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placental malaria

Not Open Access | TLR4-endothelin axis controls syncytiotrophoblast motility and confers fetal protection in placental malaria

June 8, 2021 - 10:52 -- NOT Open Access
Pandya Y, Marta A, Barateiro A, Bandeira CL, Dombrowski JG, Costa J, Marinho CRF, Penha-Gonçalves C
Infect Immun. 2021 Jun 1:IAI0080920

Pregnancy associated malaria is often associated with adverse pregnancy outcomes. Placental circulatory impairments are an intriguing and unsolved component of malaria pathophysiology. Here, we uncovered a TLR4-TRIF-endothelin axis that controls trophoblast motility and is linked to fetal protection during Plasmodium infection. In a cohort of 401 pregnancies from Northern Brazil we found that infection during pregnancy reduced expression of endothelin receptor B in syncytiotrophoblasts while endothelin expression was only affected during acute infection.

Predictors of placental malaria in Upper West Regional Hospital-Ghana

June 1, 2021 - 12:57 -- Open Access
Mwin PK, Kuffuor A, Nuhu K, Okine R, Kubio C, Wurapa F, Osei FA, Afari E
BMC Pregnancy Childbirth. 2021 May 26;21(1):403

Placental malaria (PM) poses life-threatening complications to pregnant women as they are at increased risk of maternal and perinatal morbidity and mortality associated with malaria. This study examined the factors associated with placental malaria in the Upper West Regional Hospital (UWR).


NOT Open Access |Peripheral Plasmodium falciparum infection in early pregnancy is associated with increased maternal microchimerism in the offspring

May 25, 2021 - 15:20 -- NOT Open Access
Simon N, Shallat J, Houck J, Jagannathan P, Prahl M, Muhindo MK, Kakuru A, Olwoch P, Feeney ME, Harrington WE
J Infect Dis. 2021 May 19:jiab275

Placental malaria has been associated with increased cord blood maternal microchimerism (MMc), which in turn may affect susceptibility to malaria in the offspring. We sought to determine the impact of maternal peripheral Plasmodium falciparum parasitemia during pregnancy on MMc and to determine whether maternal cells expand during primary parasitemia in the offspring.

Cryo-EM reveals the architecture of placental malaria VAR2CSA and provides molecular insight into chondroitin sulfate binding

May 25, 2021 - 14:39 -- Open Access
Wang K, Dagil R, Salanti A, et al.
Nat Commun. 2021 May 19;12(1):2956

Placental malaria can have severe consequences for both mother and child and effective vaccines are lacking. Parasite-infected red blood cells sequester in the placenta through interaction between parasite-expressed protein VAR2CSA and the glycosaminoglycan chondroitin sulfate A (CS) abundantly present in the intervillous space. Here, we report cryo-EM structures of the VAR2CSA ectodomain at up to 3.1 Å resolution revealing an overall V-shaped architecture and a complex domain organization.

NOT Open Access | Progress and new horizons toward a VAR2CSA-based placental malaria vaccine

February 8, 2021 - 10:47 -- NOT Open Access
Doritchamou JYA, Suurbaar J, Tuikue Ndam N
Expert Rev Vaccines. 2021 Feb 4:1-12

Several malaria vaccines are under various phases of development with some promising results. In placental malaria (PM) a deliberately anti-disease approach is considered as many studies have underlined the key role of VAR2CSA protein, which therefore represents the leading vaccine candidate. However, evidence indicates that VAR2CSA antigenic polymorphism remains an obstacle to overcome.

Structural basis for placental malaria mediated by Plasmodium falciparum VAR2CSA

January 20, 2021 - 07:28 -- Open Access
Ma R, Lian T, Huang R, Renn JP, Petersen JD, Zimmerberg J, Duffy PE, Tolia NH
Nat Microbiol. 2021 Jan 15

Plasmodium falciparum VAR2CSA binds to chondroitin sulfate A (CSA) on the surface of the syncytiotrophoblast during placental malaria. This interaction facilitates placental sequestration of malaria parasites resulting in severe health outcomes for both the mother and her offspring. Furthermore, CSA is presented by diverse cancer cells and specific targeting of cells by VAR2CSA may become a viable approach for cancer treatment. In the present study, we determined the cryo-electron microscopy structures of the full-length ectodomain of VAR2CSA from P. falciparum strain NF54 in complex with CSA, and VAR2CSA from a second P. falciparum strain FCR3.

Not Open Access | Molecular architecture and domain arrangement of the placental malaria protein VAR2CSA suggests a model for carbohydrate binding

December 30, 2020 - 14:19 -- NOT Open Access
Bewley MC, Gautam L, Jagadeeshaprasad MG, Gowda DC, Flanagan JM
J Biol Chem. 2020 Dec 25;295(52):18589-18603

VAR2CSA is the placental-malaria-specific member of the antigenically variant Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family. It is expressed on the surface of Plasmodium falciparum-infected host red blood cells and binds to specific chondroitin-4-sulfate chains of the placental proteoglycan receptor. The functional ∼310 kDa ectodomain of VAR2CSA is a multidomain protein that requires a minimum 12-mer chondroitin-4-sulfate molecule for specific, high affinity receptor binding. However, it is not known how the individual domains are organized and interact to create the receptor-binding surface, limiting efforts to exploit its potential as an effective vaccine or drug target.

Infant sex modifies associations between placental malaria and risk of malaria in infancy

December 3, 2020 - 13:06 -- Open Access
Abel Kakuru, Michelle E. Roh, Prasanna Jagannathan, et al.
Malaria Journal 2020 19:449, 3 December 2020

Placental malaria (PM) has been associated with a higher risk of malaria during infancy. However, it is unclear whether this association is causal, and is modified by infant sex, and whether intermittent preventive treatment in pregnancy (IPTp) can reduce infant malaria by preventing PM.

Factors associated with sub-microscopic placental malaria and its association with adverse pregnancy outcomes among HIV-negative women in Dar es Salaam, Tanzania: a cohort study

October 28, 2020 - 10:49 -- Open Access
Kalinjuma AV, Darling AM, Mugusi FM, Abioye AI, Okumu FO, Aboud S, Masanja H, Hamer DH, Hertzmark E, Fawzi WW
BMC Infect Dis. 2020 Oct 27;20(1):796

Malaria infection during pregnancy has negative health consequences for both mothers and offspring. Sub-microscopic malaria infection during pregnancy is common in most African countries. We sought to identify factors associated with sub-microscopic placental malaria, and its association with adverse pregnancy outcomes among HIV-negative pregnant women in Dar es Salaam, Tanzania.

Generation of a malaria negative Ugandan birth weight standard for the diagnosis of small for gestational age

October 6, 2020 - 12:37 -- Open Access
Zakama AK, Weekes T, Kajubi R, Kakuru A, Ategeka J, Kamya M, Muhindo MK, Havlir D, Jagannathan P, Dorsey G, Gaw SL
PLoS One. 2020 Oct 2;15(10):e0240157

Placental malaria is a known risk factor for small for gestational age (SGA) neonates. However, currently utilized international and African birthweight standards have not controlled for placental malaria and/or lack obstetrical ultrasound dating. We developed a neonatal birthweight standard based on obstetrically dated pregnancies that excluded individuals with clinical malaria, asymptomatic parasitemia, and placental malaria infection. We hypothesized that current curves underestimate true ideal birthweight and the prevalence of SGA.


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