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Impact of Sickle Cell Trait and Naturally Acquired Immunity on Uncomplicated Malaria after Controlled Human Malaria Infection in Adults in Gabon
Controlled human malaria infection (CHMI) by direct venous inoculation (DVI) with 3,200 cryopreserved Plasmodium falciparum sporozoites (PfSPZ) consistently leads to parasitemia and malaria symptoms in malaria-naive adults. We used CHMI by DVI to investigate infection rates, parasite kinetics, and m...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society of Tropical Medicine and Hygiene
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5929186/ https://www.ncbi.nlm.nih.gov/pubmed/29260650 http://dx.doi.org/10.4269/ajtmh.17-0343 |
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author | Lell, Bertrand Mordmüller, Benjamin Dejon Agobe, Jean-Claude Honkpehedji, Josiane Zinsou, Jeannot Mengue, Juliana Boex Loembe, Marguerite Massinga Adegnika, Ayola Akim Held, Jana Lalremruata, Albert Nguyen, The Trong Esen, Meral KC, Natasha Ruben, Adam J. Chakravarty, Sumana Lee Sim, B. Kim Billingsley, Peter F. James, Eric R. Richie, Thomas L. Hoffman, Stephen L. Kremsner, Peter G. |
author_facet | Lell, Bertrand Mordmüller, Benjamin Dejon Agobe, Jean-Claude Honkpehedji, Josiane Zinsou, Jeannot Mengue, Juliana Boex Loembe, Marguerite Massinga Adegnika, Ayola Akim Held, Jana Lalremruata, Albert Nguyen, The Trong Esen, Meral KC, Natasha Ruben, Adam J. Chakravarty, Sumana Lee Sim, B. Kim Billingsley, Peter F. James, Eric R. Richie, Thomas L. Hoffman, Stephen L. Kremsner, Peter G. |
author_sort | Lell, Bertrand |
collection | PubMed |
description | Controlled human malaria infection (CHMI) by direct venous inoculation (DVI) with 3,200 cryopreserved Plasmodium falciparum sporozoites (PfSPZ) consistently leads to parasitemia and malaria symptoms in malaria-naive adults. We used CHMI by DVI to investigate infection rates, parasite kinetics, and malaria symptoms in lifelong malaria–exposed (semi-immune) Gabonese adults with and without sickle cell trait. Eleven semi-immune Gabonese with normal hemoglobin (IA), nine with sickle cell trait (IS), and five nonimmune European controls with normal hemoglobin (NI) received 3,200 PfSPZ by DVI and were followed 28 days for parasitemia by thick blood smear (TBS) and quantitative polymerase chain reaction (qPCR) and for malaria symptoms. End points were time to parasitemia and parasitemia plus symptoms. PfSPZ Challenge was well tolerated and safe. Five of the five (100%) NI, 7/11 (64%) IA, and 5/9 (56%) IS volunteers developed parasitemia by TBS, and 5/5 (100%) NI, 9/11 (82%) IA, and 7/9 (78%) IS by qPCR, respectively. The time to parasitemia by TBS was longer in IA (geometric mean 16.9 days) and IS (19.1 days) than in NA (12.6 days) volunteers (P = 0.016, 0.021, respectively). Five of the five, 6/9, and 1/7 volunteers with parasitemia developed symptoms (P = 0.003, NI versus IS). Naturally adaptive immunity (NAI) to malaria significantly prolonged the time to parasitemia. Sickle cell trait seemed to prolong it further. NAI plus sickle cell trait, but not NAI alone, significantly reduced symptom rate. Twenty percent (4/20) semi-immunes demonstrated sterile protective immunity. Standardized CHMI with PfSPZ Challenge is a powerful tool for dissecting the impact of innate and naturally acquired adaptive immunity on malaria. |
format | Online Article Text |
id | pubmed-5929186 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The American Society of Tropical Medicine and Hygiene |
record_format | MEDLINE/PubMed |
