From within host dynamics to the epidemiology of infectious disease: Scientific overview and challenges

Mathematical Biosciences

Volumn 270, Issue , 2015, Pages 143-155

  Gutierrez, Juan B ^a   Galinski, Mary R ^b   Cantrell, Stephen ^c   Voit, Eberhard O ^d  

^a UNIVERSITY OF GEORGIA   (United States)

^b EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c University of Miami   (United States)

^d GEORGIA INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

Epidemiology; Host parasite interactions; Infectious diseases; Malaria; Modeling; Systems biology

Indexed keywords

BIOLOGY; DYNAMICS; EPIDEMIOLOGY; MODELS; VIRUSES;

BIOLOGICAL ORGANIZATION; COMPUTATIONAL APPROACH; HOST-PARASITE INTERACTIONS; INFECTIOUS DISEASE; MALARIA; MULTI-SCALE MODELING; OHIO STATE UNIVERSITY; SYSTEMS BIOLOGY;

DISEASES;

ANOPHELES; ANTIGENIC VARIATION; ASYMPTOMATIC INFECTION; BASIC REPRODUCTION NUMBER; BIOMICS; EDITORIAL; ERYTHROPOIESIS; GEOGRAPHIC DISTRIBUTION; HOST PARASITE INTERACTION; HUMAN; IMMUNE EVASION; INFECTION; MALARIA; MATHEMATICAL MODEL; MIXED INFECTION; NONHUMAN; PARASITE CONTROL; PARASITE TRANSMISSION; PARASITEMIA; REINFECTION; SYSTEMS BIOLOGY; COMMUNICABLE DISEASES; THEORETICAL MODEL;

PROTOZOA;

COMMUNICABLE DISEASES; HOST-PARASITE INTERACTIONS; HUMANS; MODELS, THEORETICAL;

EID: 84949529520     PISSN: 00255564     EISSN: 18793134     Source Type: Journal    
DOI: 10.1016/j.mbs.2015.10.002     Document Type: Editorial

References (185)

