UNSW Embryology

Abnormal Development - Malaria

© Dr Mark Hill (2009)

Acknowledgements

Introduction

Malaria, described as a disease of poverty and underdevelopment, is caused by a protozoan parasite infecting mainly red blood cells (erythrocytes). Pregnant women have an increased susceptibility to malaria infection and this can lead to an infection of the placenta by sequestration of the infected red blood cells leading to low birth weight and other fetal developmental effects. There are four types of malaria caused by the protozoan parasite Plasmodium falciparum (main), Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae. World Malaria day - A Day to Act

Plasmodium falciparum

Page Links: Introduction | Some Recent Findings | Malaria Statistics | Placental Malaria | References | WWW Links | Glossary

Some Recent Findings

WHO World Malaria day - A Day to Act 25 April is a day of unified commemoration of the global effort to provide effective control of malaria around the world. This year's World Malaria Day marks a critical moment in time. The international malaria community has merely two years to meet the 2010 targets of delivering effective and affordable protection and treatment to all people at risk of malaria, as called for by the UN Secretary-General, Ban Ki-Moon. (WHO World Malaria day - A Day to Act)

Malaria Statistics

• 300 to 500 million cases
• 2 to 3 million deaths per year
• About 90 percent of all deaths occur in sub-Saharan Africa

(Data from: WHO Malaria)

Placental Malaria

Pregnant women have an increased susceptibility to malaria infection. This condition is common in regions where malaria is endemic with women carrying their first pregnancy (primigravida). Malarial infection of the placenta occurs by binding (sequestration) of infected erythrocytes in the venules of the placenta, this olso occurs in other maternal organs.

The mechanism of binding appears to be through infected erythrocytes expressing P. falciparum erythrocyte membrane protein-1 (PfEMP1) family of proteins. The family member VAR2CSA protein has been shown to bind placental chondroitin sulfate proteoglycan.

have been shown to bind to chondroitin sulfate A (CSA) in the placenta through the VAR2CSA protein.

(More? Placental Abnormalities)

Stages of Plasmodium falciparum

Plasmodium falciparum

Stages of Plasmodium falciparum as drawn from microscopic observation of thin blood smears (1971).

• Fig. 1: Normal red cell
• Figs. 2-18: Trophozoites (among these, Figs. 2-10 correspond to ring-stag trophozoites)
• Figs. 19-26: Schizonts (Fig. 26 is a ruptured schizont)
• Figs.27, 28: Mature macrogametocytes (female)
• Figs. 29, 30: Mature microgametocytes (male)

Illustrations from: Coatney GR, Collins WE, Warren M, Contacos PG. The Primate Malarias. Bethesda: U.S. Department of Health, Education and Welfare; 1971.

(From CDC: Diagnostic findings - Historic Images)

Plasmodium falciparum Infection

A transmission electron micrograph of a Plasmodium falciparum merozoite into an uninfected erythrocyte (original source unknown)

(Image Source: National Institute of Allergy and Infectious Diseases (NIAID)

References

Reviews | Articles | Search NCBI Bookshelf | Search PubMed

Reviews

• Tuikue Ndam N, Deloron P. Towards a vaccine against pregnancy-associated malaria. Parasite. 2008 Sep;15(3):515-21. Review. PMID: 18814733
• Beeson JG, Duffy PE.    [See Related Articles] The immunology and pathogenesis of malaria during pregnancy. Curr Top Microbiol Immunol. 2005;297:187-227.
• Uneke CJ. Impact of placental Plasmodium falciparum malaria on pregnancy and perinatal outcome in sub-Saharan Africa: I: introduction to placental malaria. Yale J Biol Med. 2007 Jun;80(2):39-50. Review.
  PMID: 18160989
• Brabin BJ, Romagosa C, Abdelgalil S, Menendez C, Verhoeff FH, McGready R, Fletcher KA, Owens S, D'Alessandro U, Nosten F, Fischer PR, Ordi J.    [See Related Articles] The sick placenta-the role of malaria. Placenta. 2004 May;25(5):359-78.
• Matteelli A, Caligaris S, Castelli F, Carosi G.    [See Related Articles] The placenta and malaria. Ann Trop Med Parasitol. 1997 Oct;91(7):803-10

Articles

• Conroy A, Serghides L, Finney C, Owino SO, Kumar S, Gowda DC, Liles WC, Moore JM, Kain KC. C5a enhances dysregulated inflammatory and angiogenic responses to malaria in vitro: potential implications for placental malaria. PLoS ONE. 2009;4(3):e4953. Epub 2009 Mar 24. PMID: 19308263
• Singh K, Gittis AG, Nguyen P, Gowda DC, Miller LH, Garboczi DN. Structure of the DBL3x domain of pregnancy-associated malaria protein VAR2CSA complexed with chondroitin sulfate A. Nat Struct Mol Biol. 2008 Sep;15(9):932-8.
  PMID: 19172746 PMC: 19172746

Search NCBI Bookshelf: Bookshelf - Malaria | Medical Microbiology - Malaria

Medical Microbiology Malaria

Search PubMed: Search March 2009 "placental malaria" 654 reference articles of which 85 were reviews.

