Abstract
Malaria continues to be a major public health concern all over the world even after effective control policies have been employed, and considerable understanding of the disease biology have been attained, from both the experimental and modelling perspective. Interactions between different general and local processes, such as dependence on age and immunity of the human host, variations of temperature and rainfall in tropical and sub-tropical areas, and continued presence of asymptomatic infections, regulate the host-vector interactions, and are responsible for the continuing disease prevalence pattern.
In this paper, a general mathematical model of malaria transmission is developed considering short and long-term age-dependent immunity of human host and its interaction with pathogen-infected mosquito vector. The model is studied analytically and numerically to understand the role of different parameters related to mosquitoes and humans. To validate the model with a disease prevalence pattern in a particular region, real epidemiological data from the north-eastern part of India was used, and the effect of seasonal variation in mosquito density was modelled based on local climactic data. The model developed based on general features of host-vector interactions, and modified simply incorporating local environmental factors with minimal changes, can successfully explain the disease transmission process in the region. This provides a general approach toward modelling malaria that can be adapted to control future outbreaks of malaria.
Similar content being viewed by others
References
Albonico, M., Chwaya, H. M., Montresor, A., Stolzfus, R. J., Tielsch, J. M., Alawi, K. S., & Savioli, L. (1997). Parasitic infections in Pemba Island school children. East Afr. Med. J., 74, 294–298.
Alves, F. P., Durlacher, R. R., Menezes, M. J., Krieger, H., Silva, L. H., & Camargo, E. P. (2002). High prevalence of asymptomatic Plasmodium vivax and Plasmodium falciparum infections in native Amazonian populations. Am. J. Trop. Med. Hyg., 66(6), 641–648.
Anderson, R. M., & May, R. M. (1991). Infectious diseases of humans: dynamics and control. London: Oxford University Press.
Aron, J. L. (1983). Dynamics of acquired immunity boosted by exposure to infection. Math. Biosci., 64, 249–259.
Aron, J. L. (1988). Mathematical modeling of immunity to malaria. Math. Biosci., 90, 385–396.
Aron, J. L., & May, R. M. (1982). The population dynamics of malaria. In R. M. Anderson (Ed.), Population dynamics of infectious disease (pp. 139–179). London: Chapman and Hall.
Bacaër, N. (2007). Approximation of the basic reproduction number R0 for vector-borne diseases with a periodic vector population. Bull. Math. Biol., 69, 1067–1091.
Bacaër, N., & Ait Dada, E. H. (2012). On the biological interpretation of a definition for the parameter R0 in periodic population models. J. Math. Biol., 65, 601–621.
Bhattacharjee, S., Sharma, C., Dhiman, R. C., & Mitra, A. P. (2006). Climate change and malaria in India. Curr. Sci., 90, 369–375.
Briet, O. J. (2002). A simple method for calculating mosquito mortality rates, correcting for seasonal variations in recruitment. Med. Vet. Entomol., 16, 22–27.
Cairns, M., Ghani, A., Okell, L., Gosling, R., Carneiro, I., Anto, F., Asoala, V., Owusu-Agyei, S., Greenwood, B., Chandramohan, D., & Milligan, P. (2011). Modelling the protective efficacy of alternative delivery schedules for intermittent preventive treatment of malaria in infants and children. PLoS ONE, 6, e18947.
Census of India (2001). Age structure of population distribution. http://censusindia.gov.in/Census_And_You/age_structure_and_marital_status.aspx.
Chatterjee, C., & Sarkar, R. R. (2009). Multi-step polynomial regression method to model and forecast malaria incidence. PLoS ONE, 4, e4726.
Chitnis, N., Cushing, J. M., & Hyman, J. M. (2006). Bifurcation analysis of a mathematical model for malaria transmission. SIAM J. Appl. Math., 67, 24–45.
Dev, V., Phookan, S., Sharma, V. P., & Anand, S. P. (2004). Physiographic and entomologic risk factors of malaria in Assam, India. Am. J. Trop. Med. Hyg., 71(4), 451–456.
