Reduced Risk of Plasmodium vivax Malaria in Papua New Guinean Children with Southeast Asian Ovalocytosis in Two Cohorts and a Case-Control Study
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{"title"=>"Reduced Risk of Plasmodium vivax Malaria in Papua New Guinean Children with Southeast Asian Ovalocytosis in Two Cohorts and a Case-Control Study", "type"=>"journal", "authors"=>[{"first_name"=>"Anna", "last_name"=>"Rosanas-Urgell", "scopus_author_id"=>"23669349400"}, {"first_name"=>"Enmoore", "last_name"=>"Lin", "scopus_author_id"=>"7201721086"}, {"first_name"=>"Laurens", "last_name"=>"Manning", "scopus_author_id"=>"16444571700"}, {"first_name"=>"Patricia", "last_name"=>"Rarau", "scopus_author_id"=>"54973974800"}, {"first_name"=>"Moses", "last_name"=>"Laman", "scopus_author_id"=>"35798443700"}, {"first_name"=>"Nicolas", "last_name"=>"Senn", "scopus_author_id"=>"14042774200"}, {"first_name"=>"Brian T.", "last_name"=>"Grimberg", "scopus_author_id"=>"13005293600"}, {"first_name"=>"Livingstone", "last_name"=>"Tavul", "scopus_author_id"=>"6507516455"}, {"first_name"=>"Danielle I.", "last_name"=>"Stanisic", "scopus_author_id"=>"6602104900"}, {"first_name"=>"Leanne J.", "last_name"=>"Robinson", "scopus_author_id"=>"55139326100"}, {"first_name"=>"John J.", "last_name"=>"Aponte", "scopus_author_id"=>"35594206200"}, {"first_name"=>"Elijah", "last_name"=>"Dabod", "scopus_author_id"=>"19336888700"}, {"first_name"=>"John C.", "last_name"=>"Reeder", "scopus_author_id"=>"55209842700"}, {"first_name"=>"Peter", "last_name"=>"Siba", "scopus_author_id"=>"12241224200"}, {"first_name"=>"Peter A.", "last_name"=>"Zimmerman", "scopus_author_id"=>"7101612694"}, {"first_name"=>"Timothy M.E.", "last_name"=>"Davis", "scopus_author_id"=>"57005974500"}, {"first_name"=>"Christopher L.", "last_name"=>"King", "scopus_author_id"=>"7401525894"}, {"first_name"=>"Pascal", "last_name"=>"Michon", "scopus_author_id"=>"14043484200"}, {"first_name"=>"Ivo", "last_name"=>"Mueller", "scopus_author_id"=>"7006910183"}], "year"=>2012, "source"=>"PLoS Medicine", "identifiers"=>{"sgr"=>"84866669398", "pmid"=>"22973182", "scopus"=>"2-s2.0-84866669398", "pui"=>"365720709", "isbn"=>"1549-1676 (Electronic)\\n1549-1277 (Linking)", "issn"=>"15491277", "doi"=>"10.1371/journal.pmed.1001305"}, "id"=>"4f4b40a1-de34-37c3-8c84-362f13e62493", "abstract"=>"BACKGROUND: The erythrocyte polymorphism, Southeast Asian ovalocytosis (SAO) (which results from a 27-base pair deletion in the erythrocyte band 3 gene, SLC4A1Δ27) protects against cerebral malaria caused by Plasmodium falciparum; however, it is unknown whether this polymorphism also protects against P. vivax infection and disease.\\n\\nMETHODS AND FINDINGS: The association between SAO and P. vivax infection was examined through genotyping of 1,975 children enrolled in three independent epidemiological studies conducted in the Madang area of Papua New Guinea. SAO was associated with a statistically significant 46% reduction in the incidence of clinical P. vivax episodes (adjusted incidence rate ratio [IRR] = 0.54, 95% CI 0.40-0.72, p<0.0001) in a cohort of infants aged 3-21 months and a significant 52% reduction in P. vivax (blood-stage) reinfection diagnosed by PCR (95% CI 22-71, p = 0.003) and 55% by light microscopy (95% CI 13-77, p = 0.014), respectively, in a cohort of children aged 5-14 years. SAO was also associated with a reduction in risk of P. vivax parasitaemia in children 3-21 months (1,111/µl versus 636/µl, p = 0.011) and prevalence of P. vivax infections in children 15-21 months (odds ratio [OR] = 0.39, 95% CI 0.23-0.67, p = 0.001). In a case-control study of children aged 0.5-10 