1. WHO, Malaria. <>, 2013. http://www.who.int/malaria/media/world_malaria_report_2013/en/.
2. WHO, World Malaria Report, <>, 2014. http://www.who.int/malaria/publications/world_malaria_report_2014/en/.
3. AIDS, AIDS: Global statistics. <>, 2014. https://www.aids.gov/hiv-aids-basics/hiv-aids-101/global-statistics/.
4. WHO, Tuberculosis. <>, 2015. http://www.who.int/mediacentre/factsheets/fs104/en/.
5. WHO, Influenza. <>, 2014. http://www.who.int/topics/influenza/en/.
6. CDC, 2013 sexually transmitted disease surveillance.<>, 2014. http://www.cdc.gov/std/stats13/default.htm.
7. Lasker, Infectious diseases. <>, 2014. http://www.laskerfoundation.org/media/pdf/factsheet15infectiousdiseases.pdf.
8. M. Moffatt, The economic cost of a flu pandemic. <>, 2015. http://economics.about.com/od/healthcareeconomics/a/flu_pandemic.htm.
9. MBI, From within host dynamics to the epidemiology of infectious disease. <>, 2014. http://mbi.osu.edu/event/?id=715.
10. Clayton D., Hills M. Statistical Models in Epidemiology 2013, Oxford University Press, Oxford, UK.
11. Feng Z. Applications of Epidemiological Models to Public Health Policymaking 2014, World Scientific Publishing, Singapore.
12. Alonso P.L., Tanner M. Public health challenges and prospects for malaria control and elimination. Nat. Med. 2013, 19:150-155.
13. Howes R.E., Dewi M., Piel F.B., Monteiro W.M., Battle K.E., Messina J.P., Sakuntabhai A., Satyagraha A.W., Williams T.N., Baird J.K., Hay S.I. Spatial distribution of G6PD deficiency variants across malaria-endemic regions. Malar. J. 2013, 12:418.
14. Moyes C.L., Henry A.J., Golding N., Huang Z., Singh B., Baird J.K., Newton P.N., Huffman M., Duda K.A., Drakeley C.J., Elyazar I.R., Anstey N.M., Chen Q., Zommers Z., Bhatt S., Gething P.W., Hay S.I. Defining the geographical range of the Plasmodium knowlesi reservoir. PLoS Negl. Trop. Dis. 2014, 8:e2780.
15. Galinski M.R., Barnwell J.W. Monkey malaria kills four humans. Trends Parasitol. 2009, 25:200-204.
16. Singh B., Kim Sung L., Matusop A., Radhakrishnan A., Shamsul S.S., Cox-Singh J., Thomas A., Conway D.J. A large focus of naturally acquired Plasmodium knowlesi infections in human beings. Lancet 2004, 363:1017-1024.
17. William T., Jelip J., Menon J., Anderios F., Mohammad R., Awang Mohammad T.A., Grigg M.J., Yeo T.W., Anstey N.M., Barber B.E. Changing epidemiology of malaria in Sabah, Malaysia: increasing incidence of Plasmodium knowlesi. Malar. J. 2014, 13:390.
18. Kelly G.C., Tanner M., Vallely A., Clements A. Malaria elimination: moving forward with spatial decision support systems. Trends Parasitol. 2012, 28:297-304.
19. Coatney G.R., Collins W.E., Warren M., Contacos P.G. The Primate Malarias (original book published in 1971) 2003, 366. Division of Parasitic Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
20. Galinski M.R., Barnwell J.W. Non-human Primate Models for Human Malaria Research 2012, 299-323. Nonhuman Primates in Biomedical Research: Diseases, Elsevier, Inc.
21. Ayala S.C., D'Alessandro A., Mackenzie R., Angel D. Hemoparasite infections in 830 wild animals from the eastern Llanos of Colombia. J. Parasitol. 1973, 59:52-59.
22. Escalante A.A., Ayala F.J. Phylogeny of the malarial genus Plasmodium, derived from rRNA gene sequences. Proc. Natl. Acad. Sci. USA 1994, 91:11373-11377.
23. Hayakawa T., Tachibana S., Hikosaka K., Arisue N., Matsui A., Horii T., Tanabe K. Age of the last common ancestor of extant Plasmodium parasite lineages. Gene 2012, 502:36-39.
24. Hall B.F., Fauci A.S. Malaria control, elimination, and eradication: the role of the evolving biomedical research agenda. J. Infect. Dis. 2009, 200:1639-1643.
25. Sibley C.H. Understanding drug resistance in malaria parasites: basic science for public health. Mol. Biochem. Parasitol. 2014, 195:107-114.
26. Sinha S., Medhi B., Sehgal R. Challenges of drug-resistant malaria. Parasite 2014, 21:61.
27. Visser B.J., van Vugt M., Grobusch M.P. Malaria: an update on current chemotherapy. Expert Opin. Pharmacother. 2014, 15:2219-2254.
28. Chen N., LaCrue A.N., Teuscher F., Waters N.C., Gatton M.L., Kyle D.E., Cheng Q. Fatty acid synthesis and pyruvate metabolism pathways remain active in dihydroartemisinin-induced dormant ring stages of Plasmodium falciparum. Antimicrob. Agents Chemother. 2014, 58:4773-4781.
29. Cheng Q., Cunningham J., Gatton M.L. Systematic review of sub-microscopic P. vivax infections: prevalence and determining factors. PLoS Negl. Trop. Dis. 2015, 9:e3413.
30. Lopes S.C., Albrecht L., Carvalho B.O., Siqueira A.M., Thomson-Luque R., Nogueira P.A., Fernandez-Becerra C., Del Portillo H.A., Russell B.M., Renia L., Lacerda M.V., Costa F.T. Paucity of Plasmodium vivax mature schizonts in peripheral blood is associated with their increased cytoadhesive potential. J. Infect. Dis. 2014, 209:1403-1407.
