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Maternal Passive Immunity and Dengue Hemorrhagic Fever in Infants

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Abstract

Dengue hemorrhagic fever (DHF) can occur in primary dengue virus infection of infants \(<1\) year of age. To understand the presumed role of maternal dengue-specific antibodies received until birth in the development of this primary DHF in infants, we investigated a mathematical model based on a system of nonlinear ordinary differential equations that mimics cells, virus and antibodies interactions. The neutralization and enhancement activities of maternal antibodies against the virus are represented by a function derived from experimental data and knowledge from the medical literature. The analytic study of the model shows the existence of two equilibriums, a disease-free equilibrium and an endemic one. We performed the asymptotic stability analysis for these two equilibriums. The local asymptotic stability of the endemic equilibrium (DHF equilibrium) corresponds to the occurrence of DHF. Numerical results are also presented in order to illustrate the mathematical analysis performed, highlighting the most important parameters that drive model dynamics. We defined the age at which DHF occurs as the time when the infection takes off that means at the inflection point of the curve of infected cell population. We showed that this age corresponds to the one at which maximum enhancing activity for dengue infection appears. This critical time for the occurrence of DHF is calculated from the model to be approximately 2 months after the time for maternal dengue neutralizing antibodies to degrade below a protective level, which corresponds to what is observed in the experimental data from the literature.

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References

  • Ben-Shachar R, Koelle K (2015) Minimal within-host dengue models highlight the specific roles of the immune response in primary and secondary dengue infections. J R Soc Interface. https://doi.org/10.1098/rsif.2014.0886

    Article  Google Scholar 

  • Brauer F, Castillo-Chavez C, Castillo-Chavez C (2001) Mathematical models in population biology and epidemiology. Springer, Berlin

    Book  Google Scholar 

  • Capeding RZ, Brion JD, Caponpon MM, Gibbons RV, Jarman RG, Yoon IK, Libraty DH (2010) The incidence, characteristics, and presentation of dengue virus infections during infancy. Am J Trop Med Hyg 82(2):330–336

    Article  Google Scholar 

  • Castanha PM, Braga C, Cordeiro MT, Souza AI, Silva CD Jr, Martelli CM, van Panhuis WG, Nascimento EJ, Marques ET (2016) Placental transfer of dengue virus (DENV)-specific antibodies and kinetics of denv infection-enhancing activity in brazilian infants. J Infect Dis 214(2):265–272

    Article  Google Scholar 

  • Cerón MG, Yang H (2018) A simple mathematical model to describe antibody-dependent enhancement in heterologous secondary infection in dengue. Math Med Biol. https://doi.org/10.1093/imammb/dqy016

    Article  Google Scholar 

  • Chau TNB, Quyen NTH, Thuy TT, Tuan NM, Hoang DM, Dung NTP, Lien LB, Quy NT, Hieu NT, Hieu LTM et al (2008) Dengue in vietnamese infants—results of infection-enhancement assays correlate with age-related disease epidemiology, and cellular immune responses correlate with disease severity. J Infect Dis 198(4):516–524

    Article  Google Scholar 

  • Chau TNB, Hieu NT, Anders KL, Wolbers M, Lien LB, Hieu LTM, Hien TT, Hung NT, Farrar J, Whitehead S et al (2009) Dengue virus infections and maternal antibody decay in a prospective birth cohort study of vietnamese infants. J Infect Dis 200(12):1893–1900

    Article  Google Scholar 

  • Clapham HE, Tricou V, Van Vinh Chau N, Simmons CP, Ferguson NM (2014) Within-host viral dynamics of dengue serotype 1 infection. J R Soc Interface. https://doi.org/10.1098/rsif.2014.0094

    Article  Google Scholar 

  • Clapham HE, Quyen TH, Kien DTH, Dorigatti I, Simmons CP, Ferguson NM (2016) Modelling virus and antibody dynamics during dengue virus infection suggests a role for antibody in virus clearance. PLoS Comput Biol 12(5):e1004951

    Article  Google Scholar 

  • Dejnirattisai W, Jumnainsong A, Onsirisakul N, Fitton P, Vasanawathana S, Limpitikul W, Puttikhunt C, Edwards C, Duangchinda T, Supasa S et al (2010) Cross-reacting antibodies enhance dengue virus infection in humans. Science 328(5979):745–748

    Article  Google Scholar 

  • Diekmann O, Heesterbeek JAP (2000) Mathematical epidemiology of infectious diseases: model building, analysis and interpretation. Wiley, New York

    MATH  Google Scholar 

  • Dowd KA, Pierson TC (2011) Antibody-mediated neutralization of flaviviruses: a reductionist view. Virology 411(2):306–315

    Article  Google Scholar 

  • Dowd KA, Mukherjee S, Kuhn RJ, Pierson TC (2014) Combined effects of the structural heterogeneity and dynamics of flaviviruses on antibody recognition. J Virol 88(20):11726–11737

    Article  Google Scholar 

  • Flipse J, Diosa-Toro MA, Hoornweg TE, Van De Pol DP, Urcuqui-Inchima S, Smit JM (2016) Antibody-dependent enhancement of dengue virus infection in primary human macrophages; balancing higher fusion against antiviral responses. Sci Rep. https://doi.org/10.1038/srep29201

    Article  Google Scholar 

  • Gonzalez-Mejia ME, Doseff AI (2009) Regulation of monocytes and macrophages cell fate. Front Biosci 14:2413–2431

    Article  Google Scholar 

  • Guzman MG, Halstead SB, Artsob H, Buchy P, Farrar J, Gubler DJ, Hunsperger E, Kroeger A, Margolis HS, Martínez E et al (2010) Dengue: a continuing global threat. Nat Rev Microbiol 8(12):S7

