Biology Reference
In-Depth Information
The Role of Host Genetics
There is strong evidence for a genetic component to host susceptibility
(see Chapter 12). Pedigree analysis of a Nepalese community has indi-
cated that 30
50% of the variability among individuals' worm burdens is
explained by host genetic differences.
77
Furthermore, at least three loci on
chromosomes 8, 11 and 13 have been associated with susceptibility to
infection.
78,79
The genetic component of susceptibility explains partly the
observation that worm burdens of members of the same household tend
to be similar.
73,80,81
However, shared household exposures are also
important. Molecular analysis of worms from the same Nepalese
community showed genotypic clustering of worms infecting members of
the same household, suggesting that households, at least in this
community, are important transmission foci (Chapter 8).
82
The impor-
tance of
e
the household in the transmission of A.
lumbricoides and
T. trichiura
was first identified in the
late 1920s to early 1930s from work conducted in China,
83
Panama
84
and
the southern United States of America.
85
These ideas were revisited by
Williams et al. in 1974
86
and by others in the late 1980s
81
and early 1990s,
87
and expounded in 1996 by Cairncross et al.
88
who described the house-
hold (for Ascaris and Trichuris) and the public environments (for hook-
worm) as “fundamental arenas of disease transmission.”
e
and to a lesser extent hookworm
e
The Role of Host Immunity
The role of either the innate or adaptive (acquired) immune response in
protecting against infection with A. lumbricoides remains incompletely
understood (Chapter 1).
89
Infection elicits the production of cytokines,
predominantly associated with a Th2-type response, and antibodies of all
isotypes, particularly IgE and Ascaris-specific IgE.
90,91
These immuno-
globulins do not seem to be protective;
92
rather, they reflect current or past
infection.
93,94
However, the concomitant rise in cytokine concentrations
has been associated with reduced infection intensities,
95,96
although the
elicited effector mechanisms remain incompletely understood.
An alternative (or complementary) approach to investigating the
operation of acquired immunity has been to use mathematical models to
demonstrate that the characteristic “peaked” or “convex” age-intensity
profile of A. lumbricoides,
19,58,97,98
in which infection peaks in school-age
(5
15-year-old) children and declines in adults (
Figure 7.2
), can be
reproduced under the assumptions of: (1) a gradual development of
protective immunity from chronic exposure to worm antigens, and
(2) a slow loss of immunological memory.
99
e
101
Such models also predict
a “peak shift,” whereby infection intensity (or prevalence) peaks at
a higher level and at an earlier host age in communities where trans-
mission is more intense, causing protective immunity to develop more
e
