Abnormal Development - Malaria

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Malaria (plasmodium falciparum)

About 10,000 women and 200,000 babies die annually because of malaria in pregnancy, which can cause miscarriages, preterm births, and low-birth-weight births.[1] There are about 156 species of Plasmodium which infect different vertebrate species. In humans there are four types of malaria caused by the protozoan parasite Plasmodium falciparum (main), Plasmodium vivax, Plasmodium ovale, Plasmodium malariae.

These malarial parasites are carried by the female mosquito (anopheles species) and about 100 different species can transmit human malaria. When an infected mosquito bites a human, the parasites can enter the bloodstream and travel for about an hour before entering the liver and then multiplying. Between 6 to 16 days (depending on the species), the parasites reenter the bloodstream to invade and multiply inside red blood cells (RBCs). These infected RBCs rupture and released more parasites that infect and destroy further RBCs.

Placental infection is common in regions where malaria is endemic with women carrying their first pregnancy (primigravida). (More? Placenta - Abnormalities)

Malaria global limits 2007.jpg
Global limits and endemicity of P. falciparum in 2007
Environmental Links: Introduction | low folic acid | iodine deficiency | Nutrition | Drugs | Australian Drug Categories | USA Drug Categories | thalidomide | herbal drugs | Illegal Drugs | smoking | Fetal Alcohol Syndrome | TORCH | viral infection | bacterial infection | fungal infection | Zoonotic Infection | Toxoplasmosis | Malaria | Maternal Diabetes | Maternal Hypertension | maternal hyperthermia | Maternal Inflammation | Maternal Obesity | Hypoxia | Biological Toxins | Chemicals | heavy metals | radiation | Prenatal Diagnosis | Neonatal Diagnosis | International Classification of Diseases | Fetal Origins Hypothesis
Mouse model malaria in pregnancy
Mouse model malaria in pregnancy[2]

Some Recent Findings

  • Nobel Prize in Physiology or Medicine 2015 - was divided, one half jointly to William C. Campbell and Satoshi Ōmura "for their discoveries concerning a novel therapy against infections caused by roundworm parasites" and the other half to Youyou Tu "for her discoveries concerning a novel therapy against Malaria". Nobel Prize in Physiology or Medicine 2015
  • Experimental Malaria in Pregnancy Induces Neurocognitive Injury in Uninfected Offspring via a C5a-C5a Receptor Dependent Pathway[2] "The in utero environment profoundly impacts childhood neurodevelopment and behaviour. A substantial proportion of pregnancies in Africa are at risk of malaria in pregnancy (MIP) however the impact of in utero exposure to MIP on fetal neurodevelopment is unknown. Complement activation, in particular C5a, may contribute to neuropathology and adverse outcomes during MIP. We used an experimental model of MIP and standardized neurocognitive testing, MRI, micro-CT and HPLC analysis of neurotransmitter levels, to test the hypothesis that in utero exposure to malaria alters neurodevelopment through a C5a-C5aR dependent pathway. We show that malaria-exposed offspring have persistent neurocognitive deficits in memory and affective-like behaviour compared to unexposed controls. These deficits were associated with reduced regional brain levels of major biogenic amines and BDNF that were rescued by disruption of C5a-C5aR signaling using genetic and functional approaches. Our results demonstrate that experimental MIP induces neurocognitive deficits in offspring and suggest novel targets for intervention."
  • Does malaria affect placental development? Evidence from in vitro models[3] "Malaria in early pregnancy is difficult to study but has recently been associated with fetal growth restriction (FGR). ...We demonstrate that in vitro models of placental development can be adapted to indirectly study the impact of malaria in early pregnancy. These infections could result in impaired trophoblast invasion with reduced transformation of maternal spiral arteries due to maternal hormonal and inflammatory disturbances, which may contribute to FGR by limiting the delivery of maternal blood to the placenta. Future prevention strategies for malaria in pregnancy should include protection in the first half of pregnancy."
  • Ultrasound evidence of early fetal growth restriction after maternal malaria infection[4] "Despite early treatment in all positive women, one or more (a)symptomatic P.falciparum or P.vivax malaria infections in the first half of pregnancy result in a smaller than expected mid-trimester fetal head diameter. Strategies to prevent malaria in pregnancy should include early pregnancy."
  • Plasmodium vivax malaria[5] "Up to 40% of the world's population is at risk for Plasmodium vivax malaria, a disease that imposes a major public health and economic burden on endemic countries. Because P. vivax produces latent liver forms, eradication of P. vivax malaria is more challenging than it is for P. falciparum."
More recent papers  
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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches

Search term: Maternal Malaria

Osvaldo Loquiha, Niel Hens, Leonardo Chavane, Marleen Temmerman, Nafissa Osman, Christel Faes, Marc Aerts Mapping maternal mortality rate via spatial zero-inflated models for count data: A case study of facility-based maternal deaths from Mozambique. PLoS ONE: 2018, 13(11);e0202186 PubMed 30412633

Chigozie Jesse Uneke, Issiaka Sombie, Henry Chukwuemeka Uro-Chukwu, Ermel Johnson Using equitable impact sensitive tool (EQUIST) to promote implementation of evidence informed policymaking to improve maternal and child health outcomes: a focus on six West African Countries. Global Health: 2018, 14(1);104 PubMed 30400931

Olusola Olafuyi, Raj K S Badhan Dose optimisation of chloroquine by pharmacokinetic modelling during pregnancy for the treatment of Zika virus infection. J Pharm Sci: 2018; PubMed 30399360

