Why does thalassemia protect against malaria




















Alpha thalassemia is common in Asia, the Mediterranean and Melanesia where malaria is or was prevalent. In the mid s researchers working on the north coast of Papua New Guinea proved that children with mild alpha thalassemia, who inherit mutations in the "alpha" part of hemoglobin genes from each parent, were protected against malaria. These children were 60 percent less likely to get severe malarial anemia than normal children, however the mechanism of such protection was unclear.

Day and colleagues based their new study on this same population of children. According to the National Human Genome Research Institute, part of the National Institutes of Health, most individuals with alpha thalassemia have milder forms of the disease, with varying degrees of anemia.

The most severe form of alpha thalassemia, which mainly affects individuals of Southeast Asian, Chinese and Filipino ancestry, results in fetal or newborn death. The authors of the study are: Karen P. Day; Freya J. Fowkes, who was a Ph D student in Dr. Note: Content may be edited for style and length. Malaria transmission is intense and perennial in both areas, with virtually all infections due to P. In both areas, poor farmer families predominate, and access to health care is limited.

The present study was approved by the responsible ethics review committees in The Netherlands, Tanzania, and Kenya; informed consent was obtained from community leaders, local government officials, and parents or guardians.

Sampling methods and eligibility criteria. For the Tanzanian survey, a census list was made listing all resident children aged 6—72 months in the study area.

By means of this list, 16 children were randomly selected from 19 communities, resulting in a total of children. Children were eligible to participate in the survey if they had no signs of severe febrile disease or severe malnutrition at the time of assessment.

Not all selected children participated; nonparticipating children were on average younger than their participating peers. To avoid bias on replacement, we resampled children from within the same age category as the nonparticipants the age categories were 6—18, 18—36, and 36—72 months until participating children were obtained.

Of children selected, 21 did not participate in the study. Two children died between the time of the census and the start of the study, 3 children were temporarily absent, the parents of 10 children refused consent, 4 children did not show up for unknown reasons, and 2 children were not eligible because they were sick and were referred to the hospital on the day of recruitment. Three weeks before the baseline assessment of the trial, children were screened for eligibility.

Field procedures. All children were examined by a clinical officer, who also measured axillary temperature. Anthropometric measurements were collected from all children. Venous blood was collected in containers with sodium heparin as anticoagulant Becton Dickinson.

Children were treated free of charge for common childhood infections and anemia according to the guidelines of the Kenyan and Tanzanian Ministries of Health. Laboratory procedures. Contrary to most other types of rapid dipstick tests, this test detects P.

The test result becomes negative rapidly after parasite clearance [ 24 , 25 ]. In Kenya, parasitemia was detected by conventional microscopy. Whole-blood hemoglobin concentrations were measured using hematology analyzers Beckman Coulter and KX [Sysmex] for samples collected from Tanzania and Kenya, respectively. Plasma was separated by centrifugation, transferred to cryotubes, and stored in liquid nitrogen. Statistical analyses. We used the following definitions: current infection, the presence of at least 1 asexual P.

Because it is difficult to interpret estimates of iron deficiency in a population with a high prevalence of both malaria and inflammation both affect plasma ferritin concentrations independently of iron status , we restricted this analysis to children without inflammation.

Anthropometric z scores were calculated using Epi Info software version 3. For variables that were not normally distributed, we calculated the geometric mean. For variables that could not be normalized by log transformation, we assessed group differences by Mann-Whitney U or Kruskal-Wallis tests. We assessed the effect of P.

In this model, we evaluated whether the effect of P. We did not adjust for the presence of inflammation because we considered that the effect of infection on hemoglobin concentration may be mediated at least in part through inflammation. Thus, we repeated the above analysis stratifying children with P.

The groups thus formed were mutually exclusive and were compared with the reference group of children without malaria and without inflammation. For each of the groups, we used multivariate analysis to evaluate directly whether the effect of infection on hemoglobin concentration depended on genotype. In Kenya and Tanzania, 10 and 9 children, respectively, were febrile at the time of examination and were excluded from the analysis.

The characteristics of the remaining children are shown in table 1. Eight Tanzanian children were afebrile but were reported sick by the clinical officer 5 were weak without localized signs but with a history of fever, 1 had signs of an upper respiratory tract infection, 2 had signs of a gastrointestinal infection, and 1 was completing a course of quinine for malaria.

For Kenyan children, none of the children included in the study were reported sick by the clinical officer, but mothers were questioned about the history of illness during the previous 2 weeks. The Tanzanian children were younger than the Kenyan children and had lower hemoglobin concentrations. In Kenya and Tanzania, the prevalence of P.

Children with P. Published : 13 March Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative.

Skip to main content. Search all BMC articles Search. Download PDF. Abstract Objective The alpha-thalassaemia trait has been associated with protection against severe malaria but its role in Plasmodium falciparum asexual parasite and gametocyte carriage remains unclear.

Sampling techniques and laboratory procedures All study participants were screened for their sickle cell status using the sodium metabisulphite method, and this grouped all SS and SC under AS phenotypes. Results Submicroscopic asexual parasite and gametocyte prevalence The study population comprised of subjects consisting of children , adults and pregnant women , of which a total of Table 1 Demographic and clinical characteristics of study population Full size table.

Full size image. Limitations The very low numbers of both asexual parasites and gametocytes is an important limitation of the study and the findings described will need to be confirmed with a larger sample size. References 1. Article Google Scholar 3. Article Google Scholar 4. Article Google Scholar 7. Article Google Scholar Google Scholar Acknowledgements We would like to thank parents and study participants from Asutsuare and surrounding villages in Ghana who agreed to be part of this study.

Competing interests The authors declare that they have no competing interests. Consent for publication Not applicable. View author publications. About this article. Cite this article Lamptey, H. Copy to clipboard. Home Spotlight Blood Beyond Borders. Blood Beyond Borders Spotlight. The rate of mutation of human genes. National Institutes of Health.

Genetics Home Reference. Am J Phys Anthropol. World Health Organization. Allison AC. The distribution of the sickle-cell trait in East Africa and elsewhere, and its apparent relationship to the incidence of subtertian malaria. Plasmodium falciparum: physiological interactions with the human sickle cell.

Exp Parasitol. Resistance to malaria through structural variation of red blood cell invasion receptors. A case-control study in northern Liberia of Plasmodium falciparum malaria in haemoglobin S and beta-thalassaemia traits. Ann Trop Med Parasitol. PLoS Med. Mediterr J Hematol Infect Dis. The Believe trial: results of a phase 3, randomized, double-blind, placebo-controlled study of luspatercept in adult beta-thalassemia patients who require regular red blood cell RBC transfusions.

Abstract N Engl J Med. Highlights of ASH in the Mediterranean. Highlights of ASH in the Mediterranean Athens, Greece March 15 — 16, At this new event, co-hosted by the Hellenic Society of Hematology, internationally recognized experts will analyze the latest updates in hematology research from the American Society of Hematology annual meeting.

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