Changes in total and differential leukocyte counts during the clinically silent liver phase in a controlled human malaria infection in malaria-naïve Dutch volunteers
Abstract Background Both in endemic countries and in imported malaria, changes in total and differential leukocyte count during Plasmodium falciparum infection have been described. To study the exact dynamics of differential leukocyte counts and their ratios, they were monitored in a group of health...
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doaj-19e8edf6d68942dabecdb36cd4a1044a2020-11-24T21:47:16ZengBMCMalaria Journal1475-28752017-11-011611810.1186/s12936-017-2108-1Changes in total and differential leukocyte counts during the clinically silent liver phase in a controlled human malaria infection in malaria-naïve Dutch volunteersMarlies E. van Wolfswinkel0Marijke C. C. Langenberg1Linda J. Wammes2Robert W. Sauerwein3Rob Koelewijn4Cornelus C. Hermsen5Jaap J. van Hellemond6Perry J. van Genderen7Institute for Tropical Diseases, Harbour HospitalInstitute for Tropical Diseases, Harbour HospitalDepartment of Medical Microbiology and Infectious Diseases, Erasmus MC and Harbour HospitalDepartment of Medical Microbiology, Radboud University Medical CenterDepartment of Medical Microbiology and Infectious Diseases, Erasmus MC and Harbour HospitalDepartment of Medical Microbiology, Radboud University Medical CenterDepartment of Medical Microbiology and Infectious Diseases, Erasmus MC and Harbour HospitalInstitute for Tropical Diseases, Harbour HospitalAbstract Background Both in endemic countries and in imported malaria, changes in total and differential leukocyte count during Plasmodium falciparum infection have been described. To study the exact dynamics of differential leukocyte counts and their ratios, they were monitored in a group of healthy non-immune volunteers in two separate Controlled Human Malaria Infection (CHMI) studies. Methods In two CHMI trials, CHMI-a and CHMI-b, 15 and 24 healthy malaria-naïve volunteers, respectively, were exposed to bites of infected mosquitoes, using the P. falciparum research strain NF54 and the novel clones NF135.C10 and NF166.C8. After mosquito bite exposure, twice-daily blood draws were taken to detect parasitaemia and to monitor the total and differential leukocyte counts. All subjects received a course of atovaquone–proguanil when meeting the treatment criteria. Results A total of 39 volunteers participated in the two trials. Thirty-five participants, all 15 participants in CHMI-a and 20 of the 24 volunteers in CHMI-b, developed parasitaemia. During liver stage development of the parasite, the median total leukocyte count increased from 5.5 to 6.1 × 109 leukocytes/L (p = 0.005), the median lymphocyte count from 1.9 to 2.2 (p = 0.001) and the monocyte count from 0.50 to 0.54 (p = 0.038). During the subsequent blood stage infection, significant changes in total and differential leukocyte counts lead to a leukocytopenia (nadir median 3.3 × 109 leukocytes/L, p = 0.0001), lymphocytopenia (nadir median 0.7 × 109 lymphocytes/L, p = 0.0001) and a borderline neutropenia (nadir median 1.5 × 109 neutrophils/L, p = 0.0001). The neutrophil to lymphocyte count ratio (NLCR) reached a maximum of 4.0. Significant correlations were found between parasite load and absolute lymphocyte count (p < 0.001, correlation coefficient − 0.46) and between parasite load and NLCR (p < 0.001, correlation coefficient 0.50). All parameters normalized after parasite clearance. Conclusions During the clinically silent liver phase of malaria, an increase of peripheral total leukocyte count and differential lymphocytes and monocytes occurs. This finding has not been described previously. This increase is followed by the appearance of parasites in the peripheral blood after 2–3 days, accompanied by a marked decrease in total leukocyte count, lymphocyte count and the neutrophil count and a rise of the NLCR.http://link.springer.com/article/10.1186/s12936-017-2108-1Controlled Human Malaria InfectionPlasmodium falciparumLeukocyte countLymphocyte countLymphocytopeniaNeutropenia |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marlies E. van Wolfswinkel Marijke C. C. Langenberg Linda J. Wammes Robert W. Sauerwein Rob Koelewijn Cornelus C. Hermsen Jaap J. van Hellemond Perry J. van Genderen |
spellingShingle |
