. Author manuscript; available in PMC: 2013 Jun 1.

Published in final edited form as: Lancet Infect Dis. 2012 Mar 23;12(6):457–468. doi: 10.1016/S1473-3099(12)70055-5

Table 1.

Case-control studies investigating the effect of haemoglobinopathies on P. falciparum malaria

Source	Location	Syndrome^a	No. patients	Age	Comment	% Haemoglobin opathy
Haemoglobin AS
Gilles et al (1967)¹⁶	Nigeria	Severe malaria	100	Range 6m - 4y		4.0
		Healthy	100	Range 6m - 4y	Aparasitaemic outpatients	18.0
Willcox et al (1983)³³	Liberia	Uncomplicated malaria	518	Range 2m - >15y	Outpatients	1.9
		Healthy	1027	Range 2m - >15y	Community surveys	7.9
Hill et al (1991)²²	The Gambia	Severe malaria	619	Median 3.0y Range <10y		1.2
		Severe non-malaria illness	332	Median 2.2y Range <10y	Inpatients with severe non- malaria illness	10.9
		Mild non-malaria illness	510	Median 1.9y Range <10y	Mild outpatient illness without malaria parasites	12.9
		Uncomplicated malaria	354	Median 3.0y Range <10y		2.8
Agarwal et al (2000)²¹	Mali	Severe malaria	67	Mean 4.3y		4.5
		Cerebral malaria	34	Mean 3.8y	Subset of severe malaria patients with coma, obtundation, or convulsions	5.9
		Severe malarial anaemia	12	Mean 1.0y	Subset of severe malaria patients with Hct <15%	0
		Uncomplicated malaria	391	Mean 9.1y		2.7
Modiano et al (2001)¹⁷	Burkina Faso	Severe malaria	359	Mean 4y Range 0.5 -15y		1.1
		Uncomplicated malaria	476	Mean 4y Range 0.5 -15y		4.0
		Healthy	3513	Mean 11y Range 1- 40y	Community cross-sectional survey	9.5
Mockenhaupt et al (2004)²⁰	Ghana	Severe malaria	290	Median 24m Range 6 - 102m		0
		Healthy, parasitaemic	290	NA	Community cross-sectional survey, matched to severe cases	7.9
		Healthy aparasitaemic	290	NA	Community cross-sectional survey, matched to severe cases	8.3
Ackerman et al (2005)¹⁸	The Gambia	Severe malaria	315	NA		1.1
		Cerebral malaria	235	NA	Subset of severe malaria patients with BCS <3	1.3
		Severe malarial anaemia	80	NA	Subset of severe malaria patients with Hb <5g/dL	0.6
		Newborns	583	NA	Cord blood specimens	8.7
May et al (2007)¹⁹	Ghana	Severe malaria	2591	Median 20m		1.4
		Cerebral malaria	581	NA	Subset of severe malaria patients with BCS <3	1.2
		Severe malarial anaemia	1649	NA	Subset of severe malaria patients with Hb <5g/dL	1.6
		Healthy	2048	Median 30m	Community cross-sectional survey, matched to severe cases	14.8
Jallow et al (2009)⁹⁹	The Gambia	Severe malaria	1060	NA		NA
		Cerebral malaria	869	NA	Subset of severe malaria patients with BCS <3	NA
		Severe malarial anaemia	318	NA	Subset of severe malaria patients with Hb <5g/dL	NA
		Newborns	1500	NA	Cord blood specimens	8.0
Haemoglobin C
Gilles et al (1967)¹⁶	Nigeria	Severe malaria	100	Range 6m - 4y		He: 6.0
		Healthy	200	Range 6m - 4y	Clinic attendance, aparasitaemic	He: 7.0
Willcox et al (1983)³³	Liberia	Uncomplicated malaria	518	Range 2m - >15y		He: 1.3
		Healthy	1027	Range 2m - >15y	Community surveys	He: 0.4
Guinet et al (1997)²⁶	Mali	Severe malaria	110	Range 6m - 9y		10.0
		Severe malarial anaemia	6	Range 6m - 9y	Subset of severe malaria patients with Hct <15% or Hb <5g/dL	0
		Uncomplicated malaria	55	Range 6m - 9y	Matched to severe cases	9.0
Agarwal et al (2000)²¹	Mali	Severe malaria	67	Mean 4.3y		Ho: 0 He: 4.5
