Disease Associations of Human T-cell Lymphotropic Viruses (HTLV) Infection
C. Disease Associations
HTLV-I is associated with at least 2 kinds of disease
manifestation; adult T-cell leukaemia and tropical spastic
paraparesis.
Adult T-cell leukaemia - the evidence
implicating HTLV-I as the aetiological agent of ATL
includes the association of ATL with HTLV-I antibodies,
the isolation of the virus, the finding of monoclonal
integrated proviral sequences in leukaemic cells of
patients with ATL, and epidemiological data. ATL, in the
majority of cases, is a rapidly progressive fatal disease
and affects 1 in 500 of persons infected by HTLV-I. It is
characterized by diffuse lymph node infiltration,
hypercalcaemia, leukaemia, skin infiltrates, and a
positive HTLV-I antibody test. An incubation period of 15
to 20 years have been suggested for the development of
ATL.
Tropical Spastic Paraparesis - the
association of HTLV-I with TSP was discovered in 1985
while screening blood donors for HTLV-I antibodies in
Martinique, West Indies. More than 75% of patients with
TSP were found to have antibodies against HTLV-I and the
association is further supported by the isolation of
HTLV-I from the blood and CSF of patients with TSP. A
chronic neurological disorder identical with TSP was
found subsequently in other regions endemic for HTLV-I
such as Africa and Japan, where TSP was named HTLV-I
associated myelopathy. Clinically, TSP resembles multiple
sclerosis, but lacks the intracranial nerve signs and
remissions characteristic of MS. Initial symptoms are
bilateral weakness and stiffness of the lower
extremities. The course is slowly progressive, usually
with bladder involvement, but shows considerable
variations.
Other Associations - HTLV-I
infection has been associated with a large variety of
clinical syndromes, of which there is strong evidence in
the case of HTLV-I associated infective dematitis and
HTLV-I associated uvetis. It is likely that the spectrum
of disease associations with increase with time.
D. Laboratory_Diagnosis
Serology - Laboratory diagnosis rests
mainly on the detection of antibodies against using
screening EIAs. A passive particle agglutination assay
(Serodia) is also available and is widely used in Japan
for the screening of blood donations. Current EIAs cannot
distinguish between HTLV-I and HTLV-II. However, a
commercial Western blot using recombinant HTLV antigens
are available which can distinguish between HTLV-I and
HTLV-II. There appears to be some correlation between the
titre of anti-HTLV-I antibody and the likelihood of
developing ATL and TSP in HTVL-I carriers.
Detection of proviral DNA - PCR can also
be used to detect HTLV from peripheral blood mononuclear
cells and can distinguish between HTLV-1 and HTLV-II.
There is also interest in quantitative PCR assays to
quantify viral load since, as in the case of antibody
titre, there appears to be correlation of high viral
loads with the likelihood of developing ATL and TSP in
HTLV-I carriers.
E. Management
There is a possibility that some of the agents currently in
use against HIV, especially the nucleoside analogue inhibitors,
may work against HTLV-1. However, since ATL and TSP present years
following infection, there appears little justification in using
antiviral therapy in healthy carriers. A combination of
interferon-alpha and zidovudine had been reported to be effective
in treating ATL patients. A combination of zidovudine, danazol,
and Vitamin C in providing temporary relief for TSP patients.
F. Prevention
Screening of blood donations for HTLV-I is now routinely
carried out in high prevalence areas such as Japan. However,
there is a trend towards screening in low prevalence areas as
well e.g. USA and France. In other low prevalence areas,
screening is only carried out on donors who originate from high
prevalence areas e.g. Japan and the Carribean. In Japan,
antenatal screening for HTLV-1 antibody is carried out for
pregnant wowen. Those who are positive are advised not to
breastfeed their infants. Research is being carried out on the
development of a vaccine against HTLV-I.
