Abnormal Development - Malaria

Embryology - 2 Dec 2023 Expand to Translate
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Introduction

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)

Global limits and endemicity of P. falciparum in 2007

Mouse model malaria in pregnancy^[2]

Some Recent Findings

Malaria in Pregnancy and Adverse Birth Outcomes: New Mechanisms and Therapeutic Opportunities^[3] "malaria infection during pregnancy is associated with adverse birth outcomes but underlying mechanisms are poorly understood. Here, we discuss the impact of malaria in pregnancy on three pathways that are important regulators of healthy pregnancy outcomes: L-arginine-nitric oxide biogenesis, complement activation, and the heme axis. These pathways are not mutually exclusive, and they collectively create a proinflammatory, antiangiogenic milieu at the maternal-fetal interface that interferes with placental function and development. We hypothesize that targeting these host-response pathways would mitigate the burden of adverse birth outcomes attributable to malaria in pregnancy."

Association of Malaria Infection During Pregnancy With Head Circumference of Newborns in the Brazilian Amazon^[4] "IMPORTANCE: Malaria during pregnancy is associated with adverse events for the fetus and newborn, but the association of malaria during pregnancy with the head circumference of the newborn is unclear. MAIN OUTCOMES AND MEASURES: The primary end point was the incidence of altered head circumference in newborns delivered from malaria-infected mothers compared with that from noninfected mothers. Secondary end points included measures of placental pathology relative to newborn head circumference. CONCLUSIONS AND RELEVANCE: This study indicates that falciparum malaria during pregnancy is associated with decreased head circumference in newborns, which is in turn associated with evidence of placental malaria."

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."

More recent papers
This table allows an automated computer search of the external PubMed database using the listed "Search term" text link. This search now requires a manual link as the original PubMed extension has been disabled. The displayed list of references do not reflect any editorial selection of material based on content or relevance. References also appear on 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. More? References \| Discussion Page \| Journal Searches \| 2019 References \| 2020 References Search term: Maternal Malaria \| Placental Malaria \| Fetal Malaria

Older papers
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table. See also the Discussion Page for other references listed by year and References on this current page. Does malaria affect placental development? Evidence from in vitro models^[5] "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^[6] "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^[7] "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."

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.

Larvae hatch when water inundates the eggs as a result of rains or the addition of water by people.
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.
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.
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.

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^[8]

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^[2]

References

↑ 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.
↑ ^2.0 ^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.
↑ Ngai M, Weckman AM, Erice C, McDonald CR, Cahill LS, Sled JG & Kain KC. (2020). Malaria in Pregnancy and Adverse Birth Outcomes: New Mechanisms and Therapeutic Opportunities. Trends Parasitol. , 36, 127-137. PMID: 31864896 DOI.
↑ Dombrowski JG, Souza RM, Lima FA, Bandeira CL, Murillo O, Costa DS, Peixoto EPM, Cunha MDP, Zanotto PMA, Bevilacqua E, Grisotto MAG, Pedroso de Lima AC, Singer JDM, Campino S, Clark TG, Epiphanio S, Gonçalves LA & Marinho CRF. (2019). Association of Malaria Infection During Pregnancy With Head Circumference of Newborns in the Brazilian Amazon. JAMA Netw Open , 2, e193300. PMID: 31050780 DOI.
↑ 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.
↑ 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.
↑ 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.
↑ 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.

Books

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

Reviews

Cutts JC, Agius PA, Zaw Lin R, Powell K, Moore B, Draper JA, Simpson FJI & Fowkes. (2020). Pregnancy-specific malarial immunity and risk of malaria in pregnancy and adverse birth outcomes: a systematic review. BMC Med , 18, 14. PMID: 31941488 DOI.

Bauserman M, Conroy AL, North K, Patterson J, Bose C & Meshnick S. (2019). An overview of malaria in pregnancy. Semin. Perinatol. , , . PMID: 30979598 DOI.

Clark RL. (2019). Genesis of placental sequestration in malaria and possible targets for drugs for placental malaria. Birth Defects Res , , . PMID: 30919596 DOI.

Milner DA. (2018). Malaria Pathogenesis. Cold Spring Harb Perspect Med , 8, . PMID: 28533315 DOI.

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

Articles

Oktavianthi S, Fauzi M, Trianty L, Trimarsanto H, Bowolaksono A, Noviyanti R & Malik SG. (2019). Placental mitochondrial DNA copy number is associated with reduced birth weight in women with placental malaria. Placenta , 80, 1-3. PMID: 31103060 DOI.

Olaleye A, Okusanya BO, Oduwole O, Esu E & Meremikwu M. (2019). A systematic review and meta-analysis of dihydroartemisinin-piperaquine versus sulphadoxine-pyrimethamine for malaria prevention in pregnancy. Int J Gynaecol Obstet , , . PMID: 31050803 DOI.

Lawford HLS, Lee AC, Kumar S, Liley HG & Bora S. (2019). Establishing a conceptual framework of the impact of placental malaria on infant neurodevelopment. Int. J. Infect. Dis. , 84, 54-65. PMID: 31028878 DOI.

Hangi M, Achan J, Saruti A, Quinlan J & Idro R. (2019). Congenital Malaria in Newborns Presented at Tororo General Hospital in Uganda: A Cross-Sectional Study. Am. J. Trop. Med. Hyg. , 100, 1158-1163. PMID: 30860019 DOI.

Dimasuay KG, Gong L, Rosario F, McBryde E, Spelman T, Glazier J, Rogerson SJ, Beeson JG, Jansson T, Devenish RJ & Boeuf P. (2017). Impaired placental autophagy in placental malaria. PLoS ONE , 12, e0187291. PMID: 29125872 DOI.

Search PubMed

Search Pubmed: Placental Malaria

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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. (2023, December 2) Embryology Abnormal Development - Malaria. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Malaria

What Links Here?

[PMID20126256-1] 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.

[PMID26402732-2] 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.

[PMID31864896-3] Ngai M, Weckman AM, Erice C, McDonald CR, Cahill LS, Sled JG & Kain KC. (2020). Malaria in Pregnancy and Adverse Birth Outcomes: New Mechanisms and Therapeutic Opportunities. Trends Parasitol. , 36, 127-137. PMID: 31864896 DOI.

[PMID31050780-4] Dombrowski JG, Souza RM, Lima FA, Bandeira CL, Murillo O, Costa DS, Peixoto EPM, Cunha MDP, Zanotto PMA, Bevilacqua E, Grisotto MAG, Pedroso de Lima AC, Singer JDM, Campino S, Clark TG, Epiphanio S, Gonçalves LA & Marinho CRF. (2019). Association of Malaria Infection During Pregnancy With Head Circumference of Newborns in the Brazilian Amazon. JAMA Netw Open , 2, e193300. PMID: 31050780 DOI.

[PMID23383132-5] 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.

[PMID22347473-6] 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.

[PMID20386602-7] 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.

[PMID22222152-8] 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.

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