years, no child with SAO was found among 27 cases with severe P. vivax or mixed P. falciparum/P. vivax malaria (OR = 0, 95% CI 0-1.56, p = 0.11). SAO was associated with protection against severe P. falciparum malaria (OR = 0.38, 95% CI 0.15-0.87, p = 0.014) but no effect was seen on either the risk of acquiring blood-stage infections or uncomplicated episodes with P. falciparum. Although Duffy antigen receptor expression and function were not affected on SAO erythrocytes compared to non-SAO children, high level (>90% binding inhibition) P. vivax Duffy binding protein-specific binding inhibitory antibodies were observed significantly more often in sera from SAO than non-SAO children (SAO, 22.2%; non-SAO, 6.7%; p = 0.008).\\n\\nCONCLUSIONS: In three independent studies, we observed strong associations between SAO and protection against P. vivax malaria by a mechanism that is independent of the Duffy antigen. P. vivax malaria may have contributed to shaping the unique host genetic adaptations to malaria in Asian and Oceanic populations. Please see later in the article for the Editors' Summary.", "link"=>"http://www.mendeley.com/research/reduced-risk-plasmodium-vivax-malaria-papua-new-guinean-children-southeast-asian-ovalocytosis-two-co", "reader_count"=>51, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>3, "Researcher"=>13, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>2, "Student > Master"=>9, "Other"=>2, "Student > Bachelor"=>6, "Lecturer"=>2, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>3, "Researcher"=>13, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>2, "Student > Master"=>9, "Other"=>2, "Student > Bachelor"=>6, "Lecturer"=>2, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>24, "Medicine and Dentistry"=>14, "Physics and Astronomy"=>1, "Social Sciences"=>2, "Computer Science"=>1, "Immunology and Microbiology"=>2, "Earth and Planetary Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>14}, "Social Sciences"=>{"Social Sciences"=>2}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Earth and Planetary Sciences"=>{"Earth and Planetary Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>24}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Papua New Guinea"=>1, "United States"=>2, "Sri Lanka"=>1, "Italy"=>1, "United Kingdom"=>1, "France"=>1, "Indonesia"=>1, "India"=>1}, "group_count"=>4}

Scopus | Further Information

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  • {"files"=>["https://ndownloader.figshare.com/files/306569", "https://ndownloader.figshare.com/files/306619", "https://ndownloader.figshare.com/files/306680"], "description"=>"<div><h3>Background</h3><p>The erythrocyte polymorphism, Southeast Asian ovalocytosis (SAO) (which results from a 27-base pair deletion in the erythrocyte band 3 gene, <em>SLC4A1Δ27</em>) protects against cerebral malaria caused by <em>Plasmodium falciparum</em>; however, it is unknown whether this polymorphism also protects against <em>P. vivax</em> infection and disease.</p> <h3>Methods and Findings</h3><p>The association between SAO and <em>P. vivax</em> infection was examined through genotyping of 1,975 children enrolled in three independent epidemiological studies conducted in the Madang area of Papua New Guinea. SAO was associated with a statistically significant 46% reduction in the incidence of clinical <em>P. vivax</em> episodes (adjusted incidence rate ratio [IRR] = 0.54, 95% CI 0.40–0.72, <em>p</em><0.0001) in a cohort of infants aged 3–21 months and a significant 52% reduction in <em>P. vivax</em> (blood-stage) reinfection diagnosed by PCR (95% CI 22–71, <em>p</em> = 0.003) and 55% by light microscopy (95% CI 13–77, <em>p</em> = 0.014), respectively, in a cohort of children aged 5–14 years. SAO was also associated with a reduction in risk of <em>P. vivax</em> parasitaemia in children 3–21 months (1,111/µl versus 636/µl, <em>p</em> = 0.011) and prevalence of <em>P. vivax</em> infections in children 15–21 months (odds ratio [OR] = 0.39, 95% CI 0.23–0.67, <em>p</em> = 0.001). In a case-control study of children aged 0.5–10 years, no child with SAO was found among 27 cases with severe <em>P. vivax</em> or mixed <em>P. falciparum</em>/<em>P. vivax</em> malaria (OR = 0, 95% CI 0–1.56, <em>p</em> = 0.11). SAO was associated with protection against severe <em>P. falciparum</em> malaria (OR = 0.38, 95% CI 0.15–0.87, <em>p</em> = 0.014) but no effect was seen on either the risk of acquiring blood-stage infections or uncomplicated episodes with <em>P. falciparum</em>. Although Duffy antigen receptor expression and function were not affected on SAO erythrocytes compared to non-SAO children, high level (>90% binding inhibition) <em>P. vivax</em> Duffy binding protein–specific binding inhibitory antibodies were observed significantly more often in sera from SAO than non-SAO children (SAO, 22.2%; non-SAO, 6.7%; <em>p</em> = 0.008).</p> <h3>Conclusions</h3><p>In three independent studies, we observed strong associations between SAO and protection against <em>P. vivax</em> malaria by a mechanism that is independent of the Duffy antigen. <em>P. vivax</em> malaria may have contributed to shaping the unique host genetic adaptations to malaria in Asian and Oceanic populations.</p> <p> <em>Please see later in the article for the Editors' Summary.</em></p> </div>", "links"=>[], "tags"=>["reduced", "malaria", "papua", "guinean", "children", "asian", "ovalocytosis", "cohorts", "case-control"], "article_id"=>120476, "categories"=>["Cancer", "Genetics", "Biotechnology", "Hematology"], "users"=>["Anna Rosanas-Urgell", "Enmoore Lin", "Laurens Manning", "Patricia Rarau", "Moses Laman", "Nicolas Senn", "Brian T. Grimberg", "Livingstone Tavul", "Danielle I. Stanisic", "Leanne J. Robinson", "John J. Aponte", "Elijah Dabod", "John C. Reeder", "Peter Siba", "Peter A. Zimmerman", "Timothy M. E. Davis", "Christopher L. King", "Pascal Michon", "Ivo Mueller"], "doi"=>["https://dx.doi.org/10.1371/journal.pmed.1001305.s001", "https://dx.doi.org/10.1371/journal.pmed.1001305.s002", "https://dx.doi.org/10.1371/journal.pmed.1001305.s003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Reduced_Risk_of_Plasmodium_vivax_Malaria_in_Papua_New_Guinean_Children_with_Southeast_Asian_Ovalocytosis_in_Two_Cohorts_and_a_Case_Control_Study/120476", "title"=>"Reduced Risk of <em>Plasmodium vivax</em> Malaria in Papua New Guinean Children with Southeast Asian Ovalocytosis in Two Cohorts and a Case-Control Study", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-09-04 00:07:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/581887"], "description"=>"<p>Significance levels adjusted for IPTi treatment, insecticide-treated net use, and village of residence.</p>", "links"=>[], "tags"=>["sao", "non-sao", "children"], "article_id"=>252347, "categories"=>["Biotechnology", "Genetics", "Infectious Diseases", "Hematology"], "users"=>["Anna Rosanas-Urgell", "Enmoore Lin", "Laurens Manning", "Patricia Rarau", "Moses Laman", "Nicolas Senn", "Brian T. Grimberg", "Livingstone Tavul", "Danielle I. Stanisic", "Leanne J. Robinson", "John J. Aponte", "Elijah Dabod", "John C. Reeder", "Peter Siba", "Peter A. Zimmerman", "Timothy M. E. Davis", "Christopher L. King", "Pascal Michon", "Ivo Mueller"], "doi"=>["https://dx.doi.org/10.1371/journal.pmed.1001305.