Staged progression epidemic models for the transmission of invasive nontyphoidal <i>Salmonella</i> (iNTS) with treatment

Zhuolin Qu; Benjamin H. McMahon; Douglas J. Perkins; James M. Hyman; Zhuolin Qu; Benjamin H. McMahon; Douglas J. Perkins; James M. Hyman

doi:10.3934/mbe.2021079

Mathematical Biosciences and Engineering

2021, Volume 18, Issue 2: 1529-1549. doi: 10.3934/mbe.2021079

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Staged progression epidemic models for the transmission of invasive nontyphoidal Salmonella (iNTS) with treatment

1.
Department of Mathematics, University of Texas at San Antonio, San Antonio 78202, TX, USA
2.
Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM, USA
3.
University of New Mexico, Center for Global Health, Department of Internal Medicine, NM, USA
4.
University of New Mexico-Kenya Global Health Programs, Kisumu and Siaya, Kenya
5.
Department of Mathematics, Tulane University, New Orleans 70112, LA, USA

Received: 31 August 2020 Accepted: 21 January 2021 Published: 29 January 2021

We develop and analyze a stage-progression compartmental model to study the emerging invasive nontyphoidal Salmonella (iNTS) epidemic in sub-Saharan Africa. iNTS bloodstream infections are often fatal, and the diverse and non-specific clinical features of iNTS make it difficult to diagnose. We focus our study on identifying approaches that can reduce the incidence of new infections. In sub-Saharan Africa, transmission and mortality are correlated with the ongoing HIV epidemic and severe malnutrition. We use our model to quantify the impact that increasing antiretroviral therapy (ART) for HIV infected adults and reducing malnutrition in children would have on mortality from iNTS in the population. We consider immunocompromised subpopulations in the region with major risk factors for mortality, such as malaria and malnutrition among children and HIV infection and ART coverage in both children and adults. We parameterize the progression rates between infection stages using the branching probabilities and estimated time spent at each stage. We interpret the basic reproduction number $ \mathcal{R}_0 $ as the total contribution from an infinite infection loop produced by the asymptomatic carriers in the infection chain. The results indicate that the asymptomatic HIV+ adults without ART serve as the driving force of infection for the iNTS epidemic. We conclude that the worst disease outcome is among the pediatric population, which has the highest infection rates and death counts. Our sensitivity analysis indicates that the most effective strategies to reduce iNTS mortality in the studied population are to improve the ART coverage among high-risk HIV+ adults and reduce malnutrition among children.
- mathematical modeling,
- invasive nontyphoidal Salmonella,
- basic reproduction number,
- risk factors,
- asymptomatic carrier
Citation: Zhuolin Qu, Benjamin H. McMahon, Douglas J. Perkins, James M. Hyman. Staged progression epidemic models for the transmission of invasive nontyphoidal Salmonella (iNTS) with treatment[J]. Mathematical Biosciences and Engineering, 2021, 18(2): 1529-1549. doi: 10.3934/mbe.2021079

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Abstract

We develop and analyze a stage-progression compartmental model to study the emerging invasive nontyphoidal Salmonella (iNTS) epidemic in sub-Saharan Africa. iNTS bloodstream infections are often fatal, and the diverse and non-specific clinical features of iNTS make it difficult to diagnose. We focus our study on identifying approaches that can reduce the incidence of new infections. In sub-Saharan Africa, transmission and mortality are correlated with the ongoing HIV epidemic and severe malnutrition. We use our model to quantify the impact that increasing antiretroviral therapy (ART) for HIV infected adults and reducing malnutrition in children would have on mortality from iNTS in the population. We consider immunocompromised subpopulations in the region with major risk factors for mortality, such as malaria and malnutrition among children and HIV infection and ART coverage in both children and adults. We parameterize the progression rates between infection stages using the branching probabilities and estimated time spent at each stage. We interpret the basic reproduction number $ \mathcal{R}_0 $ as the total contribution from an infinite infection loop produced by the asymptomatic carriers in the infection chain. The results indicate that the asymptomatic HIV+ adults without ART serve as the driving force of infection for the iNTS epidemic. We conclude that the worst disease outcome is among the pediatric population, which has the highest infection rates and death counts. Our sensitivity analysis indicates that the most effective strategies to reduce iNTS mortality in the studied population are to improve the ART coverage among high-risk HIV+ adults and reduce malnutrition among children.

