Skip to main content
Top
Published in: Malaria Journal 1/2014

Open Access 01-12-2014 | Research

Submicroscopic infection of placenta by Plasmodium produces Th1/Th2 cytokine imbalance, inflammation and hypoxia in women from north-west Colombia

Authors: Olga M Agudelo, Beatriz H Aristizabal, Stephanie K Yanow, Eliana Arango, Jaime Carmona-Fonseca, Amanda Maestre

Published in: Malaria Journal | Issue 1/2014

Login to get access

Abstract

Background

A large-scale study was set up in order to study the epidemiology, clinical aspects, and immunopathology of gestational and placental malaria in north-west Colombia. In this region, recent reports using a qPCR technique, confirmed frequencies of infection, by Plasmodium falciparum or Plasmodium vivax, up to 45%. Given the high rates of infection observed both in mother and placenta, a first exploratory study was proposed in order to characterize the effect on the inflammation status, tissue damage and hypoxia in Plasmodium spp. infected placentas.

Methods

A descriptive, prospective, cross-sectional design was applied to pregnant women with (PM+) and without (PM-) placental malaria. Messenger RNA expression of Fas, FasL; COX-1, COX-2, HIF, VEGF, and the cytokines IL-2, IL-4, IL-10, IFN-γ and TNF, were measured in peripheral and placental blood using a quantitative PCR. The percentage of apoptotic cells was determined with a TUNEL assay.

Results

In total 50 placentas were studied: 25 were positive for submicroscopic infection and 25 were negative for Plasmodium infection. Expression of IL-4 and IL-10 was observed high in placental tissue of PM+, while IL-2 was high in peripheral blood of the same group. Expression of TNF and IFNγ in peripheral blood of the PM + group was high. Similarly, the apoptotic index and Fas expression were significantly high in PM+. However, FasL expression was observed low in PM + compared to PM-. Inflammation markers (HIF, VEGF) and hypoxia markers (COX-1, COX-2) were high in the PM + group.

