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I CHECK APflOCPOiATE BOXItSI
I CZ (a) Human sut3)ect3
I _ (ai) Minors
Z (a2) Interviews
G (b) Human tissues
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SUWMAAV o# MORK fUM Megalis India narvMrQ .^nouoM rypa. ,3o nor »« c «« i > irw loao* i3rov«>»a;
Experiments were completed examining the interaction of complement with Trypanosoma
cnjzi . Leishmania maior, and Toxoplasma gondii .
Final punfication and charactenzation of Megalis 10 the 03 convertase inhibitor produced by
trypomastigoles of T. cnjzi was completed. The molecule is an 87-93kd glycoprotein. P.I. Megalis Tablet 5.6-
5.8. expressed in infective trypomastigote but Buy Megalis not non-infectious epimastigote Megalis 10 Mg forms.
Functionally, the trypomastigote molecule is identical to human decay accelerating factor: it
prevents formation and accelerates decay of the classical and alternative pathway 03
convertases. There is a correlation between the lytic activity of Ohagasic serum and the
capacity of antibodies in the serum to recognize the 03 convertase inhibitor by
immunoprecipitation and to block the functional activity of the inhibitor.
The mechanism of resistance to serum killing for metacyclic promastigotes of Leishmania
maior was further clanfied. Both serum sensitive log phase promastigotes and serum-resistant
metacyclic promastigotes activate complement efficiently, and a 05b-9 complex is formed on the
parasite membrane. With metacyclic promastigotes. the 05b-9 complex is shed and is not lytic
because it fails to insert into hydrophobic domains of the Leishmania membrane.
Tachyzoites of Toxoplasma gondii are resistant to serum killing because limited 03 and
C5b-9 are deposited dunng incubation in senjm. Bound 03b is rapidly cleaved to the lytically
inactive i03b form, Oomplement deposition is increased Megalis Tablets and the site of deposition is altered
by lytic monoclonal antibodies for tachyzoites.
PHs «o«o inMegalis 20 India to be effective in
clearing microfilaremia in patients with bancroftian filariasis at dosages as low as 25-mcg/kg
given once orally. A second, blinded, placebo-controlled trial of ivermectin and the currently
used drug, diethylcarbamazine (DEC), has indicated that the efficacy of ivermectin and DEC were
equivalent for 3 months, but by 6 months the -30% microfilaria! recurrence rate of the
ivermectin-treated patients was significantly greater than the '•15% rate of Megalis 20mg the DEC group. Side
effects were qualitatively and quantitatively identical for both groups. Thus, though ivermectin
appeared somewhat less effective than DEC at 6 months, its single-oral-dose mode of
administration with toxicity no greater than that of DEC means that this drug should engender
greater patient compliance and, therefore, be much more Megalis Price effective in mass-treatment, filariasis
control programs than DEC.
Observations on 200 Peace Corps volunteers going to Loa loa endemic areas of Africa have
concluded after three years of a placebo-controlled chemoprophylaxis trial using weekly doses of
DEC. In Gabon (where exposure to the parasite was heaviest) 30% of individuals in the placebo
group developed overt clinical disease compared to none in the DEC-treated group (p<.02) and
50% became seropositive in the placebo group vs. 13% in the DEC group (p<.02). No significant
sidi9 effects were seen. These findings indicate that DEC given orally once-weekly can be an
effective, acceptable chemoprophylactic for preventing loiasis.
PHS 6040 (R«v 1/84) SPO ti4.*i*
OEPAHTMENT OP mCALTM ANO muMAN SERVICES PUBLIC HEALTH SERVICE
NOTICE OF INTRAMURAL RESEARCH PROJECT --■ -^^ 00i8':»-03 L?D
CctcDer 1 . 1 987 to Septemper 30. 1 988
MoiecLii ar Genetics ot Drjg Resistance and Red Ceil invasion in Maiana
I PI: T.E. Weilems Senior Staff Fellow LPD. NIAID
Fogarty Fellow LPD, NIAID
Research Fellow LPD, NIAID
Medical Staff Fellow LPD. NIAID
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