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Published in: Malaria Journal 1/2015

Open Access 01-12-2015 | Research

Calibration of an intrahost malaria model and parameter ensemble evaluation of a pre-erythrocytic vaccine

Authors: Kevin A McCarthy, Edward A Wenger, Grace H Huynh, Philip A Eckhoff

Published in: Malaria Journal | Issue 1/2015

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Abstract

Background

A pre-erythrocytic vaccine could provide a useful tool for burden reduction and eventual eradication of malaria. Mathematical malaria models provide a mechanism for evaluating the effective burden reduction across a range of transmission conditions where such a vaccine might be deployed.

Methods

The EMOD model is an individual-based model of malaria transmission dynamics, including vector lifecycles and species-specific behaviour, coupled to a mechanistic intrahost model of malaria parasite and host immune system dynamics. The present work describes the extension of the EMOD model to include diagnoses of severe malaria and iterative calibration of the immune system parameters and parasite antigenic variation to age-stratified prevalence, incidence and severe disease incidence data obtained from multiple regions with broadly varying transmission conditions in Africa. An ensemble of calibrated model parameter sets is then employed to evaluate the potential impact of routine immunization with a pre-erythrocytic vaccine.

Results

The reduction in severe malaria burden exhibits a broad peak at moderate transmission conditions. Under sufficiently intense transmission, a vaccine that reduces but does not eliminate the probability of acquisition from a single challenge bite may delay infections but produces minimal or no net reduction. Conversely, under sufficiently weak transmission conditions, a vaccine can provide a high fractional reduction but avert a relatively low absolute number of cases due to low baseline burden.