Dev, V., Sangma, B. M., & Dash, A. P. (2010). Persistent transmission of malaria in Garo hills of Meghalaya bordering Bangladesh, north-east India. Malar. J., 9, 263. doi:10.1186/1475-2875-9-263.
Diaz, H., Ramirez, A. A., Olarte, A., & Clavijo, C. (2011). A model for the control of malaria using genetically modified vectors. J. Theor. Biol., 276, 57–66.
Diekmann, O., Heesterbeek, J. A. P., & Metz, J. A. J. (1990). On the definition and the computation of the basic reproduction ratio R0 in models for infectious diseases. J. Math. Biol., 35, 503–522.
Dietz, K. (1993). The estimation of the basic reproduction number for infectious diseases. Stat. Methods Med. Res., 2, 23–41.
Dietz, K., Molineaux, L., & Thomas, A. (1974). A malaria model tested in the African savannah. Bull. World Health Organ., 50, 347–357.
Doolan, D. L., Dobaño, C., & Baird, J. K. (2009). Acquired immunity to malaria. Clin. Microbiol. Rev., 22(1), 13–36.
Drakeley, C. J., Akim, N. I. J., Sauerwein, R. W., Greenwood, B. M., & Targett, G. A. T. (2000). Estimates of the infectious reservoir of Plasmodium falciparum malaria in the Gambia and in Tanzania. Trans. R. Soc. Trop. Med. Hyg., 94, 472–476.
Drakeley, C. J., Carneiro, I., Reyburn, H., Malima, R., Lusingu, J. P. A., et al. (2005). Altitude-dependent and -independent variations in Plasmodium falciparum prevalence in northeastern Tanzania. J. Infect. Dis., 191, 1589–1598.
Drakeley, C. J., Sutherland, C., Bouserna, J. T., Sauerwein, R. W., & Targett, G. A. T. (2006). The epidemiology of Plasmodium falciparum gametocytes: weapons of mass dispersion. Trends Parasitol., 22, 424–430.
Elderkin, R. H., Berkowitz, D. P., Farris, F. A., Gunn, C. F., Hickernell, F. J., Kass, S. N., Mansfield, F. I., & Taranto, R. G. (1977). On the steady state of an age dependent model for malaria. In V. Lakshmikantham (Ed.), Nonlinear systems and applications (pp. 491–512). New York: Academic.
Ermert, V., Fink, A. H., Jones, A. E., & Morse, A. P. (2011). Development of a new version of the Liverpool malaria model, I: refining the parameter settings and mathematical formulation of basic processes based on a literature review. Malar. J., 10, 35. doi:10.1186/1475-2875-10-35.
Filipe, J. A. N., Riley, E. M., Darkeley, C. J., Sutherland, C. J., & Ghani, A. C. (2007). Determination of the processes driving the acquisition of immunity to malaria using a mathematical transmission model. PLoS Comput. Biol., 3(12), 2569–2579.
Ghani, Z. C., Sutherland, C. J., Riley, E. M., Drakeley, C. J., Griffin, J. T., Gosling, R. D., & Filipe, J. A. N. (2009). Loss of population levels of immunity to malaria as a result of exposure-reducing interventions: consequences for interpretation of disease trends. PLoS ONE, 2, e4383.
Griffin, J. T., Hollingsworth, T. D., Okell, L. C., Churcher, T. S., White, M., et al. (2010). Reducing Plasmodium falciparum malaria transmission in Africa: a model-based evaluation of intervention strategies. PLoS Med., 7(8), e1000324. doi:10.1371/journal.pmed.1000324.
Gu, W. D., Mbogo, C. M., Githure, J. I., Regens, J. L., Killeen, G. F., et al. (2003). Low recovery rates stabilize malaria endemicity in areas of low transmission in coastal Kenya. Acta Trop., 86, 71–81.
Gurarie, D., Karl, S., Zimmerman, P. A., King, C. H., St. Pierre, T. G, et al. (2012). Mathematical modeling of malaria infection with innate and adaptive immunity in individuals and agent-based communities. PLoS ONE, 7(3), e34040. doi:10.1371/journal.pone.0034040.
