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Dynamic Modeling of Herpes Simplex Virus Type-2 (HSV-2) Transmission: Issues in Structural Uncertainty

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Abstract

The sexually transmitted infection (STI) Herpes simplex virus type-2 (HSV-2) is of public health concern because it is a very common frequently unrecognized lifelong infection, which may facilitate HIV transmission. Within HIV/STI modeling, structural uncertainty has received less attention than parametric uncertainty. By merging the compartments of a “complex” model, a “simple” HSV-2 model is developed. Sexual interactions between female sex workers (FSWs) and clients are modeled using data from India. Latin Hypercube Sampling selects from parameter distributions and both models are run for each of the 10,000 parameter sets generated. Outputs are compared (except for 2,450 unrealistic simulations). The simple model is a good approximation to the complex model once the HSV-2 epidemic has reached 60% of the equilibrium prevalence (95% of the 7,550 runs produced <10% relative error). The simple model is a reduced version of the complex model that retains details implicitly. For late-stage epidemics, the simple model gives similar prevalence trends to the complex model. As HSV-2 epidemics in many populations are advanced, the simple model is accurate in most instances, although the complex model may be preferable for early epidemics. The analysis highlights the issue of structural uncertainty and the value of reducing complexity.

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References

  • Anderson, R.M., Garnett, G.P., 2000. Mathematical models of the transmission and control of sexually transmitted diseases. Sex Transm. Dis. 27(10), 636–43.

    Article  Google Scholar 

  • Antoulas, A.C., Sorensen, D., August 2001. Approximation of large-scale dynamical systems: an overview. http://www-ece.rice.edu/~aca/mtns00.pdf. Site accessed: 26 August 2006.

  • Auvert, B., Puren, A., Taljaard, D., Sobngwi-Tambekou, J., Lagarde, E., Sitta, R., 2005. Can male circumcision prevent acquisition of HSV-2 infection? In: 3rd IAS Conference on HIV Pathogenesis and Treatment, 24–7 July, Rio de Janeiro, Brazil.

  • Baggaley, R.F., Ferguson, N.M., Garnett, G.P., 2005. The epidemiological impact of antiretroviral use predicted by mathematical models: a review. Emerg. Themes Epidemiol. 2 (9)

  • Benedetti, J., Corey, L., Ashley, R., 1994. Recurrence rates in genital herpes after symptomatic first-episode infection. Ann. Int. Med. 121(11), 847–54.

    Google Scholar 

  • Benedetti, J.K., Zeh, J., Corey, L., 1999. Clinical reactivation of genital Herpes simplex virus infection decreases in frequency over time. Ann. Int. Med. 131(1), 14–0.

    Google Scholar 

  • Bentley, M.E., Morrow, K.M., Fullem, A., Chesney, M.A., Horton, S.D., Rosenberg, Z. , 2000. Acceptability of a novel vaginal microbicide during a safety trial among low-risk women. Fam. Plann. Perspect. 32(4), 184–88.

    Article  Google Scholar 

  • Blower, S., 2004. Modelling the genital herpes epidemic. Herpes 11(Suppl 3), 138A–46A.

    Google Scholar 

  • Blower, S.M., Dowlatabadi, H., 1994. Sensitivity and uncertainty analysis of complex models of disease transmission: an HIV model, as an example. Int. Stat. Rev. 62, 229–43.

    Article  MATH  Google Scholar 

  • Blower, S., Ma, L., 2004. Calculating the contribution of Herpes simplex virus type-2 epidemics to increasing HIV incidence: treatment implications. Clin. Infect. Dis. 39(Suppl 5), S240–S247.

    Article  Google Scholar 

  • Blower, S.M., Hartel, D., Dowlatabadi, H., Anderson, R.M., May, R.M., 1991. Drugs, sex and HIV: a mathematical model for New York City. Philos. Trans. R. Soc. Lond. B Biol. Sci. 331(1260), 171–87.

