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Sensitivity in vitro of Plasmodium falciparum to chloroquine and mefloquine in two regions of Benin
584 TRANSACTIONS OF THE ROYALSOCIETY OF TROPICAL MEDICINEAND HYGIENE(1989)83, 584-585
Sensitivity falciparum mefloquine
in vitro of Plasmodium to chloroquine and in two regions of Benin
J: P. Cbippaux’, A. Massougbodji* P. Olliaro3, F. Gay’, S. Caligaris3 and M. Danis’* ‘Centre ORSTOM de Cotonou, B.P. 390, People’s Republic of Benin: ‘Fact& des Sciences de la SanJ. BP. 188. Co&, PeopYs Republic of Beniy; ,‘Clinica di Malattie Infettive e Tropicali, Universlta di Bresci!, TrapItaly; ‘D&J artement de Parasitolo&Mt?decine tale et Unit6 INSERM 313, HGpital PitikSal@ri&e, Paris, France
In Benin, resistance to chloroquine was first detected in non-immune visitors in 1986(LE BRASet al., 1986; ROSENHEIM et al., 1987) and has been confirmed in field surveys during 1987 in Cotonou (GUIGUEMDEet al., 1987) and Zou Province (DJIVOH et al., 1988). The present report updates and better defines the geographical distribution of resistance of Plasmodium falciparum to chloroquine, the most widely used antimalarial drug, and to mefloquine, a possible second-line drug. Table.
resistance to chloroquine as defined by WHO, whereas only one strain proved to be highly resistant to mefloquine and 3 other strains were defined as borderline in agreement with the WHO definition. Chloroquine resistance appeared suddenly and increased dramatically in Benin. Therefore, it seems that the hypothesis that chloroquine-resistant strains have been circulating undetected for years in the past is no longer justifiable. Due to the small sample size, our data were grouped into 2 geographical areas corresponding to administrative subdivisions (the region of Cotonou in Atlantic Province, a lagoon zone, and the region of Dassa Zoumt in Zou Province, a savannah zone), regardless of other variables. The prevalence of P. falciparum infection in Zou Province was very much higher than in the region of Cotonou (P~~O*OOl), the latter having the highest number of chlorcquine resistant strains. (X-squared tests have shown a significant difference in the prevalence of chloroquine resistant strains in the 2 areas (P
Results of WHO io vitro microtests
Cotonou region po;dProvmce
No. of persons examined
No. with malaria”
2137 637 2774
459 (215%) 240 (37.7%) 699 (252%)
In vitro tests Mefloquine Chloroquine No, No. resistant No. No. resistant
41 :t
aParasitaemia S500/mm3. From October to November 1987, when the rainy seasonended, we carried out WHO standard in vitro microtests between Cotonou and Dassa Zoume, 230 km from the sea, in the Atlantic and Zou Provinces. On the basis of our knowledge of the epidemiology of malaria in the southern region of Benin, we chooseschoolchildren aged 7 to 12 years as the study population. Subjects with more than 500 P. falciparum asexual parasites per mm3 of blood and no history of antimalarial intake in the previous 14 d met the criteria for inclusion and were further studied. Sample collection, test procedure and evaluation of results were performed according to WHO standard procedures (WHO, 1984). Results are given in the Table. Blood samplesfrom 113 subjects were cultured in the presenceof chloroquine and/or mefloquine; 89 chloroquine tests (59 of which were evaluable) and 79 mefloquine (68 evaluable) were performed. 22 strains (37.3%) showed ‘Author for reprint requests.
occurred simultaneously with the rise of parasitological and entomological indices observed during the 1986 rainy season(AKOGBETO et al., 1990). At present, we have no explanation for this dramatic rise. A survey carried out at the same time by means of an in vitro hypoxanthine incorporation semi-microtest should give results which ,we hope will help to provide an explanation. Acknoweledgements
We gratefully acknowledgeme assistanceof Mr M. Monfort, Chief of the Mission Francaised’Aide et de Coofiration, Cotonouand we are indebted to Mr Lee Yellott for his help in the English translationof the manuscript. References
Akegbetq,M., Chippa”, J. P. & Coluzzi, M. (1990). Le paludlsme urbain cher B Cotonou, RCpublique Populake du B&in. 1. Etude Entomologique. - _ .Epidkniok~&!ie Tropicale, in press. Djivoh, C., Massougbodji, A., Turk, P., Fayomi, E. B., Gay, F. & Danis, M. (1988). Fable niveati de chloro-
585
quinor&istance de Pkzsmod~um fulciparum dans la Province du Zou au B&in. Bulletin de la So&k dePa&&gie Exotique, 81, 332-337. Gui uemde, T. R., Ouedraogo, J. B. & Gbary, A. R. (1987). ii tude de la chimiosensibilit6 de P. falcpuruma Cotonou.
