Extravascular Dermal Trypanosomes in Suspected and Confirmed Cases of gambiense Human African Trypanosomiasis.
Trypanosoma brucei gambiense
human African trypanosomiasis
reservoir
skin
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213
Informations de publication
Date de publication:
01 07 2021
01 07 2021
Historique:
received:
10
04
2020
accepted:
25
06
2020
pubmed:
9
7
2020
medline:
8
7
2021
entrez:
9
7
2020
Statut:
ppublish
Résumé
The diagnosis of gambiense human African trypanosomiasis (gHAT) typically involves 2 steps: a serological screen, followed by the detection of living trypanosome parasites in the blood or lymph node aspirate. Live parasites can, however, remain undetected in some seropositive individuals, who, we hypothesize, are infected with Trypanosoma brucei gambiense parasites in their extravascular dermis. To test this hypothesis, we conducted a prospective observational cohort study in the gHAT focus of Forecariah, Republic of Guinea. Of the 5417 subjects serologically screened for gHAT, 66 were enrolled into our study and underwent a dermatological examination. At enrollment, 11 seronegative, 8 unconfirmed seropositive, and 18 confirmed seropositive individuals had blood samples and skin biopsies taken and examined for trypanosomes by molecular and immunohistological methods. In seropositive individuals, dermatological symptoms were significantly more frequent, relative to seronegative controls. T.b. gambiense parasites were present in the blood of all confirmed cases (n = 18) but not in unconfirmed seropositive individuals (n = 8). However, T. brucei parasites were detected in the extravascular dermis of all unconfirmed seropositive individuals and all confirmed cases. Skin biopsies of all treated cases and most seropositive untreated individuals progressively became negative for trypanosomes 6 and 20 months later. Our results highlight the skin as a potential reservoir for African trypanosomes, with implications for our understanding of this disease's epidemiology in the context of its planned elimination and underlining the skin as a novel target for gHAT diagnostics.
Sections du résumé
BACKGROUND
The diagnosis of gambiense human African trypanosomiasis (gHAT) typically involves 2 steps: a serological screen, followed by the detection of living trypanosome parasites in the blood or lymph node aspirate. Live parasites can, however, remain undetected in some seropositive individuals, who, we hypothesize, are infected with Trypanosoma brucei gambiense parasites in their extravascular dermis.
METHODS
To test this hypothesis, we conducted a prospective observational cohort study in the gHAT focus of Forecariah, Republic of Guinea. Of the 5417 subjects serologically screened for gHAT, 66 were enrolled into our study and underwent a dermatological examination. At enrollment, 11 seronegative, 8 unconfirmed seropositive, and 18 confirmed seropositive individuals had blood samples and skin biopsies taken and examined for trypanosomes by molecular and immunohistological methods.
RESULTS
In seropositive individuals, dermatological symptoms were significantly more frequent, relative to seronegative controls. T.b. gambiense parasites were present in the blood of all confirmed cases (n = 18) but not in unconfirmed seropositive individuals (n = 8). However, T. brucei parasites were detected in the extravascular dermis of all unconfirmed seropositive individuals and all confirmed cases. Skin biopsies of all treated cases and most seropositive untreated individuals progressively became negative for trypanosomes 6 and 20 months later.
CONCLUSIONS
Our results highlight the skin as a potential reservoir for African trypanosomes, with implications for our understanding of this disease's epidemiology in the context of its planned elimination and underlining the skin as a novel target for gHAT diagnostics.
Identifiants
pubmed: 32638003
pii: 5868540
doi: 10.1093/cid/ciaa897
pmc: PMC8246823
doi:
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12-20Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 209511/Z/17/Z
Pays : United Kingdom
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.
Références
Trop Med Int Health. 2004 May;9(5):542-50
pubmed: 15117297
PLoS Biol. 2019 Jan 11;17(1):e3000105
pubmed: 30633739
Eur J Clin Microbiol Infect Dis. 2012 Jun;31(6):905-13
pubmed: 21901632
Microbes Infect. 2011 Oct;13(11):943-52
pubmed: 21658462
Lancet. 2017 Nov 25;390(10110):2397-2409
pubmed: 28673422
Parasite. 2011 Nov;18(4):295-302
pubmed: 22091459
Elife. 2016 Sep 22;5:
pubmed: 27653219
Trans R Soc Trop Med Hyg. 1970;64(6):797-817
pubmed: 5495630
Biochem J. 1998 Nov 1;335 ( Pt 3):681-9
pubmed: 9794811
PLoS Negl Trop Dis. 2018 Dec 6;12(12):e0006890
pubmed: 30521525
Expert Rev Mol Diagn. 2015 May;15(5):607-15
pubmed: 25786994
Lancet Infect Dis. 2020 Feb;20(2):e38-e46
pubmed: 31879061
Am J Trop Med Hyg. 2002 Sep;67(3):289-95
pubmed: 12408669
PLoS Pathog. 2016 Jul 21;12(7):e1005744
pubmed: 27441553
Trends Parasitol. 2016 Feb;32(2):157-168
pubmed: 26643519
Trends Parasitol. 2018 Mar;34(3):197-207
pubmed: 29396200
PLoS Negl Trop Dis. 2016 Feb 18;10(2):e0004441
pubmed: 26890882
Arch Dermatol. 1995 Oct;131(10):1178-82
pubmed: 7574836
Infect Immun. 1993 Nov;61(11):4540-5
pubmed: 8406850
Acta Trop. 1995 Dec;60(3):189-99
pubmed: 8907397