Marlies E. van Wolfswinkel Marijke C. C. Langenberg Linda J. Wammes Robert W. Sauerwein Rob Koelewijn Cornelus C. Hermsen Jaap J. van Hellemond Perry J. van Genderen Changes in total and differential leukocyte counts during the clinically silent liver phase in a controlled human malaria infection in malaria-naïve Dutch volunteers Malaria Journal Controlled Human Malaria Infection Plasmodium falciparum Leukocyte count Lymphocyte count Lymphocytopenia Neutropenia |
author_facet |
Marlies E. van Wolfswinkel Marijke C. C. Langenberg Linda J. Wammes Robert W. Sauerwein Rob Koelewijn Cornelus C. Hermsen Jaap J. van Hellemond Perry J. van Genderen |
author_sort |
Marlies E. van Wolfswinkel |
title |
Changes in total and differential leukocyte counts during the clinically silent liver phase in a controlled human malaria infection in malaria-naïve Dutch volunteers |
title_short |
Changes in total and differential leukocyte counts during the clinically silent liver phase in a controlled human malaria infection in malaria-naïve Dutch volunteers |
title_full |
Changes in total and differential leukocyte counts during the clinically silent liver phase in a controlled human malaria infection in malaria-naïve Dutch volunteers |
title_fullStr |
Changes in total and differential leukocyte counts during the clinically silent liver phase in a controlled human malaria infection in malaria-naïve Dutch volunteers |
title_full_unstemmed |
Changes in total and differential leukocyte counts during the clinically silent liver phase in a controlled human malaria infection in malaria-naïve Dutch volunteers |
title_sort |
changes in total and differential leukocyte counts during the clinically silent liver phase in a controlled human malaria infection in malaria-naïve dutch volunteers |
publisher |
BMC |
series |
Malaria Journal |
issn |
1475-2875 |
publishDate |
2017-11-01 |
description |
Abstract Background Both in endemic countries and in imported malaria, changes in total and differential leukocyte count during Plasmodium falciparum infection have been described. To study the exact dynamics of differential leukocyte counts and their ratios, they were monitored in a group of healthy non-immune volunteers in two separate Controlled Human Malaria Infection (CHMI) studies. Methods In two CHMI trials, CHMI-a and CHMI-b, 15 and 24 healthy malaria-naïve volunteers, respectively, were exposed to bites of infected mosquitoes, using the P. falciparum research strain NF54 and the novel clones NF135.C10 and NF166.C8. After mosquito bite exposure, twice-daily blood draws were taken to detect parasitaemia and to monitor the total and differential leukocyte counts. All subjects received a course of atovaquone–proguanil when meeting the treatment criteria. Results A total of 39 volunteers participated in the two trials. Thirty-five participants, all 15 participants in CHMI-a and 20 of the 24 volunteers in CHMI-b, developed parasitaemia. During liver stage development of the parasite, the median total leukocyte count increased from 5.5 to 6.1 × 109 leukocytes/L (p = 0.005), the median lymphocyte count from 1.9 to 2.2 (p = 0.001) and the monocyte count from 0.50 to 0.54 (p = 0.038). During the subsequent blood stage infection, significant changes in total and differential leukocyte counts lead to a leukocytopenia (nadir median 3.3 × 109 leukocytes/L, p = 0.0001), lymphocytopenia (nadir median 0.7 × 109 lymphocytes/L, p = 0.0001) and a borderline neutropenia (nadir median 1.5 × 109 neutrophils/L, p = 0.0001). The neutrophil to lymphocyte count ratio (NLCR) reached a maximum of 4.0. Significant correlations were found between parasite load and absolute lymphocyte count (p < 0.001, correlation coefficient − 0.46) and between parasite load and NLCR (p < 0.001, correlation coefficient 0.50). All parameters normalized after parasite clearance. Conclusions During the clinically silent liver phase of malaria, an increase of peripheral total leukocyte count and differential lymphocytes and monocytes occurs. This finding has not been described previously. This increase is followed by the appearance of parasites in the peripheral blood after 2–3 days, accompanied by a marked decrease in total leukocyte count, lymphocyte count and the neutrophil count and a rise of the NLCR. |
topic |
Controlled Human Malaria Infection Plasmodium falciparum Leukocyte count Lymphocyte count Lymphocytopenia Neutropenia |
url |
http://link.springer.com/article/10.1186/s12936-017-2108-1 |
work_keys_str_mv |
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