Search term = placental malaria | maternal malaria | malaria

WWW Links

WHO - WHO Malaria | Malaria Factsheet

CDC Publications (USA) CDC - Malaria

Brown University - Maternal Malaria

NSW Public Health Bulletin (Australia)

Glossary of Terms

A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z

Other Infections

Below is a list of some known maternal (then fetal) infections that impact upon neurological development.

Only a very brief overview is given, for more details see see Abnormal Development Notes or Bacterial Infection and the listed internal and external links.

Cytomegalovirus

Viral infection causes systemic infection and extensive brain damage and cell death by necrosis.

NCBI Bookshelf (external link) Medical Microbiology: Cytomegalovirus | Search Medical Microbiology "Cytomegalovirus"

Herpes Simplex Virus

Viral infection causes systemic infection and extensive brain damage and cell death by necrosis.

NCBI Bookshelf (external link) Search Medical Microbiology "Herpes Simplex Virus"

Purulent Meningitus

Bacterial infection by E. coli or streptocci B. can cause vascular thrombosis involving choroid plexus which can effect CSF flow, and can cause hydrocephalus.

NCBI Bookshelf (external link) Search Medical Microbiology "Purulent Meningitus"

Toxoplasmosis

Toxoplasma infection causes random necrosis throughout the brain and can cause hydrocephalus.

NCBI Bookshelf (external link) Medical Microbiology: 84. Toxoplasma Gondii | Figure 84-1. Girl with hydrocephalus due to congenital toxoplasmosis. | Search Medical Microbiology "Toxoplasmosis"

Australian NHMRC Recommendations

The Australian NHMRC (1988) recommends neonates be assessed for follow-up care under the following conditions.

(see the NHMRC WWW Page)

• Birthweight less than 1500g or gestational age less than 32 weeks
• Small-for-gestational-age neonates
• Perinatal asphyxia
• Apgar score less than 3 at 5 minutes
• clinical evidence of neurological dysfunction
• delay in onset of spontaneous respiration for more than 5 minutes and requiring mechanical ventilation
• Clinical evidence of central nervous system abnormalities ie., seizures, hypotonia
• Hyperbilirubinaemia of greater than 350umol/l in full term neonates
• Genetic, dysmorphic or metabolic disorders or a family history of serious genetic disorder
• Perinatal or serious neonatal infection including children of mothers who are HIV positive
• Psychosocial problems eg., infants of drug-addicted or alcoholic mothers.

Finally

Each section of the notes covering early development and specific systems contain references to specific abnormalities (on Page 2 of each notes section). The best source for Australian statistical data is the Australian Institute of Health and Welfare National Perinatal Statistics Unit, UNSW which publishes "Congenital Malformations Australia" every 2 years. Be aware that some congenital abnormalities, by their nature, affect multiple systems. In the USA, the Center for Disease Control (CDC) keeps and publishes relevant statistical information. A very difficult issue in abnormal development are the many different Ethical implications.

This current page is a link to Normal and Abnormal Development and Population Data.

Where to Next?

You should look at normal development. Development Notes

Alternatively, go on to look at Systematic Development of organs and tissues.

Quick Links

Development Notes ----------------- Menstrual Cycle Week 1 Week 2 Week 3 Week 4 Placenta Serial Images Genes/DNA Molecular Dev Abnormal Dev Postnatal Dev Notes Index

System Notes ----------------- Heart/Cardiovascular Respiratory Coelomic cavity Gastrointestinal Tract Head and Neck Neural Neural Crest Eye Ear Nose Endocrine Urogenital Musculoskeletal Integumentary

Finally

For those wanting to see dynamic processes of development (and have a reasonably quick connection) then the Movies pages are good for watching changes occur.

Movies ----------------- Embryo Growth Carnegie Stages Ultrasound Images Stage 13/14 Embryo Stage 22 Embryo Heart Septation Neural Neural Crest Other Embryos Larsen Movies

Other Embryos

The study of human development has relied extensively on studying the process in other model animals. For those wanting to see the process of development in other species then the other embryos pages are a good start.

Other Embryos ----------------- Chicken Fly Frog Mouse Rabbit Rat Worm Zebrafish Guinea Pig

UNSW Embryology ISBN: 978 0 7334 2609 4

UNSW CRICOS Provider Code No. 00098G