Hay, S. I., Rogers, D. J., Toomer, J. F., & Snow, R. W. (2000). Annual Plasmodium falciparum entomological inoculation rates (EIR) across Africa: literature survey, Internet access and review. Trans. R. Soc. Trop. Med. Hyg., 94, 113–127.
Hay, S. I., Guerra, C., Tatem, A., Noor, A., & Snow, R. (2004). The global distribution and population at risk of malaria: past, present and future. Lancet Infect. Dis., 4, 327–336.
Heesterbeek, J. A. P., & Dietz, K. (1996). The concept of R0 in epidemic theory. Stat. Neerl., 50(1), 89–110.
Heffernan, J. M., Smith, R. J., & Wahl, M. (2005). Perspectives on the basic reproductive ratio. J. R. Soc. Interface, 2(4), 281–293. doi:10.1098/rsif.2005.0042.
Hogh, B., Thompson, R., Hetzel, C., Fleck, S. L., Kruse, N. A., Jones, I., Dgedge, M., Barreto, J., & Sinden, R. E. (1995). Specifc and nonspecifc responses to Plasmodium falciparum blood-stage parasites and observations on the gametocytemia in schoolchildren living in a malaria-endemic area of Mozambique. Am. J. Trop. Med. Hyg., 52, 50–59.
Hoshen, M. B., & Morse, A. P. (2004). A weather-driven model of malaria transmission. Malar. J., 3, 32. doi:10.1186/1475-2875-3-32.
Kelly-Hope, L. A., & McKenzie, F. E. (2009). The multiplicity of malaria transmission: a review of entomological inoculation rate measurements and methods across sub-Saharan Africa. Malar. J., 8, 268. doi:10.1186/1475-2875-8-268.
Killeen, G. F., Chitnis, N., Moore, S. J., & Okumu, F. O. (2011). Target product profile choices for intra-domiciliary malaria vector control pesticide products: repel or kill? Malar. J., 10, 207. doi:10.1186/1475-2875-10-207.
Koella, J. C. (1991). On the use of mathematical models of malaria transmission. Acta Trop., 49, 1–25.
Li, J., Welch, R. M., Nair, U. S., Sever, T. L., Irwin, D. E., Cordon-Rosales, C., & Padilla, N. (2002). Dynamic malaria models with environmental changes. In Proceedings of the thirty-fourth southeastern symposium on system theory (pp. 396–400). Huntsville: AL.
Macdonald, G. (1950). The analysis of infection rates in diseases in which superinfections occur. Trop. Dis. Bull., 47, 907–915.
Macdonald, G. (1956). Epidemiological basis of malaria control. Bull. World Health Organ., 15, 613–626.
Malaria Site. http://www.malariasite.com/malaria/MalariaInMangalore.htm.
Mandal, S., Sarkar, R. R., & Sinha, S. (2011). Mathematical models of malaria: a review. Malar. J., 10, 202. doi:10.1186/1475-2875-10-202.
Martens, W. J. M., Niessen, L. W., Rotmans, J., Jetten, T. H., & McMichael, A. J. (1995). Potential impact of global climate change on malaria risk. Environ. Health Perspect., 103, 458–464.
McKenzie, F. E. (2000). Why model malaria? Parasitol. Today, 16(12), 511–516.
Mert, A., Ozaras, R., Tabak, F., Bilir, M., Ozturk, R., & Aktuglu, Y. (2003). Malaria in Turkey: a review of 33 cases. Eur. J. Epidemiol., 18, 579–582.
Molineaux, L., & Gramiccia, G. (1980). The Garki project. Geneva: World Health Organization.
Nah, K., Kim, Y., & Lee, J. M. (2010). The dilution effect of the domestic animal population on the transmission of P. vivax malaria. J. Theor. Biol., 266, 299–306.
Ngwa, G. A., & Shu, W. S. (2000). A mathematical model for endemic malaria with variable human and mosquito populations. Math. Comput. Model., 32, 747–763.
