533
CORRESPONDENCE
We wish to thank Professor James R. Busvine for his technical advice. We are, etc., L.L. SH~LDT D. J. SEIBERT M.L.HOLLOWAY U.S. Naval Medical Research Unit No. 5, APO New York 09319 U.S.A. M. M. COLE Gainesville, Florida 32604 U.S.A. D.E. WEIDHAAS Insects Affecting Man Research Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Gainesville, Florida 32604 U.S.A. References
Armed Forces Pest Control Board (1959). Technical Information Memorandum No. 3, Washington. Miller, R. N., Wisseman, Jr., C. L., Sweeney, G. W., Verschueren, A. & Fabrikant, I. B. (1972). First report of resistance of human body lice to malathion. Transactions of the Royal Society of Tropical Medicine and Hygiene, 66, 372-375.
World Health Organization (1970). Information circular on insecticide resistance, insect behaviour, and vector genetics. VBC/IRG 70.12, Geneva (mimeographed document). World Health Organization (1976). Resistance of vectors and reservoirs of disease to pesticides. WHO Technical Report Series No. 585, Geneva. Chloroquine
resistant Plasmodium falciparum Bangladesh
in
Srn-Since March 1975 we have operated an entomological field station at Chunaraghat in Sylhet District, Bangladesh: this is a tea-growing region that borders the Indian state of Tripura. As part of our study of the breeding dynamics of Anopheles balabacensis, we conduct, each month, 14 consecutive all-night biting catches both indoors and outdoors and examine a thick blood film from nearly all the 178 people that comprise the population of the isolated village where the biting catches are done. All those found positive for P. falciparum are immediately treated with 25 mg chloroquine base per kg body-weight (maximum 1,500 mg). It became evident during the autumn of 1975 that falciparum contracted at this site was not responding to chloroquine as expected. Five of our 15 insect collectors contracted P. falciparum, in spite of weekly prophylactic doses of 300-900 mg chloroquine base, and four of these later recrudesced after having each received 1,500 mg chloroquine over the recommended three-day period. Since in each case the period between treatment and reappearance of parasitaemia was spent in non-transmission zones, the possibility of reinfection can be excluded. Secondly, even though we can demonstrate by Anopheles dissection that no transmission took place -at the site from late October 1975 through March 1976, and that in suite of monthly treatment -of all cases, there had apparently been no decrease in prevalence as at 24th December, 1975. Nearly all the 54 falciparum cases detected in December had been positive the preceding month and had subsequently been treated. By 29th March, 1976, 18 cases of asexual falciparum remained, each of which had been treated in at least three of the preceding five non-transmission months. Thirdly, in September 1975, 16 children from this village population, between the
ages of five and 15, who were positive for falciparum trophozoites were treated by us with 10 mg per kg body-weight and checked for drug excretion 24 hours later. Of 14 who had an unambiguously positive WilsonEdeson urine reaction, six had parasitaemias (ranging from 96 to 13,000 trophozoites per cu mm) when a second blood smear was examined nine days after drug administration. In October a similar test was done, but without urine analysis, on 15 adults receiving a total 900 mg each and 12 children receiving the full recommended dose of 25 mg per kg. Seven days after treatment six of the adults and seven of the children were positive for asexual stages. In all the cases cited above, chloroquine was swallowed in the presence of one of us or of the area Malaria Supervisor. Among the village population malaria symptoms are mild, apparently because of acquired immunity; all children less than five years old not cured by the standard chloroquine regime were treated with “Fansidar”. The occurrence of chloroquine resistance in east Bengal has long been predicted (CLYDE, et al., 1973) and it was possibly present here as early as 1970, when it was reported on the basis of clinical and parasitological evidence in Mymensingh District by local Malaria Eradication personnel &HAN, 1971).- Since then the National Malaria Eradication Program has been performing trials strictly following WHO standards (1973) in an attempt to determine the extent and severity of resistance. Recent trials, the detailed results of which will be published later, confirm R-Z level resistance in several regions other than the one in Sylhet where our cases of apparent resistance were found, and one of us has recently helped treat, under hospital conditions in Dacca, two cases of resistance contracted in Barisal and Comilla Districts, respectively (ROSENBERG et al.. 1976). We publish this interim note because many ‘people concerned with malaria are unaware that chloroquineresistant P. falciparum occurs in Bangladesh. We are grateful to the Director, Dr. Mahboober Rahman, and staff of the Bangladesh Malaria Eradication Program for invaluable assistance. Our work is supported in part by NIH grant R07-AI 10048-16 and STOl-AI 100020-19. We are, etc., RONALD ROSENBERG The Johns Hopkins University-Znternational Center for Medical Research, 550 N. Broadway Suite 115, Baltimore 21205, U.S.A. N.P.MAHESWARY Malaria Eradication Program, No. 88, Road 4, Dhanmondi, Dacca, Bangladesh References
Clyde, D. F., McCarthy, V. C., DuPont, H. L. & Hornick, R. B. (1973). Characterization of a drug resistant- strain of-P. falciparum from Burma. Journcd of Trouical Medicine
and Hygiene.
76. 54-60.
Khan, k. A. (1971). Suspected chloroquine resistant P. falciparum in East Pakistan. Dip. P.H. Thesis, University of the Punjab. Rosenberg, R., Alam, A. K. M. J. &Brown, K. H. (1976). Two cases of chloroquine resistant Falcinarum Malaria. Bangladesh Medical Journal (in press). World Health Organization (1973). Chemotheraov of rnaiaria and resistance to antimalarials. World Health Organization
Technical Report Series, No. 529.
