Optimising Controlled Human Malaria Infection Studies Using Cryopreserved P. falciparum Parasites Administered by Needle and Syringe

Susanne H Sheehy; Alexandra J Spencer; Alexander D Douglas; B Kim Lee Sim; Rhea J Longley; Nick J Edwards; Ian D Poulton; Domtila Kimani; Andrew Richard Williams; Nicholas A Anagnostou; Rachel Roberts; Simon Kerridge; Merryn Voysey; Eric R James; Peter F Billingsley; Anusha Gunasekera; Alison M Lawrie; Stephen L Hoffman; Adrian V S Hill

doi:10.1371/journal.pone.0065960

Optimising Controlled Human Malaria Infection Studies Using Cryopreserved P. falciparum Parasites Administered by Needle and Syringe

Susanne H Sheehy, Alexandra J Spencer, Alexander D Douglas, B Kim Lee Sim, Rhea J Longley, Nick J Edwards, Ian D Poulton, Domtila Kimani, Andrew Richard Williams, Nicholas A Anagnostou, Rachel Roberts, Simon Kerridge, Merryn Voysey, Eric R James, Peter F Billingsley, Anusha Gunasekera, Alison M Lawrie, Stephen L Hoffman, Adrian V S Hill

63 Citationer (Scopus)

Abstract

Background:Controlled human malaria infection (CHMI) studies have become a routine tool to evaluate efficacy of candidate anti-malarial drugs and vaccines. To date, CHMI trials have mostly been conducted using the bite of infected mosquitoes, restricting the number of trial sites that can perform CHMI studies. Aseptic, cryopreserved P. falciparum sporozoites (PfSPZ Challenge) provide a potentially more accurate, reproducible and practical alternative, allowing a known number of sporozoites to be administered simply by injection.Methodology:We sought to assess the infectivity of PfSPZ Challenge administered in different dosing regimens to malaria-naive healthy adults (n = 18). Six participants received 2,500 sporozoites intradermally (ID), six received 2,500 sporozoites intramuscularly (IM) and six received 25,000 sporozoites IM.Findings:Five out of six participants receiving 2,500 sporozoites ID, 3/6 participants receiving 2,500 sporozoites IM and 6/6 participants receiving 25,000 sporozoites IM were successfully infected. The median time to diagnosis was 13.2, 17.8 and 12.7 days for 2,500 sporozoites ID, 2,500 sporozoites IM and 25,000 sporozoites IM respectively (Kaplan Meier method; p = 0.024 log rank test).Conclusions:2,500 sporozoites ID and 25,000 sporozoites IM have similar infectivities. Given the dose response in infectivity seen with IM administration, further work should evaluate increasing doses of PfSPZ Challenge IM to identify a dosing regimen that reliably infects 100% of participants.Trial Registration:ClinicalTrials.gov NCT01465048.

Originalsprog	Engelsk
Tidsskrift	PLOS ONE
Vol/bind	8
Udgave nummer	6
Sider (fra-til)	e65960
ISSN	1932-6203
DOI	https://doi.org/10.1371/journal.pone.0065960
Status	Udgivet - 18 jun. 2013
Udgivet eksternt	Ja

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10.1371/journal.pone.0065960

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Sheehy, S. H., Spencer, A. J., Douglas, A. D., Sim, B. K. L., Longley, R. J., Edwards, N. J., Poulton, I. D., Kimani, D., Williams, A. R., Anagnostou, N. A., Roberts, R., Kerridge, S., Voysey, M., James, E. R., Billingsley, P. F., Gunasekera, A., Lawrie, A. M., Hoffman, S. L., & Hill, A. V. S. (2013). Optimising Controlled Human Malaria Infection Studies Using Cryopreserved P. falciparum Parasites Administered by Needle and Syringe. PLOS ONE, 8(6), e65960. https://doi.org/10.1371/journal.pone.0065960

Sheehy, SH, Spencer, AJ, Douglas, AD, Sim, BKL, Longley, RJ, Edwards, NJ, Poulton, ID, Kimani, D, Williams, AR, Anagnostou, NA, Roberts, R, Kerridge, S, Voysey, M, James, ER, Billingsley, PF, Gunasekera, A, Lawrie, AM, Hoffman, SL & Hill, AVS 2013, 'Optimising Controlled Human Malaria Infection Studies Using Cryopreserved P. falciparum Parasites Administered by Needle and Syringe', PLOS ONE, bind 8, nr. 6, s. e65960. https://doi.org/10.1371/journal.pone.0065960

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title = "Optimising Controlled Human Malaria Infection Studies Using Cryopreserved P. falciparum Parasites Administered by Needle and Syringe",

abstract = "Background:Controlled human malaria infection (CHMI) studies have become a routine tool to evaluate efficacy of candidate anti-malarial drugs and vaccines. To date, CHMI trials have mostly been conducted using the bite of infected mosquitoes, restricting the number of trial sites that can perform CHMI studies. Aseptic, cryopreserved P. falciparum sporozoites (PfSPZ Challenge) provide a potentially more accurate, reproducible and practical alternative, allowing a known number of sporozoites to be administered simply by injection.Methodology:We sought to assess the infectivity of PfSPZ Challenge administered in different dosing regimens to malaria-naive healthy adults (n = 18). Six participants received 2,500 sporozoites intradermally (ID), six received 2,500 sporozoites intramuscularly (IM) and six received 25,000 sporozoites IM.Findings:Five out of six participants receiving 2,500 sporozoites ID, 3/6 participants receiving 2,500 sporozoites IM and 6/6 participants receiving 25,000 sporozoites IM were successfully infected. The median time to diagnosis was 13.2, 17.8 and 12.7 days for 2,500 sporozoites ID, 2,500 sporozoites IM and 25,000 sporozoites IM respectively (Kaplan Meier method; p = 0.024 log rank test).Conclusions:2,500 sporozoites ID and 25,000 sporozoites IM have similar infectivities. Given the dose response in infectivity seen with IM administration, further work should evaluate increasing doses of PfSPZ Challenge IM to identify a dosing regimen that reliably infects 100% of participants.Trial Registration:ClinicalTrials.gov NCT01465048.",