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Parasite_density_by_LM_in_species_in_SAO_wt_916_27_red_squares_and_non_SAO_children_wt_wt_blue_rhombi_/252347", "title"=>"Parasite density (by LM) in species in SAO (wt/Δ27, red squares) and non-SAO children (wt/wt, blue rhombi).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-04 00:39:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/581950"], "description"=>"<p>Kaplan-Meier Curves with log-rank test for difference.</p>", "links"=>[], "tags"=>["blood-stage", "infections", "plasmodium", "sao", "non-sao", "children"], "article_id"=>252426, "categories"=>["Biotechnology", "Genetics", "Infectious Diseases", "Hematology"], "users"=>["Anna Rosanas-Urgell", "Enmoore Lin", "Laurens Manning", "Patricia Rarau", "Moses Laman", "Nicolas Senn", "Brian T. Grimberg", "Livingstone Tavul", "Danielle I. Stanisic", "Leanne J. Robinson", "John J. Aponte", "Elijah Dabod", "John C. Reeder", "Peter Siba", "Peter A. Zimmerman", "Timothy M. E. Davis", "Christopher L. King", "Pascal Michon", "Ivo Mueller"], "doi"=>["https://dx.doi.org/10.1371/journal.pmed.1001305.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Time_to_first_blood_stage_infections_with_different_Plasmodium_species_in_SAO_dashed_and_non_SAO_children_solid_/252426", "title"=>"Time-to-first blood-stage infections with different Plasmodium species in SAO (dashed) and non-SAO children (solid).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-04 00:40:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/582066"], "description"=>"<p>Each spot represents analysis of 5×10<sup>5</sup> erythrocytes from a single donor.</p>", "links"=>[], "tags"=>["receptor", "erythrocytes", "mab", "fy6", "sao", "non-sao", "cells", "binding", "pvdbpii"], "article_id"=>252532, "categories"=>["Biotechnology", "Genetics", "Infectious Diseases", "Hematology"], "users"=>["Anna Rosanas-Urgell", "Enmoore Lin", "Laurens Manning", "Patricia Rarau", "Moses Laman", "Nicolas Senn", "Brian T. Grimberg", "Livingstone Tavul", "Danielle I. Stanisic", "Leanne J. Robinson", "John J. Aponte", "Elijah Dabod", "John C. Reeder", "Peter Siba", "Peter A. Zimmerman", "Timothy M. E. Davis", "Christopher L. King", "Pascal Michon", "Ivo Mueller"], "doi"=>["https://dx.doi.org/10.1371/journal.pmed.1001305.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Duffy_receptor_expression_on_erythrocytes_as_measured_by_mAb_Fy6_on_SAO_and_non_SAO_cells_left_panel_and_binding_of_PvDBPII_to_its_receptor_on_SAO_and_non_SAO_cells_right_panel_/252532", "title"=>"Duffy receptor expression on erythrocytes as measured by mAb Fy6 on SAO and non-SAO cells (left panel) and binding of PvDBPII to its' receptor on SAO and non-SAO cells (right panel).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-04 00:42:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/582098"], "description"=>"a<p>Infections diagnosed by post-PCR LDR-FMA.</p>b<p>Infections diagnosed by expert LM.</p>c<p>AORs with analyses adjusted for the following variables: IPTi treatment group, insecticide treatment bednet usage, village of residence.</p><p>PR, prevalence rate.</p>", "links"=>[], "tags"=>["sao", "prevalence", "infants"], "article_id"=>252585, "categories"=>["Biotechnology", "Genetics", "Infectious Diseases", "Hematology"], "users"=>["Anna Rosanas-Urgell", "Enmoore Lin", "Laurens Manning", "Patricia Rarau", "Moses Laman", "Nicolas Senn", "Brian T. Grimberg", "Livingstone Tavul", "Danielle I. Stanisic", "Leanne J. Robinson", "John J. Aponte", "Elijah Dabod", "John C. Reeder", "Peter Siba", "Peter A. Zimmerman", "Timothy M. E. Davis", "Christopher L. King", "Pascal Michon", "Ivo Mueller"], "doi"=>["https://dx.doi.org/10.1371/journal.pmed.1001305.