Conclusion

During placental malaria expression of some pro-inflammatory cytokines is up-regulated and markers of hypoxia and tissue damage are increased in cases of submicroscopic infection.
Appendix
Available only for authorised users
Literature
1.
go back to reference Dellicour S, Tatem AJ, Guerra CA, Snow RW, ter Kuile FO: Quantifying the number of pregnancies at risk of malaria in 2007: a demographic study. PLoS Med. 2010, 7: e1000221-10.1371/journal.pmed.1000221.PubMedCentralCrossRefPubMed Dellicour S, Tatem AJ, Guerra CA, Snow RW, ter Kuile FO: Quantifying the number of pregnancies at risk of malaria in 2007: a demographic study. PLoS Med. 2010, 7: e1000221-10.1371/journal.pmed.1000221.PubMedCentralCrossRefPubMed
2.
go back to reference Desai M, ter Kuile FO, Nosten F: Epidemiology and burden of malaria in pregnancy. Lancet Infect Dis. 2007, 7: 93-104. 10.1016/S1473-3099(07)70021-X.CrossRefPubMed Desai M, ter Kuile FO, Nosten F: Epidemiology and burden of malaria in pregnancy. Lancet Infect Dis. 2007, 7: 93-104. 10.1016/S1473-3099(07)70021-X.CrossRefPubMed
3.
go back to reference Rogerson SJ, Hviid L, Duffy PE, Leke RF, Taylor DW: Malaria in pregnancy: pathogenesis and immunity. Lancet Infect Dis. 2007, 7: 105-117. 10.1016/S1473-3099(07)70022-1.CrossRefPubMed Rogerson SJ, Hviid L, Duffy PE, Leke RF, Taylor DW: Malaria in pregnancy: pathogenesis and immunity. Lancet Infect Dis. 2007, 7: 105-117. 10.1016/S1473-3099(07)70022-1.CrossRefPubMed
4.
go back to reference Fried M, Duffy PE: Adherence of Plasmodium falciparum to chondroitin sulfate A in the human placenta. Science. 1996, 272: 1502-1504. 10.1126/science.272.5267.1502.CrossRefPubMed Fried M, Duffy PE: Adherence of Plasmodium falciparum to chondroitin sulfate A in the human placenta. Science. 1996, 272: 1502-1504. 10.1126/science.272.5267.1502.CrossRefPubMed
5.
go back to reference Umbers AJ, Boeuf P, Clapham C, Stanisic DI, Baiwog F, Mueller I, Siba P, King CL, Beeson JG, Glazier J, Rogerson SJ: Placental malaria-associated inflammation disturbs the insulin-like growth factor axis of fetal growth regulation. J Infect Dis. 2011, 203: 561-569. 10.1093/infdis/jiq080.PubMedCentralCrossRefPubMed Umbers AJ, Boeuf P, Clapham C, Stanisic DI, Baiwog F, Mueller I, Siba P, King CL, Beeson JG, Glazier J, Rogerson SJ: Placental malaria-associated inflammation disturbs the insulin-like growth factor axis of fetal growth regulation. J Infect Dis. 2011, 203: 561-569. 10.1093/infdis/jiq080.PubMedCentralCrossRefPubMed
6.
go back to reference Muehlenbachs A, Fried M, McGready R: A novel histological grading scheme for placental malaria applied in areas of high and low malaria transmission. J Infect Dis. 2010, 202: 1608-1616. 10.1086/656723.PubMedCentralCrossRefPubMed Muehlenbachs A, Fried M, McGready R: A novel histological grading scheme for placental malaria applied in areas of high and low malaria transmission. J Infect Dis. 2010, 202: 1608-1616. 10.1086/656723.PubMedCentralCrossRefPubMed
7.
go back to reference Nosten F, Rogerson SJ, Beeson JG, McGready R, Mutabingwa TK, Brabin B: Malaria in pregnancy and the endemicity spectrum: what can we learn?. Trends Parasitol. 2004, 20: 425-432. 10.1016/j.pt.2004.06.007.CrossRefPubMed Nosten F, Rogerson SJ, Beeson JG, McGready R, Mutabingwa TK, Brabin B: Malaria in pregnancy and the endemicity spectrum: what can we learn?. Trends Parasitol. 2004, 20: 425-432. 10.1016/j.pt.2004.06.007.CrossRefPubMed
8.
