Deacon, H.E.

Freese, J.A.

Sharp, B.L.

English

AJOL - African Journals Online

Drug-resistant Plasmodiumfalciparum malaria in theeastern TransvaalH. E. Deacon, J. A. Freese, B. L. SharpIn March 1993, a study was undertaken in the. KomatipoortlMalelane area to monitor the in vitrosensitivity of Plasmodium falciparum to antimalarialdrugs currently in use in South Africa. Of the 12 isolatescollected, 7 were successfully tested for sensitivity tochloroquine and quinine, 6 for mefloquine susceptibility,and 5 for sensitivity to Fansidar. Four of the isolates wereresistant to chloroquine at Rill level, 1 at Rlllevel, and 2were sensitive. All isolates were found to be sensitive toboth quinine and mefloquine. Results suggested possibleresistance to Fansidar. These findings have implicationsfor tourists travelling to this area.S Afr Med J 1994; 84: 394-395.Resistance to chloroquine was first detected in 1958in both South America and south-east Asia.'It was first reported from Africa in 1979, from both Kenya'and Tanzania.' Reports of in vivo and in vitro resistance tochloroquine then followed in the 1980s from all the southernAfrican countries, including Botswana: Mozambique,5Angola,"'? Namibia,' Zimbabwe· and Swaziland.9 Chloroquineresistance was first reported in South Africa in 1'985.Bac et aI. 'O reported on an in vivo resistant case from Vendawhich was confirmed in vitro; Visagie and Sieling" reportedon an in vivo case of chloroquine resistance from LouisTrichardt, and Herbst et al. '2 reported on 6 in vitrochloroquine-resistant isolates from the KwazululNatal area.A number of further studies have been completed inKwazulul Natal confirming the presence of highlychloroquine-resistant Plasmodium falciparum. '3-15Other than some case reports of chloroqUine resistance inthe Transvaal,'o,,, no further published data from in vivostudies or in vitro tests of field isolates exist for the area.Freese et al. '6 reported on the in vitro sensitivity of 5culture-adapted isolates collected in the eastern Transvaal.Four of the 5 isolates studied were found to be resistant tochloroquine. Although the culture conditions may haveresulted in the selection of resistant clones in these isolates,the results of the investigation nevertheless indicated thepresence of chloroquine-resistant parasites in the localP. falciparum population.National Malaria Research Programme of the South AfricanMedical Research Council (Natal), DurbanH. E. Deacon. B.SC. HONSJ. A. Freese. 8.SC. HONSB. L Sharp. PHD.It should be borne in mind that more than 40% of casesare classified as imported into the eastern and northernTransvaal provinces, of which a high percentage originatefrom other southern African countries where drug resistanceis known to occur (Department of National Health andPopulation Development - notification data).The South African Medical Research Council recentlyinitiated an investigation into the drug susceptibility of P.falciparum in the Transvaal area. In a survey carried out inMarch 1993 in the KomatipoortlMalelane area of the easternTransvaal, the in vitro sensitivity of P. falciparum toantimalarial drugs currently in use in South Africa wasmonitored.Materials and methodsBlood containing P. falciparum was obtained from patientsreporting to local clinics and doctors in the area (Le. .:passively detected cases)" and tested within 6 hours ofcollection for sensitivity to chloroquine, quinine, mefloqoineand sUlphadoxine/pyrimethamine (Fansidar), using amodification of the WHO in vitro microtechnique.14Isolates were considered to be suitable for the test if theycontained 500 - 80 000 ring forms of P. falciparum permicrolitre blood. Patients with mixed malarial infections andthose who had received antimalarial drugs during the 14days prior to the test were excluded from the investigation.The minimum inhibitory concentration (MIC) of eachisolate, defined as the lowest concentration at whichschizont maturation (SM) was completely inhibited, wasdetermined for each drug. The discriminating MICs'forresistant isolates are: chloroquine> 0,16 j.Lmol/l, quinine>5,12 j.Lmol/l, and mefloquine > 0,64 j.LmoVI.'6ResultsOf the 12 isolates found to be suitable