31. Kondrashin A., Baranova A.M., Ashley E.A., Recht J., White N.J., Sergiev V.P. Mass primaquine treatment to eliminate vivax malaria: lessons from the past. Malar. J. 2014, 13:51.
32. Maude R.J., Nguon C., Dondorp A.M., White L.J., White N.J. The diminishing returns of atovaquone-proguanil for elimination of Plasmodium falciparum malaria: modelling mass drug administration and treatment. Malar. J. 2014, 13:380.
33. Poirot E., Skarbinski J., Sinclair D., Kachur S.P., Slutsker L., Hwang J. Mass drug administration for malaria. Cochrane Database Syst. Rev. 2013, 12.
34. White N.J., Pukrittayakamee S., Hien T.T., Faiz M.A., Mokuolu O.A., Dondorp A.M. Malaria. Lancet 2014, 383:723-735.
35. Baird J.K. Pernicious and threatening Plasmodium vivax as reality. Am. J. Trop. Med. Hyg. 2014, 91:1-2.
36. Cunnington A.J., Riley E.M., Walther M. Stuck in a rut? Reconsidering the role of parasite sequestration in severe malaria syndromes. Trends Parasitol. 2013, 29:585-592.
37. Price R.N., Douglas N.M., Anstey N.M. New developments in Plasmodium vivax malaria: severe disease and the rise of chloroquine resistance. Curr. Opin. Infect. Dis. 2009, 22:430-435.
38. Ali I.M., Evehe M.S., Netongo P.M., Atogho-Tiedeu B., Akindeh-Nji M., Ngora H., Domkam I.K., Diakite M., Baldip K., Ranford-Cartwright L., Mimche P.N., Lamb T., Mbacham W.F. Host candidate gene polymorphisms and associated clearance of P. falciparum amodiaquine and fansidar resistance mutants in children less than 5 years in Cameroon. Pathog. Glob. Health 2014, 108:323-333.
39. Alout H., Yameogo B., Djogbenou L.S., Chandre F., Dabire R.K., Corbel V., Cohuet A. Interplay between Plasmodium infection and resistance to insecticides in vector mosquitoes. J. Infect. Dis. 2014, 210:1464-1470.
40. Nair S., Nkhoma S.C., Serre D., Zimmerman P.A., Gorena K., Daniel B.J., Nosten F., Anderson T.J., Cheeseman I.H. Single-cell genomics for dissection of complex malaria infections. Genome Res. 2014, 24:1028-1038.
41. Nwakanma D.C., Duffy C.W., Amambua-Ngwa A., Oriero E.C., Bojang K.A., Pinder M., Drakeley C.J., Sutherland C.J., Milligan P.J., Macinnis B., Kwiatkowski D.P., Clark T.G., Greenwood B.M., Conway D.J. Changes in malaria parasite drug resistance in an endemic population over a 25-year period with resulting genomic evidence of selection. J. Infect. Dis. 2014, 209:1126-1135.
42. Ocholla H., Preston M.D., Mipando M., Jensen A.T., Campino S., MacInnis B., Alcock D., Terlouw A., Zongo I., Oudraogo J.B., Djimde A.A., Assefa S., Doumbo O.K., Borrmann S., Nzila A., Marsh K., Fairhurst R.M., Nosten F., Anderson T.J., Kwiatkowski D.P., Craig A., Clark T.G., Montgomery J. Whole-genome scans provide evidence of adaptive evolution in Malawian Plasmodium falciparum isolates. J. Infect. Dis. 2014, 210:1991-2000.
43. Preston M.D., Assefa S.A., Ocholla H., Sutherland C.J., Borrmann S., Nzila A., Michon P., Hien T.T., Bousema T., Drakeley C.J., Zongo I., Ouedraogo J.B., Djimde A.A., Doumbo O.K., Nosten F., Fairhurst R.M., Conway D.J., Roper C., Clark T.G. PlasmoView: a web-based resource to visualise global Plasmodium falciparum genomic variation. J. Infect. Dis. 2014, 209:1808-1815.
44. Preston M.D., Campino S., Assefa S.A., Echeverry D.F., Ocholla H., Amambua-Ngwa A., Stewart L.B., Conway D.J., Borrmann S., Michon P., Zongo I., Ouedraogo J.B., Djimde A.A., Doumbo O.K., Nosten F., Pain A., Bousema T., Drakeley C.J., Fairhurst R.M., Sutherland C.J., Roper C., Clark T.G. A barcode of organellar genome polymorphisms identifies the geographic origin of Plasmodium falciparum strains. Nat. Commun. 2014, 5:4052.
45. Taylor S.M., Fairhurst R.M. Malaria parasites and red cell variants: when a house is not a home. Curr. Opin. Hematol. 2014, 21:193-200.
46. Yamagishi J., Natori A., Tolba M.E., Mongan A.E., Sugimoto C., Katayama T., Kawashima S., Makalowski W., Maeda R., Eshita Y., Tuda J., Suzuki Y. Interactive transcriptome analysis of malaria patients and infecting Plasmodium falciparum. Genome Res. 2014, 24:1433-1444.
47. Zimmerman P.A., Ferreira M.U., Howes R.E., Mercereau-Puijalon O. Red blood cell polymorphism and susceptibility to Plasmodium vivax. Adv. Parasitol. 2013, 81:27-76.
48. Ariey F., Witkowski B., Amaratunga C., Beghain J., Langlois A.C., Khim N., Kim S., Duru V., Bouchier C., Ma L., Lim P., Leang R., Duong S., Sreng S., Suon S., Chuor C.M., Bout D.M., Menard S., Rogers W.O., Genton B., Fandeur T., Miotto O., Ringwald P., Le Bras J., Berry A., Barale J.C., Fairhurst R.M., Benoit-Vical F., Mercereau-Puijalon O., Menard D. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature 2014, 505:50-55.
49. Straimer J., Gnadig N.F., Witkowski B., Amaratunga C., Duru V., Ramadani A.P., Dacheux M., Khim N., Zhang L., Lam S., Gregory P.D., Urnov F.D., Mercereau-Puijalon O., Benoit-Vical F., Fairhurst R.M., Menard D., Fidock D.A. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates. Science 2014.
