R e v is t a d a S o c ie d a d e B r a s i le i r a d e M e d i c in a T ro p ic a l 2 1 ( 2 ) : 8 5 -8 6 , A b r-J u n , 1 9 8 8 .
L O W D O S E G L U C A N T I M E
T H E R A P Y I N
L E I S H M A N I A V IA N N IA
B R A Z I L I E N S I S
(Lvb) IN F E C T I O N S
J.M.L. Costa and P.D. Marsden
G o o d drug trials in leish m an ia sis w ith ca refully con trolled groups are rare. R ec en tly B a llo u et a l1 w ere able to esta b lish that 2 0 m g Sbv/k g b o d y w t for 2 0 d a ys
w as m ore effica c io u s in clo sin g leish m a n ial ulcers due to L e i s h m a n i a b r a z i l i e n s i s p a n a m e n s i s than lO m g
Sb¥/k g /b o d y w t for a sim ilar period. C o n d itio n s for this trial were m u ch m ore favourable than th o se w here w e w ork n a m ely field clin ics in the c a ca o grow ing region o f B ah ia , B razil. H ere a lm o st a ll hum an in fe c
tion s are due to L vb . W e h a v e had prim itive field clin ic facilities and an ovew h elm in g press o f patients. In 1 9 8 4
an ep id em ic occurred in the region o f C orte d e P edra
w here the in cid en ce figure for 1 9 8 4 reached 83 patien ts per 1 ,0 0 0 with a cu te cu ta n eo u s u lceration due to L vb4 (F ra n ç a e t al, in press).
D u rin g the ep idem ic our clin ic fa cilities w ere so strained tha t w e w ere ob lig ed to u se lo w d o s e s o f p en tav alen t an tim on ial sin ce the sup p ly w a s lim ited.
M a n y p atients received o n ly on e a m p o ule (the equi v alen t o f 8m g Sbv/k g b o d y w t for a 5 0 k ilo m an) for a short co u rse o f 10 d a y s o n 1 ,2 or 3 o cc a sio n s . O thers w h en the su p p ly w as better receiv ed 2 am poules ( 1 6 m g Sbv/k g b o d y w t for sim ilar p eriod s). P rev io u sly
w e h a ve reported the effica cy o f ten d a y co u rses at a higher d o sa g e 2 8 m g /S b v/k g do by wt5 b u t n ow w e had the opp ortun ity to exam ine-the effic a c y o f m uch low er d o ses.
T h e current recom m en da tion n ow tha t glu can -tim e is a v aila b le from govern m en t sou rces is 2 0 m g
Sbv/k g per d a y for 2 0 d a y s, b u t w e su s p e ct that m an y p atien ts d o n o t co m p lete the series. D u e to d istan ce from th e clin ic d o se s u su a lly h a v e to b e g iven at h om e.
T h e results are set o u t in T ab le. T o our surprise w e h ad u lcer closu re w ithin a few m on ths in m an y patients u sing the lo w e st d o se o f an tim on ial n a m ely
8m g S b v/k g /d a y o r 10 d ays. O f a total o f 4 0 p atients 16 clo s ed w ith a single cou rse, another 9 w ith tw o co u rses and o n ly 4 failed to c lo s e after 3 cou rses o f 10 d a y s. W ith d ou ble the d o se in sim ilar interrupted p eriod s g o o d results w ere a ch ieved w ith o ne, tw o or three series. W h ile id ea lly lon ger co u rses are to be
preferred the field co nd ition s at the tim e precluded su ch regim ens. A ls o , as is so co m m on in the field, w e
N ú c le o d e M ed icin a T ropica l,
U n iv ersid ad e d e B rasília
cou ld n ot g aran tee tha t th e p atien t to o k the am p o ules o f glucan tim e in the m an n er prescribed. H o w ev er b oth th ese a sp ects m itigate ag ain st u lcer clo su re and w e w ish to draw atten tion to relatively g o o d results in L vb in fection s w ith lo w d o se s o f drug in interrupted schedu les.