go back to reference Uneke CJ: Diagnosis of Plasmodium falciparum malaria in pregnancy in sub-Saharan Africa: the challenges and public health implications. Parasitol Res. 2008, 102: 333-342. 10.1007/s00436-007-0782-6.CrossRefPubMed Uneke CJ: Diagnosis of Plasmodium falciparum malaria in pregnancy in sub-Saharan Africa: the challenges and public health implications. Parasitol Res. 2008, 102: 333-342. 10.1007/s00436-007-0782-6.CrossRefPubMed
9.
go back to reference Uckan D, Steele A, Cherry , Wang BY, Chamizo W, Koutsonikolis A, Gilbert-Barness E, Good RA: Trophoblasts express Fas ligand: a proposed mechanism for immune privilege in placenta and maternal invasion. Mol Hum Reprod. 1997, 3: 655-662. 10.1093/molehr/3.8.655.CrossRefPubMed Uckan D, Steele A, Cherry , Wang BY, Chamizo W, Koutsonikolis A, Gilbert-Barness E, Good RA: Trophoblasts express Fas ligand: a proposed mechanism for immune privilege in placenta and maternal invasion. Mol Hum Reprod. 1997, 3: 655-662. 10.1093/molehr/3.8.655.CrossRefPubMed
10.
go back to reference 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: e4953-10.1371/journal.pone.0004953.PubMedCentralCrossRefPubMed 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: e4953-10.1371/journal.pone.0004953.PubMedCentralCrossRefPubMed
11.
go back to reference Lucchi NW, Peterson DS, Moore JM: Immunologic activation of human syncytiotrophoblast by Plasmodium falciparum. Malar J. 2008, 7: 42-10.1186/1475-2875-7-42.PubMedCentralCrossRefPubMed Lucchi NW, Peterson DS, Moore JM: Immunologic activation of human syncytiotrophoblast by Plasmodium falciparum. Malar J. 2008, 7: 42-10.1186/1475-2875-7-42.PubMedCentralCrossRefPubMed
12.
go back to reference Boeuf P, Tan A, Romagosa C, Radford J, Mwapasa V, Molyneux ME, Meshnick SR, Hunt NH, Rogerson SJ: Placental hypoxia during placental malaria. J Infect Dis. 2008, 197: 757-765. 10.1086/526521.PubMedCentralCrossRefPubMed Boeuf P, Tan A, Romagosa C, Radford J, Mwapasa V, Molyneux ME, Meshnick SR, Hunt NH, Rogerson SJ: Placental hypoxia during placental malaria. J Infect Dis. 2008, 197: 757-765. 10.1086/526521.PubMedCentralCrossRefPubMed
13.
go back to reference Sarr D, Aldebert D, Marrama L, Frealle E, Gaye A, Brahim HO, Niang M, Dangou JM, Mercereau-Puijalon O, Lehesran J, Jambou R: Chronic infection during placental malaria is associated with up-regulation of cycloxygenase-2. Malar J. 2010, 9: 45-10.1186/1475-2875-9-45.PubMedCentralCrossRefPubMed Sarr D, Aldebert D, Marrama L, Frealle E, Gaye A, Brahim HO, Niang M, Dangou JM, Mercereau-Puijalon O, Lehesran J, Jambou R: Chronic infection during placental malaria is associated with up-regulation of cycloxygenase-2. Malar J. 2010, 9: 45-10.1186/1475-2875-9-45.PubMedCentralCrossRefPubMed
14.
go back to reference Gamain B, Smith JD, Viebig NK, Gysin J, Scherf A: Pregnancy-associated malaria: parasite binding, natural immunity and vaccine development. Int J Parasitol. 2007, 37: 273-283. 10.1016/j.ijpara.2006.11.011.CrossRefPubMed Gamain B, Smith JD, Viebig NK, Gysin J, Scherf A: Pregnancy-associated malaria: parasite binding, natural immunity and vaccine development. Int J Parasitol. 2007, 37: 273-283. 10.1016/j.ijpara.2006.11.011.CrossRefPubMed
15.