50. Wendler J.P., Okombo J., Amato R., Miotto O., Kiara S.M., Mwai L., Pole L., O'Brien J., Manske M., Alcock D., Drury E., Sanders M., Oyola S.O., Malangone C., Jyothi D., Miles A., Rockett K.A., MacInnis B.L., Marsh K., Bejon P., Nzila A., Kwiatkowski D.P. A genome wide association study of Plasmodium falciparum susceptibility to 22 antimalarial drugs in Kenya. PLoS One 2014, 9:e96486.
51. Winzeler E.A., Manary M.J. Drug resistance genomics of the antimalarial drug artemisinin. Genome Biol. 2014, 15:544.
52. Patel K., Simpson J.A., Batty K.T., Zaloumis S., Kirkpatrick C.M. Modelling the time course of antimalarial parasite killing: a tour of animal and human models, translation and challenges. Br. J. Clin. Pharmacol. 2015, 79:97-107.
53. Taylor A.R., Flegg J.A., Nsobya S.L., Yeka A., Kamya M.R., Rosenthal P.J., Dorsey G., Sibley C.H., Guerin P.J., Holmes C.C. Estimation of malaria haplotype and genotype frequencies: a statistical approach to overcome the challenge associated with multiclonal infections. Malar. J. 2014, 13:102.
54. Liehl P., Meireles P., Albuquerque I.S., Pinkevych M., Baptista F., Mota M.M., Davenport M.P., Prudencio M. Innate immunity induced by Plasmodium liver infection inhibits malaria reinfections. Infect. Immun. 2015.
55. Frevert U., Nacer A. Immunobiology of Plasmodium in liver and brain. Parasite Immunol. 2013, 35:267-282.
56. Baer K., Klotz C., Kappe S.H., Schnieder T., Frevert U. Release of hepatic Plasmodium yoelii merozoites into the pulmonary microvasculature. PLoS Pathog. 2007, 3:e171.
57. Graewe S., Rankin K.E., Lehmann C., Deschermeier C., Hecht L., Froehlke U., Stanway R.R., Heussler V. Hostile takeover by Plasmodium: reorganization of parasite and host cell membranes during liver stage egress. PLoS Pathog. 2011, 7.
58. Thiberge S., Blazquez S., Baldacci P., Renaud O., Shorte S., Menard R., Amino R. In vivo imaging of malaria parasites in the murine liver. Nat. Protoc. 2007, 2:1811-1818.
59. Clark M.A., Goheen M.M., Spidale N.A., Kasthuri R.S., Fulford A., Cerami C. RBC barcoding allows for the study of erythrocyte population dynamics and P. falciparum merozoite invasion. PLoS One 2014, 9.
60. Galinski M.R., Meyer E.V., Barnwell J.W. Plasmodium vivax: modern strategies to study a persistent parasite's life cycle. Adv. Parasitol. 2013, 81:1-26.
61. Harvey K.L., Gilson P.R., Crabb B.S. A model for the progression of receptor-ligand interactions during erythrocyte invasion by Plasmodium falciparum. Int. J. Parasitol. 2012, 42:567-573.
62. Kerlin D.H., Gatton M.L. Preferential invasion by Plasmodium merozoites and the self-regulation of parasite burden. PLoS One 2013, 8:e57434.
63. Aikawa M., Miller L.H., Rabbege J. Caveola-vesicle complexes in the plasmalemma of erythrocytes infected by Plasmodium vivax and P cynomolgi. Unique structures related to Schuffner's dots. Am. J. Pathol. 1975, 79:285-300.
64. Akinyi S., Hanssen E., Meyer E.V., Jiang J., Korir C.C., Singh B., Lapp S., Barnwell J.W., Tilley L., Galinski M.R. A 95 kDa protein of Plasmodium vivax and P. cynomolgi visualized by three-dimensional tomography in the caveola-vesicle complexes (Schuffner's dots) of infected erythrocytes is a member of the PHIST family. Mol. Microbiol. 2012, 84:816-831.
65. Kirk K., Lehane A.M. Membrane transport in the malaria parasite and its host erythrocyte. Biochem. J. 2014, 457:1-18.
66. 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.
67. Aguilar R., Magallon-Tejada A., Achtman A.H., Moraleda C., Joice R., Cistero P., Li Wai Suen C.S., Nhabomba A., Macete E., Mueller I., Marti M., Alonso P.L., Menendez C., Schofield L., Mayor A. Molecular evidence for the localization of Plasmodium falciparum immature gametocytes in bone marrow. Blood 2014, 123:959-966.
68. Joice R., Nilsson S.K., Montgomery J., Dankwa S., Egan E., Morahan B., Seydel K.B., Bertuccini L., Alano P., Williamson K.C., Duraisingh M.T., Taylor T.E., Milner D.A., Marti M. Plasmodium falciparum transmission stages accumulate in the human bone marrow. Sci. Transl. Med. 2014, 6:244re5.
69. Johnston G.L., Smith D.L., Fidock D.A. Malaria's missing number: calculating the human component of R0 by a within-host mechanistic model of Plasmodium falciparum infection and transmission. PLoS Comput. Biol. 2013, 9.
70. Alano P. The sound of sexual commitment breaks the silencing of malaria parasites. Trends Parasitol. 2014, 30:509-510.
71. Ataide R., Mayor A., Rogerson S.J. Malaria, primigravidae, and antibodies: knowledge gained and future perspectives. Trends Parasitol. 2014, 30:85-94.
72. Takem E.N., D'Alessandro U. Malaria in pregnancy. Mediterr. J. Hematol. Infect. Dis. 2013, 5.
73. Thanapongpichat S., McGready R., Luxemburger C., Day N.P., White N.J., Nosten F., Snounou G., Imwong M. Microsatellite genotyping of Plasmodium vivax infections and their relapses in pregnant and non-pregnant patients on the Thai-Myanmar border. Malar. J. 2013, 12:275.
