A WITHIN HOST MODEL OF BLOOD STAGE MALARIA WITH TREATMENT

We consider a mathematical model for malaria involving, susceptible red blood cells (RBCs), latent infected red blood cells (RBCs), active IRBCs, intracellular parasites, extracellular parasites and effector cells. We extend the model to include effect of treatment on the prognosis of malaria. One of the questions addressed in our study is: what range of the parameter, n1, which denotes the number of intracellular parasites released from a naturally dying activated infected red blood cell can lead to malaria pathogenesis? Sensitivity analysis revealed that poor parametric estimation can lead to wrong disease prognosis, and consequently to over or under-prescription of treatment drugs. In malaria endemic areas where the parasite is developing resistance to the drugs, this can limit options of treatment drugs. We recommend that the administration of malaria treatment drugs should be done under supervision as is the case for TB to ensure complete adherence to treatment and reduce the emergence of malaria drug resistant strains. Secondly, we recommend that individuals with malaria or showing symptoms of the disease should be tested for other chronic infections which could complicate the treatment of malaria.

[1]  R Heinrich,et al.  Mathematical modelling of the within-host dynamics of Plasmodium falciparum , 2000, Parasitology.

[2]  K. Sauer,et al.  IL-21 Is Required to Control Chronic Viral Infection , 2009, Science.

[3]  Ashrafi M. Niger,et al.  Immune Response and Imperfect Vaccine in Malaria Dynamics , 2011 .

[4]  F. McKenzie,et al.  Age-structured red blood cell susceptibility and the dynamics of malaria infections , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[5]  R. Anderson,et al.  The dynamics of drug action on the within-host population growth of infectious agents: melding pharmacokinetics with pathogen population dynamics. , 1998, Journal of theoretical biology.

[6]  Winston Garira,et al.  Modelling Immune Response and Drug Therapy in Human Malaria Infection , 2008 .

[7]  Junjie Wei,et al.  Periodicity and synchronization in blood-stage malaria infection , 2011, Journal of mathematical biology.

[8]  Michael W. Bolton,et al.  Altered Immune Responses in Rhesus Macaques Co-Infected with SIV and Plasmodium cynomolgi: An Animal Model for Coincident AIDS and Relapsing Malaria , 2009, PloS one.

[9]  M. Kalos,et al.  Development and application of a multiplexable flow cytometry‐based assay to quantify cell‐mediated cytolysis , 2010, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[10]  J. Lieberman,et al.  Most antiviral CD8 T cells during chronic viral infection do not express high levels of perforin and are not directly cytotoxic. , 2003, Blood.

[11]  I. Coppens,et al.  Metamorphosis of the malaria parasite in the liver is associated with organelle clearance , 2010, Cell Research.

[12]  J. Y. T. Mugisha,et al.  An Age-structured Mathematical Model for the Within Host Dynamics of Malaria and the Immune System , 2008, J. Math. Model. Algorithms.

[13]  D. Stevens,et al.  Combination immunotherapy and antifungal chemotherapy. , 1998, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[14]  Ana Rodriguez,et al.  The silent path to thousands of merozoites: the Plasmodium liver stage , 2006, Nature Reviews Microbiology.

[15]  T. Day,et al.  Modelling malaria pathogenesis , 2008, Cellular microbiology.

[16]  D. Sacks BAC talk about cell type-specific regulation of human IL-10 , 2009, Proceedings of the National Academy of Sciences of the United States of America.

[17]  David P Wilson,et al.  Sampling and sensitivity analyses tools (SaSAT) for computational modelling , 2008, Theoretical Biology and Medical Modelling.

[18]  E. Wherry,et al.  Memory CD8 T-Cell Differentiation during Viral Infection , 2004, Journal of Virology.

[19]  J. Petravic,et al.  Understanding the relationship between Plasmodium falciparum growth rate and multiplicity of infection. , 2015, The Journal of infectious diseases.

[20]  A. Cowman,et al.  Invasion of Red Blood Cells by Malaria Parasites , 2006, Cell.

[21]  A. Friedman,et al.  A model on the influence of age on immunity to infection with Mycobacterium tuberculosis , 2008, Experimental Gerontology.

[22]  Rogerio Amino,et al.  Manipulation of Host Hepatocytes by the Malaria Parasite for Delivery into Liver Sinusoids , 2006, Science.

[23]  J. Watmough,et al.  Reproduction numbers and sub-threshold endemic equilibria for compartmental models of disease transmission. , 2002, Mathematical biosciences.