go back to reference Campos IM, Uribe ML, Cuesta C, Franco-Gallego A, Carmona-Fonseca J, Maestre A: Diagnosis of gestational, congenital, and placental malaria in Colombia: comparison of the efficacy of microscopy, nested polymerase chain reaction, and histopathology. Am J Trop Med Hyg. 2011, 84: 929-935. 10.4269/ajtmh.2011.10-0507.PubMedCentralCrossRefPubMed Campos IM, Uribe ML, Cuesta C, Franco-Gallego A, Carmona-Fonseca J, Maestre A: Diagnosis of gestational, congenital, and placental malaria in Colombia: comparison of the efficacy of microscopy, nested polymerase chain reaction, and histopathology. Am J Trop Med Hyg. 2011, 84: 929-935. 10.4269/ajtmh.2011.10-0507.PubMedCentralCrossRefPubMed
16.
go back to reference Arango EM, Samuel R, Agudelo OM, Carmona-Fonseca J, Maestre A, Yanow SK: Molecular detection of malaria at delivery reveals a high frequency of submicroscopic infections and associated placental damage in pregnant women from Northwest Colombia. Am J Trop Med Hyg. 2013, 89: 178-183. 10.4269/ajtmh.12-0669.PubMedCentralCrossRefPubMed Arango EM, Samuel R, Agudelo OM, Carmona-Fonseca J, Maestre A, Yanow SK: Molecular detection of malaria at delivery reveals a high frequency of submicroscopic infections and associated placental damage in pregnant women from Northwest Colombia. Am J Trop Med Hyg. 2013, 89: 178-183. 10.4269/ajtmh.12-0669.PubMedCentralCrossRefPubMed
17.
go back to reference McGready R, Tan SO, Ashley EA, Pimanpanarak M, Viladpai-Nguen J, Phaiphun L, Wüstefeld K, Barends M, Laochan N, Keereecharoen L, Lindegardh N, Singhasivanon P, White NJ, Nosten F: A randomised controlled trial of artemether-lumefantrine versus artesunate for uncomplicated Plasmodium falciparum treatment in pregnancy. PLoS Med. 2008, 5: e263-CrossRef McGready R, Tan SO, Ashley EA, Pimanpanarak M, Viladpai-Nguen J, Phaiphun L, Wüstefeld K, Barends M, Laochan N, Keereecharoen L, Lindegardh N, Singhasivanon P, White NJ, Nosten F: A randomised controlled trial of artemether-lumefantrine versus artesunate for uncomplicated Plasmodium falciparum treatment in pregnancy. PLoS Med. 2008, 5: e263-CrossRef
18.
19.
go back to reference Arango E, Maestre A, Carmona J: Efecto de la infección submicroscópica o policlonal de Plasmodium falciparum sobre la madre y el producto de la gestación Revisión sistemática. Rev Bras Epidemiol. 2010, 13: 373-386. 10.1590/S1415-790X2010000300002.CrossRefPubMed Arango E, Maestre A, Carmona J: Efecto de la infección submicroscópica o policlonal de Plasmodium falciparum sobre la madre y el producto de la gestación Revisión sistemática. Rev Bras Epidemiol. 2010, 13: 373-386. 10.1590/S1415-790X2010000300002.CrossRefPubMed
20.
go back to reference Rantala AM, Taylor SM, Trottman PA, Luntamo M, Mbewe B, Maleta K, Kulmala T, Ashorn P, Meshnick SR: Comparison of real-time PCR and microscopy for malaria parasite detection in Malawian pregnant women. Malar J. 2010, 9: 269-10.1186/1475-2875-9-269.PubMedCentralCrossRefPubMed Rantala AM, Taylor SM, Trottman PA, Luntamo M, Mbewe B, Maleta K, Kulmala T, Ashorn P, Meshnick SR: Comparison of real-time PCR and microscopy for malaria parasite detection in Malawian pregnant women. Malar J. 2010, 9: 269-10.1186/1475-2875-9-269.PubMedCentralCrossRefPubMed
21.
go back to reference Carmona-Fonseca J, Maestre A: Incidencia de la malaria gestacional, congénita y placentaria en Urabá (Antioquia, Colombia), 2005–2007. Rev Colomb Obstet Ginecol. 2009, 60: 15- Carmona-Fonseca J, Maestre A: Incidencia de la malaria gestacional, congénita y placentaria en Urabá (Antioquia, Colombia), 2005–2007. Rev Colomb Obstet Ginecol. 2009, 60: 15-
22.