References

[1]	J. A. Crump, M. Sjölund-Karlsson, M. A. Gordon, C. M. Parry, Epidemiology, clinical presentation, laboratory diagnosis, antimicrobial resistance, and antimicrobial management of invasive Salmonella infections, Clin. Microbiol. Rev., 28 (2015), 901-937. doi: 10.1128/CMR.00002-15
[2]	I. V. Uche, C. A. MacLennan, A. Saul, A systematic review of the incidence, risk factors and case fatality rates of invasive nontyphoidal Salmonella (iNTS) disease in Africa (1966 to 2014), PLoS Negl. Trop. Dis., 11 (2017), 5118.
[3]	B. Tack, J. Vanaenrode, J. Y. Verbakel, J. Toelen, J. Jacobs, Invasive non-typhoidal Salmonella infections in sub-Saharan Africa: A systematic review on antimicrobial resistance and treatment, BMC Med., 18 (2020), 1-22. doi: 10.1186/s12916-019-1443-1
[4]	J. Z. Kubicek-Sutherland, D. M. Vu, A. Noormohamed, H. M. Mendez, L. R. Stromberg, C. A. Pedersen, et al., Direct detection of bacteremia by exploiting host-pathogen interactions of lipoteichoic acid and lipopolysaccharide, Sci. Rep., 9 (2019), 6203. doi: 10.1038/s41598-019-42502-5
[5]	N. A. Feasey, G. Dougan, R. A. Kingsley, R. S. Heyderman, M. A. Gordon, Invasive non-typhoidal salmonella disease: An emerging and neglected tropical disease in Africa, The Lancet, 379 (2012), 2489-2499. doi: 10.1016/S0140-6736(11)61752-2
[6]	M. A. Gordon, H. T. Banda, M. Gondwe, S. B. Gordon, M. J. Boeree, A. L. Walsh, et al., Non-typhoidal salmonella bacteraemia among HIV-infected malawian adults: high mortality and frequent recrudescence, AIDS, 16 (2002), 1633-1641. doi: 10.1097/00002030-200208160-00009
[7]	K. H. Keddy, S. Takuva, A. Musekiwa, A. J. Puren, A. Sooka, A. Karstaedt, et al., An association between decreasing incidence of invasive non-typhoidal salmonellosis and increased use of antiretroviral therapy, Gauteng Province, South Africa, 2003-2013, PLoS ONE, 12 (2017), 173091. doi: 10.1371/journal.pone.0176775
[8]	J. J. Gilchrist, C. A. MacLennan, Invasive nontyphoidal Salmonella disease in Africa, EcoSal Plus, 8 (2019), 7.
[9]	M. A. Gordon, Invasive non-typhoidal Salmonella disease-epidemiology, pathogenesis and diagnosis, Curr. Opin. Infect. Dis., 24 (2011), 484. doi: 10.1097/QCO.0b013e32834a9980
[10]	J. A. Crump, R. S. Heyderman, A perspective on invasive Salmonella disease in Africa, Clin. Infect. Dis., 61 (2015), 235-240. doi: 10.1093/cid/civ709
[11]	S. Kariuki, G. Revathi, F. Gakuya, V. Yamo, J. Muyodi, C. Hart, Lack of clonal relationship between non-typhi Salmonella strain types from humans and those isolated from animals living in close contact, FEMS Immunol. Med. Microbiol., 33 (2002), 165-171. doi: 10.1111/j.1574-695X.2002.tb00587.x
[12]	S. Kariuki, M. A. Gordon, N. Feasey, C. M. Parry, Antimicrobial resistance and management of invasive salmonella disease, Vaccine, 33 (2015), 21-29.
[13]	S. Kariuki, G. Revathi, N. Kariuki, J. Kiiru, J. Mwituria, J. Muyodi, et al., Invasive multidrug-resistant non-typhoidal Salmonella infections in Africa: zoonotic or anthroponotic transmission, J. Med. Microbiol., 55 (2006), 585-591. doi: 10.1099/jmm.0.46375-0
[14]	S. Kariuki, C. Mbae, S. Van Puyvelde, R. Onsare, S. Kavai, C. Wairimu, et al., High relatedness of invasive multi-drug resistant non-typhoidal Salmonella genotypes among patients and asymptomatic carriers in endemic informal settlements in Kenya, PLoS Negl. Trop. Dis., 14 (2020), 8440.
[15]	I. Bakach, M. R. Just, M. Gambhir, I. C.-H. Fung, Typhoid transmission: A historical perspective on mathematical model development, Trans. R. Soc. Trop. Med. Hyg., 109 (2015), 679-689. doi: 10.1093/trstmh/trv075