for the test, 7 weresuccessfully tested for sensitivity to chloroquine and quinine,6 for mefloquine susceptibility, and 5 for sensitivity toFansidar. Four of the isolates were resistant to chloroquin~at Rill level (with MICs ranging from 0,64 to 1,28 j.Lmol/l); 1at RII level (MIC 0,32 j.LmoVI);' and 2 were sensitive (MICs0,04 and 0,16 j.Lmol/l) (Table I). All isolates were found to besensitive to both quinine (MIC 1,28 j.Lmol/1 for all 7 isolates)and mefloquine (MICs ranging from 0,04 to 0,16 j.LmoVI).The Fansidar MICs ranged from 0,2 to 60 j.LmoVI.Table I. In vitro sensitivity of eastern Transvaal isolates ofPlasmodium falciparum to four antimalarial drugsIsolate Chloroquine Quinine Mefloquine FansidarNo. MIC (IJmoVl) MIC (IJmoVl) MIC (IJmol/l) MIC (IJmoVl)1 0,32 1,28 NS NS5 1,28 1,28 0,16 0,66 0,64 1,28 0,16 20,09 0,64 1,28 0,04 60,014 1,28 1,28 0,08 0,215 0,16 1,28 0,16 0,216 0,04 1,28 0,16 NSNS - tests with SM less than 5% were considered not to be successful. ..Volume 84 No. 7 July 1994 SAMJ'DiscussionThese results confirm the presence of chloroquine-resistantp. falciparum in the eastern Transvaal. No information is,however, available concerning the in vivo response of thesame parasites to chloroquine. There was a wide range ofsusceptibility to sulphadoxine/pyrimethamine (MICs rangedfrom 0,2 to 60 J,lmoVI). The isolates fell into two distinctgroups, those with MICs < 1 J,lmoVI and those with MICs~ 20 J,lmol/l. It was not possible to draw conclusionsregarding the Fansidar resistance status of these isolates asthe discriminatory MIC values for resistant isolates in theWHO sUlphadoxine/pyrimethainine in vitro test have not yetbeen determined. Various authors have found that resistantand sensitive isolates can easily be distinguished by theirMICs"" and it is therefore possible that 2 isolates in this studywith MICs ~ 20 I1moVI may in fact be resistant to Fansidar.Since all the cases were classified as local transmission bythe authorities, the results indicate that there is transmissionof chloroquine-resistant and possibly Fansidar-resistant P.falciparum malaria in this region. These data are consideredimportant to the planning of malaria control strategies for thearea. Continued monitoring of the susceptibility to Fansidar(both in vivo and in vitro) should be seen as a priority.Immunity to malaria is known to shorten the duration ofindividuarinfections and to enhance the effect of antimalarialdrugs!' Chloroquine may still have a role to play in malariacontrol but resistance to this drug would pose a threat tonon-immune tourists travelling to this area.As outlined earlier, chloroquine-resistant P. falciparum iswidespread in southern Africa. A large number of our malariacases are imported into the country (> 30%) (Department ofNational Health and Population Development - notificationdata) and it is therefore not surprising that chloroquineresistance should be detected in our malarious areas.Currently, the eastern Transvaal is still documented as a low-risk area where chloroquine alone or no prophylaxis isrecommended.22 We believe that the eastern Transvaalshould be reclassified as a moderate to high-risk area(mainly from November to May) where prophylaxis such aschloroquine plus proguanil or mefloquine or doxycyclineshould be recommended to tourists.This study will continue in the next malaria season.We thank the Department of National Health andPopulation Development at Nelspruit for their valuableassistance and co-operation, and for allowing use of theirinfrastructure. We also thank Mrs Hettie Muller for makingmalarial case notification data available for the Transvaalregion. A special acknOWledgement to Mr Piet Burger fromKomatipoort for his friendly assistance in the field. This workw,as funded by the South African Medical Research Council.REFERENCES1. Report of a WHO Scientific Group_ Advances in Malaria Chemotherapy. (TechnicalReport Series 711). Geneva: WHO 1984: 1-218.2. Fogh S. Jepson S, Effersae P. Chloroquine-resistant Plasmodium falciparum inKenya. Trans R Sac Trop Med Hyg 1979; 73: 228-229.3. Kean BH. Chloroquine-resistant falciparum malaria from Africa. JAMA 1979; 241:395-396.4. Proceedings of the Malaria Workshop, co-ordinated by the South African MedicalResearch Council at Nelspruit. 