scholarly journals Age-related Changes in Malaria Clinical Phenotypes During Infancy are Modified by Sickle Cell Trait

2021 ◽  
Author(s):  
Nicholas Zehner ◽  
Harriet Adrama ◽  
Abel Kakuru ◽  
Teddy Andra ◽  
Richard Kajubi ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Malaria Incidence ◽  
Protective Efficacy ◽  
Plasmodium Falciparum Malaria ◽  
Clinical Phenotypes ◽  
Young Infants ◽  
Symptomatic Malaria ◽  
Age Related ◽  
Malaria Incidence Rate

Abstract Background Young infants are protected against Plasmodium falciparum malaria. Mechanisms driving this protection remain unclear due to a poor understanding of malaria clinical phenotypes during infancy. Methods We enrolled a birth cohort of 678 infants in Busia, Uganda, an area of high malaria transmission. We followed infants through 12 months of age, and quantified protection against parasitemia and clinical disease. Results Symptomatic malaria incidence increased from 1.2 to 2.6 episodes per person year between 0-<6 months and 6-12 months of age, while the monthly probability of asymptomatic parasitemia given infection decreased from 32% to 21%. Sickle cell trait (HbAS) was protective against symptomatic malaria (incidence rate ratio (IRR) = 0.57 comparing HbAS vs. HbAA, 95% CI 0.44-0.74, p<0.001), but age modified this relationship (Pint=<0.001), with non-linear protection that waned between 0-9 months of age before increasing. Increasing age was associated with higher parasite densities at the time of infection, and, in infants with HbAS, a reduced ability to tolerate high parasite densities without fever. Conclusions Age-dependent changes in HbAS protective efficacy in infancy were accompanied by differential loss of anti-parasite and anti-disease protection among HbAS and HbAA infants. This provides a framework for investigating mechanisms underlying infant protection against malaria.

scholarly journals Evidence for both innate and acquired mechanisms of protection from Plasmodium falciparum in children with sickle cell trait

Blood ◽  
2012 ◽  
Vol 119 (16) ◽  
pp. 3808-3814 ◽  
Author(s):  
Lauren Gong ◽  
Catherine Maiteki-Sebuguzi ◽  
Philip J. Rosenthal ◽  
Alan E. Hubbard ◽  
Chris J. Drakeley ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Relative Density ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Plasmodium Falciparum Malaria ◽  
Force Of Infection ◽  
Symptomatic Malaria ◽  
Molecular Force ◽  
High Parasite Density ◽  
Within Subjects

AbstractSickle cell trait (HbAS) is known to be protective against Plasmodium falciparum malaria, but it is unclear when during the course of infection this protection occurs and whether protection is innate or acquired. To address these questions, a cohort of 601 children 1-10 years of age were enrolled in Kampala, Uganda, and followed for 18 months for symptomatic malaria and asymptomatic parasitemia. Genotyping was used to detect and follow individual parasite clones longitudinally within subjects. Children with HbAS were protected against the establishment of parasitemia, as assessed by the molecular force of infection at older but not younger ages (at 2 years of age: incidence rate ratio [IRR] = 1.16; 95% confidence interval [95% CI], 0.62-2.19; P = .6; at 9 years of age: IRR = 0.50; 95% CI, 0.28-0.87; P = .01), suggesting an acquired mechanism of protection. Once parasitemic, children with HbAS were less likely to progress to symptomatic malaria, with protection again being the most pronounced at older ages (at 2 years of age: relative risk [RR] = 0.92; 95% CI, 0.77-1.10; P = .3; at 9 years of age: RR = 0.68; 95% CI, 0.51-0.91; P = .008). Conversely, the youngest children were best protected against high parasite density (at 2 years of age: relative density = 0.24; 95% CI, 0.10-0.54; P = .001; at 9 years of age: relative density = 0.59; 95% CI, 0.30-1.19; P = .14), suggesting an innate mechanism of protection against this end point.

scholarly journals PfEMP1-specific IgG reactivity among Beninese pregnant women with sickle cell trait

2021 ◽  
Author(s):  
Mary Lopez-Perez ◽  
Firmine Viwami ◽  
Zakaria Seidu ◽  
Anja T R Jensen ◽  
Justin Doritchamou ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Sickle Cell ◽  
Infected Erythrocyte ◽  
Sickle Cell Trait ◽  
Placental Malaria ◽  
Plasmodium Falciparum Malaria ◽  
Risk Of Infection ◽  
Native Proteins ◽  
Malaria Exposure ◽  
Specific Igg