    Article  Google Scholar 

  • Blower, S.M., Porco, T.C., Darby, G., 1998. Predicting and preventing the emergence of antiviral drug resistance in HSV-2. Nat. Med. 4(6), 673–78.

    Article  Google Scholar 

  • Blower, S., Wald, A., Gershengorn, H., Wang, F., Corey, L., 2004. Targeting virological core groups: a new paradigm for controlling Herpes simplex virus type-2 epidemics. J. Infect. Dis. 190(9), 1610–617.

    Article  Google Scholar 

  • Boily, M.C., Masse, B., 1997. Mathematical models of disease transmission: a precious tool for the study of sexually transmitted diseases. Can. J. Public Health 88(4), 255–65.

    Google Scholar 

  • Boily, M.C., Baggaley, R.F., Wang, L., Masse, B.R., White, R.G., Hayes, R. et al., 2007a. The risk of HIV-1 infection per sexual contact in absence of antiretroviral therapy: a systematic review and meta-analysis of observational studies. In: 17th International Society for Sexually Transmitted Diseases Research, 29 July–1 August, Seattle, Washington, USA [Abstract O-058]. http://www.isstdr.org/index.php?id=97.

  • Boily, M.C., Lowndes, C.M., Vickerman, P., Kumaranayake, L., Blanchard, J., Moses, S., , 2007b. Evaluating large-scale HIV prevention interventions: study design for an integrated mathematical modelling approach. Sex Transm. Infect. 83(7), 582–89.

    Article  Google Scholar 

  • Brown, Z.A., Selke, S., Zeh, J., Kopelman, J., Maslow, A., Ashley, R.L. , 1997. The acquisition of Herpes simplex virus during pregnancy. N. Engl. J. Med. 337(8), 509–16.

    Article  Google Scholar 

  • Brugha, R., Keersmaekers, K., Renton, A., Meheus, A., 1997. Genital herpes infection: a review. Int. J. Epidemiol. 26(4), 698–09.

    Article  Google Scholar 

  • Bryson, Y., Dillon, M., Bernstein, D.I., Radolf, J., Zakowski, P., Garratty, E., 1993. Risk of acquisition of genital Herpes simplex virus type-2 in sex partners of persons with genital herpes: a prospective couple study. J. Infect. Dis. 167(4), 942–46.

    Google Scholar 

  • Cancre, N., Tall, A., Rogier, C., Faye, J., Sarr, O., Trape, J.-F. , 2000. Bayesian analysis of an epidemiologic model of plasmodium falciparum malaria infection in Ndiop, Senegal. Am. J. Epidemiol. 152(8), 760–70.

    Article  Google Scholar 

  • Celum, C.L., 2004. The interaction between Herpes simplex virus and human immunodeficiency virus. Herpes 11(Suppl 1), 36A–5A.

    Google Scholar 

  • Cheong, W.K., Thirumoorthy, T., Doraisingham, S., Ling, A.E., 1990. Clinical and laboratory study of first episode genital herpes in Singapore. Int. J. STD & AIDS 1(3), 195–98.

    Google Scholar 

  • Corey, L., Handsfield, H.H., 2000. Genital herpes and public health: addressing a global problem. J. Am. Med. Assoc. 283(6), 791–94.

    Article  Google Scholar 

  • Corey, L., Wald, A., 1999. Sexually Transmitted Diseases, McGraw-Hill, New York. Chap. 21: Genital herpes, pp. 285–12.

    Google Scholar 

  • Corey, L., Adams, H.G., Brown, Z.A., Holmes, K.K., 1983a. Genital Herpes simplex virus infections: clinical manifestations, course, and complications. Ann. Intern. Med. 98(6), 958–72.

    Google Scholar 

  • Corey, L., Fife, K.H., Benedetti, J.K., Winter, C.A., Fahnlander, A., Connor, J.D. , 1983b. Intravenous acyclovir for the treatment of primary genital herpes. Ann. Intern. Med. 98(6), 914–21.