go back to reference Carmona-Fonseca J, Arango E, Maestre A: Placental malaria in Colombia: histopathologic findings in Plasmodium vivax and P. falciparum infections. Am J Trop Med Hyg. 2013, 88: 1093-1101. 10.4269/ajtmh.12-0363.PubMedCentralCrossRefPubMed Carmona-Fonseca J, Arango E, Maestre A: Placental malaria in Colombia: histopathologic findings in Plasmodium vivax and P. falciparum infections. Am J Trop Med Hyg. 2013, 88: 1093-1101. 10.4269/ajtmh.12-0363.PubMedCentralCrossRefPubMed
23.
go back to reference Padilla JC, Uribe G, Araújo RM, Narváez PC, Valencia SH: Epidemiology and control of malaria in Colombia. Mem Inst Oswaldo Cruz. 2011, 106: 114-122.CrossRef Padilla JC, Uribe G, Araújo RM, Narváez PC, Valencia SH: Epidemiology and control of malaria in Colombia. Mem Inst Oswaldo Cruz. 2011, 106: 114-122.CrossRef
24.
go back to reference Agudelo OM, Arango EM, Maestre A, Carmona-Fonseca J: Prevalence of gestational, placental and congenital malaria in north-west Colombia. Malar J. 2013, 12: 341-10.1186/1475-2875-12-341.PubMedCentralCrossRefPubMed Agudelo OM, Arango EM, Maestre A, Carmona-Fonseca J: Prevalence of gestational, placental and congenital malaria in north-west Colombia. Malar J. 2013, 12: 341-10.1186/1475-2875-12-341.PubMedCentralCrossRefPubMed
25.
go back to reference Plowe CV, Djimde A, Bouare M, Doumbo O, Wellems TE: Pyrimethamine and proguanil resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase: polymerase chain reaction methods for surveillance in Africa. Am J Trop Med Hyg. 1995, 52: 565-568.PubMed Plowe CV, Djimde A, Bouare M, Doumbo O, Wellems TE: Pyrimethamine and proguanil resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase: polymerase chain reaction methods for surveillance in Africa. Am J Trop Med Hyg. 1995, 52: 565-568.PubMed
26.
go back to reference Shokoples SE, Ndao M, Kowalewska-Grochowska K, Yanow SK: Multiplexed real-time PCR assay for discrimination of Plasmodium species with improved sensitivity for mixed infections. J Clin Microbiol. 2009, 47: 975-980. 10.1128/JCM.01858-08.PubMedCentralCrossRefPubMed Shokoples SE, Ndao M, Kowalewska-Grochowska K, Yanow SK: Multiplexed real-time PCR assay for discrimination of Plasmodium species with improved sensitivity for mixed infections. J Clin Microbiol. 2009, 47: 975-980. 10.1128/JCM.01858-08.PubMedCentralCrossRefPubMed
27.
28.
go back to reference Gavrieli Y, Sherman Y, Ben-Sasson SA: Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol. 1992, 119: 493-501. 10.1083/jcb.119.3.493.CrossRefPubMed Gavrieli Y, Sherman Y, Ben-Sasson SA: Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol. 1992, 119: 493-501. 10.1083/jcb.119.3.493.CrossRefPubMed
29.
go back to reference Guller S, Ma YY, Fu HH, Krikun G, Abrahams VM, Mor G: The placental syncytium and the pathophysiology of preeclampsia and intrauterine growth restriction: a novel assay to assess syncytial protein expression. Ann N Y Acad Sci. 2008, 1127: 129-133. 10.1196/annals.1434.015.PubMedCentralCrossRefPubMed Guller S, Ma YY, Fu HH, Krikun G, Abrahams VM, Mor G: The placental syncytium and the pathophysiology of preeclampsia and intrauterine growth restriction: a novel assay to assess syncytial protein expression. Ann N Y Acad Sci. 2008, 1127: 129-133. 10.1196/annals.1434.015.PubMedCentralCrossRefPubMed
30.
go back to reference Crocker IP, Tanner OM, Myers JE, Bulmer JN, Walraven G, Baker PN: Syncytiotrophoblast degradation and the pathophysiology of the malaria-infected placenta. Placenta. 2004, 25: 273-282. 10.1016/j.placenta.2003.09.010.CrossRefPubMed Crocker IP, Tanner OM, Myers JE, Bulmer JN, Walraven G, Baker PN: Syncytiotrophoblast degradation and the pathophysiology of the malaria-infected placenta. Placenta. 2004, 25: 273-282. 10.1016/j.placenta.2003.09.010.CrossRefPubMed
