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placental malaria

Can complement fix placental malaria

September 15, 2021 - 11:19 -- Open Access
Author(s): 
Doritchamou JYA, Duffy PE.
Reference: 
Med. 2021 Sep 10;19(1):231

Placental malaria (PM) is a deadly public health problem caused by the human parasite Plasmodium falciparum, and this scourge will get worse as existing control measures lose potency. Our understanding of PM pathogenesis suggests a vaccine is feasible, but first-generation candidates yielded only modest variant-specific activity in early trials.

Structural insights into global mutations in the ligand-binding domain of VAR2CSA and its implications on placental malaria vaccine

September 1, 2021 - 15:45 -- Open Access
Author(s): 
Gill J, Chakraborti S, Bharti P, Sharma A
Reference: 
Int J Infect Dis. 2021 Aug 24:S1201-9712(21)00687-1

Placental malaria is a public health burden particularly in Africa as it causes severe symptoms and results in stillbirths or maternal deaths. Plasmodium falciparum protein VAR2CSA drives placental malaria (PM) in pregnant women by adhering to chondroitin sulfate A (CSA) on the placenta. VAR2CSA is a primary vaccine candidate for PM with two vaccines based on it already under clinical trials.

Not Open Access | The effect of intermittent preventive treatment of malaria during pregnancy and placental malaria on infant risk of malaria

July 6, 2021 - 14:33 -- NOT Open Access
Author(s): 
Andronescu LR, Sharma A, Peterson I, Kachingwe M, Kachepa W, Liang Y, Gutman JR, Mathanga DP, Chinkhumba J, Laufer MK
Reference: 
J Infect Dis. 2021 Jul 3:jiab351

Intermittent preventive treatment of malaria during pregnancy (IPTp) with dihydroartemisinin-piperaquine (DP) provides greater protection from placental malaria than sulfadoxine-pyrimethamine (SP). Some studies suggest placental malaria alters the risk of malaria infection in infants, but few studies have quantified the effect of IPTp on infant susceptibility to malaria.

Developing a multivariate prediction model of antibody features associated with protection of malaria-infected pregnant women from placental malaria

June 30, 2021 - 09:30 -- Open Access
Author(s): 
Aitken EH, Damelang T, Rogerson SJ, et al.
Reference: 
Elife. 2021 Jun 29;10:e65776

Plasmodium falciparum causes placental malaria, which results in adverse outcomes for mother and child. P. falciparum-infected erythrocytes that express the parasite protein VAR2CSA on their surface can bind to placental chondroitin sulfate A. It has been hypothesized that naturally acquired antibodies towards VAR2CSA protect against placental infection, but it has proven difficult to identify robust antibody correlates of protection from disease. The objective of this study was to develop a prediction model using antibody features that could identify women protected from 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
Author(s): 
Pandya Y, Marta A, Barateiro A, Bandeira CL, Dombrowski JG, Costa J, Marinho CRF, Penha-Gonçalves C
Reference: 
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
Author(s): 
Mwin PK, Kuffuor A, Nuhu K, Okine R, Kubio C, Wurapa F, Osei FA, Afari E
Reference: 
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).

Methods

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
Author(s): 
Simon N, Shallat J, Houck J, Jagannathan P, Prahl M, Muhindo MK, Kakuru A, Olwoch P, Feeney ME, Harrington WE
Reference: 
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
Author(s): 
Wang K, Dagil R, Salanti A, et al.
Reference: 
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
Author(s): 
Doritchamou JYA, Suurbaar J, Tuikue Ndam N
Reference: 
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
Author(s): 
Ma R, Lian T, Huang R, Renn JP, Petersen JD, Zimmerberg J, Duffy PE, Tolia NH
Reference: 
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.

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