author = "Sheehy, {Susanne H} and Spencer, {Alexandra J} and Douglas, {Alexander D} and Sim, {B Kim Lee} and Longley, {Rhea J} and Edwards, {Nick J} and Poulton, {Ian D} and Domtila Kimani and Williams, {Andrew Richard} and Anagnostou, {Nicholas A} and Rachel Roberts and Simon Kerridge and Merryn Voysey and James, {Eric R} and Billingsley, {Peter F} and Anusha Gunasekera and Lawrie, {Alison M} and Hoffman, {Stephen L} and Hill, {Adrian V S}",

year = "2013",

month = jun,

day = "18",

doi = "10.1371/journal.pone.0065960",

language = "English",

volume = "8",

pages = "e65960",

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TY - JOUR

T1 - Optimising Controlled Human Malaria Infection Studies Using Cryopreserved P. falciparum Parasites Administered by Needle and Syringe

AU - Sheehy, Susanne H

AU - Spencer, Alexandra J

AU - Douglas, Alexander D

AU - Sim, B Kim Lee

AU - Longley, Rhea J

AU - Edwards, Nick J

AU - Poulton, Ian D

AU - Kimani, Domtila

AU - Williams, Andrew Richard

AU - Anagnostou, Nicholas A

AU - Roberts, Rachel

AU - Kerridge, Simon

AU - Voysey, Merryn

AU - James, Eric R

AU - Billingsley, Peter F

AU - Gunasekera, Anusha

AU - Lawrie, Alison M

AU - Hoffman, Stephen L

AU - Hill, Adrian V S

PY - 2013/6/18

Y1 - 2013/6/18

N2 - Background:Controlled human malaria infection (CHMI) studies have become a routine tool to evaluate efficacy of candidate anti-malarial drugs and vaccines. To date, CHMI trials have mostly been conducted using the bite of infected mosquitoes, restricting the number of trial sites that can perform CHMI studies. Aseptic, cryopreserved P. falciparum sporozoites (PfSPZ Challenge) provide a potentially more accurate, reproducible and practical alternative, allowing a known number of sporozoites to be administered simply by injection.Methodology:We sought to assess the infectivity of PfSPZ Challenge administered in different dosing regimens to malaria-naive healthy adults (n = 18). Six participants received 2,500 sporozoites intradermally (ID), six received 2,500 sporozoites intramuscularly (IM) and six received 25,000 sporozoites IM.Findings:Five out of six participants receiving 2,500 sporozoites ID, 3/6 participants receiving 2,500 sporozoites IM and 6/6 participants receiving 25,000 sporozoites IM were successfully infected. The median time to diagnosis was 13.2, 17.8 and 12.7 days for 2,500 sporozoites ID, 2,500 sporozoites IM and 25,000 sporozoites IM respectively (Kaplan Meier method; p = 0.024 log rank test).Conclusions:2,500 sporozoites ID and 25,000 sporozoites IM have similar infectivities. Given the dose response in infectivity seen with IM administration, further work should evaluate increasing doses of PfSPZ Challenge IM to identify a dosing regimen that reliably infects 100% of participants.Trial Registration:ClinicalTrials.gov NCT01465048.

AB - Background:Controlled human malaria infection (CHMI) studies have become a routine tool to evaluate efficacy of candidate anti-malarial drugs and vaccines. To date, CHMI trials have mostly been conducted using the bite of infected mosquitoes, restricting the number of trial sites that can perform CHMI studies. Aseptic, cryopreserved P. falciparum sporozoites (PfSPZ Challenge) provide a potentially more accurate, reproducible and practical alternative, allowing a known number of sporozoites to be administered simply by injection.Methodology:We sought to assess the infectivity of PfSPZ Challenge administered in different dosing regimens to malaria-naive healthy adults (n = 18). Six participants received 2,500 sporozoites intradermally (ID), six received 2,500 sporozoites intramuscularly (IM) and six received 25,000 sporozoites IM.Findings:Five out of six participants receiving 2,500 sporozoites ID, 3/6 participants receiving 2,500 sporozoites IM and 6/6 participants receiving 25,000 sporozoites IM were successfully infected. The median time to diagnosis was 13.2, 17.8 and 12.7 days for 2,500 sporozoites ID, 2,500 sporozoites IM and 25,000 sporozoites IM respectively (Kaplan Meier method; p = 0.024 log rank test).Conclusions:2,500 sporozoites ID and 25,000 sporozoites IM have similar infectivities. Given the dose response in infectivity seen with IM administration, further work should evaluate increasing doses of PfSPZ Challenge IM to identify a dosing regimen that reliably infects 100% of participants.Trial Registration:ClinicalTrials.gov NCT01465048.

U2 - 10.1371/journal.pone.0065960

DO - 10.1371/journal.pone.0065960

M3 - Journal article

C2 - 23823332

SN - 1932-6203

VL - 8

SP - e65960

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 6

ER -

Optimising Controlled Human Malaria Infection Studies Using Cryopreserved P. falciparum Parasites Administered by Needle and Syringe

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