    Google Scholar 

  • Corey, L., Langenberg, A.G., Ashley, R., Sekulovich, R.E., Izu, A.E., Douglas, J.M. Jr. , 1999. Recombinant glycoprotein vaccine for the prevention of genital HSV-2 infection: two randomized controlled trials. Chiron HSV Vaccine Study Group. J. Am. Med. Assoc. 282(4), 331–40.

    Article  Google Scholar 

  • Corey, L., Wald, A., Celum, C.L., Quinn, T.C., 2004a. The effects of herpes simplex virus-2 on HIV-1 acquisition and transmission: a review of two overlapping epidemics. J. Acquir. Immune Defic. Syndr. 35(5), 435–45.

    Article  Google Scholar 

  • Corey, L., Wald, A., Patel, R., Sacks, S.L., Tyring, S.K., Warren, T. , 2004b. Once-daily valacyclovir to reduce the risk of transmission of genital herpes. N. Engl. J. Med. 350(1), 11–0.

    Article  Google Scholar 

  • Cowan, F.M., French, R.S., Mayaud, P., Gopal, R., Robinson, N.J., de Oliveira, S.A. , 2003. Seroepidemiological study of Herpes simplex virus types 1 and 2 in Brazil, Estonia, India, Morocco, and Sri Lanka. Sex Transm. Infect. 79(4), 286–90.

    Article  Google Scholar 

  • Critchfield, G.C., Willard, K.E., 1986. Probabilistic analysis of decision trees using Monte Carlo simulation. Med. Decis. Mak. 6(2), 85–2.

    Article  Google Scholar 

  • Delany, S., Mayaud, P., Clayton, T., Mlaba, N., Akpomiemie, G., Hira, K. et al., 2007. Impact of HSV-2 suppressive therapy on genital and plasma HIV-1 RNA in HIV-1 and HSV-2-seropositive women not taking ART: a randomized, placebo-controlled trial in Johannesburg, South Africa. In: 14th Conference on Retroviruses and Opportunistic Infections, 25–8 February; Los Angeles, USA [Abstract 154LB]. http://www.retroconference.org/2007, accessed 28 May 2007.

  • Diamond, C., Selke, S., Ashley, R., Benedetti, J., Corey, L., 1999. Clinical course of patients with serologic evidence of recurrent genital herpes presenting with signs and symptoms of first episode disease. Sex Transm. Dis. 26(4), 221–25.

    Article  Google Scholar 

  • Dietz, K., Hadeler, K.P., 1988. Epidemiological models for sexually transmitted diseases. J. Math. Biol. 26(1), 1–5.

    MATH  MathSciNet  Google Scholar 

  • Doubilet, P., Begg, C.B., Weinstein, M.C., Braun, P., McNeil, B.J., 1985. Probabilistic sensitivity analysis using Monte Carlo simulation. A practical approach. Med. Decis. Mak. 5(2), 157–77.

    Article  Google Scholar 

  • Eames, K.T.D., Keeling, M.J., 2002. Modeling dynamic and network heterogeneities in the spread of sexually transmitted diseases. Proc. Natl. Acad. Sci. 99(20), 13330–3335.

    Article  Google Scholar 

  • Ferguson, N.M., Garnett, G.P., 2000. More realistic models of sexually transmitted disease transmission dynamics: sexual partnership networks, pair models, and moment closure. Sex Transm. Dis. 27(10), 600–09.

    Article  Google Scholar 

  • Fisman, D.N., Lipsitch, M., Hook, E.W. 3rd, Goldie, S.J., 2002. Projection of the future dimensions and costs of the genital Herpes simplex type-2 epidemic in the united states. Sex Transm. Dis. 29(10), 608–22.

    Article  Google Scholar 

  • Foss, A.M., Vickerman, P., Watts, C., Mayaud, P., Weiss, H., Ramesh, B.M. et al., 2007. Modeling the interactions between HSV-2 and HIV: implications for the HIV epidemic in southern India. In: 17th International Society for Sexually Transmitted Diseases Research, 29 July–1 August; Seattle, Washington, USA [Abstract 329]. http://www.isstdr.org/index.php?id=97.

