Plasma, urinary chloroquine levels and plasmodium falciparum parasitaemia in children treated for malaria at Kenyatta National Hospital.

Abstract

Between June 1984 and February 1985, 32 patients with Plasmodium falciparum malaria were studied. They were aged between 3 months - 12 years. The clinical response, parasitaemia levels, plasma and urinary chloroquine levels, and in vivo and in vitro chloroquine sensitivity were determined. The parasite counts ranged from 39/300 w.b.c. - 9,630/300 w.b.c. On the third day 21(66%) of the patients showed clinical cure (i.e. symptomatic relief without necessarily having parasite clearance). Of these 6(19%) had cleared their parasites on chloroquine therapy, while 15(48%) were asymptomatic but still had parasitaemia. One patient was dropped from parasitaemia analysis because of incomplete counts. The other 10(32%) patients still had clinical malaria and parasitaemia on day 3. Persisting symptoms on both days 3 and 7 were fever and vomiting in 10(32%) patients and 8(26%) patients respectively. They had associated parasitaemia. A total of 13(42%) patients cleared on chloroquine during the study. The average clearance time on chloroquine was 5 days. The other 18(58%) patients failed to clear. Of these 10(32%) had their treatment changed on day 3 based on clinical and parasitological grounds. In the remaining 8(26%) patients treatment was changed between day 7 and 28 of follow up.They all had clinical malaria. The pattern of in vivo response was: Sensitive (S) - 13(42~ ; Resistant (R) at RI 4(13%); Rll 8(26%) and RIll 6(19%). There was therapeutic plasma chloroquine levels pretreatment in 19/22 (86%) of samples analyzed. One of these had toxic levels of 0.7467 ug/ml. More patients attained toxic levels following administration of chloroquine in the hospital by the 2nd and 3rd day 8/22(36%). The therapeutic range fur plasma chloroquine is 0.01ug/ml -0.03ug/ml.The upper limit of tolerable level was taken as O.4Wg/ml. In vitro sensitivity tests by Rieckmann microtest were successfully done in 19 cases. The minimal Inhibitory Concentration (MIC) was taken as 114nM/L (O.03648wg/ml). Of the isolates 3/19(16%) were sensitive in vitro. They were also sensitive in vivo. The other 16/19(84%) were resistant in vitro. Of these 7(37%) were resistant at concentrations equal to or above 640nM/L (0.2048~g/ml). This was the highest attainable concentration on the plates used. There was disparity found between resistance in vitro and resistance in vivo. 6(32%) isolates were resistant in vitro but sensitive in vivo. Their MIC was mostly 640nM/L(0.2048~g/ml) and over. All resistant in vivo cases,were also resistant in vitro. Urinary chloroquine assays showed 10/12 (63%) of samples analyzed had detectable chloroquine pretreatment. There was no correlation between plasma chloroquine levels and parasite clearance by day 3. All patients were from rural areas and were visiting Nairobi. Resistance in vivo and in vitro was demonstrated from Eastern, Nyanza, Western and Central provinces. There are pockets of resistant P. falciparum strains in endemic areas in Kenya as has been demonstrated at the coast and Kisumu in previous studies and now in Eastern Province in this study.