Hostname: page-component-8448b6f56d-42gr6 Total loading time: 0 Render date: 2024-04-18T07:05:58.628Z Has data issue: false hasContentIssue false
  • English
  • Français

Potential cerebral malaria therapy: intramuscular arteether and vitamin D co-administration

Published online by Cambridge University Press:  21 July 2016

HEMLATA DWIVEDI ,
SUNIL KUMAR SINGH ,
BHAVANA SINGH CHAUHAN ,
SARIKA GUNJAN  and
RENU TRIPATHI
HEMLATA DWIVEDI
Affiliation:
Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, India Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, New Delhi, India
SUNIL KUMAR SINGH
Affiliation:
Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, India
BHAVANA SINGH CHAUHAN
Affiliation:
Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, India Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, New Delhi, India
SARIKA GUNJAN
Affiliation:
Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, India Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, New Delhi, India
RENU TRIPATHI*
Affiliation:
Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, India Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, New Delhi, India
*
*Corresponding author. Division of Parasitology, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, Uttar Pradesh, India. E-mail: renu1113@rediffmail.com
Get access Rights & Permissions [Opens in a new window]

Summary

Cerebral malaria (CM) shows lethality rate of 15–25% despite effective antimalarial chemotherapy. The effective adjunct treatment to counteract the CM pathogenesis is urgently required. In murine CM model, most interventions studied till date are administered before the onset of CM symptoms, which belittle its translational value to human. We studied intramuscular arteether–vitamin D (ART–VD) combination treatment for CM outcome improvement after the onset of neurological symptoms. The intramuscular dose of 50 µg kg−1 VD for 3 days combined with a loading dose of 25 mg kg−1α/β arteether followed by 12·5 mg kg−1 dose for two consecutive days led to significant improvement in survival (73% in combination group vs 29 and 0% in arteether and VD monotherapy, respectively) and clinical recovery. The treatment in all the groups partially restored the blood–brain barrier integrity and reduced the level of serum proinflammatory cytokines tumour necrosis factor-α and interferon-γ. The brain transcripts of inflammatory chemokines viz. CXCL10, CXCL9, CCL4 and CCL5 and T cell migration in the brain microvasculature were significantly diminished in all the treatment groups. ART–VD treatment significantly reduced intercellular cell adhesion molecule-1 expression. Taken together, our findings show that coordinated actions of ART–VD improve the outcome of experimental CM.

