Immunoepidemiology of malaria Klaus Dietz Department of Medical
![Immuno-epidemiology of malaria Klaus Dietz Department of Medical Biometry University of Tübingen, Germany DIMACS Immuno-epidemiology of malaria Klaus Dietz Department of Medical Biometry University of Tübingen, Germany DIMACS](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-1.jpg)
![Outline • • • What is immuno-epidemiology? What is malaria? Why model malaria immunity? Outline • • • What is immuno-epidemiology? What is malaria? Why model malaria immunity?](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-2.jpg)
![Serological surveys as immuno-epidemiological tools Desowitz RS, Saave JJ, Stein B. The application of Serological surveys as immuno-epidemiological tools Desowitz RS, Saave JJ, Stein B. The application of](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-3.jpg)
![A theoretical framework for immuno-epidemiology Woolhouse, M. E. J. et al. : Acquired immunology A theoretical framework for immuno-epidemiology Woolhouse, M. E. J. et al. : Acquired immunology](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-4.jpg)
![Hellriegel, B. : Immunoepidemiology-bridging the gap between immunology and epidemiology. Trends in Parasitology, 17, Hellriegel, B. : Immunoepidemiology-bridging the gap between immunology and epidemiology. Trends in Parasitology, 17,](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-5.jpg)
![A cartoon of immuno-epidemiological models Parasite density Immunity level Morbidity level A cartoon of immuno-epidemiological models Parasite density Immunity level Morbidity level](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-6.jpg)
![STI project on the mathematical modeling of the impact of malaria vaccines on the STI project on the mathematical modeling of the impact of malaria vaccines on the](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-7.jpg)
![Network Computing Network Computing](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-8.jpg)
![Volunteer Computing Project Volunteer Computing Project](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-9.jpg)
![Malaria cycle Source: Wellcome Trust Malaria cycle Source: Wellcome Trust](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-10.jpg)
![Infected Red Blood Cells (IREs) by asexual (red) and sexual (green) parasites in Patient Infected Red Blood Cells (IREs) by asexual (red) and sexual (green) parasites in Patient](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-11.jpg)
![n = 54; mean 212 days, median 216 days n = 54; mean 212 days, median 216 days](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-12.jpg)
![Present geographical distribution of malaria Present geographical distribution of malaria](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-13.jpg)
![The challenge of malaria The President And Mrs. Bush Will Host The White House The challenge of malaria The President And Mrs. Bush Will Host The White House](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-14.jpg)
![Growth of the yearly number of malaria publications Doubling time: 10 years and 7 Growth of the yearly number of malaria publications Doubling time: 10 years and 7](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-15.jpg)
![Why model malaria immunity? • Not necessary, if one is aiming for eradication: • Why model malaria immunity? • Not necessary, if one is aiming for eradication: •](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-16.jpg)
![Original Eradication Plans • Interruption of transmission of main species infecting humans by DDT Original Eradication Plans • Interruption of transmission of main species infecting humans by DDT](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-17.jpg)
![Pampana: Textbook on malaria eradication • If malaria eradication will be achieved it will Pampana: Textbook on malaria eradication • If malaria eradication will be achieved it will](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-18.jpg)
![(graph by Martin Eichner) hypo- meso- hyper- holo-endemic Cerebral malaria incidence (per 1000 per (graph by Martin Eichner) hypo- meso- hyper- holo-endemic Cerebral malaria incidence (per 1000 per](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-19.jpg)
![Points of attack of potential malaria vaccines Smith et al (2006) Points of attack of potential malaria vaccines Smith et al (2006)](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-20.jpg)
![Malaria immunity models • Dietz, K: Mathematical models for transmission and control of malaria. Malaria immunity models • Dietz, K: Mathematical models for transmission and control of malaria.](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-21.jpg)
![Ronald Ross (1857 -1932) Second Nobel price in Medicine in 1902 Ronald Ross (1857 -1932) Second Nobel price in Medicine in 1902](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-22.jpg)
![Infection without (Ross) and with (Macdonald) superinfections Ross („premunition“) 0 1 Macdonald 0 1 Infection without (Ross) and with (Macdonald) superinfections Ross („premunition“) 0 1 Macdonald 0 1](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-23.jpg)
![Age-specific prevalence Age-specific prevalence](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-24.jpg)
![Prevalence by age Prevalence by age](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-25.jpg)