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Associations_between_SAO_and_prevalence_of_P_vivax_and_P_falciparum_infection_in_infants_3_21_mo_/252585", "title"=>"Associations between SAO and prevalence of <i>P. vivax</i> and <i>P. falciparum</i> infection in infants 3–21 mo.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-09-04 00:43:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/582131"], "description"=>"a<p>Infections diagnosed by post-PCR LDR-FMA.</p>b<p>Infections diagnosed by expert LM.</p>c<p>AHRs with analyses adjusted for the following significant confounders: <i>P. vivax</i>, presence of LM+ Pv infection at baseline; <i>P. falciparum</i>, distance from residence to local health centre; <i>P. malariae</i>, none.</p>d<p>AHRs with analyses adjusted for the following significant confounders: <i>P. vivax</i>, age >9 y; <i>P. falciparum</i>, distance from residence to local school elementary school+LDR-FMA positive Pf infection at baseline; <i>P. malariae</i>, distance from residence to local health centre and to local elementary school.</p>e<p>As LM-positive <i>P. malariae</i> infection were observed among SAO children, confidence interval could not be estimated and <i>p</i>-value obtained by log-rank test.</p>", "links"=>[], "tags"=>["sao", "follow-up", "children"], "article_id"=>252612, "categories"=>["Biotechnology", "Genetics", "Infectious Diseases", "Hematology"], "users"=>["Anna Rosanas-Urgell", "Enmoore Lin", "Laurens Manning", "Patricia Rarau", "Moses Laman", "Nicolas Senn", "Brian T. Grimberg", "Livingstone Tavul", "Danielle I. Stanisic", "Leanne J. Robinson", "John J. Aponte", "Elijah Dabod", "John C. Reeder", "Peter Siba", "Peter A. Zimmerman", "Timothy M. E. Davis", "Christopher L. King", "Pascal Michon", "Ivo Mueller"], "doi"=>["https://dx.doi.org/10.1371/journal.pmed.1001305.t003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Associations_between_SAO_and_to_first_Plasmodium_spp_infection_during_follow_up_in_children_5_14_y_/252612", "title"=>"Associations between SAO and to first <i>Plasmodium spp.</i> infection during follow-up in children 5–14 y.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-09-04 00:43:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/582179"], "description"=>"a<p>IRR-AHRs with analyses adjusted for the following potential confounders: gender, village of residence, average bednet usage, season of recruitment, and IPTi treatment group.</p><p>PYAR, person year at risk.</p>", "links"=>[], "tags"=>["sao", "incidence", "malaria", "follow-up", "infants"], "article_id"=>252652, "categories"=>["Biotechnology", "Genetics", "Infectious Diseases", "Hematology"], "users"=>["Anna Rosanas-Urgell", "Enmoore Lin", "Laurens Manning", "Patricia Rarau", "Moses Laman", "Nicolas Senn", "Brian T. Grimberg", "Livingstone Tavul", "Danielle I. Stanisic", "Leanne J. Robinson", "John J. Aponte", "Elijah Dabod", "John C. Reeder", "Peter Siba", "Peter A. Zimmerman", "Timothy M. E. Davis", "Christopher L. King", "Pascal Michon", "Ivo Mueller"], "doi"=>["https://dx.doi.org/10.1371/journal.pmed.1001305.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Associations_between_SAO_and_incidence_of_malaria_during_follow_up_in_infants_3_8211_21_mo_/252652", "title"=>"Associations between SAO and incidence of malaria during follow-up in infants 3–21 mo.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-09-04 00:44:12"}

PMC Usage Stats | Further Information

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Relative Metric

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