1921
Volume 93, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract

There has been renewed interest in the use of sporozoite-based approaches for controlled human malaria infections (CHMIs), and several sets of human challenge studies have recently completed. A study undertaken in Tanzania and published in 2014 found dose dependence between 10,000 and 25,000 sporozoite doses, as well as divergent times-to-parasitemia relative to earlier studies in European volunteers, with important implications for planning future studies. Analysis of time-to-event data has had extensive development in recent years, but these methods have had limited exposure outside biostatistics. Expansion of the published analyses to include recent methodological approaches optimized for the types of data used could provide a richer analysis of these studies and may result in alternative findings. Specifically, in a re-analysis of these data using survival analysis techniques, the differences recorded in prepatent periods between the two dosing regimens do not reach statistical significance, and there is no evidence for statistically significant differences in prepatent periods between the Dutch and Tanzanian study sites. Although these findings do not impact the reported safety and tolerability of challange with cryopreserved sporozoites (PfSPZ), or invalidate the authors' hypotheses regarding naturally acquired immunity and its effect on parasite growth rates and prepatent periods, they highlight important opportunities to more fully use datasets from these trials and related CHMI experiments in the planning of future challenge studies.

[open-access] This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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2015-12-09
2017-09-25
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References

  1. Epstein JE, Tewari K, Lyke KE, Sim BKL, Billingsley PF, Laurens MB, Gunasekera A, Chakravarty S, James ER, Sedegah M, Richman A, Velmurugan S, Reyes S, Li M, Tucker K, Ahumada A, Ruben AJ, Li T, Stafford R, Eappen AG, Tamminga C, Bennett JW, Ockenhouse CF, Murphy JR, Komisar J, Thomas N, Loyevsky M, Birkett A, Plowe CV, Loucq C, Edelman R, Richie TL, Seder RA, Hoffman SL, , 2011. Live attenuated malaria vaccine designed to protect through hepatic CD8+ t cell immunity. Science 334: 475480.[Crossref]
  2. Seder RA, Chang L-J, Enama ME, Zephir KL, Sarwar UN, Gordon IJ, Holman LA, James ER, Billingsley PF, Gunasekera A, Richman A, Chakravarty S, Manoj A, Velmurugan S, Li M, Ruben AJ, Li T, Eappen AG, Stafford RE, Plummer SH, Hendel CS, Novik L, Costner PJM, Mendoza FH, Saunders JG, Nason MC, Richardson JH, Murphy J, Davidson SA, Richie TL, Sedegah M, Sutamihardja A, Fahle GA, Lyke KE, Laurens MB, Roederer M, Tewari K, Epstein JE, Sim BKL, Ledgerwood JE, Graham BS, Hoffman SL, , 2013. Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine. Science 341: 13591365.[Crossref]
  3. Roestenberg M, McCall M, Hopman J, Wiersma J, Luty AJ, van Gemert GJ, van de Vegte-Bolmer M, van Schaijk B, Teelen K, Arens T, Spaarman L, de Mast Q, Snounou G, Renia L, van der Ven A, Hermsen CC, Sauerwein R, , 2009. Protection against a malaria challenge by sporozoite inoculation. N Engl J Med 361: 468477.[Crossref]
  4. Billingsley P, Sim BK, Bijker E, Roestenberg M, Lyke K, Laurens M, Mordmueller B, Gomez P, Shekalaghe S, Hodgson S, Hill A, Juma E, Ogutu B, Lell B, Alonso P, Abdullah S, Kremsner P, Tanner M, Sauerwein R, Hoffman S, , 2014. Controlled human malaria infections using aseptic, purified cryopreserved Plasmodium falciparum sporozoites administered by needle and syringe. Malar J 13 (Suppl 1): 12.[Crossref]
  5. Hodgson SH, Juma E, Salim A, Magiri C, Kimani D, Njenga D, Muia A, Cole AO, Ogwang C, Awuondo K, Lowe B, Munene M, Billingsley PF, James ER, Gunasekera A, Sim BKL, Njuguna P, Rampling TW, Richman A, Abebe Y, Kamuyu G, Muthui M, Elias SC, Molyneux S, Gerry S, Macharia A, Williams TN, Bull PC, Hill AVS, Osier FH, Draper SJ, Bejon P, Hoffman SL, Ogutu B, Marsh K, , 2014. Evaluating controlled human malaria infection in Kenyan adults with varying degrees of prior exposure to Plasmodium falciparum using sporozoites administered by intramuscular injection. Infect Dis 5: 686.
  6. Shekalaghe S, Rutaihwa M, Billingsley PF, Chemba M, Daubenberger CA, James E, Mpina M, Juma OA, Schindler T, Huber E, Gunasekera A, Manoj A, Simon B, Savarino E, Church LWP, Hermsen CC, Sauerwein RW, Plowe CV, Venkatesan M, Sasi P, Lweno O, Mutani P, Hamad A, Mohammed A, Urassa A, Mzee T, Padilla D, Ruben A, Sim BKL, Tanner M, Abdullah S, Hoffman SL, , 2014. Controlled human malaria infection of Tanzanians by intradermal injection of aseptic, purified, cryopreserved Plasmodium falciparum sporozoites. Am J Trop Med Hyg 91: 471480.[Crossref]