Walid Algady, Sandra Louzada, Danielle Carpenter, Paulina Brajer, Anna Färnert, Ingegerd Rooth, Billy Ngasala, Fengtang Yang, Marie-Anne Shaw, Edward J Hollox The Malaria-Protective Human Glycophorin Structural Variant DUP4 Shows Somatic Mosaicism and Association with Hemoglobin Levels. Am. J. Hum. Genet.: 2018, 103(5);769-776 PubMed 30388403

Mosquito Lifecycle

Aedes aegypti and other mosquitoes have a complex life-cycle with dramatic changes in shape, function, and habitat. Female mosquitoes lay their eggs on the inner, wet walls of containers with water.
  1. Larvae hatch when water inundates the eggs as a result of rains or the addition of water by people.
  2. In the following days, the larvae will feed on microorganisms and particulate organic matter, shedding their skins three times to be able to grow from first to fourth instars.
  3. When the larva has acquired enough energy and size and is in the fourth instar, metamorphosis is triggered, changing the larva into a pupa. Pupae do not feed; they just change in form until the body of the adult, flying mosquito is formed.
  4. Then, the newly formed adult emerges from the water after breaking the pupal skin.

The entire life cycle lasts 8-10 days at room temperature, depending on the level of feeding. Thus, there is an aquatic phase (larvae, pupae) and a terrestrial phase (eggs, adults) in the Ae. aegypti life-cycle.

Mosquito lifecycle.jpg

Placental Malaria

Pregnant women have an increased susceptibility to malaria infection. Malarial infection of the placenta by sequestration of the infected red blood cells leading to low birth weight and other effects.

Placental volume - second trimester[6]
  • Several infective agents may cross into the placenta from the maternal circulation, as well as enter the embryo/fetal circulation.
  • Pregnant women have an increased susceptibility to malaria infection.
  • Malarial infection of the placenta by sequestration of the infected red blood cells leading to low birth weight and other effects.

Mouse Model

Mouse E18 neurovasculature MicroCT.jpg

Mouse E18 neurovasculature MicroCT[2]


  1. Dellicour S, Tatem AJ, Guerra CA, Snow RW & ter Kuile FO. (2010). Quantifying the number of pregnancies at risk of malaria in 2007: a demographic study. PLoS Med. , 7, e1000221. PMID: 20126256 DOI.
  2. 2.0 2.1 2.2 McDonald CR, Cahill LS, Ho KT, Yang J, Kim H, Silver KL, Ward PA, Mount HT, Liles WC, Sled JG & Kain KC. (2015). Experimental Malaria in Pregnancy Induces Neurocognitive Injury in Uninfected Offspring via a C5a-C5a Receptor Dependent Pathway. PLoS Pathog. , 11, e1005140. PMID: 26402732 DOI.
  3. Umbers AJ, Stanisic DI, Ome M, Wangnapi R, Hanieh S, Unger HW, Robinson LJ, Lufele E, Baiwog F, Siba PM, King CL, Beeson JG, Mueller I, Aplin JD, Glazier JD & Rogerson SJ. (2013). Does malaria affect placental development? Evidence from in vitro models. PLoS ONE , 8, e55269. PMID: 23383132 DOI.
  4. Rijken MJ, Papageorghiou AT, Thiptharakun S, Kiricharoen S, Dwell SL, Wiladphaingern J, Pimanpanarak M, Kennedy SH, Nosten F & McGready R. (2012). Ultrasound evidence of early fetal growth restriction after maternal malaria infection. PLoS ONE , 7, e31411. PMID: 22347473 DOI.
  5. Westenberger SJ, McClean CM, Chattopadhyay R, Dharia NV, Carlton JM, Barnwell JW, Collins WE, Hoffman SL, Zhou Y, Vinetz JM & Winzeler EA. (2010). A systems-based analysis of Plasmodium vivax lifecycle transcription from human to mosquito. PLoS Negl Trop Dis , 4, e653. PMID: 20386602 DOI.
  6. Rijken MJ, Moroski WE, Kiricharoen S, Karunkonkowit N, Stevenson G, Ohuma EO, Noble JA, Kennedy SH, McGready R, Papageorghiou AT & Nosten FH. (2012). Effect of malaria on placental volume measured using three-dimensional ultrasound: a pilot study. Malar. J. , 11, 5. PMID: 22222152 DOI.


  • Guidelines for the Treatment of Malaria. 3rd edition. Geneva: World Health Organization; 2015. Available from: http://www.ncbi.nlm.nih.gov/books/NBK294440/
  • Bioinformatics in Tropical Disease Research: A Practical and Case-Study Approach Gruber, Arthur; Durham, Alan M.; Huynh, Chuong; del Portillo, Hernando A., editors Bethesda (MD): National Library of Medicine (US), NCBI; 2008 Control of Gene Expression in Plasmodium


Ataíde R, Mayor A & Rogerson SJ. (2014). Malaria, primigravidae, and antibodies: knowledge gained and future perspectives. Trends Parasitol. , 30, 85-94. PMID: 24388420 DOI.

Rogerson SJ, Mwapasa V & Meshnick SR. (2007). Malaria in pregnancy: linking immunity and pathogenesis to prevention. Am. J. Trop. Med. Hyg. , 77, 14-22. PMID: 18165470

Rogerson SJ, Hviid L, Duffy PE, Leke RF & Taylor DW. (2007). Malaria in pregnancy: pathogenesis and immunity. Lancet Infect Dis , 7, 105-17. PMID: 17251081 DOI.

Beeson JG & Duffy PE. (2005). The immunology and pathogenesis of malaria during pregnancy. Curr. Top. Microbiol. Immunol. , 297, 187-227. PMID: 16265906


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  • CDC Division of Parasitic Diseases and Malaria Malaria
  • Toronto General Hospital/Research Institute Kevin Kain

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Cite this page: Hill, M.A. (2018, November 16) Embryology Abnormal Development - Malaria. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Malaria

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