		Cerebral malaria	34	Mean 3.8y	Subset of severe malaria patients with coma, obtundation, or convulsions	Ho: 0 He: 2.9
		Severe malarial anaemia	12	Mean 1.0y	Subset of severe malaria patients with Hct <15%	Ho: 0 He: 0
		Uncomplicated malaria	391	Mean 9.1y		Ho: 1.5 He: 15.9
Modiano et al (2001)¹⁷	Burkina Faso	Severe malaria	359	Mean 4y Range 0.5 – 15y		Ho: 0.3 He: 17.6
		Uncomplicated malaria	476	Mean 4y Range 0.5 – 15y		Ho: 0 He: 15.6
		Healthy	3513	Mean 11y Range 1- 40y	Community cross-sectional survey	Ho: 1.7 He: 21.7
Mockenhaupt et al (2004)²⁰	Ghana	Severe malaria	290	Median 24m Range 6 – 102m		Ho: 0 He: 16.6
		Healthy, parasitaemic	290	NA	Community cross-sectional survey, matched to severe cases	Ho: 1.0 He: 24.5
		Healthy, aparasitaemic	290	NA	Community cross-sectional survey, matched to severe cases	Ho: 1.7 He: 19.0
May et al (2007)¹⁹	Ghana	Severe malaria	2591	Median 20m		Ho: 0.2 He: 9.4
		Cerebral malaria	581	NA	Subset of severe malaria patients with BCS <3	Ho: NA He: 7.2
		Severe malarial anaemia	1649	NA	Subset of severe malaria patients with Hb <5g/dL	Ho: NA He: 9.2
		Healthy	2048	Median 30m	Community cross-sectional survey, matched to severe cases	Ho: 0.5 He: 8.7
Haemoglobin E
Oo et al (1995)²⁷	Myanmar	Severe malaria	200	19 - 45y		28.0
		Uncomplicated malaria	109	19 - 45y	Hospitalized	27.5
Hutagalung et al (1999)²⁸	Thailand	Severe malaria	33	14 - 45y		3.0
		Uncomplicated malaria	184	14 - 45y	Hospitalized	22.3
α-thalassaemia
Allen et al (1997)²⁹	Papua New Guinea	Severe malaria	249	NA		Ho: 44.6 He: 37.3
		Severe malarial anaemia	155	Median 2.1y	Subset of severe malaria patients with Hb <5g/dL	Ho: 36.1 He: 43.9
		Healthy	249	NA	Community survey, matched to severe cases	Ho: 57.0 He: 31.3
Lell et al (1999)¹⁰⁰	Gabon	Severe malaria	100	Mean 44m		Ho: 10.0 He: 37.0
		Uncomplicated malaria	100	Mean 44m		Ho: 10.0 He: 43.0
Mockenhaupt et al (2004)³⁰	Ghana	Severe malaria	261	<5y		Ho: 5.0 He: 23.7
		Healthy, parasitaemic	614	<5y	Community cross-sectional survey, matched to severe cases	Ho: 3.3 He: 33.2
		Healthy, aparasitaemic	479	<5y	Community cross-sectional survey, matched to severe cases	Ho: 3.6 He: 31.9
Williams et al (2005)³¹	Kenya	Severe malaria	655	NA		Ho: 12.7 He: 47.0
		Fatal malaria	72	NA	Death in hospital	Ho: 8.4 He: 10.4
		Healthy	648	<7y	Community survey, matched	Ho: 16.7 He: 50.6
May et al (2007)¹⁹	Ghana	Severe malaria	2591	Median 20m		Ho: 2.0 He: 25.2
		Cerebral malaria	581	NA	Subset of severe malaria patients with BCS <3	Ho: 2.2 He: 23.8
		Severe malarial anaemia	1649	NA	Subset of severe malaria patients with Hb <5g/dL	Ho: 1.8 He: 24.7
		Healthy	2048	Median 30m	Community cross-sectional survey, matched to severe cases	Ho: 2.0 He: 27.3
β-thalassaemia
Willcox et al (1983)³³	Liberia	Uncomplicated malaria	526	2m - >15y		5.7
		Healthy	1132	2m - >15y	Community surveys	9.7

Abbreviations: Hb: haemoglobin; NA: data not available; Ho: homozygote; He: heterozygote; BCS: Blantyre Coma Score; Hct: hematocrit.

Unless otherwise stated, patients with severe malaria, severe malarial anaemia, cerebral malaria and uncomplicated malaria met definitions described in the Methods section. Healthy patients were recruited as described in the Comments column.