![Implications of unrealistic assumptions about the strength of immunity • Underestimating the strength of Implications of unrealistic assumptions about the strength of immunity • Underestimating the strength of](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-26.jpg)
![Garki Model (Dietz, Molineaux, Thomas, 1974) Garki Book (Molineaux L and Gramiccia G, 1980 Garki Model (Dietz, Molineaux, Thomas, 1974) Garki Book (Molineaux L and Gramiccia G, 1980](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-27.jpg)
![Garki model fit Garki model fit](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-28.jpg)
![Fit to Garki data of the STI project Fit to Garki data of the STI project](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-29.jpg)
![Prevalence by vectorial capacity Prevalence by vectorial capacity](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-30.jpg)
![Gupta, S. and Day, K. P. : A theoretical framework for the immunoepidemiology of Gupta, S. and Day, K. P. : A theoretical framework for the immunoepidemiology of](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-31.jpg)
![„Might malaria yield to mathematics“ (Economist, March 12 th 1994) „Recent epidemiological work suggests „Might malaria yield to mathematics“ (Economist, March 12 th 1994) „Recent epidemiological work suggests](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-32.jpg)
![Innate and adaptive immunity Stevenson and Riley (2004) • Research on the immunology of Innate and adaptive immunity Stevenson and Riley (2004) • Research on the immunology of](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-33.jpg)
![](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-34.jpg)
![Fig 1 A Fig 1 A](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-35.jpg)
![Fig 1 B Fig 1 B](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-36.jpg)
![Fig 1 C Fig 1 C](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-37.jpg)
![Correlations between innate immunity threshold, parasite growth rate and peak density Correlations between innate immunity threshold, parasite growth rate and peak density](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-38.jpg)
![Correlation between innate and adaptive immunity thresholds and between two parameters for adaptive immunity Correlation between innate and adaptive immunity thresholds and between two parameters for adaptive immunity](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-39.jpg)
![Feverthresholds Feverthresholds](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-40.jpg)
![Vaccine effect on initial multiplication factor Vaccine effect on initial multiplication factor](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-41.jpg)
![Fig 3 B A 4 3 2 1 0 Fig 3 B A 4 3 2 1 0](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-42.jpg)
![Vaccine efficacy Vaccine efficacy](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-43.jpg)
![Conclusions from the within-host model for the first wave • The 800 data points Conclusions from the within-host model for the first wave • The 800 data points](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-44.jpg)
![Concluding remarks • Historic data (neurosyphilis patients, Garki project) are still relevant today and Concluding remarks • Historic data (neurosyphilis patients, Garki project) are still relevant today and](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-45.jpg)
![Acknowledgements • Louis Molineaux, Geneva • Tom Smith and his team at the STI, Acknowledgements • Louis Molineaux, Geneva • Tom Smith and his team at the STI,](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-46.jpg)
- Slides: 46
![Immunoepidemiology of malaria Klaus Dietz Department of Medical Biometry University of Tübingen Germany DIMACS Immuno-epidemiology of malaria Klaus Dietz Department of Medical Biometry University of Tübingen, Germany DIMACS](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-1.jpg)
Immuno-epidemiology of malaria Klaus Dietz Department of Medical Biometry University of Tübingen, Germany DIMACS Worksop 11 -13 December 2006
![Outline What is immunoepidemiology What is malaria Why model malaria immunity Outline • • • What is immuno-epidemiology? What is malaria? Why model malaria immunity?](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-2.jpg)
Outline • • • What is immuno-epidemiology? What is malaria? Why model malaria immunity? Malaria immunity models: a brief history A within-host malaria model Concluding remarks
![Serological surveys as immunoepidemiological tools Desowitz RS Saave JJ Stein B The application of Serological surveys as immuno-epidemiological tools Desowitz RS, Saave JJ, Stein B. The application of](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-3.jpg)
Serological surveys as immuno-epidemiological tools Desowitz RS, Saave JJ, Stein B. The application of the indirect haemagglutination test in recent studies on the immuno-epidemiology of human malaria and the immune response in experimental malaria. Mil Med. , 131: 1157 -1166 (1966). Suzuki M. Malaria immuno-epidemiology: a trial to link field study with basic science. Gaoxiong Yi Xue Ke Xue Za Zhi. 7: 224 -232 (1991). . . malaria serological assessment was carried out in endemic areas in Haiti, Indonesia, Sudan and in Brazil Amazon. The serological survey was useful in finding latent foci in a controlled area, for the assessment of past epidemics, . .