$kp7wnt TechniqueOCCGE, Bobo Dioulasso, no. 9,
Le Bras, j., Hatin, I., Bourte, P., Coca-Cianci, O., Garin, J. P., Rey, M,., Charmot, G. & Roue, R. (1986). Chloroquine-reslstant falciparum malaria in Benin. Lancer, 4, 1043-1044. Rosenhelm, M., Prazuck, T., Brandicourt, O., Diquet, B.,
Robert
Cochrane
Datry, A., Danis, M. & Gentilini,
M. (1987). Five cases
of chloroquine-resistant malaria in Benin, Africa. Transactions of the Royal Society of Tropical Medicine and Hygiene, 81, 498. WHO (1984). Instructions for use of the micro test kit for he assessmentof the response of Plasmodium falciparum to chloroquine and m&q&e in vitro. Geneva: World Health
Organization, document no. MAP/8401.
Received 19 January 1989; revised 29 March 1989; accepted for publication 29 March 1989
Fund for Leprosy
The fund, in memory of the great leprologist Robert Cochrane, is administered by the Royal Society of Tropical Medicine and Hygiene. It is to be used to finance up to three travel fellowships each year to a maximum value of cl,200 each. The Fund will support travel **Leprosy workers who need **Experienced leprologists to There is no restriction on the met.
for to obtain practical training in field work or in research provide practical clinical training in a developing country country of origin or destination providing the above requirements are
Application forms are available from the Society and completed forms must be received by the Society at least six mom@ ahead of the proposed trip. All applications must be sponsored by a suitable representative of the applicant’s employer or study centre, and agreed by the host organization. A two-page report on the travel/study should be submitted, within one month of the recipient’s return, to: The Honorary Secretaries, Royal Society of Tropical Medicine and Hygiene, Manson House, 26 Portland Place, London WlN 4EY, UK.
Sensitivity falciparum mefloquine
in vitro of Plasmodium to chloroquine and in two regions of Benin
J: P. Cbippaux’, A. Massougbodji* P. Olliaro3, F. Gay’, S. Caligaris3 and M. Danis’* ‘Centre ORSTOM de Cotonou, B.P. 390, People’s Republic of Benin: ‘Fact& des Sciences de la SanJ. BP. 188. Co&, PeopYs Republic of Beniy; ,‘Clinica di Malattie Infettive e Tropicali, Universlta di Bresci!, TrapItaly; ‘D&J artement de Parasitolo&Mt?decine tale et Unit6 INSERM 313, HGpital PitikSal@ri&e, Paris, France
In Benin, resistance to chloroquine was first detected in non-immune visitors in 1986(LE BRASet al., 1986; ROSENHEIM et al., 1987) and has been confirmed in field surveys during 1987 in Cotonou (GUIGUEMDEet al., 1987) and Zou Province (DJIVOH et al., 1988). The present report updates and better defines the geographical distribution of resistance of Plasmodium falciparum to chloroquine, the most widely used antimalarial drug, and to mefloquine, a possible second-line drug. Table.
