda (F)
G Chagaluka (G)
E Nkosi (E)
T Sochera (T)
A Malenga (A)
B Gushu (B)
T Phiri (T)
A Chisale (A)
N Mitole (N)
E Chokani (E)
A Munthali (A)
D Kyeyune Byabazaire (D)
B Wabwire (B)
B M'baya (B)
G Frost (G)
K Walsh (K)
D M Gibb (DM)
E C George (EC)
M Thomason (M)
D Baptiste (D)
L McCabe (L)
A S Walker (AS)
A Ali (A)
K Khamis (K)
M Madula (M)
G Abongo (G)
P Saramago Goncalves (P)
P Revill (P)
S Walker (S)
A Fox (A)
R Heydermann (R)
I Bates (I)
B Urban (B)
M Boele von Hensbroek (M)
F Kyomuhendo (F)
S Nakalanzi (S)
J Chabuka (J)
N Mkandawire (N)
J Evans (J)
F Fitzgerald (F)
E Molyneux (E)
I Lubega (I)
M Murphy (M)
P Kazembe (P)
J Crawley (J)
T Peto (T)
P Musoke (P)
J Todd (J)
G Mirembe (G)
F Tenu (F)

Commentaires et corrections

Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn

Informations de copyright

Copyright © 2019 Massachusetts Medical Society.

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Auteurs

Kathryn Maitland (K)

From the Department of Pediatrics (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the Centre for Health Economics, University of York, York (P.S.G.), the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), and the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.) - all in the United Kingdom; the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., E.N.), and the Uganda Blood Transfusion Services (BTS), National BTS (D.K.B.), Kampala, Busitema University Faculty of Health Sciences, Mbale Campus and Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and Mbale BTS (B.W.), Mbale, and the Soroti Regional Referral Hospital, Soroti (C.E., F.A., M.N.) - all in Uganda; the College of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program (M.M., G.C.). and Malawi BTS (B.M.), Blantyre, Malawi; and the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi, Kenya (K.M., A.M. S.U., T.N.W.).

Sarah Kiguli (S)

From the Department of Pediatrics (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the Centre for Health Economics, University of York, York (P.S.G.), the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), and the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.) - all in the United Kingdom; the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., E.N.), and the Uganda Blood Transfusion Services (BTS), National BTS (D.K.B.), Kampala, Busitema University Faculty of Health Sciences, Mbale Campus and Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and Mbale BTS (B.W.), Mbale, and the Soroti Regional Referral Hospital, Soroti (C.E., F.A., M.N.) - all in Uganda; the College of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program (M.M., G.C.). and Malawi BTS (B.M.), Blantyre, Malawi; and the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi, Kenya (K.M., A.M. S.U., T.N.W.).

Peter Olupot-Olupot (P)

From the Department of Pediatrics (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the Centre for Health Economics, University of York, York (P.S.G.), the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), and the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.) - all in the United Kingdom; the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., E.N.), and the Uganda Blood Transfusion Services (BTS), National BTS (D.K.B.), Kampala, Busitema University Faculty of Health Sciences, Mbale Campus and Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and Mbale BTS (B.W.), Mbale, and the Soroti Regional Referral Hospital, Soroti (C.E., F.A., M.N.) - all in Uganda; the College of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program (M.M., G.C.). and Malawi BTS (B.M.), Blantyre, Malawi; and the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi, Kenya (K.M., A.M. S.U., T.N.W.).

Charles Engoru (C)

From the Department of Pediatrics (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the Centre for Health Economics, University of York, York (P.S.G.), the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), and the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.) - all in the United Kingdom; the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., E.N.), and the Uganda Blood Transfusion Services (BTS), National BTS (D.K.B.), Kampala, Busitema University Faculty of Health Sciences, Mbale Campus and Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and Mbale BTS (B.W.), Mbale, and the Soroti Regional Referral Hospital, Soroti (C.E., F.A., M.N.) - all in Uganda; the College of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program (M.M., G.C.). and Malawi BTS (B.M.), Blantyre, Malawi; and the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi, Kenya (K.M., A.M. S.U., T.N.W.).

Macpherson Mallewa (M)

From the Department of Pediatrics (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the Centre for Health Economics, University of York, York (P.S.G.), the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), and the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.) - all in the United Kingdom; the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., E.N.), and the Uganda Blood Transfusion Services (BTS), National BTS (D.K.B.), Kampala, Busitema University Faculty of Health Sciences, Mbale Campus and Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and Mbale BTS (B.W.), Mbale, and the Soroti Regional Referral Hospital, Soroti (C.E., F.A., M.N.) - all in Uganda; the College of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program (M.M., G.C.). and Malawi BTS (B.M.), Blantyre, Malawi; and the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi, Kenya (K.M., A.M. S.U., T.N.W.).

