Children with Plasmodium vivax infection previously observed in Namibia, were Duffy negative and carried a c.136G > A mutation

Abstract Background In a previous study, using a molecular approach, we reported the presence of P. vivax in Namibia. Here, we have extended our investigation to the Duffy antigen genetic profile of individuals of the same cohort with and without Plasmodium infections. Methods Participants with P. vivax (n = 3), P. falciparum (n = 23) mono-infections and co-infections of P. vivax/P. falciparum (n = 4), and P. falciparum/P. ovale (n = 3) were selected from seven regions. Participants with similar age but without any Plasmodium infections (n = 47) were also selected from all the regions. Duffy allelic profile was examined using standard PCR followed by sequencing of amplified products. Sequenced samples were also examined for the presence or absence of G125A mutation in codon 42, exon 2. Results All individuals tested carried the − 67 T > C mutation. However, while all P. vivax infected participants carried the c.G125A mutation, 7/28 P. falciparum infected participants and 9/41 of uninfected participants did not have the c.G125A mutation. The exon 2 region surrounding codon 42, had a c.136G > A mutation that was present in all P. vivax infections. The odds ratio for lack of this mutation with P. vivax infections was (OR 0.015, 95% CI 0.001–0.176; p = 0.001). Conclusion We conclude that P. vivax infections previously reported in Namibia, occurred in Duffy negative participants, carrying the G125A mutation in codon 42. The role of the additional mutation c.136 G > A in exon 2 in P. vivax infections, will require further investigations.

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Role of IL-1β, IL-6 and TNF-α cytokines and TNF-α promoter variability in Plasmodium vivax infection during pregnancy in endemic population of Jharkhand, India

Molecular Immunology ◽

10.1016/j.molimm.2018.03.019 ◽

2018 ◽

Vol 97 ◽

pp. 82-93 ◽

Cited By ~ 5

Author(s):

Krishn Pratap Singh ◽

Shayan Shakeel ◽

Namrata Naskar ◽

Aakanksha Bharti ◽

Asha Kaul ◽

...

Keyword(s):

Plasmodium Vivax ◽

Vivax Infection ◽

Tnf Α ◽

Endemic Population

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Molecular evidence of Plasmodium vivax infection in Duffy negative symptomatic individuals from Dschang, West Cameroon

Malaria Journal ◽

10.1186/s12936-017-1722-2 ◽

2017 ◽

Vol 16 (1) ◽

Cited By ~ 20

Author(s):

Gianluca Russo ◽

Giovanni Faggioni ◽

Giacomo Maria Paganotti ◽

Ghyslaine Bruna Djeunang Dongho ◽

Alice Pomponi ◽

...

Keyword(s):

Plasmodium Vivax ◽

Vivax Infection ◽

Molecular Evidence ◽

Duffy Negative

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Distribution of Duffy Phenotypes among Plasmodium vivax Infections in Sudan

Genes ◽

10.3390/genes10060437 ◽

2019 ◽

Vol 10 (6) ◽

pp. 437

Author(s):

Musab M.A. Albsheer ◽

Kareen Pestana ◽

Safaa Ahmed ◽

Mohammed Elfaki ◽

Eiman Gamil ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Plasmodium Vivax ◽

Real Time Pcr ◽

Blood Cells ◽

Vivax Infection ◽

Quantitative Real Time Pcr ◽

East African ◽

African Countries ◽

Human Red Blood Cells ◽

Duffy Negative

Negative Duffy expression on the surface of human red blood cells was believed to be a barrier for Plasmodium vivax infection in most Africans. However, P. vivax has been demonstrated to infect Duffy-negative individuals in several Central and East African countries. In this study, we investigated the distribution of Duffy blood group phenotypes with regard to P. vivax infection and parasitemia in Sudan. Out of 992 microscopic-positive malaria samples, 190 were identified as P. vivax positive infections. Among them, 186 were P. vivax mono-infections and 4 were mixed P. vivax and Plasmodium falciparum infections. A subset of 77 samples was estimated with parasitemia by quantitative real-time PCR. Duffy codons were sequenced from the 190 P. vivax positive samples. We found that the Duffy Fy(a-b+) phenotype was the most prevalent, accounting for 67.9% of all P. vivax infections, while homozygous Duffy-negative Fy(a-b-) accounted for 17.9% of the P. vivax infections. The prevalence of infection in Fy(a-b+) and Fy(a+b-)were significantly higher than Fy(a-b-) phenotypes (p = 0.01 and p < 0.01, respectively). A significantly low proportion of P. vivax infection was observed in Duffy negative individuals Fy(a-b-). This study highlights the prevalence of P. vivax in Duffy-negatives in Sudan and indicates low parasitemia among the Duffy-negative individuals.