A ls o tw o y ea rs later w e w ere ab le to trace 5 3 o f the 7 9 p resented patients and o n ly tw o had a ctive lesio n s and n o p atien t h ad d ev e lo p sig ns o f m u co sa l d isea se. A p reviou s stu d y o f ours su ggests that in tw o
y ears fo llow u p 5 0% o f the patients w h o w ill d ev elo p m u co sa l d is ea se h a v e clin ica l ev id en ce o f this m etas tasis6 . T h e se resu lt underline our ign oran ce regarding the m o s t b en eficia l d o se s o f p en ta va len t an tim on ial for
p atien ts w ith sim p le skin ulcers d u e to Lvb. T h e y su gg est tha t lo w er d o se s o f an tim on ial co uld b e u sed than is currently su ggested for this form o f the d ise a s e w ith little risk o f m u co sa l m etastasis. In v iew o f the c o s t o f glucan tim e and the d ifficulty o f field ap p lication
this p o s sib ility sho uld b e further ex plored . It m u st be em p h a sised that esta b lish ed m u co sa l lesio n s due to L vb p resen t quite a different p rob lem and such m ini m al d o se s are n o t in d ica ted 8. S in ce there are n o n ew strategies for leish m a n ia sis con trol the u se o f lo w d o se s for sim p le cu ta n eo u s d ise a se (a procedure lo ng ad vo cated b y th e B razilia n M inistry o f H ea lth ) shou ld be
consid ered. N o n resp on ders co uld receiv e higher d o ses.
W e are still ignorant o f the im m u n o lo gical factor determ ining h ea lin g in ulcers due to L vb. B o th m acro
phage and ly m p h o cyte fun ction appear to b e intact2 and sin ce the h ea lin g p ro cess can be sp o ntan eou s
drugs are a b v io u sly n o t es sen tia l to trigger this res p on se7.
In a region such as the o ne under con sid eration
a n y p atien t w ith prim ary cutan eou s leish m an ia sis m u st b e a d v ised as to the in co n v e n ien c es o f antim onial therapy, the n e c e ss it y to rest after injection s, to refrain
from a lco h o lic or ex ercise e x c e s s and the im portance o f com pleting the recom m en d ed series o f injections. H e m u st a lso b e w arned o f early sig ns o f m u co sa l
in v olv em en t (n a sa l b lock a ge, ep ista xis, flesh lea vin g the n o s e (gra nu lo m a ) and if th ese occur the n ec ess ity
to seek m ed ical help. T h e current p ractical approach to the problem the o f this frequent B ra zilian en d em ic d isea se is th e estab lish m en t o f a dequ ate clin ica l fa cilities in the area to m e et'th e p eo p le s need.
C o m u n ic a ç ã o . C o s ta J M L . L o w d o s e g lu c a n tim e th e r a p y in Leishm ania viannia braziliensis (Lbv) in fec tio n s. R e v is t a d a S o c ie d a d e B r a s i le i r a d e M e d i c in a T ro p ic a l 2 1 : 8 5 -8 6 , A b r-J u n , 1 9 8 8 .
P A T IE N T S T R E A T E D W IT H O N E , T W O O R T H R E E O R M O R E S E R IE S O F 10
D A Y S G L U C A N T I M E A T T W O D I F F E R E N T D O S A G E
S C H E D U L E S (C O S T A (1 9 8 6 )
D o s e Sbv/k g /d a y N u m b er o f In itial o b serv a tio n A t m ore than 2 years*
X 1 0 S eries M ea n fo llo w up N u m b er a c tiv e / M ea n closure tim e N u m b er a c tiv e/
(m on ths) N u m b er h ea led (m o nths) N u m b er h ealed
8 1 1 3.6 1 /1 7 4 0 /1 5
8 2 12 0 /9 5 .2 0 ,3
8 3 or m ore 12 4 /1 4 5 .7 1/1 0
16 1 14 2 /1 2 3 .9 0 /6
16 2 13 .8 3 /1 3 5 .7 0 / 9
16 3 or m ore 1 5 .9 3 /1 4 8 .7 1/10
T o tals 1 3 /7 9 2 /5 3
(*) O f 53 p atients seen a t m ore th an tw o years tw o h ad failed to heal and no relapse w as recorded.
R E F E R E N C E S
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