![A theoretical framework for immunoepidemiology Woolhouse M E J et al Acquired immunology A theoretical framework for immuno-epidemiology Woolhouse, M. E. J. et al. : Acquired immunology](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-4.jpg)
A theoretical framework for immuno-epidemiology Woolhouse, M. E. J. et al. : Acquired immunology and epidemiology of Schistosoma haematobium. , Nature 351, 757759, 1991 („Acquisition of this immunity seems to be related to the cumulative effects of repeated infection and provides only partial protection. These characteristics are consistent with immuno-epidemiological data for both S. mansoni and S. haematobium infections of humans. “)
![Hellriegel B Immunoepidemiologybridging the gap between immunology and epidemiology Trends in Parasitology 17 Hellriegel, B. : Immunoepidemiology-bridging the gap between immunology and epidemiology. Trends in Parasitology, 17,](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-5.jpg)
Hellriegel, B. : Immunoepidemiology-bridging the gap between immunology and epidemiology. Trends in Parasitology, 17, 102 -106, 2001 „Immunoepidemiology combines individual - and population-oriented approaches to create new perspectives. It examines how inter-individual differences in immune responses affect the population dynamics of micro- and macro-parasites to produce the epidemiological patterns of infection observed in heterogeneous host populations. “
![A cartoon of immunoepidemiological models Parasite density Immunity level Morbidity level A cartoon of immuno-epidemiological models Parasite density Immunity level Morbidity level](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-6.jpg)
A cartoon of immuno-epidemiological models Parasite density Immunity level Morbidity level
![STI project on the mathematical modeling of the impact of malaria vaccines on the STI project on the mathematical modeling of the impact of malaria vaccines on the](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-7.jpg)
STI project on the mathematical modeling of the impact of malaria vaccines on the clinical epidemiology and natural history of Plasmodium falciparum malaria Thomas A. Smith and team • Many millions of simulation runs, each in the order of hours • Need for supercomputing
![Network Computing Network Computing](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-8.jpg)
Network Computing
![Volunteer Computing Project Volunteer Computing Project](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-9.jpg)
Volunteer Computing Project
![Malaria cycle Source Wellcome Trust Malaria cycle Source: Wellcome Trust](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-10.jpg)
Malaria cycle Source: Wellcome Trust
![Infected Red Blood Cells IREs by asexual red and sexual green parasites in Patient Infected Red Blood Cells (IREs) by asexual (red) and sexual (green) parasites in Patient](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-11.jpg)
Infected Red Blood Cells (IREs) by asexual (red) and sexual (green) parasites in Patient G 141
![n 54 mean 212 days median 216 days n = 54; mean 212 days, median 216 days](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-12.jpg)
n = 54; mean 212 days, median 216 days
![Present geographical distribution of malaria Present geographical distribution of malaria](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-13.jpg)
Present geographical distribution of malaria
![The challenge of malaria The President And Mrs Bush Will Host The White House The challenge of malaria The President And Mrs. Bush Will Host The White House](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-14.jpg)
The challenge of malaria The President And Mrs. Bush Will Host The White House Summit On Malaria On December 14, 2006, In Washington, DC, To Discuss And Highlight Measures For Combating This Preventable Disease In June, President Bush announced a new commitment to combat malaria. His proposal calls for an additional $1. 2 billion over the next five years. The money will pay for insecticide-treated nets, it will allow for indoor spraying against mosquitoes, and it will provide effective new combination drugs to treat malaria. Our goal with this new funding is to reach more than 175 million people in 15 nations. (1. 37 $/Person/year)
![Growth of the yearly number of malaria publications Doubling time 10 years and 7 Growth of the yearly number of malaria publications Doubling time: 10 years and 7](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-15.jpg)
Growth of the yearly number of malaria publications Doubling time: 10 years and 7 months
![Why model malaria immunity Not necessary if one is aiming for eradication Why model malaria immunity? • Not necessary, if one is aiming for eradication: •](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-16.jpg)
Why model malaria immunity? • Not necessary, if one is aiming for eradication: • Macdonald, G. : Theory of the eradication of malaria. Bull. WHO 15, 369 -387, 1956. • WHO global malaria eradication campaign 1955