CORRESPONDENCE
We wish to thank Professor James R. Busvine for his technical advice. We are, etc., L.L. SH~LDT D. J. SEIBERT M.L.HOLLOWAY U.S. Naval Medical Research Unit No. 5, APO New York 09319 U.S.A. M. M. COLE Gainesville, Florida 32604 U.S.A. D.E. WEIDHAAS Insects Affecting Man Research Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Gainesville, Florida 32604 U.S.A. References
Armed Forces Pest Control Board (1959). Technical Information Memorandum No. 3, Washington. Miller, R. N., Wisseman, Jr., C. L., Sweeney, G. W., Verschueren, A. & Fabrikant, I. B. (1972). First report of resistance of human body lice to malathion. Transactions of the Royal Society of Tropical Medicine and Hygiene, 66, 372-375.
World Health Organization (1970). Information circular on insecticide resistance, insect behaviour, and vector genetics. VBC/IRG 70.12, Geneva (mimeographed document). World Health Organization (1976). Resistance of vectors and reservoirs of disease to pesticides. WHO Technical Report Series No. 585, Geneva. Chloroquine
resistant Plasmodium falciparum Bangladesh
in
Srn-Since March 1975 we have operated an entomological field station at Chunaraghat in Sylhet District, Bangladesh: this is a tea-growing region that borders the Indian state of Tripura. As part of our study of the breeding dynamics of Anopheles balabacensis, we conduct, each month, 14 consecutive all-night biting catches both indoors and outdoors and examine a thick blood film from nearly all the 178 people that comprise the population of the isolated village where the biting catches are done. All those found positive for P. falciparum are immediately treated with 25 mg chloroquine base per kg body-weight (maximum 1,500 mg). It became evident during the autumn of 1975 that falciparum contracted at this site was not responding to chloroquine as expected. Five of our 15 insect collectors contracted P. falciparum, in spite of weekly prophylactic doses of 300-900 mg chloroquine base, and four of these later recrudesced after having each received 1,500 mg chloroquine over the recommended three-day period. Since in each case the period between treatment and reappearance of parasitaemia was spent in non-transmission zones, the possibility of reinfection can be excluded. Secondly, even though we can demonstrate by Anopheles dissection that no transmission took place -at the site from late October 1975 through March 1976, and that in suite of monthly treatment -of all cases, there had apparently been no decrease in prevalence as at 24th December, 1975. Nearly all the 54 falciparum cases detected in December had been positive the preceding month and had subsequently been treated. By 29th March, 1976, 18 cases of asexual falciparum remained, each of which had been treated in at least three of the preceding five non-transmission months. Thirdly, in September 1975, 16 children from this village population, between the
ages of five and 15, who were positive for falciparum trophozoites were treated by us with 10 mg per kg body-weight and checked for drug excretion 24 hours later. Of 14 who had an unambiguously positive WilsonEdeson urine reaction, six had parasitaemias (ranging from 96 to 13,000 trophozoites per cu mm) when a second blood smear was examined nine days after drug administration. In October a similar test was done, but without urine analysis, on 15 adults receiving a total 900 mg each and 12 children receiving the full recommended dose of 25 mg per kg. Seven days after treatment six of the adults and seven of the children were positive for asexual stages. In all the cases cited above, chloroquine was swallowed in the presence of one of us or of the area Malaria Supervisor. Among the village population malaria symptoms are mild, apparently because of acquired immunity; all children less than five years old not cured by the standard chloroquine regime were treated with “Fansidar”. The occurrence of chloroquine resistance in east Bengal has long been predicted (CLYDE, et al., 1973) and it was possibly present here as early as 1970, when it was reported on the basis of clinical and parasitological evidence in Mymensingh District by local Malaria Eradication personnel &HAN, 1971).- Since then the National Malaria Eradication Program has been performing trials strictly following WHO standards (1973) in an attempt to determine the extent and severity of resistance. Recent trials, the detailed results of which will be published later, confirm R-Z level resistance in several regions other than the one in Sylhet where our cases of apparent resistance were found, and one of us has recently helped treat, under hospital conditions in Dacca, two cases of resistance contracted in Barisal and Comilla Districts, respectively (ROSENBERG et al.. 1976). We publish this interim note because many ‘people concerned with malaria are unaware that chloroquineresistant P. falciparum occurs in Bangladesh. We are grateful to the Director, Dr. Mahboober Rahman, and staff of the Bangladesh Malaria Eradication Program for invaluable assistance. Our work is supported in part by NIH grant R07-AI 10048-16 and STOl-AI 100020-19. We are, etc., RONALD ROSENBERG The Johns Hopkins University-Znternational Center for Medical Research, 550 N. Broadway Suite 115, Baltimore 21205, U.S.A. N.P.MAHESWARY Malaria Eradication Program, No. 88, Road 4, Dhanmondi, Dacca, Bangladesh References
Clyde, D. F., McCarthy, V. C., DuPont, H. L. & Hornick, R. B. (1973). Characterization of a drug resistant- strain of-P. falciparum from Burma. Journcd of Trouical Medicine
and Hygiene.
76. 54-60.
Khan, k. A. (1971). Suspected chloroquine resistant P. falciparum in East Pakistan. Dip. P.H. Thesis, University of the Punjab. Rosenberg, R., Alam, A. K. M. J. &Brown, K. H. (1976). Two cases of chloroquine resistant Falcinarum Malaria. Bangladesh Medical Journal (in press). World Health Organization (1973). Chemotheraov of rnaiaria and resistance to antimalarials. World Health Organization
Technical Report Series, No. 529.