  • Freeman, E.E., Bakker, R., White, R.G., Orroth, K.K., Buve, A., Hayes, R. et al., 2006a. Four cities modelling: simulated effect of HSV-2 prophylactic vaccines on population-level HIV incidence in sub-Saharan Africa. In: XVI International AIDS Conference, 13–8 August; Toronto, Canada [Abstract TUPE0414]. http://www.iasociety.org/abstract/show.asp?abstract_id=2192424.

  • Freeman, E.E., Weiss, H.A., Glynn, J.R., Cross, P.L., Whitworth, J.A., Hayes, R.J., 2006b. Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. AIDS 20(1), 73–3.

    Article  Google Scholar 

  • Gadkari, D.A., Quinn, T.C., Gangakhedkar, R.R., Mehendale, S.M., Divekar, A.D., Risbud, A.R. , 1998. HIV-1 DNA shedding in genital ulcers and its associated risk factors in Pune, India. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 18(3), 277–81.

    Google Scholar 

  • Garnett, G.P., Anderson, R.M., 1996. Sexually transmitted diseases and sexual behavior: insights from mathematical models. J. Infect. Dis. 17(Suppl 2), S150–S161.

    Google Scholar 

  • Garnett, G.P., Dubin, G., Slaoui, M., Darcis, T., 2004. The potential epidemiological impact of a genital herpes vaccine for women. Sex Transm. Infect. 80(1), 24–9.

    Article  Google Scholar 

  • Gershengorn, H.B., Blower, S.M., 2000. Impact of antivirals and emergence of drug resistance: HSV-2 epidemic control. AIDS Patient Care STDS 14(3), 133–42.

    Article  Google Scholar 

  • Gershengorn, H.B., Darby, G., Blower, S.M., 2003. Predicting the emergence of drug-resistant HSV-2: new predictions. BMC Infect. Dis. 3(1), 1.

    Article  Google Scholar 

  • Ghani, A.C., Aral, S.O., 2005. Patterns of sex worker-client contacts and their implications for the persistence of sexually transmitted infections. J. Infect. Dis. 1(Suppl 1), S34–S41.

    Article  Google Scholar 

  • Guinan, M.E., MacCalman, J., Kern, E.R., Overall, J.C. Jr., Spruance, L.S., 1981. The course of untreated recurrent genital Herpes simplex infection in 27 women. N. Engl. J. Med. 304(13), 759–63.

    Google Scholar 

  • Hawkes, S., Santhya, K.G., 2002. Diverse realities: sexually transmitted infections and HIV in India. Sex Transm. Infect. 78(Suppl 1), i31–i39.

    Article  Google Scholar 

  • Hoeting, J.A., Madigan, D., Raftery, A.E., Volinsky, C.T., 1999. Bayesian model averaging: a tutorial. Stat. Sci. 14(4), 382–17.

    Article  MATH  MathSciNet  Google Scholar 

  • Holmes, K.K., Levine, R., Weaver, M., 2004. Effectiveness of condoms in preventing sexually transmitted infections. Bull. World Health Organ. 82(6), 454–61.

    Google Scholar 

  • ICHAP, 2004/2005. HSV-2 prevalence of general population in Bagalkot District: sub-sample of GPS (stratified random sample). India-Canada Collaborative HIV/AIDS Project (ICHAP).

  • Iman, R.L., Conover, W.J., 1982. A distribution-free approach to inducing rank correlation among input variables. Commun. Stat.: Simul. Comput. 11, 311–34.

    Article  MATH  Google Scholar 

  • Iman, R.L., Davenport, J.M., 1982. Rank correlation plots for use with correlated input variables. Commun. Stat.: Simul. Comput. 11, 335–60.

    Article  Google Scholar 

  • Iman, R.L., Helton, J.C., 1988. An investigation of uncertainty and sensitivity analysis techniques for computer models. Risk Anal. 8, 71–0.