resistance to chloroquine as defined by WHO, whereas only one strain proved to be highly resistant to mefloquine and 3 other strains were defined as borderline in agreement with the WHO definition. Chloroquine resistance appeared suddenly and increased dramatically in Benin. Therefore, it seems that the hypothesis that chloroquine-resistant strains have been circulating undetected for years in the past is no longer justifiable. Due to the small sample size, our data were grouped into 2 geographical areas corresponding to administrative subdivisions (the region of Cotonou in Atlantic Province, a lagoon zone, and the region of Dassa Zoumt in Zou Province, a savannah zone), regardless of other variables. The prevalence of P. falciparum infection in Zou Province was very much higher than in the region of Cotonou (P~~O*OOl), the latter having the highest number of chlorcquine resistant strains. (X-squared tests have shown a significant difference in the prevalence of chloroquine resistant strains in the 2 areas (P
Results of WHO io vitro microtests
Cotonou region po;dProvmce
No. of persons examined
No. with malaria”
2137 637 2774
459 (215%) 240 (37.7%) 699 (252%)
In vitro tests Mefloquine Chloroquine No, No. resistant No. No. resistant
41 :t
aParasitaemia S500/mm3. From October to November 1987, when the rainy seasonended, we carried out WHO standard in vitro microtests between Cotonou and Dassa Zoume, 230 km from the sea, in the Atlantic and Zou Provinces. On the basis of our knowledge of the epidemiology of malaria in the southern region of Benin, we chooseschoolchildren aged 7 to 12 years as the study population. Subjects with more than 500 P. falciparum asexual parasites per mm3 of blood and no history of antimalarial intake in the previous 14 d met the criteria for inclusion and were further studied. Sample collection, test procedure and evaluation of results were performed according to WHO standard procedures (WHO, 1984). Results are given in the Table. Blood samplesfrom 113 subjects were cultured in the presenceof chloroquine and/or mefloquine; 89 chloroquine tests (59 of which were evaluable) and 79 mefloquine (68 evaluable) were performed. 22 strains (37.3%) showed ‘Author for reprint requests.
occurred simultaneously with the rise of parasitological and entomological indices observed during the 1986 rainy season(AKOGBETO et al., 1990). At present, we have no explanation for this dramatic rise. A survey carried out at the same time by means of an in vitro hypoxanthine incorporation semi-microtest should give results which ,we hope will help to provide an explanation. Acknoweledgements
We gratefully acknowledgeme assistanceof Mr M. Monfort, Chief of the Mission Francaised’Aide et de Coofiration, Cotonouand we are indebted to Mr Lee Yellott for his help in the English translationof the manuscript. References
Akegbetq,M., Chippa”, J. P. & Coluzzi, M. (1990). Le paludlsme urbain cher B Cotonou, RCpublique Populake du B&in. 1. Etude Entomologique. - _ .Epidkniok~&!ie Tropicale, in press. Djivoh, C., Massougbodji, A., Turk, P., Fayomi, E. B., Gay, F. & Danis, M. (1988). Fable niveati de chloro-
585
quinor&istance de Pkzsmod~um fulciparum dans la Province du Zou au B&in. Bulletin de la So&k dePa&&gie Exotique, 81, 332-337. Gui uemde, T. R., Ouedraogo, J. B. & Gbary, A. R. (1987). ii tude de la chimiosensibilit6 de P. falcpuruma Cotonou.
$kp7wnt TechniqueOCCGE, Bobo Dioulasso, no. 9,
Le Bras, j., Hatin, I., Bourte, P., Coca-Cianci, O., Garin, J. P., Rey, M,., Charmot, G. & Roue, R. (1986). Chloroquine-reslstant falciparum malaria in Benin. Lancer, 4, 1043-1044. Rosenhelm, M., Prazuck, T., Brandicourt, O., Diquet, B.,
Robert
Cochrane
Datry, A., Danis, M. & Gentilini,
M. (1987). Five cases
of chloroquine-resistant malaria in Benin, Africa. Transactions of the Royal Society of Tropical Medicine and Hygiene, 81, 498. WHO (1984). Instructions for use of the micro test kit for he assessmentof the response of Plasmodium falciparum to chloroquine and m&q&e in vitro. Geneva: World Health
Organization, document no. MAP/8401.
Received 19 January 1989; revised 29 March 1989; accepted for publication 29 March 1989
Fund for Leprosy
The fund, in memory of the great leprologist Robert Cochrane, is administered by the Royal Society of Tropical Medicine and Hygiene. It is to be used to finance up to three travel fellowships each year to a maximum value of cl,200 each. The Fund will support travel **Leprosy workers who need **Experienced leprologists to There is no restriction on the met.
for to obtain practical training in field work or in research provide practical clinical training in a developing country country of origin or destination providing the above requirements are
Application forms are available from the Society and completed forms must be received by the Society at least six mom@ ahead of the proposed trip. All applications must be sponsored by a suitable representative of the applicant’s employer or study centre, and agreed by the host organization. A two-page report on the travel/study should be submitted, within one month of the recipient’s return, to: The Honorary Secretaries, Royal Society of Tropical Medicine and Hygiene, Manson House, 26 Portland Place, London WlN 4EY, UK.