Conclusions

Roll-out of routine immunization with pre-erythrocytic malaria vaccines can provide substantial burden reduction across a range of transmission conditions typical to many regions in Africa.
Appendix
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Literature
1.
go back to reference WHO: World Malaria Report: 2013. Geneva: World Health Organization; 2013. WHO: World Malaria Report: 2013. Geneva: World Health Organization; 2013.
2.
go back to reference Akachi Y, Atun R: Effect of investment in malaria control on child mortality in sub-Saharan Africa in 2002–2008. PLoS ONE 2011, 6:e21309. 10.1371/journal.pone.0021309CrossRefPubMedCentralPubMed Akachi Y, Atun R: Effect of investment in malaria control on child mortality in sub-Saharan Africa in 2002–2008. PLoS ONE 2011, 6:e21309. 10.1371/journal.pone.0021309CrossRefPubMedCentralPubMed
3.
go back to reference Lim SS, Fullman N, Stokes A, Ravishankar N, Masiye F, Murray CJL, Gakidou E: Net benefits: a multicountry analysis of observational data examining associations between insecticide-treated mosquito nets and health outcomes. PLoS Med 2011, 8:e1001091. 10.1371/journal.pmed.1001091CrossRefPubMedCentralPubMed Lim SS, Fullman N, Stokes A, Ravishankar N, Masiye F, Murray CJL, Gakidou E: Net benefits: a multicountry analysis of observational data examining associations between insecticide-treated mosquito nets and health outcomes. PLoS Med 2011, 8:e1001091. 10.1371/journal.pmed.1001091CrossRefPubMedCentralPubMed
4.
go back to reference Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI: The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature 2005, 434:214–217. 10.1038/nature03342CrossRefPubMedCentralPubMed Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI: The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature 2005, 434:214–217. 10.1038/nature03342CrossRefPubMedCentralPubMed
6.
go back to reference Eckhoff PA: Malaria parasite diversity and transmission intensity affect development of parasitological immunity in a mathematical model. Malar J 2012, 11:419. 10.1186/1475-2875-11-419CrossRefPubMedCentralPubMed Eckhoff PA: Malaria parasite diversity and transmission intensity affect development of parasitological immunity in a mathematical model. Malar J 2012, 11:419. 10.1186/1475-2875-11-419CrossRefPubMedCentralPubMed
7.
go back to reference Eckhoff P: Mathematical models of within-host and transmission dynamics to determine effects of malaria interventions in a variety of transmission settings. Am J Trop Med Hyg 2013, 88:817–827. 10.4269/ajtmh.12-0007CrossRefPubMedCentralPubMed Eckhoff P: Mathematical models of within-host and transmission dynamics to determine effects of malaria interventions in a variety of transmission settings. Am J Trop Med Hyg 2013, 88:817–827. 10.4269/ajtmh.12-0007CrossRefPubMedCentralPubMed
8.
go back to reference 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. 10.1371/journal.pone.0044950CrossRefPubMedCentralPubMed 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. 10.1371/journal.pone.0044950CrossRefPubMedCentralPubMed
9.
10.
go back to reference Girard MP, Reed ZH, Friede M, Kieny MP: A review of human vaccine research and development: malaria. Vaccine 2007, 25:1567–1580. 10.1016/j.vaccine.2006.09.074CrossRefPubMed Girard MP, Reed ZH, Friede M, Kieny MP: A review of human vaccine research and development: malaria. Vaccine 2007, 25:1567–1580. 10.1016/j.vaccine.2006.09.074CrossRefPubMed
12.
go back to reference Hemingway J, Ranson H: Insecticide resistance in insect vectors of human disease. Annu Rev Entomol 2000, 45:371–391. 10.1146/annurev.ento.45.1.371CrossRefPubMed Hemingway J, Ranson H: Insecticide resistance in insect vectors of human disease. Annu Rev Entomol 2000, 45:371–391. 10.1146/annurev.ento.45.1.371CrossRefPubMed
13.
go back to reference RTS,S Clinical Trials Partnership: Efficacy and safety of the RTS,S/AS01 malaria vaccine during 18 months after vaccination: a phase 3 randomized, controlled trial in children and young infants at 11 African sites. PLoS Med 2014, 11:e1001685. 10.1371/journal.pmed.1001685CrossRef RTS,S Clinical Trials Partnership: Efficacy and safety of the RTS,S/AS01 malaria vaccine during 18 months after vaccination: a phase 3 randomized, controlled trial in children and young infants at 11 African sites. PLoS Med 2014, 11:e1001685. 10.1371/journal.pmed.1001685CrossRef