Pedro Saramago Goncalves (P)

From the Department of Pediatrics (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the Centre for Health Economics, University of York, York (P.S.G.), the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), and the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.) - all in the United Kingdom; the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., E.N.), and the Uganda Blood Transfusion Services (BTS), National BTS (D.K.B.), Kampala, Busitema University Faculty of Health Sciences, Mbale Campus and Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and Mbale BTS (B.W.), Mbale, and the Soroti Regional Referral Hospital, Soroti (C.E., F.A., M.N.) - all in Uganda; the College of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program (M.M., G.C.). and Malawi BTS (B.M.), Blantyre, Malawi; and the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi, Kenya (K.M., A.M. S.U., T.N.W.).

Robert O Opoka (RO)

From the Department of Pediatrics (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the Centre for Health Economics, University of York, York (P.S.G.), the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), and the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.) - all in the United Kingdom; the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., E.N.), and the Uganda Blood Transfusion Services (BTS), National BTS (D.K.B.), Kampala, Busitema University Faculty of Health Sciences, Mbale Campus and Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and Mbale BTS (B.W.), Mbale, and the Soroti Regional Referral Hospital, Soroti (C.E., F.A., M.N.) - all in Uganda; the College of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program (M.M., G.C.). and Malawi BTS (B.M.), Blantyre, Malawi; and the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi, Kenya (K.M., A.M. S.U., T.N.W.).

Ayub Mpoya (A)

From the Department of Pediatrics (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the Centre for Health Economics, University of York, York (P.S.G.), the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), and the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.) - all in the United Kingdom; the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., E.N.), and the Uganda Blood Transfusion Services (BTS), National BTS (D.K.B.), Kampala, Busitema University Faculty of Health Sciences, Mbale Campus and Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and Mbale BTS (B.W.), Mbale, and the Soroti Regional Referral Hospital, Soroti (C.E., F.A., M.N.) - all in Uganda; the College of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program (M.M., G.C.). and Malawi BTS (B.M.), Blantyre, Malawi; and the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi, Kenya (K.M., A.M. S.U., T.N.W.).

Florence Alaroker (F)

From the Department of Pediatrics (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the Centre for Health Economics, University of York, York (P.S.G.), the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), and the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.) - all in the United Kingdom; the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., E.N.), and the Uganda Blood Transfusion Services (BTS), National BTS (D.K.B.), Kampala, Busitema University Faculty of Health Sciences, Mbale Campus and Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and Mbale BTS (B.W.), Mbale, and the Soroti Regional Referral Hospital, Soroti (C.E., F.A., M.N.) - all in Uganda; the College of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program (M.M., G.C.). and Malawi BTS (B.M.), Blantyre, Malawi; and the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi, Kenya (K.M., A.M. S.U., T.N.W.).

Julius Nteziyaremye (J)

From the Department of Pediatrics (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the Centre for Health Economics, University of York, York (P.S.G.), the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), and the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.) - all in the United Kingdom; the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., E.N.), and the Uganda Blood Transfusion Services (BTS), National BTS (D.K.B.), Kampala, Busitema University Faculty of Health Sciences, Mbale Campus and Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and Mbale BTS (B.W.), Mbale, and the Soroti Regional Referral Hospital, Soroti (C.E., F.A., M.N.) - all in Uganda; the College of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program (M.M., G.C.). and Malawi BTS (B.M.), Blantyre, Malawi; and the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi, Kenya (K.M., A.M. S.U., T.N.W.).

George Chagaluka (G)

From the Department of Pediatrics (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the Centre for Health Economics, University of York, York (P.S.G.), the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), and the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.) - all in the United Kingdom; the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., E.N.), and the Uganda Blood Transfusion Services (BTS), National BTS (D.K.B.), Kampala, Busitema University Faculty of Health Sciences, Mbale Campus and Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and Mbale BTS (B.W.), Mbale, and the Soroti Regional Referral Hospital, Soroti (C.E., F.A., M.N.) - all in Uganda; the College of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program (M.M., G.C.). and Malawi BTS (B.M.), Blantyre, Malawi; and the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi, Kenya (K.M., A.M. S.U., T.N.W.).

Neil Kennedy (N)

From the Department of Pediatrics (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the Centre for Health Economics, University of York, York (P.S.G.), the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), and the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.) - all in the United Kingdom; the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., E.N.), and the Uganda Blood Transfusion Services (BTS), National BTS (D.K.B.), Kampala, Busitema University Faculty of Health Sciences, Mbale Campus and Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and Mbale BTS (B.W.), Mbale, and the Soroti Regional Referral Hospital, Soroti (C.E., F.A., M.N.) - all in Uganda; the College of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program (M.M., G.C.). and Malawi BTS (B.M.), Blantyre, Malawi; and the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi, Kenya (K.M., A.M. S.U., T.N.W.).

