116 / 124
116
que, a selecção no cromossoma 2 era a mais forte, este
locus
foi submetido a
subsequentes análises genéticas, tendo sido encontradas duas mutações
diferentes (V739F e V770F) num gene que codifica para um enzima de
desubiquitinação (gene
ubp-1
).
SANTOS, Ana Pereira dos (2007)
Anaplasma phagocytophilum
and
human granulocytic anaplasmosis in Portugal, Dissertação de
Doutoramento no ramo de Ciências Biomédicas, especialidade de
Microbiologia. IHMT. Lisboa.
Resumo:
Anaplasma phagocytophilum
and granulocytic anaplasmosis are of
increasing interest to the scientific community as indicated by the expanding
number of reports published in the past two decades, and especially since the
emergence of the first cases of human granulocytic anaplasmosis (HGA). The
growing recognition of the Public Health importance of
A. phagocytophilum
in
North America and in Europe, along with its recent detection in Portugal has
signalled the need for more detailed studies that address the emergence of
HGA and its causative agent in our country.
Initially based on an methodological training in research units dedicated to
Anaplasmataceae, this work enabled the transfer of technology as currently
applied to
A. phagocytophilum
research and made possible the development of
a new line of investigation at
Centro de Estudos de Vectores e Doenças
Infecciosas
,
Instituto Nacional de Saúde Dr. Ricardo Jorge
(
CEVDI/INSA
). By
establishing the foundations for concerted study on
A. phagocytophilum
and
HGA, the work described herein has facilitated development of a broad
approach toward fundamental issues in Anaplasmataceae ecobiology and
disease by focusing attention on identification of potential ixodid vectors,
mammals likely to be involved in the infectious agent’s life cycles either as
reservoirs or affected hosts, and garnered the evidence indicating the potential
for human exposure in Portugal.
The studies conducted in ixodid ticks proves the involvement of two
Ixodes
species in
A. phagocytophilum
cycles, including
Ixodes ricinus
on Madeira
Island and
I. ventalloi
on the mainland. The detection of
A. phagocytophilum
DNA in
I. ricinus
reinforces prior studies and suggests its persistence on
Madeira Island. This thesis also adds new data to the understanding of the
natural history of
A. phagocytophilum
by providing the first evidence of
infections in
I. ventalloi
ticks. The fact that some infected arthropods infest
domestic cats not only mandates the inclusion of these mammals on the
national list of vertebrate hosts parasitized by
I. ventalloi
ticks, but also shows
their potential complicity in
A. phagocytophilum
maintenance. Moreover,
molecular data shows the existence of
A. phagocytophilum
variant genotypes in
Portuguese ticks. Partial gene sequences from infected ticks demonstrates
nucleotide polymorphisms that support a close relationship of
A.
phagocytophilum
on Madeira Island
I. ricinus
to North American strains isolated
from humans as well as genotypes detected in Central and Northern Europe.
Yet, these variants diverge from those found in mainland
I. ventalloi
, which
represents a new genotype of undetermined pathogenicity.
Serological evidence of exposure to
A. phagocytophilum
or a close related
agent is shown in
Mus spretus
mice, horses, and dogs in mainland. Molecular