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Haemoglobinopathies and the clinical epidemiology of malaria: a systematic review and meta-analysis

Summary Background Haemoglobinopathies can reduce the risk of malaria syndromes. We aimed to quantify the relation between different haemoglobin mutations and malaria protection to strengthen the foundation for translational studies of malaria pathogenesis and immunity. Methods We systematically sea... Full description

Journal Title: The Lancet infectious diseases 2012, Vol.12 (6), p.457-468
Main Author: Taylor, Steve M, Dr
Other Authors: Parobek, Christian M, BS , Fairhurst, Rick M, MD
Format: Electronic Article Electronic Article
Language: English
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Quelle: Alma/SFX Local Collection
Publisher: London: Elsevier Ltd
ID: ISSN: 1473-3099
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title: Haemoglobinopathies and the clinical epidemiology of malaria: a systematic review and meta-analysis
format: Article
creator:
  • Taylor, Steve M, Dr
  • Parobek, Christian M, BS
  • Fairhurst, Rick M, MD
subjects:
  • alpha-Thalassemia - blood
  • Anemias. Hemoglobinopathies
  • Biological and medical sciences
  • Diseases of red blood cells
  • Epidemiology
  • Hematologic and hematopoietic diseases
  • Hemoglobin, Sickle
  • Hemoglobinopathies - blood
  • Hemoglobinopathies - genetics
  • Human protozoal diseases
  • Humans
  • Infectious Disease
  • Infectious diseases
  • Malaria
  • Malaria - blood
  • Malaria - epidemiology
  • Malaria - prevention & control
  • Malaria, Falciparum - epidemiology
  • Medical sciences
  • Parasitic diseases
  • Protozoal diseases
  • Risk Factors
ispartof: The Lancet infectious diseases, 2012, Vol.12 (6), p.457-468
description: Summary Background Haemoglobinopathies can reduce the risk of malaria syndromes. We aimed to quantify the relation between different haemoglobin mutations and malaria protection to strengthen the foundation for translational studies of malaria pathogenesis and immunity. Methods We systematically searched the Medline and Embase databases for studies that estimated the risk of malaria in patients with and without haemoglobinopathies up to Sept 9, 2011, and identified additional studies from reference lists. We included studies that enrolled mainly children or pregnant women and had the following outcomes: Plasmodium falciparum severe malaria, uncomplicated malaria, asymptomatic parasitaemia, or pregnancy-associated malaria, and Plasmodium vivax malaria. Two reviewers identified studies independently, assessed quality of the studies, and extracted data. We produced odds ratios (ORs; 95% CIs) for case-control studies and incidence rate ratios (IRRs; 95% CIs) for prospective studies. We did the meta-analysis with a random-effects model when equivalent outcomes were reported in more than one study. Findings Of 62 identified studies, 44 reported data for haemoglobin AS, 19 for haemoglobin AC and CC, and 18 for α-thalassaemia. Meta-analysis of case-control studies showed a decreased risk of severe P falciparum malaria in individuals with haemoglobin AS (OR 0·09, 95% CI 0·06–0·12), haemoglobin CC (0·27, 0·11–0·63), haemoglobin AC (0·83, 0·67–0·96), homozygous α-thalassaemia (0·63, 0·48–0·83), and heterozygous α-thalassaemia (0·83, 0·74–0·92). In meta-analysis of prospective trials only haemoglobin AS was consistently associated with protection from uncomplicated malaria (IRR 0·69, 95% CI 0·61–0·79); no haemoglobinopathies led to consistent protection from asymptomatic parasitaemia. Few clinical studies have investigated β-thalassaemia, haemoglobin E, P vivax malaria, or pregnancy-associated malaria. Interpretation Haemoglobin AS, CC, and AC genotypes and homozygous and heterozygous α-thalassaemia provide significant protection from severe malaria syndromes, but these haemoglobinopathies differ substantially in the degree of protection provided and confer mild or no protection against uncomplicated malaria and asymptomatic parasitaemia. Through attenuation of severity of malaria, haemoglobinopathies could serve as a model for investigation of the mechanisms of malaria pathogenesis and immunity. Funding US National Institute of Allergy and Infectious Diseases.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 1473-3099