    Article  Google Scholar 

  • Guzman MG, Alvarez M, Halstead SB (2013) Secondary infection as a risk factor for dengue hemorrhagic fever/dengue shock syndrome: an historical perspective and role of antibody-dependent enhancement of infection. Arch Virol 158(7):1445–1459

    Article  Google Scholar 

  • Halstead SB, Lan NT, Myint TT, Shwe TN, Nisalak A, Kalyanarooj S, Nimmannitya S, Soegijanto S, Vaughn DW, Endy TP (2002) Dengue hemorrhagic fever in infants: research opportunities ignored. Emerg Infect Dis 8(12):1474

    Article  Google Scholar 

  • Jain A, Chaturvedi UC (2010) Dengue in infants: an overview. FEMS Immunol Med Microbiol 59(2):119–130

    Article  Google Scholar 

  • Khamim K, Hattasingh W, Nisalak A, Kaewkungwal J, Fernandez S, Thaisomboonsuk B, Pengsaa K et al (2015) Neutralizing dengue antibody in pregnant Thai women and cord blood. PLoS Negl Trop Dis 9(2):e0003396

    Article  Google Scholar 

  • Kirkilionis M, Walcher S (2004) On comparison systems for ordinary differential equations. J Math Anal Appl 299(1):157–173. https://doi.org/10.1016/j.jmaa.2004.06.025

    Article  MathSciNet  MATH  Google Scholar 

  • Kliks SC, Nimmanitya S, Nisalak A, Burke DS (1988) Evidence that maternal dengue antibodies are important in the development of dengue hemorrhagic fever in infants. Am J Trop Med Hyg 38(2):411–419

    Article  Google Scholar 

  • Nikin-Beers R, Ciupe SM (2015) The role of antibody in enhancing dengue virus infection. Math Biosci 263:83–92

    Article  MathSciNet  Google Scholar 

  • Palmeira P, Quinello C, Silveira-Lessa AL, Zago CA, Carneiro-Sampaio M (2011) IgG placental transfer in healthy and pathological pregnancies. Clin Dev Immunol. https://doi.org/10.1155/2012/985646

    Article  Google Scholar 

  • Pengsaa K, Luxemburger C, Sabchareon A, Limkittikul K, Yoksan S, Chambonneau L, Chaovarind U, Sirivichayakul C, Lapphra K, Chanthavanich P et al (2006) Dengue virus infections in the first 2 years of life and the kinetics of transplacentally transferred dengue neutralizing antibodies in Thai children. J Infect Dis 194(11):1570–1576

    Article  Google Scholar 

  • Reich N, Shrestha S, King A, Rohani P, Lessler J, Kalayanarooj S, Yoon I, Gibbons R, Burke D, Cummings D (2013) Interactions between serotypes of dengue highlight epidemiological impact of cross-immunity. J R Soc Interface. https://doi.org/10.1098/rsif.2013.0414

    Article  Google Scholar 

  • Sasmal SK, Dong Y, Takeuchi Y (2017) Mathematical modeling on T-cell mediated adaptive immunity in primary dengue infections. J Theor Biol 429:229–240

    Article  Google Scholar 

  • Simmons CP, Chau TNB, Thuy TT, Tuan NM, Hoang DM, Thien NT, Lien LB, Quy NT, Hieu NT, Hien TT et al (2007) Maternal antibody and viral factors in the pathogenesis of dengue virus in infants. J Infect Dis 196(3):416–424

    Article  Google Scholar 

  • Tricou V, Minh NN, Farrar J, Tran HT, Simmons CP (2011) Kinetics of viremia and NS1 antigenemia are shaped by immune status and virus serotype in adults with dengue. PLoS Negl Trop Dis 5(9):e1309

    Article  Google Scholar 

  • Van Den Driessche P, Watmough J (2002) Reproduction numbers and sub-threshold endemic equilibria for compartmental models of disease transmission. Math Biosci 180(1–2):29–48

    Article  MathSciNet  Google Scholar 

  • Wikramaratna PS, Simmons CP, Gupta S, Recker M (2010) The effects of tertiary and quaternary infections on the epidemiology of dengue. PloS One 5(8):e12347

    Article  Google Scholar 

Download references

Acknowledgements

CPF thanks to 16/23738-3 São Paulo Research Foundation (FAPESP), Brazil. FLPS thanks to 18/03116-3 São Paulo Research Foundation (FAPESP), Brazil.

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Authors and Affiliations

  1. Inria, Université de Lyon, Université Lyon 1, 43 Bd. du 11 novembre 1918, 69200, Villeurbanne Cedex, France

    Mostafa Adimy

  2. São Paulo State University (UNESP), Rua Prof. Dr. Antônio Celso Wagner Zanin, 250, District of Rubião Junior, Botucatu, SP, 18618-689, Brazil

    Paulo F. A. Mancera, Fernando L. P. Santos & Cláudia P. Ferreira

  3. School of Technology, University of Campinas (UNICAMP), Rua Paschoal Marmo, 1888, Limeira, SP, 13484-332, Brazil

    Diego S. Rodrigues

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  1. Mostafa Adimy
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  2. Paulo F. A. Mancera
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  3. Diego S. Rodrigues
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  4. Fernando L. P. Santos
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  5. Cláudia P. Ferreira
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Correspondence to Cláudia P. Ferreira.

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Adimy, M., Mancera, P.F.A., Rodrigues, D.S. et al. Maternal Passive Immunity and Dengue Hemorrhagic Fever in Infants. Bull Math Biol 82, 24 (2020). https://doi.org/10.1007/s11538-020-00699-x

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