| dc.description.abstract | The areas around Lake Victoria in Western Kenya are endemic for schistosomiasis
mansoni,a disease that infects more than 200 million people worldwide, majority of
whom are children. Kenya and other countries where the disease is endemic are
currently carrying out mass drug administration using praziquantel targeting school
children for morbidity control and reduction in prevalence. Prevalence and intensity
of infection of this disease in endemic areas tends to increase with age, plateauing and
eventually falling from early adulthood. It is hypothesised that this age associated
prevalence and intensity of infection is a reflection of a similar age-dependent
development of protective anti-schistosome immune responses. The immunological
age profile of children in western Kenya infected with Schistosoma mansoni has never
been determined. Mass drug administration (MDA) with praziquantel was
hypothesised to alter this profile. This study therefore sought to profile immune
responses associated with protection against re-infection of schistosomiasis in 6-17
year old school children, and the effect of one round of mass drug administration
(MDA) with praziquantel on these responses in pre- and early teenage years. It was a
repeated cross-sectional study in which a total of 387 participants were recruited, 288
at baseline and 99 1 year later from all classes of primary and secondary schools in
Asembo area of Rarieda Sub-county of Siaya County in Western Kenya. Each
consenting participant provided 3 consecutive stool samples for diagnosis of
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schistosomiasis by Kato-Katz and about 10 ml of blood for immunological assays.
Anti-schistosome crude soluble worm antigen preparation (SWAP) and soluble egg
antigen (SEA) and recombinant tegument allergen-like (TAL) antibodies were
assayed by ELISA. Parasite antigen-specific cytokines were also assayed from whole
blood culture supernatants by ELISA, while CD19+CD23+ B lymphocytes were
determined by flow cytometry.Data was analysed using GraphPad Prism software,
version 5. Parametric data was analysed by ANOVA and Tukey’s multiple
comparison post-test. Kruskal Wallis test and Mann Whitney U tests were used for
non-parametric data. While most of the anti-SWAP and anti-SEA antibodies did not
differ significantly across the different age-groups, anti-SEA IgE and total IgG were
significantly different across the age-groups (P<0.0001). Subsequent post-hoc
analysis showed that the 9-11 and 12-14 year old age groups had higher anti-SEA IgE
(median, 433.8 arbitrary units (AU); Interquartile range, IQR, 692.0 AU and median,
268.1; IQR 497.9 AU respectively) compared to the 15-17 year olds (median, 90.3;
IQR 160.0 AU; P<0.0001. The pattern for anti-SEA IgG was quite the opposite, with
9-11 year olds producing less IgG (median, 20.6; IQR, 120.2 AU) than 15-17 year
olds (median, 201.2; IQR, 488.6 AU; P<0.0001). Moreover, 12-14 year olds had less
IgG antibody (median, 54.9; IQR, 177.1 AU) than 15-17 year olds (median, 201.2;
IQR 488.6 AU; P<0.0001). The rest of the antibodies assayed, CD23+ B cell levels
did not differ significantly with age (P>0.05). Anti-Schistosoma mansoni-Tegument
Allergen-like (SmTAL) antibodies similarly did not differ significantly across the age
groups (P>0.05). In post-treatment comparisons, anti-SEA IgE levels were higher in
the combined post-treatment group in contrast to anti-SEA IgG. In addition, the posttreatment
schistosomiasis egg positive group had higher anti-SEA IgG4 levels
(median, 117.4; IQR, 553.2 AU; P<0.0001) compared to the schistosomiasis negative
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group (median, 3.7; IQR, 37.2 AU). The same IgG4 levels against SmTAL-2 antigen
was higher in the pre-treatment group (median, 16.0; IQR, 183.6 AU) relative to
schistosomiasis egg negative post-treatment group (median 0.0; IQR, 1.6 AU;
P<0.05). Anti-SmTAL-5 IgE was similarly reduced post-treatment. A decline-posttreatment
was also observed with the proportion of CD23+ B cell levels posttreatment
(mean, 61.7; SEM, 1.2) relative to pre-treatment proportions (mean, 67.4;
SEM, 0.8 %; P<0.05) . For cytokines, post-hoc analysis for IL-5 showed that the
schistosomiasis negative post-treatment group had higher mean levels of this cytokine
(mean, 84.9; SEM, 32.1 pg) compared to mean baseline levels (mean, 6.4; SEM, 2.1
pg; P<0.0001) and schistosomiasis positive post-treatment group (mean, 21.7; SEM,
7.3 pg; P<0.001). Soluble egg antigen stimulated mean IL-13 levels were higher in
the combined post-treatment group (mean, 137.8; SEM 41.7 pg) compared to mean
baseline levels (mean, 19.9; SEM, 4.0 pg; P<0.05). Similarly, mean IL-13 levels
produced in response to SWAP were higher in the combined follow-up group (mean,
127.0; SEM, 28.3 pg; P<0.001) and in the schistosomiasis positive post-treatment
group (mean, 134.6; SEM, 42.3 pg; P< 0.05) relative to mean baseline levels (mean,
29.3; SEM, 6.2 pg) Taken together, these results are indicative of the complex nature
of immune responses in individuals of comparable demographic and epidemiological
conditions. It is clear from these results that a single treatment of schistosomiasis with
praziquantel may not result in augmented anti-schistosome immune responses that
correlate to resistance to reinfection. It remains possible, however, that multiple
rounds of annual mass drug administration may have beneficial effects leading to the
development of resistance in children, necessitating further longitudinal research in
this area. | en_US |
