Skip to main content
Top
Published in: Malaria Journal 1/2016

Open Access 01-12-2016 | Research

Quantitative, model-based estimates of variability in the generation and serial intervals of Plasmodium falciparum malaria

Authors: John H. Huber, Geoffrey L. Johnston, Bryan Greenhouse, David L. Smith, T. Alex Perkins

Published in: Malaria Journal | Issue 1/2016

Login to get access

Abstract

Background

The serial interval is a fundamentally important quantity in infectious disease epidemiology that has numerous applications to inferring patterns of transmission from case data. Many of these applications are apropos of efforts to eliminate falciparum malaria from locations throughout the world, yet the serial interval for this disease is poorly understood quantitatively.

Methods

To obtain a quantitative estimate of the serial interval for falciparum malaria, the sum of the components of the falciparum malaria transmission cycle was taken based on a combination of mathematical models and empirical data. During this process, a number of factors were identified that account for substantial variability in the serial interval across different contexts.

Results

Treatment with anti-malarial drugs roughly halves the serial interval due to an abbreviated period of human infectiousness, seasonality results in different serial intervals at different points in the transmission season, and variability in within-host dynamics results in many individuals whose serial intervals do not follow average behaviour. Furthermore, 24.5 % of secondary cases presenting clinically did so prior to the primary cases being identified through active detection of infection.