Eva Nabawanuka (E)

From the Department of Pediatrics (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the Centre for Health Economics, University of York, York (P.S.G.), the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), and the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.) - all in the United Kingdom; the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., E.N.), and the Uganda Blood Transfusion Services (BTS), National BTS (D.K.B.), Kampala, Busitema University Faculty of Health Sciences, Mbale Campus and Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and Mbale BTS (B.W.), Mbale, and the Soroti Regional Referral Hospital, Soroti (C.E., F.A., M.N.) - all in Uganda; the College of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program (M.M., G.C.). and Malawi BTS (B.M.), Blantyre, Malawi; and the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi, Kenya (K.M., A.M. S.U., T.N.W.).

Margaret Nakuya (M)

From the Department of Pediatrics (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the Centre for Health Economics, University of York, York (P.S.G.), the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), and the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.) - all in the United Kingdom; the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., E.N.), and the Uganda Blood Transfusion Services (BTS), National BTS (D.K.B.), Kampala, Busitema University Faculty of Health Sciences, Mbale Campus and Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and Mbale BTS (B.W.), Mbale, and the Soroti Regional Referral Hospital, Soroti (C.E., F.A., M.N.) - all in Uganda; the College of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program (M.M., G.C.). and Malawi BTS (B.M.), Blantyre, Malawi; and the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi, Kenya (K.M., A.M. S.U., T.N.W.).

Cate Namayanja (C)

From the Department of Pediatrics (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the Centre for Health Economics, University of York, York (P.S.G.), the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), and the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.) - all in the United Kingdom; the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., E.N.), and the Uganda Blood Transfusion Services (BTS), National BTS (D.K.B.), Kampala, Busitema University Faculty of Health Sciences, Mbale Campus and Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and Mbale BTS (B.W.), Mbale, and the Soroti Regional Referral Hospital, Soroti (C.E., F.A., M.N.) - all in Uganda; the College of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program (M.M., G.C.). and Malawi BTS (B.M.), Blantyre, Malawi; and the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi, Kenya (K.M., A.M. S.U., T.N.W.).

Sophie Uyoga (S)

From the Department of Pediatrics (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the Centre for Health Economics, University of York, York (P.S.G.), the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), and the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.) - all in the United Kingdom; the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., E.N.), and the Uganda Blood Transfusion Services (BTS), National BTS (D.K.B.), Kampala, Busitema University Faculty of Health Sciences, Mbale Campus and Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and Mbale BTS (B.W.), Mbale, and the Soroti Regional Referral Hospital, Soroti (C.E., F.A., M.N.) - all in Uganda; the College of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program (M.M., G.C.). and Malawi BTS (B.M.), Blantyre, Malawi; and the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi, Kenya (K.M., A.M. S.U., T.N.W.).

Dorothy Kyeyune Byabazaire (D)

From the Department of Pediatrics (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the Centre for Health Economics, University of York, York (P.S.G.), the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), and the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.) - all in the United Kingdom; the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., E.N.), and the Uganda Blood Transfusion Services (BTS), National BTS (D.K.B.), Kampala, Busitema University Faculty of Health Sciences, Mbale Campus and Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and Mbale BTS (B.W.), Mbale, and the Soroti Regional Referral Hospital, Soroti (C.E., F.A., M.N.) - all in Uganda; the College of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program (M.M., G.C.). and Malawi BTS (B.M.), Blantyre, Malawi; and the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi, Kenya (K.M., A.M. S.U., T.N.W.).

Bridon M'baya (B)

From the Department of Pediatrics (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the Centre for Health Economics, University of York, York (P.S.G.), the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), and the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.) - all in the United Kingdom; the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., E.N.), and the Uganda Blood Transfusion Services (BTS), National BTS (D.K.B.), Kampala, Busitema University Faculty of Health Sciences, Mbale Campus and Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and Mbale BTS (B.W.), Mbale, and the Soroti Regional Referral Hospital, Soroti (C.E., F.A., M.N.) - all in Uganda; the College of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program (M.M., G.C.). and Malawi BTS (B.M.), Blantyre, Malawi; and the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi, Kenya (K.M., A.M. S.U., T.N.W.).

Benjamin Wabwire (B)

From the Department of Pediatrics (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the Centre for Health Economics, University of York, York (P.S.G.), the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), and the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.) - all in the United Kingdom; the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., E.N.), and the Uganda Blood Transfusion Services (BTS), National BTS (D.K.B.), Kampala, Busitema University Faculty of Health Sciences, Mbale Campus and Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and Mbale BTS (B.W.), Mbale, and the Soroti Regional Referral Hospital, Soroti (C.E., F.A., M.N.) - all in Uganda; the College of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program (M.M., G.C.). and Malawi BTS (B.M.), Blantyre, Malawi; and the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi, Kenya (K.M., A.M. S.U., T.N.W.).

