Abstract:
Human African trypanosomiasis is an infectious,
neglected, vector-borne protozoan disease which has an
early haemolymphatic phase followed by meningoencephalitis
due to neuroinvasion of the central nervous system
by trypanosomes. The determination of the earliest
timing when the blood-brain barrier (BBB) is breached
during neuropathogenesis of sleeping sickness has critical
implications on the choice of therapy, without which the
infection is fatal. Interleukin 10 (IL-10) and IgM have
been proposed as potentially important biomarkers when
this occurs. The vervet monkey is susceptible to experimental
infection with same aetiological agent as that
which causes HAT, providing a useful pathogenesis
model. Fourteen vervet monkeys were experimentally
infected with Trypanosoma brucei rhodesiense. The animals
were treated with diminazene aceturate (DA) and melarsoprol
(MelB) 28 and 140 days post infection (dpi),
respectively. Serum and CSF samples were obtained at
weekly intervals and assayed for immunospecific IgM and
IL-10 by ELISA. There was no detectable immunospecific
IgM in the CSF before 49 dpi. The CSF IgM increased progressively
to peak levels that coincided with the appearance
of relapse parasites in blood 140 dpi. The serum IgM
levels increased significantly over control levels starting
21 dpi and peaked between 133 and 140 dpi. The serum
IL-10 levels increased rapidly and were significantly elevated
between 14 and 21 dpi. Following sub-curative
treatment with DA the serum IL-10 levels declined and
remained below detection limit until 127 dpi which coincided
with relapse of parasitaemia. A significant rise in
white cell counts in CSF was recorded starting 35 dpi.
When curative treatment with MelB was carried out, there
was a rapid decline of the three parameters leading to
attainment of preinfection levels of IgM and white cell
counts within 30 days. However CSF IgM levels remained
above pre-detection levels to the end of the study. We
were unable to measure/detect IL-10 in the CSF. Serum
and CSF concentrations of immunospecific IgM as well as
serum IL-10 changes follow a similar pattern that mimics
the progression of the disease and may present reliable ad
useful biomarkers of the disease stage.