14.
go back to reference Olotu AI Ph.D. Thesis. In Long Term Efficacy of a Pre-Erythrocytic Malaria Vaccine and Correlates of Protection in Children Residing in a Malaria Endemic Country. University of Oxford; 2013. Olotu AI Ph.D. Thesis. In Long Term Efficacy of a Pre-Erythrocytic Malaria Vaccine and Correlates of Protection in Children Residing in a Malaria Endemic Country. University of Oxford; 2013.
15.
go back to reference White MT, Bejon P, Olotu A, Griffin JT, Bojang K, Lusingu J, Salim N, Abdulla S, Otsyula N, Agnandji ST, Lell B, Asante KP, Owusu-Agyei S, Mahama E, Agbenyega T, Ansong D, Sacarlal J, Aponte JJ, Ghani AC: A combined analysis of immunogenicity, antibody kinetics and vaccine efficacy from phase 2 trials of the RTS,S malaria vaccine. BMC Med 2014, 12:117.CrossRefPubMedCentralPubMed White MT, Bejon P, Olotu A, Griffin JT, Bojang K, Lusingu J, Salim N, Abdulla S, Otsyula N, Agnandji ST, Lell B, Asante KP, Owusu-Agyei S, Mahama E, Agbenyega T, Ansong D, Sacarlal J, Aponte JJ, Ghani AC: A combined analysis of immunogenicity, antibody kinetics and vaccine efficacy from phase 2 trials of the RTS,S malaria vaccine. BMC Med 2014, 12:117.CrossRefPubMedCentralPubMed
16.
go back to reference Regules JA, Cummings JF, Ockenhouse CF: The RTS, S vaccine candidate for malaria. Expert Rev Vaccines 2011, 10:589–599. 10.1586/erv.11.57CrossRefPubMed Regules JA, Cummings JF, Ockenhouse CF: The RTS, S vaccine candidate for malaria. Expert Rev Vaccines 2011, 10:589–599. 10.1586/erv.11.57CrossRefPubMed
17.
go back to reference Konaté AT, Yaro JB, Ouédraogo AZ, Diarra A, Gansané A, Soulama I, Kangoyé DT, Kaboré Y, Ouédraogo E, Ouédraogo A, Tiono AB, Ouédraogo IN, Chandramohan D, Cousens S, Milligan PJ, Sirima SB, Greenwood BM, Diallo DA: Morbidity from malaria in children in the year after they had received intermittent preventive treatment of malaria: a randomised trial. PLoS ONE 2011, 6:e23391. 10.1371/journal.pone.0023391CrossRefPubMedCentralPubMed Konaté AT, Yaro JB, Ouédraogo AZ, Diarra A, Gansané A, Soulama I, Kangoyé DT, Kaboré Y, Ouédraogo E, Ouédraogo A, Tiono AB, Ouédraogo IN, Chandramohan D, Cousens S, Milligan PJ, Sirima SB, Greenwood BM, Diallo DA: Morbidity from malaria in children in the year after they had received intermittent preventive treatment of malaria: a randomised trial. PLoS ONE 2011, 6:e23391. 10.1371/journal.pone.0023391CrossRefPubMedCentralPubMed
18.
go back to reference Aponte JJ, Menendez C, Schellenberg D, Kahigwa E, Mshinda H, Vountasou P, Tanner M, Alonso PL: Age interactions in the development of naturally acquired immunity to Plasmodium falciparum and its clinical presentation. PLoS Med 2007, 4:e242. 10.1371/journal.pmed.0040242CrossRefPubMedCentralPubMed Aponte JJ, Menendez C, Schellenberg D, Kahigwa E, Mshinda H, Vountasou P, Tanner M, Alonso PL: Age interactions in the development of naturally acquired immunity to Plasmodium falciparum and its clinical presentation. PLoS Med 2007, 4:e242. 10.1371/journal.pmed.0040242CrossRefPubMedCentralPubMed
19.
go back to reference Maire N, Tediosi F, Ross A, Smith T: Predictions of the epidemiologic impact of introducing a pre-erythrocytic vaccine into the expanded program on immunization in sub-Saharan Africa. Am J Trop Med Hyg 2006,75(2 suppl):111–118.PubMed Maire N, Tediosi F, Ross A, Smith T: Predictions of the epidemiologic impact of introducing a pre-erythrocytic vaccine into the expanded program on immunization in sub-Saharan Africa. Am J Trop Med Hyg 2006,75(2 suppl):111–118.PubMed
20.
go back to reference Smith T, Killeen GF, Maire N, Ross A, Molineaux L, Tediosi F, Hutton G, Utzinger J, Dietz K, Tanner M: Mathematical modeling of the impact of malaria vaccines on the clinical epidemiology and natural history of Plasmodium falciparum malaria: overview. Am J Trop Med Hyg 2006,75(2 suppl):1–10.PubMed Smith T, Killeen GF, Maire N, Ross A, Molineaux L, Tediosi F, Hutton G, Utzinger J, Dietz K, Tanner M: Mathematical modeling of the impact of malaria vaccines on the clinical epidemiology and natural history of Plasmodium falciparum malaria: overview. Am J Trop Med Hyg 2006,75(2 suppl):1–10.PubMed
21.