    Article  Google Scholar 

  • Isukapalli, S.S., Roy, A., Georgopoulos, P.G., 1998. Stochastic response surface methods (SRSMs) for uncertainty propagation: application to environmental and biological systems. Risk Anal. 18(3), 351–63.

    Article  Google Scholar 

  • Isukapalli, S.S., Roy, A., Georgopoulos, P.G., 2000. Efficient sensitivity/uncertainty analysis using the combined stochastic response surface method and automated differentiation: application to environmental and biological systems. Risk Anal. 20(5), 591–02.

    Article  Google Scholar 

  • Jacob, M., Rao, P.S., Sridharan, G., John, T.J., 1989. Epidemiology & clinical profile of genital herpes. Indian J. Med. Res. 89, 4–1.

    Google Scholar 

  • Joshi, S., Chandorkar, A., Krishnan, G., Walimbe, A., Gangakhedkar, R., Risbud, A. , 2001. Cervical intraepithelial changes & HIV infection in women attending sexually transmitted disease clinics in Pune, India. Indian J. Med. Res. 113, 161–69.

    Google Scholar 

  • KHPT, 2005. Mapping of high risk groups in (urban) Karnataka: Karnataka Health Promotion Trust (KHPT).

  • KHPT, 2006. IBBA in FSW from Mysore District, Karnataka Health Promotion Trust (KHPT).

  • Koelle, D.M., Benedetti, J., Langenberg, A., Corey, L., 1992. Asymptomatic reactivation of Herpes simplex virus in women after the first episode of genital herpes. Ann. Intern. Med. 116(6), 433–37.

    Google Scholar 

  • Korenromp, E.L., Bakker, R., De Vlas, S.J., Robinson, N.J., Hayes, R., Habbema, J.D., 2002. Can behavior change explain increases in the proportion of genital ulcers attributable to herpes in sub-Saharan Africa? A simulation modeling study. Sex Transm. Dis. 29(4), 228–38.

    Article  Google Scholar 

  • Kretzschmar, M., Dietz, K., 1998. The effect of pair formation and variable infectivity on the spread of an infection without recovery. Math. Biosci. 148(1), 83–13.

    Article  MATH  MathSciNet  Google Scholar 

  • Kumaranayake, L., Watts, C., Vickerman, P., Terris-Prestholt, F., 2006. Economic evaluation of HIV prevention activities: dynamic challenges for cost-effectiveness analysis. In: Roberts, J. (Ed.), The Economics of Infectious Diseases, pp. 65–3. Oxford University Press, Oxford.

    Google Scholar 

  • Kura, M.M., Hira, S., Kohli, M., Dalal, P.J., Ramnani, V.K., Jagtap, M.R., 1998. High occurrence of HBV among STD clinic attenders in Bombay, India. Int. J. STD AIDS 9(4), 231–33.

    Article  Google Scholar 

  • Lafferty, W.E., Coombs, R.W., Benedetti, J., Critchlow, C., Corey, L., 1987. Recurrences after oral and genital Herpes simplex virus infection. Influence of site of infection and viral type. N. Engl. J. Med. 316(23), 1444–449.

    Article  Google Scholar 

  • Langenberg, A.G., Corey, L., Ashley, R.L., Leong, W.P., Straus, S.E., 1999. A prospective study of new infections with Herpes simplex virus type-1 and type-2. Chiron HSV Vaccine Study Group. N. Engl. J. Med. 341(19), 1432–438.

    Article  Google Scholar 

  • Lipsitch, M., Bacon, T.H., Leary, J.J., Antia, R., Levin, B.R., 2000. Effects of antiviral usage on transmission dynamics of Herpes simplex virus type-1 and on antiviral resistance: predictions of mathematical models. Antimicrob. Agents Chemother. 44(10), 2824–835.

    Article  Google Scholar 

  • Manning, W.G., Fryback, D.G., Weinstein, M.C., 1996. Reflecting uncertainty in cost-effectiveness analysis. In: Gold, M., Siegel, J., Russell, L. (Eds.), Cost-effectiveness in Health and Medicine, pp. 247–75. Oxford University Press, New York.