Gary Frost (G)

From the Department of Pediatrics (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the Centre for Health Economics, University of York, York (P.S.G.), the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), and the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.) - all in the United Kingdom; the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., E.N.), and the Uganda Blood Transfusion Services (BTS), National BTS (D.K.B.), Kampala, Busitema University Faculty of Health Sciences, Mbale Campus and Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and Mbale BTS (B.W.), Mbale, and the Soroti Regional Referral Hospital, Soroti (C.E., F.A., M.N.) - all in Uganda; the College of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program (M.M., G.C.). and Malawi BTS (B.M.), Blantyre, Malawi; and the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi, Kenya (K.M., A.M. S.U., T.N.W.).

Imelda Bates (I)

From the Department of Pediatrics (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the Centre for Health Economics, University of York, York (P.S.G.), the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), and the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.) - all in the United Kingdom; the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., E.N.), and the Uganda Blood Transfusion Services (BTS), National BTS (D.K.B.), Kampala, Busitema University Faculty of Health Sciences, Mbale Campus and Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and Mbale BTS (B.W.), Mbale, and the Soroti Regional Referral Hospital, Soroti (C.E., F.A., M.N.) - all in Uganda; the College of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program (M.M., G.C.). and Malawi BTS (B.M.), Blantyre, Malawi; and the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi, Kenya (K.M., A.M. S.U., T.N.W.).

Jennifer A Evans (JA)

From the Department of Pediatrics (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the Centre for Health Economics, University of York, York (P.S.G.), the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), and the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.) - all in the United Kingdom; the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., E.N.), and the Uganda Blood Transfusion Services (BTS), National BTS (D.K.B.), Kampala, Busitema University Faculty of Health Sciences, Mbale Campus and Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and Mbale BTS (B.W.), Mbale, and the Soroti Regional Referral Hospital, Soroti (C.E., F.A., M.N.) - all in Uganda; the College of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program (M.M., G.C.). and Malawi BTS (B.M.), Blantyre, Malawi; and the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi, Kenya (K.M., A.M. S.U., T.N.W.).

Thomas N Williams (TN)

From the Department of Pediatrics (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the Centre for Health Economics, University of York, York (P.S.G.), the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), and the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.) - all in the United Kingdom; the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., E.N.), and the Uganda Blood Transfusion Services (BTS), National BTS (D.K.B.), Kampala, Busitema University Faculty of Health Sciences, Mbale Campus and Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and Mbale BTS (B.W.), Mbale, and the Soroti Regional Referral Hospital, Soroti (C.E., F.A., M.N.) - all in Uganda; the College of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program (M.M., G.C.). and Malawi BTS (B.M.), Blantyre, Malawi; and the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi, Kenya (K.M., A.M. S.U., T.N.W.).

Elizabeth C George (EC)

From the Department of Pediatrics (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the Centre for Health Economics, University of York, York (P.S.G.), the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), and the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.) - all in the United Kingdom; the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., E.N.), and the Uganda Blood Transfusion Services (BTS), National BTS (D.K.B.), Kampala, Busitema University Faculty of Health Sciences, Mbale Campus and Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and Mbale BTS (B.W.), Mbale, and the Soroti Regional Referral Hospital, Soroti (C.E., F.A., M.N.) - all in Uganda; the College of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program (M.M., G.C.). and Malawi BTS (B.M.), Blantyre, Malawi; and the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi, Kenya (K.M., A.M. S.U., T.N.W.).

Diana M Gibb (DM)

From the Department of Pediatrics (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the Centre for Health Economics, University of York, York (P.S.G.), the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), and the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.) - all in the United Kingdom; the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., E.N.), and the Uganda Blood Transfusion Services (BTS), National BTS (D.K.B.), Kampala, Busitema University Faculty of Health Sciences, Mbale Campus and Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and Mbale BTS (B.W.), Mbale, and the Soroti Regional Referral Hospital, Soroti (C.E., F.A., M.N.) - all in Uganda; the College of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program (M.M., G.C.). and Malawi BTS (B.M.), Blantyre, Malawi; and the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi, Kenya (K.M., A.M. S.U., T.N.W.).

A Sarah Walker (AS)

From the Department of Pediatrics (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the Centre for Health Economics, University of York, York (P.S.G.), the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), and the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.) - all in the United Kingdom; the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., E.N.), and the Uganda Blood Transfusion Services (BTS), National BTS (D.K.B.), Kampala, Busitema University Faculty of Health Sciences, Mbale Campus and Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and Mbale BTS (B.W.), Mbale, and the Soroti Regional Referral Hospital, Soroti (C.E., F.A., M.N.) - all in Uganda; the College of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program (M.M., G.C.). and Malawi BTS (B.M.), Blantyre, Malawi; and the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi, Kenya (K.M., A.M. S.U., T.N.W.).

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