Double blind study on efficacy and safety of single doses of ivermectin and diethylcarbamazine for treatment of Polynesian Wuchererta bancrofti carriers.. Results of a safety trial on si
Trang 1464
Her& Hascoet, laboratory assistant; Miss Veronique Chenon
and Mrs Sylvianne Teururai, nurses; and Mr I% ichart Regis,
computer expert, Institut Malard e
References
Addiss, D G., Eberhard, M L., Lammie, I’ J., Bayard
McNeeley, M., Lee, S H., McNeeley, D F & Spencer, H
C (1993) Comparative efficacy of clearing-dose and single
high-dose ivermectin and diethylcarbamazine against Wu-
chereria bancrofti microfilaraemia AmericanJournal of Tropical
Medicine and Hygiene, 48,178-185
Cartel, J.-L., Spiegel, A., Nguyen, L., Genelle, B & Roux, J.-
F (1991) Double blind study on efficacy and safety of single
doses of ivermectin and diethylcarbamazine for treatment of
Polynesian Wuchererta bancrofti carriers Results at six months
Tropical Medicine and Parasitology, 42,38-40
Cartel, J.-L., Nguyen, N L., Spiegel, A., Moulia-Pelat, J.-P.,
Plichart, R., Martin, I’ M V., Manuellan, A B & Lardeux,
F (1992a) Wuchereria bancrofci infection m human and mos-
quito populations of a Polynesian village ten years after inter-
ruption of mass chemoprophylaxis with diethylcarbamazine
Transactions of the Royal Society of Tropical Medicine and Hy-
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Cartel, J L., Nguyen, N L., Moulia-Pelat, J.-P., Plichart, R.,
Martin, I’ M V & Spiegel, A (1992b) Mass chemoprophy-
laxis of lymphatic filariasis with a single dose of ivermectin in
a Polynesian community with a high Wucheretia bancrofti in-
fection rate Transactions of the Rcyal Sociey of Tropical Me-
dicine and Hygiene, 86,537-540
Cartel, J.-L., Moulia-Pelat, J.-P., Glaziou, I’., Nguyen, L N.,
Chanteau, S & Roux, J.-F (1992~) Results of a safety trial
on single dose treatments with 400 pgikg of ivermectin in
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Diallo, S., Aziz, M A., Ndir, O., Badiane, S., Bah, I B &
Gaye, 0 (1987) Dose-ranging study of ivermectin in treat-
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ciety of Tropical Medicine and Hygiene, 86,287-288
Kar, S K., l’atnaik, S., Mania, J & Kumaraswami, V (1993) Ivermectin in the treatment of bancroftian lilarial infection in Orissa, India Southeast AsianJournal of Tropical Medicine and Public Health, 24,80-86
Kumaraswami, V., Ottesen, E A., Vijayasekaran, V., Uma Devi, S., Swaminathan, M., Aziz, M A., Sarma, G R., Rag- neathi Prabhakar & Tripathy, S I’ (1988) Ivermectin for treatment of Wuchereria bancrofti filariasis Efficacy and ad- verse reactions Journal of the American Medical Association, 259,31X)-3153
Moulia-Pelat, J I’., Glaziou, Ph., Nguyen, N L., Chanteau, S., Plichart, R., Beylier, I., Martin, I’ M V & Cartel, J.-L (1994) Ivermectin 400 ugikg: long-term suppression of microfilariae in Bancroftian filariasis Transactions of the Royal Society of Tropical Medicine and Hygiene, 88, 107-109 Ottesen, E A., Vijayasekaran, V., Kumaraswami, V., Perumal Pillai, S V., Sadanandam, M A., Frederick, B S., Prabha- kar, R & Tripathy, S l’ (1990) A controlled trial of iver- mectin and diethylcarbamazine in lymphatic lilariasis New EnglandJournal of Medicine, 322,1113-l 117
Perolat, I’., Guidi, C., Riviere, F & Roux, J (1986) Filariose
de Bancroft en Polyntsie Francaise Situation epidtmio- logique et perspectives apres 35 ans de lutte Bulletin de la So- ciete de Pathologie Ewotique, 79, 78-88
Richards, F O., jr, Eberhard, M L., Bryan, R T., McNeeley,
D F., Lammie, I’ J., McNeeley, M B., Bernard, Y., Hightower, A W & Spencer? H C (1991) Comparison of high dose ivermectin and dtethylcarbamazine for activity against bancroftian lilariasis in Haiti American Journal of Tropical Medicine and Hygiene, 44,3-10
Roux, J., Cartel, J.-L., Perolat, I’., Boutin, J I’., Sechan, Y., Lariviere, M & Aziz, M A (1989) Etude de l’ivermectine pour le traitement de la filariose lymphatique due & Wuchere- ria bancrofti var pacijica en I’olyntsie Francaise Bulletin de la Soci& de Pathologie Exotique, 82,72-81