![Original Eradication Plans Interruption of transmission of main species infecting humans by DDT Original Eradication Plans • Interruption of transmission of main species infecting humans by DDT](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-17.jpg)
Original Eradication Plans • Interruption of transmission of main species infecting humans by DDT spraying • Malaria disappears spontaneously in under 3 years Source: Gabaldon
![Pampana Textbook on malaria eradication If malaria eradication will be achieved it will Pampana: Textbook on malaria eradication • If malaria eradication will be achieved it will](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-18.jpg)
Pampana: Textbook on malaria eradication • If malaria eradication will be achieved it will be first of all due to the computer • Macdonald: DDT spraying and mass drug administration every two months will interrupt malaria transmission in Africa
![graph by Martin Eichner hypo meso hyper holoendemic Cerebral malaria incidence per 1000 per (graph by Martin Eichner) hypo- meso- hyper- holo-endemic Cerebral malaria incidence (per 1000 per](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-19.jpg)
(graph by Martin Eichner) hypo- meso- hyper- holo-endemic Cerebral malaria incidence (per 1000 per year) (ages 0 -9 years) 3. 0 Sukuta (Gambia) 2. 5 2. 0 Kilifi N (Kenya) 1. 5 Kilifi S (Kenya) 1. 0 0. 5 Siaya (Kenya) Bakau (Gambia) 0 0 0. 5 1. 0 1. 5 Force of infection (per year) 2. 0 2. 5 Snow et al. (1997) The Lancet
![Points of attack of potential malaria vaccines Smith et al 2006 Points of attack of potential malaria vaccines Smith et al (2006)](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-20.jpg)
Points of attack of potential malaria vaccines Smith et al (2006)
![Malaria immunity models Dietz K Mathematical models for transmission and control of malaria Malaria immunity models • Dietz, K: Mathematical models for transmission and control of malaria.](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-21.jpg)
Malaria immunity models • Dietz, K: Mathematical models for transmission and control of malaria. 10911133 (1988) • Molineaux, L and Dietz, K: Review of intra-host models of malaria. Parassitologia 41: 221 -231 (1999) • Mc. Kenzie, FE and Bossert, WH: An integrated model of Plasmodium falciparum dynamic. J Theor. Biology 232, 411 -426 (2005)
![Ronald Ross 1857 1932 Second Nobel price in Medicine in 1902 Ronald Ross (1857 -1932) Second Nobel price in Medicine in 1902](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-22.jpg)
Ronald Ross (1857 -1932) Second Nobel price in Medicine in 1902
![Infection without Ross and with Macdonald superinfections Ross premunition 0 1 Macdonald 0 1 Infection without (Ross) and with (Macdonald) superinfections Ross („premunition“) 0 1 Macdonald 0 1](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-23.jpg)
Infection without (Ross) and with (Macdonald) superinfections Ross („premunition“) 0 1 Macdonald 0 1 k
![Agespecific prevalence Age-specific prevalence](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-24.jpg)
Age-specific prevalence
![Prevalence by age Prevalence by age](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-25.jpg)
Prevalence by age
![Implications of unrealistic assumptions about the strength of immunity Underestimating the strength of Implications of unrealistic assumptions about the strength of immunity • Underestimating the strength of](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-26.jpg)
Implications of unrealistic assumptions about the strength of immunity • Underestimating the strength of immunity leads to an • underestimate of the basic reproduction number and consequently an • underestimate of the necessary eradication efforts and an • overestimate of the expected control effects
![Garki Model Dietz Molineaux Thomas 1974 Garki Book Molineaux L and Gramiccia G 1980 Garki Model (Dietz, Molineaux, Thomas, 1974) Garki Book (Molineaux L and Gramiccia G, 1980](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-27.jpg)
Garki Model (Dietz, Molineaux, Thomas, 1974) Garki Book (Molineaux L and Gramiccia G, 1980 http: //whqlibdoc. who. int/publications) Garki Data: http: //www. sti. ch/de/forschung/biostatistics/downloads. html
![Garki model fit Garki model fit](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-28.jpg)
Garki model fit
![Fit to Garki data of the STI project Fit to Garki data of the STI project](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-29.jpg)
Fit to Garki data of the STI project
![Prevalence by vectorial capacity Prevalence by vectorial capacity](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-30.jpg)
Prevalence by vectorial capacity
![Gupta S and Day K P A theoretical framework for the immunoepidemiology of Gupta, S. and Day, K. P. : A theoretical framework for the immunoepidemiology of](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-31.jpg)