74. Walker P.G., Griffin J.T., Cairns M., Rogerson S.J., van Eijk A.M., ter Kuile F., Ghani A.C. A model of parity-dependent immunity to placental malaria. Nat. Commun. 2013, 4:1609.
75. G. Corradin, and H. Engers, Malaria vaccine development: over 40 years of trials and tribulations. <>, 2014. http://www.futuremedicine.com/doi/book/10.2217/9781780844411.
76. Joyner C.J., Barnwell J., Galinski M.R. No more monkeying around: Primate malaria model systems are key to understanding plasmodium vivax liver-stage biology, hypnozoites, and relapses. Front. Microbiol. 2015, 6:145.
77. White M.T., Karl S., Battle K.E., Hay S.I., Mueller I., Ghani A.C. Modelling the contribution of the hypnozoite reservoir to Plasmodium vivax transmission. Elife 2014, 3.
78. Betuela I., Rosanas-Urgell A., Kiniboro B., Stanisic D.I., Samol L., de Lazzari E., Del Portillo H.A., Siba P., Alonso P.L., Bassat Q., Mueller I. Relapses contribute significantly to the risk of Plasmodium vivax infection and disease in Papua New Guinean children 1-5 years of age. J. Infect. Dis. 2012, 206:1771-1780.
79. Krotoski W.A., Collins W.E., Bray R.S., Garnham P.C., Cogswell F.B., Gwadz R.W., Killick-Kendrick R., Wolf R., Sinden R., Koontz L.C., Stanfill P.S. Demonstration of hypnozoites in sporozoite-transmitted Plasmodium vivax infection. Am. J. Trop. Med. Hyg. 1982, 31:1291-1293.
80. Reyes-Sandoval A., Bachmann M.F. Plasmodium vivax malaria vaccines: why are we where we are?. Hum. Vaccin. Immunother. 2013, 9:2558-2565.
81. Chua C.L., Brown G., Hamilton J.A., Rogerson S., Boeuf P. Monocytes and macrophages in malaria: protection or pathology?. Trends Parasitol. 2013, 29:26-34.
82. Doolan D.L., Dobano C., Baird J.K. Acquired immunity to malaria. Clin. Microbiol. Rev. 2009, 22:13-36. [Table of Contents].
83. Ioannidis L.J., Nie C.Q., Hansen D.S. The role of chemokines in severe malaria: more than meets the eye. Parasitology 2014, 141:602-613.
84. Moreno A., Cabrera-Mora M., Garcia A., Orkin J., Strobert E., Barnwell J.W., Galinski M.R. Plasmodium coatneyi in rhesus macaques replicates the multisystemic dysfunction of severe malaria in humans. Infect. Immun. 2013, 81:1889-1904.
85. Praba-Egge A.D., Montenegro S., Cogswell F.B., Hopper T., James M.A. Cytokine responses during acute simian Plasmodium cynomolgi and Plasmodium knowlesi infections. Am. J. Trop. Med. Hyg. 2002, 67:586-596.
86. Teo A., Hasang W., Randall L.M., Feng G., Bell L., Unger H., Langer C., Beeson J.G., Siba P.M., Mueller I., Molyneux M.E., Brown G.V., Rogerson S.J. Decreasing malaria prevalence and its potential consequences for immunity in pregnant women. J. Infect. Dis. 2014, 210:1444-1455.
87. Viriyavejakul P., Khachonsaksumet V., Punsawad C. Liver changes in severe Plasmodium falciparum malaria: histopathology, apoptosis and nuclear factor kappa B expression. Malar. J. 2014, 13:106.
88. Wunderlich F., Al-Quraishy S., Dkhil M.A. Liver-inherent immune system: its role in blood-stage malaria. Front. Microbiol. 2014, 5:559.
89. Blyuss K.B. The effects of symmetry on the dynamics of antigenic variation. J. Math. Biol. 2013, 66:115-137.
90. Guizetti J., Scherf A. Silence, activate, poise and switch! Mechanisms of antigenic variation in Plasmodium falciparum. Cell Microbiol. 2013, 15:718-726.
91. Warimwe G.M., Recker M., Kiragu E.W., Buckee C.O., Wambua J., Musyoki J.N., Marsh K., Bull P.C. Plasmodium falciparum var gene expression homogeneity as a marker of the host-parasite relationship under different levels of naturally acquired immunity to malaria. PLoS One 2013, 8:e70467.
92. Galinski M.R., Corredor V. Variant antigen expression in malaria infections: posttranscriptional gene silencing, virulence and severe pathology. Mol. Biochem. Parasitol. 2004, 134:17-25.
93. Korir C.C., Galinski M.R. Proteomic studies of Plasmodium knowlesi SICA variant antigens demonstrate their relationship with P. falciparum EMP1. Infect. Genet. Evol. 2006, 6:75-79.
94. Lapp S.A., Korir-Morrison C., Jiang J., Bai Y., Corredor V., Galinski M.R. Spleen-dependent regulation of antigenic variation in malaria parasites: Plasmodium knowlesi SICAvar expression profiles in splenic and asplenic hosts. PLoS One 2013, 8:e78014.
95. Voss T.S., Bozdech Z., Bartfai R. Epigenetic memory takes center stage in the survival strategy of malaria parasites. Curr. Opin. Microbiol. 2014, 20:88-95.
96. Avril M., Brazier A.J., Melcher M., Sampath S., Smith J.D. DC8 and DC13 var genes associated with severe malaria bind avidly to diverse endothelial cells. PLoS Pathog. 2013, 9.
97. Smith J.D., Rowe J.A., Higgins M.K., Lavstsen T. Malaria's deadly grip: cytoadhesion of Plasmodium falciparum infected erythrocytes. Cell Microbiol. 2013.
