Table 2.

Prospective studies investigating the effect of haemoglobinopathies on P. falciparum malaria

Source	Outcome	Location	n	Ages	Incidence in unexposeda	Incidence Rate Ratio (95% C.I.)
Haemoglobin AS
Williams et al (2005)23,b	Severe malaria	Kenya	2655	< 5y	0.022/y	0.17 (0.07 – 0.40)
Williams et al (2005)24,b	Severe malaria	Kenya	2104	< 5y	0.020/y	0.29 (0.12 – 0.62)
Williams et al (2005)23	Cerebral malaria	Kenya	2655	< 5y	0.004/y	0.14 (0.02 – 1.17)
Aidoo et al (2002)25	Severe malaria anaemia	Kenya	1022	< 5y	0.048/y	0.40 (0.30 – 0.60)
Williams et al (2005)23	Severe malarial anaemia	Kenya	2655	< 5y	0.005/y	0.11 (0.01 – 0.97)
Parikh et al (2004)34	Uncomplicated malaria	Uganda	307	6m – 5y	2.04/y	0.72 (0.5 – 1.1)
Williams et al (2005)23,b	Uncomplicated malaria	Kenya	370	< 11y	2.36/y	0.67 (0.57 – 0.80)
Williams et al (2005)24,b	Uncomplicated malaria	Kenya	323	< 8y	3.06/y	0.49 (0.33 – 0.74)
Migot-Nabias et al (2006)96	Uncomplicated malaria	Senegal	169	2 – 10y	NA	Reduced incidence in HbAS (IRR not reported)
Clark et al (2008)36	Uncomplicated malaria3	Uganda	558	1 – 10y	0.82/y	0.68 (0.52 – 0.90)
Crompton et al (2008)35	Uncomplicated malaria3	Mali	176	2 – 10y	1.76/y	0.46 (0.27 – 0.79)
Enevold et al (2008)40	Uncomplicated malaria	Tanzania	159	6m – 19y	35%/6m	RR: 1.55 (0.51 – 4.77)
Kreuels et al (2010)37	Uncomplicated malaria3	Ghana	852	3m – 2y	1.2/y	0.78 (0.66 – 0.92)
Summary23,34-37	Uncomplicated malaria					0.69 (0.61 – 0.79)
Le Hesran et al (1999)59	P. falciparum parasitaemia	Cameroon	240	< 5y	NA	No difference (IRR not reported)
Stirnadel et al (1999)58	P. falciparum parasitaemia	Tanzania	204	< 1y	NA	No difference (IRR not reported)
Haemoglobin C
Rihet et al (2004)101	Uncomplicated malaria3	Mali	256	1 – 24y	NA	Reduced incidence with HbC (IRR not reported)
Crompton et al (2008)35	Uncomplicated malaria3	Mali	176	2 – 10y	1.76/y	He: 1.02 (0.72 – 1.42)
Kreuels et al (2010)37	Uncomplicated malaria3	Ghana	852	3m – 2y	1.2/y	He: 1.08 (0.93 – 1.26)
Summary35,37	Uncomplicated malaria					He: 1.05 (0.88 – 1.26)
α-thalassaemia
Williams et al (2005)31	Severe malaria	Kenya	2104	< 5y	0.061/y	Ho: 0.54 (0.30 – 0.99) He: 0.60 (0.39 – 0.90)
Wambua et al (2006)32	Severe malarial anaemia	Kenya	2104	< 5y	0.010/y	Ho: 0.35 (0.11 – 1.18) He: 0.33 (0.14 – 0.78)
Wambua et al (2006)32	Cerebral malaria	Kenya	2104	< 5y	0.002/y	Ho: 0.60 (0.24 – 1.50) He: 0.48 (0.24 – 0.97)
Williams et al (1996)39	Uncomplicated malaria3	Vanuatu	544	< 5y	0.7/y	Ho: 2.30 (1.32 – 4.07) He: 1.10 (0.77 – 1.61)
Williams et al (2005)31	Uncomplicated malaria	Kenya	370	< 11y	2.46/y	Ho: 0.83 (0.70 – 0.97) He: 0.93 (0.82 – 1.04)
Migot-Nabias et al (2006)96	Uncomplicated malaria3	Senegal	169	2 – 10y	NA	No difference (IRR not reported)
Enevold et al (2008)40	Uncomplicated malaria	Tanzania	159	6m – 19y	45%/6m	Ho: RR 0.12 (0.02 – 0.83) He: RR 0.30 (0.10 – 0.85)
Crompton et al (2008)35	Uncomplicated malaria3	Mali	176	2 – 10y	1.76/y	Ho: 1.60 (0.51 – 3.81) He: 1.14 (0.90 – 1.46)
Lin et al (2010)67	Uncomplicated malaria3	Papua New Guinea	206	5 – 14y	NA	Ho: 0.84 (0.49 – 1.44) He: 0.63 (0.36 – 1.10)
Summary23,35,39	Uncomplicated malaria					Ho: 1.12 (0.69 – 1.81) He: 0.98 (0.87 – 1.11)
Lin et al (2010)67	P. falciparum parasitaemia (PCR)	Papua New Guinea	206	5 – 14y	NA	Ho: 0.51 (0.32 – 0.81) He: 0.56 (0.36 – 0.87)

Abbreviations: NA: data not available; IRR: incidence rate ratio; RR: risk ratio; Ho: homozygote; He: heterozygote; PCR: polymerase chain reaction. No prospective studies investigated the effects of HbE or β-thalassaemia on malaria.

^aAnnual incidence rate in the unexposed population (i.e., HbAA or αα/αα genotype) of the indicated outcome.

^bStudies with overlapping cohorts. Because the cohort in Williams et al (2005)²³ subsumes that of Williams et al (2005),²⁴ only data from Williams et al (2005)²³ was included in the meta-analyzed summary IRR for uncomplicated malaria in HbAS children.