    Google Scholar 

  • Mark, K.E., Wald, A., Magaret, A.S., Selke, S., Olin, L.P., Huang, M.-L. et al., 2007. Rapid onset and clearance of genital HSV reactivations in immunocompetent adults: the virus is usually “on” In: 17th International Society for Sexually Transmitted Diseases Research, 29 July – 1 August; Seattle, Washington, USA [Abstract O-030]. http://www.isstdr.org/index.php?id=97.

  • McKay, M.D., Conover, W.J., Beckman, R.J., 1979. A comparison of three methods for selecting values of input variables in the analysis of output from a computer code. Technometrics 21, 239–46.

    Article  MATH  MathSciNet  Google Scholar 

  • Mertz, G.J., Schmidt, O., Jourden, J.L., Guinan, M.E., Remington, M.L., Fahnlander, A. , 1985. Frequency of acquisition of first-episode genital infection with Herpes simplex virus from symptomatic and asymptomatic source contacts. Sex Transm. Dis. 12(1), 33–9.

    Google Scholar 

  • Mertz, G.J., Coombs, R.W., Ashley, R., Jourden, J., Remington, M., Winter, C. , 1988. Transmission of genital herpes in couples with one symptomatic and one asymptomatic partner: a prospective study. J. Infect. Dis. 157(6), 1169–177.

    Google Scholar 

  • Mertz, G.J., Benedetti, J., Ashley, R., Selke, S.A., Corey, L., 1992. Risk factors for the sexual transmission of genital herpes. Ann. Intern. Med. 116(3), 197–02.

    Google Scholar 

  • NACO, 2001. National baseline high risk and bridge population behavioural surveillance survey—part I (FSW and their clients) and India. http://www.nacoonline.org/publication.htm.

  • Nagot, N., Ouedraogo, A., Foulongne, V., Konate, I., Weiss, H.A., Vergne, L. , 2007. Reduction of HIV-1 RNA levels with therapy to suppress Herpes simplex virus. N. Engl. J. Med. 356(8), 790–99.

    Article  Google Scholar 

  • National Informatics Centre, 2004. Official website of Bagalkot District. http://bagalkot.nic.in/. Site accessed: 19 May 2004.

  • Newton, E.A., Kuder, J.M., 2000. A model of the transmission and control of genital herpes. Sex Transm. Dis. 27(7), 363–70.

    Article  Google Scholar 

  • Orroth, K.K., White, R.G., Korenromp, E.L., Bakker, R., Changalucha, J., Habbema, J.D. , 2006. Empirical observations underestimate the proportion of human immunodeficiency virus infections attributable to sexually transmitted diseases in the Mwanza and Rakai sexually transmitted disease treatment trials: simulation results. Sex Transm. Dis. 33(9), 536–44.

    Article  Google Scholar 

  • Ramesh, B.M., Rajeswari, N.V., Sankangoudar, S., 2003. Female commercial sex workers in Karnataka: a baseline survey, 2002, Bangalore and Dharwad, India-Canada Collaborative HIV/AIDS Project (ICHAP) and Population Research Centre, March 2003.

  • Rana, R.K., Pimenta, J.M., Rosenberg, D.M., Warren, T., Sekhin, S., Cook, S.F. , 2006. Sexual behaviour and condom use among individuals with a history of symptomatic genital herpes. Sex Transm. Infect. 82(1), 69–4.

    Article  Google Scholar 

  • Reynolds, S.J., Risbud, A.R., Shepherd, M.E., Zenilman, J.M., Brookmeyer, R.S., Paranjape, R.S. , 2003. Recent Herpes simplex virus type-2 infection and the risk of human immunodeficiency virus type-1 acquisition in India. J. Infect. Dis. 187(10), 1513–521.