Keywords

cerebral malariaarteethervitamin Dadjunct therapyPlasmodium berghei ANKA
Type
Research Article
Information
Parasitology , Volume 143 , Issue 12 , October 2016 , pp. 1557 - 1568
Check for updates
Copyright
Copyright © Cambridge University Press 2016 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Armah, H., Dodoo, A. K., Wiredu, E. K., Stiles, J. K., Adjei, A. A., Gyasi, R. K. and Tettey, Y. (2005 a). High-level cerebellar expression of cytokines and adhesion molecules in fatal, paediatric, CM. Annals of Tropical Medicine and Parasitology 99, 629–647.CrossRefGoogle Scholar
Armah, H., Wired, E. K., Dodoo, A. K., Adjei, A. A., Tettey, Y. and Gyasi, R. (2005 b). Cytokines and adhesion molecules expression in the brain in human CM. International Journal of Environmental Research and Public Health 2, 123–131.Google Scholar
Baptista, F. G., Pamplona, A., Pena, A. C., Mota, M. M., Pied, S. and Vigario, A. M. (2010). Accumulation of Plasmodium berghei-infected red blood cells in the brain is crucial for the development of CM in mice. Infection and Immunity 78, 4033–4039.Google Scholar
Berendt, A. R., Tumer, G. D. and Newbold, C. I. (1994). CM: the sequestration hypothesis. Parasitology Today 10, 412–414.Google Scholar
Berer, A., Stockl, J., Majdic, O., Wagner, T., Kollars, M., Lechner, K., Geissler, K. and Oehler, L. (2000). 1,25-Dihydroxyvitamin D(3) inhibits dendritic cell differentiation and maturation in vitro . Experimental Hematology 28, 575–583.CrossRefGoogle Scholar
Campanella, G. S., Tager, A. M., El Khoury, J. K., Thomas, S. Y., Abrazinski, T. A., Manice, L. A., Colvin, R. A. and Luster, A. D. (2008). Chemokine receptor CXCR3 and its ligands CXCL9 and CXCL10 are required for the development of murine cerebral malaria. Proceedings of the National Academy of Sciences of the United States of America 105, 4814–4819.Google Scholar
Chakravorty, S. J. and Craig, A. (2005). The role of ICAM-1 in Plasmodium falciparum cytoadherence. European Journal of Cell Biology 84, 15–27.Google Scholar
Clark, C. J., Mackay, G. M., Smythe, G. A., Bustamante, S., Stone, T. W. and Phillips, R. S. (2005). Prolonged survival of a murine model of CM by kynurenine pathway inhibition. Infection and Immunity 73, 5249–5251.CrossRefGoogle Scholar
Clark, I. A. and Rockett, K. A. (1994). The cytokine theory of human CM. Parasitology Today 10, 410–412.Google Scholar
Craig, A. G., Grau, G. E., Janse, C., Kazura, J. W., Milner, D., Barnwell, J. W., Turner, G. and Langhorne, J. (2012). The role of animal models for research on severe malaria. PLoS Pathogens 8, e1002401.Google Scholar
Dende, C., Meena, J., Nagarajan, P., Panda, A. K., Rangarajan, P. N. and Padmanaban, G. (2015). Simultaneously targeting inflammatory response and parasite sequestration in brain to treat Experimental CM. Science Report 5, 12671.Google Scholar
Dietrich, J. B. (2002). The adhesion molecule ICAM-1 and its regulation in relation with the blood–brain barrier. Journal of Neuroimmunology 128, 58–68.Google Scholar
Dormoi, J., Briolant, S., Pascual, A., Desgrouas, C., Travaille, C. and Pradines, B. (2013). Improvement of the efficacy of dihydroartemisinin with atorvastatin in an experimental CM murine model. Malaria Journal 12, 302.Google Scholar
El-Assaad, F., Combes, V., Grau, G. E. and Jambou, R. (2014). Potential efficacy of citicoline as adjunct therapy in treatment of CM. Antimicrobial Agents and Chemotherapy 58, 602–605.CrossRefGoogle Scholar
Engwerda, C., Belnoue, E., Gruner, A. C. and Renia, L. (2005). Experimental models of CM. Current Topics in Microbiology and Immunology 297, 103–143.Google Scholar
Equils, O., Naiki, Y., Shapiro, A. M., Michelsen, K., Lu, D., Adams, J. and Jordan, S. (2006). 1,25-Dihydroxyvitamin D inhibits lipopolysaccharide-induced immune activation in human endothelial cells. Clinical and Experimental Immunology 143, 58–64.CrossRefGoogle ScholarPubMed
Esposito, S. and Lelii, M. (2015). Vitamin D and respiratory tract infections in childhood. BMC Infectious Diseases 15, 487.CrossRefGoogle ScholarPubMed
Eyles, D. W., Burne, T. H. and McGrath, J. J. (2013). Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. Frontiers in Neuroendocrinology 34, 47–64.Google Scholar
