In vitro response of Plasmodium falciparum to mefloquine in south-eastern Iran

OF THE ROYAL SOCIETYOF TROPICALMEDICINE AND HYGIENE (1987) 81, CORRESWNDENCE

T~,N~A~TI~N~

164

effects of heat on the cardiovascular system (DAVIDSON& PARRY,1978; ANON., 1979). The heat stressis not only climatic, with clustering of casesin the hot, humid months (PARRYet al., 1977) but cultural, with the use of artificial heating as a birth ritual (ANON., 1979). It has been argued by Sanderson that a hot humid climate causes reflex vasodilation and increased cardiac output in the presence of a low peripheral resistance (SANDERSON,1977). In such circumstances a high salt and water load will cause increasing expansion of the extracellular and circulating volumes until the cardiac output is great enough to increaserenal perfusion sufficient to excrete the salt load (SANDERSON, 1977). Although in the Nepalese, artificial postpartum heating is not a feature of childbirth, we suggest that in susceptible women the combined effects of the hot, humid climate and a birth ritual of incorporating a high salt intake, are sufficient to causegross postpartum heart failure. A. HENDERSON W. MELIA Medical Unit, British Military Hospital, Hong Kong, BFPO 1 References

Anon. (1970). Postmrtum fluid retention. Lancer.. i._ 960961.‘

-

Bmckington, I. F. (1971).Postpartumhypertensiveheart failure. American Journal of Cardiology, 27, 650-658. Davidson, N. M. & Parry, E. H. 0. (1978). Peripartum cardiac failure. Quarterly Journal of Medicine, 47, 431-

436.

Homans, D. C. (1985). Current Concepts: peripartum car&omyopathy. New Eng&nd3ournul of Medicine, 312, 1432-1436. Hull, E. 81 Hidden, E. (1938). Posipartum heart failure. Southern Medical 3owna1, 31, 265-275. Julian, D. G. & Szekely, P. (1985). Peripartum cardiomyopathy . Progress in Cardiovascular Diseases, 27,

223-240.

Parry, E. H. O., Davidson, N. MC?., Lapido, G. D. A. 81 Watkins, H. (1977). Seasonalvariation of cardiac failure in Northern Nigeria. Lancer, i, 1023-1025. Sanderson, J. E. (1977). Oedema and heart failure in the tropics. Lancer, ii, 1159-l 161. Accepted

for publication 4th July, 1986.

In vitro response of Plasmodium falciparum

to

mefloquine in south-eastern Iran Falciparum

Table l-Zn

malaria

is prevalent

vitro response

in the south-

preliminary study carried out in Iran-Shahr area, Sistan and Baluchestan province in 1983 (EDRISSIAN & SHAHABI, 1985). In a further study of the response of P. fulcipurum to chloroquine in the same area, the susceptibility of the parasite was also assessedagainst mefloquine by the in vitro microtest (RIECKMANNet al., 1978) using standard hits supplied by WHO. 118 blood samples infected with P. falciparum, collected from malaria out-patients referred to the Iran-Shahr malaria laboratory between 10 September and 9 November 1985, were tested. In 74 samples (62.7%) the young asexual parasites developed to schizonts (2 10% in the control wells) in mefloquine-treated plates. In 9 of the developed samples (12-l%), growth of the parasites continued in the presence of higher concentrations of mefloquine, i.e. 1.60 and 3.20 pmoYlitre of blood, which indicates resistance. The results are summarized in Table 1. The effective concentration required for inhibition of growth of 50% of the parasites (EC 50) in the resistant strains was 0.90 pmol/l, 6 times higher than the EC 50 for the sensitive strains (O-15 pmol/l). All nine strains resistant to mefloquine in vitro were rather highly sensitive to chloroquine. Thus it is unlikely that cross-resistancehas emerged due to the large scale application of chloroquine in the studied area. Resistance to mefloquine has been induced exwrimentallv in P. bewhei in mice (PETERSet al.. i977), in P: falcipancm &t vitro (LAMB~OS & NOTSCH;

1984) and by treatment of a falciparum malaria patient (BYGBJERGet al., 1983), but mefloquine has never been available in our study area. Therefore a relative innate tolerance or resistanceto mefloquine in vitro might be considered to exist in some P. fulciparum strains in the area. However, such findings in vitro may not have any therapeutic significance (World Health Organization, 1985). Gh. H. EDRISSIAN M. GHORBANI A. AFSHAR A. KANANI M. T. SATVAT School of Public Health and Institute of Public Health Research, Teheran University, P.O. Box 6446, Teheran, Iran.

of P. falciparum to mefloquine in south-eastern Iran (1985)

Strains

0

0.10

Resistant (9) Sensitive (6%

1261 (0) 7081

1218 (3.4) 5399 (23.7)

(0)

eastern part of Iran. Resistance of Plasmodium fulcipurum to chloroquine has been found at RI level in a

Number asexual parasites developed to schizonts (Oh growth inhibition) at mefloquine concentrations (tunoY1) shown 0.80 1.14 1.60 0.20 040 687 358 1206 1033 (45.5) (71.6) (946:) (18.0) (4.3) 243 2535 794 (993:) (88.7) (96.5) W*l)