Okell, L. C., Drakeley, C. J., Bousema, T., Whitty, C. J. M., & Ghani, A. C. (2008). Modelling the impact of artemisinin combination therapy and long-acting treatments on malaria transmission intensity. PLoS Med., 5(11), e226. doi:10.1371/journal.pmed.0050226.
Pampana, E. (1969). A textbook of malaria eradication. London: Oxford University Press.
Parham, P. E., & Michael, E. (2010). Modeling the effects of weather and climate change on malaria transmission. Environ. Health Perspect., 118, 620–626. doi:10.1289/ehp.0901256.
Rafikov, M., Bevilacqua, L., & Wyse, A. P. P. (2009). Optimal control strategy of malaria vector using genetically modified mosquitoes. J. Theor. Biol., 258, 418–425.
Reiner, R. C., Perkins, T. A., Barker, C. M., Niu, T., Chaves, L. F., et al. (2013). A systematic review of mathematical models of mosquito-borne pathogen transmission. J. R. Soc. Interface, 10, 20120921.
Ross, R. (1911). The prevention of malaria. London: Murray.
Ross, R. (1915). Some a priori pathometric equations. Br. Med. J., 1, 546–547.
Roy, S. B., Sarkar, R. R., & Sinha, S. (2011). Theoretical investigation of malaria prevalence in two indian cities using the response surface method. Malar. J., 10, 301. doi:10.1186/1475-2875-10-301.
Russell, P. F., West, L. S., Manwell, R. D., & MacDonald, G. (1963). Practical malariology. London: Oxford University Press.
Sabatinelli, G., Majori, G., D’Ancona, F., & Romi, R. (1994). Malaria epidemiological trends in Italy. Eur. J. Epidemiol., 10, 399–403.
Segel, L. A. (1980). Mathematical models in molecular and cellular biology. Cambridge: Cambridge University Press.
Sharma, V. P., & Bos, R. (2003). Determinants of malaria in South-Asia. In E. Casman & H. Dowlatabadi (Eds.), The contextual determinants of malaria. Washington: Resources for the Future.
Smith, D. L., Battle, K. E., Hay, S. I., Barker, C. M., Scott, T. W., & McKenzie, F. E. (2012). Ross, Macdonald, and a theory for the dynamics and control of mosquito-transmitted pathogens. PLoS Pathog., 8(4), e1002588. doi:10.1371/journal.ppat.1002588.
Tanser, F. C., Sharp, B., & le Sueur, D. (2003). Potential effect of climate change of malaria transmission in Africa. Lancet, 362, 1792–1798.
Trape, J. F., Rogier, C., Konate, L., Diagne, N., Bouganali, H., Canque, B., Legros, F., Badji, A., Ndiaye, G., Ndiaye, P., Brahimi, K., Faye, O., Druilhe, P., & Da-Silva, L. P. (1994). 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., 51, 123–137.
Vinetz, J. M., & Gilman, R. H. (2002). Asymptomatic Plasmodium parasitemia and the ecology of malaria transmission. Am. J. Trop. Med. Hyg., 66(6), 639–640.
World Health Organization (WHO) and WHO global malaria programme. Available http://www.who.int/topics/malaria/en/ and http://www.who.int/malaria/aboutus.html.
Yang, H. M. (2000). Malaria transmission model for different levels of acquired immunity and temperature-dependent parameters (vector). Rev. Saude Publica, 34, 223–231.
Yé, Y., Hoshen, M., Kyobutungi, C., Louis, V. R., & Sauerborn, R. (2009). Local scale prediction of Plasmodium falciparum malaria transmission in an endemic region using temperature and rainfall. Glob. Health Action, 2, 13. doi:10.3402/gha.v2i0.1923.
Acknowledgement
We thank Department of Science and Technology, Government of India, for the financial support (SR/SO/AS-25/2008).
Author information
Authors and Affiliations
Corresponding author
Appendices
Appendix A: Immunity Functions
The parameters ρ and η, which depend on the level of immunity of the host, have been incorporated in the model (7a)–(7g) through immunity functions. The details mathematical formulation is described in the following text.