Favre, N., Da Laperousaz, C., Ryffel, B., Weiss, N. A., Imhof, B. A., Rudin, W., Lucas, R. and Piguet, P. F. (1999). Role of ICAM-1 (CD54) in the development of murine CM. Microbes and Infection 1, 961–968.Google Scholar
Garcion, E., Wion-Barbot, N., Montero-Menei, C. N., Berger, F. and Wion, D. (2002). New clues about vitamin D functions in the nervous system. Trends in Endocrinology and Metabolism 13, 100–105.CrossRefGoogle ScholarPubMed
Gordon, E. B., Hart, G. T., Tran, T. M., Waisberg, M., Akkaya, M., Skinner, J., Zinocker, S., Pena, M., Yazew, T., Qi, C. F., Miller, L. H. and Pierce, S. K. (2015). Inhibiting the Mammalian target of rapamycin blocks the development of experimental CM. MBio 6, e00725.CrossRefGoogle Scholar
Hayes, C. E., Nashold, F. E., Spach, K. M. and Pedersen, L. B. (2003). The immunological functions of the vitamin D endocrine system. Cellular and Molecular Biology 49, 277–300.Google ScholarPubMed
He, X., Yan, J., Zhu, X., Wang, Q., Pang, W., Qi, Z., Wang, M., Luo, E., Parker, D. M., Cantorna, M. T., Cui, L. and Cao, Y. (2014). Vitamin D inhibits the occurrence of experimental CM in mice by suppressing the host inflammatory response. Journal of Immunology 193, 1314–1323.Google Scholar
Idro, R., Jenkins, N. E. and Newton, C. R. (2005). Pathogenesis, clinical features, and neurological outcome of CM. Lancet Neurology 4, 827–840.CrossRefGoogle Scholar
Idro, R., Marsh, K., John, C. C. and Newton, C. R. (2010). CM: mechanisms of brain injury and strategies for improved neurocognitive outcome. Pediatric Research 68, 267–274.Google Scholar
Ioannidis, L. J., Nie, C. Q. and Hansen, D. S. (2014). The role of chemokines in severe malaria: more than meets the eye. Parasitology 141, 602–613.CrossRefGoogle ScholarPubMed
John, C. C., Kutamba, E., Mugarura, K. and Opoka, R. O. (2010). Adjunctive therapy for CM and other severe forms of Plasmodium falciparum malaria. Expert Review of Anti-Infective Therapy 8, 997–1008.Google Scholar
Kesby, J. P., Eyles, D. W., Burne, T. H. and McGrath, J. J. (2011). The effects of vitamin D on brain development and adult brain function. Molecular and Cellular Endocrinology 347, 121–127.CrossRefGoogle ScholarPubMed
Luong, K. V. and Nguyen, L. T. (2015). The role of vitamin D in malaria. Journal of Infection in Developing Countries 9, 8–19.Google Scholar
Martinesi, M., Bruni, S., Stio, M. and Treves, C. (2006). 1,25-Dihydroxyvitamin D3 inhibits tumor necrosis factor-alpha-induced adhesion molecule expression in endothelial cells. Cell Biology International 30, 365–375.CrossRefGoogle ScholarPubMed
Miller, L. H., Ackerman, H. C., Su, X. Z. and Wellems, T. E. (2013). Malaria biology and disease pathogenesis: insights for new treatments. Nature Medicine 19, 156–167.Google Scholar
Mishra, S. K. and Newton, C. R. (2009). Diagnosis and management of the neurological complications of falciparum malaria. Nature Reviews Neurology 5, 189–198.Google Scholar
Newton, C. R., Taylor, T. E. and Whitten, R. O. (1998). Pathophysiology of fatal falciparum malaria in African children. The American Journal of Tropical Medicine and Hygiene 58, 673–683.CrossRefGoogle ScholarPubMed
Ni, W., Watts, S. W., Ng, M., Chen, S., Glenn, D. J. and Gardner, D. G. (2014). Elimination of vitamin D receptor in vascular endothelial cells alters vascular function. Hypertension 64, 1290–1298.CrossRefGoogle ScholarPubMed
Nie, C. Q., Bernard, N. J., Norman, M. U., Amante, F. H., Lundie, R. J., Crabb, B. S., Heath, W. R., Engwerda, C. R., Hickey, M. J., Schofield, L. and Hansen, D. S. (2009). IP-10-mediated T cell homing promotes cerebral inflammation over splenic immunity to malaria infection. PLoS Pathogens 5, e1000369.CrossRefGoogle ScholarPubMed
Papandreou, D. and Hamid, Z. T. (2015). The role of vitamin D in diabetes and cardiovascular disease: an updated review of the literature. Disease Markers 2015, 580474.Google Scholar
Pasvol, G. (2005). The treatment of complicated and severe malaria. British Medical Bulletin 75–76, 29–47.Google Scholar
