{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T17:22:57Z","timestamp":1776360177063,"version":"3.51.2"},"reference-count":40,"publisher":"Proceedings of the National Academy of Sciences","issue":"26","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1997,12,23]]},"abstract":"<jats:p>\n            In the South West Pacific region, the striking geographical correlation between the frequency of \u03b1\n            <jats:sup>+<\/jats:sup>\n            -thalassemia and the endemicity of\n            <jats:italic>Plasmodium falciparum<\/jats:italic>\n            suggests that this hemoglobinopathy provides a selective advantage against malaria. In Vanuatu, paradoxically, \u03b1\n            <jats:sup>+<\/jats:sup>\n            -thalassemia increases the incidence of contracting mild malaria in the first 2 years of life, but severe disease was too uncommon to assess adequately. Therefore, we undertook a prospective case-control study of children with severe malaria on the north coast of Papua New Guinea, where malaria transmission is intense and \u03b1\n            <jats:sup>+<\/jats:sup>\n            -thalassemia affects more than 90% of the population. Compared with normal children, the risk of having severe malaria was 0.40 (95% confidence interval 0.22\u20130.74) in \u03b1\n            <jats:sup>+<\/jats:sup>\n            -thalassemia homozygotes and 0.66 (0.37\u20131.20) in heterozygotes. Unexpectedly, the risk of hospital admission with infections other than malaria also was reduced to a similar degree in homozygous (0.36; 95% confidence interval 0.22\u20130.60) and heterozygous (0.63; 0.38\u20131.07) children. This clinical study demonstrates that a malaria resistance gene protects against disease caused by infections other than malaria. The mechanism of the remarkable protective effect of \u03b1\n            <jats:sup>+<\/jats:sup>\n            -thalassemia against severe childhood disease remains unclear but must encompass the clear interaction between this hemoglobinopathy and both malarial and nonmalarial infections.\n          <\/jats:p>","DOI":"10.1073\/pnas.94.26.14736","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:35:50Z","timestamp":1027694150000},"page":"14736-14741","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":225,"title":["\u03b1\n            <sup>+<\/sup>\n            -Thalassemia protects children against disease caused by other infections as well as\u2009malaria"],"prefix":"10.1073","volume":"94","author":[{"given":"S. J.","family":"Allen","sequence":"first","affiliation":[{"name":"Institute of Molecular Medicine, University of Oxford, The John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom; and Papua New Guinea Institute of Medical Research, P.O. Box 60, Goroka, 441 EHP, Papua New Guinea"}]},{"given":"A.","family":"O\u2019Donnell","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, University of Oxford, The John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom; and Papua New Guinea Institute of Medical Research, P.O. Box 60, Goroka, 441 EHP, Papua New Guinea"}]},{"given":"N. D. E.","family":"Alexander","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, University of Oxford, The John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom; and Papua New Guinea Institute of Medical Research, P.O. Box 60, Goroka, 441 EHP, Papua New Guinea"}]},{"given":"M. P.","family":"Alpers","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, University of Oxford, The John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom; and Papua New Guinea Institute of Medical Research, P.O. Box 60, Goroka, 441 EHP, Papua New Guinea"}]},{"given":"T. E. A.","family":"Peto","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, University of Oxford, The John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom; and Papua New Guinea Institute of Medical Research, P.O. Box 60, Goroka, 441 EHP, Papua New Guinea"}]},{"given":"J. B.","family":"Clegg","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, University of Oxford, The John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom; and Papua New Guinea Institute of Medical Research, P.O. Box 60, Goroka, 441 EHP, Papua New Guinea"}]},{"given":"D. J.","family":"Weatherall","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, University of Oxford, The John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom; and Papua New Guinea Institute of Medical Research, P.O. Box 60, Goroka, 441 EHP, Papua New Guinea"}]}],"member":"341","published-online":{"date-parts":[[1997,12,23]]},"reference":[{"key":"e_1_3_2_1_2","volume-title":"The Thalassaemia Syndromes","author":"Weatherall D J","year":"1981","unstructured":"D J Weatherall, J B Clegg The Thalassaemia Syndromes (Blackwell, Oxford, 1981)."},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/321744a0"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00280500"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1080\/00034983.1988.11812202"},{"key":"e_1_3_2_5_2","first-page":"390","volume":"48","author":"Modiano G","year":"1991","unstructured":"G Modiano, G Morpurgo, L Terrenato, A Novelletto, A Di Rienzo, B Colombo, M Purpura, M Mariani, S Santachiara-Benerecetti, A Brega, K A Dixit, S L Shrestha, A Lania, W Wanachiwanawin, L Luzzatto Am J Hum Genet 48, 390\u2013397 (1991).","journal-title":"Am J Hum Genet"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(93)90129-E"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(84)91754-9"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1986.35.3"},{"key":"e_1_3_2_9_2","first-page":"267","volume":"28","author":"Moir J S","year":"1985","unstructured":"J S Moir, J L Tulloch, H Vrbova, D J Jolley, P F Heywood, M P Alpers PNG Med J 28, 267\u2013278 (1985).","journal-title":"PNG Med J"},{"key":"e_1_3_2_10_2","first-page":"157","volume":"95","author":"Hayes R J","year":"1992","unstructured":"R J Hayes, K Marsh, R W Snow J Trop Med Hyg 95, 157\u2013166 (1992).","journal-title":"J Trop Med Hyg"},{"key":"e_1_3_2_11_2","unstructured":"Warrell D. 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