Abstract Background Sickle cell trait (HbAS) protects against severe Plasmodium falciparum malaria, but not against placental malaria (PM). In this study, PfEMP1-specific antibodies were measured in HbAA and HbAS Beninese pregnant women as a proxy of exposure to specific PfEMP1 variants. Methods Plasma samples collected at delivery from 338 HbAA and 63 HbAS women were used to measure IgG levels to six recombinant PfEMP1 proteins and three corresponding native proteins expressed on the infected erythrocyte (IE) surface. IgG-mediated inhibition of VAR2CSA + IEs adhesion to CSA was also tested. Results Levels of PfEMP1-specific IgG were similar in the two groups, except for native IT4VAR09 on IEs, where IgG levels were significantly higher in HbAS women. Adjusted odds ratios for women with positive IgG to HB3VAR06 and PFD1235w suggest a lower risk of infection with these virulent variants among HbAS individuals. The percentage of IEs binding to CSA did not differ between HbAA and HbAS women, but correlated positively with levels of anti-VAR2CSA and parity. Women with PM had lower levels of anti-VAR2CSA-specific IgG and lower IgG-mediated inhibition of IE adhesion to CSA. Conclusions The findings support similar malaria exposure in HbAA and HbAS women and a lack of HbAS-dependent protection against placental infection among pregnant women.

scholarly journals Common α-globin variants modify hematologic and other clinical phenotypes in sickle cell trait and disease

PLoS Genetics ◽  
2018 ◽  
Vol 14 (3) ◽  
pp. e1007293 ◽  
Author(s):  
Laura M. Raffield ◽  
Jacob C. Ulirsch ◽  
Rakhi P. Naik ◽  
Samuel Lessard ◽  
Robert E. Handsaker ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Clinical Phenotypes

scholarly journals Sterile "Abscess" of the Spleen and the Sickle Cell Trait

2018 ◽  
Vol 10 (1) ◽  
pp. 2018003 ◽  
Author(s):  
Lucio Luzzatto
Keyword(s):  
Plasmodium Falciparum ◽  
Case Report ◽  
Falciparum Malaria ◽  
Ultrasound Imaging ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Plasmodium Falciparum Malaria ◽  
Splenic Infarction ◽  
Sterile Abscess

Dear Editor:I read with interest the case report by Dr P Magro et al. [MJHID 9: e2017023, 2017] regarding a boy with sickle cell trait (AS), who was appropriately treated for Plasmodium falciparum malaria and who, upon ultrasound imaging, was thought to have multiple abscesses in the spleen, eventually interpreted as splenic infarction. 

Sickle cell trait and the eye

1977 ◽  
Vol 137 (3) ◽  
pp. 281a-281
Author(s):  
P. E. Mickelson
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Trait

Microsurgery in the Sickle Cell Trait Population: Is It Actually Safe?

2020 ◽  
pp. 1-2
Author(s):  
Michael Alperovich ◽  
Eric Park ◽  
Michael Alperovich ◽  
Omar Allam ◽  
Paul Abraham
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Free Flap ◽  
Near Infrared ◽  
Sickle Cell Trait ◽  
Cell Disease ◽  
Flap Transfer ◽  
Free Flap Transfer ◽  
Patient Reported ◽  
Deep Inferior Epigastric Perforator

Although sickle cell disease has long been viewed as a contraindication to free flap transfer, little data exist evaluating complications of microsurgical procedures in the sickle cell trait patient. Reported is the case of a 55-year-old woman with sickle cell trait who underwent a deep inferior epigastric perforator (DIEP) microvascular free flap following mastectomy. The flap developed signs of venous congestion on postoperative day two but was found to have patent arterial and venous anastomoses upon exploration in the operating room. On near-infrared indocyanine green angiography, poor vascular flow was noted despite patent anastomoses and strong cutaneous arterial Doppler signals. Intrinsic microvascular compromise or sickling remains a risk in the sickle cell trait population as it does for the sickle cell disease population. Just like in sickle cell disease patients, special care should be taken to optimize anticoagulation and minimize ischemia-induced sickling for patients with sickle cell trait undergoing microsurgery.

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