98. Abdi A.I., Fegan G., Muthui M., Kiragu E., Musyoki J.N., Opiyo M., Marsh K., Warimwe G.M., Bull P.C. Plasmodium falciparum antigenic variation: relationships between widespread endothelial activation, parasite PfEMP1 expression and severe malaria. BMC Infect. Dis. 2014, 14:170.
99. Brancucci N.M., Bertschi N.L., Zhu L., Niederwieser I., Chin W.H., Wampfler R., Freymond C., Rottmann M., Felger I., Bozdech Z., Voss T.S. Heterochromatin protein 1 secures survival and transmission of malaria parasites. Cell Host Microbe 2014, 16:165-176.
100. Coleman B.I., Skillman K.M., Jiang R.H., Childs L.M., Altenhofen L.M., Ganter M., Leung Y., Goldowitz I., Kafsack B.F., Marti M., Llinas M., Buckee C.O., Duraisingh M.T. A Plasmodium falciparum histone deacetylase regulates antigenic variation and gametocyte conversion. Cell Host Microbe 2014, 16:177-186.
101. Mantel P.Y., Hoang A.N., Goldowitz I., Potashnikova D., Hamza B., Vorobjev I., Ghiran I., Toner M., Irimia D., Ivanov A.R., Barteneva N., Marti M. Malaria-infected erythrocyte-derived microvesicles mediate cellular communication within the parasite population and with the host immune system. Cell Host Microbe 2013, 13:521-534.
102. Marcilla A., Martin-Jaular L., Trelis M., de Menezes-Neto A., Osuna A., Bernal D., Fernandez-Becerra C., Almeida I.C., Del Portillo H.A. Extracellular vesicles in parasitic diseases. J. Extracell. Vesicles 2014, 3:25040.
103. Regev-Rudzki N., Wilson D.W., Carvalho T.G., Sisquella X., Coleman B.M., Rug M., Bursac D., Angrisano F., Gee M., Hill A.F., Baum J., Cowman A.F. Cell-cell communication between malaria-infected red blood cells via exosome-like vesicles. Cell 2013, 153:1120-1133.
104. Douglas N.M., Anstey N.M., Buffet P.A., Poespoprodjo J.R., Yeo T.W., White N.J., Price R.N. The anaemia of Plasmodium vivax malaria. Malar. J. 2012, 11:135.
105. Perkins D.J., Were T., Davenport G.C., Kempaiah P., Hittner J.B., Ong'echa J.M. Severe malarial anemia: innate immunity and pathogenesis. Int. J. Biol. Sci. 2011, 7:1427-1442.
106. Jakeman G.N., Saul A., Hogarth W.L., Collins W.E. Anaemia of acute malaria infections in non-immune patients primarily results from destruction of uninfected erythrocytes. Parasitology 1999, 119:127-133.
107. Fonseca L.L., Voit E.O. Comparison of mathematical frameworks for modeling erythropoiesis in the context of malaria infection. Math. Biosci. 2015, this volume.
108. Gama J.A., Abby S.S., Vieira-Silva S., Dionisio F., Rocha E.P. Immune subversion and quorum-sensing shape the variation in infectious dose among bacterial pathogens. PLoS Pathog. 2012, 8.
109. Nowak M.A., May R.M. Mathematical biology of HIV infections: antigenic variation and diversity threshold. Math. Biosci. 1991, 106:1-21.
110. Agur Z., Abiri D., Van der Ploeg L. Ordered appearance of antigenic variants of African trypanosomes explained in a mathematical model based on a stochastic switch process and immune-selection against putative switch intermediates. Proc. Natl. Acad. Sci. 1989, 86:9626-9630.
111. Recker M., Buckee C.O., Serazin A., Kyes S., Pinches R., Christodoulou Z., Springer A.L., Gupta S., Newbold C.I. Antigenic variation in Plasmodium falciparum malaria involves a highly structured switching pattern. PLoS Pathog. 2011, 7.
112. Gupta S., Trenholme K., Anderson R., Day K. Antigenic diversity and the transmission dynamics of Plasmodium falciparum. Science 1994, 263:961-963.
113. Arnot D.E., Jensen A.T. Antigenic variation and the genetics and epigenetics of the PfEMP1 erythrocyte surface antigens in Plasmodium falciparum malaria. Adv. Appl. Microbiol. 2011, 74:77-96.
114. Eckhoff P. P. falciparum infection durations and infectiousness are shaped by antigenic variation and innate and adaptive host immunity in a mathematical model. PLoS ONE 2012, 7:e44950.
115. Smith J.D., Chitnis C.E., Craig A.G., Roberts D.J., Hudson-Taylor D.E., Peterson D.S., Pinches R., Newbold C.I., Miller L.H. Switches in expression of Plasmodium falciparum var genes correlate with changes in antigenic and cytoadherent phenotypes of infected erythrocytes. Cell 1995, 82:101-110.
116. Ross R. An application of the theory of probabilities to the study of a priori pathometry. Part I. Proc. Roy. Soc. A: Math. Phys. Eng. Sci. 1916, 92:204-230.
117. Ross R., Hudson H. An application of the theory of probabilities to the study of a priori pathometry. Part III. Proc. Roy. Soc. A: Math. Phys. Eng. Sci. 1917, 93:225-240.
118. Ross R., Hudson H. An application of the theory of probabilities to the study of a priori pathometry. Part II. Proc. Roy. Soc. A: Math. Phys. Eng. Sci. 1917, 93:212-225.
119. Macdonald G. The Epidemiology and Control of Malaria 1957, Oxford University Press, London.
120. Anderson R.M., May R.M. Infectious Diseases of Humans: Dynamics and Control 1992, OUP, Oxford.