Conclusions

These results have important implications for epidemiological applications that rely on quantitative estimates of the serial interval of falciparum malaria and other diseases characterized by prolonged infections and complex ecological drivers.
Literature
1.
go back to reference Gething PW, Patil AP, Smith DL, Guerra CA, Elyazar IRF, Johnston GL, et al. A new world malaria map: plasmodium falciparum endemicity in 2010. Malar J. 2011;10:378.CrossRefPubMedPubMedCentral Gething PW, Patil AP, Smith DL, Guerra CA, Elyazar IRF, Johnston GL, et al. A new world malaria map: plasmodium falciparum endemicity in 2010. Malar J. 2011;10:378.CrossRefPubMedPubMedCentral
3.
go back to reference Fine P. The interval between successive cases of an infectious disease. Am J Epidemiol. 2003;158:1039–47.CrossRefPubMed Fine P. The interval between successive cases of an infectious disease. Am J Epidemiol. 2003;158:1039–47.CrossRefPubMed
4.
go back to reference Lessler J, Brookmeyer R, Reich NG, Nelson KE, Cummings DA, Perl TM. Identifying the probable timing and setting of respiratory virus infections. Infect Control Hosp Epidemiol. 2010;31:809–15.CrossRefPubMed Lessler J, Brookmeyer R, Reich NG, Nelson KE, Cummings DA, Perl TM. Identifying the probable timing and setting of respiratory virus infections. Infect Control Hosp Epidemiol. 2010;31:809–15.CrossRefPubMed
5.
go back to reference Jombart T, Cori A, Didelot X, Cauchemez S, Fraser C, Ferguson N. Bayesian reconstruction of disease outbreaks by combining epidemiologic and genomic data. PLoS Comput Biol. 2014;10:e1003457.CrossRefPubMedPubMedCentral Jombart T, Cori A, Didelot X, Cauchemez S, Fraser C, Ferguson N. Bayesian reconstruction of disease outbreaks by combining epidemiologic and genomic data. PLoS Comput Biol. 2014;10:e1003457.CrossRefPubMedPubMedCentral
6.
go back to reference Reiner RC, Le Manach A, Kunene S, Ntshalintshali N, Hsiang, Perkins TA, et al. Mapping residual transmission for malaria elimination. eLife. 2015;4:e09520.CrossRefPubMedPubMedCentral Reiner RC, Le Manach A, Kunene S, Ntshalintshali N, Hsiang, Perkins TA, et al. Mapping residual transmission for malaria elimination. eLife. 2015;4:e09520.CrossRefPubMedPubMedCentral
7.
8.
go back to reference Perkins TA, Metcalf CJE, Grenfell BT, Tatem AJ. Estimating drivers of autochthonous transmission of chikungunya virus in its invasion of the Americas. PLoS Currents Outbreaks. 2015;1:1–9. Perkins TA, Metcalf CJE, Grenfell BT, Tatem AJ. Estimating drivers of autochthonous transmission of chikungunya virus in its invasion of the Americas. PLoS Currents Outbreaks. 2015;1:1–9.
10.
go back to reference Carrat F, Vergu E, Ferguson NM, Lemaitre M, Cauchemez S, Leach S, et al. Time lines of infection and disease in human influenza: a review of volunteer challenge studies. Am J Epidemiol. 2008;167:775–85.CrossRefPubMed Carrat F, Vergu E, Ferguson NM, Lemaitre M, Cauchemez S, Leach S, et al. Time lines of infection and disease in human influenza: a review of volunteer challenge studies. Am J Epidemiol. 2008;167:775–85.CrossRefPubMed
11.
go back to reference te Beest DE, Henderson D, van der Maas NAT, de Greeff SC, Wallinga J, Mooi FR, et al. Estimation of the serial interval of pertussis in Dutch households. Epidemics. 2014;7:1–6.CrossRef te Beest DE, Henderson D, van der Maas NAT, de Greeff SC, Wallinga J, Mooi FR, et al. Estimation of the serial interval of pertussis in Dutch households. Epidemics. 2014;7:1–6.CrossRef
12.
go back to reference Aldstadt J, Yoon I-K, Tannitisupawong D, Jarman RG, Thomas SJ, Gibbons RV, et al. Space-time analysis of hospitalised dengue patients in rural Thailand reveals important temporal intervals in the pattern of dengue virus transmission. Trop Med Int Health. 2012;17:1076–85.CrossRefPubMedPubMedCentral Aldstadt J, Yoon I-K, Tannitisupawong D, Jarman RG, Thomas SJ, Gibbons RV, et al. Space-time analysis of hospitalised dengue patients in rural Thailand reveals important temporal intervals in the pattern of dengue virus transmission. Trop Med Int Health. 2012;17:1076–85.CrossRefPubMedPubMedCentral
13.
go back to reference Hackett LW. Malaria in Europe, an ecological study. Oxford University Press; 1937. Hackett LW. Malaria in Europe, an ecological study. Oxford University Press; 1937.
14.
go back to reference Ferguson HM, Dornhaus A, Beeche A, Borgemeister C, Gottlieb M, Mulla MS, et al. Ecology: a prerequisite for malaria elimination and eradication. PLoS Med. 2010;7:e1000303.CrossRefPubMedPubMedCentral Ferguson HM, Dornhaus A, Beeche A, Borgemeister C, Gottlieb M, Mulla MS, et al. Ecology: a prerequisite for malaria elimination and eradication. PLoS Med. 2010;7:e1000303.CrossRefPubMedPubMedCentral
15.
go back to reference Boelle PY, Thomas G, Vergu E, Renault P, Valleron AJ, Flahault A. Investigating transmission in a two-wave epidemic of chikungunya fever. Reunion Island. Vector-borne Zoonotic Dis. 2008;8:207–17.CrossRefPubMed Boelle PY, Thomas G, Vergu E, Renault P, Valleron AJ, Flahault A. Investigating transmission in a two-wave epidemic of chikungunya fever. Reunion Island. Vector-borne Zoonotic Dis. 2008;8:207–17.CrossRefPubMed
16.
go back to reference Fairley NH. Sidelights on malaria in man obtained by subinoculation experiments. Trans R Soc Trop Med Hyg. 1947;40:621–76.CrossRefPubMed Fairley NH. Sidelights on malaria in man obtained by subinoculation experiments. Trans R Soc Trop Med Hyg. 1947;40:621–76.CrossRefPubMed
17.
go back to reference Johnston G, Smith D, Fidock D. 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:e1003025.CrossRefPubMedPubMedCentral Johnston G, Smith D, Fidock D. 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:e1003025.CrossRefPubMedPubMedCentral