fulltext: fulltext
issn:
  • 1473-3099
  • 1474-4457
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descriptionSummary Background Haemoglobinopathies can reduce the risk of malaria syndromes. We aimed to quantify the relation between different haemoglobin mutations and malaria protection to strengthen the foundation for translational studies of malaria pathogenesis and immunity. Methods We systematically searched the Medline and Embase databases for studies that estimated the risk of malaria in patients with and without haemoglobinopathies up to Sept 9, 2011, and identified additional studies from reference lists. We included studies that enrolled mainly children or pregnant women and had the following outcomes: Plasmodium falciparum severe malaria, uncomplicated malaria, asymptomatic parasitaemia, or pregnancy-associated malaria, and Plasmodium vivax malaria. Two reviewers identified studies independently, assessed quality of the studies, and extracted data. We produced odds ratios (ORs; 95% CIs) for case-control studies and incidence rate ratios (IRRs; 95% CIs) for prospective studies. We did the meta-analysis with a random-effects model when equivalent outcomes were reported in more than one study. Findings Of 62 identified studies, 44 reported data for haemoglobin AS, 19 for haemoglobin AC and CC, and 18 for α-thalassaemia. Meta-analysis of case-control studies showed a decreased risk of severe P falciparum malaria in individuals with haemoglobin AS (OR 0·09, 95% CI 0·06–0·12), haemoglobin CC (0·27, 0·11–0·63), haemoglobin AC (0·83, 0·67–0·96), homozygous α-thalassaemia (0·63, 0·48–0·83), and heterozygous α-thalassaemia (0·83, 0·74–0·92). In meta-analysis of prospective trials only haemoglobin AS was consistently associated with protection from uncomplicated malaria (IRR 0·69, 95% CI 0·61–0·79); no haemoglobinopathies led to consistent protection from asymptomatic parasitaemia. Few clinical studies have investigated β-thalassaemia, haemoglobin E, P vivax malaria, or pregnancy-associated malaria. Interpretation Haemoglobin AS, CC, and AC genotypes and homozygous and heterozygous α-thalassaemia provide significant protection from severe malaria syndromes, but these haemoglobinopathies differ substantially in the degree of protection provided and confer mild or no protection against uncomplicated malaria and asymptomatic parasitaemia. Through attenuation of severity of malaria, haemoglobinopathies could serve as a model for investigation of the mechanisms of malaria pathogenesis and immunity. Funding US National Institute of Allergy and Infectious Diseases.
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subjectalpha-Thalassemia - blood ; Anemias. Hemoglobinopathies ; Biological and medical sciences ; Diseases of red blood cells ; Epidemiology ; Hematologic and hematopoietic diseases ; Hemoglobin, Sickle ; Hemoglobinopathies - blood ; Hemoglobinopathies - genetics ; Human protozoal diseases ; Humans ; Infectious Disease ; Infectious diseases ; Malaria ; Malaria - blood ; Malaria - epidemiology ; Malaria - prevention & control ; Malaria, Falciparum - epidemiology ; Medical sciences ; Parasitic diseases ; Protozoal diseases ; Risk Factors
ispartofThe Lancet infectious diseases, 2012, Vol.12 (6), p.457-468
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descriptionSummary Background Haemoglobinopathies can reduce the risk of malaria syndromes. We aimed to quantify the relation between different haemoglobin mutations and malaria protection to strengthen the foundation for translational studies of malaria pathogenesis and immunity. Methods We systematically searched the Medline and Embase databases for studies that estimated the risk of malaria in patients with and without haemoglobinopathies up to Sept 9, 2011, and identified additional studies from reference lists. We included studies that enrolled mainly children or pregnant women and had the following outcomes: Plasmodium falciparum severe malaria, uncomplicated malaria, asymptomatic parasitaemia, or pregnancy-associated malaria, and Plasmodium vivax malaria. Two reviewers identified studies independently, assessed quality of the