Gupta, S. and Day, K. P. : A theoretical framework for the immunoepidemiology of Plasmodium falciparum malaria. Parasite Immunology, 16, 361 -370 (1994) 0 1 2 k n
![Might malaria yield to mathematics Economist March 12 th 1994 Recent epidemiological work suggests „Might malaria yield to mathematics“ (Economist, March 12 th 1994) „Recent epidemiological work suggests](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-32.jpg)
„Might malaria yield to mathematics“ (Economist, March 12 th 1994) „Recent epidemiological work suggests that there may be a stronger chance of controlinling malaria than was once thought likely… Comparing the distribution of the strains among people by age with the spread produced by their* model, they found a very close match if the average number of secondary cases caused by a single case was between six and seven. “ *Gupta, Anderson, Day and Trenholme
![Innate and adaptive immunity Stevenson and Riley 2004 Research on the immunology of Innate and adaptive immunity Stevenson and Riley (2004) • Research on the immunology of](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-33.jpg)
Innate and adaptive immunity Stevenson and Riley (2004) • Research on the immunology of malaria has tended to focus on adaptive immunity • Accumulating evidence…indicates a crucial role for innate immune responses in protective immunity to malaria • Innate responses are essential to limit the initial phase of parasite replication, controlling the first wave of parasitemia and allowing the host time to develop specific adaptive responses that will enable the infection to be cleared
![](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-34.jpg)
![Fig 1 A Fig 1 A](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-35.jpg)
Fig 1 A
![Fig 1 B Fig 1 B](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-36.jpg)
Fig 1 B
![Fig 1 C Fig 1 C](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-37.jpg)
Fig 1 C
![Correlations between innate immunity threshold parasite growth rate and peak density Correlations between innate immunity threshold, parasite growth rate and peak density](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-38.jpg)
Correlations between innate immunity threshold, parasite growth rate and peak density
![Correlation between innate and adaptive immunity thresholds and between two parameters for adaptive immunity Correlation between innate and adaptive immunity thresholds and between two parameters for adaptive immunity](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-39.jpg)
Correlation between innate and adaptive immunity thresholds and between two parameters for adaptive immunity
![Feverthresholds Feverthresholds](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-40.jpg)
Feverthresholds
![Vaccine effect on initial multiplication factor Vaccine effect on initial multiplication factor](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-41.jpg)
Vaccine effect on initial multiplication factor
![Fig 3 B A 4 3 2 1 0 Fig 3 B A 4 3 2 1 0](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-42.jpg)
Fig 3 B A 4 3 2 1 0
![Vaccine efficacy Vaccine efficacy](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-43.jpg)
Vaccine efficacy
![Conclusions from the withinhost model for the first wave The 800 data points Conclusions from the within-host model for the first wave • The 800 data points](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-44.jpg)
Conclusions from the within-host model for the first wave • The 800 data points for 100 patients could well be described by a simple model with four interpretable parameters per patient. • All parameters show large variation. • The maximum parasitaemia is mainly controlled by innate immunity. • The benefit of a vaccine targetting the asexual blood stages is expected to be strongly host dependent. • At low immunogenicity the expected vaccine efficacy against severe malaria is much higher than against fever.
![Concluding remarks Historic data neurosyphilis patients Garki project are still relevant today and Concluding remarks • Historic data (neurosyphilis patients, Garki project) are still relevant today and](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-45.jpg)
Concluding remarks • Historic data (neurosyphilis patients, Garki project) are still relevant today and in the future because new data about the natural course of malaria can for ethical reasons no longer be collected. • Estimates for basic reproduction numbers are model dependent. • In spite of the fact that malaria is probably the disease with the largest number of models there is still no generally acceptable model.
![Acknowledgements Louis Molineaux Geneva Tom Smith and his team at the STI Acknowledgements • Louis Molineaux, Geneva • Tom Smith and his team at the STI,](https://slidetodoc.com/presentation_image/2bfb50cb4acca9ca9da189cb4eb14ba6/image-46.jpg)
Acknowledgements • Louis Molineaux, Geneva • Tom Smith and his team at the STI, Basle • Martin Eichner, Günter Raddatz, Tübingen
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