The influence of helminths on immune responses to HIV.
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Date
2009
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Abstract
In South Africa, co-infection with HIV and intestinal parasites is a major challenge in
disadvantaged communities who live in densely populated under-serviced urban
informal settlements. This pilot cross sectional study evaluates the immunological effects
of co-infection with Ascaris lumbricoides and Trichuris trichura on the immune response
to HIV.
The work was a substudy of a prospective double blind, placebo-controlled investigation
to test whether regular deworming changes the immune profile of HIV positive
individuals with concurrent helminth infection. The substudy has a cross sectional design
and presents pilot data that defines immune profiles of HIV-1 positive individuals with
and without gastrointestinal helminth (Ascaris lumbricoides and Trichuris trichura)
infection. The hypothesis was that concurrent helminth infection adversely affects
immune responses against HIV. It was conducted in an area of high helminth
endemnicity and limited infrastructural resources. Individuals with known HIV infection
were recruited from an HIV Support Group and HIV negative individuals residing in the
same area (for demographic matching) were used for comparison. The substudy was to
provide pilot data for future larger scale and possible interventional studies. The current
work is limited by the cross sectional design, moderate sample size and practical
challenges.
The profile of lymphocyte phenotypes, viral loads, eosinophils, activation markers,
expression of the nuclear proliferation antigen-Ki67 and activation regulator antigen
CTLA-4 were analysed using flow cytometry in HIV positive and negative subgroups with
or without helminth infection. The type-1, type-2 and inflammatory cytokines were
analysed using multiplex cytokine array technology. These were correlated with immune
responses to HIV. Non parametric statistics were used to describe differences in the
variables between the subgroups.
A major finding of the study was the result of the supplementary use of the serological
marker, Ascaris lumbricoides-specific IgE in addition to the presence (or absence) of
helminth eggs in stools to classify intestinal helminth infection status. Two significant
outcomes of this measure were the enhancement of diagnosis of current or recent
helminth infection and, more importantly, the distinction of different phenotypes of
individuals who displayed different immunological responses to co-infection with HIV and
helminths. The different helminth infection phenotypes are defined by stool egg positivity
(egg⁺) or negativity (egg⁻) with either high or low Ascaris-specific IgE (IgEhi or IgElo)
respectively. The four subgroups, egg⁺IgEhi, egg⁺IgElo, egg⁻IgEhi and egg⁻IgElo showed
different interactions with regards to immune response to HIV. It should be noted that no
Trichuris specific IgE tests are commercially available but that there is significant
antigenic cross-reactivity with Ascaris antigen.
The presence of helminth stool eggs and high Ascaris IgE (egg⁺IgEhi) was associated
with the following characteristics: reduction in numbers of all lymphocyte populations,
frequent eosinophilia, highly activated immune profiles, antigen specific proliferative
hyporesponsiveness, impaired type 1 cytokine responses in unstimulated and antigen
stimulated cells and increased TNFα levels. In HIV infected individuals, the egg⁺IgEhi
helminth infection status was associated with lower but not significant CD4⁺ counts and
higher viral loads. A strong negative correlation was observed between viral loads, CD4⁺
and CD8⁺ cells in this subgroup.
Subgroups with high IgE (egg⁺IgEhi and egg⁻IgEhi) had elevated Th2 markers with lower
CD4⁺ counts and higher viral loads in the HIV⁺ group. The inverse correlation between
viral load and CD4⁺ counts found in all the HIV⁺ participants was strongest in these two
subgroups.
Individuals with parasite eggs in stool and low Ascaris IgE (egg⁺/IgElo) presented a
modified Th2 profile. This subgroup had high absolute numbers of all lymphocyte subsets
in both HIV⁻ and HIV⁺ groups with higher CD4⁺ counts in the HIV⁻ and lower viral load in
the HIV⁺ groups as well as higher interferon gamma, lower IL-4 and higher IL-10.
In conclusion, the results suggest that helminth infections may be associated with
deleterious effects on the immune responses to HIV in certain groups of susceptible
individuals. The underlying reasons for the different stool egg/Ascaris IgE combinations
in settings with high exposure to helminthes is currently not clear but genetic
predisposition and environmental factors could play a role. Future studies of helminth-
HIV co-infection have to ensure adequate definition of helminth infection status by the
use of both stool examination and measurement of helminth-specific IgE as the infection
phenotype is associated with differential effects on HIV associated immune responses.
This may also apply to co-infection with other pathogens, including tuberculosis. The
long-term effect of helminth co-infection in HIV positive people was not assessed in this
study but requires further studies.
Description
Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2009.
Keywords
HIV infections., Immunology., Medical microbiology., Helminths., Theses--Immunology.