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Pregnancy-associated malaria
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Pregnancy-associated malaria
Pregnancy-associated malaria (PAM) or placental malaria is a presentation of malaria in pregnancy which is life-threatening to both pregnant women and unborn fetuses. PAM occurs when a pregnant woman contracts malaria, generally as a result of Plasmodium falciparum infection, and because she is pregnant, is at greater risk of associated complications such as placental malaria. Placental malaria interferes with the transmission of vital substances through the fetal placenta, which can result in stillbirths, miscarriages, and dangerously low birth weights.
Prevention and treatment of malaria are essential components of prenatal care in tropical and subtropical geographic areas affected by malaria, and thus has received much international attention.
Symptoms of malaria include malaise, headaches, fatigue, fever, muscle aches, abdominal pain, nausea and vomiting. More severe cases may present with seizures and even coma. Women affected by PAM that have natural resistance to malaria may experience normal, mild, or no symptoms of malaria and therefore often will not seek proper medical care.
Transmission of malaria occurs when humans are bitten by mosquitos infected with the Plasmodium falciparum parasite, which enters the bloodstream as sporozoites.Over the next 7–30 days, the sporozites will convert to merozites in the liver and re-enter the bloodstream to infect erythrocytes.
Pregnant women and unborn fetuses are more susceptible to malaria infection due to the complications of pregnancy and the aggregation of erythrocytes around the placenta. Infected erythrocytes express the VAR2CSA variant of P. falciparum erythrocyte membrane protein 1 (PfEMP1) which allows them to bind to chondroitin sulfate A (CSA) on placental proteoglycans and accumulate in the intervillous spaces of the placenta, blocking nutrient flow and causing inflammation.
Women are most susceptible to infection early in their first pregnancy due to absence of antibodies. Those infected with human immunodeficiency virus (HIV) are also at greater risk of infection and associated symptoms due to the heightened parasite burden within the placenta during pregnancy.
P. falciparum expresses proteins on the surface of parasite-infected erythrocytes (IE) helping them bind to an unusually low-sulfated form of chondroitin sulfate A (CSA) in the placental intervillous space. By this process, the parasite avoids being filtered through the spleen where it would be cleared from the bloodstream and killed. When selected in vitro for CSA-binding, the only upregulated gene expressed in the P. falciparum parasites was the var2csa gene. Parasite clones - where the var2csa gene was disrupted - lost the ability to adhere to CSA by blocking the binding of IE. Its protein, VAR2CSA (Variant Surface antigen 2-CSA), belongs to the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family and contains six Duffy binding-like (DBL) domains. The regions that mediate binding to CSA have not been defined, but DBL2, DBL3, and DBL6 have shown the highest affinity for CSA binding when testing with recombinant single-domains.
A unique var gene (PFL0030c or var2csa) encodes this particular PfEMP1, which is differently regulated than other genes from the var family. It is also only expressed as protein in pregnant women, even though the transcript is present in children, men and non-pregnant women. It has a unique regulatory region, a uORF located upstream from the ORF that codes for the VAR2CSA protein. The expression of a protein named PTEF (after Plasmodium falciparum translation-enhancing factor) has been described to be necessary for the translation machinery to overcome the uORF and produce VAR2CSA protein, but the mechanism behind it remains to be elucidated.
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Pregnancy-associated malaria AI simulator
(@Pregnancy-associated malaria_simulator)
Pregnancy-associated malaria
Pregnancy-associated malaria (PAM) or placental malaria is a presentation of malaria in pregnancy which is life-threatening to both pregnant women and unborn fetuses. PAM occurs when a pregnant woman contracts malaria, generally as a result of Plasmodium falciparum infection, and because she is pregnant, is at greater risk of associated complications such as placental malaria. Placental malaria interferes with the transmission of vital substances through the fetal placenta, which can result in stillbirths, miscarriages, and dangerously low birth weights.
Prevention and treatment of malaria are essential components of prenatal care in tropical and subtropical geographic areas affected by malaria, and thus has received much international attention.
Symptoms of malaria include malaise, headaches, fatigue, fever, muscle aches, abdominal pain, nausea and vomiting. More severe cases may present with seizures and even coma. Women affected by PAM that have natural resistance to malaria may experience normal, mild, or no symptoms of malaria and therefore often will not seek proper medical care.
Transmission of malaria occurs when humans are bitten by mosquitos infected with the Plasmodium falciparum parasite, which enters the bloodstream as sporozoites.Over the next 7–30 days, the sporozites will convert to merozites in the liver and re-enter the bloodstream to infect erythrocytes.
Pregnant women and unborn fetuses are more susceptible to malaria infection due to the complications of pregnancy and the aggregation of erythrocytes around the placenta. Infected erythrocytes express the VAR2CSA variant of P. falciparum erythrocyte membrane protein 1 (PfEMP1) which allows them to bind to chondroitin sulfate A (CSA) on placental proteoglycans and accumulate in the intervillous spaces of the placenta, blocking nutrient flow and causing inflammation.
Women are most susceptible to infection early in their first pregnancy due to absence of antibodies. Those infected with human immunodeficiency virus (HIV) are also at greater risk of infection and associated symptoms due to the heightened parasite burden within the placenta during pregnancy.
P. falciparum expresses proteins on the surface of parasite-infected erythrocytes (IE) helping them bind to an unusually low-sulfated form of chondroitin sulfate A (CSA) in the placental intervillous space. By this process, the parasite avoids being filtered through the spleen where it would be cleared from the bloodstream and killed. When selected in vitro for CSA-binding, the only upregulated gene expressed in the P. falciparum parasites was the var2csa gene. Parasite clones - where the var2csa gene was disrupted - lost the ability to adhere to CSA by blocking the binding of IE. Its protein, VAR2CSA (Variant Surface antigen 2-CSA), belongs to the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family and contains six Duffy binding-like (DBL) domains. The regions that mediate binding to CSA have not been defined, but DBL2, DBL3, and DBL6 have shown the highest affinity for CSA binding when testing with recombinant single-domains.
A unique var gene (PFL0030c or var2csa) encodes this particular PfEMP1, which is differently regulated than other genes from the var family. It is also only expressed as protein in pregnant women, even though the transcript is present in children, men and non-pregnant women. It has a unique regulatory region, a uORF located upstream from the ORF that codes for the VAR2CSA protein. The expression of a protein named PTEF (after Plasmodium falciparum translation-enhancing factor) has been described to be necessary for the translation machinery to overcome the uORF and produce VAR2CSA protein, but the mechanism behind it remains to be elucidated.