  7. Sheehy SH, Douglas AD, Draper SJ, , 2013. Challenges of assessing the clinical efficacy of asexual blood-stage Plasmodium falciparum malaria vaccines. Hum Vaccin Immunother 9: 18311840.[Crossref]
  8. Darton TC, Blohmke CJ, Moorthy VS, Altmann DM, Hayden FG, Clutterbuck EA, Levine MM, Hill AVS, Pollard AJ, , 2015. Design, recruitment, and microbiological considerations in human challenge studies. Lancet Infect Dis 15: 840851.[Crossref]
  9. Spring M, Polhemus M, Ockenhouse C, , 2014. Controlled human malaria infection. J Infect Dis 209 (Suppl 2): S40S45.[Crossref]
  10. Roestenberg M, O'Hara GA, Duncan CJA, Epstein JE, Edwards NJ, Scholzen A, van der Ven AJAM, Hermsen CC, Hill AVS, Sauerwein RW, , 2012. Comparison of clinical and parasitological data from controlled human malaria infection trials. PLoS One 7: e38434.[Crossref]
  11. Arévalo-Herrera M, Forero-Peña DA, Rubiano K, Gómez-Hincapie J, Martínez NL, Lopez-Perez M, Castellanos A, Céspedes N, Palacios R, Oñate JM, Herrera S, , 2014. Plasmodium vivax sporozoite challenge in malaria-naïve and semi-immune Colombian volunteers. PLoS One 9: e99754.[Crossref]
  12. Collett D, , 2003. Modelling Survival Data in Medical Research, 2nd edition. Boca Raton, FL: CRC Press.
  13. Klein M, Kleinbaum DG, , 2005. Survival Analysis, 2nd edition. New York, NY: Springer Science+Business Media, Inc.
  14. Hosmer DW, Lemeshow S, May S, , 2011. Applied Survival Analysis: Regression Modeling of Time to Event Data, 2nd edition. Hoboken, NJ: John Wiley and Sons.
  15. Lover AA, Coker RJ, , 2014. Re-assessing the relationship between sporozoite dose and incubation period in Plasmodium vivax malaria: a systematic re-analysis. Parasitology 141: 859868.[Crossref]
  16. Mills M, , 2011. Introducing Survival and Event History Analysis. Los Angeles, CA: SAGE Publications Ltd.[Crossref]
  17. Mills M, , 2011. The fundamentals of survival and event history analysis. Introducing Survival and Event History Analysis. Chapter 1. Los Angeles, CA: Sage Publications. Available at: http://www.sagepub.com/upm-data/39847_9781848601017_Mills.pdf.
  18. White IR, Horton NJ, Carpenter J, Pocock SJ, , 2011. Strategy for intention to treat analysis in randomised trials with missing outcome data. BMJ 342: d40.[Crossref]
  19. Gupta SK, , 2011. Intention-to-treat concept: a review. Perspect Clin Res 2: 109112.[Crossref]
  20. Theunissen C, Janssens P, Demulder A, Nouboussié D, Van Esbroeck M, Van Gompel A, Van den Ende J, , 2009. Falciparum malaria in patient 9 years after leaving malaria-endemic area. Emerg Infect Dis 15: 115116.[Crossref]
  21. Markus MB, , 2012. Dormancy in mammalian malaria. Trends Parasitol 28: 3945.[Crossref]
  22. Thompson FM, Porter DW, Okitsu SL, Westerfeld N, Vogel D, Todryk S, Poulton I, Correa S, Hutchings C, Berthoud T, Dunachie S, Andrews L, Williams JL, Sinden R, Gilbert SC, Pluschke G, Zurbriggen R, Hill AVS, , 2008. Evidence of blood stage efficacy with a virosomal malaria vaccine in a Phase IIa clinical trial. PLoS One 3: e1493.[Crossref]
  23. Li H, Han D, Hou Y, Chen H, Chen Z, , 2015. Statistical inference methods for two crossing survival curves: a comparison of methods. PLoS One 10: e0116774.[Crossref]
  24. Royston P, Parmar MK, , 2013. Restricted mean survival time: an alternative to the hazard ratio for the design and analysis of randomized trials with a time-to-event outcome. BMC Med Res Methodol 13: 152.[Crossref]
  25. Andersen PK, Perme MP, , 2010. Pseudo-observations in survival analysis. Stat Methods Med Res 19: 7199.[Crossref]
  26. Nakagawa S, Cuthill IC, , 2007. Effect size, confidence interval and statistical significance: a practical guide for biologists. Biol Rev Camb Philos Soc 82: 591605.[Crossref]
  27. Parner ET, Andersen PK, , 2010. Regression analysis of censored data using pseudo-observations. Stata J 10: 408422.
  28. Lambert PC, Royston P, , 2009. Further development of flexible parametric models for survival analysis. Stata J 9: 265290.
  29. Jackson CR, , 2015. Package “flexsurv.” CRAN. Available at: http://cran.r-project.org/web/packages/flexsurv/flexsurv.pdf. Accessed July 1, 2015.
  30. Moorthy VS, Reed Z, Smith PG, , 2009. MALVAC 2008: measures of efficacy of malaria vaccines in Phase 2b and Phase 3 trials—scientific, regulatory and public health perspectives. Vaccine 27: 624628.[Crossref]
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Supplementary Data

Supplementary PDF

  • Received : 04 May 2015
  • Accepted : 12 Aug 2015

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