121. Dietz K. Mathematical Models for Transmission and Control of Malaria, Principles and Practice of Malariology 1988, 1091-1133. Churchill Livingston, Edinburgh.
122. Filipe J.A.N., Riley E.M., Drakeley C.J., Sutherland C.J., Ghani A.C. Determination of the processes driving the acquisition of immunity to malaria using a mathematical transmission model. PLoS Comput. Biol. 2007, 3:e255.
123. Rodriguez D., Torres-Sorando L. Models of infectious diseases in spatially heterogeneous environments. Bull. Math. Biol. 2001, 63:547-571.
124. Smith D.L., Dushoff J., McKenzie F.E. The risk of a mosquito-borne infectionin a heterogeneous environment. PLoS Biol. 2004, 2:e368.
125. Kermack W., McKendrick A.G. A contribution to the mathematical theory of epidemics. Proc. Roy. Soc. Lond. A Math. Phys. Char. 1927, 115:700-721.
126. Brauer F., Castillo-Chávez C. Mathematical Models in Population Biology and Epidemiology 2012, Springer.
127. Bottius E., Guanzirolli A., Trape J.-F.C., Rogier C., Konate L., Druilhe P. Malaria: even more chronic in nature than previously thought; evidence for subpatent parasitaemia detectable by the polymerase chain reaction. Trans. Roy. Soc. Trop. Med. Hyg. 1996, 90:15-19.
128. Laishram D.D., Sutton P.L., Nanda N., Sharma V.L., Sobti R.C., Carlton J.M., Joshi H., others The complexities of malaria disease manifestations with a focus on asymptomatic malaria. Malar. J. 2012, 11:29.
129. Farnert A., Snounou G., Rooth I., Bjorkman A. Daily dynamics of Plasmodium falciparum subpopulation in asymptomatic children in a holoendemic area. Am. J. Trop. Med. Hyg. 1997, 56:538-547.
130. da Silva-Nunes M., Moreno M., Conn J., Gamboa D., Abelesb S., Vinetz J.M., Ferreira M. Amazonian malaria: asymptomatic human reservoirs, diagnostic challenges, environmentally driven changes in mosquito vector populations, and the mandate for sustainable control strategies. Acta Tropica 2012, 121:281-291.
131. Schweitzer A., Anderson R. Dynamic interaction between CD4+ T cells and parasitic helminths: mathematical models of heterogeneity in outcome. Parasitology 1992, 105:513-522.
132. Gupta S., Maiden M.C., Feavers I.M., Nee S., May R.M., Anderson R.M. The maintenance of strain structure in populations of recombining infectious agents. Nat. Med. 1996, 2:437-442.
133. Dushoff J. Incorporating immunological ideas in epidemiological models. J. Theor. Biol. 1996, 180:181-187.
134. Anderson R.M. Complex dynamic behaviours in the interaction between parasite populations and the host's immune system. Int. J. Parasitol. 1998, 28:551-566.
135. Reluga T.C., Medlock J., Perelson A.S. Backward bifurcations and multiple equilibria in epidemic models with structured immunity. J. Theor. Biol. 2008, 252:155-165.
136. Nickerson D., Nash M.P., Nielsen P.M.F., Smith N.P., Hunter P.J. Computational multiscale modeling in the physiome project: modeling cardiac electromechanics. IBM J. Res. Develop. 2006, 50:617-630.
137. Physiome, The physiome project. <>, 2015. http://physiomeproject.org/.
138. Virtual-Liver. <>, 2015. http://www.virtual-liver.de/.
139. Holzhütter H.G., Drasdo D., Preusser T., Lippert J., Henney A.M. The virtual liver: a multidisciplinary, multilevel challenge for systems biology. Wiley Interdis. Rev. Syst. Biol. Med. 2012, 4:221-235.
140. Voit E.O. A systems-theoretical framework for health and disease: inflammation and preconditioning from an abstract modeling point of view. Math. Biosci. 2009, 217:11-18.
141. Childs L.M., Abuelezam N.N., Dye C., Gupta S., Murray M.B., Williams B.G., Buckee C.O. Modelling challenges in context: lessons from malaria, HIV, and tuberculosis. Epidemics 2015.
142. Riley S., Eames K., Isham V., Mollison D., Trapman P. Five challenges for spatial epidemic models. Epidemics 2014, in press.
143. Cantrell R.S., Cosner C. Spatial Ecology via Reaction-Diffusion Equations 2003, John Wiley & Sons.
144. Murray J.D. Mathematical Biology. II Spatial Models and Biomedical Applications (Interdisciplinary Applied Mathematics V. 18) 2001, Springer-Verlag, New York Inc.
145. Kot M., Lewis M.A., van den Driessche P. Dispersal data and the spread of invading organisms. Ecology 1996, 77:2027-2042.
146. Kot M., Schaffer W.M. Discrete-time growth-dispersal models. Math. Biosci. 1986, 80:109-136.
147. Ovaskainen O., Hanski I. Spatially structured metapopulation models: Global and local assessment of metapopulation capacity. Theor. Pop. Biol. 2001, 60:281-302.
148. Cantrell R.S., Cosner C., Fagan W.F. The implications of model formulation when transitioning from spatial to landscape ecology. Math. Biosci. Eng. 2012, 9:27-60.
149. Gao D., Ruan S. A multipatch malaria model with logistic growth populations. SIAM J. Appl. Math. 2012, 72:819-841.
150. Cosner C., Beier J.C., Cantrell R.S., Impoinvil D., Kapitanski L., Potts M.D., Troyo A., Ruan S. The effects of human movement on the persistence of vector-borne diseases. J. Theor. Biol. 2009, 258:550-560.