18.
go back to reference Johnston G, Gething P, Hay S, Smith DL, Fidock DA. Modeling within-host effects of drugs on Plasmodium falciparum transmission and prospects for malaria elimination. PLoS Comput Biol. 2014;10:e1003434.CrossRefPubMedPubMedCentral Johnston G, Gething P, Hay S, Smith DL, Fidock DA. Modeling within-host effects of drugs on Plasmodium falciparum transmission and prospects for malaria elimination. PLoS Comput Biol. 2014;10:e1003434.CrossRefPubMedPubMedCentral
19.
go back to reference Molineaux L, Diebner HH, Eichner M, Collins WE, Jeffery GM, Dietz K. Plasmodium falciparum parasitaemia described by a new mathematical model. Parasitology. 2001;122:379–91.CrossRefPubMed Molineaux L, Diebner HH, Eichner M, Collins WE, Jeffery GM, Dietz K. Plasmodium falciparum parasitaemia described by a new mathematical model. Parasitology. 2001;122:379–91.CrossRefPubMed
20.
go back to reference Diebner HH, Eichner M, Molineaux L, Collins WE, Jeffery GM, Dietz K. Modelling the transition of asexual blood stages of Plasmodium falciparum to gametocytes. J Theor Biol. 2000;202:113–27.CrossRefPubMed Diebner HH, Eichner M, Molineaux L, Collins WE, Jeffery GM, Dietz K. Modelling the transition of asexual blood stages of Plasmodium falciparum to gametocytes. J Theor Biol. 2000;202:113–27.CrossRefPubMed
21.
go back to reference Eichner M, Diebner HH, Molineaux L, Collins WE, Jeffery GM, Dietz K. Genesis, sequestration and survival of Plasmodium falciparum gametocytes: parameter estimates from fitting a model to malariatherapy data. Trans R Soc Trop Med Hyg. 2001;95:497–501.CrossRefPubMed Eichner M, Diebner HH, Molineaux L, Collins WE, Jeffery GM, Dietz K. Genesis, sequestration and survival of Plasmodium falciparum gametocytes: parameter estimates from fitting a model to malariatherapy data. Trans R Soc Trop Med Hyg. 2001;95:497–501.CrossRefPubMed
22.
go back to reference Smith TA, Killeen GF, Maire N, Ross A, Molineaux L, Tediosi F, et al. 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 TA, Killeen GF, Maire N, Ross A, Molineaux L, Tediosi F, et al. 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
23.
24.
go back to reference Killeen G, McKenzie F, Foy B, Schieffelin C, Billingsley PF, Beier JC. A simplified model for predicting malaria entomologic inoculation rates based on entomologic and parasitologic parameters relevant to control. Am J Trop Med Hyg. 2000;62:535–44.PubMedPubMedCentral Killeen G, McKenzie F, Foy B, Schieffelin C, Billingsley PF, Beier JC. A simplified model for predicting malaria entomologic inoculation rates based on entomologic and parasitologic parameters relevant to control. Am J Trop Med Hyg. 2000;62:535–44.PubMedPubMedCentral
25.
go back to reference Macdonald G. The analysis of the sporozoite rate. Trop Dis Bull. 1952;49:569–86.PubMed Macdonald G. The analysis of the sporozoite rate. Trop Dis Bull. 1952;49:569–86.PubMed
26.
go back to reference Sturrock HJW, Hsiang MS, Cohen JM, Smith DL, Greenhouse B, Bousema T, et al. Targeting asymptomatic malaria infections: active surveillance in control and elimination. PLoS Med. 2013;10:e1001467.CrossRefPubMedPubMedCentral Sturrock HJW, Hsiang MS, Cohen JM, Smith DL, Greenhouse B, Bousema T, et al. Targeting asymptomatic malaria infections: active surveillance in control and elimination. PLoS Med. 2013;10:e1001467.CrossRefPubMedPubMedCentral
28.
go back to reference Cauchemez S, Ledrans M, Poletto C, Quenel P, de Valk H, Colizza V, et al. Local and regional spread of chikungunya fever in the Americas. Euro Surveill. 2014;19:20854.CrossRefPubMedPubMedCentral Cauchemez S, Ledrans M, Poletto C, Quenel P, de Valk H, Colizza V, et al. Local and regional spread of chikungunya fever in the Americas. Euro Surveill. 2014;19:20854.CrossRefPubMedPubMedCentral
29.
go back to reference Childs LM, Buckee CO. Dissecting the determinants of malaria chronicity: why within-host models struggle to reproduce infection dynamics. J R Soc Interface. 2014;12:20142379. Childs LM, Buckee CO. Dissecting the determinants of malaria chronicity: why within-host models struggle to reproduce infection dynamics. J R Soc Interface. 2014;12:20142379.
30.
go back to reference Wallinga J, Lipsitch M. How generation intervals shape the relationship between growth rates and reproductive numbers. Proc Biol Soc. 2007;274:599–604.CrossRef Wallinga J, Lipsitch M. How generation intervals shape the relationship between growth rates and reproductive numbers. Proc Biol Soc. 2007;274:599–604.CrossRef
31.
go back to reference Champredon D, Dushoff J. Intrinsic and realized generation intervals in infectious-disease transmission. Proc Biol Soc. 2015;282:20152026.CrossRef Champredon D, Dushoff J. Intrinsic and realized generation intervals in infectious-disease transmission. Proc Biol Soc. 2015;282:20152026.CrossRef
32.
go back to reference Vynnycky E, Fine PEM. The long-term dynamics of tuberculosis and other diseases with long serial intervals: implications of and for changing reproduction numbers. Epidemiol Infect. 1998;121:309–24.CrossRefPubMedPubMedCentral Vynnycky E, Fine PEM. The long-term dynamics of tuberculosis and other diseases with long serial intervals: implications of and for changing reproduction numbers. Epidemiol Infect. 1998;121:309–24.CrossRefPubMedPubMedCentral
Metadata
Title
Quantitative, model-based estimates of variability in the generation and serial intervals of Plasmodium falciparum malaria
Authors
John H. Huber
Geoffrey L. Johnston
Bryan Greenhouse
David L. Smith
T. Alex Perkins
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2016
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-016-1537-6

Other articles of this Issue 1/2016

Malaria Journal 1/2016 Go to the issue