Polidoro, L., Properzi, G., Marampon, F., Gravina, G. L., Festuccia, C., Di Cesare, E., Scarsella, L., Ciccarelli, C., Zani, B. M. and Ferri, C. (2013). Vitamin D protects human endothelial cells from H(2)O(2) oxidant injury through the Mek/Erk-Sirt1 axis activation. Journal of Cardiovascular Translational Research 6, 221–231.Google Scholar
Ponsford, M. J., Medana, I. M., Prapansilp, P., Hien, T. T., Lee, S. J., Dondorp, A. M., Esiri, M. M., Day, N. P., White, N. J. and Turner, G. D. (2012). Sequestration and microvascular congestion are associated with coma in human CM. Journal of Infectious Diseases 205, 663–671.Google Scholar
Renia, L., Howland, S. W., Claser, C., Charlotte Gruner, A., Suwanarusk, R., Hui Teo, T., Russell, B. and Ng, L. F. (2012). CM: mysteries at the blood–brain barrier. Virulence 3, 193–201.Google Scholar
Sahu, P. K., Satpathi, S., Behera, P. K., Mishra, S. K., Mohanty, S. and Wassmer, S. C. (2015). Pathogenesis of CM: new diagnostic tools, biomarkers, and therapeutic approaches. Frontiers in Cellular and Infection Microbiology 5, 75.Google Scholar
Sandberg, L., Bistrom, M., Salzer, J., Vagberg, M., Svenningsson, A. and Sundstrom, P. (2016). Vitamin D and axonal injury in multiple sclerosis. Multiple Sclerosis 22, 1027–1031.CrossRefGoogle ScholarPubMed
Souraud, J. B., Briolant, S., Dormoi, J., Mosnier, J., Savini, H., Baret, E., Amalvict, R., Soulard, R., Rogier, C. and Pradines, B. (2012). Atorvastatin treatment is effective when used in combination with mefloquine in an experimental CM murine model. Malaria Journal 11, 13.Google Scholar
Stach, K., Kalsch, A. I., Nguyen, X. D., Elmas, E., Kralev, S., Lang, S., Weiss, C., Borggrefe, M. and Kalsch, T. (2011). 1alpha,25-dihydroxyvitamin D3 attenuates platelet activation and the expression of VCAM-1 and MT1-MMP in human endothelial cells. Cardiology 118, 107–115.Google Scholar
Taoufiq, Z., Gay, F., Balvanyos, J., Ciceron, L., Tefit, M., Lechat, P. and Mazier, D. (2008). Rho kinase inhibition in severe malaria: thwarting parasite-induced collateral damage to endothelia. The Journal of Infectious Diseases 197, 1062–1073.CrossRefGoogle ScholarPubMed
Taoufiq, Z., Pino, P., N'Dilimabaka, N., Arrouss, I., Assi, S., Soubrier, F., Rebollo, A. and Mazier, D. (2011). Atorvastatin prevents Plasmodium falciparum cytoadherence and endothelial damage. Malaria Journal 10, 52.Google Scholar
Tripathi, R., Vishwakarma, R. A. and Dutta, G. P. (2008). New antimalarial drug development: pre-clinical status of α and β artelinate as fast acting blood schizontocides. Proceedings of Indian National Science Academy 74, 111–117.Google Scholar
Uberti, F., Lattuada, D., Morsanuto, V., Nava, U., Bolis, G., Vacca, G., Squarzanti, D. F., Cisari, C. and Molinari, C. (2014). Vitamin D protects human endothelial cells from oxidative stress through the autophagic and survival pathways. Journal of Clinical Endocrinology and Metabolism 99, 1367–1374.CrossRefGoogle ScholarPubMed
Waisberg, M., Vickers, B. K., Yager, S. B., Lin, C. K. and Pierce, S. K. (2012). Testing in mice the hypothesis that melanin is protective in malaria infections. PLoS ONE 7, e29493.Google Scholar
Wassmer, S. C., Taylor, T. E., Rathod, P. K., Mishra, S. K., Mohanty, S., Arevalo-Herrera, M., Duraisingh, M. T. and Smith, J. D. (2015). Investigating the pathogenesis of severe malaria: a multidisciplinary and cross-geographical approach. The American Journal of Tropical Medicine and Hygiene 93, 42–56.CrossRefGoogle ScholarPubMed
Wilson, N. O., Jain, V., Roberts, C. E., Lucchi, N., Joel, P. K., Singh, M. P., Nagpal, A. C., Dash, A. P., Udhayakumar, V., Singh, N. and Stiles, J. K. (2011). CXCL4 and CXCL10 predict risk of fatal CM. Disease Markers 30, 39–49.CrossRefGoogle Scholar
Wilson, N. O., Solomon, W., Anderson, L., Patrickson, J., Pitts, S., Bond, V., Liu, M. and Stiles, J. K. (2013). Pharmacologic inhibition of CXCL10 in combination with anti-malarial therapy eliminates mortality associated with murine model of CM. PLoS ONE 8, e60898.Google Scholar
Zanini, G. M., Martins, Y. C., Cabrales, P., Frangos, J. A. and Carvalho, L. J. (2012). S-nitrosoglutathione prevents experimental CM. Journal of Neuroimmune Pharmacology 7, 477–487.Google Scholar
Supplementary material: File

Dwivedi supplementary material

Table S1

Download Dwivedi supplementary material(File)
File 21.4 KB