6-7 Apr 1991.5. Schwalbach J, Schapira A. Suleimanov G. Chloroquine-resistant malaria inMozambique. Lancet 1985; 2: 897-898.6. Kyr6neppa H, lumio J, Ukkonen R, Pettersson T. Chloroquine-resistant malariafrom Angola. Lancet 1984; 2: 1244.7. Blumenfeld AM, Sleling Wl. Davidson A, Isaacson M. Probable chloroquine-resistant Plasmodium talciparum malaria in south-western Africa. S Afr Med J1984; 66: 207-208.8. Dallas ABC, Mutambu Sl, Taylor P. Chloroquine-resistant Plasmodium falciparummalaria in Zimbabwe. C6nt Atr J Med 1984; 30: 204-205.SAMJARTICLES9. Raviglione MC. Appearance af chloroquine-resistant falciparum malaria inSwaziland. Lancet 1987; 2: 44-45.10. Sac DJ, Cox GA, Isaacson M. In vivo and in vitro chloroquine-resistantfalciparum malaria in Venda. S Atr Med J 1985; 67: 937-938.11. Visagie NJ, Sieling WL. Chloroquine-resistant Plasmodium talciparum malaria inSouth Africa. S AIr Med J 1985; 66: 600-601.12. Herbst JM. Taylar LA, Joubert SM. In vitro chloroquine-resistant Plasmodiumfalciparum malaria in the NataVKwazulu area S Atr Med J 1985; 68: 749-750.13. Herbst JM, Taylor LA, Joubert SM. Chloroquine resistance in Plasmodiumlalciparum in Natal. S AIr Med J 1987; 72: 627·629.14. Freese JA. Sharp Bl, Ngxongo SM, Markus MS. In vitro confirmation ofchloroquine-resistant Plasmodium falciparum malaria in Kwalulu. S Afr Med J1988; 74: 576-578.15. Hansford CF. Chloroquine resistance in Plasmodium faleiparum in Kwazulu, 1983-1988. S AIr Med J 1989; 76: 546-547.16. Freese JA. Markus MS. Golenser J. In vitro sensitivity of southern Africanreference isolates of Plasmodium falciparum to chloroquine and pyrimethamine.Bull WHO 1991; 69: 707-712.17. Sharp Bl. Ngxongo S. Botha ~J. Ridl F, le Sueur D. An analysis of 10 years ofretrospective malaria data from the Kwazulu areas of Natal. S Atr J Sei 1988; 84:102-106.18. Wernsdorfer WH, Payne D. Drug sensitivity tests in malaria parasites. In:Wernsdorfer WHo McGregor I, eds. Malaria: Principles and Practice otMalariology, vol2. Edinburgh: Churchill Uvingstone, 1988: 1765-1800.19. Jsaacson M, Cox GA, Sieling Wl. Chloroquine resistant Plasmodium talciparummalaria in Namibia. Lancet 1984; 2: 42.20. Schapira A. The resistance of falciparum malaria in Africa to 4-aminoquinolinesand antifolates. Scand J Inlect Dis (suppn 1990; 75: 1-60.21. Wernsdorfer WHo The development and spread of drug-resistant malaria.Par.sitology Today 1991; 71: 297-303.22. Baker L, Van Schoor JD, Bartlett GA, lombard JH. Malaria prophylaxis - theSouth African viewpoint. S Atr Med J 1993; 83; 126-129.Accepted 1 June 1994.Antimalarial measures -type, sources of advice andcompliance among touriststo Natal/KwaZuluG. B. Wilken, L. BakerTypical advice on antimalarial measures provided bypharmacies as well as actual behaviour in this regard andsources of advice accessed by tourists to northern Natal/Kwazulu were canvassed by telephonic interviews with 70pharmacies and 53 'care providers' (members of travelparties). Doctors (26%) and phannacists (40%) were themost commonly approached sources of antimalarialadvice. Professional recommendations frequently involvedchloroquine-based drugs (80% of recommended drugs),despite the chloroqUine-resistant status of the study area.Drug choice reflected the limited availability of newalternatives to chloroquine at the time the study wasconducted, as well as ignorance of drug resistance in thearea Possible reasons for the inappropriate nature of manyof the reported recommendations, as well as an approachto the dissemination of future prophylactic policydocuments, are discussed.S Afr Med J 1994; 84: 395-398.National Malaria Research Programme of the South AfricanMedical Research Council, DurbanG. B. Wilken, MSC.TPS Drug Information Services, JohannesburgL Baker, DIP. PHAAM.SAMJ Volume 84 No.7 July 1994,395

Drug-resistant Plasmodium falciparum malaria in the eastern Transvaal

https://www.ajol.info/index.php/samj/article/download/149364/138860

Drug-resistant Plasmodium falciparum malaria in the eastern Transvaal

Abstract

Similar works

Full text

Available Versions

AJOL - African Journals Online