[16]	C. H. Watson, W. J. Edmunds, A review of typhoid fever transmission dynamic models and economic evaluations of vaccination, Vaccine, 33 (2015), 42-54. doi: 10.1016/j.vaccine.2015.04.013
[17]	R. Ivanek, E. L. Snary, A. J. Cook, Y. T. Groehn, A mathematical model for the transmission of Salmonella Typhimurium within a grower-finisher pig herd in Great Britain, J. Food Prot., 67 (2004), 2403-2409. doi: 10.4315/0362-028X-67.11.2403
[18]	Y. Xiao, R. G. Bowers, D. Clancy, N. P. French, Understanding the dynamics of Salmonella infections in dairy herds: A modelling approach, J. Theor. Biol., 233 (2005), 159-175. doi: 10.1016/j.jtbi.2004.09.015
[19]	P. Chapagain, J. Van Kessel, J. Karns, D. Wolfgang, E. Hovingh, K. Nelen, et al., A mathematical model of the dynamics of Salmonella Cerro infection in a US dairy herd, Epidemiol. Infect., 136 (2008), 263-272. doi: 10.1017/S0950268807008400
[20]	A. J. Grant, O. Restif, T. J. McKinley, M. Sheppard, D. J. Maskell, P. Mastroeni, Modelling within-host spatiotemporal dynamics of invasive bacterial disease, PLoS Biol., 6 (2008), 74. doi: 10.1371/journal.pbio.0060074
[21]	C. Manore, T. Graham, A. Carr, A. Feryn, S. Jakhar, H. Mukundan, H. C. Highlander, Modeling and cost benefit analysis to guide deployment of POC diagnostics for non-typhoidal Salmonella infections with antimicrobial resistance, Sci. Rep., 9 (2019), 11245. doi: 10.1038/s41598-019-44824-w
[22]	N. A. Feasey, B. N. Archer, R. S. Heyderman, A. Sooka, B. Dennis, M. A. Gordon, K. H. Keddy, Typhoid fever and invasive nontyphoid salmonellosis, Malawi and South Africa, Emerg. Infect. Dis., 16 (2010), 1448. doi: 10.3201/eid1609.100125
[23]	N. A. Feasey, D. Everett, E. B. Faragher, A. Roca-Feltrer, A. Kang'ombe, B. Denis, et al., Modelling the contributions of malaria, HIV, malnutrition and rainfall to the decline in paediatric invasive non-typhoidal Salmonella disease in Malawi, PLoS Negl. Trop. Dis., 9 (2015), 3979.
[24]	K. H. Keddy, A. Musekiwa, A. Sooka, A. Karstaedt, T. Nana, S. Seetharam, et al., Clinical and microbiological features of invasive nontyphoidal Salmonella associated with HIV-infected patients, Gauteng Province, South Africa, Medicine (Baltimore), 96 (2017), 6448. doi: 10.1097/MD.0000000000006448
[25]	M. Badri, S. D. Lawn, R. Wood, Short-term risk of AIDS or death in people infected with HIV-1 before antiretroviral therapy in South Africa: A longitudinal study, The Lancet, 368 (2006), 1254-1259. doi: 10.1016/S0140-6736(06)69117-4
[26]	Kenya National Bureau of Statistics, Kenya demographic and health survey 2014, Available at http://dhsprogram.com/pubs/pdf/FR308/FR308.pdf.
[27]	Kenya National Bureau of Statistics, Analytical report on population projections, Ministry of State for Planning, XIV.
[28]	M. Oneko, S. Kariuki, V. Muturi-Kioi, K. Otieno, V. O. Otieno, J. M. Williamson, et al., Emergence of community-acquired, multidrug-resistant invasive nontyphoidal Salmonella disease in rural western Kenya, 2009-2013, Clin. Infect. Dis., 61 (2015), 310-316. doi: 10.1093/cid/civ674
[29]	B. Mayanja, J. Todd, P. Hughes, L. Van der Paal, J. Mugisha, E. Atuhumuza, et al., Septicaemia in a population-based HIV clinical cohort in rural Uganda, 1996-2007: Incidence, aetiology, antimicrobial drug resistance and impact of antiretroviral therapy, Trop. Med. Int. Health, 15 (2010), 697-705. doi: 10.1111/j.1365-3156.2010.02528.x