Received 3 August 1993; revised 3 September 1993; accepted for publication 8 September I993
TRANSACTIONS OF THE ROYAL SOCIETY OP TROPICAL MEDICINE AND HYGIENE (1994) 88, 464-465
/Short
A randomized comparative study of
fleroxacin and ceftriaxone in enteric
fever
Tran Tinh Hien, Nguyen Minh Duong, Huynh Duy
Ha, Nguyen Thi Tuyet Hoa, To Song Diep, Le Thi
Phi and Keith Arnold Centre for Tropical Diseases, Cho
Quart Hospital, Ho Chi Mirth City, Viet Nam
Typhoid or enteric fever is a common disease in Viet
Nam In 1992 in south Viet Nam there were 9179 clinical
cases reported to the Pasteur Institute of Ho Chi Minh
City and over 600 cases of enteric fever were clinically di-
agnosed at Cho Quan hospital, of whom 32% provided
positive blood cultures
Chloramphenicol-resistant typhoid was first described
in Viet Nam from Cho Quan hospital in 1973 (BUTLER et
al., 1973), and from Nguyen Van Hoc hospital in 1975
(BROWN et al., 1975) In the mid 1970s the prevalence of
chloramphenicol resistance was 75% (BUTLER et al.,
1977), but by the late 1980s it had dropped to 45% (Hoa,
unpublished observation) In the early 1990s physicians
noticed (as they had in 1973) that patients with typhoid
fever were not responding to chloramphenicol (pro-
Address for correspondence: Dr Tran Tinh Hien, Cho Quan
Hospital, 190 Hen Ham Tu, Quan 5, Ho Chi Minh City, Viet
Nam
longed fever and persistence of signs and symptoms), and in addition they were not responding to ampicillin or
to co-trimoxazole This indicated that there was an ur- gent need for new effective antibiotics for the treatment
of typhoid fever
The third generation cephalosporins have been re- ported to be very effective (ISLAM et al., 1988), especially ceftriaxone in a short treatment course of 3 d (LASSERRE
et al., 1991) The quinolones are also effective (AS- PERILLA et al., 1990), in particular fleroxacin in a short treatment course of 7 d (ARNOLD et al., 1993) An earlier quinolone, oxolinic acid, although effective in vitro against Salmonella typhi, had been found to be ineffective for typhoid fever at Cho Quan hospital at the time of the first appearance of chloramphenicol resistance (SANFORD
et al., 1976)
Figure Percentages of enteric fever patients still febrile after treatment with ceftriaxone ( , 13 patients) and fleroxacin ( -, 16 patients)
Trang 2465
Table Clinical and microbiological features of emetic fever patients
and treatment results
Number
Male/female ratio
Age (years)
Weight (kg)
Duration of fever
before trearmcnr (d)
Leucocyte count
( x 10%)”
No of blood isolates
5’ typhi
s parat~phe’ A
‘~jcrobiolo~i~ cure
Clinical &e
Fever c’learance time (h)
16
1115
24 (7; 17-43)
46 (8; 33-56)
15 (3; 9-21) 5.81 (1.78; 3-5-S-S) 5
14
16116 ;loO%)
16116 (100%)
81 (40; 36-170)
15
1114
29 (15; 1672)
44 (5; 35-51)
17 (9; 7-33) 52 (1.92; 4-10.0)
13
L
13114 (93%)b
13115 (87%)
160 (75; 78-306)
“Means (standard deviations and ranges in parentheses)
bOne patient receiving one dose of ceftriaxone followed by dyspnoea and
hypotension was excluded from rhe microbiological analysis but was
included in the clinical evaluation
‘rz= 13 for ceftriaxone Significant difference between the 2 drugs
(P-0.02); no other difference was significant
A study, approved by the hospital scientific and ethical
committee, was carried out at Cho Quan Hospital in Ho
Chi Minh City, Viet Nam, during 1992-1993 to compare
a 7 d course of fleroxacin (orally) with a 5 d course of cef-
triaxone (intravenously) because, although ceftriaxone is
effective., an oral treatment is preferable Forty-six pa-
tients with a clinical diagnosis of typhoid fever (axillary
temperature above 37.5”C over 7 d, ‘toxic’ appearance
and negative malaria blood film) were allocated at ran-
dom to receive either fleroxacin 400 mg orally in a single
dose daily for 7 d or ceftriaxone 2 g intravenously once a
day for 5 d, after their informed verbal consent had been
obtained The temperature was measured every 6 h,
blood cultures and stool cultures were prepared before
treatment was started and on day 7, with an additional