studies, and extracted data. We produced odds ratios (ORs; 95% CIs) for case-control studies and incidence rate ratios (IRRs; 95% CIs) for prospective studies. We did the meta-analysis with a random-effects model when equivalent outcomes were reported in more than one study. Findings Of 62 identified studies, 44 reported data for haemoglobin AS, 19 for haemoglobin AC and CC, and 18 for α-thalassaemia. Meta-analysis of case-control studies showed a decreased risk of severe P falciparum malaria in individuals with haemoglobin AS (OR 0·09, 95% CI 0·06–0·12), haemoglobin CC (0·27, 0·11–0·63), haemoglobin AC (0·83, 0·67–0·96), homozygous α-thalassaemia (0·63, 0·48–0·83), and heterozygous α-thalassaemia (0·83, 0·74–0·92). In meta-analysis of prospective trials only haemoglobin AS was consistently associated with protection from uncomplicated malaria (IRR 0·69, 95% CI 0·61–0·79); no haemoglobinopathies led to consistent protection from asymptomatic parasitaemia. Few clinical studies have investigated β-thalassaemia, haemoglobin E, P vivax malaria, or pregnancy-associated malaria. Interpretation Haemoglobin AS, CC, and AC genotypes and homozygous and heterozygous α-thalassaemia provide significant protection from severe malaria syndromes, but these haemoglobinopathies differ substantially in the degree of protection provided and confer mild or no protection against uncomplicated malaria and asymptomatic parasitaemia. Through attenuation of severity of malaria, haemoglobinopathies could serve as a model for investigation of the mechanisms of malaria pathogenesis and immunity. Funding US National Institute of Allergy and Infectious Diseases.
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abstractSummary Background Haemoglobinopathies can reduce the risk of malaria syndromes. We aimed to quantify the relation between different haemoglobin mutations and malaria protection to strengthen the foundation for translational studies of malaria pathogenesis and immunity. Methods We systematically searched the Medline and Embase databases for studies that estimated the risk of malaria in patients with and without haemoglobinopathies up to Sept 9, 2011, and identified additional studies from reference lists. We included studies that enrolled mainly children or pregnant women and had the following outcomes: Plasmodium falciparum severe malaria, uncomplicated malaria, asymptomatic parasitaemia, or pregnancy-associated malaria, and Plasmodium vivax malaria. Two reviewers identified studies independently, assessed quality of the studies, and extracted data. We produced odds ratios (ORs; 95% CIs) for case-control studies and incidence rate ratios (IRRs; 95% CIs) for prospective studies. We did the meta-analysis with a random-effects model when equivalent outcomes were reported in more than one study. Findings Of 62 identified studies, 44 reported data for haemoglobin AS, 19 for haemoglobin AC and CC, and 18 for α-thalassaemia. Meta-analysis of case-control studies showed a decreased risk of severe P falciparum malaria in individuals with haemoglobin AS (OR 0·09, 95% CI 0·06–0·12), haemoglobin CC (0·27, 0·11–0·63), haemoglobin AC (0·83, 0·67–0·96), homozygous α-thalassaemia (0·63, 0·48–0·83), and heterozygous α-thalassaemia (0·83, 0·74–0·92). In meta-analysis of prospective trials only haemoglobin AS was consistently associated with protection from uncomplicated malaria (IRR 0·69, 95% CI 0·61–0·79); no haemoglobinopathies led to consistent protection from asymptomatic parasitaemia. Few clinical studies have investigated β-thalassaemia, haemoglobin E, P vivax malaria, or pregnancy-associated malaria. Interpretation Haemoglobin AS, CC, and AC genotypes and homozygous and heterozygous α-thalassaemia provide significant protection from severe malaria syndromes, but these haemoglobinopathies differ substantially in the degree of protection provided and confer mild or no protection against uncomplicated malaria and asymptomatic parasitaemia. Through attenuation of severity of malaria, haemoglobinopathies could serve as a model for investigation of the mechanisms of malaria pathogenesis and immunity. Funding US National Institute of Allergy and Infectious Diseases.
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