[30]	E. Mfueni, B. Devleesschauwer, A. Rosas-Aguirre, C. Van Malderen, P. T. Brandt, B. Ogutu, et al., True malaria prevalence in children under five: Bayesian estimation using data of malaria household surveys from three sub-Saharan countries, Malar. J., 17 (2018), 65. doi: 10.1186/s12936-018-2211-y
[31]	World Health Organization, Mother-to-child transmission of HIV, http://www.who.int/hiv/topics/mtct/en/ (31 July 2017).
[32]	C. C. Hung, M. N. Hung, P. R. Hsueh, S. Y. Chang, M. Y. Chen, S. M. Hsieh, et al., Risk of recurrent nontyphoid salmonella bacteremia in HIV-infected patients in the era of highly active antiretroviral therapy and an increasing trend of fluoroquinolone resistance, Clin. Infect. Dis., 45 (2007), 60-67. doi: 10.1086/518571
[33]	N. A. Feasey, A. Houston, M. Mukaka, D. Komrower, T. Mwalukomo, L. Tenthani, et al., A reduction in adult blood stream infection and case fatality at a large African hospital following antiretroviral therapy roll-out, PLoS ONE, 9 (2014), 92226. doi: 10.1371/journal.pone.0092226
[34]	M. A. Gordon, S. M. Graham, A. L. Walsh, L. Wilson, A. Phiri, E. Molyneux, et al., Epidemics of invasive Salmonella enterica serovar Enteritidis and S. enterica serovar Typhimurium infection associated with multidrug resistance among adults and children in Malawi, Clin. Infect. Dis., 46 (2008), 963-969. doi: 10.1086/529146
[35]	M. A. Gordon, A. M. Kankwatira, G. Mwafulirwa, A. L. Walsh, M. J. Hopkins, C. M. Parry, et al., Invasive non-typhoid salmonellae establish systemic intracellular infection in HIV-infected adults: An emerging disease pathogenesis, Clin. Infect. Dis., 50 (2010), 953-962. doi: 10.1086/651080
[36]	G. C. Davenport, J. B. Hittner, V. Otieno, Z. Karim, H. Mukundan, P. W. Fenimore, et al., Reduced parasite burden in children with falciparum malaria and bacteremia coinfections: role of mediators of inflammation, Mediators Inflamm., 2016 (2016), 1-14.
[37]	E. M. Novelli, J. B. Hittner, G. C. Davenport, C. Ouma, T. Were, S. Obaro, et al., Clinical predictors of severe malarial anaemia in a holoendemic Plasmodium falciparum transmission area, Br. J. Haematol., 149 (2010), 711-721. doi: 10.1111/j.1365-2141.2010.08147.x
[38]	T. Were, G. C. Davenport, J. B. Hittner, C. Ouma, J. M. Vulule, J. M. Ong'echa, D. J. Perkins, Bacteremia in Kenyan children presenting with malaria, J. Clin. Microbiol., 49 (2011), 671-676. doi: 10.1128/JCM.01864-10
[39]	J. Z. Kubicek-Sutherland, G. Xie, M. Shakya, P. K. Dighe, L. L. Jacobs, H. Daligault, et al., Comparative genomic and phenotypic characterization of invasive non-typhoidal Salmonella isolates from Siaya, Kenya, PLoS Negl. Trop. Dis, 2020.
[40]	J. M. Hyman, J. Li, E. A. Stanley, The differential infectivity and staged progression models for the transmission of HIV, Math. Biosci., 155 (1999), 77-109. doi: 10.1016/S0025-5564(98)10057-3
[41]	Kenya National Bureau of Statistics, Analytical report on migration, Ministry of State for Planning, XII.
[42]	N. A. Feasey, C. Masesa, C. Jassi, E. B. Faragher, J. Mallewa, M. Mallewa, et al., Three epidemics of invasive multidrug-resistant Salmonella bloodstream infection in Blantyre, Malawi, 1998-2014, Clin. Infect. Dis., 61 (2015), 363-371. doi: 10.1093/cid/civ691
[43]	N. Chitnis, J. M. Hyman, J. M. Cushing, Determining important parameters in the spread of malaria through the sensitivity analysis of a mathematical model, Bull. Math. Biol., 70 (2008), 1272-1296. doi: 10.1007/s11538-008-9299-0

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