blood culture on day 3 Routine laboratory investigations
for hepatic, renal and haematological assessment were
done before and after treatment Patients were requested
to return to the hospital for follow-up on days 14 and 2s
after the end of treatment
Thirty-one patients had enteric fever confirmed by
positive blood culture before treatment (27 S typhi and 4
S paratyphi A); their clinical and microbiological fea-
tures and the results of treatment are shown in the Table
All isolates were S.tv~hi exceut for 4 S.z~~ratv&i A, 2 in
each treatment group Of the ‘s typhi, &I% w;e resistant
to chloramphenicol, 46% to ampicillin, and 46% to co-
trimoxazole (44% were resistance to all 3 drugs); all were
sensitive to fleroxacin and ceftriaxone bv disk diffusion
The S paratyphi A isolates were sensitive to all drugs
Of the 3 1 patients, 29 were evaluable for time to defer-
vescence (axillary temperature <37,5”C): 16 in the fle-
roxacin-treated group and 13 of the 15 ceftriaxone-
treated patients The Figure shows more rapid
defervescence with fleroxaxin than with ceftriaxone
(mean fever clearance times were signi~ca~tly different,
81 h vs 160 h: Map-Whitnev U non-narametric test
P=O*OZ) Blood cultures from these 29 patients were negl
ative on days 3 and 7 One patient receiving ceftriaxone
developed side effects following the first dose (dyspnoea
and hypotension) and was changed to alternative therapy
and therefore excluded from the microbiological analysis
results A second patient receiving ceftriaxone remained
febrile for 14 d and, although blood cultures on days 3
and 7 were negative, a bone marrow culture on day 14
was positive for S typhi Clinical cure (reduction of
maximum daily axillary temperature to <37.X and
complete disappearance of all other signs and symptoms
within 14 d with no clinical evidence of infection during
further follow-up) and microbiologic~ cure (initial pa-
thogen eliminated from blood, bone marrow and stool within 14 d, all cultures remaining negative for at least 21 d) were assessed and both rates were 100% for fleroxacin For ceftriaxone, the clinical cure rate was 87% and the microbiological cure rate 93% Only 3 positive stool cul- tures were obtained before treatment in each group and one patient was still stool positive on day 7 in the cef- triaxone group; in the fleroxacin group one patient with a negative pre-treatment stool culture had a positive cul- ture on day 7 Since only 16 of the 31 patients returned for follow-up on days 14 and 28 (all of them were clini- cally, well, afebrile and with no complaint), it was not possible reliably to evaluate either drug for its effective- ness in preventing relapse or development of the carrier state
There was no significant abnorm~ity in the laboratory tests on follow-up at day 7 Side effects of the drugs were
a probable anaphylactic response to ceftriaxone, atid nau- sea, vomiting and insomnia were reported by a few pa- tients receiving fleroxacin
Towards the end of this study multiple-drug resistance was found to be increasing in Viet Nam, and the latest results (mid-1993) show that resistance to chlorampheni- co1 is 91.2%, to ampicillin 92.8%, and to co-trimoxazole 96%, with a combined resistance to all 3 drugs of 88~7% (249 strains tested); sensitivity to ceftriaxone and the qui- nolone, however, was 100% (unpublished data, Cho Quan Hospital)
In conclusion, this study confirmed that both ceftriax- one and fleroxacin, given as a single daily dose over 5 and
7 d respectively, are effective for treating multiple-drug resistant typhoid fever However, fleroxacin is easier to administer, more rapidly lowers the temperature, and is available in an oral as well as a parenteral form
Acknowledgement
We are grateful for the support of Dr Nguyen Huu Tri, Di- rector of the Centre for Tropical Diseases, the Roche Asian Re- search Foundation, and the doctors, nursing and laboratory staff of the hospital
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Received 1 September 1993; revised 29 ~~v~be~ 1993; accepted f~~~~blicution 30 bobber 1993