151. Stoddard S.T., Morrison A.C., Vazquez-Prokopec G.M., Soldan V.P., Kochel T.J., Kitron U., Elder J.P., Scott T.W. The role of human movement in the transmission of vector-borne pathogens. PLoS Neg. Trop. Dis. 2009, 3:e481.
152. Voit E.O. Models-of-data and models-of-processes in the post-genomic era. Math. Biosci. 2002, 180:263-274.
153. Yin W., Kissinger J.C., Moreno A., Galinski M.R., Styczynski M.P. From genome-scale data to models of infectious disease: a Bayesian network-based strategy to drive model development. Math. Biosci. 2015.
154. KEGG. <>, 2015. http://www.genome.jp/kegg/.
155. MetaCyc. , 2015. http://MetaCyc.org.
156. BRENDA. <>, 2015. http://www.brenda-enzymes.org/.
157. Bodenmiller B., Zunder E.R., Finck R., Chen T.J., Savig E.S., Bruggner R.V., Simonds E.F., Bendall S.C., Sachs K., Krutzik P.O., Nolan G.P. Multiplexed mass cytometry profiling of cellular states perturbed by small-molecule regulators. Nat. Biotech. 2012, 30:858-867.
158. Mihret A., Abebe M. Cytokines and chemokines as biomarkers of tuberculosis. J. Mycobac. Dis. 2013, 3.
159. Voit E.O., Brigham K.L. The role of systems biology in predictive health and personalized medicine. The Open Path. J. 2008, 2:68-70.
160. S-System Approach to Understanding Complexity 1991, Van Nostrand, Reinhold, NY. E.O. Voit (Ed.).
161. Voit E.O., Savageau M.A. Equivalence between S-systems and Volterra-systems. Math. Biosci. 1986, 78:47-55.
162. Voit E.O. Biochemical systems theory: A review. Int. Scholarly Res. Network (ISRN-Biomathematics) Art. 2013, 897658:1-53.
163. Savageau M.A. Allometric morphogenesis of complex systems: Derivation of the basic equations from first principles. Proc. Natl. Acad. Sci. USA 1979, 76:6023-6025.
164. Peschel M., Mende W. The Predator-Prey Model: Do we Live in a Volterra World? 1986, Akademie-Verlag, Berlin.
165. Voit E.O. Canonical modeling: a review of concepts with emphasis on environmental health. Environ. Health Perspect. 2000, 108(Suppl. 5):895-909.
166. Alves R., Sorribas A. Special issue on biological design principles. Math. Biosci. 2011, 231:1-2.
167. Jacobsen K., Pilyugin S.S. Analysis of a mathematical model for tumor therapy with a fusogenic oncolytic virus. Math. Biosci. 2015.
168. Yang Y., Zou L., Ruan S. Global dynamics of a delayed within-host viral infection model with both virus-to-cell and cell-to-cell transmissions. Math. Biosci. 2015.
169. Cosner C. Models for the effects of host movement in vector-borne disease systems. Math. Biosci. 2015.
170. Schwartz E.J., Choi B., Rempala G.A., Estimating Epidemic Parameters Estimating epidemic parameters: application to H1N1 pandemic data. Math. Biosci. 2015.
171. Feng Z., Cen X., Zhao Y., Velasco-Hernandez J.X. Coupled within-host and between-host dynamics and evolution of virulence. Math. Biosci. 2015.
172. Yan Y., Adam B., Moreno A., Galinski M., Kissinger J.C., Gutierrez J.B. Mathematical model of susceptibility, resistance, and resilience in the within-host dynamics between a Plasmodium parasite and the immune system. Math. Biosci. 2015.
173. Allen L.J.S., Schwartz E.J. Free-virus and cell-to-cell transmission in models of equine infectious anemia virus infection. Math. Biosci. 2015.
174. Barfield M., Orive M.E., Holt R.D. The role of pathogen shedding in linking within- and between-host pathogen dynamics. Math. Biosci. 2015.
175. Gutierrez J.B., Lai M.-J., Slavov G. Bivariate spline solution of time dependent nonlinear PDE for a population density over irregular domains. Math. Biosci. 2015.
176. Voit E.O. A First Course in Systems Biology 2012, Garland Science, New York, NY.
177. Osbeck L.M., Nersessian N.J., Malone K.R., Newstetter W.C. Science as Psychology: Sense-Making and Identity in Science Practice 2010, Cambridge University Press, Cambridge, UK.
178. Galison P.L. Image and Logic: A Material Culture of Microphysics 1997, University of Chicago Press.
179. Star S.L., Griesemer J.R. Institutional ecology, 'translations' and boundary objects: amateurs and professionals in Berkeley's Museum of Vertebrate Zoology. Soc. Stud. Sci. 1989, 19:387-420.
180. Savageau M.A. The challenge of reconstruction. New Biol. 1991, 3:101-102.
181. Nat.Res.Council Beyond Productivity: Information, Technology, Innovation, and Creativity 2003, National Academies Press.
182. Spiro R.J. Cognitive Flexibility Theory Advanced Knowledge Structures in Ill-structured Domains 1988, University of Illinois Press.
183. Voit E.O., Newstetter W.C., Kemp M.L. A feel for systems. Mol. Syst. Biol. 2012, 8:609.
184. MaHPIC, Malaria Host-Pathogen Interaction Center. <>, 2012. http://www.systemsbiology.emory.edu/.
185. Voit E.O., Qi Z., Kikuchi S. Mesoscopic models of neurotransmission as intermediates between disease simulators and tools for discovering design principles. Pharmacopsychiatry 2012, 45(Suppl 1):S22-S30.