go back to reference Horrocks P, Kyes SA, Bull PC, Deitsch KW: Molecular Aspects of Antigenic Variation in Plasmodium falciparum . In Mol Approaches Malar Edited by: Sherman IW. 2005, 399–415. Horrocks P, Kyes SA, Bull PC, Deitsch KW: Molecular Aspects of Antigenic Variation in Plasmodium falciparum . In Mol Approaches Malar Edited by: Sherman IW. 2005, 399–415.
22.
go back to reference Recker M, Buckee CO, Serazin A, Kyes S, Pinches R, Christodoulou Z, Springer AL, Gupta S, Newbold CI: Antigenic variation in Plasmodium falciparum malaria involves a highly structured switching pattern. PLoS Pathog 2011, 7:e1001306. 10.1371/journal.ppat.1001306CrossRefPubMedCentralPubMed Recker M, Buckee CO, Serazin A, Kyes S, Pinches R, Christodoulou Z, Springer AL, Gupta S, Newbold CI: Antigenic variation in Plasmodium falciparum malaria involves a highly structured switching pattern. PLoS Pathog 2011, 7:e1001306. 10.1371/journal.ppat.1001306CrossRefPubMedCentralPubMed
23.
go back to reference Holder AA, Guevara Patiño JA, Uthaipibull C, Syed SE, Ling IT, Scott-Finnigan T, Blackman MJ: Merozoite surface protein 1, immune evasion, and vaccines against asexual blood stage malaria. Parassitologia 1999, 41:409–414.PubMed Holder AA, Guevara Patiño JA, Uthaipibull C, Syed SE, Ling IT, Scott-Finnigan T, Blackman MJ: Merozoite surface protein 1, immune evasion, and vaccines against asexual blood stage malaria. Parassitologia 1999, 41:409–414.PubMed
24.
go back to reference Molineaux L, Gramiccia G: The Garki Project : Research on the Epidemiology and Control of Malaria in the Sudan Savanna of West Africa. Geneva: World Health Organization; 1980:311. Molineaux L, Gramiccia G: The Garki Project : Research on the Epidemiology and Control of Malaria in the Sudan Savanna of West Africa. Geneva: World Health Organization; 1980:311.
25.
go back to reference Smith T, Charlwood JD, Kihonda J, Mwankusye S, Billingsley P, Meuwissen J, Lyimo E, Takken W, Teuscher T, Tanner M: Absence of seasonal variation in malaria parasitaemia in an area of intense seasonal transmission. Acta Trop 1993, 54:55–72. 10.1016/0001-706X(93)90068-MCrossRefPubMed Smith T, Charlwood JD, Kihonda J, Mwankusye S, Billingsley P, Meuwissen J, Lyimo E, Takken W, Teuscher T, Tanner M: Absence of seasonal variation in malaria parasitaemia in an area of intense seasonal transmission. Acta Trop 1993, 54:55–72. 10.1016/0001-706X(93)90068-MCrossRefPubMed
26.
go back to reference Rogier C, Tall A, Diagne N, Fontenille D, Spiegel A, Trape JF: Plasmodium falciparum clinical malaria: lessons from longitudinal studies in Senegal. Parassitologia 1999, 41:255–259.PubMed Rogier C, Tall A, Diagne N, Fontenille D, Spiegel A, Trape JF: Plasmodium falciparum clinical malaria: lessons from longitudinal studies in Senegal. Parassitologia 1999, 41:255–259.PubMed
27.
go back to reference Trape JF, Rogier C, Konate L, Diagne N, Bouganali H, Canque B, Legros F, Badji A, Ndiaye G, Ndiaye P: The Dielmo project: a longitudinal study of natural malaria infection and the mechanisms of protective immunity in a community living in a holoendemic area of Senegal. Am J Trop Med Hyg 1994, 51:123–137.PubMed Trape JF, Rogier C, Konate L, Diagne N, Bouganali H, Canque B, Legros F, Badji A, Ndiaye G, Ndiaye P: The Dielmo project: a longitudinal study of natural malaria infection and the mechanisms of protective immunity in a community living in a holoendemic area of Senegal. Am J Trop Med Hyg 1994, 51:123–137.PubMed
28.
go back to reference Rogier C, Trape J-F: Etude de l’acquisition de la prémunition en zones d’holo- et de méso-endémie palustre et Dielmo et a Ndiop (Sénégal): Résultats préliminaires, 1990–1994. Méd Trop (Marseille) 1995, 55:71–76. Rogier C, Trape J-F: Etude de l’acquisition de la prémunition en zones d’holo- et de méso-endémie palustre et Dielmo et a Ndiop (Sénégal): Résultats préliminaires, 1990–1994. Méd Trop (Marseille) 1995, 55:71–76.
29.
go back to reference Smith T, Schellenberg JA, Hayes R: Attributable fraction estimates and case definitions for malaria in endemic areas. Stat Med 1994, 13:2345–2358. 10.1002/sim.4780132206CrossRefPubMed Smith T, Schellenberg JA, Hayes R: Attributable fraction estimates and case definitions for malaria in endemic areas. Stat Med 1994, 13:2345–2358. 10.1002/sim.4780132206CrossRefPubMed