3.20 (99-i)

TR~NSA~~ONS

OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGENE (1987) 81, CORRESPONDENCE

References Bygbjerg, I. C., Shapira,A., FIachs, H. Gomxne?G. 81 Jepsen,S. (1983).i$eflcquine resistanceof falclparum c7;from Tanzamaenhancedby treatment.Luncet,j, Edrissian,bh. H. & Shahabi,S. (1985).Preliminary study of the responseof P. fulcipomm to chloroquinein Sistan and Baluchestanprovince of Iran. Tmnsacti~ of the ~60&$Gciety

of Tropical Medicine and Hygme,

19,

Lambros, 6 & Notsch, J. D. (1984). P. fulcipatum mefloquineresistanceproducedin tine. Bulletin of the World Health Organization,

62, 433-438.

Peters, W., Portus, J. & Robinson, B. L. (1977). The

chemotherapyof rodent malariaXXVIII. The develop-

ment of resistance to me&pine. Annals of Tropical Medicine and Parasirology, 71, 419-427.

Rieckmann,K. H., Campbell,G. H., Sax,L. & Mrema,J.

E. (1978). Drug sensitivity of P. falciparum. An in vitro microtechnique. Lancet, i, 22. World Health Organization(1985).Applied field researchin malaria. UNDP/World Bank/WHO, TDR, 7th Prog-

rammeReport, 1 Jan. 1983-31Dec. 1984,p. 2/56.

Accepted

fm

publication

19

314

1986

Hepatitis B immunization of infants with a reduced number of injections: study of a schedule of three injections at three-month intervals Mobile immunization teams working in rural areas of developing countries face enormous problems, notably associatedwith limitations of medical personnel and difficult communication. Classical vaccination progranimes, comprising a 4-week interval plus a booster dose one year later, cannot therefore be used efficiently in many developing countries. These reasons, and the need for such mobile teams to cover wide areas, led to increasing delays between immunization interval periods (CABAU et al., 1970; BUREAUet al., 1977). The immunogenic effect of two dosesof hepatitis B vaccine administered to infants at 6-month intervals, plus a booster dose 6 months later, has been reported (COIJRSAGETet al., 1986). The results are comparable to those observed with a protocol of either two doses given at 2-month intervals and a booster dose a year after the first dose, or 3 injections at one-month intervals plus a booster dose during the 12th month (YVONNET et al., 1984). However, protection was very insufficient during the first 6 months before the secondinjection and the anamnestic responseafter the booster dose was lower than that produced by the other two schedules. Furthermore, the booster injection should be given simuitaneousiy with yellow fever and measles vaccines. Using the schedules outlined above, it must be given to infants aged 15 to 18 months, which is too late for the administration of the other 2 vaccines. In order to reduce the disadvantages associated with such a protocol, an immunization schedule comprising 3 injections at 3-month intervals (TO, T3, T6) was studied. The last injection was considered as booster. All infants were from the Fatick area in Senegal. Blood samples were taken at the time of each injection and also 2 months after the booster dose (T8). HBsAg, anti-HBs and anti-H& were searched for by mean of radioimmunoassays (Ausria II@‘, Ausab@,Cotabe, Abbott Laboratories).

165

Hepatitis B vaccine (Hevac B@)containing 5 g of HBsAg was used. Other vaccines used in the senegaiese immunization programme were also administered to these children, ie: BCG and diphtheria/ tetanus/pertussis/polio (DTP-Polio) at TO, and DTPPolio at T3 and T6. The anti-HBs response3 months after one injection of 5 pg HB vaccine was studied in 46 infants found to be seronegative at the time of vaccination. Anti-HBs antibodies were detected in 38 of them (82.6%). The geometric mean titre (GMT) at that time was 28.1 mIU/mi. The anti-HBs responseafter the second vaccination was determined at the time of the booster dose injection (T6). 45 infants were positive for anti-HBs (97*8%), with an anti-HBs GMT of 195 mIU/mi. Blood samples were obtained from 37 infants two months after the booster dose (T8). Anti-HBs was detected in all of them, and the anti-HBs GMT rose to 1065 mIU/mi (see Table). These results have been compared with those obtained in seronegative infants given two doses of HB vaccine at 6-month intervals, plus a booster dose6 months later (COURSAGETet al., 1986). The seroconversion rates at the times of booster doseinjections are quite similar following the 2 schedules: 97.8% after the first protocol, and 89.7% after the second with GMTs of 195 and 83.7 mIU/ml respectively. Six months after the first dose, however, 97.8% of infants in the present study had anti-HBs antibodies compared to 65.8% from the study with a 6-month interval period @
after first injection

3

6

8

No. tested

46

46

37

No. positive

38

45

% positive

82.6

97,a

No.>10

35

43

76.1

93.5

%>lO

mIU/ml nlIu/ml

Gcoincuic

(mIU/ml)

37 loo.0 37 100~0

mean titre 28

195

1065