31.
go back to reference Aschkenazi S, Straszewski S, Verwer KM, Foellmer H, Rutherford T, Mor G: Differential regulation and function of the Fas/Fas ligand system in human trophoblast cells. Biol Reprod. 2002, 66: 1853-1861. 10.1095/biolreprod66.6.1853.CrossRefPubMed Aschkenazi S, Straszewski S, Verwer KM, Foellmer H, Rutherford T, Mor G: Differential regulation and function of the Fas/Fas ligand system in human trophoblast cells. Biol Reprod. 2002, 66: 1853-1861. 10.1095/biolreprod66.6.1853.CrossRefPubMed
32.
go back to reference Tkachuk AN, Moormann AM, Poore JA, Rochford RA, Chensue SW, Mwapasa V, Meshnick SR: Malaria enhances expression of CC chemokine receptor 5 on placental macrophages. J Infect Dis. 2001, 183: 967-972. 10.1086/319248.CrossRefPubMed Tkachuk AN, Moormann AM, Poore JA, Rochford RA, Chensue SW, Mwapasa V, Meshnick SR: Malaria enhances expression of CC chemokine receptor 5 on placental macrophages. J Infect Dis. 2001, 183: 967-972. 10.1086/319248.CrossRefPubMed
33.
go back to reference Kossodo S, Monso C, Juillard P, Velu T, Goldman M, Grau GE: Interleukin-10 modulates susceptibility in experimental cerebral malaria. Immunology. 1997, 91: 536-540. 10.1046/j.1365-2567.1997.00290.x.PubMedCentralCrossRefPubMed Kossodo S, Monso C, Juillard P, Velu T, Goldman M, Grau GE: Interleukin-10 modulates susceptibility in experimental cerebral malaria. Immunology. 1997, 91: 536-540. 10.1046/j.1365-2567.1997.00290.x.PubMedCentralCrossRefPubMed
34.
go back to reference Kabyemela ER, Muehlenbachs A, Fried M, Kurtis JD, Mutabingwa TK, Duffy PE: Maternal peripheral blood level of IL-10 as a marker for inflammatory placental malaria. Malar J. 2008, 7: 26-10.1186/1475-2875-7-26.PubMedCentralCrossRefPubMed Kabyemela ER, Muehlenbachs A, Fried M, Kurtis JD, Mutabingwa TK, Duffy PE: Maternal peripheral blood level of IL-10 as a marker for inflammatory placental malaria. Malar J. 2008, 7: 26-10.1186/1475-2875-7-26.PubMedCentralCrossRefPubMed
35.
go back to reference Cooke BM, Mohandas N, Cowman AF, Coppel RL: Cellular adhesive phenomena in apicomplexan parasites of red blood cells. Vet Parasitol. 2005, 132: 273-295. 10.1016/j.vetpar.2005.07.002.CrossRefPubMed Cooke BM, Mohandas N, Cowman AF, Coppel RL: Cellular adhesive phenomena in apicomplexan parasites of red blood cells. Vet Parasitol. 2005, 132: 273-295. 10.1016/j.vetpar.2005.07.002.CrossRefPubMed
37.
go back to reference Koga K, Aldo PB, Mor G: Toll-like receptors and pregnancy: trophoblast as modulators of the immune response. J Obstet Gynaecol Res. 2009, 35: 191-202. 10.1111/j.1447-0756.2008.00963.x.CrossRefPubMed Koga K, Aldo PB, Mor G: Toll-like receptors and pregnancy: trophoblast as modulators of the immune response. J Obstet Gynaecol Res. 2009, 35: 191-202. 10.1111/j.1447-0756.2008.00963.x.CrossRefPubMed
Metadata
Title
Submicroscopic infection of placenta by Plasmodium produces Th1/Th2 cytokine imbalance, inflammation and hypoxia in women from north-west Colombia
Authors
Olga M Agudelo
Beatriz H Aristizabal
Stephanie K Yanow
Eliana Arango
Jaime Carmona-Fonseca
Amanda Maestre
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2014
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-13-122

Other articles of this Issue 1/2014

Malaria Journal 1/2014 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.