    Article  Google Scholar 

  • Reynolds, S.J., Shepherd, M.E., Risbud, A.R., Gangakhedkar, R.R., Brookmeyer, R.S., Divekar, A.D. , 2004. Male circumcision and risk of HIV-1 and other sexually transmitted infections in India. Lancet 363(9414), 1039–040.

    Article  Google Scholar 

  • Rowley, J.T.F., 1992. The demographic and economic consequences of the AIDS epidemic in sub-Saharan Africa. Thesis for Doctor of Philosophy and Diploma of Imperial College in the Faculty of Science of the University of London. Ph.D. thesis, Imperial College London.

  • Schacker, T., Zeh, J., Hu, H.L., Hill, E., Corey, L., 1998. Frequency of symptomatic and asymptomatic herpes simplex virus type 2 reactivations among human immunodeficiency virus-infected men. J. Infect. Dis. 178(6), 1616–622.

    Article  Google Scholar 

  • Schinazi, R.B., 1999. Strategies to control the genital herpes epidemic. Math. Biosci. 159(2), 113–21.

    Article  MATH  MathSciNet  Google Scholar 

  • Schwartz, E.J., Blower, S., 2005. Predicting the potential individual- and population-level effects of imperfect Herpes simplex virus type-2 vaccines. J. Infect. Dis. 191(10), 1734–746.

    Article  Google Scholar 

  • Schwartz, E.J., Bodine, E.N., Blower, S., 2007. Effectiveness and efficiency of imperfect therapeutic HSV-2 vaccines. Hum. Vaccin. 3(6).

  • Sharma, V.K., Khandpur, S., 2004. Changing patterns of sexually transmitted infections in India. Natl. Med. J. India 17(6), 310–19.

    Google Scholar 

  • Spiegelhalter, D.J., Best, N.G., Carlin, B.P., van der Linde, X., 2002. A Bayesian measures of model complexity and fit. J. R. Stat. Soc. B 64(4), 583–39.

    Article  MATH  Google Scholar 

  • Stanberry, L.R., Spruance, S.L., Cunningham, A.L., Bernstein, D.I., Mindel, A., Sacks, S. , 2002. Glycoprotein-D-adjuvant vaccine to prevent genital herpes. N. Engl. J. Med. 347(21), 1652–661.

    Article  Google Scholar 

  • Stein, M., 1987. Large sample properties of simulations using Latin hypercube sampling. Technometrics 29(2), 143–51.

    Article  MATH  MathSciNet  Google Scholar 

  • Sweat, M., Gregorich, S., Sangiwa, G., Furlonge, C., Balmer, D., Kamenga, C. , 2000. Cost-effectiveness of voluntary HIV-1 counselling and testing in reducing sexual transmission of HIV-1 in Kenya and Tanzania. Lancet 356, 113–21.

    Article  Google Scholar 

  • Vickerman, P., Watts, C.H., 2003. Injecting drug use and the sexual transmission of HIV: simple model insights. Int. J. Drug Policy 14, 89–3.

    Article  Google Scholar 

  • Wald, A., Link, K., 2002. Risk of human immunodeficiency virus infection in Herpes simplex virus type-2-seropositive persons: a meta-analysis. J. Infect. Dis. 185(1), 45–2.

    Article  Google Scholar 

  • Wald, A., Zeh, J., Selke, S., Ashley, R.L., Corey, L., 1995. Virologic characteristics of subclinical and symptomatic genital herpes infections. N. Engl. J. Med. 333(12), 770–75.

    Article  Google Scholar 

  • Wald, A., Corey, L., Cone, R., Hobson, A., Davis, G., Zeh, J., 1997. Frequent genital Herpes simplex virus 2 shedding in immunocompetent women. Effect of acyclovir treatment. J. Clin. Invest. 99(5), 1092–097.

    Article  Google Scholar 

  • Wald, A., Zeh, J., Selke, S., Warren, T., Ryncarz, A.J., Ashley, R. , 2000. Reactivation of genital Herpes simplex virus type-2 infection in asymptomatic seropositive persons. N. Engl. J. Med. 342(12), 844–50.