spelling | pubmed-59291862018-05-08 Impact of Sickle Cell Trait and Naturally Acquired Immunity on Uncomplicated Malaria after Controlled Human Malaria Infection in Adults in Gabon Lell, Bertrand Mordmüller, Benjamin Dejon Agobe, Jean-Claude Honkpehedji, Josiane Zinsou, Jeannot Mengue, Juliana Boex Loembe, Marguerite Massinga Adegnika, Ayola Akim Held, Jana Lalremruata, Albert Nguyen, The Trong Esen, Meral KC, Natasha Ruben, Adam J. Chakravarty, Sumana Lee Sim, B. Kim Billingsley, Peter F. James, Eric R. Richie, Thomas L. Hoffman, Stephen L. Kremsner, Peter G. Am J Trop Med Hyg Articles Controlled human malaria infection (CHMI) by direct venous inoculation (DVI) with 3,200 cryopreserved Plasmodium falciparum sporozoites (PfSPZ) consistently leads to parasitemia and malaria symptoms in malaria-naive adults. We used CHMI by DVI to investigate infection rates, parasite kinetics, and malaria symptoms in lifelong malaria–exposed (semi-immune) Gabonese adults with and without sickle cell trait. Eleven semi-immune Gabonese with normal hemoglobin (IA), nine with sickle cell trait (IS), and five nonimmune European controls with normal hemoglobin (NI) received 3,200 PfSPZ by DVI and were followed 28 days for parasitemia by thick blood smear (TBS) and quantitative polymerase chain reaction (qPCR) and for malaria symptoms. End points were time to parasitemia and parasitemia plus symptoms. PfSPZ Challenge was well tolerated and safe. Five of the five (100%) NI, 7/11 (64%) IA, and 5/9 (56%) IS volunteers developed parasitemia by TBS, and 5/5 (100%) NI, 9/11 (82%) IA, and 7/9 (78%) IS by qPCR, respectively. The time to parasitemia by TBS was longer in IA (geometric mean 16.9 days) and IS (19.1 days) than in NA (12.6 days) volunteers (P = 0.016, 0.021, respectively). Five of the five, 6/9, and 1/7 volunteers with parasitemia developed symptoms (P = 0.003, NI versus IS). Naturally adaptive immunity (NAI) to malaria significantly prolonged the time to parasitemia. Sickle cell trait seemed to prolong it further. NAI plus sickle cell trait, but not NAI alone, significantly reduced symptom rate. Twenty percent (4/20) semi-immunes demonstrated sterile protective immunity. Standardized CHMI with PfSPZ Challenge is a powerful tool for dissecting the impact of innate and naturally acquired adaptive immunity on malaria. The American Society of Tropical Medicine and Hygiene 2018-02 2017-12-18 /pmc/articles/PMC5929186/ /pubmed/29260650 http://dx.doi.org/10.4269/ajtmh.17-0343 Text en © The American Society of Tropical Medicine and Hygiene This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Articles Lell, Bertrand Mordmüller, Benjamin Dejon Agobe, Jean-Claude Honkpehedji, Josiane Zinsou, Jeannot Mengue, Juliana Boex Loembe, Marguerite Massinga Adegnika, Ayola Akim Held, Jana Lalremruata, Albert Nguyen, The Trong Esen, Meral KC, Natasha Ruben, Adam J. Chakravarty, Sumana Lee Sim, B. Kim Billingsley, Peter F. James, Eric R. Richie, Thomas L. Hoffman, Stephen L. Kremsner, Peter G. Impact of Sickle Cell Trait and Naturally Acquired Immunity on Uncomplicated Malaria after Controlled Human Malaria Infection in Adults in Gabon |
title | Impact of Sickle Cell Trait and Naturally Acquired Immunity on Uncomplicated Malaria after Controlled Human Malaria Infection in Adults in Gabon |
title_full | Impact of Sickle Cell Trait and Naturally Acquired Immunity on Uncomplicated Malaria after Controlled Human Malaria Infection in Adults in Gabon |
title_fullStr | Impact of Sickle Cell Trait and Naturally Acquired Immunity on Uncomplicated Malaria after Controlled Human Malaria Infection in Adults in Gabon |
title_full_unstemmed | Impact of Sickle Cell Trait and Naturally Acquired Immunity on Uncomplicated Malaria after Controlled Human Malaria Infection in Adults in Gabon |
title_short | Impact of Sickle Cell Trait and Naturally Acquired Immunity on Uncomplicated Malaria after Controlled Human Malaria Infection in Adults in Gabon |
title_sort | impact of sickle cell trait and naturally acquired immunity on uncomplicated malaria after controlled human malaria infection in adults in gabon |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5929186/ https://www.ncbi.nlm.nih.gov/pubmed/29260650 http://dx.doi.org/10.4269/ajtmh.17-0343 |
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