30.
go back to reference Snow RW, Craig M, Deichmann U, Marsh K: Estimating mortality, morbidity and disability due to malaria among Africa’s non-pregnant population. Bull World Health Organ 1999, 77:624–640.PubMedCentralPubMed Snow RW, Craig M, Deichmann U, Marsh K: Estimating mortality, morbidity and disability due to malaria among Africa’s non-pregnant population. Bull World Health Organ 1999, 77:624–640.PubMedCentralPubMed
31.
go back to reference Patil AP, Okiro EA, Gething PW, Guerra CA, Sharma SK, Snow RW, Hay SI: Defining the relationship between Plasmodium falciparum parasite rate and clinical disease: statistical models for disease burden estimation. Malar J 2009, 8:186. 10.1186/1475-2875-8-186CrossRefPubMedCentralPubMed Patil AP, Okiro EA, Gething PW, Guerra CA, Sharma SK, Snow RW, Hay SI: Defining the relationship between Plasmodium falciparum parasite rate and clinical disease: statistical models for disease burden estimation. Malar J 2009, 8:186. 10.1186/1475-2875-8-186CrossRefPubMedCentralPubMed
32.
go back to reference Carnevale P, Frezil J, Bosseno M, Lepont F, Lancien J: Study of agressivity of Anopheles gambiae in relation to age and sex. Bull World Health Organ 1978, 56:147–154.PubMedCentralPubMed Carnevale P, Frezil J, Bosseno M, Lepont F, Lancien J: Study of agressivity of Anopheles gambiae in relation to age and sex. Bull World Health Organ 1978, 56:147–154.PubMedCentralPubMed
33.
go back to reference Port GR, Boreham PFL, Bryan JH: The relationship of host size to feeding by mosquitoes of the Anopheles gambiae Giles complex (Diptera: Culicidae). Bull Entomol Res 1980, 70:133–144. 10.1017/S0007485300009834CrossRef Port GR, Boreham PFL, Bryan JH: The relationship of host size to feeding by mosquitoes of the Anopheles gambiae Giles complex (Diptera: Culicidae). Bull Entomol Res 1980, 70:133–144. 10.1017/S0007485300009834CrossRef
34.
go back to reference Smith T, Maire N, Dietz K, Killeen GF, Vounatsou P, Molineaux L, Tanner M: Relationship between the entomologic inoculation rate and the force of infection for Plasmodium falciparum malaria. Am J Trop Med Hyg 2006,75(2 Suppl):11–18.PubMed Smith T, Maire N, Dietz K, Killeen GF, Vounatsou P, Molineaux L, Tanner M: Relationship between the entomologic inoculation rate and the force of infection for Plasmodium falciparum malaria. Am J Trop Med Hyg 2006,75(2 Suppl):11–18.PubMed
35.
go back to reference Raftery AE, Bao L: Estimating and projecting trends in HIV/AIDS generalized epidemics using incremental mixture importance sampling. Biometrics 2010, 66:1162–1173. 10.1111/j.1541-0420.2010.01399.xCrossRefPubMedCentralPubMed Raftery AE, Bao L: Estimating and projecting trends in HIV/AIDS generalized epidemics using incremental mixture importance sampling. Biometrics 2010, 66:1162–1173. 10.1111/j.1541-0420.2010.01399.xCrossRefPubMedCentralPubMed
36.
go back to reference Steele RJ, Raftery AE, Emond MJ: Computing normalizing constants for finite mixture models via incremental mixture importance sampling (IMIS. J Comput Graph Stat 2006, 15:712–734. 10.1198/106186006X132358CrossRef Steele RJ, Raftery AE, Emond MJ: Computing normalizing constants for finite mixture models via incremental mixture importance sampling (IMIS. J Comput Graph Stat 2006, 15:712–734. 10.1198/106186006X132358CrossRef
37.
go back to reference Snow RW, Omumbo JA, Lowe B, Molyneux CS, Obiero JO, Palmer A, Weber MW, Pinder M, Nahlen B, Obonyo C, Newbold C, Gupta S, Marsh K: Relation between severe malaria morbidity in children and level of Plasmodium falciparum transmission in Africa. Lancet 1997, 349:1650–1654. 10.1016/S0140-6736(97)02038-2CrossRefPubMed Snow RW, Omumbo JA, Lowe B, Molyneux CS, Obiero JO, Palmer A, Weber MW, Pinder M, Nahlen B, Obonyo C, Newbold C, Gupta S, Marsh K: Relation between severe malaria morbidity in children and level of Plasmodium falciparum transmission in Africa. Lancet 1997, 349:1650–1654. 10.1016/S0140-6736(97)02038-2CrossRefPubMed
38.
go back to reference Okiro EA, Al-Taiar A, Reyburn H, Idro R, Berkley JA, Snow RW: Age patterns of severe paediatric malaria and their relationship to Plasmodium falciparum transmission intensity. Malar J 2009, 8:4. 10.1186/1475-2875-8-4CrossRefPubMedCentralPubMed Okiro EA, Al-Taiar A, Reyburn H, Idro R, Berkley JA, Snow RW: Age patterns of severe paediatric malaria and their relationship to Plasmodium falciparum transmission intensity. Malar J 2009, 8:4. 10.1186/1475-2875-8-4CrossRefPubMedCentralPubMed