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Acquired Antibody Responses against Plasmodium vivax Infection Vary with Host Genotype for Duffy Antigen Receptor for Chemokines (DARC)

PLoS ONE ◽

10.1371/journal.pone.0011437 ◽

2010 ◽

Vol 5 (7) ◽

pp. e11437 ◽

Cited By ~ 19

Author(s):

Amanda Maestre ◽

Carlos Muskus ◽

Victoria Duque ◽

Olga Agudelo ◽

Pu Liu ◽

...

Keyword(s):

Plasmodium Vivax ◽

Antigen Receptor ◽

Vivax Infection ◽

Antibody Responses ◽

Host Genotype ◽

Duffy Antigen

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Functional Role of the Chemokine Binding Duffy Antigen Receptor Complex (DARC) in Human Inflammation In Vivo.

Blood ◽

10.1182/blood.v108.11.20.20 ◽

2006 ◽

Vol 108 (11) ◽

pp. 20-20

Author(s):

Florian B. Mayr ◽

Petra Jilma-Stohlawetz ◽

Christa Firbas ◽

Anthony F. Suffredini ◽

Hartmut Derendorf ◽

...

Keyword(s):

Inflammatory Response ◽

Functional Role ◽

Blood Group Antigen ◽

Receptor Complex ◽

Human Endotoxemia ◽

Time Points ◽

Duffy Antigen ◽

Duffy Negative

Abstract Background: The Duffy receptor is a promiscuous receptor for chemokines that binds selected members of both the C-X-C and C-C families with high affinity. Duffy antigen may influence plasma levels of proinflammatory cytokines by acting as a “chemokine sink”. Additionally, Duffy knockout mice experienced an exaggerated response to endotoxin in comparison to wild-type mice. The current trial was designed to elucidate the functional role of the Duffy blood group antigen in human inflammation. We hypothesized that “Duffy negative“ volunteers might show an increased inflammatory response to endotoxin (LPS) infusion in terms of cytokine response. The human endotoxemia model is a well established model of systemic inflammation, where a well defined, self-limited inflammatory stimulus permits the elucidation of key players involved in the inflammatory response. We therefore used this model to investigate the functional role of the Duffy Antigen Receptor Complex (DARC) in the inflammatory response after endotoxin challenge. Methods: Thirty-two healthy male volunteers received an intravenous infusion of 2ng/kg endotoxin, 16 Caucasians (Duffy antigen positive on erythrocytes) and 16 subjects of African descent (“Duffy negatives”). Cytokines, chemokines, as well as their receptors were quantified by ELISA, RT-PCR and FACS. Results: Plasma levels of TNF, IL-6, IL-8 and IL-8 mRNA in whole blood increased to a similar extent in both groups after LPS infusion. In contrast, peak MCP-1 levels at 3 hours were roughly 2-fold higher in Duffy positive subjects 16ng/mL as compared to Duffy negative subjects (7ng/mL p<0.001). Similarly, GRO-alpha levels were 2.5-fold higher in Duffy positive subjects at 2 hours after LPS infusion (210pg/mL vs 85pg/mL; p= 0.0001), whereas baseline values showed no difference between both groups. There was no difference in the LPS induced release of MIP-1 beta (which was used as a negative control). Baseline levels of MCP-1 and GRO-alpha in erythrocyte lysates were significantly higher in Duffy positive individuals, whereas IL-8 and MIP-1beta levels were comparable between both groups. Values of MCP-1 and GRO-α, both known to bind to the Duffy antigen, increased extensively in erythrocyte lysates of Duffy positive subjects over time (P=<0.001 vs. time). In contrast, MCP-1 only moderately changed over time in Duffy negative subjects (P<0.03 vs. time), whereas GRO-alpha remained comparable to baseline at all time points (P=0.2 vs. time). As a consequence, MCP-1 and GRO-alpha were several hundred-fold higher in Duffy positive subjects at all time points and reached peak levels at 2–4 hours. Additionally, IL-8, which also binds to erythrocytes via the Duffy antigen, was roughly 7-fold higher in erythrocyte lysates of Duffy positive subjects 2 hours after LPS infusion. As expected, MIP-1beta remained similar at all time points and was comparable between both groups. The expected increase in CD11b, and decrease in CCR-2 and CXCR-1, CXCR-2 occurred without differences between groups. Conclusion: This study characterized for the first time the in vivo function of the Duffy Antigen in humans. The blood group antigen has a profound effect on erythrocyte-bound chemokines and free chemokines in a model of human endotoxemia.

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