In the proposed model (7a)–(7g), human immunity is considered to act in two ways: (i) reduces the probability (η) of clinical disease and (ii) regulate the rate of removal of parasites (ρ). The immunity, responsible for the first kind of work is called Clinical immunity (C(a,t)) and the immunity, which is responsible for clearance of parasite is called Parasite immunity (P(a,t)).
Clinical Immunity
Every people born with some level of immunity called maternal immunity (C m ), which decays exponentially with a half life d m but simultaneously accumulates some immunity (C f ), which is determined by the force of infection and this also decays exponentially with mean life d e . Therefore, clinical immunity can be written as
where C m and C f can be found by solving the following set of equations:
At the time of birth, maternal immunity (C m ) is assumed to be half of the total clinical immunity at the age of 25 years (Drakeley et al. 2006) and C f is zero. The response of the clinical immunity η is assumed to vary by the following way:
Parasite Immunity
This immunity is responsible for clearance of parasite and develops/matures relatively in latter age of life through a delay phase (J A ). The immunity level in delay phase (J A ) accumulates through force of infection (σI m ), matures in parasite immunity (P(a,t)) at a rate (1/d l ), and decays exponentially with mean life d A . Parasite immunity can be obtained by solving the following set of equations:
At the time of birth, J A =P=0.
The recovery rate from the disease (ρ) is assumed to be a saturating increasing function of the immunity level P(a,t):
where ρ 0 and r are the age dependent and age independent baseline recovery rate, respectively; w A denotes maximum amplification of baseline recovery rate; H A is the level of parasite immunity at half saturation.
Appendix B: Existence of Endemic Equilibrium Point
The proof for existence of endemic equilibrium points of the model is presented below.
Proof
The equilibrium point E ∗ of system (7a)–(7g) can be expressed in terms of \(S_{m}^{*}\) as shown in expressions (9a–9f). It can be shown easily that the existence (positivity) and uniqueness of the equilibrium point E ∗ holds if \(S_{m}^{*}\) is positive and ∈[0,1). Condition for \(S_{m}^{*}\ \in [0, 1)\) We have the expression for \(S_{m}^{*}\) in Eq. (10) as
From the expression for A, B, and C, it is clear that for all set of real parameter values, A<0, B>0, and C<0. Also, the expression for (A+B+C) can be written in terms of basic reproduction number R 0 as
Now we can observe the following situations, which determine the existence and uniqueness of the equilibrium point E ∗:
-
(i)
For R 0<1, both the roots of \(S_{m}^{*}\) will lie between 0 and 1 if the following conditions hold true:
$$\biggl \vert \frac{C}{A} \biggr \vert < 1\quad \mathrm{and}\quad C (A + B + C) > 0 $$But for R 0<1, the second condition does not hold i.e. \(\vert \frac{C}{A} \vert \ > 1\).
Therefore, for R 0<1, only one equilibrium point exist which is disease free.
-
(ii)
If R 0=1, then A+B+C=0.
In this case roots are \(S_{m}^{*} = 1\) and \(S_{m}^{*} = \frac{C}{A}\).
The second root exists if and only if, \(\vert \frac{C}{A} \vert \le 1\).
But this condition does not hold true, hence only one equilibrium point \(S_{m}^{*} = 1\) exists, which indicates again a disease free state.
-
(iii)
For R 0>1, we have C (A+B+C)<0; this implies one and only one root lies between 0 and 1, which is the endemic equilibrium point E ∗.
Hence, for R 0>1, there exists one and only one endemic equilibrium point E ∗, and this proves the lemma.
Hence the Lemma 3.3 can be proved following the above-mentioned conditions.
Appendix C: Coefficients of the Characteristic Equation (18)
The expressions of C 1, C 2, C 3, and C 4 of the characteristic equation (18) are as follows:
Appendix D: Proof of Theorem 3.4
For τ=0, the system (7a)–(7g) is stable around the disease free equilibrium point if all the roots of the characteristic Eq. (18) are negative, and unstable if at least one root is positive.
Three of the seven roots of Eq. (18) can be easily found as −μ h , −μ m and −μ m which are always negative and to know the sign of other four roots we apply Descarte’s rule of sign.