    Article  Google Scholar 

  • Wald, A., Langenberg, A.G., Link, K., Izu, A.E., Ashley, R., Warren, T. , 2001. Effect of condoms on reducing the transmission of Herpes simplex virus type-2 from men to women. J. Am. Med. Assoc. 285(24), 3100–106.

    Article  Google Scholar 

  • Wald, A., Langenberg, A.G.M., Kexel, E., Izu, A., Ashley, R., Corey, L., 2002a. Condoms protect men and women against Herpes simplex virus type-2 (HSV-2) acquisition. In: National STD Prevention Conference; San Diego, CA [Abstract 274]. http://www.cdc.gov/std/Media/2002ConfAbOther2.htm.

  • Wald, A., Zeh, J., Selke, S., Warren, T., Ashley, R., Corey, L., 2002b. Genital shedding of Herpes simplex virus among men. J. Infect. Dis. 186(Suppl 1), S34–S39.

    Article  Google Scholar 

  • Wald, A., Huang, M.L., Carrell, D., Selke, S., Corey, L., 2003. Polymerase chain reaction for detection of Herpes simplex virus (HSV) DNA on mucosal surfaces: comparison with HSV isolation in cell culture. J. Infect. Dis. 188(9), 1345–351.

    Article  Google Scholar 

  • Wald, A., Langenberg, A.G.M., Krantz, E., Douglas, J.M. Jr., Handsfield, H.H., DiCardo, R.P. , 2005. The relationship between condom use and herpes simplex virus acquisition. Ann. Intern. Med. 143(10), 707–13.

    Google Scholar 

  • Watts, C., Kumaranayake, L., Vickerman, P., Terris-Prestholt, F., 2002. The public health benefits of microbicides in lower-income countries. The Rockefeller Foundation 2002. http://www.rockfound.org/Documents/488/rep7_publichealth.pdf., New York.

  • Weiss, H.A., Thomas, S.L., Munabi, S.K., Hayes, R.J., 2006. Male circumcision and risk of syphilis, chancroid, and genital herpes: a systematic review and metaanalysis. Sex Transm. Infect. 82(2), 101–10.

    Article  Google Scholar 

  • White, P.J., Garnett, G.P., 1999. Use of antiviral treatment and prophylaxis is unlikely to have a major impact on the prevalence of Herpes simplex virus type-2. Sex Transm. Infect. 75(1), 49–4.

    Article  Google Scholar 

  • White, R.G., Orroth, K.K., Korenromp, E.L., Bakker, R., Wambura, M., Sewankambo, N.K. , 2004. Can population differences explain the contrasting results of the Mwanza, Rakai, and Masaka HIV/sexually transmitted disease intervention trials?: a modeling study. J. Acquir. Immune Defic. Syndr. 37(4), 1500–513.

    Article  Google Scholar 

  • Williams, J.R., Jordan, J.C., Davis, A., Garnett, G.P., 2007. Suppressive valacyclovir therapy: impact on the population spread of HSV-2 infection. Sex Transm. Dis. 34(3), 123–31.

    Article  Google Scholar 

  • Zuckerman, R.A., Lucchetti, A., Whittington, W.L., Sanchez, J., Coombs, R.W., Zuniga, R. , 2007. Herpes simplex virus (HSV) suppression with valacyclovir reduces rectal and blood plasma HIV-1 levels in HIV-1/HSV-2-seropositive men: a randomized, double-blind, placebo-controlled crossover trial. J. Infect. Dis. 196(10), 1500–508.

    Article  Google Scholar 

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Correspondence to Anna M. Foss.

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Foss, A.M., Vickerman, P.T., Chalabi, Z. et al. Dynamic Modeling of Herpes Simplex Virus Type-2 (HSV-2) Transmission: Issues in Structural Uncertainty. Bull. Math. Biol. 71, 720–749 (2009). https://doi.org/10.1007/s11538-008-9379-1

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  • DOI: https://doi.org/10.1007/s11538-008-9379-1

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