39.
go back to reference Gupta S, Snow RW, Donnelly CA, Marsh K, Newbold C: Immunity to non-cerebral severe malaria is acquired after one or two infections. Nat Med 1999, 5:340–343. 10.1038/6560CrossRefPubMed Gupta S, Snow RW, Donnelly CA, Marsh K, Newbold C: Immunity to non-cerebral severe malaria is acquired after one or two infections. Nat Med 1999, 5:340–343. 10.1038/6560CrossRefPubMed
40.
go back to reference Gething PW, Patil AP, Smith DL, Guerra CA, Elyazar IR, Johnston GL, Tatem AJ, Hay SI: A new world malaria map: Plasmodium falciparum endemicity in 2010. Malar J 2011, 10:378. 10.1186/1475-2875-10-378CrossRefPubMedCentralPubMed Gething PW, Patil AP, Smith DL, Guerra CA, Elyazar IR, Johnston GL, Tatem AJ, Hay SI: A new world malaria map: Plasmodium falciparum endemicity in 2010. Malar J 2011, 10:378. 10.1186/1475-2875-10-378CrossRefPubMedCentralPubMed
41.
go back to reference Smith DL, Dushoff J, Snow RW, Hay SI: The entomological inoculation rate and Plasmodium falciparum infection in African children. Nature 2005, 438:492–495. 10.1038/nature04024CrossRefPubMedCentralPubMed Smith DL, Dushoff J, Snow RW, Hay SI: The entomological inoculation rate and Plasmodium falciparum infection in African children. Nature 2005, 438:492–495. 10.1038/nature04024CrossRefPubMedCentralPubMed
42.
go back to reference Griffin JT, Ferguson NM, Ghani AC: Estimates of the changing age-burden of Plasmodium falciparum malaria disease in sub-Saharan Africa. Nat Commun 2014, 5:3136.CrossRefPubMedCentralPubMed Griffin JT, Ferguson NM, Ghani AC: Estimates of the changing age-burden of Plasmodium falciparum malaria disease in sub-Saharan Africa. Nat Commun 2014, 5:3136.CrossRefPubMedCentralPubMed
43.
go back to reference Woolhouse MEJ, Dye C, Etard J-F, Smith T, Charlwood JD, Garnett GP, Hagan P, Hii JLK, Ndhlovu PD, Quinnell RJ, Watts CH, Chandiwana SK, Anderson RM: Heterogeneities in the transmission of infectious agents: implications for the design of control programs. Proc Natl Acad Sci U S A 1997, 94:338–342. 10.1073/pnas.94.1.338CrossRefPubMedCentralPubMed Woolhouse MEJ, Dye C, Etard J-F, Smith T, Charlwood JD, Garnett GP, Hagan P, Hii JLK, Ndhlovu PD, Quinnell RJ, Watts CH, Chandiwana SK, Anderson RM: Heterogeneities in the transmission of infectious agents: implications for the design of control programs. Proc Natl Acad Sci U S A 1997, 94:338–342. 10.1073/pnas.94.1.338CrossRefPubMedCentralPubMed
44.
go back to reference Walther M, Woodruff J, Edele F, Jeffries D, Tongren JE, King E, Andrews L, Bejon P, Gilbert SC, Souza JBD, Sinden R, Hill AVS, Riley EM: Innate immune responses to human malaria: heterogeneous cytokine responses to blood-stage Plasmodium falciparum correlate with parasitological and clinical outcomes. J Immunol 2006, 177:5736–5745. 10.4049/jimmunol.177.8.5736CrossRefPubMed Walther M, Woodruff J, Edele F, Jeffries D, Tongren JE, King E, Andrews L, Bejon P, Gilbert SC, Souza JBD, Sinden R, Hill AVS, Riley EM: Innate immune responses to human malaria: heterogeneous cytokine responses to blood-stage Plasmodium falciparum correlate with parasitological and clinical outcomes. J Immunol 2006, 177:5736–5745. 10.4049/jimmunol.177.8.5736CrossRefPubMed
45.
go back to reference White MT, Griffin JT, Drakeley CJ, Ghani AC: Heterogeneity in malaria exposure and vaccine response: implications for the interpretation of vaccine efficacy trials. Malar J 2010, 9:82. 10.1186/1475-2875-9-82CrossRefPubMedCentralPubMed White MT, Griffin JT, Drakeley CJ, Ghani AC: Heterogeneity in malaria exposure and vaccine response: implications for the interpretation of vaccine efficacy trials. Malar J 2010, 9:82. 10.1186/1475-2875-9-82CrossRefPubMedCentralPubMed
Metadata
Title
Calibration of an intrahost malaria model and parameter ensemble evaluation of a pre-erythrocytic vaccine
Authors
Kevin A McCarthy
Edward A Wenger
Grace H Huynh
Philip A Eckhoff
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2015
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-14-6

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