For all real positive parameter values C 1 and C 2>0
-
(i)
If R 0>1 then C 4<0⇒ Irrespective to the sign of C 3, the system (7a)–(7g) is unstable around the disease free equilibrium point.
-
(ii)
If R 0<1 then C 4>0. In this case the stability of the system (7a)–(7g) around the disease free equilibrium point depends on the sign of C 3. If C 3>0, the system (7a)–(7g) is stable around the disease free equilibrium point and it is unstable if C 3<0. The condition for C 3>0 is as follows:
$$ \sigma < \frac{(\gamma + \mu_{h})(\rho + \mu_{h})(R_{S} + \mu_{h}) + [(\gamma + \mu_{h})(\rho + \mu_{h}) + (R_{S} + \mu_{h})(\gamma + \rho + 2\mu_{h})]\mu_{m}}{\alpha \gamma [(1 - \eta )C_{IA} + \eta C_{IS}]} $$ -
(iii)
If R 0<(μ h /μ m ), then C 3>0 and, as the human mortality rate μ h is less than mosquito mortality rate μ m (i.e. μ h /μ m <1), therefore, C 4>0 and, therefore, all the eigenvalues are negative and the system (7a)–(7g) is stable around the disease free equilibrium point.
-
(iv)
If R 0=1, then C 3<0, (as μ m /μ h >1). Therefore, all roots of the characteristic equation (18) are not negative. So, for R 0=1 the system (7a)–(7g) will not be stable.
Hence, the theorem holds true.
Appendix E: Proof of Theorem 3.5
For τ=0, the system (7a)–(7g) is stable around the endemic equilibrium point if all the roots of the characteristic equation (14) are negative, and is unstable if at least one root is positive. Two roots of the characteristic equation (14) are −μ m , −μ m <0, and to find the other roots for τ=0 we rewrite the equation in the following form:
where \(A = \alpha (C_{IA}I_{hA}^{*} + C_{IS}I_{hS}^{*}) + \mu_{m} > 0\) and the expressions for A 1, A 2, A 3, A 4 and B 1, B 2, B 3 are given in (17a–17g). For all real parameter values A 1, A 2, A 3, and A 4>0. By the Routh–Hurwitz criterion (Segel 1980), the polynomial (E.1) has roots with negative real part if all the coefficients of the polynomial are positive, i.e.
-
(i)
(A 1+A)>0
-
(ii)
\((A_{2} + A A_{1} + \alpha \sigma S_{m}^{*}B_{1}) > 0\)
-
(iii)
\(\{ A_{3} + A A_{2} + \alpha \sigma S_{m}^{*}(B_{2} + B_{1} \mu_{h})\} > 0\)
-
(iv)
\(\{ A_{4} + A A_{3} + \alpha \sigma S_{m}^{*}(B_{3} + B_{2} \mu_{h})\} > 0\)
-
(v)
\((A A_{4} + \alpha \sigma S_{m}^{*}B_{3} \mu_{h}) > 0\)
As A 1 and A both are positive, therefore, (i) is always true. Other conditions hold true if the parameters satisfy the condition (19a) and (19b), where the expressions for X 1, Y 1, X 2, and Y 2 are as follows:
Appendix F: Real and Imaginary Parts of the Expression (16)
where
with A 0=α(C IS I hS +C IA I hA )+μ m .
Appendix G: Age Distribution of Population in India
To compare the simulated result with the real malaria cases, one should keep in mind the age distribution of population in that locality. Although due to lack of data availability, we have considered the age-wise population distribution, obtained from 2001 census data of India as a standard population distribution in India (Census of India 2001). According to this distribution, the percentage of population at age a is
Here, a max is the maximum age group of people available in the population.
Rights and permissions
About this article
Cite this article
Mandal, S., Sinha, S. & Sarkar, R.R. A Realistic Host-Vector Transmission Model for Describing Malaria Prevalence Pattern. Bull Math Biol 75, 2499–2528 (2013). https://doi.org/10.1007/s11538-013-9905-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11538-013-9905-7